[Paleopsych] NYRB: Vive la Différence!

[Premise Checker]

Vive la Différence!
http://www.nybooks.com/articles/17973
By H. Allen Orr

[Thanks to Alice for this.]

Adam's Curse: A Future Without Men
by Bryan Sykes
Norton, 320 pp., $25.95; $15.95 (paper)

Y: The Descent of Men
by Steve Jones
Houghton Mifflin, 252 pp., $25.00

The X in Sex: How the X Chromosome Controls Our Lives
By David Bainbridge
Harvard University Press, 205 pp., $22.95; $14.95 (paper)

The human genome is made up of forty-six chromosomes, the rod-like structures 
that reside in the nucleus of every cell. These chromosomes carry all of our 
genes, which, in turn, are made of DNA. Two of these chromosomes, called the X 
and the Y, are different from the rest: they are "sex chromosomes." Men carry 
one X and one Y chromosome, while women carry two X chromosomes. All the 
obvious physical differences between the sexes ultimately spring from this 
humble difference in chromosomal constitution.

During the last few years, real progress has been made in our understanding of 
the sex chromosomes and we now know much more about our X and Y than we did a 
mere decade ago. In 2003, for example, essentially the entire stretch of DNA 
carried on the human Y chromosome was decoded, revealing the number and, in 
many cases, identity of the genes that make up this seat of maleness. More 
important, owing to a breakthrough that occurred in the early Nineties, 
biologists now understand just how sex is decided in human beings-geneticists 
identified the master "switch gene" that determines whether an embryo will 
develop into a male or a female.

These discoveries might seem surprisingly recent. In view of the confident 
pronouncements in the medical press about all things having to do with sex and 
gender (homosexuality, for example, was said to be genetically determined), 
you'd be forgiven for assuming that the biology of how a human being becomes a 
boy or a girl has long been understood. To be fair, though, there were good 
reasons for the slow progress. How sex is determined represents a rare problem 
in which the study of simpler organisms like fruit flies led biologists astray. 
Sex determination in human beings specifically and in mammals generally doesn't 
work the way it does in most of the species that geneticists like to study. 
Moreover, genetic studies in human beings are simply harder to perform than 
those in species like the fruit fly: a generation is more like two decades than 
two weeks, and we can't dictate who mates with whom, an ethical constraint that 
doesn't arise with flies.

Although the three books discussed here cover much of the same ground, one 
stands out from the rest. Bryan Sykes's Adam's Curse is both far more 
ambitious, and controversial, than Steve Jones's or David Bainbridge's book. 
Sykes, a professor of genetics at Oxford University and author of the 
best-selling The Seven Daughters of Eve, sounds loud alarms about an impending 
biological crisis involving the Y chromosome. He also makes bold 
sociobiological claims about the effect of the Y chromosome on our lives. 
Because Sykes is a leading researcher in the study of sex chromosomes (not to 
mention a science adviser to the House of Commons), his pronouncements merit 
special attention.

1. Sykes begins his book with the discovery of the master gene that decides sex 
in human beings. For decades, biologists understood that human beings have 
so-called Y-dominant sex determination. Roughly speaking, if you carry a Y 
chromosome, you're a male, while if you don't carry a Y chromosome, you're a 
female. As a result, rare individuals born with two X's and a Y are boys, while 
rare individuals born with one X and no Y are girls. There is therefore 
something on the Y, not the X, that decides sex. Identifying this something, 
however, proved extraordinarily difficult.

As often occurs in human genetics, the key breakthrough involved extremely rare 
exceptions to the above rules. In the late 1980s, several people were found 
whose sex appeared not to match their sex chromosomes. Some were patients who 
had an X and a Y chromosome and yet were female. Careful study revealed that 
these patients' Y chromosomes were incomplete-they lacked a small, defined 
piece of the normal chromosome. Others were patients who carried two X 
chromosomes and (apparently) no Y and yet were male. Careful study revealed 
that these patients carried a very small piece of the Y chromosome, typically 
too small to be seen under a microscope. Remarkably, the small bit of the Y 
missing from the female patients roughly corresponded to the small piece 
present in the male patients. This proved that sex does not depend on the 
presence or absence of an entire Y chromosome and further suggested that 
whatever gene or genes decide sex reside in the relevant small region of the Y. 
The race to locate the human "sex determination gene" was on.

As Sykes recounts it, the race was filled with false starts. In 1987, a 
research team at the Whitehead Institute near Boston announced the discovery of 
ZFY, a gene that sits in the appropriate part of the Y and that had certain 
molecular features that, the team believed, made it a strong candidate for the 
sex gene in humans. Soon, however, the ZFY story unraveled (for one thing, ZFY 
turned out to also sit on the X chromosome, which made little sense) and the 
race, briefly suspended, began anew.

In the 1990s, another research team led by Peter Goodfellow and Robin 
Lovell-Badge at the Human Molecular Genetics Laboratory and National Institute 
for Medical Research in London identified another Y chromosome gene which they 
confidently named SRY, for Sex Determining Region of the Y chromosome. Their 
confidence was, in this case, well placed. During the following year, the same 
team performed a critical experiment proving that SRY does in fact determine 
sex in mammals. Injecting a copy of the SRY gene into mouse eggs, the team 
produced a mouse that carried two X chromosomes and SRY-and it was male. SRY 
was able, therefore, to force an embryo otherwise destined to become female to 
develop instead as male. As Sykes recalls, the "star mouse, swinging on a stick 
and sporting enormous testicles to prove the point, made the cover of the 
edition of Nature" that announced the discovery of SRY.

Although many details of how SRY works remain uncertain, some things are clear: 
SRY is a special kind of gene that has the power to switch other genes on or 
off. Genes exist in two states: on, in which they make a protein product (say, 
hemoglobin for your red blood cells), or off, in which they sit idly, making no 
protein product. SRY can switch some genes from one of these states to the 
other. No one imagines, therefore, that the many physical features that 
distinguish boys from girls-penises not vaginas, testes not ovaries, and so 
on-reflect the immediate effects of SRY alone. Rather, SRY sits at the top of a 
genetic cascade: if present, it switches on a set of other genes, some of which 
may in turn switch on yet other genes, and so on. (These other genes do not 
reside on the Y, but are scattered throughout the genome.) The cumulative 
effect of all this genetic switching is the development of testes; and the 
testes in turn produce hormones that then complete the development of a male 
anatomy. As this description implies, it is also now clear that the original 
state of a human embryo is female. It takes active work by SRY to divert the 
normal path of development from female to male, a process that, in human 
beings, starts when the fetus is seven weeks old.

Sykes gives an excellent account of the subtleties of human sex determination. 
Indeed he skillfully leads us through a number of other topics in human 
genetics, including his own research on the use of Y chromosome 
"fingerprinting" to reconstruct the movement of men throughout history. 
Contemporary Polynesian men, for example, often carry Y chromosomes whose DNA 
clearly derives from Europe, a vestige of the conjugal visits of European 
sailors in the age of exploration. And an astonishing number of men who live 
within the borders of the old Mongol Empire carry what is genetically the same 
Y chromosome. Sykes suggests that this extraordinarily popular Y may descend 
from Genghis Khan himself, who typically slaughtered the men he conquered and 
bedded the women he vanquished throughout much of Central Asia.

Fascinating as all this is, though, it turns out to be preliminary, a long 
preamble to Sykes's real purpose: to warn the world of his most important 
discovery-that human beings face an immense genetic disaster. And here Sykes's 
book takes a sharp turn for the worse.

2. Although Sykes doesn't describe this impending disaster until fairly late in 
his book, the subtitle to Adam's Curse gives it right away: we face a future 
without men. Sykes is convinced that the male of the species is doomed. Unless 
something is done-and soon- men face an "inevitable eventual extinction." You 
won't be surprised to learn that the alleged causes of this crisis reside in 
the Y chromosome. Sykes's publishers have, predictably, latched on to this dire 
news and the cover of his book speaks in ominous tones of the certain 
extinction of half of humanity. Also not surprisingly, the press has played 
along, with pieces in The New York Times and The Guardian warning that men may 
be a thing of the past.[1]

Sykes's case for the extinction of men hinges on an unusual problem plaguing 
many genes on the Y chromosome-they tend to pick up debilitating mutations and 
to ultimately degenerate into genetic junk. A couple of hundred million years 
ago or so, the X and Y were a pair of perfectly ordinary chromosomes that each 
carried a full complement of the same thousand genes. Since then, however, the 
Y has been slowly degenerating. As a result, while the human X still carries 
its thousand genes, the Y carries only about a hundred. Sykes believes that the 
genes that remain on the Y-including SRY as well as others required for the 
fertility of men-will also degenerate. The disastrous consequence, he says, 
will be the disappearance of fertile males. (Sykes sometimes says that males 
will become sterile, while at other times he suggests they'll disappear. 
Genetically, at least, the difference doesn't make a difference: if all males 
are sterile, they may as well not be there.)

Sykes even tries to calculate when disaster will strike. He concludes that, 
given the high rate of mutation on the Y, nearly all men will be almost 
completely sterile in about 125,000 years. In the meantime, male fertility will 
steadily fall. Adam's curse is, then, a rather serious affair. Not 
surprisingly, Sykes suggests some ways to avert this looming disaster. He seems 
most serious about using biotechnological methods to relocate Y chromosome 
genes, moving them to kinder, gentler chromosomes, where their continued 
existence is presumably assured. (Such a transfer is, in principle, possible, 
though some technical hurdles would have to be cleared.)

I'm afraid that this is all just silly. There are several related theories of 
why most genes on the Y chromosome degenerate and none of them predicts that 
men will become extinct. To see why not, we need to understand why Y 
chromosomes degenerate in the first place. All theories of Y degeneration (full 
disclosure: one of them is mine) hinge on an unusual feature of the Y: it 
doesn't "recombine." Recall that half your chromosomes come from your mother 
and half from your father. When you make sperm or eggs, each of your 
chromosomes from your mother pairs up with the corresponding one from your 
father. During this process, the two chromosomes often swap genetic material, 
an event called recombination. Consequently, any chromosome entering your sperm 
or egg likely carries some genes from your mother and others from your father. 
Oddly, though, the Y doesn't play this game: while all other chromosomes 
(including the X) recombine, the Y does not.[2]

This is important because recombination, it turns out, makes it easy for 
natural selection to get rid of bad mutations. Put conversely, natural 
selection is somewhat compromised when dealing with chromosomes that don't 
recombine. All our theories of population genetics thus predict that the Y will 
slowly but surely accumulate mutations that have slightly bad effects. But the 
key point is this: the process I have described will not spiral out of control, 
yielding sterile or absent men, for two reasons. The first is that the 
evolutionary forces that cause genes on the Y chromosome to degenerate turn out 
to be very weak; that's why it's taken hundreds of millions of years for our Y 
to fall into its current state of disrepair. In contrast, the evolutionary 
forces that maintain male fertility-and that even maintain a 50:50 ratio of 
males to females in populations-are very strong. The latter, strong forces, 
overcome the former, weak ones, and males neither become sterile nor disappear.

Second, not all genes on the Y chromosome are created equal. Some, indeed the 
great majority, originally resided on both the Y and X chromosomes. Natural 
selection will often tolerate loss of this kind of gene from the Y since 
there's a "backup" copy on the X that can still perform the gene's functions. 
Other genes, though, now exist only on the Y. Natural selection will most 
assuredly not tolerate the loss of this kind of gene since no backup copy sits 
on the X. The critical point is that most of the male fertility genes now 
residing on the human Y exist only on that chromosome and there's no way that 
selection will allow their loss.

Sykes's calculation suggests otherwise because it's wrong. He seems to assume 
that Y chromosomes carrying mutations that partially sterilize men will get 
passed on to future generations as often as normal, unmutated chromosomes. But 
they won't-that's what it means to be partially sterile. This misstep leads 
Sykes astray. There are simply no sound evolutionary grounds to support his 
sensational claims of the extinction of men.[3]

This is not to say that Y chromosomes can't be lost from a species. They can 
and sometimes are. But it is to say that the Y can disappear only after it's 
become dispensable, i.e., only after genetic changes take place that render 
Y-less males healthy and fertile. Sykes gets this logic backward. Telling the 
story of a rodent called the mole vole that's lost its Y, he marvels that these 
lucky voles made the genetic changes needed to avoid male extinction "only just 
in time" before their Y disappeared. But this is like saying that you got out 
of your clothes only just in time before they were thrown in the wash. In 
reality, the later event is contingent on the earlier.

The bottom line is that Sykes's alarmist talk of the extinction of men is just 
that-alarmist-and I wouldn't lose too much sleep over the possibility. And I 
certainly wouldn't give much thought (much less funding) to his technological 
fix to this nonproblem. There are enough real problems out there.

3. Talk of sex chromosomes and of single genes that determine sex naturally 
raises the specter of genetic determinism. Are certain behaviors and thoughts 
fundamentally male and others essentially female? To just what extent does 
recent biological research support the notion that genes determine our 
identity, sexual or otherwise?

The answer to this question depends entirely on the particular trait or 
character under discussion. If the character of interest is having testes or 
not, we are confronted with a biological determinism of the first magnitude. 
Whether an embryo develops testes depends essentially entirely on its genes; 
indeed you'd be hard pressed to find anything more genetically hardwired. If 
this brand of biological determinism alarms you, you are destined to be 
alarmed.

But things are considerably less clear if the trait of interest is, say, 
aggressiveness, or a curiosity about genes. Unfortunately, this (not so subtle) 
distinction is often lost on Sykes. Sociobiological claims of an almost 
unbelievably unnuanced sort run throughout Adam's Curse. Sykes's chief claim is 
that the Y chromosome causes its bearers to do crazy things. Sykes tells his 
readers that men, violent and sex-crazed, are "driven on by the lash of their Y 
chromosomes," and that the Y has "claimed the power to force us, men and women 
alike, to submit...to its will." Indeed it soon appears that the Y is legally 
liable for war, the subjugation of women, and empire building:

   Driven on and on by the crazed ambition of the Y-chromosome to multiply 
without limit, wars began to enable men to annex adjacent lands and enslave 
their women. Nothing must stand in the way of the Y-chromosome. Wars, slavery, 
empires-all ultimately coalesce on that one mad pursuit. In places Sykes is so 
overcome by the power of the Y chromosome that he passes from breathless 
exaggeration to patent absurdity. In a remarkable passage, he argues that 
Genghis Khan's Y chromosome was so successful that it's hard to know who was in 
charge:

   Is the Khan chromosome's achievement owing to the sexual exploits and 
military conquests of the Mongol emperor? Or was the Great Khan himself driven 
to success in war, and in bed, by the ambition of his Y chromosome? Since Sykes 
tells us-and on the previous page-that 16 million men now carry the Khan Y 
chromosome, the answer seems painfully clear: if the Y is in charge, the world 
would now have 16 million Genghis Khans on its hands.

Although Sykes's excesses might be excused as the inevitable hyperbole of a 
popularizer, their cumulative effect is serious and does, I think, do real 
damage: it's hard to believe that a biologically naive reader could walk away 
from Adam's Curse with a sensible view of the connection between genes and 
behavior.


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In any case, Steve Jones's Y and David Bainbridge's The X in Sex prove that 
popular books on human genetics-indeed on human sex chromosomes-need not trade 
in sociobiological excess. Sykes, Jones, and Bainbridge cover much of the same 
ground -all recount the discovery of SRY, discuss the role of hormones in 
sexual development, and describe Darwin's theory of sexual selection. But their 
positions on genetic determinism differ profoundly.

Jones, professor of genetics at University College, London, and the author of 
The Language of Genes and Darwin's Ghost, offers his latest book as an update 
of Darwin's 1871 classic The Descent of Man. Although Darwin was more of a 
hereditarian than many evolutionists like to admit, Jones himself turns out to 
be very cautious about attributing human behavior to genes. While he obviously 
understands that carrying the Y chromosome or not means that men and women will 
express at least some different genes, his treatment of the consequences of 
this difference is far more measured than Sykes's. Indeed Jones is, in places, 
explicitly anti-sociobiological. He reminds us, for example, that the Y 
chromosome has all too often served as "a useful alibi for man's excesses" and 
emphasizes that manhood tells a social tale as much as one written in nucleic 
acids [DNA] and must, with all that it implies, be constructed. Once the 
foundations of the male state are laid, what rises from them has little to do 
with DNA. Such sentiments are all too rarely expressed in popular writing about 
human evolution or genetics and it is to Jones's credit that his smart and 
informative book bucks the trend.

For his part, Bainbridge, a lecturer at the Royal Veterinary College, London, 
and author of Making Babies: The Science of Pregnancy, essentially eschews the 
entire controversy over evolutionary psychology. He sticks instead to hard 
science. Although Bainbridge is given to talking about how chromosomes "control 
our lives" or "become our dictator," he focuses almost entirely on the role of 
chromosomes in human disease, not in human cognition, emotion, or behavior. And 
when it comes to disease, there is, of course, little doubt that chromosomes do 
often control our lives.

Bainbridge's book is largely devoted to the X chromosome, not the Y. He spends 
much of his time on "sex-linked" conditions that affect men more than women; 
these range from annoyances like baldness to devastating diseases like muscular 
dystrophy.[4] Bainbridge also devotes many fascinating pages to complex 
ailments like autoimmune disease that, for reasons which remain unclear, 
disproportionately afflict women. (Hashimoto's thyroiditis, for instance-a 
leading cause of underactive thyroids-affects fifty times more women than men.)

But Bainbridge's chief concern is with the biology of human sex determination 
and with the many ways in which it can, and does, go wrong. In the end, his 
message is that while human beings obviously come in two predominant sexes, 
both cultural and biological forces give rise to a surprisingly "continuous 
spectrum of gender." While Bainbridge makes it fairly clear that he wouldn't be 
surprised if genes sometimes cause men and women to act or think differently, 
he's largely silent about the nature and extent of any such differences. While 
it's hard to know for sure, I suspect that this silence reflects the cautious 
neutrality of a sensible scientist confronted with mixed data and mountains of 
speculation.

For the truth is, of course, that we have little idea how much of the variation 
in human behavior-whether between the sexes or within them-is caused by genes. 
While I could defend this claim by pointing to a body of technical literature 
filled with conflicting assertions about the heritability of human behavior, 
there's no need for such a thing. The same point is made (albeit inadvertently) 
by the three books under review. Although all are written by smart male British 
biologists who read essentially the same scientific literature and who live and 
work within a hundred miles of each other, their views on the role of genes in 
human behavior are widely divergent, ranging from enthusiastic endorsement to 
considerable skepticism to apparent neutrality. This lack of consensus speaks 
for itself.

Notes

[1] See Claudia Dreifus, "Is Genghis Khan an Ancestor? Mr. DNA Knows," The New 
York Times, June 8, 2004. See also Bryan Sykes, "Do We Need Men?" The Guardian, 
August 28, 2003.

[2] This is almost, but not exactly, true. Tiny regions of the Y do in fact 
recombine with the X. I ignore these "pseudoautosomal regions" here, as they 
make up a small part of the Y chromosome and play no role in what follows.

[3] For a review of how and why Y chromosomes fall apart, see B. Charlesworth 
and D. Charlesworth, "The Degeneration of Y Chromosomes," Pro-ceedings of the 
Royal Society of London, Vol. 355 (2000), pp. 1563-1572.

[4] Because mutations on the X chromosome, not the Y, cause these conditions, 
it might not be obvious why they typically affect men, not women. The reason is 
that women, who carry two X chromosomes, can partly "mask" the effects of a 
mutated X with their other (and usually unmutated) X chromosome. Men, who have 
a single X, can't mask mutations in this way. This explanation, however, gets 
complicated in two ways. First, women randomly "inactivate" (turn off) one of 
their X chromosomes within each of their cells. So women mask the bad effects 
of mutated X chromosomes partly because those cells that happen to leave the 
good X turned on can "cover" for those cells that leave the bad X turned on. 
Second, recent work shows that this traditional account is somewhat incomplete. 
It turns out that, while most of the genes on one of a woman's X's are turned 
off, 15 percent are not. The result is that women, within their cells, express 
two copies of these X chromosomal genes while men express one. (See L. Carrell 
and H.F. Willard, "X-Inactivation Profile Reveals Extensive Variability in 
X-Linked Gene Expression in Females," Nature, Vol. 434, 2005, pp. 400-404.)