PERCEPTION OF PUBERTY IN THE TIME OF SHAKESPEARE – THEATRE AS A MIRROR ON THE WORLD IN THE SEVENTEENTH CENTURY

A live conversation by George Werther in Athens, September 2018

With contributions by Ze’ev Hochberg and Alan Rogol

 

The subject of puberty or adolescence in the 17th century is fascinating. Where better to go than to the Bard (William Shakespeare), who had a lot to say about puberty in a variety of his works. Perhaps the most germane quote is this one, from “A Winter’s Tale”, spoken by the Old Shepherd:

I would there were no age between ten and

three-and-twenty, or that youth would sleep out the

rest; for there is nothing in the between but getting

wenches with child, wronging the ancientry, stealing,

fighting- Hark you now! Would any but these boiled brains

of nineteen and two-and-twenty hunt this weather?

-William Shakespeare, The Winter’s Tale, 3.3.58–64

Translation: I wish children could jump from age 10 to 23 (avoiding puberty). During this period they indulge in rampant sexual activity, making young girls pregnant, they abuse their elders, they steal, they fight. By age 19-22 their brains have been addled!

In this short speech, we see an eloquent summary of the “adverse” social impact of puberty, including rampant sexual activity resulting in unwanted pregnancy, disrespect for elders, violence, theft. The Old shepherd attributes this to “boiled brains”. He suggests it would be best to skip ages 10 to 23 (!!).

On the other hand, adolescence as an idyllic time from the point of view of the individual, especially in retrospect, is also referenced in Winter’s Tale when Hermione asks Polixenes about his early relationship with her husband.

He replies:

We were, fair queen

Two lads that thought there was no more behind

But such a day tomorrow as today

And to be boy eternal

We were as twinned lambs that did frisk in the sun

And bleat the one at the other: what we changed

Was innocence for innocence; we know not

The doctrine of ill-doing, nor dreame

That any did

 Translation: As youth, we lived for the moment, and believed that we would be ever-young (Peter Pan-like). We were innocent with no malice, and thought ill of no-one. In other words as adolescents they lived idyllic and very happy lives. Their perspective was at complete odds to their elders.

Shakespeare was of course a master of insight into the human condition, such that in Winter’s Tale he provides the dual perspective of the trials of adolescence from the parent or elder perspective, while also getting inside the head of the hedonistic adolescent boy.

These observations and others are very well discussed in a recent publication by Victoria Sparey: Performing Puberty: Fertile Complexions in Shakespeare’s Plays https://muse.jhu.edu/article/592004>. Shakespeare Bulletin, Volume 33, Number 3, Fall 2015<https://muse.jhu.edu/issue/32417, pp. 441-467. She describes many references to puberty in Shakespeare’s plays, also including Romeo and Juliet (of course), Twelfth Night, Merchant of Venice, As You Like It, Henry IV Part 1, Measure for Measure, and Much Ado About Nothing. A recurring theme is the effect of puberty on various characters, which must be seen in the context of contemporary perceptions of the mechanisms in involved, and the effects of puberty on both body and behaviour.

THE LIFE CYCLE IN THE TIME OF SHAKESPEARE

In brief, the life cycle, in Shakespeare’s time, was seen as involving processes of heating and cooling, so that youth were hot and dry, where adolescents became dissociated from the excessive moisture of childhood (Cuffe, 1607), but still possessed the surplus heat that promoted such heat-fuelled acts as violence and argument. With increasing age, Cuffe writes that “cooling’ then occurs : An age is a period and tearmes of mans life, wherein his natural complexion and temperature naturally and of its owne accord is evidently changed”. Francis Bacon (1638) added, quite insightfully: The Ladder of Mans Bodie, is this [. . .]. To bee Borne; To Sucke; To be Weaned; To Feed upon Pap; To Put forth Teeth, the First time about the Second yeare of Age; To Begin to goe; To Begin to speaks; To Put forth Teeth, the Second time, about seven years of Age; To come to Pubertie, about twelve, or fourteene yeares of Age; To be Able for Generation, and the Flowing of the Menstrua; To have Haires about the Legges, and Armeholes; To Put forth a Beard; And thus long, and sometimes later, to Growing Stature; To come to full years of Strength and Agility.

Translation: The sequence of development in man is birth, suckling, early eating of soft mush, dental development, walking in the second year, then speaking, secondary dentition from seven years, puberty from 12-14 years, with reproductive ability, menstruation, pubic and axillary hair, facial hair, linear growth, to final adult height and muscularity.
This of course was based on the seven-year stages of man’s life cycle first described by Pythagoras and Hippocrates in Ancient Greece.

HUMORAL THEORY

Interestingly, in this period, namely around 1620, the concept of adolescence was rather vague, but there were certainly theories at that time about the mechanisms of puberty. These theories, as for general thoughts about the ages of man, related to “humors” or bodily fluids, both their abundance and their heat content. – such that each stage of the life cycle was thought to be closely related to the state of the body’s humors. Ageing was thought to represent a process of cooling and drying out.

The humoral theory said that the male is hot and dry and the female is cold and moist. Hippocrates in fact described women as “cold men”. Shakespeare adhered to Hippocrates’ four humor theories. The adolescent male (who we will discuss further as a key Shakespearean actor) is somewhere between these two points, being somewhere between the hot male and the cool female.

A woman’s moister and cooler body was related to menstruation (which removes the “heat”). Menstruation was then the critical event which differentiated men and women.

Bodily changes were discussed in ripening and fruitful terms. In 1592 Lemnius warned against men marrying too soon as “ere they be fully rype. – they lack manly strength and theyre seed is cold and thin”. So that the heat of puberty precipitated the ripening of the seed via generative heat. As  adolescence proceeded and “budding and blossoming” occurred, a requisite was that both male and female bodies became “hotter”, so that they could eventually participate in sexual intercourse. This is in contrast of course with the male/female hot/cold model and the fact that this event begins in adolescence sets the male/female differences apart from that time.

Thus, while most changes were gender-specific, some were not, including sexual desire, which was thought to be a manifestation of humoral excess in a body no longer requiring heat and moisture for body growth. – this “heat to spare” was said by Aristotle to influence the mind to sexual activity. Interestingly, it was also thought that humidity arising from the seed of the male, subject to greater heat than in the female, would rise higher in the body to alter vocal chords, while humidity in the female was associated with swelling breasts. So testosterone/oestrogen were in a sense recognised.

BODY HAIR

 Body hair was paid much attention and given much significance: Aristotle said Hairinesse is a sign of abundance of a man’s generative strength (again testosterone). Will Greenwood noted this in 1657 – lack of a beard was associated with men who were commonly cold and impotent.  Beards were thus also a matter of much discussion, as a sign of sexual maturation. In Henry IV Part 1, Falstaff challenges Hal’s manliness “whose chin is not fledged” by stressing that the beardless youth will remain so: “I will sooner have a beard in the palm of my hand than he shall get one on his cheek”. …”a barber will never earn sixpence from the prince”   In other words, Falstaff is challenging Hal’s manliness by suggesting that he (Falstaff) is more likely to grow hair on his palm than Hal is to grow hair on his chin. He also jests that he will never give a barber business (he will never need a shave).

Beards and other signs of puberty were then often used by Shakespeare and others in many plays, examples of some being listed above. The references were often derogatory regarding lack of masculinity, but sometimes highlighted the social or sexual tensions in various scenarios.  So the issue of the beard became a common one in Shakespeare’s hands, be it in humour or insult, or simply in observation or prediction of a man’s biological state. In contrast, Coriolanus is described as already exhibiting masculinity at age 16 when he was beardless …”with his Amazonian Chin he drove”. (Amazons)

In 1607, Henry Cuffe described male puberty “when our cheeks and other more hidden parts begin to be clothed that mossie excrement of hair”. In contrast, early texts explained the lack of body hair in women -:the matter and cause of the hayre of the bodies is expelled in their monthly tearmes…”. In other words, menstruation (while demonstrating generative potential) removed the excess moisture from the body that produced beards in men. The excess heat and moisture in men’s seed rose to his face and produced a beard, while the cooler but still heated humoral excess in women was released via menstruation.

In “As You Like It” an awaited beard is used to assess the adolescent Orlando’s readiness for romantic coupling with Rosalind, who asks: “Is his chin worth a beard?”. Celia responds that he “hath but a little beard“. The anticipation of Orlando’s further masculine development and his “love sickness for Rosalind is then measured by his beard. He “lacks the symptoms of a “beard neglected” The promise of his chin encourages her to await his sexual maturation –  she “will stay the growth of his beard”. 

This left the issue of pubic hair to be explained. This became a subject of humorous puns; whereby female pubic hair was described as an alternative “beard”. Chaucer played on this in The Miller’s Tale. Of course, female pubic hair was also recognised as a sign of sexual maturity. It was mistakenly thought that humoral excess from the woman’s seed stimulated hair growth around her genitalia AFTER menstruation had begun.

In “Twelfth Night”, when Viola (a girl played by a boy actor) is disguised as Cesario (a boy), discussion centres on “Beards”, both facial and pubic. Feste mocks Cesario’s (actually Viola) lack of a beard, to which “Cesario” responds “I am almost sick for one, though I would not have it grow on my chin”. Does she/he mean reference to Duke Orsino (for whom she is lovesick) or is she referring to pubic beard. Feste believes he is speaking to a male youth awaiting the growth of his beard, but “Cesario” (actually Viola)  is likely referring to pubic hair – signifying Viola’s longing for pubertal progression via menarche and subsequent pubic hair growth.

BLUSHING

Blushing was thought to represent an alternative response to excess heat on the face of a woman (rather than the facial hair of a man) -indicating ripeness or fertility – erotic because it was thought to result from excess heat arising from the young woman’s seed – heated passion, Vermillion blush.

In Measure for Measure, Isabella’s virginity is identified by her “cheek-roses”. Rosy cheeks give her sexual “ripeness” – the heated process of her maturation is evidenced by her blushing (which would have been exaggerated by cosmetics on stage). Lucio tells her she is “too cold”. “Be that you are – that is a woman as you are well expressed by external warrants – in other words her blushing tells Lucio that she is a “ripened” woman, and he says she should act that way and not be “cold”. In Winter’s Tale, Perdita has blushing cheeks. The shepherd tells her: “Come quench your blushes and present yourself”. When she interacts with her suitor Florizel, “he tells her something/That makes her blood look on’t.” In other words he makes her blush, presumably via some sexual suggestiveness.

In Much Ado About Nothing, Claudio says, regarding Hero’s blushing face “Behold, how like a maid she blushes”..She knows the heat of a luxurious bed/Her blush is guiltiness” Her blush gives away her sexual awareness or experience.

THE BLANK CANVAS OF THE ANDROGYNOUS EARLY PUBERTAL MALE

Theatre companies thus could stage male or female puberty in young male pubescent bodies via blushing of the womanly cheek, the youthful male’s promising chin, or the emasculating lack of a beard. Women were not actors, possibly because the theatre was not considered a fit place for women. All the actors in Shakespeare’s time of course were male, so that young boys played both boys and girls. In a sense, prepubertal or early pubertal boys were regarded as “ambiguous” or a “blank page” upon which gender was written. This is further confounded by “cross-dressing” heroines in As You Like It and Twelfth Night, where a boy plays a girl who pretends to be a boy! It is suggested that “eroticised boys are a middle term between men and women. Nevertheless, the “boy” actor was regarded as ambiguous or feminine, despite early pubertal changes – with a shift to masculine as the voice breaks.

“Boy actors must fit naturally into the parts of pretty well-bred girls, have waistlines that would suit a stomacher, and sufficient agility and grace to manage the cumbersome skirts of an Elizabethan farthingale. The boy actor must cut a fashionable figure too in doublet, cloak and trunk-hose; girls travestied as boys were always immensely popular with an Elizabethan audience and Shakespeare allowed his comic heroines frequent excuses to put on masculine apparel to give their mentality and speech a slightly ambiguous hermaphroditic cast. With their strange mixture of innocence and experience, romantic feeling and sharpspoken candour, masculine bravado and feminine nervosity, they tread a delicate line between the sexes. None of them is a completely mature woman; they belong to a period of human existence when the mildest girl is sometimes tomboyish and even the most energetic boy may now and then have girlish tears” (Quennell 1964)

This is in some ways reminiscent of current transgender issues in our society!

 SOME FAMOUS SHAKESPEAREAN ADOLESCENTS

“Romeo and Juliet” is clearly concerned with many aspects of adolescence and puberty. As you will recall, it deals with the “extremes of adolescent action”, namely passionate infatuation (Juliet was 13 years old!!). It has been described as “rites of passage, phallic violence, and adolescent motherhood – typical for youth in Verona. This was on a background of dealing with patriarchal familial bonds.

Also, Romeo demonstrates the typical adolescent intense crush and fickleness, where his desperation at losing Rosaline is immediately replaced by his equal passion for Juliet: “Did my heart love till now? Forswear it, sight/for I ne’er saw true beauty till this night.”

Similarly, Juliet, initially a compliant innocent young girl, is transformed by passion as she encounters Romeo – her loyalty and devotion to family are swept away. She becomes devious and lies to her parents and defies her father…sounds familiar? Worse still, the loss of her lover Romeo drives her to a self-destructive act – again familiar in modern times. The consequent fantasy that adolescent suicide will make the parents so remorseful that they will mend their ways is realised in the case of the Montagues and the Capulets, who erect statues in their memory and end their blood feud.

Miranda, Prospero’s daughter in “The Tempest” is in contrast to Juliet, whose adolescent passion and ardour is released and her lust is not curbed. On the other hand, Miranda is different: When Prospero finds Ferdinand and Miranda in his cave playing chess (!!!) – reflecting their infantile narcissism, Prospero tells Ferdinand; “If thou dost break her virgin knot before all sanctimonious ceremonies may with full and holy rite be administered, barren hate, sour-eyed disdain and discord shall betrew the union of your bed with weeds so loathly that you shall hate it both”.. they obey (perhaps unsurprisingly after such a dire warning by her father)- and curb their lusts, which were then confined to the chessboard.

PARENTS AND PUBERTY IN EARLY THEATRE – GREENSICKNESS

Much has been written about the girl entering puberty from the days of the ancient Greeks, but this literature is not widely known. I am indebted to Ursula Potter from the University of Sydney. She publishes on the early modern period and how theatre represents sexuality, puberty, gender etc.

Potter writes in a paper from 2013 {Navigating the Dangers of Female Puberty in Renaissance Drama), focusing on the issue of “Greensickness: and how it was understood and dealt with in Theatre of the time.  She sets the scene by quoting from Jane Sharp’s midwifery manual of 1671: The Midwives Book: Or the Whole Art of Midwifery Discovered. Sharp warns that once the courses flow at fourteen maids will not be easily ruled…..lustful thoughts draw away their minds and some fall into Consumptions, others rage and grow almost mad with love”. “Consumption” meant “Greensickness”, a popular term until the late 19th century. Many other terms were used, including Chlorosis, Tahiti fever, virgin’s disease, white jaundice, leukohlegmata, and cachexia.

The term “greensickness” referred to sexually green youth. The symptoms included eating disorder, amenorrhoea, fatigue, irrational behaviour, promiscuity or frigidity(!), depression and suicidal tendencies. It was the Forme Fruste of anorexia nervosa! It was mostly seen in well to do girls living an indolent lifestyle, and who usually were forced to delay sexual activity until after marriage. It was considered a condition related to the onset of menarche and the absence of sexual activity. It was attributed to the danger of retained menses or female seed once the girl had reached “ripeness”. The “cure”, as colourfully described by the midwife Jane Sharpe, was “marriage” or more specifically sexual activity “to open the obstructions and make the courses come down”. Several 17th century authors concurred, including the physician Lazare Riviere who wrote: “It is very good Advice in the Beginning of the Disease, before the Patient begins manifestly to rave, or in the space between her fits, when she is pretty well, to marry her to a lusty young man. For so the Womb being satisfied the Patient may per adventure be cured.

 Several plays of the era thus suggested that young women needed regular sexual activity in order to remain healthy, while at the same time these plays satirised the likely over-diagnosis of “greensickness”. For example, Johnson in “The Magnetick Lady”(1632), parodies the pandering by physicians to their wealthy clients’ obsession with green sickness. Another of these plays is “The Two Noble Kinsmen” by Shakespeare and Fletcher. The jailer’s 15 year old daughter suffers from many of the symptoms of green sickness, including weeping, loss of appetite, insomnia, and suicidal thoughts – put down to unrequited lust. She says, regarding the prisoner Palamon:

“Let him do

What he will with me, so he use me kindly,

For use me so he shall, or I’ll proclaim him,

And to his face, no man”

 In other words, she is desperate for sexual union with this man – if he refuses she will proclaim him to be unmanly. This need for sexual gratification again points to the “cure” for green sickness. She further graphically fantasizes:

“He’ll tickle’t up/ in two hours if his hand be in”.

 THE ORIGIN OF “HYSTERIA”

 Tickling the uterus was a therapy available to young women suffering from “fits” or other green sickness-like symptoms thought to be related to unrequited sexual urge – if sexual intercourse was not an option (such as an unmarried young woman). In “The Hidden Treasures of the Art of Physick” is written:

“If the Sick be a married Woman let her have carnal Conjunction with her Husband as soon as ever the Fit is over. If that cannot be had, that is, if she be a Maid or Widow, let a Mid-wife tickle the Neck of the Womb with her finger anointed with Oyl of Musk, Cloves or the like, that so the offensive Sperm may be avoided”.

This approach to distressed young unmarried women, seen as due to sexual frustration, and “cured” by tickling of the uterus, was thus thought to elegantly deal with both the relief of the sexual frustration (and secondary “cure” of the various symptoms), while also preventing pregnancy. Astonishingly, this approach remained until well into the 20th century, providing the basis for much of Freud’s theories of “Hysteria”, a word derived from the Greek word for uterus hystera (ὑστέρα).

SHAKESPEARE AND TNE OVER-BEARING FATHER

Plays of the era suggested that “greensickness” was overdiagnosed and that over-protective fathers and doctors were often to blame, respectively due to fear of sexual development of their daughters, and by regarding puberty as a clinical condition.

In “The Two Noble Kinsmen” Shakespeare however shows the doctor to demonstrate common sense, in contrast to the father of the sexually frustrated daughter. The doctor’s prescription  is to satisfy her body by giving her what she desires, namely a previous suitor to “lie with her”. The father’s concerns about her potential loss of chastity is answered by the doctor:

“That’s but a niceness.

Nev’r cast your child away for honesty.

Cure her first this way: then if she will be honest,

She has the path before her”

In other words, Shakespeare is condemning fathers as fools who would risk a daughter’s life rather than lose her virginity. This approach by Shakespeare came late in his writing career.

In a recent book by Deanne Williams, entitled The Performance of Girlhood, reviewed by Potter, she deals with the issue of how girlhood was represented in early modern theatre (16-17C).  She particularly addresses the Issue of father-daughter relationships in Shakespeare’s plays and how this changes over time, She notes that while in earlier plays daughters are often portrayed as erratic and immature, in later plays such as Pericles, Tempest and Winter’s Tale, daughters such as Hermione in Winter’s Tale are seen to be educated and developing independence.

A further fascinating observation regarding father-daughter relationships is that Shakespeare’s successful heroines who survive perilous circumstances, such as Rosalind (As You Like It), Portia (Merchant of Venice), Beatrice, and Helena – do so because their fathers are either dead or absent. In contrast, those who are having hard times have fathers who adhere to outdated concepts of daughterly conduct, failing to recognize girlhood as a distinct stage of development. So once again, Shakespeare comes to believe that over-bearing fathers are responsible for stifling their daughters’ development and independence, whether it be in fear of their daughters’ sexuality  (as discussed re Greensickness), or in their overall success in surviving adversity and achieving adult independence and resilience. These are indeed profound observations of the human condition, no less relevant in today’s world.

 CONCLUSION

Representations of adolescence in Shakesepeare’s plays is thus a fascinating subject, with some critics arguing that he ignores the adolescent period, while more recent scholarship speaks to a far more nuanced and complex approach.

Puberty and most of its elements were thus recognized in Shakespeare’s time and indeed as early as the ancient Greeks. Concepts included recognition of the developmental stages of puberty, with some errors, humoral explanations of physiology, which are in some ways remarkably close to hormonal explanations, specifics of male and female manifestations in behaviour as well as physically, some distortions of pathophysiology, but again some remarkably astute observations, with cures that persisted till early 20C. Roles of fathers and mothers. Lots about transgender!! A lot to learn.

DISCUSSION

 Ze’ev Hochberg: In the depiction of puberty in the literature, you would think that at the time of Shakespeare and in today’s literature puberty would be described similarly. The depiction of puberty at that time and today is very different. As you said, in Shakespeare’s time the emphasis was on the heat, on sexual activity and on temptation of the adolescent. If you read modern literature, adolescence is mostly described as an age of confusion. I would think that it has to do with the age of puberty then and now. In Shakespeare’s time, puberty was much later than it is today, probably some four years later. What’s happening today is that physical puberty comes much earlier, but the mental component of adolescence comes later, so that there is a mismatch with the readiness of the child. This is the basis for the confusion among today’s adolescents, whereas in Shakespeare’s time there was probably a greater synchrony between physical puberty and mental puberty, so that his description is more accurate with respect to the essence of adolescence, an age of heat and temptations.

Werther: You are right. It is interesting though from what I have read, in the plays, they still talk about menarche occurring at somewhere around age 13, which is not that different from today, but of course you are saying that is not historically correct.

Alan Rogol: I wanted to make two comments. The first one, from what Ze’ev said: Actually, the two times seven, fourteen, at that time was probably about right. It didn’t come till later in the Industrial Revolution that it went up to seventeen, and then came back down. But one other thing that we used to say as paediatricians and endocrinologists that you went to a child, to an adolescent, to a young adult. But some of the psychology these days is now you had emerging adulthood which comes after adolescence, but before being able to be on your own. I think that is exactly the dichotomy that Ze’ev brought up.

There is one other thing that came up: When they are ready for fertility, several of your references noted that they hadn’t reached their full muscularity and full body composition for boys, which is often early in the third decade. So I think he actually had some pretty good observations.

Werther: Yes, one of the references I gave was that boys should not have sex too early because “their seed is thin”, reflecting what you just said.

A conversation between Ma’ayan Harel, lecturer in the Department of Literature, Language and Arts at the Open University, and in the Program in Research of Child and Youth Culture at Tel Aviv University, and Ze’ev Hochberg, Professor Emeritus of Medicine, Technion, Haifa.
Transcribed into Hebrew by Shira Rappaport. Translated from Hebrew by Cassandra Gomes

With contributions by George Werther, Michael Ranke and Ad Kaptein

Editor: Jan-Maarten Wit

Ze’ev Hochberg: The terms puberty and adolescence are often used interchangeably. Whereas puberty refers to the activation of the neuroendocrine circuits that culminates in gonadal matura-tion and the secondary sex characteristics, the package we call adolescence includes such puber-tal development plus the growth spurt, cognitive and brain maturation and social aspects in learn-ing, intimacy and mutual support, intensification of pre-existing friendships, development of new relationships, and the attainment of biosocial skills needed for successful reproduction. The col-lective endpoint of the adolescence package is the socially and reproductively mature adult. To promote reproductive and parenting success in the service of reproductive fitness, hormonal and mental maturation are intimately coupled through iterative transactions between cognition, social maturation, and endocrine systems, with the latter producing sex hormones. Are you aware of that kind of a holistic approach to adolescence in the bildungsroman or otherwise in the litera-ture?

Ma’ayan Harel: From reading the articles you’ve written, and from this introduction, I see that your emphasis is on evolution and biology, while my thoughts on adolescence and the bildungs-roman are from a structural and sociological point of view. It seems to me that our conversation will take place in this gap, in the tension between the two poles that, naturally, feed one another. It’s a good starting point for this conversation.

Hochberg: This is the essence of our forum ‘Edge,’ which we call ‘The Third World’—the inter-action between the worlds of science, sociology, and the humanities. I come from the field of evolutionary medicine, not from the common medical field. This is also my subject of research.

Harel: I tend to think of literature, primarily, as a social and historical construct. Therefore, I’m interested in the gap between evolutionary and biological theories on development and sociologi-cal and historical thoughts, but also in the connection between them.

Hochberg: When I think of literature, which is not my area of expertise, I admire the ability of those who do not professionally see adolescents to describe what happens to them. In the ex-treme case we have David Grossman’s Book of Intimate Grammar, where the protagonist Aaron has clearly what we call in the clinic constitutional delay of growth and puberty. At my clinic, I often meet children with that problem, sort of ‘Grossmans’—assuming that the book is about Grossman himself. I’m not sure of that.

Harel: In the interpretation of the bildungsroman as a genre, this discussion, for example in Grossman’s work, can be based on biological and developmental questions that you’re dealing with. It’s also possible, however, to examine it in a broader context—for example, what it means to write such a novel in the twentieth century, a significant turning point in the conception of bildungsroman. Therefore, we see that it’s not only the biological aspect that is present, but dif-ferent outlooks into the matter. In other words, we can approach Grossman’s novel, and the is-sues that are brought up in it, not only as a biographical story of a child who is not developing, but also as a change in the literary preoccupation with the bildungsroman throughout the twenti-eth century.

Hochberg: Why the twentieth century? What happened in the transition from the nineteenth cen-tury?

Harel: At the end of the eighteenth and beginning of the nineteenth century, bildungsroman de-veloped in the optimistic world of enlightenment and education, thoughts about progress and development, and men’s ability to integrate into society. In this thought there was tension be-tween romantic views on childhood and adolescence and on man as a useful member of society. Bildungsroman served to draw a path for the bourgeois class, for whom literature was a common denominator.
Once the bourgeois class flourished and the individual was given strength to find his own path, to change and develop, the bildungsroman became the perfect genre for this purpose. In the twentieth century, especially in the wake of World War I and, naturally, afterwards, the belief in the strength of men—the optimism attached to it—was undermined, a fact that had a tremen-dous impact on literature and the possibility of growth and development.

Hochberg: And post-modernism?

Harel: Post-modernism radicalized aspects of modernist literature. From many perspectives, the bildungsroman turned into a novel that instead of dealing with development, growth, and maturi-ty, dealt with what is called anti-Bildung’ —the protagonist’s refusal to grow, the refusal to grow and develop into a world that has lost its principles, into a world that is made of doubts. Several times it is reflected mainly on the characters. Maturation, if it takes place at all, is internal and mental, rather than physical and biological. This is manifested in many novels, not only in He-brew literature, and one of its climax is in The Tin Drum by Gunther Grass, where it’s not clear who exactly is the character, if he’s a child or an adult, sane or insane.

Hochberg: I wanted to approach with you the gap between mental and body maturity. We think that five thousand years ago, the age of menarche was twelve; ten thousand years ago, in the ag-ricultural revolution, it happened even earlier. Perhaps at age ten. The first menstrual period, from then on, happened gradually at a later age. A hundred and fifty years ago it reached its peak—sixteen and a half. In evolutionary medicine, we view delayed puberty as a human strategy. The strategy is based on being tall, on being as big as possible, on delaying growth and reproduction as much as possible. In the past it must have gone hand in hand—body and mental development.
Then what truly happened during the industrial revolution, together with the improve-ment in life conditions and food production, the age of puberty declined. If puberty was at six-teen and a half a hundred and fifty years ago, today is at twelve and a half. We returned to what it was five thousand years ago. But mentally, maturity comes later. Today children stay at home and turn into adults at the age of twenty, twenty-five even. As you said, also in literature we can see the tension between body and mental growth.

Harel: That’s right. Many times the protagonist does not succeed in containing this tension be-tween the mental complexity or the psychological depth and his physical appearance. This is prominent in Grossman’s novel. The creative and psychological depth that such young child reaches in spite of a body that refuses to mature.

Hochberg: A body that starts maturing?

Harel: In Grossman’s, the body does not start maturing, it refuses to mature.

Hochberg: We call in medicine it delayed puberty.

Harel: We can also see it from an additional allegorical way, not only as a psychological-body tension, but a tension between the individual and the society in which he lives. In other words, the body’s refusal to grow and the choice of sinking into an internal, mental maturity, and so on, often symbolize defiance or protest against social demands. The social demands to become a use-ful citizen in a society that does not correspond to the turbulent internal world. Bildungsroman, from the start, takes place in this tension. Here we find a deep contradiction between the indi-vidual, his needs, his wishes and desires and socialization and the social circumstances he must abide to. In the classic bildungsroman, this tension exists but it’s solved in a way that fits the sur-rounding social values. On the other hand, in the twentieth century bildungsroman onwards, these tensions are often left unresolved, and these novels end ambiguously. As in Grossman’s, it’s not clear what happens to the hero Aaron. Did he get into the refrigerator? Did he not get into the refrigerator? Did he die in the end? Did he remain alive? What happened to him? It brings up significant questions. From a literary point of view, every question posted at the end of a work as an analogy to an aspect of life is extremely significant. This is also reflected in novels which end in very tragic ways, even in death or suicide.

Hochberg: Which novels do you mean, for example?

Harel: For example, Thomas Hardy’s Jude the Obscure (1895). It was written at the transition into the twentieth century; it actually bodes the transition to modernism. This is a novel about a young man who is constantly trying to find his way to maturity, especially intellectual growth. He wants to become an educated person; he wants to learn. There is a town that is similar to Ox-ford in England. He cannot, for various reasons, fulfill his passion, and is actually forced to live his entire life as a stonemason. He also passes through severe gender and marital crises, until he eventually dies.

Hochberg: And in terms of classic novels? What examples do you have form the classics?

Harel: The classic novel on maturity is, first of all, Goethe’s Wilhelm Meister’s Apprenticeship. It is a novel about a man from the bourgeois class who has the soul of an artist. He wants to be an actor and so on. After he’s passed through a journey and deals with many characters along the way, he succeeds in entering high society, increasing his social status. He becomes a rich man, marries, and brings children to the world. He actually fulfills all the steps in development, and renounces his passion to art.

Hochberg: Do you call it a bildungsroman? I thought a bildungsroman needed to start in child-hood and adolescence.

Harel: It doesn’t start in childhood, but the entire first part is a story within a story in which Wilhelm describes his childhood, the tension he felt towards his father, which is also an im-portant topic in a bildungsroman; his passion about the theater and how it started; his decision to leave his home and so on. It closes, however, with a normative end, complete even. He brings a child to the world and the child becomes his successor. It is a great ending. Dickens’ novels, nat-urally, are almost all bildungsroman. Most of them ends in a positive hope. As I said, however, Jude the Obscure ends in a tremendous tragedy, when the children who are born to the hero commit suicide. It is shocking, and he himself dies later on, unable to realize any of his goals. It is a pattern that is repeated throughout the twentieth century in several bildungsroman. What’s in-teresting is that the most modern optimistic novels, those that remind the most the classic bild-ungsroman, are for youth. Bildungsroman changed its message from a novel intended for the adult audience to a novel for children and youth, and then you can really see the return to classi-cal topics, because this genre contains a simpler aspect in terms of plot. Nonetheless, there is a great drama that takes place beyond, perhaps running in parallel to aspects that you’re talking about—the difficulty in comprehending human biology with the mind; the difficulty in integrat-ing biology with the natural development of the world and its social and technological aspects. I think this is quite interesting.

Hochberg: Is it true that fewer bildungsroman deal with girls or women—perhaps because most writers were men?

Harel: In literature, there is a broad sub-genre called the female bildungsroman. Not necessarily about childhood, but about the growth of a woman.

Hochberg: In biology, there is a very big difference between girls and boys, male and female an-imals. Maturity for girls from a biological perspective starts earlier, around two years earlier in comparison to boys. Very suddenly a girl’s body becomes that of a woman; she’s seen by others as a young woman, even though she isn’t fertile yet. She will become fertile around the age of eighteen, even though she got her first period at the age of twelve. There is a very long period between puberty and reproductive maturity. The boy, on the other hand, starts to mature later, soon he becomes fertile, but he looks young and immature. His voice keeps on twittering, he’s face hair will grow later, and he still looks young, so the environment does not regard him as an adult. Here is a significant difference between boys and girls.

Harel: It’s a very interesting issue. Bildungsroman is a male novel at its basis. The basis of the genre is truly founded around the experience of the European, bourgeois male. Nonetheless, very quickly, especially in the British novel, there was the rise of the female bildungsroman, whose perspective was truly written by women. For example, Jane Eyre by Charlotte Bronte, Wuthering Heights by her sister, Emily Bronte, novels by George Elliot, among others. There, the sub-genre of female bildungsroman was defined in a later period, especially in the wake of the feminist revolution, which is different from the male bildungsroman in many aspects. One of the most no-ticeable differences is the devotion to matters concerning family, relationships, marital issues, sexuality, which are much more pronounced than in novels by and about men.

Hochberg: And it’s always written by women?

Harel: It’s mostly written by women. There were attempts from men writing female bildungsro-man later. The female writers are mainly British, and later on also from the United States.

Hochberg: Because in England women belong more clearly to a status which differentiates them?

Harel: Over there started the tradition that women also write novels, some pretending to be men, others publishing their novels under pseudonyms, others under heading “a man” or something. But that is where the female writing revolution truly started. These novels are very interesting because women’s reality was not the reality of the professional narrative or class-like phenomena, as it was for men. The question is if they could actually undergo a “bildung” process. From the surface, there was great emphasis on finding a partner as a goal in development and the conver-gence into traditional female roles, and so on. This is from the surface. On the other hand, in these novels there are, often times, all sorts of subversive elements that contradict the roles des-ignated to women; they are related in order to undermine the linear model of female develop-ment. For example, in female bildungsroman it is very noticeable the connection between the fe-male hero and other female and male protagonist. In other words, there is a sense that women’s growth depends on environmental context, dialogues, and encounters that take place through her interactions with other characters.

Hochberg: With other girls?

Harel: Especially with female characters who embody the anti-thesis to the main character. For example, Jane Eyre is a classic novel in this aspect. We find the character Jane, who is an orphan girl, as most of the heroes in bildungsroman of her generation, who goes from institution to insti-tution looking for her path, until she arrives at Thornfield Hall, where she becomes a governess. The startling encounter of her life is also with Bertha, the landlord’s first wife, who is taken as mad and locked upstairs in the attic. She is a character who is described in harsh tones in the novel. She is described as violent, a beast, and very passionate, unlike the female main characters in bildungsroman, who are often times, despite their sexuality, lacking in sexual character, and comply to social norms of repressing sexual desires to adapt to social standards. The encounter between Jane and Berta, according to many interpretations of this novel, reveals the instinctive, unconscious, and repressed aspects of Jane’s personality. This is also evident in other novels where the female main character, ostensibly respectable, suddenly meets another character through whom her development takes place, out of confrontation, observation, dialogue, or direct confrontation of the female character’s struggle with sexuality.

Hochberg: This is, however, related to the experiences of adolescence for boys and girls, which are really different. The famous anthropologist Margaret Mead wrote about her experience in Samoa. As a young woman, at the age of twenty, she travelled to Samoa where she stayed al-most a year. She describes that during puberty, there are groups of girls and boys. Boys and girls leave their houses. All the girls live together, and all the boys as well, but the boys play games and practice crafts, while the girls talk among themselves and also practice with older boys and young men the sexual experiences. As I said earlier, they are not fertile at this stage. Therefore, the experience of a boy and a girl at this age is completely different.

Harel: It’s fascinating what you’ve just said, because it reflects exactly the models of female and male bildungsroman. The female bildungsroman is most of the time devoted to interpreting and discussing issues concerning empathy, interaction, and dialogues between female and male char-acters, and between female characters and male characters, who are not their sexual partners. For example, characters of a brother and a sister who are sort of androgynous and pass through mu-tual experiences of maturation. This aspect stands out in several works by women. On the other hand, in the male bildungsroman, the maturity process they pass is through a struggle, through tension and confrontation with other male characters. In other words, the Oedipal model of “murdering the father” in order to obtain his place, his position in the world, is prominent in these novels.

Hochberg: Even in very young age boys enjoy quarreling with other boy.

Harel: In literature, the true example of male maturity requires real confrontation. It requires an Oedipal male character who needs to leave his birth home or his biological father. Most of the times there are no biological fathers in bildungsroman, most of the protagonists are orphans. It’s a starting point of almost every bildungsroman—orphans in different degrees. There are orphans from mother and father, there are orphans from only one parent, there are orphans who have par-ents but they don’t know them, and there are heroes, such as in Grossman’s case, who have fami-lies but the family suffocates them—it’s not an orphan character, but very unusual in the bild-ungsroman.

Hochberg: And novels about boarding school, do you call them bildungsroman?

Harel: Which ones, for example?

Hochberg: James Joyce’s Portrait of the Artist as a Young Man or Harry Potter.

Harel: Yes, Harry Potter is a bildungsroman, a very interesting one because it has fantastic ele-ments. Therefore, it deviates from the regular bildungsroman, which is realistic and rooted in the real world. Harry is an orphan who is searching for his way. Also there you find several male characters who are placed on his way. His father died, but he has a mentor. Also, Dumbledore, the principal of the school and a dominant figure in his life. Also Lord Voldermort is, in fact, a male character, who must be dealt with in several ways in order to achieve his independence, to mature.

Hochberg: In my research, I talk about the topic of behavior programming in a very young age. The impact of the mental environment at a young age, at age one and then again at six, on behav-iors later on. The theory called socialization says that around the age of one, the child senses the world in which he lives in; if he lives in a threatening world, he will develop the view of the world as unsafe.

Harel: Yes, attachment theories.

Hochberg: Right. Bowlby’s. Therefore, if the world is unsafe, from a biological perspective, it means that it’s best to mature as early as possible, to run from one partner to another, take risks in sex, and establish a large family. In an unsafe world, you don’t know if otherwise your DNA will prevail for future generations.

Harel: So the world of the protagonist in a bildungsroman is an unsafe world.

Hochberg: From an early age?

Harel: From a very early age, because they are orphans; because many times they have no at-tachment. They move freely in a world without connections. Recalling once again Hardy’s Jude the Obscure, which I talked about earlier. Over there the hero raises himself. Or in Dickens’s Great Expectations, for example, which is a definite bildungsroman. In the opening scene of the novel, the hero says that he doesn’t know who his parents are, and doesn’t even know how they look like. So he used to go to the cemetery and imagine his parents in the shape of the letters on their tombstones. The only way he could bring up some sort of memory or imagination is entirely fictional; he even makes up his own name. This is extreme. So, the starting point of heroes in bildungsroman, both men and women, is often very shaky, usually something that forces maturi-ty, or the need to search and find himself an identity. Even when they have a home, in some con-stellation, then several times the bildungsroman is based on the need to leave home. In the act of leaving—leaving to a quest—the question is why there is the need for orphanhood in order for maturation to take place. Overall, because it widens the gap or the wound, which goes back to what you said. It’s a literary plot trigger for an intensive maturity process, sometimes a rushed one, sometimes not, that leads to building an identity. At the moment that you have no roots and you don’t have to hold on to them, you must, as fast as possible, build to yourself an alternate identity.

Hochberg: On the other hand, it comes to mind Salinger’s Catcher in the Rye, where the hero doesn’t want to grow up; he remains childish.

Harel: Right, this is a modernist bildungsroman. Apropos, among what we discussed earlier, this is another example of a complete modernist bildungsroman about a hero who doesn’t want to mature, in a way that approaches another topic that I deal with—the issue of illness and the ten-sion between insanity and sanity. The main question here is if our hero is sane from a mental per-spective or not. This is not clear at any point. In the classic novel it goes in the direction of the search for identity and maturity; and in the modernist novel it deals with the pit of orphanhood and absence, but it often fails to fulfill it because of significant ruptures in these novels. So, there is no successful solution, only failed attempts.

Hochberg: Another bildungsroman which I love is The Portrait of an Artist as a Young Man, and the issue around the tension and surge of sexuality.

Harel: Over there we find another interesting topic which is connected to another sub-genre in the bildungsroman. If we talked about female sub-genre, so Joyce’s bildungsroman can be de-scribed as an artist’s bildungsroman. This is something that was dealt with a lot in the literature of the twentieth century. Over there we find, several times, a gap, great tension, and confronta-tions between physical desires, from a biological perspective even, and the view of art as spiritual purification. Spirituality and physicality collide, as you mentioned. Also in Grossman’s roman we find it. Grossman builds his hero, Aaron, as an artist. His talent, shown through the book, is actu-ally concerning words—verbal, language, the capacity of reinventing words, to create art. It is the beginning of a talent that is not fulfilled in this novel, but portrayed in contrast to an unde-veloped biology. Art is, often times, the answer to the body and its needs, an emotional-mental response. This is also a prominent subject in modernism—the preoccupation with art, its roots, and the tension between art and other things such as the body, biology, and even society.

Hochberg: From a biological and medical points of view, we find children with disorder in pu-berty. Girls with early puberty, almost in every case girl, because in the case of boys, earlier pu-berty is very rare and almost always a sign of a serious illness. And boys with delayed puberty, because in the case of girls delayed puberty is almost always a sign of a serious illness. So girls come to us with early puberty and boys with delayed puberty. It’s not clear who suffers the most. Grossman gives a beautiful perspective into the issue. Aaron, with delayed puberty, goes to a gym class together with other boys who have passed puberty, and he can’t run together with them.

Harel: He deals with it a lot.

Hochberg: And with girls there is the issue of, for example, girls at the age of seven or six that start to mature physically. She goes out on the streets with a woman’s body and what happens as a result? A research from Sweden has shown that girls who develop earlier, even within the nor-mal range of puberty from 8-13, will have more problems with drugs, alcohol, and teenage preg-nancy, and have less chance of going to university. This is connected to a social issue because they connect to older children. Do we have these cases in literature?

Harel: Literature doesn’t deal much with the subject of early puberty. It’s more convenient to deal with the issue of delayed puberty, the delay of adolescence, and less with the issue of earlier maturation. If there are such cases, they are negative characters whose sexuality is very pro-nounced, “promiscuous” characters, a trait that can’t be controlled, as you mentioned earlier. It’s important to mention that women characters of this type, who have sexual intercourse from an early age, are always supporting characters in literature, and not the main ones. I thought a lot about this after I read what you’ve written.

Hochberg: Who are the characters that mature earlier?

Harel: For example, if we return to Jane Eyre, Berta is a character who is very sexual. I don’t know if she matured early, there is no indication of this aspect in the novel, because the biog-raphy of supporting characters is not given. There are also female figures who are described in an androgynous way, for example in Wilhelm Meister’s Apprenticeship, one of the main characters that the hero meets on his journey, Mignon, is fascinated by the world of musicians and artists. She is a type of character, a girl around the age of twelve, whose gender is not clear; it’s not clear if she’s already an adult or younger. Also his relationship with her is a paternal one on the one hand; on the other hand, it borders incest. This matter is blurred there. However, Mignon dies in the end. This is what happens to characters that portray the undesirable, the less wanted option from a moral point of view.

Hochberg: This is perhaps a different topic we could discuss some other time. It is a hot topic in our field today, where we discuss people whose sexual identity is not clearly defined or are transgender. In the medical field, they call it these days “gender dysphoria.” It has turned into an entire branch in medicine, about people who later on in life change their sex, but before they change it, they find themselves in identity crises.

Harel: Usually in the bildungsroman this doesn’t happen to the hero, which most of the time has an established gender identity. Many times, however, he meets along the way all sorts of charac-ters whose identities are blurred, some sort of literary warning sign—think of what will happen to you if you don’t turn into a man as demanded, or don’t turn into a woman as needed. And these characters are very important because they offer alternative paths that are not paved by the main plot.

Hochberg: We could certainly carry this on forever, but we’ll stop it here, and on my side, with the feeling that this is the Third World, where medicine and science meet the humanities.

COMMENTS:
George Werther, Professorial Fellow, University of Melbourne, Senior Endocrinologist, Royal Children’s Hospital, Melbourne, Australia

This is a fascinating discussion which explores the relationship between the physiolo-gy/pathophysiology of puberty and impacts on the societal and emotional experience of the indi-vidual concerned. The instrument at the basis of this exploration is the concept of the Bildungs-roman, a term coined in 1819 by Karl Morgenstern. It refers to the growing up or “coming of age” of a sensitive person who goes in search of answers to life’s questions, an essential feature being an early emotional loss, often parental, with the child setting out on a difficult journey to achieve maturity, involving conflict with society, and ultimate acceptance into it.

Harel, a literary academic and Hochberg, a paediatric endocrinologist expert in evolution and ad-olescence, here discuss the relationship between adolescence in society and the biological chang-es of puberty, more particularly the effect of delay in these processes, either through biological mechanisms, or via psychosocial pressures where childhood is held onto by the individual in or-der to avoid an adult interaction with society.

Their discussion uses the concept of Bildungsroman exemplified in a number of novels, both classic and modern, to explore the interaction between biology and psychosocial and emotional development. The first example they discuss is Israeli writer David Grossman’s The Book of In-timate Grammar about a 12 year-old boy who remains prepubertal (with presumed Maturational Delay) as his friends mature at a time of tension before the Six Day War. He is both biologically and psychologically stuck in childhood as he struggles to deal with his visions of the adult world.

Several other examples are discussed, the earliest being regarded as the classic form of Bildungs-roman, namely Goethe’s Wilhelm Meister’s Apprenticeship, as well as Dickens’ Great Expecta-tions, and more modern examples such as Salinger’s Catcher in the Rye.

Hochberg refers to the evolutionary changes in the timing of puberty, explained in part through environmental pressures over long periods, such that puberty occurs later under stressful condi-tions, as a survival mechanism by leading to taller adults, and reflected on an individual basis. In the last 150 years puberty onset has dramatically occurred much earlier. In parallel, we hear from Harel that the Bildungsroman changed from the 19th to the 20th century, reflecting the transition through the Age of Enlightenment, with optimism at the beginning of the 20th century. As the 20th century descends into the turmoil of two World Wars, and the optimism fades, the Bild-ungsroman changes from an individual who finds his way from childhood to adulthood despite its challenges, to a child resisting the transition, both psychologically and biologically, which may never be properly resolved. This is seen in The Book of Intimate Grammar, as well as in Gunther Grass’s The Tin Drum.

The final point of discussion is the difference between male and female Bildungsroman, noting that the earliest representations in novels were exclusive to males. However we are informed about a sub-category, known as female Bildungsroman, referring to the growth of women. The Bronte sisters’ Jane Eyre and Wuthering Heights are given as examples. It is noted, and this must relate to biology, that while in the male form Bildungsroman involves a struggle through tension with other male characters, in the female form, the emphasis is on discusssion, empathy between females and with males.

Comparison is made by Hochberg with the work of Margaret Mead in Samoa, where the experi-ence of boys and girls in puberty is very different, to an extent reflecting the difference in Bild-ungsroman.The common physiologic variant of delayed puberty in boys, as in Grossman’s The Book of Intimate Grammar is again noted, being less common in girls. In contrast, early puberty is a common variant in girls, but not so in boys. When such characters appear in literature, their early sexuality is seen as a negative trait.

This was a very interesting and discussion which is likely to provide readers with new infor-mation and insights into the relationship between puberty (and its variants) and psychoso-cial/behavioural paradigms – not just on an individual level, but also on a broader society scale, and over time. While not all of the parallels between the biology of puberty and the psychoso-cial variants of novels are compelling, the overall discussion and concepts are well worthy of dis-cussion and debate.

Ad Kaptein, Professor of Medical Psychology, Leiden University Medical Centre, The Netherlands

It is a pleasure studying the manuscript “Sexual maturation and the Bildungsroman”. The manu-script explores an issue which is hardly ever covered in medicine, and neither is it covered a lot in the Medical Humanities arena. This in itself makes the paper a valuable contribution to a burgeon-ing area.

Hochberg adopts a rather biomedical stance in emphasizing biomedical explanations for behav-iour. I’m not arguing with that view. However, in the context of the current manuscript a more balanced biopsychosocial view might be worth considering. Puberty/adolescence pertain not only to medical phenomena – on the contrary: the psychological and social changes and ramifications seem at least as important as the biomedical changes, as far as I’m concerned. The authors might consider touching upon this point a bit stronger (on page 1, for instance). The mistake in the Grossman book illustrates my point: the correct title is Book of Intimate (not Internal!) Grammar.

It might be useful to present the reader with a definition/description of ‘Bildungsroman’. The authors do suggest a number of ‘Bildungsroman’ ; it might be a suggestion to give a quite exten-sive list (if the authors are willing and able to do this) of those novels. They might touch upon the issue of ‘post modernism’ there as well.

I’m not an MD but I wonder about the point the authors make about young girls not being able to get pregnant immediately after starting menstruating. Girls of 12 years old are known to give birth, isn’t it? Young Black working class girls in the US, for instance? Young girls being raped give birth, don’t they? I’m not sure I get the point about shifting age of start of menstruating.

How do the authors view the contribution of theory and empirical research in the Medical Hu-manities to ‘sexual maturation and Bildungsroman’?

Michael Ranke, Professor of Pediatrics, Tübingen University, Germany

I think it is very interesting to have a discussion between a developmental biologist-pediatrician and an expert in literature in order to evaluate how adolescence and development in medical terms find their mirroring in the literature, specifically in what is called “bildungsroman”. This category of developmental novel has emerged specifically during the 19th century. During the 19th century this genre describes the development of the characters (mostly males) painted out of the perspective of the conflict with the “ideals of innocent youth” and the ” raw reality of the en-vironment” and ends – as in Goethe´s Wilhelm Meister- in some form of maturity and harmony.

This reflects the idealized view of a relatively stable world. We know today that the adolescent biology is not only different in its time course in males and females and over the centuries, but that sexuality of adolescents finds different expressions in different cultures. The modern bild-ungsroman of the 20th century reflects more the complexity of the conflicts between the individ-ual within an unstable social setting also more directly addressing the sexual issues given during the maturational processes, including gender ambiguities, which are often only discussed in dis-guise in 19th century novels. I think (even if I have not read all of the mentioned books) that these aspects have been nicely shown in the discussion by the two protagonists of the dialogue. I enjoyed reading very much.

Paul Saenger Professor of Pediatrics Emeritus, Albert Einstein College of Medicine of Yeshiva University
I was very pleased that you touched on the Blechtrommel by the late Guenter Grass. Oskar Matzerath the small protagonist of the novel did not want to grow up and he was quite a mischievous youngster . In the OSCAR winning movie made by Volker Schloendorff he used a rather small GH deficient actor from Munich who was at time under the care of Otfried Butenandt at the University of Munich.. I thought this small item add a personal note of the true endocrine problem of the actor playing Oskar. in this Nobel prize winning novel.

As far as Margaret Mead is concerned there were for many years doubt about the veracity of her field work in Samoa. Critics felt that she was duped by the islanders she interviewed and the ” free love ” they described was actually a hoax played on her. To my knowledge this question was never completely resolved. This does of course not diminish her contributions to anthropological science.

I thought the discussion was quite interesting to follow.

A live conversation between Alan D Rogol (Charlottesville) and Robert M Malina (Austin) Moderated by Martin Ritzén (Stockholm).
Contributors: Jan-Maarten Wit, Abiola Oduwole, George Chrousos, Ze’ev Hochberg, Ivo Arnhold, Mark Sperling
Transcription: Shira Rappoport

Martin Ritzén: This conversation is about pubertal maturation and its influence on sports, which is really quite an interesting field. Think about the 13-14 years old boy who has not entered puberty, he has flunked out of his ice- hockey team because he is too short and too light. Should we do something about it? He may want to have testosterone to get stronger; is that acceptable? Children of same age but vast differences in physical maturation; should they compete with each other? That is the question for Alan or Bob. What about the health aspects of hard physical training during maturation; is that good or is it bad for a child? Is it acceptable to subject a boy who is completely prepubertal to the same degree of training as one who has advanced puberty, or even an adult? As for the degree of maturation, we have the extreme example of DSDs: XY females, e.g. 5alpa reductase type II deficiency who start to respond to their high testosterone in puberty. You could call that extreme maturation. They will become very muscular and compete very well in sports.
We have two excellent conversers. Alan Rogol, who has done a lot of work on sports and on endocrinology of sports. We have Bob Malina, who is unique in the contributions of scientific work on the relation of puberty to sports and physical maturation. So we have an excellent team to start the discussion, then I hope to have a free discussion with the rest of you.

Alan Rogol: I am happy to be the warm-up player to my longtime friend and colleague, Bob Malina. You’ll hear from him. Bio-Banding that’s what it’s called in sport. It actually is not a new concept at all although it’s relatively new to sport as Bob will discuss, but mainly from the point of view of his former students and himself.
Sean Cumming and the University of Bath in the UK will be major players. I sent around at least one paper that he wrote [J Sports Sci 2017; 19:1-9]. In fact, this concept fell out of issues related to the human as a work machine.
This concept goes back a hundred years or probably even more than that. In general, all of us in this room understand at least the outward signs of pubertal maturation leaving pubertal development or the psycho-social aspects aside, although Bob will bring up some of those aspects as part of his training in that area.
Sport at least at the pubertal age selects those who mature early especially in those sports for which chronological age groups are prominent, around the world of football, soccer for us, and basketball – those are the prominent ones. Within any age group the players’ birthdates are not randomly distributed, but those in the first quarter of the year are more prominent, likely due to maturity status. And so that is January to March, if it’s a whole year, that quarter is enriched in the kids. Why is this so? At least for boys sports strength and power are critical and maturity status and strength and power are causally related. We are all more familiar with the growth aspects than we are with the strength and power aspects. I have copied several papers which I will open up but one of the papers that people ought to read is David Handelsman Sex difference in athletic performance emerge coinciding with the onset of male puberty. Clin Endocrinol 2017; 87(1):68-72.
What about girls? We don’t talk about them so much except Bob and I and a few others were part of FIG which is the French for Federation Internationale de Gymnastic. Do you know why the girls in gymnastics are so little? Too much training, how much is too much? It turns out that they’re prisoners of their genes.
We’ve written about that [Sports Med 2013; 43(9):783-802].
One of the things we don’t talk so much about when we talk about training is the volume of training: “we’ve been training for 16 hours a week, 32 hours a week… ” What does that mean in terms of energy expenditure? Yet some sports scientists have actually looked frame by frame at every 15 seconds or every minute what the girls do during four hours of gymnastics training. A lot of it is stretching; a lot of it is learning dance moves etc. It’s not all strength and power. And so although they train 30 hours a week, that’s not really necessarily at a heart rate that is 70, 80, or 90 percent of heart rate max.
So I think that those issues will be brought out. Although in fairness if you look at the adult data Ann Loucks, who is the most prominent, talks about energy balance [J Clin Endocrinol Metab 2006; 91(8):3158-64]. Pulsatile LH release, menstrual function depends on the net energy balance. If one does enough exercise or not eat enough one has disturbed hypothalamic-pituitary-gonadal dysfunction. Essentially it’s calories no matter how the calories are distributed (accrued or spent) that one works so hard or one does not eat enough so, on the one hand one has anorexia nervosa but on the other and one has perfectly well eating athletes, but not enough for the amount of energy that they expend.
Thus, what is important for athletic success? Number one on the list, genes. Not exercise; not anything else. And so one might say you better pick your parents (actually a few generations before your parents) very carefully, if you want to be a successful athlete.
Part of the training issue of course is both physical and psychological stress. George Chrousos will speak about that aspect. So in part of the discussion we will need to wait for what George has to say.
Bob Malina will now continue with the specific issue of bio banding.

Robert (Bob) Malina: Thank you Alan for the introduction and thanks for the opportunity to be here. Of course this is all a very different community for me to be interacting with. But I’ll do my best to give you a fair shake as to some of the issues involved. Bio-banding is now the in-word. Specifically, what they’re doing with it in UK is using a non-invasive estimate of maturity status-percentage of predicted adult height attained at the time of observation. And they’re applying it in the context of soccer. But as Alan said this is not a new concept. Perhaps the first person to talk about grouping boys by maturity status was a man named Ward Crampton back in 1908. His paper was published in the American Physical Education Review. In fact, Jim Tanner thought he was talking about sport, but Crampton never once mentioned sport. It was aimed at how boys should be grouped s for work? Crampton used pubic hair-prepubertal, pubertal or adult. But a year later (1909) a man named Rotch began using hand-wrist bone age; he called it Anatomical Age, and indicated its potential relevance for sport. So this (maturity-matching or bio-banding) is not a new concept; it has been with us for a while.
Historically it has focused mostly on boys and it makes perfect sense. Sport is ruthlessly selective, whether it’s voluntary (dropping out), cutting you’re (excluded because you’re not good enough or not big enough and so on). But sport is in many ways a business and in boys more so than girls’ sports are dominated by early maturing boys. American football, soccer or football, ice hockey, baseball, swimming, track and field athletics (except for distance runners) sports are dominated by early maturing boys.
So this is not new. My major professor of anthropology Dr. Krogman published a paper back in 1959 on skeletal age of little league baseball players: participants the World Series that are held every year in the summer. His conclusion was that men are beating the boys. The age limit for little league is 12. So not yet 13 years by a specific cut-off date. Krogman used Todd’s method of assessing skeletal maturation (1937) and several years earlier (1956) the president of the Little League (Creighton Hale) used maturing assessments, specifically did it with pubic hair with Crampton’s criteria and showed the same results. . Clearly the men were beating the boys and this has since been verified in other sports.
To put things in perspective one of the first studies of young girls was from Sweden- work on swimmers (1963), where he found that girls in swimming were in general average maturing with no dominance of early or late maturers. In fact, the best swimmers were slightly maturing except for small samples. The exception for boys is gymnastics, where you still see the late maturing boy t and some average maturing boys persist, but by and large it’s late maturers. In girls in the aesthetic sports: late maturers dominate-artistic gymnastics, figure skating, also ballet. Otherwise most girls in sport tend to be average in their pubertal maturation. You get a few late maturers in distance running and related sports. So, it is hard to generalize from one sex to the other.
So, why is there such concern for this bio-banding now? Well, historically in the sports sciences there’s been a reluctance to use invasive methods of assessing maturity – skeletal age or pubic hair. Also most in the sports science don’t know how to assess maturity status. One of the big limitation is when you provide a skeletal age, only a bone age, many in sports sciences have no idea what’s involved in doing it. Of course assessment of secondary sex characteristics is very, very difficult. It’s considered personally invasive. That’s an interesting paper Medicine and Science in Sports and Exercise several years ago (2013) which evaluated how well orthopedists could assess the pubertal status of their patients; the conclusion was that the assessments were unreliable. So, just because you’re a physician is no guarantee you know what you’re talking about when it comes to pubic hair assessment. I do not say that negatively, but this is a problem in the literature.
So, there’s been interest in noninvasive methods, and back in the early 80s Alex Roche (1983) from the Fels Institute, who just died earlier this year, e proposed the use of the percentage of predicted adult height as a potential noninvasive estimate of maturity status. Hypothetically, the youngster closer to his or her adult height is more mature than a youngster of the same age who is not there. And Roche and a colleague proposed a series of equations to predict adult height based on age, height and weight of the child and mid-parent height. And of course, if you go back to the longitudinal growth studies of the University of California, Berkeley by Nancy Bailey Harold Jones and colleagues the percentage of adult height attained at each age is reported for the total sample and also for early, average, and late maturing boys and girls in Bayer and Bailey’s monograph back in the late 50s. So, there is a long tradition of using percentage of adult height and Alex proposed it as a maturity indicator. Several individuals used it in the studies of physical activity. I applied it in a study of young American football players, and it worked reasonably well. It had moderate concordance with the skeletal age, which we did in a separate study. And Sean Cumming applied it in his doctoral thesis at Michigan State University. When he got to England colleagues from soccer (football) asked him to give it a try with soccer. There was a group in England concerned with how can we modify the system to give all boys a more equal chance?
Now to put it in perspective, any of you ever heard of Alex Ferguson the coach at Man U? One of my colleagues was a trainer at Man U. And they appealed to the English Premier League to hold two or three boys back to let them play down based on skeletal age to give them a chance to catch up. That’s how perceptive he (Ferguson) was. I can’t mention names but the three youngsters are now playing professionally. So this is something was on the back of their minds. So there was I think fertile ground to try this approach.
So, what have they tried in England, and they have been working with boys, 12 to 14 years. They have done a series of what they call bio-banded tournaments, where the boys were grouped by percentage of predicted adult height using Alec Roche’s equations. They tried several categories, but the one they used was grouping players between 85 and 90 % of predicted adult height. Most boys are about 91-92 percent of adult height at the time of peak height velocity that comes from the Polish and other studies. Putting that band into perspective I used it with a group of soccer players for whom I had data. And most players below 85 percent were pubic hair stage 1 (prepubertal) or 2 (early puberty). In the 85 % to 90 % band, you had mostly pubic hair 2 and 3 a few 4s and maybe a few 1s. And these are actually boys who play soccer in Portugal. The tournaments were very well received by the coaches and especially by the boys. This is the work of Sean Coming a sports psychologist by training and he was interested in how did early and late maturing boys react. And it was amazing: reactions were very favorable in terms that there was more emphasis on technique and skill than sheer physical size because you take a group of 13 to 14-year-old boys, the defenders will dominate because they are physically big and so on. This was the highlight I think of it as the youngsters received the bio-banded tournament very well. The coaches generally perceived the tournament as well and the feedback from the youngsters in terms of learning the skills and proficiency in the sport was the most important thing. And it has been very successful in UK. You will probably see this applied in US because the man now running U.S. youth soccer came from England and he worked with Sean and he was the one to help adapt it. So you’ll probably see that soon in us.
So, this is what the bio banding at present and right now it is actually well-received. Sure it is not perfect. There’s always error involved, but this is being done.

Rogol: Bob you mentioned, tournaments, what about training? Different training for those who are more mature vs less mature?
Malina: That’s a different issue. Sure. Many people will have you modify your training programs for the late maturing boy as opposed to early maturing boy. Typically, if the boy is early maturing – strength and power, early on it is a lot more focused on skill and so on. But I would like to add one more method that is out there now. It is being used mostly in US and now worldwide: it is predicting maturity offset time, time before or after peak height velocity.
It is predicted from age, height, sitting height, estimate leg length and weight. The original equations have since been modified. For boys. There are two equations with age and height, and age and sitting height. For girls one equation with age and height. Chronological age minus maturity offset provides an estimate of predicted age at peak height velocity. It is widely used and widely misused. We have done three validation studies two with the Wroclaw Growth Study (Poland) and one with the Fels Longitudinal Study (US). Predicted maturity offset depends on chronological age and body size at prediction. If applied longitudinally, predicted offset/age at PHV varies from age-to-age in the same child. The protocol does not work with early maturing boys and girls. It’s good for average maturing boys close to the time of peak height velocity meaning between about 13.5 to 14.5 years I’ll be happy to share those papers with you; one is still in press.
Studies tend to group youngsters as pre PHV, around PHV and post PHV But why predict peak height velocity in a 16 year old boy? He’s already been past it. But the sports scientists don’t understand. I’m sorry I say that critically but they need to be educated on what they’re looking for a quick fix.
A couple of comments: Alan mentioned about training. Time does not equal training. They spent X hours in gymnastics in the study you mentioned. They actually spent more time resting between repetitions than training. Now only sports like swimming where you know what the distance is swimming or they’re running and so on this is somewhat different. Nevertheless, time training is often misrepresentative of what’s actually going on. And I honestly think if I were to study the effects of training on children nowadays I would study the adults involved. If there’s a problem with intensive training; it is not the youngsters, it is not the training, it is the adults! And I say from experience working with women athletes at the University of Texas we had several with disordered eating problems in the early 90s. You could trace every one of them to the coach. In case of swimming, the coach wanted them at weights at which they swam their best times, i.e., when they were teenagers. But now they are adult women. And in the case of track and field athletics it was the coach; she wanted them at less than12 percent body fat. So to me if I were to go back and study sport I would study the adults and the environments in which the youngsters train and that’s vastly overlooked.
So at that to open floor for discussion.

George Chrousos: About 30 years ago we did the big exercise study with the human performance laboratory at the Naval Hospital, which is excellent. And we studied young men mostly from the Navy who ran or didn’t ran daily. First, we did their VO2 max, and found that If you stress people, the amount of VO2 max was the one that correlated with the hormones elevations. Let me remind you that ACTH, cortisol, prolactin, growth hormone; a large number of hormones go up when you exercise. So, there were three groups of people – sedentary, very little exercise; running I think 25 miles a week; and running over 40 miles a week. When we analyzed the data, So what do you see was all or none effect with the high exercise. No it was the people who ran over 40 miles a week had high urinary free cortisol, and had suppressed ACTH responses to CRH. So the conclusion is that if you exceed the certain amount of exertion you become hypercortisolemic. And it fits very well with what people are finding in these athletes. They develop osteoporosis, have suppressive immune system and so forth. So the first question that was mentioned here the amount of exercise. I think there is a level for each one of us. If you go beyond that who will be stressed chronically stressed, and we will damage our body.
We did another study with a psychology group at the NIH. Middle class boys and girls from around the Bethesda area where we examined them with Tanner staging and so forth and did a number of psychological – psycho medical tests, such as the CBCL test. That shows degrees of adjustment or maladjustment to the environment. What was very clear was that girls that matured early had a lot of problems; not boys. Boys that matured early were the best, and exactly the opposite with boys that delayed their puberty had many more problems than boys that started earlier – problems that you pick up at the CBCL – the standard testing for these ages. There is one for the patient and one for the mother, evaluation of behaviors feelings. A standardized test. And of course these people were children who were within the normal range but you could pick up the correlation between the test and the maturation.
Let me tell you another thing. We tried to examine the people who exercise a lot over 40 miles a week psychologically. Nobody would stop doing it. They didn’t want to stop. And they actually scored very high. They were very well adjusted. One had a damage in one of the muscles and stopped. And while he stopped he was depressed. We just couldn’t convince him to stop. So there is a degree of addiction to exercise. So it’s also quantitative exercise. You cannot exceed a certain level, which is different for each one of us.

Ritzén: Does hard endurance exercise cause damage to children psychologically or physically. Who would like to comment?
Chrousos: I think that if you exceed a certain level you will damage the people. Now I remember that we had a good opportunity to study exhaustive exercise in young men and women. There is a so-called Spartathon where people come from all over the world and they run from Athens to Sparta. It’s like a marathon but it’s a quick walking basically. So, they have to do it within 36 hours. And when they arrive the ones that don’t stop in the middle. There are people waiting for them from the Sparta hospital, and take them directly to the hospital. And we had to measure everything in them. And I have to tell you I’ve never seen this high levels of interleukin 6. The amount of inflammation and proteolysis in their muscle was unbelievable. Cortisol was sky high. And then we had the two days later to do the same. And they were completely corrected. It was amazing. Everything went down. So exercise can be quite an inflammatory response. This is an inflammatory state but obviously the body can overcome it. All these people the Spartans they’re all very well fit right. They run the whole year you have to be ready for that. So as there is a certain level we manage very well actually it may even be beneficial. But beyond a certain level of constant inflammation you’re going to be damaged. You need the time in between to repair.

Question: Was there a difference between pubertals and adults?

Chrousos: Well we didn’t study that. They were all young adults.

Jan-Maarten Wit: I have a question on this bio banding. Why don’t you use serum testosterone instead of this complicated formula – in the boys of course? I’s not so invasive to take a blood sample for testosterone levels, I would say.

Malina: I do not think they’ve got the facilities and the technology for the coaches and trainers to do it in-situ. That’s part of the problem.

Wit: There are of course doctors with each football team, and they can just order the testosterone. That’s just not such a big issue. It’s even possible to measure testosterone in saliva or urine.

Malina: Perhaps, but I’m just not sure of the variations in hormones. And when you work with adolescent boys if you’re going to be able to do so. I don’t know enough about the endocrinology of it. And I’m not sure the sports scientists know that either.

Ritzén: It seems that all the different ways of assessing maturity is set up in order to avoid blood testing. Blood testing would be the ideal method. But that may not be practically feasible.

Chrousos: If you get two saliva samples let’s say 8 a.m. and 8 p.m. and measure cortisone alpha-amylase and testosterone, then you get a tremendous amount of information twice a day to show circadian variation.

Wit: Early morning is more informative than an evening sample.

Ze’ev Hochberg: I didn’t do any research myself on that, but I see my patients. And my patients tell me about their life, and sport is part of their life. When you talk about biobanding, do you limit your ideas to boys and girls who train to become professional and take part in competing teams? Or this has also to do with sport activity at school or socially.
My second question: you talk mostly about physical maturation, physical puberty. What about the mental part of adolescence? Some kids show a discrepancy between their physical and the mental maturity. How do you band them? Do you bioband them by their physique only?
And lastly, you mentioned girls who do gymnastics, and you mentioned that they rest a lot during the training, they do not exercise the whole time. But the girls I see who come to me with delayed puberty and train, they spend like six hours a day six times a week going to the training center, which put them into tremendous stress in terms of their school performance. They never manage to do their homework. And then after training they take the bus to go back home etc. So, these girls spend six seven hours a day, seven times a week in gym. What do you think is the impact of that life style?

Malina: I hope I get all the parts of the question. All the work done on biobanding in England right now is based on youngsters in soccer academies. They are 12, 13, 14 years so they already are select in many ways before the major selections are going to come up. I know of nobody who has done it in a social context. But there’s a very rich literature on maturation and behavior that goes back to the Berkeley studies. I would recommend if you ever get a chance go back and read those papers by Harold Jones and colleagues talking about the behavioral characteristics of early late maturing boys and girls. These all go back to the 40s and 50s and are incredibly good studies because Jones also studied muscular strength. And clearly the early maturing boy is strong and is also really behaviorally way ahead of the game.
Now, athletes of course are a unique sample. They are selected, ruthlessly selected. And as a rule the behavioral characteristics of youth athletes have not been systematically studied especially in a bio behavioral context. So, the unique thing that I think Sean Cumming is coming up with is the perceptions of the early and late maturing boys; the early maturing boys 12 year old playing up and the late maturing 14 year old boy playing down.
That is what I believe they are pursuing right now. So those results are in but the extremes of maturity forced to play up or down their Reactions of the players to the biobanding being have been very favorable in the context of that sport (soccer). In terms other behavioral dimensions, it has not been study.
Your question about the young athletes who may spend six hours a day or eight hours or X hours a week in training gymnastics, I agree with you, but I think it is more important to study the gymnastics environment, because if there’s a negative effect it’s the adults who run the sport. Why are these children there for that many hours? Are they driven or are the parents driven? That is the issue that has not been studied. I find it hard to believe that children do this by themselves. Because in youth sports in US right now, parents are investing so much money in their children’s sport; They are expecting future prospects and perhaps big returns.

Hochberg: Has anybody studied the consequences?

Malina: Not yet. I say if there’s a problem in youth sport it is the adults it is not the sport. If you let children in sport do it on their own, you have no trouble. Trouble is that sport for youngsters right now is so over organized. And there are at least three or four newspaper articles in the last month about how much parents are investing in their child’s sport to the point some are spending a thousand or two thousand dollars a month. Something is inherently wrong with that. And the expectation for the children is unreal. And to put it in perspective the probability of getting a scholarship in the US (that’s the motivation) – less than 2 percent of high school athletes get a college scholarship, and in US the only full scholarships are for American football and basketball- in basketball both sexes; in football obviously men. Every other scholarship is partial. Give you an example about baseball. Baseball teams in college have 25 players. There are 11 scholarships that are divided among 25 athletes. So the notion of a full scholarship is a pie in the sky; it may or may not exist.

Ritzén: We’re talking about sport and the influence of sport. Has anyone compared the parents of young children being trained pianists? They’re probably training many hours a day, even more than sports. Are they equally hampered by their being away from school work or being away from peers or whatever, training all the time? That comparison might be interesting.
Mark Sperling: There was a study by the author, whose name escapes me right now but will come, who studied the home environments of youngsters who did music. I think also youngsters who became mathematicians and swimmers, and they all had very common environments in terms of the emphasis on training.

Abiola Oduwole: I saw it never in Africa. Our own problem is not the younger ones wanting to be like an adult. But what we have is an older boy wanting to play in the younger age group. Usually when you do the born age, when you look at them physically they actually do look young and they’re not tall. So would you say it could be used vice versa if somebody is not yet mature could he play in a younger age group? If the person is more mature should he play in the older age group; they are being penalized and fined and sometimes jailed for moving through the age groups. And you have some 12 years old who are looking as mature as 16 and yet they’re not being allowed to play and they can’t. And so they play with 12 year old and they override everybody and they’re the best. And yet you have these 17 who is better in that younger age group but not good if you look at it in the older age. So what do we do here. Can we apply that?

Malina: That is a tough call and it’s a good question on Africa because the big issue they have had in soccer is specifically is age verification. I asked a colleague, Tom Riley, about age verification and they say he’s an African 12 which means he could be 13 or 14 because this is part of the problem in parts of Africa.; he indicated that the boy is an African 12 which means he could be 13 or 14; this is part of the problem in parts of Africa.. The youngsters who were very talented in soccer had no birth certificates or verification of their birth dates. And so that was an issue. And that is still an issue for FIFA verifying the ages of some of the players in some tournaments. They know it’s a problem. And youngsters playing up or playing down. And especially in developing countries it’s a different issue. And I don’t know how to control it because in the case of soccer if you are talented they’re going to find you and they’re going to do everything they can to get you into the system whether your age is correct or not correct. FIFA now is using MRI of the distal radius to verify chronological age.
I could give you a 14-year-old boy whose distal radius is fused. He would be eliminated by FIFA even though he is of the right age.

Rogol: On the same point I have a paper here I brought it on purpose. Its title is an essential approach to the age assessment in undocumented minors in conflict with the law (Rev Ital Med Adoles 2016(April); 14(1):5-11. So, exactly the same issue without a birth certificate. And Bob has shown and others have shown that a 12 years old can have a 16-year-old bone age and a 16-year-old can have a 12 year bone age. And remember when we say 12 it’s not 12.00 it’s 12 plus or minus.

Ritzén: At the moment in Sweden we have very current discussion about asylum seekers. If they are below 18 years old, they are treated in a much nicer way and they are allowed to stay in the country etc. If they’re above 18 they are like adults. So that has become a big issue. The legislation has now accepted that there is an error with the current methods to determine the “true” chronological age, using bone age. “dental age” and MRI of the knee. But you have to accept that there are errors when you go by these cutoffs.
Rogol: One other point that I wanted to make about stress that was talked about there are people in the U.S. Army who do what’s called Ranger training, so they jump out of perfectly good airplanes, they’re in swamps, they’re not eating, bullets are going over their heads. And if you evaluate Ranger training: hard training, marching, little for a week or two. Their testosterone levels are very low and their gonadotropins are low as well, so they’re hypogonadotropic. You let them out of that training, feed them and in three days they’re back to normal [J Appl Physiol 2000;88(5):1820–30.].
George Werther: Can I just ask to comment on the role of androgen abuse in this situation. Talk about how it’s a huge advantage for children with early puberty, boys with early puberty. How much of an issue is that say in the in the soccer situation in the UK and elsewhere with people wanting to be elite athletes. How much of an issue is androgen abuse? Obviously, covert androgen abuse in males and possibly even in females.

Malina: I’ve only heard it in the context of track and field athletics with older teenagers. I’ve not heard of it much at the younger ages and I have not heard of it much in soccer. So, it is a potential issue because someone is always looking for an edge.

Oduwole: Are they testing for androgen in the younger age groups?

Malina: I believe they do not.

Oduwole: In Africa, a lot of parents want their child to play football because it’s big money. So I’m sure that they’re attracted to androgens, not necessary the ones that we are familiar with. Student had been given androgen to advance their peak height velocity so that they can start making money.

Rogol: On the same issue, in both Texas and in New Jersey the high school athletic authorities decided to test high school athletes, (American football) and detected vanishingly few, if any. The cost of doing it in America is about $100 for androgens, not for other drugs, but for androgens. They’ve stopped testing and these are people who are really at risk for taking anabolic steroids because they’re in sports in which are either contact sports or even worse, collision sports like ice hockey and football. So it’s been tried. It’s been found to be economically infeasible. Not to say anything about practically infeasible as well.

Wit: You said there’s a big role of adults actually in this whole issue. In Holland, and I think in other countries, over the last two years there was a lot of speaking about sexual abuse and harassment of young athletes actually by the trainers. That has also something to do maybe to pubertal stage of these children and adolescents. Are there some ideas in your field about that issue?
Malina: There’re many ideas because they are in the news on a regular basis. The most recent one in US is a physician at Michigan State who was molesting young female gymnasts who come into his clinic. And I never realized it when I was at Michigan State at the time why he was so seemingly threatened by the fact we were studying youth gymnasts. I guess we were “invading his territory”, and we were doing routine anthropometry and there was another adult in the room with me preferably a young woman too. We were going to measure the young girls. But then I realize in retrospect that he really did not want me there. So, this is a big issue and this “a very private issue”, and it is surfacing more and more in the newspapers. We need to look at these environments. Many accept the medical doctors – people inherently trust medical doctors. And so you’ve got to watch the situation. But it needs to be done.
Ritzén: I would like to make an analogy between pre pubertal children in sport and men and women in sport. I’ve been heavily involved in trying to define the conditions when hyper androgenic women are allowed to compete in the female category. The only difference that we find that defined a wide gap between the two genders is testosterone levels in blood. So, looking at physical characteristics will be very difficult and also intimidating if you have what was called “nude parade” that was used a long time ago. That’s when a number of doctors were checking undressed women if they were female enough. But we found testosterone to be the only simple dividing measure. If proper reference ranges for salivary testosterone in men and women are established, then in future it may not be so difficult to come by. Essays are becoming easier and less expensive. Testosterone is a very important factor when it comes to performance in sport –at least middle distance running.

Hochberg: So what is the bottom line? Is biobanding now the standard for sports for youngsters?

Malina: Good point. No I don’t think biobanding is going to be the answer to everything. It is now very much an experimental stage in the UK. It has not been applied elsewhere that I am aware of yet. It is very much in the news and it’s been well received by a number of academies in England and specifically in soccer. I have not seen or talked about any other sport to date and the whole issue is maturity status. I honestly don not think that most people who work with athletes they see it every day but they don’t know what to do about it.
And many of them accept that as the nature of sport. As I said at the expense of repetition. Sport is ruthlessly selective. This this is going to go on and in all sports. Many start, but very few make it to the top.
And when you study the elite athlete keep in mind yes you’re studying a very select sample. You’re missing out on everybody who dropped out along the way. We also need to study the dropouts because they can tell us a lot, but we do not study them. We are interested in the successful ones. And that is a big part of the issue. And then another thing in sport is that many people looking for the magic bullet-what is going to give me the answer. One examination is not going to tell you anything. You need to follow the youngsters over time. And this is typically not done. So it is multifaceted.
To get back to the question of age verification. Those of you who work with skeletal age are aware of Tanner Whitehouse (TW) 2 or 3. TW3 skeletal ages are systematically younger by about a year or more beginning about 10 years in boys. So if I have an early maturing boy with TW2, he may be average with TW3. What does that have to do the training? The differences are systematic. But have has not received that much attention, yet.

Ivo Arnhold: So, we have heard that sport is very selective and that too much sports is prejudicial to your health. So, what would be the flags? or what should we do if we want the parents and society to know if their children are doing enough sport that is good for their health, but not too much? that may be different from one boy to the other. What measures could we look for in terms of ensuring this?

Malina: I personally think is the question you raise very important but more for the general population. We confuse sport with physical activity. They are not equal. Sport is one form of physical activity and most children do not get enough activity. That’s where I think our focus should be. But then you have a very small percentage who are the elite athletes who are getting a lot of activity in perhaps a highly stressful context. And that is a very special group to study. So it is a two edged sword. They are almost at the one extreme and so on, and you just got to be very careful with them, and there is no simple answer. But we cannot go from the athlete to the general population because the athletes are off the curve. And often we make that mistake and in public. Now of course your good athletes are at so many different levels. If you go to local high schools here, you have many athletes but you are lucky maybe one will get out of there to the next level. So this is part of the issue with the generalization across sport, and in news media they generalize. This is potentially misleading. So you have got to be very careful with that and hopefully translate for the public.

Wit: We have not spoken yet about that question. That’s also an important issue in the young athletes. So, are there other elements in the diets that can increase muscular power, like extra proteins or proteins from various products that have a positive influence on either one. So is there any relationship there?

Malina: I’m not a nutritionist. I do not know for sure. But for most young kids who train in sport, at least in the U.S., their diets are fairly adequate. If you’re training in sport academies, your diet is monitored for you.
But, this is just part of the issue. Keep in mind eating is a social behavior influenced by many other things. We eat foods we do not eat nutrients. And many people miss that point that our elite athletes are monitored fairly regularly, at least at the University level; everything is regulated. At the high school level they are eating at home unless they attend a special academy or special swim clubs in U.S. or gymnastics academies. The IMG Academy in Florida, is a big business now. It is basically a school for athletes, and they live there. That is where many elite tennis players went to school, but for the general athlete I do not think we have such control over their diets because they are eating at home. And that is an altogether different environment. If you’re in a club, you perhaps are monitored; at home, forget it. You’re eating what your family eats and that is 99 percent, if not more of the youngsters who do sports.

Wit: And they don’t take extra nutrients like amino acid, vitamins or that kind of stuff? I had the impression that a lot of athletes believe actually in the role of vitamins etc. It’s not really sure that that has any effect.

Ritzén: I think the parents believe it. It is time to try to summarize:
We covered a few aspects on sports and maturation. One is the safety issue. Is it safe for children to do a lot of endurance training? George Chrousos pointed out that inflammatory markers are very high in athletes that practice that kind of training, and we should be aware of that. Psychological effects: Ze’ev pointed out that a lot of time spent on sports takes the same amount of time away from other activities. Is that good for the kid? Or not? I haven’t really been convinced that there are obvious negative health effects except for the rise in inflammatory markers in hard intensive training.
Then we brought up a different question, trying to create a level playing field for those competing with each other. Looking at the year of birth is not very good. Definitely bad, especially at the ages of 12 to 15 or so, when some have entered puberty and some have not.
Biobanding has been one such attempt to create such level playing field. The variation is very large and is not a very sharp a scientific instrument. If you really want to assess one factor that has proven to be important for performance, I would come back to testosterone, and may be measuring testosterone in saliva is acceptable to the child. The major drawback is the practical management and the assays that at present are rather expensive. Maybe for a selected group of people and maybe in future that might be one way of creating a level playing field for those that compete with each other. In order to give those born in December an equal opportunity to those born in January.

Malina: I just read a paper the other day, reporting Fels’ skeletal ages on soccer players from an English academy and from Aspire in Qatar. The paper –stated that skeletal age overrules the relative age effect. Relative age effect means month of birth – those born in the first three months. Once you adjust the relative age for skeletal age variation, skeletal age rules.

Ritzén: That’s not very surprising. The bad thing is about X-ray. It will not be accepted by society to take X-rays of children in order to do sports. So, I think we have to leave many good methods for assessing maturity trying to get something that is acceptable for society and acceptable for the child and acceptable for the competitors.

COMMENTS TO THIS CONVERSATION ARE TO BE MAILED TO MARTIN RITZEN Martin.Ritzen@ki.se

A live conversation between Jan-Maarten Wit (Leiden), Andrea Merker (Stockholm ) and Robert M Malina (Austin), moderated by Ivo Arnhold (Sao Paulo, Brazil)
Contributors: Abiola Oduwole, Ze’ev Hochberg, Mark Sperling, Martin Ritzen, Alexander Jorge
Transcribed from the live conversation by Uri Klempner

Ivo Arnhold: We start with 1) the theoretical considerations on girls and boys growth references versus standards by Robert Malina, followed by 2) WHO growth standards by Andrea Merker, followed by 3) theoretical reasons why at least at the present time the global standard is not likely to represent all healthy people on the globe by Jan-Maarten Wit, followed by 4) the pros and cons of using WHO standards in countries that have their own national growth references and brought by Andrea Merker as pro and Jan-Maarten as con, and then 5) the pros and cons of using WHO standards in countries that do not have their own national growth references by Bob Malina as pro and Jan-Maarten against. We want to make sure that that at the end we have enough time for the general discussion and suggestions for future communication between scientists and the lay public on this topic. So to start I will pass it on to Bob.

1) Theoretical considerations on girl´s and boy´s growth references versus standards

Robert Malina: I’ll talk a little bit from experience because back in the late 60s early 70s I trained the technicians for several of the American health surveys. I did the anthropometry field training for them and so on. And these in many ways were the precursors for the US growth charts first in the late 70s, the first version by Peter Hamill et al. in 1977 (Vital Health Stat 11.1977;(165)i-iv, 1-74) and then a 2000 version (Kuczmarski et al, Vital Health Stat 11.2002;(246):1-190.). In the context of growth charts, the charts are a reference for comparison.
Very often people talk about growth standards. The word standard is a problem because a standard implies this is what you should strive for. It is a value judgment. What is the standard? What’s the standard of beauty? and so on. So to me, growth charts are a point of comparison, and any time you come to the perspective of a point of comparison it is a choice. Why am I comparing? Am I comparing a single child? Or am I comparing a sample of children? and so on.
This is part of the issue and in the development of the US charts; by way of background they are based on five or six consecutive surveys and there was no secular change across those surveys in the US. The samples initially were selected to represent the American White and American Black population and then eventually they oversampled Blacks, and then Hispanics to fill out the Hispanic part of the American population (the Hispanic Health Survey). And so the unique feature of the U.S. reference data is that it is based on an ethnically heterogeneous group, which is probably suitable for the U.S. population, seeing as evidence for genotypic differences in height are not that marked among the different ethnic groups. One advantage of the U.S. reference values is they are based on adequate sample sizes; you are talking five or six hundred children per age group in each sex. It is thus a good probability that the 95th and the 97th percentiles are real children. On the flip side, if you have proportionally small sample sizes, the upper percentiles are projections which may or may not be real. So that is a unique thing for the U.S. dataset. And of course it is also a heterogeneous population and so on.
But what many people do not realize about the American growth charts: the situation for body weight is altogether different. In the last survey before 2000, this was perhaps the beginning of the obesity overweight epidemic in the US. So when they updated the US reference charts in 2000, they did not use the body weights of the last survey. Why? They made a public health decision that this (i.e., increase in body weight relative to height) was not healthy; unfortunately, many people have not read the background of the US charts, which is often overlooked in discussions of the US growth charts. The WHO charts are a little bit different because part of the charts are based on the original 1977 US charts.
Of course, growth charts are based on cross-sectional data. It is a cross-section of the population. Now, growth charts based on longitudinal data for individual youngsters are altogether different. Many of you use Tanner’s modifications of the American charts (Tanner and Daviers, J Pediatr 1985;107:317-29). The charts were based on the Harpenden data (UK) shifted to the left for early maturation to accommodate US children and youth. It shows basically the British data shifted to the left to adjust for potential population differences in maturation. And of course, any time you use a growth chart during adolescence somehow or other you must consider inter-individual differences in pubertal timing and the growth spurt. You are more aware of that than I, because you work with individual cases. I am working with samples, which is a very different perspective.
Another concern is placing growth charts in the context of secular change, the tendency for larger size and early maturation. In the U.S., we have had no secular change in height, on average, through the 2006 and 2008 surveys. Medians are pretty much superimposable over time; the differences are relatively small for height. Weight is a different story. I am focusing largely on height because it is what most of us work with.
Secular changes of course begin in childhood; they are not just limited to adolescence. This is relevant to the most recent version of Tanner-Whitehouse 3 skeletal age protocol (TW3 SAs). The rationale for changing the protocol was to accommodate secular trends to larger size and earlier maturation. Yet, the secular change in maturation in TW3 SA is only apparent in adolescence not before. But, data from Belgium and also the Netherlands suggested a secular increase in height but no change in the timing of puberty and the growth spurt (see Malina et al., Sports Med. 2017 Nov 21. doi: 10.1007/s40279-017-0827-7). Moreover, in many places the trend has largely stopped. Japan is a good example and for many years. The US is the same. So, as far as I can see, secular changes are real and are taking place in many populations, but in the traditional populations considered (largely populations of European ancestry), the secular trends have slowed considerably or stopped. So, with this, I will stop.

Jan-Maarten Wit: With regard to the situation in US where you have no secular change: is this because of the influx of other ethnicities? If that is so, I would expect a larger standard deviation over time. So, have you seen a larger SD in the last 50-60 years in the U.S?

Malina: Standard deviations or the percentiles in different surveys pretty much overlap consistently. And of course, most of these were done prior to the big influx, because the most recent influx occurred around 2000 and thereafter. We are a nation of immigrants so keep in mind this is always a potential confounder. On the other hand, it is an indicator of real human variability. So in many ways the percentiles of the U.S. charts I think can accommodate a good deal of it. We are going to miss a few but that is to be expected.

Ze’ev Hochberg: In a recent report on the secular trend, in 1896 Americans were the among the tallest in the world, whereas in 1996 they were around number 50, mostly due to the minimal secular trend among Americans (Elife 2016;5:e1341).

2) WHO growth standards

Andrea Merker: I am a Ph.D. student from Karolinska Institutet in Stockholm. My Ph.D. project focuses on growth curves and growth in extreme short stature.
To give a short background on the WHO curves, this project started in the 1990s. A group of experts considered that the growth pattern of healthy breast-fed children was significantly different from the NCHS growth reference from the 1970s. This expert group concluded that growth during infancy and early childhood ages is globally quite similar, and that growth during these ages is driven by the environment including nutrition.
This was the starting point and most probably also a reason for why the WHO multinational growth reference study (MGRS) focuses on ages 0 to 5 years. The aim was thus to produce a global “standard”, i.e. a reference showing normative growth irrespective of background population. Another motive for developing a growth standard might have been merely political, meaning to promote breast feeding as growth of the breast-fed child should be the biological norm.
Also, I think we have to distinguish between the (so-called) standard for 0 to 5 years on one hand and a reference for 5 to 19 years on the other hand. Only the first part of the charts, meaning ages 0 to 5 years, is a product of a prospective multinational study, based on 8500 children from Brazil, Ghana, India, Norway, Oman and the US, with a longitudinal part 0 to 2 years and cross-sectional data covering ages 2 to 5 years. The second part is based on the data from the (US) NCHS77 reference, as Bob has already mentioned. The NCHS77 growth reference is based on US data from the 60´s and 70´s. The full NCHS77 reference was previously used as the official WHO growth curve. A smooth connection between the standard and reference part was created by mixing data points from both data sets during overlapping ages.
Regarding weight for age, the WHO presents data only up to 10 years of age and recommends following BMI for ages thereafter.
The WHO standard has, according to WHO, been endorsed by more than 140 countries; often by national breast-feeding centers but also by the International Pediatric Association and the International Union of Nutritional Science. To what extent the WHO charts are used in these countries is uncertain. In the US, for example, the WHO curves are recommended only between 0 and 2 years of age, for older ages CDC2000 growth reference are recommended. In UK, the WHO charts are recommended between 2 weeks of age and 4 years followed by the UK90 growth reference. In Canada, the WHO charts are recommended between 0 and 19 years.
So then of course we can discuss differences between references. Studies have shown that about 60 percent of children in Bangladesh aged 0 to 5 years have a height below minus 2 standard deviations of the WHO standard. Dutch children, on the other hand, are at five years about 0.7 standard deviations taller. And I think that at adult height Dutch people are at least one standard deviation taller.
There are always differences in methods between references including how the data was collected, inclusion criteria, and data presentation (e.g. SD or centiles), data exclusion rules or smoothing techniques. One should also discuss what differences are clinically meaningful although data might be statistically different.
Lastly, it can sometimes be difficult to compare differences due to differences in growth tempo.

Wit: The difference between the Dutch nation-wide reference and the WHO charts is even more than 0.7 SD: young adults are on average 8 centimeters taller than the mean adult height derived from WHO charts.

Merker: A systematic review (Natale & Rajagopalan, BMJ Open. 2014;4:e003735) comparing the means of the WHO child growth study to other studies with similar methodological background showed generally small, maybe negligible, differences for height. Weight varied more than height. Development of head circumference showed most differences.

3) Theoretical reasons why at least at the present time the global standard is not likely to represent all healthy people on the globe

Wit: I will talk about some theoretical arguments. I believe that WHO is actually not suitable for the whole world. The dogma of WHO preparation is that the actual environment at present is the only factor important for stature. And that ethnicity, DNA difference and so on do not play any role at all. This has been the dogma also in their papers. I would like to challenge this dogma.
It’s also worthwhile to mention before that there are also bio-statisticians who say that there was some selection bias in the WHO study, because if breast feeding was not continued long enough, the babies were excluded from the study. The children who were tallest stayed in the study longer than the ones who were in the lower half of the population. So you have already a sort of selection there and that has been demonstrated by the Dutch statistician Stef van Buuren (Nestle Nutr Workshop Ser Pediatr Program. 2010;65:167, Discussion 175).
Now, about the four arguments that I would like to propose that are speaking against the WHO dogma. In the first place, if you look at data of heights in the whole world, the difference between the shortest countries or ethnicities and tallest ones is about 20 centimeters. So that’s the whole range. It is about three standard deviations, if you think in terms of adult height. But 20 cm is the real measured difference actually between two countries. That’s a lot. That’s of course the starting point.
What about the secular change? The whole concept of secular change is not mentioned in any of the WHO papers. They do as if it doesn’t exist. Now, it is certain that there is a secular change. I think everybody here in this room knows that. There is more secular change in the high income countries than in the low income countries. In many countries, like indeed in the US, there is no or hardly any secular change. As far as I know the US is the only high income country where there is no secular change. Most other high income countries still show a secular change, although in some (like Sweden and the Netherlands) height appears to have reached the maximum for the given genetic background. In some low income countries a secular change is seen over the last decades, but not in all. Secular change is probably not only positive. If one looks back at long term history there is a sort of wave that can go up and down. In European countries the change has been positive in the last 150 years, but before that time it has not always been positive.

Hochberg: In the comparison of 1896 to 1996, the secular trend was negative in some countries in Africa.

Wit: Is it? In the paper that I saw, secular change in African countries was actually not negative and not positive. Mean height has remained stable over time. Of course one has to look at the quality of the data in the studies, because it’s fairly difficult to do a good study in such countries. The methodology is often of unknown quality.
So what about secular change? How fast is it? In general, the secular change is very slow. Even in high income countries it is about 1.2 cm per decade. That is not much. So if you look at the initial difference between the countries of 20 cm, it will take multiple generations for a country that is at the low side in this distribution to get close to the average of all countries. Secular change is not only very slow, but it is also not continuing forever. In Sweden, I think in the 1980s the secular change has stopped. In the Netherlands it stopped in 2000. Average height in the 4th nation-wide growth study in 1997 and the 5th growth study in 2010 are completely equal (Schonbeck et al, Pediatr Res. 2013;73:371). So we believe at the present time that the secular change in Holland has now stopped, maybe because we have reached our optimum for our DNA. But there are also people who think that there are negative environmental changes, for example that people do not drink enough milk anymore.
What would the secular change be if a low- or middle income country would be able to rapidly guarantee optimal living conditions, including optimal food? Could one expect that in 2030, as is the aim of WHO, stunting would be out of the world? How would it ever be possible, even if there would be an optimal secular change, to have that aim actually accomplished? So this is the first thing about secular change that I would like to mention.
The other thing is that secular change is something that happens in the whole population. So also the healthy well-fed rich children in the 1850s were short. Actually the healthy well-fed German children in a Hamburg school in that time in 1860 were as short as healthy well-fed Indonesian boys at the present time (Hermanussen and Wit, Horm Res Paediatr. 2017;88:38). So the position of the whole distribution was changed. So, apparently it’s not the actual feeding pattern of a person, but there’s something changing very slowly about the whole distribution of a population.
It is also interesting that the secular change does not respond very quickly to circumstances. You have the example of the last World War: German males who were born in 1920-1925 had some hold up of the secular change but very short and only neutral. It was not going down, it just stabilized, and then it went off again in the later birth cohorts. And we saw the same thing in Japanese students. So there is some effect of the environment on the secular change, but it’s actually small and only temporary.
There is the assumption that it is more the social economic conditions that have to do with the secular change. However, there may be other factors. A recent study showed that tall men had a relatively high number of children. So, this may suggest that secular trend may be associated with selection for gene variants that are associated with tall stature. However, my colleague Michael Hermanussen commented that this could be an exception, because normally people who have more money have less children than people who have low income.
I still think that there might also be genetic differences. As I mentioned, WHO said that doesn’t play any role, and that it’s only the environment. But there are some indirect data that genetic differences exist. It would be strange if with more than 400 genes that are associated with height, ethnicities would not differ in the distribution of height-associated gene variants, while there are so many other physical characteristics that differ between ethnicities.
For example, South Asian children living in the Netherlands for more than two generations are still much shorter than the ethnic Dutch, while they have excellent economic conditions. So it appears likely that the difference in height is not related to the environment or the food they eat; it’s more likely that there are genetic differences associated with body stature between children of South Asian and northern European origin. In line with this argument, in England and in the Netherlands babies of South Asian origin are about 400 g lighter than the average of all other ethnicities. So the growth pattern seems to be rather special in South Asian children, which has probably little to do with the environment. (Visser et al, Early Hum Dev 2009;85:737).
Besides differences in stature, there are also differences in body shape. Japanese boys are almost at WHO level half way through adolescence, but they mature earlier and their adult height is about 5-6 cm shorter than WHO. Although they have already had a very long period of positive secular change (that has now almost stopped actually), they are still shorter than WHO in adult height. So that is also in my opinion an indication that there are genetic differences that have something to do with height. So the idea of WHO that only the current environment is the determining factor of body stature is incorrect, in my opinion.

4) Pros and cons of using WHO standards in countries that have their own national growth references

Pros
Merker: So, about the pros of the WHO curve. We decided to differentiate between countries that have a long-standing growth charts’ tradition like in the Netherlands and other Northern European countries, and countries that don’t have own national curves. In Sweden, for instance, we have a long tradition of our own growth curves with a special curve layout.
First, I’d like to highlight that the WHO growth standard is an extensive work using a very sound method. And yes, a lot of children have not been included in the data analysis because the mothers did not comply with e.g. the breast feeding or non-smoking criteria. For the longitudinal part (0-2 years), data from only 13% of the recruited children was used for the reference construction. And for the cross-sectional part it was only 31% of the data. Also, extreme data were excluded by removing the upper 3% from the cross-sectional sample before the final curves were modeled. But still I think it has been an extensive and well-structured work, and that these curves serve as a good “matrix” for following an individual’s growth as well as for comparing different populations towards a fixed standard.
Secondly, we should have in mind what are the curves used for. Are they for clinical use and for following an individual child? Or are they used for public health services or epidemiological surveys with the intention to compare populations for instance. I think if we would like to compare populations with each other, then the WHO curve is a very good benchmark. If 60% of children in Bangladesh grow below -2 SDS, this also gives a picture of growth and health in Bangladesh compared to other countries in the world, and might suggest that public health initiatives are still needed.
Also, with the WHO standard tables and charts that are published one can easily calculate standard deviation scores. One can easily express and illustrate the growth pattern of a certain child, which makes it easier to discuss the growth pattern of an individual with any colleague around the world.
For clinical practice, the child’s growth pattern in relation to the growth pattern in the family might be more important than the absolute position in any growth chart or a potential position above or below a certain cut-off line. In that sense, any growth curve might be seen as a “matrix” for following the individual’s growth. It might therefore be an advantage to stay with a single matrix, for example the WHO matrix, instead of shifting between different references.
In short, I think that the WHO growth standard/ reference is quite good for comparison purposes and for research.

Cons
Wit: I would like to focus on the situation of the countries where height is considerably taller than the WHO standard. I am speaking about the Netherlands, Denmark, Sweden, Norway, Germany, etc. Adult height in the Netherlands is 8 cm taller the WHO standard, and young adults in Germany and the Nordic countries are probably 6 cm taller. I also focus on the clinical use of the charts. If one would use WHO standards instead of the national reference diagrams, one would lose sensitivity to pick up short stature syndromes. This has been documented for Turner’s syndrome quite nicely in Norway and Finland. In the Finnish study, by the age of 2 years 72% of girls with Turner syndrome have height measurement below the 3rd percentile using national reference charts, in contrast to only 36% using the WHO standard (Saari et al, JAMA Pediatr. 2013;167:194). At the opposite part of the spectrum, if for a tall child one would use the WHO standard instead of national reference charts the specificity would be lower to pick up pathological causes of tall stature. For North-European countries, it would be unwise to use the WHO standard. Just because clinicians would like to use growth charts in the clinic and pick up pathology.

Abiola Oduwole: We’ve also been worried because we’ve found out that the WHO chart is good for us. Using the WHO chart it is now obvious that stunting is not as common as previously observed. Environment do affect growth, as studies comparing rural/urban or high and low social class show more stunting in the rural and lower social economic class. In fact, children from the upper economic class as shown by our studies have similar curves with CDC chart. This has also been observed as previously stated in the US. Despite these observations we’re worried that we need to have a growth chart specifically for ourselves, that we may be missing out short stature, tall stature children just because we’re using the standard. We are now using our own standard in the clinic so to pick up those kind of children. The chart needs a review and more participants and should be longitudinal to pick out secular trend and influence of the environment and culture. Nigeria also has one of the highest prevalences of children with heamoglobinopathy. Most of these children are classified as stunted or short stature. Developing a growth chart just as it was done for Turner syndrome and Downs Syndrome may be worthwhile. So, I agree that each country should actually have their own growth charts, which they could use for their own citizens. Then, maybe the WHO charts should be for comparing countries; that is OK, but to observe the children of a country, to be fair and not miss out the two extremes, personalized growth is advocated.

5) Pros and cons of using WHO standards in countries that do not have their own national growth references

Pros
Malina: I will speak largely in the context of Mexico. I began working in Mexico in 1968 studying indigenous children in the south of Mexico Oaxaca, which felt the last earthquake severely. And I worked there most of the 70s and I was back in the field in 2000 and was back just a few years ago. But I will share with you data from one community that I studied in 1968, 1978, and again in 2000. And these are schoolchildren of 6 to 17. I chose to use the NCHS (the U.S. reference) as my point of comparison.

I will use the boys 6-11 years as an example. The data are age adjusted. In ‘68 and ‘78 their heights were well below the fifth percentile of the US reference. For example, the average for boys in ‘68 was 117 cm, and in ‘78 it was 117.5 cm; the U.S. fifth percentile is 123.8 cm. This gives you some idea how short they were. But their body weights were at the U.S. fifth percentile – 21.3 kg in ’68 and 22.2 kg in ’78; the U.S. fifth percentile was 22.7 kg. As a result, the BMI in 1968 was at the U.S. 25th percentile. And in 2000, it was at the U.S. median. The same trend was apparent in girls and for adolescents. So, I am working with a very short population that has weights that are almost too much for their heights; this is characteristic of indigenous children and of indigenous populations in Mexico, especially in the south. The state of Oaxaca has 16 different indigenous (linguistic) groups.

And historically in Mexico, the heights of indigenous adults decrease from north to south. This was first shown in the 1890s, and has been subsequently replicated. It is still true of contemporary indigenous children. Using data from a special school program for indigenous children in 2012, those in the north of Mexico are the tallest; heights decrease somewhat into the central part of the country, but once you get to the south and south-southeast (Yucatan peninsula) they are, on average, the shortest. Mexico has no growth charts. They have one but it is based on the work of Ramos Galvan which is based on children from his private practice in Mexico City and do not apply to indigenous children.

I want to raise the question regarding the overweight issue. What do population differences have to do with the definition of overweight? In the group that I work with, they also have proportionately short legs. And what is the impact of proportionally short legs (or a longer trunk) and short stature on the significance or meaning of the BMI? I do not know the answer but that is something we need to consider.

Oduwole: Could that be genetic?

Malina: I would say probably a combination. I give you a case in point in this single village. The youngsters made a significant gain in height from ‘78 to 2000; 6 cm gained over 20 years. But what happened in the village at that time? Well in the mid-80s, the village went through the epidemiological transition, meaning preschool mortality was finally lower than adult mortality. So something happened in their lives. All these youngsters were born after the epidemiological transition. So conditions are improving. What they are specifically? We can hypothesize diet, they now have a doctor coming to the community every day, and have a nurse there seven days a week. So things are changing but ever so slowly; it is going to take another generation. Hopefully, I will be around to do another follow up!

Wit: 6 cm in 20 years; that’s not so slow.

Malina: No. That is major, it is a major gain, and in the younger children it is mostly in the legs, in the adolescent boys just the legs, and in girls it is still ambivalent. So there may be a sex difference. I do not know the answer but I am just telling you what I see in the field and in the data. There is a slight secular change in adult height. But that began probably among those born in the 50s and 60s. So it is changing but we do not know the answer.

Mark Sperling: So, you chose South Mexico with an indigenous population which would be different from Mexico City with its Spanish and French and now other European admixture. But all over the world now my impression is there’s a lot more admixture of genes with population shifts than there was even 50 years ago. And even in Eastern European countries, which I just visited recently, I see faces that are clearly Middle Eastern or African that I’m sure didn’t exist until the 80s 90s maybe 2000. And so, has there been a change in the admixture of the genes that you know in Oaxaca rather than just environment? Jan-Maarten said that WHO claims it is environment rather than a change in the genetic admixture.

Hochberg: On a similar topic with regard to national growth charts: countries don’t have really any biological significance. A country is a political entity, and the fact that we group its children together into a reference doesn’t mean much. I was convinced by Jan-Maarten today that for countries like northern Europe or the Scandinavians it makes sense to use the country specific nation reference. But this is a small enclave with regard to the rest of the world. If you think about the boy in Bangladesh who is growing very steadily on the 25th percentile of his national reference. I don’t know if they have a reference for growth. He’s stunted, this boy. So the information of stunting of that boy who apparently grows normally would be missed if they use a national reference.
Using the standard makes a lot of sense to me, and I actually like it the way that WHO has done it. It’s OK to exclude the Netherlands and Sweden but for the rest of the world, it makes a lot of sense to me.
I think that the fact that WHO strives to eliminate stunting by 2030 – we don’t need to hold our breath to 2030. It’s OK if it takes another generation or two. And here you tell us about 6 cm in a period of 20 years. I am impressed.
In the study of Barry Bogin of Maya children who moved to America, they show that within a single generation the Maya children grew as well as American children. So this is not genes admixture. This is rather the environment that is changing. It was just mentioned here that leg length grew more than anything else. The same Bogin advocates for many years now that the leg length is a better measure for the effect of stunting by the environment. When you see change in leg length, this is the effect of the environment.

Malina: I will just comment about the admixture question. The issue in most Indigenous communities is not admixture, it is out-migration. Something is missing here. This is apparent in the work of Barry Bogin dealing with Guatemalan children of Mayan ancestry in Florida and in Guatemala. They are getting progressively taller, and the gain was in leg length. My Oaxaca children are midway between the Mayans in Guatemala and in the U.S. There is a community in New Jersey that I recently heard of that is populated largely by people from Oaxaca, specifically from the community I have worked in. The difficulty right now is that they do not identify themselves given to the idiot we have in the white house. We have to be very careful; it’s a very sensitive issue. They are interested but to identify them, will create political problems for them.

Sperling: I think these are all valid points, what’s happening in Holland, or the populations you described. I now live in New York so I’m amazed at the tall Chinese that I see; they appear to be really quite tall, based perhaps on my bias, evolutionary bias. But I do think that we have an opportunity in today’s world to try and distinguish genetics, which is clearly an important factor, from environment. And you have these populations, large segments of population, that have moved to cities like New York or Antwerp or Mexico City that would give an opportunity to look at the difference between environment versus genetics. And that doesn’t apply to the child who is growing up in Bangladesh, because there, that genetic admixture does not exist. It’s primarily environmental.

Malina: We have data to some extent on that issue. In Mexico you have what they call Colonias where largely poor people live; the children from Colonias in Oaxaca are the exact same size as children in Colonias in Mexico City.

Your comment about the Chinese, I am assuming you mean the Han Chinese. I am not aware of studies of indigenous children of different ethnic groups in China. There are a lot more interesting groups in China that need to be studied.

Cons
Wit: Let me first start with the arguments against the use of the WHO charts in low-and middle income countries. Last year Michael Hermanussen and I were asked to advise the Indonesian Pediatric Association in the debate that was going on in that society to continue using WHO standards or to develop their own national reference charts. The clinical pediatricians had observed that a high percentage of healthy well-fed Indonesian children are way below the 3rd percentile of the WHO standard, and thus would be considered stunted. This was confirmed by an Indonesian study that was done on multiple islands published by Batubara et al, and it was again confirmed by nationwide data. At 18 years, height in males and females was approximately 12 cm and 9 cm shorter than WHO standards, respectively. The form of the 50th percentile stature in males suggests that adult height maybe a few centimeters taller than the mean stature at 18 years, so there’s a sort of delayed puberty also there. So that difference with WHO charts for adult height might be a little less than it looks now. I think the main problem caused by using WHO standards is that completely healthy well-fed children in such country are called stunted. This is also a problem at the clinical level, in determining which child needs to be further investigated for short stature. If one would perform a diagnostic work-up for every child with a height <-2 SDS for the WHO standard chart, the diagnostic yield would be low.
It's also a problem at the policy level. I mentioned that WHO has set targets that before 2030 the frequency of stunting should be brought down to normal. There is a difference between the slow pace of secular trend in a country with an increasing standard of living and the fast increase in height observed in children who move from one country to another, for example to the US. Such fast change was also seen after the Wall fell in Germany; the Eastern German kids were much shorter when the Wall fell, but they showed an enormous increase in height for about five years until they were equally tall as West-German children. East-German children were in a good nutritional state, so there are apparently other factors that have an effect on growth.
It has also been shown that food supplementation programs aiming at diminishing the incidence of stunting have no or only very little effect on body stature.
So I think that if WHO standards are used for assessing pathological stunting in many low and mid-income countries, this would lead to a waste of resources. It would aim at the wrong targets. The aim should be to improve the socio-economic conditions in which children live, social justice, hygiene, nutrition, education, etc. Furthermore, we need significantly more research to better understand the reasons for these differences in heights.
Not only in Indonesia, but also in most other South Asian children height is considerably below the WHO standard. Even in social strata that are well nourished, wealthy, healthy and well educated. Using standards that are too high for the well-fed local population does not only lead to overestimation of stunting, thus loss of specificity, but also low sensitivity for detecting pathological causes of tall stature.
I'd like to add that we did also a study on the children of Moroccan and Turkish origin in the Netherlands. In 1997 there was still a 5 cm difference in children and 10 cm in adult height between children of Moroccan and Turkish origin and the individuals of Dutch origin. Thirteen years later these minority groups had accomplished a large secular change of about 3 cm, while the height of children of Dutch origin had stabilized (Schonbeck et al, PLoS One. 2015;10:e0124686). So, one can predict that in another 10, 15 or maybe 25 years, individuals belonging to these minority groups may have a similar height.
With regard to the comment of Bob Malina, I can confirm that indeed short legs have an influence on BMI. When an individual has short legs, there is relatively more trunk. The trunk represents more weight than legs, so BMI is higher in an individual with relatively short legs.

Malina: Have you followed the data from the INCAP (Institute of Nutrition of Central America and Panama) supplementation study in Guatemala? The program lasted for 5 or 6 years. I believe the evidence is suggesting that the youngsters who were on supplementation beginning in the late 60s were as young adults taller than their parents. And the children born to those who were supplemented up to age 3 are taller than those before. So there simply may be a generational effect on the effects of the INCAP supplementation program. That is a study that should be considered in this context.

General discussion
Arnhold: I would like to ask Andrea to add information on the Colombian experience. There the WHO’s standard is used, but still Colombians are considering to change to their own reference charts, apparently. Can you comment on advantages and the reasons?

Merker: Yes, I’m working together with pediatric endocrinologists from Colombia on constructing national curves for Colombia. This project was initiated quite long time ago. Meanwhile, the WHO came also to Colombia with their trucks to roll out its standard while heavily marketing them.
In this Colombian growth project, I’m responsible for the data analysis and the clinicians have asked me for arguments against the WHO charts. They also wondered what curves to use. I think that an advantage of our Colombian curves is that they include also body proportions (sitting height and leg length) and waist circumference references. These are an important complement to any clinical evaluation. For instance, when one is screening for Turner syndrome, a typical increased sitting height relative to total height can easily be appreciated.
For Colombia, we have been saying that it’s of utmost importance to follow the child´s growth, not just having one measurement that should decide whether the child is sick or not.
Another comment regarding weight, the official WHO curves only cover 0 to 10 years. A Canadian group of pediatric endocrinologists have subsequently modeled weight all through 19 years of age (Rodd, Metzger and Sharma, the Canadian Pediatric Endocrine Group (CPEG) Working Committee for National Growth Charts, BMC Pediatr. 2014;14:32). So this extension should of course be implemented in those countries that use the WHO charts.
Also, can I comment on the construction of own (national, regional or ethnic specific) curves? Some people want “own curves”, but constructing representative references or curves takes resources. It takes for instance resources to get a sample that is representative or big enough to construct references. And a sufficient sample size is needed to get reliable cut-off levels and outer lines beyond 2 standard deviations. Creating national growth charts demands money and other resources that some countries might instead wish to invest in other health care programs.

Oduwole: We, the pediatric endocrinologists in Nigeria, have a group chat. What we found is that those who are in private schools had growth curves that are similar to the American growth chart. And those who were in public school had growth curves that was quite similar to the WHO. So I think it depends on nutrition. Accessibility to good health programs has a lot of influence on growth. Because those that are in private schools have access to hospitals, access to good food, access to supplements, whereas those in public schools don’t have half of that. So obviously the ones who are in the private school with a lot of things which kids in the American school do have, are similar in growth. Whereas those who don’t have, they’re more likely to have an issue; we have a lot of stunted children there, whereas 30% of those in private schools are obese and overweight. So it depends. I agree with you. Something is going on.

Wit: I think it’s very important to look at the various parts of the world. I think in Africa probably WHO charts are okay. From the data I have seen I have the impression that the South Asian children will probably need many decades to come close to the WHO standard. I saw data from Pakistan, also from private schools, on well fed children, whose height was far below the WHO standard, similarly to the situation in Indonesia. So it is dependent on the area, I think.

Alexander Jorge: For the first 5 years of life, where the genetic influence is lower, an international growth curve should be appropriate to assess growth and to identify children that are malnourished or in a stressful environment. After the second to the fifth year of life the genetic influence starts to increase and then one may have two different sorts of populations. First, in populations in genetic isolation a national growth chart is very important, as well in populations that are considerably taller, possibly due to improvement in nutrition in subsequent generations. In contrast, populations like Brazil have a huge admixture, so that it’s really difficult to construct a growth reference curve that is specific for our country. It changes every day because we have different population every day in our country.
With regard to sitting height, there are of course some conditions with an increased sitting height/height ratio, like SHOX haploinsufficiency. But I saw a lot of adult patients in whom their sitting height increased only because they gained weight, while their height did not change. I think it’s impossible to give a general rule to use a universal growth standard or a national reference. It depends on the age of children that we are analyzing as well as the changing population. Like in Holland, the Turkish and Moroccan individuals start admixture with locals, which changes the picture completely. What growth chart do we need for mixed ethnicity children?

Malina: You raise very good points. It goes back to what question you are asking. Are you just surveying a population? Any survey is relative. For Brazil, I just read a paper where they have new growth charts based on predicted time before peak height velocity (just published in Nutrition and Metabolism). If you are four years before peak height velocity here’s your chart. Unreal. However, the equations to predict time before peak height velocity were developed on youth of European ancestry and also have major limitations.

Martin Ritzén: I agree with Jan Maarten that the WHO figures have underestimated the genetic influence. It’s a mixture of populations from different parts of the world with different backgrounds and different growth potential and whatever. But when we sit with a patient with short stature, we look at the parents, that’s the first question. How tall are the parents, how tall are siblings? And we make a family tree with heights. So it’s obvious to all of us that genetic influence is very important. So I wonder if the WHO charts were constructed for a political purpose in order to even out all differences.

Malina: I sent you that 1974 paper by Jean Pierre Habicht et al. (The Lancet 303,611-615). When I was at INCAP we compared upper and lower class children from birth to 7 years from several parts of the world. There were no differences among the upper class children. The major difference was between social classes. When that paper came out, Jim Tanner criticized that paper because we were saying if the children’s environment is healthy then the growth of the children is pretty uniform. We caught a lot of flak for that paper, back in 1974 before the growth charts.

Arnhold: If the WHO concentrated on breastfeeding and not smoking, these charts were already looking more at the standard reference. This may be a political way of increasing the duration of breastfeeding and avoiding smoking.

Wit: WHO has started from the dogma that everybody is equal, so heights should be equal too. Then the conclusion is that it’s only environment that has an influence on growth. I think the data show otherwise.

Merker: The WHO growth child standard is a nutritionally driven initiative with the focus to improve infant and child health, thus focusing on growth at ages 0 to 5 years only.

Comment by Gabrriele Haeusler Associate Professor, Medical University of Vienna

1.To my opinion, the terms growth standard, growth reference, and growth chart were best explained by Tim Cole in his 2012 review in Ann Hum Biol 39: 382.
I guess, these definitions would make this discussion easier to follow:
A growth reference is a statistical summary of anthropometry in a reference group of children, usually presented as the frequency distribution at different ages. The reference group is often representative of some geographic region at a particular time, e.g. Great Britain in 1990 (Freeman et al.1995). The statistical summary involves the mean and standard deviation or alternatively the median and selected centiles, conditioned (usually) on age and sex. Growth references describe how children grow and the references can be applied to other children to establish whether or not their measurements are typical of the reference group.
A growth standard is essentially the same as a growth reference except that the underlying reference sample is selected on health grounds. Thus, it represents a healthy pattern of growth and the standard shows how children ought to grow rather than how they do grow.
A growth chart is a growth reference or standard presented as a visual display for clinical use and in this sense it is a graphic design. (Note that the term ‘growth reference’ or ‘growth standard’ is sometimes applied to the growth chart that displays the reference or standard, but strictly speaking this usage is wrong.)…”
2. I would like to introduce two papers discussing the issue which standards/references to use: Ziegler-EE, Nelson SE: The WHO growth standards: Strengths and limitations. Curr Opin Clin Nutr Metab Care 2012; 15: 298-302 and WHO 2006 Child Growth Standards and 2007 Growth Reference Charts: A Discussion paper by the Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition (2013). J Pediatr Gastroenterol Nutr; 57: 258.
They suggest that the WHO growth standards should be used for age 0-2(5) years ( for the good reasons explained in detail by Andrea Merker above) followed by national references . The authors recommend that NATIONAL bodies should decide, whether the WHO 5-19 reference should be used (a decision paying attention to the genetic population background).
We have done so in Austria and combined the WHO 2006 growth STANDARS with 4-19 cross sectional 2013 national growth REFERENCES ( Gleiss-A…Haeusler-G, Ann Hum Biol 2013, see attachment ) in our growth CHARTS and for calculation of SDS.
3.In my view, the use of national growth references gives the background for evidence-based diagnostic work-up for short stature as proposed in the Dutch paper by Grote et al 2008 in Arch Dis Child: The deviation from the reference by a defined SD score, together with information on parental height and percentile crossing sets the ground for a diagnostic workup.
The case of the mentioned boy growing on the 25th percentile (Ze’ev’s example) would not be suspicious for GHD or SHOX deficiency- but at the same time is one of many good reasons to improve health care and other important issues in underpriviledged countries in general.
4. Body proportions are very important, both with respect to diagnostic workup (mild skeletal dysplasias like SHOX deficiency do not have to wait until GH testing has shown a normal result) and observations on population catch-up growth (the paper by Bogin has been mentioned already). Note that catch-up growth in China has been predominantly established by longer legs!
In our 2013 Ann Hum Biol paper (Gleiss-A et al) we provide the data for sitting height, leg length and ratio SH/LL. As our references for height are very similar to the latest German and Belgian data, we think that our references could easily be used at least in these countries! After the Zurich Longitudinal Study by Prader et al we do not have valid reference data on body proportions.
BMI: In our 2015 paper (Mayer-M et al) we propose to use Equi-BMI- a term introduced/method developed by Cole in order to account for the obesity trend. The Austrian Equi-BMI data are likely suitable for other European countries, too!

COMMENTS TO THIS CONVERSATION ARE TO BE MAILED TO IVO ARNHOLD [iarnhold@usp.br]

Ze’ev Hochberg, MD, PhD, Emeritus Professor of Medicine, Technion – Israel Institute of Technology, Haifa, Israel
Melvin Konner, MD, PhD, Emeritus Professor of Anthropology, Emory University, Atlanta, GA, USA
Editor: Ivo Arnhold; Reviewer: Alan D Rogol

Hochberg and Konner: In this Conversation, we suggest that the duration of human maturation has been underestimated; an additional 4-6-year pre-adult period, which overlaps with what psychologists call “emerging adulthood”, should be included in models of human maturation. As we define it, the transition between adolescence and emerging adulthood occurs when the decelerating pubertal height velocity equals the pubertal takeoff velocity (to be detailed later).

Hochberg: When using physical, physiological, intellectual, social, emotional, and behavioral measures, at the end of adolescence, an individual cannot be considered an adult. When adolescents in developed societies mature and achieve adult body size, their behavior often remains immature. Specialists in adolescent medicine have recognized this incongruity, and have redefined adolescence to include young adults up to age 24 years, of whom many have not yet assumed lifelong adult roles. Reproduction in contemporary forager societies also begins several years after adolescence and post-adolescent individuals are often limited in their gathering and/or hunting skills. In a comparative mammalian context, primates produce few offspring; the reproductive strategy of humans includes an even slower growth rate than that of nonhuman primates of comparable size, but human growth may be even more prolonged than is generally realized.

Konner: Arnett proposed emerging adulthood as a phase of life between adolescence and full-fledged adulthood, with distinctive demographic, social, and subjective psychological features1,2. This life-history stage, by his definition, applies to individuals aged between 18 and 25 years, the period during which they become more economically independent by training and/or education. Previously, the psychodynamic theorist Erik Erikson identified a stage that he called a prolonged adolescence or psychosocial moratorium in young people in developed societies 3,4. Much more recently, Hopwood and colleagues explored genetic and environmental influences on personality development during the transition to adulthood in a sample of same-sex monozygotic and dizygotic twins assessed in late adolescence (~ age 17), emerging adulthood (~24y), and young adulthood (~29) 5. This transition also involved changes in personality traits in the direction of greater maturity and increased stability. They found that trait changes were more profound in the first relative to the second half of the transition to adulthood; that traits tend to become more stable during the second half of this transition; and that both genetic and non-shared environmental factors accounted for personality changes. Interestingly, the United Nations has defined emerging adulthood during the period from 15 – 24 years of age, as a period of vulnerability worldwide and has made it a priority for multiple interventions.

Defining the Transition from Adolescence to Emerging Adulthood
Hochberg: Using an evolutionary approach to understand emerging adulthood, I argue that it is not just a sociological transition period but also a true life-history phase in biological terms. Life-history theory is a powerful tool for understanding child growth, maturation, and development from an evolutionary perspective. It provides evidence that emerging adulthood exists in some other mammals, which implies genetic evolution, and we discuss emerging adulthood in foraging as well as developed societies, which implies the occurrence of adaptive plasticity and cultural influences. I propose that genetic and cultural evolution have interacted to produce the emerging adulthood stage in human life history.

Determining the exact time at which transitions between life-history stages happen is challenging. Saltation (growth spurts), stasis and transitions occur during human growth, and stages have a central place in evolutionary life-history theory, but the turning points are theoretical constructions in which some aspects of a transition are highlighted6.

Puberty produces an endocrine transformation with striking somatic and behavioral changes, including in the domains of body image, sex identity, aggression, and impulsivity. To define a maturational stage between adolescence and adulthood, we need first to define the end of adolescence. During this transition, growth velocity decelerates, hormone levels increase, aggression becomes less overt, and learning and maturation ease hormonal impact.
Using maturational measures avoids the pitfalls of defining emerging adulthood according to chronological age. Tanner stage V recognizes the conclusion of puberty in boys. I define the transition between adolescence and emerging adulthood as occurring when growth returns to its prepubertal trajectory, and the boy or girl is at Tanner stage IV. The boys at this stage have a testicular volume between 12 and 20 ml. Body composition continues to change during emerging adulthood, in terms of relative fat mass (females exhibit less trunk fat than males), lean body mass, and bone mineral content and mineral density increase.

Konner: But the most important maturational changes after adolescence are in the brain. Brain size may be a pacemaker in mammalian life history; the length of the brain’s developmental trajectory was until recently underestimated. It is now clear that brain development does not stop with the completion of puberty, when adult brain size is attained. Brain maturation continues beyond adolescence, extending until around age 25 years, and this recently discovered prolongation provides critical support for emerging adulthood as a post-adolescent maturational stage. The cortical architectural units or minicolumns in the prefrontal cortex of humans are wider than those of the great apes, with an increase after puberty in humans, but not in chimpanzees. In chimpanzees, but not in humans, myelination becomes complete at about the time of sexual maturity. Interestingly, human brain regions with protracted development are the same that have undergone the greatest degree of volumetric enlargement in primate evolution.

Hochberg: In a large-scale longitudinal pediatric neuroimaging study, it was reported that brain maturation continues after adolescence: the post-adolescent increases in white matter are linear and the changes in the cortical gray matter are non-linear. Cortical white matter in particular continues to increase into the mid-twenties, which is likely related to the efficiency and speed of cortical connectivity7,8. In another study, Sowell and her colleagues spatially and temporally mapped brain maturation in North American adolescents (age 12-16) and young adults (age 23-30) using a whole-brain structural magnetic resonance images9. They found that the pattern of brain maturation during these years was distinct from earlier development and was localized to large regions of the dorsal, medial, and orbital frontal cortex and lenticular nuclei. They also reported that relatively little change occurred at other brain locations. They concluded that cognitive functions improve throughout adolescence, and this improvement is associated with simultaneous post-adolescent reductions in gray matter density (as white matter increases) in frontal and striatal regions. As a growing body of knowledge shows that criminal behavior has a neurobiological basis, such brain changes may mitigate the guilt of adolescent delinquents who have not yet gone through them.

Konner: Investigation of white matter maturation during adolescence, using diffusion tensor imaging, reported that sex hormones influence white matter development and maturation and that white matter connectivity and the executive control of behavior is still immature in adolescence. Thus, functional connectivity continues to change during and after adolescence, and these developmental differences in functional connectivity patterns were associated with higher cognitive or emotional functions and basic visual and sensorimotor functions.
Other studies support this contention10 11; brain development and maturation continue in emerging adulthood, and the idea that brain maturation is finalized during adolescence is no longer tenable.

Hochberg: Psychologically, emerging adulthood is a stage when an individual’s cognitive abilities increase to reach their peak in their third decade and possibly beyond. The critical abilities are those that enable the learning of new things, that is, working memory and fluid intelligence; these peak in the mid-20s.

Emerging adulthood is also a social stage: it is a period of learning intimacy and mutual support, intensification of pre-existing friendships, family-oriented socialization, political awareness, developing new relationships, and the attainment of biosocial skills that are needed for successful mating and reproduction. It is a stage of understanding self-concepts and ideal concepts, emphasized interpersonal reactivity and obligation, self-expressiveness, and contempt towards particular ideologies. The attainment of these cognitive, emotional, and social abilities is the result of a complex interplay of maturation and interaction with the environment, and, at least in the earlier years of emerging adulthood, they are in part the phenotypic expression of brain maturation.

Konner: There is also evidence that brain growth continues into the third decade in some individuals, especially boys. In these individuals, hypothalamic maturation, puberty, and the resultant hormonal surges are dissociated from and even precede development and maturity of frontal cortex.

Hochberg: Emerging adulthood begins as a physiological, but most importantly a neural transformation in which behavioral and social functions interact, with consequences for impulse control in domains that have put the individual at risk during puberty. We argue that this life-history phase has unfolded throughout hominin evolution.
Growth-related Definition of the Transition to Emerging Adulthood
Hochberg: To define the transition from adolescence to emerging adulthood, I use the age at which growth velocity returns to the prepubertal trajectory (Figure). The adolescent growth spurt can be identified from the growth velocity curve, and its takeoff is signaled when the rate of growth changes from deceleration to acceleration at the end of the juvenile stage. This inflection point marks the beginning of the adolescent growth spurt. The point at which the curvilinear growth velocity spurt returns to the pre-takeoff (decelerating) trajectory defines for us the end of adolescence and the beginning of emerging adulthood.

Figure legend: Schematic representation of the age-dependent pubertal take-off velocity and the return to prepubertal trajectory, showing early, average, and late maturers. The age-dependent decline in peak height velocity is a function of the decelerating prepubertal trajectoty. PGV – peak growth velocity, TV – takeoff velocity, RTV – return to prepubertal growth velocity curve.

In an allometric analysis of 21 species of anthropoid (human-like) primates, the age at return to takeoff velocity and the adult body mass positively correlated. The age at return to takeoff velocity in both females and males occurs later in human beings than other primates because of the lateness of our growth spurt when body mass is considered. Overall, the growth spurt in most primates is minimal, and little is known about the relationship between the age at return to prepubertal growth velocity and the appearance of secondary sexual characteristics at puberty. Takeoff velocity occurs early in gorillas, and despite their greater body mass, female gorillas become sexually mature at a younger age than female chimpanzees. Similar to humans, vervet (Cercopithecus aethiops) and rhesus monkeys (Macaca mulatta) show a relatively late return to prepubertal growth velocity. Interestingly, this positive correlation between the age at return to prepubertal growth velocity curve and body mass also exists in six pre-industrial societies described in Walker’s Database for Indigenous Cultural Evolution (http://dice.missouri.edu/)

The Evolutionary Context of Emerging Adulthood
I: Evolutionary Life-History Theory
Hochberg: Life history has been defined as the allocation of an organism’s energy towards growth, maintenance, reproduction, raising offspring to independence. Evolutionary life-history theory attempts to explain and predict tradeoffs that optimize energy expenditure, reproductive advantage, and risk. Central to the concept of sexual selection is the attainment and optimization of reproductive competence, and the key traits for selection are growth, maturation, and the age at transition to adulthood when an individual is independent and capable of reproduction12.

Konner: Human beings and the great apes share similar developmental traits, including some aspects of emerging adulthood. Low reproductive success among young females has been reported to be a general primate phenomenon. Non-human great apes have a 2-year period of post-menarcheal infertility, extended in many human foragers to 3 years.

Male preference for fully developed adult females has been described in 15 primate species. Jane Goodall reported that following menarche, which usually occurs at age 10 years, the female chimpanzee averages 19 cycles before she becomes pregnant for the first time at age 12 years. She will have about 60% of her lifetime sexual encounters during this post-menarcheal period. Chimpanzees and bonobos live in multi-male and multi-female groups and mate more often than needed to conceive. Accordingly, primatologists have suggested that adolescent sterility or subfertility is a period in which sexual and social skills are practiced without taking responsibility for the care of a newborn.

In their emerging adulthood, female vervet monkeys (Cercopithecus aethiops) display a high degree of interest in young infants and will touch, cuddle, carry, and groom infants whenever they can. This play-mothering by young females may be an opportunity to not only practice motor skills, but also as opportunities to practice their expected maternal role in society.

The sexual encounters of young females with males, who are unaware of their low reproductive potential, are also used as a means of barter for other commodities in the biological market, such as food. Fecundity in males depends on the male’s age, size, and experience. Similar to humans, where reproductive success is in-line with hunting ability, reproductive success among Barbary macaques (Macaca sylvanus) is much lower in young males than fully adult males. In male chimpanzees, pre-fertility copulation is common.

While it is challenging to ascertain the life-history stages of ancient hominids, the timing of their dental maturation from the fossil record has shed some light on their life-history stages. Australopithecines are anatomical intermediates between apes and human beings and chimpanzees and bonobos are often regarded as living species that can to some extent represent the australopithecines. Based on detailed reconstructions of dental specimens from the fossil record, the life-history stages of the australopithecines resemble those of wild chimpanzees, and not those of modern human beings. Homo species (the last 2.2-million years) mature more slowly and the attainment of certain maturational milestones, such as the onset of puberty, adolescence, and the assumption of reproduction, probably occurred later, in parallel with their increasing longevity, body mass, and height.

A life-history tradeoff is a fitness cost that occurs when a beneficial change in one trait is linked to a detrimental change in another trait. The Charnov model of mammalian life-history evolution derives the flow of life-history consequences from the adult mortality rate13:
Adult mortality  Age at maturity  Adult weight  Fecundity  Juvenile mortality
According to this model, any factor or influence that decreases adult mortality, such as large adult body mass, sociality, or living in a low-predation environment, would favor delayed maturation. A large body size is potentially protective and a mortality deterrent for mammals. Reproductive value (RV), a measure combining the cost of growth and the remaining length of reproductive life, increases with body mass while growth rates decline; the optimal age to stop investing in growth is when the expected RV starts to decline. Body mass and age are mathematically coupled because body weight increases during growth, and growth stops at a certain age when body weight is optimal. Accordingly, juvenile survival becomes important when maturation is delayed. Furthermore, increasing juvenile survival and extending the adolescent stage in an individual’s life history increases that individual’s RV. Hence, including emerging adulthood in the life-history strategy of a species to increase juvenile survival of that species is highly favored. The offspring number of most species with a large body size is small, and juvenile mortality decreases when reproduction is late.

Several tradeoffs could underlie the prolonged period of emerging adulthood in the life-history strategy of human beings: a) reproducing at an earlier or later age; b) reproducing at a young age or continuing to grow and develop; c) being a fully adult parent with a large parental investment in each offspring of a small family or a younger parent with a smaller parental investment in each offspring of large family. In facultative tradeoffs, individuals adjust their energy budgets and risk to environmental conditions within a genetically specified range or norm of reaction. The Charnov model predicts that a long life span will be associated with slower maturation, repeated reproduction, a single offspring at a time, and long parental care.

Slow rates of growth, reproduction, and aging among primates reflect their low total energy expenditure. Emerging adulthood is part of the historical lengthening of both ends of the pre-reproductive life span of human females (early puberty and late reproduction) in response to improved nutrition and decreased mortality due to infectious disease 14,15. Microevolutionary tradeoffs that might underlie an extended emerging adulthood stage of life history include the allocation of energy to growth or reproduction, and the energy investment in courtship or parenting.

For higher primates, performing the sexual act requires good cognitive ability and specific sexual behaviors. During human evolution, the acquisition of certain abilities resulted in the lengthening of maturation and development.

When comparing humans to our ape relatives, the Charnov model of mammalian life-history evolution helps explain prolonged growth and maturation, including the period of emerging adulthood. Using Charnov’s model, we also suggest that emerging adulthood is the foundation of the high productivity of human beings: the metabolic potential of human beings exceeds the metabolic requirements of survival and this excess is first used to support growth and brain development before being allocated to reproduction.

Hochberg: Despite the fact that the human pre-adult life-history is longer than that of the chimpanzee, and that human infants are larger than chimpanzee infants at birth, hunter-gatherer women characteristically have higher fertility than chimpanzee females. Anatomically modern human parents care for their offspring throughout their offspring’s adolescence and emerging adulthood, and this extended period of care is longer than that of other primates.

Konner: The unique evolutionary path to the genus Homo was shaped by an increasing reliance on calorie-dense, large-package, skill-intensive food resources, and this increased reliance entailed co-evolutionary selective processes, “which, in turn, operated to produce the extreme intelligence, long developmental period, three-generational system of resource flows, and exceptionally long adult life characteristic of our species” 16. Kaplan and Robson emphasized the role of human males in provisioning meat to their family and band members. They also highlighted the contributions of grandmothers and other family and band members to provisioning and childcare, reflecting the importance of their contribution to survival and success in emerging adulthood.

Although the average menarcheal age of the gorilla, the bonobo, and the chimpanzee is 7-8, 9, and 11 years, respectively, their age at first birth is 10-12, 13-15, and 14-15 years, respectively. Despite their rapid development compared with humans, the great apes have a distinct period of post-menarcheal life with no fecundity. In parallel with other great apes, the menarcheal age of human forager populations ranges from 13-19 years, and their first birth occurs about four years later when they are between 17-23 years of age. In contrast to the great apes, the primiparous women of forager populations were supported and provisioned by mature adults: grandmothers, who were usually post-reproductive; their husbands, who were typically several years older and have often passed through the emerging adulthood stage of their life history before marriage; other adults.

Despite similarities among primates, the prolongation of dependency during emerging adulthood is unique to human life history, and is part of the evolutionary success of Homo sapiens.
II. Development of the Human Reproductive Strategy
Hochberg: Across forager societies, there is a consistent 3-4-year period between menarche and the birth of the first child; adult reproductive behaviors are learned during this period of emerging adulthood. The evolution of human development culminated in environment-dependent and late reproductive maturation. According to life-history theory, the reduction in juvenile and adult mortality postponed reproduction and necessitated substantial parental investment in each offspring.

Despite cross-cultural variations in the age of initiation of sexual activity and the age at marriage, the period of emerging adulthood in all cultures involves readiness for mating. Strong emotions often accompany early sexual activity; during adolescence, the frequency of depressive episodes is temporarily increased in boys and girls, and the frequency of these episodes is higher in girls than in boys. Sex hormones are responsible for intensifying the behavioral and psychological changes that occur during adolescence, but in emerging adulthood and into adulthood, average rates of depression, anxiety, and risk-taking decline.

Interestingly, serum testosterone levels continue to rise after puberty and peak in the third decade in men. This age-dependent increase in serum testosterone levels does not occur in chimpanzees: serum testosterone levels are higher in adolescent chimpanzees (age 7-10) than in adults (age >11 y). Male and female sex drive are intensified (and/or enabled) by the activation effects of the sex steroids as part of a switching mechanism that re-allocates resources from growth to reproductive activity during emerging adulthood.

Konner: The “fight or flight” response to perceived threat influences life-history tradeoffs during development. As part of their readiness for mating, the bullying behavior of adolescent males diminishes at transition to emerging adulthood. This could be due to adolescent’s learning more subtle ways of outcompeting competitors. While relational aggression becomes more subtle and sophisticated, the underlying motive for dominance and resource control is still there.

Hochberg: Bullying is a complex social problem that can have serious negative consequences for both bullies and victims. The negative effects of bullying are well documented, not only in terms of the psychological harm that is inflicted upon victims, but also in terms of the maladaptive outcomes for children who engage in bullying. As moral emotions mature toward emerging adulthood, i.e., guilt and shame versus indifference and pride, so does bullying diminish. Whereas it is not yet clear whether or not moral disengagement strategies change with age or are equally available to individuals across the age range, it seems that some strategies for
moral disengagement subside when early adult social and cognitive development emerge.

III: Adolescence and Emerging adulthood among the !Kung and Other Foragers
(! Signifies a click in the Bushmen JU language)

Hochberg: Contemporary forager societies are modern representatives of pre-agricultural forager societies. The mean age difference between men and women at the time of their first marriage in 191 national populations and traditional societies is 3.5 years. The acquisition of subsistence skills depends on both physical development and social access.

Konner: The !Kung are contemporary foraging people of the Kalahari Desert, whose demography and life history have been extensively studied. Traditionally, their average age of menarche was 16.6 years (range 16-18), and about 50% of these young women are married before menarche to men who were on average ten years older. The results of a retrospective study of !Kung women who were 45 years or older estimated that their age at first childbirth was 19 years (range 17-22). This 3-year period between the age of menarche and the age at first birth is probably due to subfertile ovarian cycling. Although their husband’s sexual advances were supposed to be delayed until menarche, women reported that this period was often stressful. This 3-year period is important for a newly married !Kung woman for at least two interwoven reasons.

First, she gradually learns to adopt adult roles and acquire adult sexuality without having to deal with the consequences of pregnancy and feeding a family. Second, a young married !Kung woman usually lives near her mother, even after the first birth, because she is dependent on her mother, father, and extended family before moving to her husband’s village-camp after a second child.

Although !Kung women usually become socially responsible mothers with two or more children by their mid-20s, these mothers are typically still being provisioned by their families. Psychosocial development during emerging adulthood is substantially longer in boys than in girls, and the transition from adolescence to adulthood is gradual. !Kung boys learn hunting and other subsistence skills and are permitted to accompany adult men on hunting trips when they are in their mid-teens. However, the husband’s obligation to provision his family with meat is also aided by relatives during the period of emerging adulthood.

To what extent do the !Kung represent other contemporary hunter-gatherer societies? The acquisition of subsistence skills is a very long process among the closely related San people of the Okavongo Delta, Botswana. Mongongo nuts are a staple food for these people and the !Kung, and acquiring the skill to crack these nuts is age-specific, because nut-cracking skill and arm strength is less important than age. Plotted against age, the ability follows an inverted U-shaped function across the lifespan, and this time-dependent function is a good example of the adaptive evolutionary value of emerging adulthood beyond adolescence. Success at nut-cracking is minimal until the late teens and then this skill improves until midlife before declining.

The Hiwi Indians of Venezuela and the Aché Indians of Paraguay are traditional hunter-gatherer groups whose hunting and subsistence skills gradually increase throughout young adulthood. Although Aché girls collect insect larvae for subsistence, children of the two tribes under age 10 years do almost no foraging and especially no hunting until their teenage years. Specifically, the skill of gathering honey and palm fiber of Aché boys and Hiwi girls progressively increases to levels that are about half of their peak adult values in adolescence. The age at which the hunting skills of Hiwi and Aché men are at their best is the late thirties, and the age at which Hiwi and Aché men and women reach their peak gathering skills for honey and palm fiber occurs when they are even older.

Research on the Tsimane foragers of Bolivian Amazonia, are also relevant to explaining the purpose of the long pre-adult life history of modern humans. Based on hunting returns and the results of specific skill tests, the peak performance of hunters is only reached several years after the completion of a long childhood and adolescence; hunters must first learn to recognize the sounds, the smells, the tracks, and the feces of critical prey species, and then learn to hunt by sightings, pursuits, and attempted kills. The hunting performance and ability of Tsimane foragers is another example of a skill whose acquisition depends on the individual’s age and not the individual’s strength.

Blurton Jones and Marlowe confirmed increases in skill and performance with age in the Hadza, hunter-gatherers of northern Tanzania. For example, accuracy when shooting with a bow and arrow among men Hadza people increases with age and reaches its peak at age 25. One cannot assume that the age-dependent increase in performance and ability is entirely due to learning and/or practice; the increase may also be due to increases in an individual’s size and strength.

The importance of size and strength is confirmed by a study of spearfishing and shell fishing efficiency among the Meriam, who live on the Mer and Dauer islands in the eastern Torres Strait. For fishing and spearfishing, which are cognitively difficult, Bird and Bird found no significant amount of variability in return rates because experiential factors correlated with age. However, for shellfish collecting, which is relatively easy to learn, they found strong age-related effects on efficiency.

Thus, the evidence from foraging societies and the conditions in the environment to which humans became adapted during our evolution show that neither reproductive behaviors (i.e. parenting and the ability to manage the relationship with a spouse) nor subsistence skills are mastered by the end of adolescence.

From the evidence collected from various foraging societies in different global locations, performance proficiency of subsistence skills of individuals increases with age and only peaks when they transit from emerging adulthood into adulthood in their twenties or later. These findings confirm that the period of emerging adulthood is marked by age-dependent maturation, ongoing brain development, strength accrual, and learning, and is a key adaptation for human survival and reproduction.
Secular Trends in Adolescence and Emerging Adulthood
Hochberg: Menarcheal age has declined in the U.S. and Europe for over a century. It has declined by four years over the past 150 years, and the age at peak height velocity in the pubertal growth spurt has decreased by four months per decade. An evolutionary approach to this secular trend challenges the concept that early adolescence is a disease process, and suggests that contemporary reproductive and life-history strategies are reflected in the substantial increase in the presentation of females with early-onset puberty.

Secular trends indicate that the duration of pre-adolescent growth and development has shortened over the past two centuries, and a decoupling between pubertal/hormonal maturation and brain maturation has occurred in adolescents in developed societies. While the mental development of adolescents and emerging adults in developed societies is as slow or slower than that of those in predeveloped societies, the onset of puberty in the developed societies now occurs at a younger age than that in the predeveloped societies. Many people in advanced developed states have increasingly recognized the need for prolonged period of education and support beyond adolescence.

Part of the misconception that early adolescence is a pathological condition is related to the assumption that the transition from adolescence to adulthood is direct. The subfertility of emerging adulthood can be explained by the period between the age at menarche, which is currently 12.5 years in Europe, and the modeled optimal age at first birth of 18 years. Indeed, puberty is followed by subfertility in adolescence and emerging adulthood due to a high proportion of non-ovulatory cycles. Currently, there are no appropriate data for a secular trend in the age at first consistent ovulation.

Despite liberal morals and adolescent sexual activity, early childbearing was uncommon in pre-agricultural societies. In a non-developed traditional society, a girl who begins to menstruate at age 15 years can take her place in that society at age 19 years as a young mother after a 4-year period of emerging adulthood and be supported by the institutions of marriage and an extended family.

In developed societies, the period of emerging adulthood of a girl who begins to menstruate at 12.5 years is prolonged. This prolongation coincides with slow development of the prefrontal cortex and other brain structures and late myelination until at least age 25 years. Gluckman and Hanson have emphasized the mismatch between early-onset of puberty and late mental development in contemporary developed societies, and it is the later part in this period of mismatch that we define as emerging adulthood, a time when young adults are still immature in their judgment and less capable of performing adult tasks17.

Summary and Conclusions
Hochberg and Konner: The idea that one of the outcomes of human evolution is a very prolonged period of adolescent growth and delayed maturity is old, and is consistent with life-history theory, comparative primatology, and the hominid fossil record. We suggest that emerging adulthood is a life-history stage that is part of the foundation the high productivity of human beings: the metabolic potential of human beings exceeds the metabolic requirements of survival and this excess is first used to support growth and brain development before being allocated to reproduction.

We contend that the duration of maturation in human beings has been underestimated, and that an additional 4-6-year pre-adult period, which (following Arnett and other psychologists) we call emerging adulthood, is not restricted to modern societies and should be included in human life history. Recent evidence from brain imaging studies has shown that brain development continues throughout emerging adulthood; development of the neocortical association areas, notably the frontal lobes, extends into the mid-twenties, and is still incomplete long after the end of puberty and linear body growth.

There is now abundant evidence that the frequency of behavioral disturbances of adolescence, such as unplanned sexual activity, risk-taking, impulsivity, depression, and delinquency, declines after adolescence despite persistent high levels of gonadal hormones. The most likely explanation for the transient nature of these behavioral disturbances of adolescence is continuing myelination of the frontal cortex and other brain regions that are involved in the management of impulses and emotions.
Adolescence is often delayed in foraging societies. Since the women in these societies have late menarche and are subsequently subfertile, the age of these young women at the time of first birth is 19 years and their husbands are generally several years older. These young parents are strongly supported by older family members, who supply needed food and advice. The mastering of subsistence skills takes many years and an individual generally becomes most proficient in these skills in their fourth decade. These realities highlight the adaptive advantages of a post-adolescent or an emerging adulthood phase of human maturation, which requires substantial brain maturation and learning.
In the developing world where traditional structural support systems have collapsed, parents are often not able to provide the experience of emerging adulthood to their children, leading the United Nations to identify youth, defined as 15-24 years of age, as a demographic group at risk and a special target for intervention.
The period of emerging adulthood has an evolutionary context and a prolonged maturational underpinning, and we present evidence that supports the idea that emerging adults require protection because they are still both learning and maturing.

References
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9. Sowell ER, Thompson PM, Holmes CJ, Jernigan TL, Toga AW. In vivo evidence for post-adolescent brain maturation in frontal and striatal regions. Nature neuroscience. 1999;2(10):859-861.
10. Kelly AC, Di Martino A, Uddin LQ, et al. Development of anterior cingulate functional connectivity from late childhood to early adulthood. Cerebral cortex. 2009;19(3):640-657.
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Does the Timing of Puberty Matter?

A live Conversation between Ze’ev Hochberg and Jean-Pierre Bourguignon, moderated by Alan Rogol

Contributors: Cheri Deal, Michael Ranke, Jan-Maarten Wit, Ron Rosenfeld, Alicia Belgorosky, Ivo Arnhold,  David Dunger, Martin Ritzen, Leo Dunkel, Raphael Rappaport, Paul Czernichow

Alan Rogol: This session aims for a basic understanding of the issue here, pubertal timing. There are no boundaries for the aspects to be considered, we expect a lively back and forth conversation, although I’m not sure that we have the time for a lot of that. However, if carried out by Internet or Skype, I’m sure we could meet the two goals. Our two protagonists, Ze’ev Hochberg and Jean-Pierre Bourguignon will outline their views and this will be followed by a second shorter second chance to fill in some added information, or as JP just said, directly address a point made by the other.

Remember, this is the alpha presentation; we are not required to answer all questions or solve all dilemmas. We can certainly carry on the conversation over time. What makes this group special is that we are all friends, and that is great to engage with them in these discussions.
Okay, Ze’ev, may we have your first chat. The way it’s going to work is we have 12.5 minutes spread between the first and the second. So, you can have up to 12.5 now, please.

Ze’ev Hochberg: I like to think of adolescence, a broader perspective: it is a life history stage when children prepare for adult roles, in terms of reproduction, independence and caring for a family. So, eventually, at the end of puberty, they will have to become adults. When I think of adolescence, I think of a package that includes puberty and its related neuroendocrine changes, the secondary characteristics of puberty, the growth spurt, the cognitive changes that occur in puberty, and the psychological development that is occurring in puberty, including the acquisition of sexual and reproductive skills. So that in the center is how to become a reproductively competent adult, the so-called ‘coming of age’.

In the last 50 years, and more so in the last two decades, the package of adolescence has disintegrated.  The reason is that neuroendocrine maturation and cognitive and psychological skills have developed at different tempos. So, while puberty comes earlier now than it used to about 100-150 years ago, the cognitive and psychological development is slower than it used to be, and the children don’t become mature adults until they’re about 25 or 30. Only then they become economically independent, they start a family, they parent children, and they care for them.  I believe that disintegration of adolescence is central to many or the social problems that our youngsters have

I like to think of puberty and adolescence in terms of human biology; I mean fitness goals mostly reproductive fitness in its evolutionary meaning. The life history stage of puberty is part of sapiens’ strategy to become a productive adult. The word strategy is not used much in medicine, but it’s used in the study of evolution. The long-term strategy is to become a reproductively competent adult and propagate one’s DNA. There are different ways to and maybe different trade-offs to do this, and the strategy differs for boys and girls.

If we talk about the importance of the timing of puberty, there are two issues I think that need to be discussed. The first question is what the causes are that determine the timing of puberty, and how these causes change in our modern world. Mostly the causes of concerns are the role of obesity and what is the role of endocrine-disrupting chemicals in determining pubertal onset.  I’m mostly interested in the effect of stress on puberty; how much stress has to do with the timing of puberty. The second question deals with the long-term consequences of early or late puberty. The two aspects, both causes and long term consequences have to do with the reproductive goals.

In the medical world we tend to think of different environments as being a good environment and a bad environment, leading to health and pathology, such as, for example, environments with or without endocrine disruptors. But if we think of puberty as a life history reproductive strategy in the world of evolution, then there are different environments, and appreciation of the benefits and the costs of a problematic environment leads to alternative tactics, design, in the evolution jargon. Not good and bad environments but different ones that require different designs. Much of it has to do with energetics and its balance. If this is a girl who lives on the streets of Bombay and she’s malnourished, it makes of course sense for her, in terms of her reproductive strategy do defer her puberty and start it later. The biology behind it is that we evolved to withstand famine by delaying reproduction to the affluent period that would come later. And this is in fact happening in India, where the age of menarche for girls in the slums or who live on the streets is four years later than it is for privileged girls in the same country.

Different environments also explain the               secular trend for the age of menarche. The fact that it is so much earlier today that it was only 150 years ago has to do with the different environment of these two societies. Early puberty today is adaptive to the affluent contemporary environment, and present day girls use this environment to gain reproductive advantage by getting into reproductive life earlier. The biology for such an advantage was set during the last two million years of our evolution. The fact that contemporary girls in the industrial society don’t actually marry and reproduce right after menarche relates to the current slower social and behavioral maturation as compared to the rapid neuroendocrine puberty.

On the issue of stress, and I mean chronic rather than acute stress, we see early or late reproductive strategy, depending on severity of the insult. If it is a minor stress, then most of the time the response to would be earlier puberty. In response to a stress such as absence of a father from the family, or the presence of a step-father or a boyfriend of the mother in the family, these stresses would result in earlier puberty. While severe stress, such as malnutrition or war, results in delayed puberty. The theoretical basis for this is the difference between secure and insecure strategy. If the child is born into a secure family, where she is well-nourished, her parents live in harmony and the economy of the family is good, this child will eventually develop a strategy of a secure world. There is no reason to hurry. Such children will have late puberty; they will start a family late to have fewer children than children who develop an insecure strategy. In socioeconomic hardship, significant family conflict, maternal mood disorders, or a poor-quality father – daughter relationship, children develop an insecure strategy and will have an earlier puberty.

This is known as the concept of socialization for the timing of puberty. Maybe we can discuss later on the consequences of later puberty, which have to deal with reproductive cancer, and with a metabolic syndrome and the consequence of growth in starting early or late, and the social effects, but they all, all of them, have to do with human biology, with reproductive strategy within the context of adolescence as a package that deals with cognitive and psychological development.

Rogol:  Jean-Pierre Bourguignon will continue on with where we are.

Jean-Pierre Bourguignon: Pierre Bourguignon: Well, thank you. I realized that while thinking about this, I had pointed more precisely the huge 5-year difference in pubertal timing among individuals, which to me is really fascinating. While somehow you have addressed that issue as well, you overall discussed the secular changes in pubertal timing. Should I want to make short my answer to the question “Does pubertal timing matter?”, I would simply say “Yes, for the brain”. I do recognize I’m brain-biased, given my research. I would somehow join what you said, Ze’ev, and put that question in a bio-psychosocial perspective, a concept that is frequently used in adolescent medicine. So, this 5-year time window is huge compared to the life span; if you think of other animal species, only primates and humans have such a huge disparity in timing. Also, if you think about the duration of the pubertal process, it’s just like a race where the first having started has crossed the finish line, while the last has not yet left the start line. So, it is quite intriguing that there is such variability in timing between individuals for a relatively short process. As a matter of fact, variability (5 years) by far exceeds duration of puberty (3 years). Coming to the bio part of my thinking, I think developmental neurobiology has made huge progresses in terms of understanding how brain is reshaped at the time of adolescence; grey matter is lost quite importantly at that time, and the causal involvement of sex steroids seems to be one possible explanation. Again, these changes will happen with some timing disparity among individuals, and that can be important in terms of behavioural consequences. Now, the psychosocial side of that disparity seems important to me.  A simplistic representation is to say that children before puberty look all the same, and puberty is really the first time in life when they experience that they are not all the same. If you think further about that, it’s just a transient situation, because after puberty we all reach adulthood. Of course, there are differences remaining, look at Alan and me [Alan: I was the placebo]. Still, this huge difference among individuals that results from disparity in pubertal timing is temporary. Now, coming to the discussion about how puberty makes sense in terms of life history, what you said about nutrition and about stress is challenged by this observation: it is amazing that though we share relatively comparable life conditions (including stress and nutrition) in industrialized countries, there is still such a huge difference in pubertal timing among individuals. I can’t really see the reason behind this. So, that’s one thing I would be really interested to know how you feel.

There is a second issue I want to pick up from what you said, Ze’ev. You took the example of obesity. To me, this condition raises the question of the difference between association and causation. Especially if we take that example and think about the developmental origin of health and disease concept, it might be that intrauterine conditions have determined a risk of obesity and a change in pubertal timing together. Then, the association is not causal at all. By the end of your discussion, you have mentioned cancer as a possible “consequence” of early pubertal timing. I really doubt that cancer is a consequence of changes in the timing of puberty. I can’t say that’s not true, but I can’t say that it is.

So these are issues for discussion.

Rogol: We are certainly on the right track for having discussions back and forth, the only one comment I wanted to make, is both of you mentioned the issue of adolescence, and if you look over the literature for the last ten years, you don’t go from adolescence to an adult, you go from adolescence to an emerging  adult. Then you go to an adult, and the last part of it, from 24-28, is when marriage, finishing school, etc., which we think is a short step, isn’t really such a short step. So, Ze’ev, will you continue please?

Hochberg: I agree Alan with that remark. I call this new life history stage ‘emerging adulthood’. At the end of puberty a child is not an adult. The end of puberty happens around age 15-16 in girls, and 18-19 in boys. By then, they don’t start their reproductive stage, they are not independent and don’t have any family responsibilities. Even the brain isn’t fully mature. The brain gets fully mature at the end of the third decade of life, so also biologically, they are not fully adult yet by the time they finish pubertal maturation. Our colleagues from adolescent medicine have recognized it, and they have developed the concept of pediatrics going through the age of 24.

I’ve tried to look into this question in terms of human and other primate’s evolution, and see if other they have an emerging adulthood. It turns out that even among the great apes, there is a period from the end of puberty to the time they start to give birth (about 2-3 years in chimpanzees and gorillas), and in traditional non-industrial societies, it takes about 4 years from the time the girl is mature to when she starts to give birth. Whereas she looks mature, she doesn’t have effective ovarian cycles yet. So, there is a period of relative sterility after the end of puberty.

And that brings me to the issue of obesity, and why is it that obesity is associated with early puberty. In my view this has also to do with the fitness advantage of having an early puberty, as a step toward reproduction.  And this is also why girls have earlier puberty as compared to boys. The reproductive constraint is mostly for females with their long periods of gestation and breast-feeding, which in traditional society take some 3-4 years – the so-called interbirth interval.

Bourguignon: Well you started talking about when adulthood is reached somehow. I understand that, and I think that we as pediatricians and pediatric endocrinologists may be biased because we are much more frequently seeing patients because puberty is starting earlier and rarely because puberty is not ending or because it’s ending later or whatever. This reminds me of a study that was published a few years ago, evaluating different birth cohorts in France. They showed that at the same time that menarche occurred earlier and earlier (this was the secular trend toward earlier menarche), the ovulatory cycles were later and later. And that’s something we couldn’t study any longer now, because contraceptive pills are taken so early that we don’t know about ovulatory cycles at least in our societies.  Maybe that could be studied in others. I think this issue, when puberty stops and when it ends, seems very important because we miss information about when puberty ends, and my hypothesis is that puberty ultimately is taking more time now, from the very beginning to the very end, than it was before. That’s what I wanted to add.

Rogol: Okay that will be the end of the formal presentations and now let’s just go ahead and pick up the microphones and ask anybody anything.

Cheri Deal: I’m very intrigued by your comment about the preservation of an enormous inter-individual variability with regard to the timing of puberty, whether you’re looking at a developed nation or a developing nation, regardless of your geographical location. And I hope I don’t sound too teleologic, because I don’t mean to, maybe just the way I’m phrasing it, apart from that question, how it may point to a biomedical perspective to something that is extremely multigenic and epigenetic, which of course opens even an even larger variability from the genomic level. I think it also points to an evolutionary perspective, and probably, the way I see it, is that it was a means of resource-sparing. You couldn’t have all the women born at a certain date becoming fertile at a certain time, because that would stress enormously the village resources or the individual community resources. So, I see this as being carried through by an evolutionary pressure.

Bourguignon: Well I agree with that, but I would just like to add something about epigenetic and genetic control. While presumably epigenetics would play a more important role in early phase of life. Quite intriguingly, if you take two examples, nutritional restriction and stress, when they are imposed during pregnancy (so during fetal life, or around birth), they result in advancement of puberty. If they are imposed closer to the time of puberty, they result in delaying puberty, and that’s interesting because you take the same environmental issues and they have an opposing effect depending on the time in life. That difference comes to possible epigenetic versus genetic mechanisms.

Hochberg: I think that we are talking of two different phenomena. The one is early programming for the best fitness strategy, which involves an epigenetic mechanism, and happens during gestation, but also postnatally at critical transition points between life history stages. At the transition from infancy to childhood, around the end of the first year of life, the child programs for his growth trajectory based on his energetic environment, but this is also the first hit for programming for a secure (late puberty) or insecure strategy – early puberty based on his or her attachment environment. This is known as Bowlby attachment theory. The second hit becomes functional at the transition from childhood to juvenility around age 6-7. A very different phenomenon is the response to a major stress, such as war or famine that would delay puberty based on factors of the stress and energy mechanisms.

Michael Ranke:  It is of course important to focus on a specific subject, particularly  if one starts something of which one doesn’t actually know where it’s going to and choses a discussion forum which someone has compared with a “salon littéraire” . You have rightly proposed puberty as a target. The problem that I see is that we primarily need to talk about evolution. This means the adaptation of a race to the environment in order for the survival of the fittest, as our thinking has been formed by the experience made in the animal world. Puberty in humans has very specific problems related to the man-made environment. So, what we have and see is puberty in its time variability. This variability in the human effects – like in other species – sexual activity. However, at the same time, reproduction in humans today is actually separated from the course of physical pubertal development. Reproduction in humans is influenced strongly by social factors, not by the optimal time of human natural fertility. The female would probably have the best reproductive ages at the age of 18-20, not at 30+ as today. And finally there is the even more complex issue of individual maturation.  Perhaps maturation is not even the right word for the becoming of a “complete” individual in an enormously complex man-influenced environment. I think altogether the problems related to puberty, growth and maturation are enormously complex and I wonder how the human species is going to come out of this – and what EDGE will be able to unravel.

Rogol: Precisely why we are having these discussions.

Jan-Maarten Wit: I was astonished a little bit by a comment by Ze’ev that psychological development would be slower now than before. I was thinking what indicator are you using in this comparison, and how do we know that? Because of course society was quite different then, so who to compare with another 150 years ago; what are the data that psychological development is slower?

Hochberg: There is a big body of data comparing children from the ages of 18-20 to young adults beyond age 25 (Behav Sci Law, 18:741, 2000). The young kids are not fully mature in terms of decision making. They are not mature enough to take full responsibility of their own life, let alone of the life of children. They are still dependent or their parents economically and mentally, and they function accordingly. They stay at their parents until they get to be 30, until they are mature enough to leave home.

Wit:  Yes, but is that psychological development, or is that another thing?

Ron Rosenfeld: My thoughts are like Michael Ranke’s. I like to view such processes as evolution and growth from an evolutionary perspective. Ze’ev made a point and I agree with it, if you look at human or primate puberty compared to other species, there are several totally distinguishing features. One is the prolonged childhood phase, or the long lag before the onset of puberty, and the second is the fact that homo sapiens is the only species that has a pubertal spurt in skeletal growth. Other species will gain weight during puberty, but only Homo sapiens has the pubertal growth spurt. And one can ask, why from an evolutionary perspective has this benefitted the species? And Cheri is right in saying that we should be careful in thinking teleologically, but the arguments are that a prolonged childhood had several advantages. First, it made male children less threatening to adult males. They weren’t rivals for reproduction. Secondly, smaller children required fewer  resources in terms of food, but perhaps, most importantly for humans is the argument that prolonged childhood gives you a prolonged period of psychological and intellectual nurturing that allows you to develop hopefully into a mature adult. And that the pubertal growth spurt that Homo sapiens has is then a way of compensating in terms of growth for the prolonged childhood. Now there’s nothing biologically imperative about a girl having menarche at 11 rather than 15, I mean, there’s nothing written in scripture saying that 15 is the right age. And what is really striking is that in spite of the marked earlier puberty, it hasn’t affected adult height. Even though one may have argued that epiphyses are going to fuse earlier, we’re going to end up shorter, in fact the secular trend has been to increasing height, despite your earlier puberty. Probably both reflecting better nutrition and better general health. I don’t think there’s anything necessarily biologically problematic about early puberty, I think the implications, Michael was suggesting, and Ze’ev also, are psychological and societal in terms of the implications of reproductive capabilities, sexual capability, at an earlier and earlier age, but I think those are societal issues or sociological issues, or psychological issues, not necessarily biological issues.

Alicia Belgorosky: I would like to comment on what Jean-Pierre Bourguignon said, because I think that the maturation of the brain is something very important. In poor countries, the association between maturation of the brain, and earlier puberty and reproductive capacity might be influenced by the fact that females are less able to take care of their own body, with the consequent increment of the incidence of early pregnancies. So, I think this is a very important point that you have mentioned. Sexual intercourse is now very early, and that is a problem, at least in poor counties. The second point that I would like to comment on is a very recent paper from Almastrup  K et al (Scientific Report, Doi 101038, 2016), where they found maturation changes in female, and in males, during the transition time between pre-puberty and puberty. They have observed that using elastic model net prediction models methylation patterns predicted pubertal development more accurately than chronological age, and they have proposed to consider the biological age instead of chronological age. Finally, the authors have raised the concept that the modulations of the epigenome might be involved in the regulation of pubertal timing. So, as Cheri has mentioned about epigenetic changes, it also occurs in this transition period. I think that perhaps it’s a new way to analyze childhood maturation.

Rogol: Thank you and I think I want to clear up one point. Many of us in this room have talked about transitions.  Most of them are the transitions from the adolescent to the emerging adult or adult, but there’s an important transition from prepuberty to puberty.

Ivo Arnhold: I’m thinking out loud, but I think maybe society wants to know from us 1) if our prepubertal body is prepared to the psychosocial changes that are happening, and this mismatch between content to which the young girl or boy is exposed to through communication much earlier than the brain exposure to sex steroids. So, I wanted to know from Jean Pierre if it would help to have the sexual hormones earlier to understand earlier the communication that society is bringing and 2) if we should also look at extending the biological reproductive life of women, if this is a societal need. And because I think evolution changes much slower than the societal pressures, so I’m just bringing up these questions. The question is: if children are exposed to communication at a younger age of sexual life and of being a young adult and how much are hormones important to understand this type of communication or should we even induce puberty earlier because of this?

Bourguignon:  It’s really hard to address that question specifically because I think it’s a whole set of things that appear. I think we know more about what could drive the changes in behavior than how children entering puberty would perceive some messages from the society, from the media, and whatever. Parenthetically, there is some evidence that the first places in the brain to change are in the hippocampus, the limbic system, where emotions are controlled. And the last change is in the frontal region where social control is happening and some people tend to think that the dissociation between change in the hippocampus and change in the frontal region could explain this eruption of behaviour at the time of adolescence.

David Dunger: I’m not quite sure I follow what you’re saying about strategies, you make it sound like a continuous process through childhood, there’s very good evidence that after prenatal growth restraint, you get catch-up growth with adequate nutrition and that has been shown in endless studies now, and that appears to program for early puberty and rapid weight gain, obesity later on. That’s been shown in 20-30 different populations. Does it matter? Well probably in the study we did in Bristol, it didn’t matter a great deal the girls go into puberty a bit earlier, they’re a bit plumper, so obesity is a risk and maybe long term metabolic risk. I kind of disagree with you about cancer, I think long term exposure to sex steroids does increase cancer risk. Does it matter in other populations? So, we did studies in South Africa. There it does matter, because these children are born very small, they come out, they’re in a different environment where they put on weight, they become obese, and they go into puberty early. They have early pregnancies, they have an increased rate of metabolic disease, and this is going to be a disaster going forward. Africa is estimated to have the highest numbers of Type II Diabetes in the world in 2020. So, it does matter. Mid-childhood, there’s very little evidence of plasticity at all, I’m very interested in all this business about stress bringing about puberty, I don’t know anything about that. The only one bit of evidence there is, is migration, which is very curious, the way these girls move from Romania to the UK, and that’s very interesting , I don’t know what the mechanism is. It’s probably nutritionally related, because they put on a lot of weight. But on the other hand, years and years ago, people looked at putting upon weight between the ages of 2 and 10, and it did nothing to rate of entry into puberty. Putting on weight between 0-2 does make a difference, but between 2 and 10 it does not.
There is another area of plasticity that is during puberty that has been shown in a couple of studies, and that is if you are one of those thin girls who go into puberty very late, you have to put on a lot of weight, because reproductive capacity requires a certain fat mass in a woman, they can’t have a pregnancy with no fat mass. A couple of studies have shown that late developing girls have low leptin levels and they have put on proportionally more weight during puberty than the others. And then the last comment is just a question. You talked about the variation in the timing of puberty, but you can go through puberty in 2 years or 5 years, there’s another variation in there which I’ve never understood, and what’s the significance of that?

Deal: In terms of the plasticity pre-pubertally, I thought some of the evidence was also that when you had reconstituted families, where young girls were no longer living with a biologic father, but with an adoptive father, that that was another trigger for onset of puberty (1). I wanted to pick up on one more comment about what are important questions and I think prolonging reproductive potential in women is a very important question. Only humans and whales (a few species of whales) have menopause. I think we need to work that understanding as well in our comprehension of earlier puberty, and what this means for total reproductive function, because it’s not just becoming reproductively functional, but it’s also how long is the woman going to be reproductively functional.

Martin Ritzen: I’m going to be very practical. I think we’re going to end up the discussion saying more research is needed, as always [laughter]. But for future projects, I see a different approach from authors of papers on early or late puberty, and my own practice when I see a patient. One of my first questions is: When did the mother have menarche, what do we know about the father’s pubertal development, what about the sibling’s pubertal development? What is the overriding influential factor for pubertal development, genetic background or the fine tuning by endocrine disruptors, or other environmental factors? If you are going to set up a new study, I suggest that you divide the subjects into different groups depending on family background. The mother almost always knows when she had menarche; this is a good staging parameter. You will probably get different results depending on whether the mother´s menarche was early, middle or late, because (epi)genetics is so important. There are very few papers that distinguish girls or boys depending on the pubertal development of their parents.

Leo Dunkel:  Eighty percent of the variation in puberty is genetically determined, and of course there must be this type of environmental cues, otherwise we wouldn’t have for instance this secular change in the timing of puberty. And I think that’s quite important, really, to have this type of biological architecture, otherwise we wouldn’t be able to have these strategies to select what is the optimal way to develop and so forth. But really, we don’t understand what the genetic core is, and really to make a steep change in this area of investigation we would really have to first understand what are the genes that are ultimately determining the timing of puberty. Practically we know nothing about those. If we look at the 200, 000 women and age of menarche for instance, based on this, we have hundreds of SNPs which explain like 3% of all this variation. So we have typical case of missing heritability and really to understand the gene environment interactions, we would really have to first understand the genetic core, and then really understand what is interacting.

Dunger:  I was just going to make a comment that in a big population study in Bristol, we did look at that, we followed the mothers up until early, late and middle gestation, and when you look at their offspring, the mothers with early puberty had babies that were born smaller who showed rapid catch up growth, who then went into puberty earlier, and the mothers who had late puberty had children who did the reverse. So it may be genes but it may be much more complicated than that, maybe much more epigenetic.

Ralph Rappaport: It’s just a very stimulating and interesting discussion, I’ve learned a lot and I just want to take the point of view of age, just to finish the discussion, because you say that age is aiming at putting science, not only science but something in addition to it, which is social, humanistic, or whatever it is, but we did not really do away with discussing and with our many more issues. I just wanted to raise one issue, aiming at something else different, and it’s not scientific, but all issues of puberty puts us in one difficult questioning which we are facing in practice and daily life, which is what is normal? And when is normal beginning, early puberty, what is early, and what is late? And this is probably not only decided by us, according to the criteria we have somebody has put up 40 years ago, it’s only depending on the view of the society, and just for an instant, I’m told that now in many clinics, at least in our country, I believe, in many other places, doctors are overloaded by questions about puberty, early puberty, much more than about short or tall. It used to be the first problem of the society that we generated perhaps, but perhaps not. I’m not clear about this. It was height and now it is according to what I hear and what I read, it is puberty. So let us ask why all of a sudden, the society grasps the issue of puberty and 3-4 years ago I like to quote a very nice paper that you may have read eventually, in the New York Times, it was 5-6 columns about early puberty in New York, and the way the mother’s behaved with girls having early breasts, and being all of a sudden just becoming just like young ladies and this is a very interesting paper to see how the society reacts to changes which are apparently certainly occurring. So, there are so many other ways to look at that issue.

Paul Czernichow: Ze’ev, you started your interesting speech by saying that there is a lack of exchange between humanities and the sciences and lay people. Speaking about the problem of variability in puberty it is striking that people in the educations system, they are not very interested by this problem. I think that the timing of puberty has an enormous impact on how the children understand the enormous amount of knowledge they need to learn and digest, and I wonder if this has been studied. In face of the large variability in puberty, we demand from the children so much learning, at least in France, but probably also in other parts of Europe. It is a very rigid system, where you enter high school at a certain age and this problem of puberty age is not taken into account.

Hochberg: I wanted to finish with the issues that Paul Czernichow raised. Does it matter to the patients and their families whether they start puberty early or late? Of course, it matters a lot to them. They come to ask us to modify it, to start it earlier, to start it later; they come with precocious or late puberty and the misery of the child himself. This is an important issue that we will not have time to discuss today.

1. Webster GD1, Graber JA1, Gesselman AN1, Crosier BS1, Schember TO. A life history theory of father absence and menarche: a meta-analysis. Evol Psychol. 2014 Apr 29;12(2):273-94.

ECGM Club Discussion:

Martin Ritzen, MD, PhD, Prof. emeritus of Pediatrics, Karolinska Institute, Sweden

I would like to draw your attention to a remarkable long term follow-up study that enrolled a cohort of all healthy girls in a geographical area in Sweden (n=466) when they were 13 years old and followed them until they were 43 years of age. The results what concerns the influence of early puberty on later development has been published in psychology journals by the Swedish professor of psychology, Håkan Stattin and his group (1). More references can be found at Web of Science. I summarized the data for a conference on pubertal development back in 2005 (2).

Several differences in somatic and psychosocial behaviour were noted when the original cohort of 466 girls was divided into three groups, depending on the age of menarche; those with early puberty (menarche before age 11), middle (age 11-13) and late puberty (menarche later than at age 13). At age 15-16, girls with menarche before age 11 (early) were more problematic, including delinquency, in several contexts. By adult age, all adverse behaviours had disappeared. Thus, the effects of early pubertal timing on psychosocial adjustment seem to be adolescence-limited.  However, at age 27 the early group had lower academic degrees, which was also the case at age 43. Regarding somatic development, at age 43, women with early menarche were shorter and heavier, had worse physical fitness, and dieted more frequently than others did. However, no difference in quality of life was found. In searching for causes of the antisocial behaviour in adolescence and the lower educational levels, early heterosexual relations seem to be the most decisive. The early girls had older boyfriends, and copied some of their adverse behaviour.

Although none of these girls had true precocious puberty, the results indicate that even early normal puberty might influence important behavioural issues in adolescence leading to lower future educational level, shorter stature and increased body weight in adulthood.  This should be considered when counselling parents of girls with early puberty.

 

COMMENTS TO THIS CONVERSATION ARE TO BE MAILED TO JEAN PIERRE BOURGUIGNON [jpbourguignon@ulg.ac.be].

 

 

What discovery impressed you most during your career?

Live Conversation between Ron Rosenfeld and Cheri Deal

With contributions by Ze’ev Hochberg, Alan Rogol, Jan-Maarten Wit, Alicia Belgorosky, Paul Czernichow. David Dunger, Ralph Rappaport, Leo Dunkel, Martin Ritzen

Cheri Deal: I have the pleasure of being able to probe Ron Rosenfeld’s brain. The question posed to Ron is “What scientific discovery did you feel, in your career, has made the most impact”. So, go ahead and give us your answer.

Ron Rosenfeld: Thank you Cheri. All of us in our investigative careers have had the experience of coming across a paper or a lecture where you said, “Wow, this has just opened up a whole new area of thinking.” And for me there’s no question that the paper (series of papers) that most impacted me were Argiris Efstratiadis knock-out models, which I think opened the entire growth hormone IGF system (Nature. 1990;345:78-80,  Cell. 1991;64:849-59)

Deal: And in what way did you feel they impacted you? Is it mostly because of IGF-1 genetics and biology? IGF-2 receptors and biology? The receptors? You say the knock-out papers, but carry that a little further for me.

Rosenfeld: Well, let me give a little bit of background. So, the first successful knock-out mouse was performed in 1989 by Evans and Smithies and Capecchi. They ended up getting the Nobel Prize for that in 2007. Efstratiadis is a Greek trained molecular biologist working at Columbia University at the time, had no particular interest in endocrinology or growth hormone or IGF, but thought that that would be an interesting question to use a knockout system. So, within 6-12 months of the initial in 1989, he had successfully knocked out a series of genes. The first one was IGF2, and it was a tour-de-force, because what he discovered, for those of you who don’t remember, was that in knocking out IGF2, you could result in a 40% loss of fetal growth, but no impact on postnatal growth.  In addition, quite remarkably, he recognized that IGF2 was an imprinted gene, and this is in fact, the first endogenous human gene to be demonstrated, to be imprinted. [Deal: Mouse gene] Mouse gene, to be correct, thank you Cheri. So, it was an extraordinary tour-de-force. Shortly thereafter, he knocked out the gene for IGF-1, and in the case of IGF-1, again, there was a 40% reduction of fetal growth, but this time an impact on postnatal growth. He then knocked out IGF1 and IGF2 in combination, the IGF-1 Receptor, IGF-1 and the IGF-1 Receptor, IGF-2 and the IGF-1 receptor, demonstrating the specific role of IGF-1, IGF-2, IGF-1 receptor in both intrauterine and postnatal growth. Finally, he knocked out both IGF-1 and the growth hormone receptor, resulting in a mouse that was only about 17% of normal mouse size. I remember very well that that year he was invited to give an honorary lecture at the endocrine society. Not sure, you must have been at that meeting, Cheri. And he shows a picture of this tiny mouse, and he said: “This mouse has done more for my career than Mickey did for Walt Disney”. And he was right. Of course, all of this, as you say Cheri, was done in mice but it totally opened up the molecular genetics of human growth. And shortly thereafter we identified (or we collectively, the endocrine community identified) patients with IGF-1 receptor defects, IGF-1 defects, IGF-2 defects, growth hormone receptor defects, Stat 5A defects and all of this was laid out by Efstratiadis’ work. So, and then he left the field of endocrinology. Said “I’ve answered all the questions I’ve wanted to ask, I’m going to move on to cancer biology”. But really, in the series of a half a dozen papers written over the period of three years, he paved the way of much of the work for many of us.
Deal: I was going to take this a bit further with regards to the Nature paper, which was the 1990 DeChiara Efstratiadis’ paper (Nature. 1990;345:78-80) that extended further in The Cell, 1991 paper. With regards to IGF2, the IGF2 knockouts, I didn’t do a PubMed search to try to get a handhold on the amount of literature published subsequent to the IGF1 knockout, but I did do PubMed to try to see what, because Ron shared with me what he was going to talk about, what the notion of IGF2 imprinting spawned. And it is absolutely remarkable because it spilled over to not only the growth field, but to the cancer field. It spilled over to the whole notion of epigenetics and plasticity and fetal determinants of adult health. It spilled over into a huge number of ageing papers, and so. For me, it was actually the IGF2 papers, which I think have contributed the most to science. I think that somewhere down the road, people are going to have to get a prize for that work.

Now the question I have for you, carrying this forward: You’re an expert in Darwin and Wallace, who came quite a bit after Lamarck. How do you think Darwin, who recognized, I believe, this notion of Lamarck’s, that you could inherit acquired characteristics, even though Lamarck never thought that was an important idea in his own career; how do you think Darwin would relate to those articles of Efstratiadis’ on IGF2 imprinting? How would he have incorporated that into his Theory of Evolution?

Rosenfeld: Cheri, such a tough question.  So first of all, you are correct that Darwin in fact, embraced many of Lamarck’s claims, including acquired characteristics. Something incidentally that Wallace took him to task about, because Wallace said there’s no evidence to support that. But certainly, neither of them would have had any thoughts about epigenetics at that point. That was far beyond them.  But I think each of them would have looked at the question of “What do these genes and different regulatory processes in these genes contribute to survival of the fittest”. And you know, we should remember that, really, survival of the fittest, means survival of your genome. How does it help you transmit your genome? The way I always remember imprinting of the IGF2 system is the idea that the fathers want their children to be large, so they’re willing to endow the IGF2 gene, whereas the mothers want the fetus to be small, so she’s going to endow the IGF2 receptor to degrade the protein. So that’s something I think Darwin and Wallace would have embraced.

Deal: Okay, now I’m going to take it further. Are any of you aware of the other theories, if we’re going to extend evolution and the reasons for imprinting in terms of survival of the species?
So, epigenetics, what you’re saying is epigenetics. We should perhaps transpose that to the phenomenon of puberty, and I think there is evidence that it definitely occurs. But getting back to the evolutionary reasons for the development of imprinted genes or for the propagation of imprinted genes. We are very anthropocentric because the notion of imprinting has existed, or of epigenetics has existed for many years prior to the demonstration in mice of Efstratiadis, in angiosperms, in flowering plants. And there, it was clearly known that this phenomenon of selective gene inactivation occurred in the endosperm, which is an analogous organ to the placenta, where of course we have the most amount of imprinted genes. And so, I find it interesting that a paper that has so influenced, or papers that have so influenced the direction of a lot of our scientific thought in many fields actually had to be brought to mammalian biology and even human biology with a demonstration of imprinted genes in humans before it really took off. And other areas, for instance, look at breeding. When you look at the donkey-horse crosses, we know that getting a hinny or a mule, depends on whether the father is the horse, or the father is the donkey. And in phenomenon like that, which are analogous to puberty in actual fact, the phenomenon of going from a caterpillar to a butterfly, and I guess we can look at that as a sort of puberty, in caterpillars and butterflies. That’s very epigenetic, and there are imprinted genes in that. And the same with the epigenetics involved in the honeybee, depending on the amount of royal jelly that is eaten, so this brings in the concept of nutrition, you deviate either to get a queen bee or a worker bee. So, all I say is that I find it astounding that we as scientists need to bring a scientific discovery back to us as humans, or at least in our animal realm, before we really take it and run with it. And that says something about scientific ideas and how they’re born, but I would like to carry that on, maybe with comments from you.

Rosenfeld: Your points are absolutely well-taken Cheri, and it harks back to Ze’ev’s introductory comments about the fact that we speak to each other all the time in our papers and our meetings, but we don’t have the opportunities often to speak to people outside our own field and to be enriched by scientific or humanistic or sociological observations that are outside of the field of paediatric endocrinology, which can often greatly assist us in understanding issues that are important to us.

Deal: Yes.

Ze’ev Hochberg: Before the era of genomics, the center discussion in evolution used to be the calculus of energetic, and the saying was that a calorie used to growth cannot be stored, and it cannot be used for reproduction. In the center of all of this is growth Hormone. Clinical conditions where you have slow growth, such as growth hormone deficiency, are associated with deposition of fat, and clinical conditions were a child grows slower, such as for example, around juvenility, the age of adrenarche at 7-8, there is deceleration of growth and at the same time, we have the adipose rebound. So, at the center of this adiposity, there is low growth hormone. And with all of these genes that Ron mentioned, there is always a change in growth, but also a change in adiposity.

Deal: Maybe I can ask you another question now. If you were going to point out the next field within the growth hormone, IGF-1 axis, or within the IGF-1, IGF2 story as the groundwork being laid by Efstratiadis pointed out, what would you say would be the next big thing?

Rosenfeld: So, as I was preparing for tonight’s meeting, I was thinking about the fact that there are limitations to mouse knock-out studies, in terms of what they can tell us about human biology. They open up a lot of issues, but humans are not mice, and we shouldn’t expect that it’s necessarily the case. When Efstratiadis knocked out IGF1 and GH receptor, he got a cumulative, an additive effect on growth. So, his conclusion was that growth hormone has growth promoting actions that are independent of the IGF system. And that observation would seem to hold true when you look at IGF-1 therapy of Laron Dwarfs. We know that IGF-1 treatment of growth hormone receptor mutants cannot duplicate the effect of growth hormone treatment in growth hormone deficiency. But I personally think that the question of whether growth hormone has growth promoting actions independent of IGF-1, or whether IGF-1 is in fact a total mediator, or the IGF- system in total is the total mediator of growth hormones, growth promoting actions in humans remain unanswered. And I think that has important therapeutic implications, clinically. So, to me that remains a very interesting question.

Alan Rogol: As many of you know,  one of the things I deal with is doping in athletes. This is exactly what the issue is that at least among bodybuilders and other athletes, that they don’t consider those two compounds the same, and if they don’t do it, there’s something behind it, that’s our charge, is to find out what’s behind it.

Deal: And further to growth hormone actions and working through the growth hormone receptor, what is your feeling about the intersection of immunology with growth hormone biology? Because I think that too is something, if you’re talking about the importance of growth hormone effects.

Rosenfeld: You’re talking about immunology, Alicia might want to address this one also, well, the central issue is that the growth hormone receptor is a cytokine receptor. And that like many cytokine receptors it signals through the Jak system. There’s got to be an important message in that. It hasn’t been adequately explored of course, but one very real possibility is that the growth failure that one sees in so many chronic diseases, not just immune dysfunction diseases, but any chronic inflammatory disease can in fact be due to interference by immune modulators with growth hormone receptor signalling, and I think that’s clearly an area that’s ripe for research. Jan-Maarten, any thoughts about this?

Jan-Maarten Wit: I think it’s also interesting that Stat3 hyperactivity seems to give a downregulation of Stat5.

Deal: And there is actually a lovely symposium on Saturday that I have the honor of chairing, and one of the papers presented will be on Stat3 biology and genetics, so we’re looking forward to that.

Rosenfeld:  Just to add to that, one of the things that is, I think, underappreciated by the endocrine community is that constitutive mutations of Jak2 and Stat5 have clear implications for cancer. And as we think about the potential ramifications of growth hormone or IGF-therapy in terms of malignancy, there’s got to be an important message there also.

Alicia Belgorosky: I wanted to say something about one question that we have to answer, Ron, this is how the IGFBP systems works, because it is something that we don’t know. There is a steady state function in some tissues, but not in other tissues. And I think that it’s a big question that we need to answer in the future. And in relation to Stat5 and the immune system, it’s something very interesting, because how, when Stat5b gene mutation, how the immune system is alternated is very interesting, and why we have the variability in phenotype in terms of immune system alteration is something very interesting to look for.

Deal: I actually wanted to turn this over to the rest of you. Because Ron had time to think about this, but when you received the agenda, all of you probably had a bit of a flashback as to what paper influenced you the most in your career, or you feel has maybe set the stage for a huge body of work and knowledge over your practicing years. So, I’d like to go around and make each one of you come forth with an idea. If you agree with Ron that’s fine too, but have you thought when you saw this agenda, did the lightbulb go on?

Belgorosky:  The technique of PCR.

Deal:  The technique of PCR. Yeah, I was so happy when I did my fellowship with Ron in California, my license plate started with PCR, and I kept that license plate, I’ll give you a photograph, I made it into a slide.

Rogol: Actually it’s quite recent and I’m suspected many of us who have had relatively long careers have been influenced by recent papers, and it’s the work of Karsenti (Cell. 2016;165:882-95). He has talked about how the hematologic system talks to the brain talks to the regulation of metabolism. It’s in terms of energy for the whole animal, and to me this was kind of, if you remember your neuroanatomy class, you were tested and if you could give 5 knife-cuts, you could get everything, but you really had to know your neuroanatomy where one knife-cut could do all of those things. I think he has really brought together in a very fundamental way, how many systems are organized, be it bone, be it energetics, be it the brain.

Hochberg: I got a present for my son’s birthday, Richard Dawkins’ the Selfish Gene. And this changed my thinking altogether. This was for me my career-changing book.

Paul Czernichov: You’re probably going to laugh at me, but when I was 24 and I discovered radioimmunoassay. We had a window open on the body and can measure the variation of hormones.  And I thought that what a fantastic tool for clinical research, and it has been a fantastic tool, even though most people are using now ELISA. I was shocked when we were measuring blood glucose in kids with diabetes, and we discovered the disasters of our treatment, and it still is. And I thought that the next step would be measuring hormones and fluids inside of the cell, and that would be probably a great achievement when we complete our understanding of what we are doing. It is something that is left over on the caravan that I think that being able to merge our IGF-1 inside of the cell. That probably would be the further step in our ability to understand what we are doing.

Rosenfeld: I just want to add Paul, to your story, that Ray Hintz told me, when he was an assistant professor, Rosalyn Yalow, from Radioimmunoassay told him, “Why are you wasting your career on IGFs, what a total waste of time, can’t you go do a real hormone?”

Jan-Maarten Wit: A paper that I found very interesting was that in the cell, one hormone is changed to another hormone, for example by the enzyme aromatase, in chondrocytes. Hormones that we first only knew in the adrenal are actually present in a lot of cells.

David Dunger: Yes, I was going to mention someone named David Barker, who I disagreed with every time I met him, because I talked about genes, he refused to talk to me at all in the last few years of his work. I don’t think he had very good ideas about what he was talking about, but he did open up this whole area of making developmental biology and its factor in adult life respectable. And these spawned thousands of thousands of grants in lots of careers.

Deal: I was delighted when you said Efstratiadis, because I was going to say the IGF2 knockouts, and I will share personal information. I was a fellow in Ron’s lab when he actually presented that Cell paper by Efstratiadis. And that to me was a lightbulb moment, and I went back to Montreal, and wrote my first big grant, and the reviewer said: “Oh, but IGF2 imprinting has been shown in mice, why do you want to show it in humans?” And that really ****ed me off. And so I got together with Constantine and his graduate student came to my lab and actually we ended up doing it without any funding. It was all internal funds that I had, and it lead to the Nature Genetics paper showing the first imprinted gene in humans, and that actually is my most cited paper. But I think that says something very much about how science works. And not only is it really hard to overthrow scientific paradigms as Kuhn wrote in his Making of the Scientific Revolution, but it is also very hard to get innovative ideas through granting agencies. What I always teach students is, Don’t worry about money, actually that came from Ron, Don’t worry about money, if you have a good idea, go for it, and I appreciate you for having said that, because I’ve always done that.

Jean-Pierre Bourguignon: So, this is back in the early 80s, I had been in research for a few years, for it was about in the mid 70s I started. And this was the work of Knobil [unsure of name, 1:48:30], first using a primate as a model which is fantastic, and second showing that changing rithm of stimulation of a cell system would come to totally unexpected effects such as increasing the frequencies, reducing response. Well that really was a shock and I think it was quite an extraordinary finding, that has raised many points including treatment with GnRH agonists. So, I think it was quite a finding.

Ralph Rappaport: Just to go back to something which may sound less glamorous. It’s a type of psychosocial dwarfism which was described by Bob Blizzard and I was there at that time, and it was to me completely new. At that time Growth Hormone could barely be measured in blood. And soon after a paper came out which I haven’t reread, but I must go back to it, it was a paper in Cell showing that a plant would not grow if you don’t put your hand every day on it. And touching the plant every day would help it to grow. And the authors have shown that there is in the machinery which I have completely forgotten in that plant, something which makes a plant feel the hand every day and help her to grow. I thought that it was a vegetable psychosocial problem, [diffuse laughter] but who knows? Here we are coming close to social and environmental issues translated into hormone secretion and action.

Deal: Any other phenomenal scientific discoveries that have stimulated your thinking?

Leo Dunkel: So actually, I didn’t think about this in advance, but I have been really impressed with the latest developments in cellular biology and molecular genetics, especially cellular reprogramming combined with genome editing. I have been interested in GnRH neurons for years and now we are able to culture from stem cells of our patient fibroblasts, culture them in the GnRH neurons and even create monogenic mutations, specific mutations in the cell. And this is totally opening new fields, because I have never been able to test these types of cells like this, and especially like creating specific mutations, so I have really been sort of fascinated and blown away by these nice techniques.

Martin Ritzen: Well I think the real breakthrough since I have come through, is improved methodology. I have been old enough to see the development of modern molecular biology and PCR and whatever, and of course that has spread the whole field of science. So, this is fantastic, as humans with new methodology. But I also like to put a word for an observant clinician’s thoughts and conclusions. One paper that I was fascinated by was published in New England Journal of Medicine, October 16^th 1994, Eric Smith’s paper on the ER-alpha knockout man, and where he could show completely unexpectedly that Estrogen (ER alpha at least) is extremely important for bone remodelling in males. Nobody had thought about that before. And he also showed that spermatogenesis is affected, which is again, estrogen directed? Estrogens needed for spermatogenesis? That again was new. So, an astute clinician that can go back and of course you remember that here, he involved good scientists from molecular biology, and that’s why he could show logical steps in the formation of this. So, if we as clinicians could find the key patients and then work them up properly, we’ll find new discoveries.

Deal: And that paper also hammers home the point, the subsequent papers that follows, that mice and men are really different, because when you look at all the knockouts, the ER Alpha, the ER Beta knockouts, the impact on growth and on puberty, gonadal development, are completely different from what you predict in the human. We have to close. So, it’s been delightful hearing from everybody, and I will turn this back to Ze’ev so he can give his comment.

Rosenfeld: Just to follow up on Michael’s earlier comments. So maybe this kind of question, “What scientific discovery impacted you”, is relevant to use because it puts what we do in a historical context, which is something that I think young researchers aren’t exposed to. Maybe this is something we should think about introducing into SP-programs, or PES programs or whatever. Have somebody talk about the historical background that impacted their research directions. I think that would be well received.

COMMENTS TO THIS CONVERSATION ARE TO BE MAILED TO JAN-MAARTEN [J.M.Wit@lumc.nl].

ECGM Conversation:  Bar Mitzvah and puberty during ancient times

Diana Sperling, PhD. Philosopher, writer, essayist, teacher, the National University Cordoba, Argentina

Alicia Belgorosky, MD, PhD, Chairwoman of Endocrine Department, Hospital de Pediatría Garrahan, Buenos Aires, Argentina

Editor: Ze’ev Hochberg, Reviewers: Ivo JP Arnhold; Jean-Pierre Bourguignon; Jan-Maarten Wit

With contributions by Ivo Arnhold, Jean-Pierre Bourguignon, Ze’ev Hochberg, Jan-Maarten Wit, Mark Sperling, Alan Rogol, Michael Ranke

Alicia Belgorosky: What was the criterion to establish the age to become a Bar Mitzvah at 13 years?

Diana Sperling: The criterion to establish that age was related to the age at puberty, that is, the age at onset of sexuality and the physical ability of reproduction. Of course, the criteria we currently analyze – from a scientific point of view or in psychoanalysis, etc –, were not necessarily conscious reasons in those times. For example, in the Jewish religion, hand washing has been mandatory before meals, prayer, and at many other moments in daily life. Only many centuries later, scientists discovered the usefulness of this ritual. In other words, in all ancient cultures or “religions”, certain knowledge about actual life was imposed and then “explained” as being commanded by God.

Belgorosky: Were they considered mature enough when that age was defined? How were the parameters for psychological and physical maturity evaluated or was this not considered?

Sperling: I will answer both questions in one: Onset of sexual maturity is what allows a boy to separate from his mother (overcome the Oedipus complex) and look for a woman outside the home. It is the beginning of exogamy, the end of incest (Freud’s Totem and Taboo). Likewise and for the same reason, the boy can become independent from his father because he is now able to read, interpret, and adopt the law by himself.  In all cultures, there are rites of passage from childhood to adulthood, both for girls and boys, which are always associated with this factor of onset of (possible) sexuality. In most ancient cultures the rite – for boys – consisted of an act of hunting or war. The boy was ready to become a hunter (provide food for himself and his future family) or warrior (to defend himself, or his family or group). The concept of “adolescence” did not exist in any of the ancient cultures: a child becomes an adult; or a son becomes a (potential) father.

In Judaism, curiously, the rite of passage is a ritual of reading: The father hands the Torah (law) to his son, who, for the first time reads it in public, in the heart of the community. In other words, he is recognized by his group as an “adult”, in the sense of an initiation of maturity and independence from his parents. We should also remember that the concepts of age, longevity, life expectancy, etc., were very different in ancient times.

It is important to clarify that the ceremony itself is not necessary, in the sense that the mere fact of becoming 13 years old turns the boy into a Bar-Mitzvah (which literally means “son of the commandment”). The ceremony in the synagogue or any other adequate environment is meant to visualize and thereby publicly recognize the new status.

Belgorosky:  What were the obligations they had after becoming Bar Mitzvah?

Sperling: The main point is that from this moment on the young man becomes part of the minyan. He is counted to be part of a group of ten persons (men, both in ancient times and in current orthodox Judaism) the necessary minimum to celebrate the majority of rituals, from prayers of mourning to the reading of certain parts of the Siddur (book of prayers). Generally, this moment also coincides, in modern communities, with the beginning of secondary school, a farewell to childhood, and thus, a greater responsibility and autonomy in study and other tasks that are taken on without entirely depending on adult surveillance.

Belgorosky:  How can this be considered from a modern anthropological and philosophical perspective? Were there any changes in different movements of Judaism? Is it possible to make a comparison with other religious movements?

 Sperling: There is no unanimity as to this point. I may say, however, that there is a quite generalized consensus that recognizes – after the delusion of rationalist self-sufficiency resulting from the Enlightenment – the importance of rituals as a fundamental part of culture. Ritual is by definition an inherent aspect of human sociability: humans are the only beings that bury, mourn, and remember the dead. In anthropology – a young science, just like sociology and psychoanalysis – scholars have identified and studied the rituals of coming of age in all cultures of all times and places. From a modern point of view, it is about the admission of the person and his new status to the heart of the community, and the person thereby ascribing to the rules of the group. The ritual is a performance, an act, not a concept: it necessarily involves the body, and thus, affection, emotions, the thought of coming of age that accompanies the biological development of human beings.

Perhaps the most significant innovation is the inclusion of the Bat-Mitzvah, the ceremony for girls, in progressive Jewish movements: conservative and reformist, additional to all other denominations, separated by orthodoxy.

Belgorosky: In relation to the concept raised by Diana Sperling about the shorter or absence of adolescent period in ancient times.

To propose an explanation or an hypothesis from the biological point of view in relation to Diana´s comments linked to what has occurred with human puberty in ancient times, I decided to write a brief update about puberty onset and puberty tempo in SGA children, assuming that in ancient times, pregnant mothers’ diets would have been clearly insufficient for the needs of the fetus and the mother.

Following Charles Darwin’s theory of evolution by natural selection, one would have expected that children born SGA, both in ancient and present times, would have a chance to recover the capacity to oxygenate their tissues at birth  by the newly learnt ability of breathing, as well as to increase their body mass by the ready provision of nutrients via lactation. Accordingly, if postnatal conditions are favorable, a large proportion of them might gain weight satisfactorily, or even excessively (1), during the first few years of postnatal life. This abnormal change in nutritional status in opposite directions might deregulate epigenetic programming as suggested by Roth et al. (2). Indeed, as discussed by Hochberg and Belsky (3) harsh rearing conditions predict earlier maturation.

According to Diana’s comments “The concept of adolescence did not exist in any of the ancient cultures: a child becomes an adult; or a son becomes a (potential) father”; it could be speculated that in ancient times, poor oxygenation and/or nutrition during prenatal and early postnatal life might have programmed a shorter onset of puberty tempo, as a mechanism of adaptation to the environment, and to acquire early reproductive capacity for the survival of the human species.

References

1. Cumming SP, Malina RM. Bio-banding in sport: Applications to competition, talent identification and strength and conditioning of youth athletes, submitted, 2017.
2. Malina RM, Rogol AD, Cumming SP, Coelho e Silva MJ, Figueiredo AJ. Biological maturation of youth athletes: assessment and implications. Brit J Sports Med 2015; 49(13):852-859
3. Myburgh GH, Cumming SP, Coelho e Silva MJCooke K, Malina RM. Growth and maturation of British junior tennis players. J Sports Sci 2016; 34(20):1957-1964.

 ECGM Club Discussion:

Ivo J P Arnhold, MD, PhD, Professor of Endocrinology, University of São Paulo School of Medicine

From an endocrine point of view, we know that in modern times and Western communities, at the age 13 years (the age of Bar Mitzvah), different boys are at very different stages of pubertal maturation and of their growth spurt. This results from the normal physiological range for individual timing of puberty. The onset of puberty is traditionally considered normal when it starts within ±2-2.5 SD of the average, that is, between 9 and 14 years for boys (1). Therefore, boys are submitted to the same ritual at different pubertal stages, which escape their control.

Furthermore, with the prolongation of the education process, at age 13, boys are still far from achieving all the social skills necessary for independent adult life. As Diana Sperling states ”this moments also coincides, in modern communities, with the beginning of secondary school, a farewell to childhood, and thus, a greater responsibility and autonomy in study and other tasks that are taken on without entirely depending on adult surveillance”.

Probably, at age 18, boys will have achieved a more uniform and complete pubertal maturity and height and will be closer to being an independent adult.

Reference:

1. Mark R. Palmert and Leo Dunkel. Delayed Puberty. N Engl J Med 2012;366:443-453

Jean-Pierre Bourguignon, MD, PhD, Professor emeritus of Paediatric Endocrinology, University of Liège, Belgium

About question #1: The usefulness of the ritual of hand washing as perceived nowadays does not tell us about the beliefs that have substantiated the initiation of such a ritual. For instance, could it be that touching the body that carries characteristics of sexual maturation and activity was thought to justify some purification? In addition, the prioritization of males (since Bat Mitzvah in girls is a more recent ritual) deserves some thought about sexually dimorphic places in socialization. This transition event has been fixed 1 year earlier (12 years) in girls than in boys. I find it very interesting that there was such an age difference. My interpretation is that it is pointing to the early visibility of pubertal changes in girls (breasts, growth acceleration) as opposed to late visibility (voice deepening, muscle mass increase, growth spurt) in boys.

About question #2 and 3: I see an additional social dimension of adolescence to that of leaving the parents for a girlfriend or a boyfriend. In between, there is an increasing importance of groups of peers of the same gender. This may be incorporated into the transition rituals by the fact that they are run as a group event or an individual event depending on culture and gender.

Did the age of Bar Mitzvah not change since the middle age and is this inconsistent with secular changes in pubertal timing? Following up on Alicia’s discussion on consequences of intrauterine growth restriction that was presumably more common in the middle age, this condition could certainly account for earlier sexual maturation. However, nutritional status in childhood could also be insufficient in those days as opposed to postnatal repletion of energy intake after IUGR in many modern societies. Because insufficient childhood nutrition tends to delay puberty, childhood underfeeding could invalidate the effects of IUGR on pubertal timing (1).

I agree with Ivo’s comment on the gap between celebration of transition at a fixed age of 12 in girls or 13 in boys and the reality of a 5-year difference in pubertal timing. This is so that some individuals may physically almost look like adults while others may appear as children when celebrating transition at those particular ages. This reality is contrasted by the desire of looking all the same (clothes, activities, hobbies) that characterizes adolescents. Somehow, this could be an attempt to compensate for biological reality of diversity in pubertal timing. Ultimately, this brings us to the question “What is normal?”, and how we use it in the conservative or interventionist management of differences in growth and maturation.

Reference:

1. Anne-Simone Parent, Delphine Franssen, Julie Fudvoye, Arlette Gérard, Jean-Pierre Bourguignon. Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: Revision of human observations and mechanistic insight from rodents. Frontiers in Neuroendocrinology 2015;38:12–36

Ze’ev Hochberg, MD, PhD, Professor emeritus of Medicine, Technion – Israel Institute of Technology, Haifa, Israel

In agreement with Ivo’s and Jean-Pierre’s comments, having a Bar-Mitzvah at a fixed age rather than stage of puberty is much like our habit of sending adolescents of various pubertal stages to the same class. I watch boys of 14 having their gym class, and see the late maturers struggling to keep up with the muscular early maturers, who may even have a mustache by that age. Their muscles are smaller and weaker, their hemoglobin is lower, and so are their lung capacity and heart volume. Yet, they are expected to accomplish similar physical tasks. They also attend class with the girls, who are at 14 so much more advanced cognitively. Delayed boys are unable to cope with the cognitive superiority of their classmate girls or the early maturing boys. Apparently, there is no simple solution other than educating teachers about the vast variation in pubertal age and its implications.

To understand the psychological implications of delayed puberty in a boy of 14, you do not have to be a psychologist or a physiologist; all you need is to read The Book of Intimate Grammar by David Grossman: a must read for pediatric endocrinologists and anthropologists. This is an artist’s view of delayed puberty and its uproar. The Bar-Mitzvah of the protagonist Aaron is looming, and he is anxious mostly about his slow growth and skinny physique. He is humiliated and self-hating as he observes signs of puberty in his pals. The Bar-Mitzvah scene is awesome; the corrupting influence of adult sexuality is all around him; his friends at the party enter puberty in full swing, their voices break, their hair sprouts under their arms, they grow inches before his eyes. He views his father’s fleshy body with horror: this is what he will become.

I easily sympathize with boys of delayed puberty, and do not hesitate much before I prescribe to them a short course of androgens to ameliorate their slowing growth. They love it also when their genitals grow, and when I see them after six months of androgens, I think of Aaron and his intimate grammar.

Jan-Maarten Wit, MD PhD, Professor emeritus of Pediatrics, Leiden University Medical Center, the Netherlands

In many cultures, the age of 12-13 years is taken as an age at which the status of the child changes. As Ze’ev writes, at that age most children go from primary to secondary school, which confronts the children with a quite different and more demanding environment. In psychology, that age is also considered the end of the latency period.

I am sure that, also in the past, people had noticed that there was quite a wide range of maturity at that age. However, it is not astonishing that that age was taken as the criterion for Bar-Mitzvah, like age is taken as the criterion for the change from primary to secondary school.

Referring to the considerations of Alicia Belgorosky that she would expect complete catch-up growth in children born small-for-gestational age, I doubt if there would be any association with the evolution theory. Rather, this may be associated with the alternative of the evolution theory, the one proposed by Jean-Baptiste de Lamarck (1744-1829). De Lamarck postulated that offspring can inherit acquired characteristics, and can therefore be considered as the father of epigenetics.

Alan D. Rogol, MD, Ph.D, Professor emeritus of Pediatrics and Pharmacology, University of Virginia, USA

This concept has been playing out in the search for talent in sport. In age group categories, at least until the age of about 15 years for boys, the best football (soccer) players are those who are more mature. Many may use their strength and power to overcome deficiencies in technical skills and it is the rare delayed boys with superior technical skills that can compete in the under 13 years or under 15 years leagues [2]. However, a new concept is coming to the fore at least in youth football, that of bio-banding [1, 2, 3], that is having youth play sport based on their level of maturity. In the UK one of my colleagues is in the midst of evaluating having “camps” where for a few weeks, the players play on teams and compete with each other irrespective of calendar age, but in terms of biological age. It is seemingly a welcome break for both those who mature early—they require ball skills because they teammates and opposing team players are all “big and strong” and those who mature late—they use skills rather than raw power to play the game.

References:

1. Cumming SP, Malina RM. Bio-banding in sport: Applications to competition, talent identification and strength and conditioning of youth athletes, submitted, 2017.
2. Malina RM, Rogol AD, Cumming SP, Coelho e Silva MJ, Figueiredo AJ. Biological maturation of youth athletes: assessment and implications. Brit J Sports Med 2015; 49(13):852-859
3. Myburgh GH, Cumming SP, Coelho e Silva MJCooke K, Malina RM. Growth and maturation of British junior tennis players. J Sports Sci 2016; 34(20):1957-1964.

Mark A Sperling MBBS,FRACP, Emeritus Professor and Chair of Pediatrics at the University of Pittsburgh, PA, USA

The Ethics of the Fathers (Pirkei Avot-literal translation from the Hebrew is “Chapters of the Fathers”) is a Jewish compilation of ethical teachings and maxims based on Rabbinic sayings during the period 200-500 C.E. It deals solely with ethical and moral principles and no laws ae expounded. Chapter 5, v 22, provides a guideline for correlating age with intellectual (study) and physical (marriage, livelihood) parameters. Thirteen was chosen as the age to assume responsibility for one’s actions, presumably because, with or without puberty, one should be able to distinguish by that age right from wrong (do’s and don’ts). Later ages are suggested for marriage and getting a job, and with guideposts for understanding, counsel and wisdom as the years go by. I enjoyed the wise discussions.

Ben Hei Hei (one of the Rabbis of the period) would say: According to the pain is the gain. He would also say: Five years is the age for the study of Scripture. Ten, for the study of Mishnah. Thirteen, for the obligation to observe the mitzvot. Fifteen, for the study of Talmud. Eighteen, for marriage. Twenty to pursue a livelihood. Thirty, for strength, Forty, for understanding. Fifty, for counsel. Sixty, for sagacity. Seventy, for elderliness. Eighty, for power. Ninety, to stoop. A hundred-year-old is as one who has died and passed away and has been negated from the world”.

Michael B. Ranke, MD, PhD, Prof. emeritus of Pediatrics, University of Tübingen, Germany

Certainly in all cultures we observe the aspect of incorporating an individual formally into the world of adults – with rights and duties (including spirituality). This is probably to a degree separate from the aspect of sexual maturation. To my knowledge in medieval Europe the age of girls given into marriage was about 16 years. This was obviously the age (somewhat distant to menarche) which allowed using the regenerative potential of the woman fully.

The aspect of menarche in classical India during the period between ca. 500 B.C. and A.D. 500 has been investigated [1] and may add to our discussion:  Abstract: Data from the writings of Indian legislators during the period between ca. 500 B.C. and A.D. 500 have been used to study menarcheal age among girls born in classical India. As these legislators were concerned mainly with the upper-caste population, it can be presumed that the recordings obtained are only from upper-caste Hindu girls. Throughout the period the age at menarche was about 12 years. A number of legislators considered the best age for conception to be around 16. When these data are compared with those obtained from classical Greece and Rome, the Indian age is found to be about 1-2 years earlier. Comparison of the data from the 19th century and present-day India reveals that the older data are about 0.8-2.2 years earlier when various areas are considered. These results contrast with the downward trend for the age at menarche seen in the industrialized countries during this century.

Reference [1] Datta B, Gupta D. The age of menarche in classical India. Ann Hum Biol. 1981;8(4):351-9.

 

Comment by Zvi Laron Professor Emeritus, Tel Aviv University
In the pursue to clarify why Bar Mitvah is held at age 13 we performed a prospective survey of 128 boys who attended our clinic regularly at intervals of 3 to 6 months. In addition to appraisal of their sexual development we noted the appearance of the first conscious ejaculation. We found that the first ejaculation occurred at a mean bone age of 13 6/12 , (mean chronological age 14 3/12y) and a mean testicular volume of 10±4ml. We concluded that the first ejaculation is the “male biological milestone” equivalent to the female “menarche”. This clinical observation made Jewish elders to decide to celebrate the start of the male reproductive capacity. This is the biological explanation of Bar Mitzvah at age 13.
Reference: Laron Z, Arad J, Gurewitz R, Grunebaum M, Dickerman Z. Age at first conscious ejaculation: a milestone in male puberty. Helv. Paediat. Acta 1980:35:;13-30

COMMENTS TO THIS CONVERSATION ARE TO BE MAILED TO IVO ARNHOLD [iarnhold@usp.br]