Microcephaly

IT is a longstanding cliche that human knowledge of the universe advances by a series of dethronements. There was a time when men thought that the whole world was alive with spirits whose main purpose and pleasure was to watch us. Great bonfires were lit to stir the sun from his midwinter torpor; kings were ritually slain and new kings proclaimed, so that the crops thus encouraged might rise from the ground. It took several thousand years for mankind to understand that the sun is not even aware of our existence, and that crops grow well or badly according to the weather, the soil, and the farmer's skill, not in response to acts of ritual sacrifice.

Even when those truths had sunk in, we still assumed that our familiar surroundings were at the center of things, with the heavenly bodies revolving around them. Then, in a new series of dethronements, from the 1530s to the 1930s, we learned that first the earth, then the sun, and then even the great galaxy itself, were humdrum objects in a universe populated by billions just like them.

We consoled ourselves with the thought that, whatever indignities we might suffer at the hands of astronomers, humanity is still a unique creation--the beauty of the world, the paragon of animals, as Hamlet said (though sardonically). However, as the 19th century advanced, and geologists and biologists began to get to grips with the immense age of the earth, and to notice the odd, suggestive similarities between living species, and the way living creatures occupy and are sustained by their environments, the line between humanity and the rest of nature began to blur a little.

At this point, however, the dethronement process was getting personal, and our resistance to it stiffened. It is, as Sherlock Holmes said, really nothing to us whether the earth goes around the sun or the sun around the earth; but to suggest that we, our precious selves, are no more than a very clever kind of monkey, is a dethronement too far for most of us. Where is the monkey that can sail a boat, write a poem, prove a theorem, pass a law, or found a city? Above all, where is the monkey that is self-aware, that can ponder his own actions and reflect on his own condition?

This resistance to the dethronement of humanity has been getting harder to maintain these past fifty years, as our techniques for observing life processes have advanced. We can now follow human ontogeny--the beginning and development of a human life--in terrific detail. It does not differ in any important way from the equivalent process for other higher animals. Similarly, every month we learn more about the brain, and about how it absorbs information and instructs the body to act. Nothing that we uncover lies outside the scope of ordinary biology, of cells responding to chemical events in neighboring cells, according to principles long understood. So far as we can observe, the brain is just an organ, with a job to do, like other organs. It works by chemistry, not magic. It seems to be as much a part of nature as a kidney, a gill, or a leaf, and operates by nature's rules.

Most threatening of all to what is left of our self-esteem, we are beginning to understand the human genome, the assemblage of 25,000 or so genes that "code up" the human organism, each gene a string of thousands, or tens of thousands, of basic building-block molecules. Other living things have genomes, too, of course, and the living creatures that most resemble us have genomes most like ours.

Of all living creatures, the one that resembles us most closely is the chimpanzee. A good approach to finding out what makes us humans so darn special would therefore be to get complete maps of the human and chimp genomes, and compare the two. Somewhere in the differences lies the secret of humanness--the thing that makes us more than just another great ape.

This work of comparison has now begun in earnest. Mapping of the human genome was completed in 2003. The chimp genome was published earlier this year. (That is, a database of all the components of all the genes of a particular chimp--an adult male named Clint--was made available to researchers.) Chimps and humans diverged from a common ancestor some time between 5 and 8 million years ago. Since that divergence--since the point when proto-humans could produce offspring with other protohumans, but not with proto-chimps--our genomes have developed differences. The actual number of differences is around 40 million at the building-block level. Since there are 3 billion building blocks in our, or a chimp's, genome, the overall difference is about 1.3 percent. Naturally it is that 1.3 percent, not the other 98.7 percent, that is most compelling to researchers. In there somewhere is the secret of our humanness. (And of the chimp's chimpness ... but that, with no slight intended to our prognathous pals, is of considerably less interest.)

But now things get nasty--politically, socially nasty. Forty million changes to the genome in 5 to 8 million years means that overall there has been one "evolutionary event" per couple of months since chimps and people parted company. Evolutionary change does not, in fact, work quite like that; but it is nonetheless the case that evolutionary events--changes to genes, as a result of which those changed genes give the host organism some survival advantage, so that the changed genes spread through the breeding population in succeeding generations--have been occurring all through that 5-to-8-million-year stretch, right down to historic times.

Why is that bad news? Because for the past 1 percent of that span--60,000 years or so, or, to put it another way, half a million or so building-block changes--modern humans have been scattered around the land surface of our planet in groups that have occupied widely different environmental niches, and haven't mixed much with each other. That's why your average Eskimo doesn't look much like your average Australian aborigine. Yes, we have bumped up against the R-word--race. This is the bitter paradox of human genetic studies. In seeking to understand what defines us, we cannot help learning about what divides us. Coming to terms with this paradox will not be easy. The results now emerging from the labs are prompting the first murmurs of a debate that will become loud and rancorous over the next few years.

BOMBSHELL PAPERS

Two papers published in the Sept. 9, 2005, issue of Science illustrate my point. The actual titles of the papers are "Microcephalin, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans," and "Ongoing Adaptive Evolution of ASPM, a Brain Size Determinant in Homo sapiens." Since "ASPM" stands for "Abnormal SPindle-like Microcephaly-associated," both these genes have something to do with microcephaly, a congenital infant condition in which the brain fails to develop properly. More precisely, it is defects of these genes that lead to microcephaly. Genes, like celebrities, draw attention to themselves by misbehaving, and it is often from the consequences of their misbehavior that they get their names. The point of these two genes themselves, in their healthy functioning, is to regulate brain size, or brain organization, in ways not yet completely understood.

The researchers published in Science are studying particular variants--"alleles"--of these genes. Of that first gene they say:

Of the second, they tell us that it

The implication of "strong positive selection" is that these new, variant forms of the genes gave great survival advantages to the humans that bore them. As the researchers say, the exact nature of those advantages is not yet known.

The time spans there--deduced from general, quite well-established principles governing rates of genetic change--are important. Modern humans apparently emerged from Africa around 50,000 to 100,000 years ago, spread over the world, and settled down as mostly inbreeding communities in a variety of environments from arctic tundra to tropical rain forest. Gene variants that showed up after that date would not necessarily spread much beyond their region of origin, and might not spread at all if they conferred survival advantage in one environment but not in another. And in fact, the present-day distribution of these alleles is far from uniform, as the papers in Science show. That second variant is, for instance, almost unknown among Native Americans, which is what you would expect, since the land bridge from Asia to the Americas across the Bering Strait ceased to be passable about 10,000 years ago as the seas rose with the end of the last Ice Age, before the gene variant appeared in Eurasia. More mysteriously, both these variants seem to be scarce in sub- Saharan Africa.

But ... but ... but ... haven't talking heads on TV science programs and in the pages of respectable newspapers been telling us for years that there are absolutely no significant genetic differences whatever between human groups defined by common ancestry? Yes; but you see, they have been lying through their teeth. (A geneticist I spoke to when preparing this article put it more diplomatically: "Statements like that are politically driven.") To be fair, those talking heads have been lying with the best of intentions. Ours is a nation founded on the proposition that all men are created equal. Of course, nobody ever supposed that to mean that we are all equally tall, equally strong, or equally clever; but if different human groups, of different common ancestry, have different frequencies of genes influencing things like, for goodness' sake, brain development, then our cherished national dream of a well-mixed and harmonious meritocracy with all groups equally represented in all niches, at all levels, may be unattainable.

Yet to believe that that undesirable thing is not so-to believe that all genes show up with the same frequencies in all human common-ancestry groups--you have to believe that, to assure the peace of mind of 21st-century American idealists, evolution came to a screeching halt 50,000 years ago. No scientifically literate person believes that, and the results written up in Science last month in any case flatly disprove it, as will the multitude of similar results no doubt soon to follow.

As a political aside, it is worth noticing that Donald Kennedy, the editor-in-chief of Science, is a conventional academic liberal, who has put his name to strongly anti-Bush, pro-Kyoto editorials on global warming. It speaks well to the spirit of true collegiality that still survives in science that these papers, whose implications must be so unwelcome to the egalitarian Left, appeared in Kennedy's magazine. In this context, it should also be noted that Nicholas Wade, science writer at the New York Times, gave reasonably fair coverage to the two papers.

(And as a further aside, fans of the Intelligent Design movement should note that none of the arguments presented in the Science papers goes against anything they believe. Sophisticated IDers do not deny the reality of evolutionary change within species, which is what these papers are talking about. ID denies only that evolution can account for new species, an idea that is not in play here. So far as the human organism over the past 50,000 years is concerned, the egalitarian Left has much more serious issues with evolution than the religious Right has. Prior to that date, the anti-Darwinian Right has all the problems, the Left really none. As a simple Darwinian rightist, I myself can glide serenely past all this illogical nitpicking ...)

DEAL WITH IT

The unhappy thing for the United States is that the problems implicit in results like these are very peculiarly our problems, America's problems. The lead researcher on both those papers is 37-year-old Bruce Lahn, who was born and raised in China. Bruce left that country in 1988, after some unhappy experiences trying to organize democracy protests at his Beijing college. He has now made his peace with the Chinese authorities, and commutes between his chair at the University of Chicago and a well-equipped lab at Sun Yat-sen University in Canton. China is an ethnostate, 92 percent of her people identifying themselves as Han Chinese, and most of the remainder belonging to related East Asian groups. For China, as for other ethnostates like Japan or Finland, these papers in Science are curious and interesting insights into recent human evolution, bearing no emotional content at all. For us Americans, they are two fizzing sticks of dynamite. My guess would be that if Bruce continues along this line of research, he will soon be spending a lot more time in China.

While I believe that results like these out of the human sciences should prompt us to begin some hard thinking about our society, and about what we can reasonably expect social policies to accomplish, I don't think that conservatives should fear these results, or strive to deny them. For all the corruption it has suffered from public financing and infection by campus political fads, science is, I shall always believe, a fundamentally conservative profession. Pseudoscience and wishful thinking--they are usually the same thing--have their natural home on the political left, Marx's "scientific socialism" being only the best-known example. True science doesn't care what we believe or what we wish for. It just tells us what is, and leaves us to come to terms with it as best we can. Science is a Daddy discipline, not a Mommy discipline.

It is not the case, as foolish people like Richard Dawkins tell us, that science excludes religion. (The research geneticist personally best known to me, another native of China, is a passionate adherent of the Falun Gong sect.) It is true, however, that in his working hours a scientist owes devotion to only one deity, the one Rudyard Kipling called "the God of Things As They Are." That God is, as Kipling himself was, profoundly conservative in all His works, and conservatives, religious or otherwise, have nothing to fear from Him. To judge from history, in fact, His greatest delight is to make fools--or slaves, or corpses--of pacifists, family-breakers, sexual liberators, dispensers of unconditional welfare, love-the-world purveyors of Uplift, Scientific Socialists, and deniers of unpleasant truths.

Some of the truths now beginning to emerge from the human sciences will strike us as very unpleasant indeed. Some of them will force us to hard thinking about our nation, our ideals, and our traditional boundless optimism towards the potentialities of human beings. We have it on good authority, though, that we shall know the truth, and the truth shall make us free. I believe that if we hold fast to faith in that proposition, and trust science to uncover the truth, neither we nor our country will come to any harm.

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