james f. crow unequal by nature: a geneticist's perspective on

In February of 2001, Craig Venter, presi-dent of Celera Genomics, commentingon the near-completion of the humangenome project, said that “we are allessentially identical twins.” A newsheadline at the time made a similarpoint: Are We All One Race? Modern Sci-ence Says So. In the article that followed,the author quoted geneticist KennethKidd: “Race is not biologically de½nable,we are far too similar.”

Venter and Kidd are eminent scien-tists, so these statements must be rea-sonable. Based on an examination of ourdna, any two human beings are 99.9percent identical. The genetic differ-ences between different groups ofhuman beings are similarly minute.

Still, we only have to look around tosee an astonishing variety of individualdifferences in sizes, shapes, and facialfeatures. Equally clear are individual dif-ferences in susceptibility to disease–andin athletic, mathematical, and musicalabilities. Individual differences extend todifferences between group averages.Most of these average differences areinconspicuous, but some–such as skincolor–stand out.

Why this curious discrepancy betweenthe evidence of dna and what we canclearly see? If not dna, what are thecauses of the differences we perceivebetween individuals and between groupsof human beings?

Dna is a very long molecule, com-posed of two strands twisted aroundeach other to produce the famous doublehelix. There are forty-six such dna mol-ecules in a human cell, each (along withsome proteins) forming a chromosome.The dna in a human chromosome, ifstretched out, would be an inch or morein length. How this is compacted into amicroscopic blob some 1/1000 inch longwithout getting hopelessly tangled is anengineering marvel that is still a puzzle.

The “business” part of the dna, thepart that carries genetic information, isthe sequence of nucleotides, or bases, in

Dædalus Winter 2002 81

James F. Crow

Unequal by nature:a geneticist’s perspectiveon human differences

James F. Crow, a Fellow of the American Acade-my of Arts and Sciences since 1966, is professoremeritus of medical genetics at the University ofWisconsin. Over a career that has spanned morethan ½fty years, he and his collaborators havestudied a variety of traits in Drosophila, dissectedthe genetics of ddt resistance, measured theeffects of minor mutations on the overall ½tness ofpopulations, described the behavior of mutationsthat do not play the game by Mendel’s rules, stud-ied the effects of nonrandom mating, and consid-ered the question “What good is sex?”

the molecule. There are four of these,commonly designated as A, G, T, and C.(I could tell you what these letters standfor, but you wouldn’t understand thisessay any better if I did, so I won’t.)

In the double helix, there are fourkinds of base pairs: AT, GC, TA, and CG.The speci½c pairing rules–Awith T andGwith C–are dictated by the three-dimensional structure of the bases.

In a chromosome, the base pairs are ina precise sequence, and the orderlyprocess of cell division assures the repro-duction of this sequence with remark-ably few errors. Chromosomes occur inpairs, one member of each pair fromeach parent, and the dna sites in thetwo corresponding chromosomes matchup. We have twenty-three pairs of chro-mosomes, or a total of forty-six, as previ-ously mentioned, in each cell. Theseforty-six chromosomes contain aboutsix billion base pairs. If we randomlychoose a pair of bases from correspon-ding sites in two persons, 99.9 percent ofthe time they will be the same. This per-centage depends only slightly onwhether the two people are from thesame or from different continents, fromthe same or from different populationgroups.

In order to make sense of how thedna of human beings can be so similar,despite all the important visible andphysiological differences among individ-uals and groups, it is helpful to recountour evolutionary history.

All mammals, including ourselves, aredescended from an ancestral species thatlived about one hundred million yearsago. In our mammalian ancestry an aver-age base has changed, say from an A to aT, at the almost unbelievably slow rate ofabout one change per billion years. Thismeans that only a small fraction of thebases, one hundred million divided byone billion, or 1/10, have changed during

that time. As a result, we share roughly90 percent of our dna with mice, dogs,cattle, and elephants.

Coming closer to home, the dna ofhuman beings and chimpanzees is 98 to99 percent identical. The differencesbetween us that we (and presumably thechimps) regard as signi½cant depend ononly 1 or 2 percent of our dna.

Much of human dna is very similar toeven more remote ancestors: reptiles, in-vertebrates, and even plants. All livingthings share many functions (e.g., respi-ration) going back to a very distant past.Most of our dna determines that we arehuman, rather than determining how weare different from any other person. So itis not so surprising that the dna of anytwo human beings is 99.9 percent identi-cal.

What produces variability betweenindividual organisms–and makes possi-ble evolutionary change–is errors in thedna copying process. Sometimes,because of this, one base is changed toanother–it mutates. Among the six bil-lion base pairs each of us inherits fromour parents, a substantial number–ahundred or more–are new mutations.

How can we reconcile this large num-ber with the extremely slow rate of evo-lutionary change? The explanation isthat only a tiny fraction of mutationspersist over time. Some mutations sur-vive as a matter of either luck or–if themutation confers a biological advan-tage–natural selection. Even if advanta-geous, an individual mutation has littlechance of surviving a long evolutionarytrip. The slow rate of evolutionarychange explains why we mammals are sosimilar in our dna.

Molecular studies of dna have beenextremely fruitful in working out theevolutionary history of life. Much ofwhat we know about human ancestrycomes from dna studies, supplemented

82 Dædalus Winter 2002

James F.Crow oninequality

by a rather spotty fossil record. The dnaevidence strongly supports the idea thatthe human species originated in Africa,and that European and Asiatic popula-tions–indeed, all non-Africans–aredescended from a small number ofmigrants from Africa. The strongest evi-dence for this is that Africans are morevariable in their dna than are other pop-ulations.

Analysis of dna allows us to measurewith some precision the genetic distancebetween different populations of humanbeings. By this criterion, Caucasians andAsians are relatively similar, whereasAsians and Africans are somewhat moredifferent. The differences between thegroups are small–but they are real.

dna analysis has provided excitingnew answers to old questions. But its½ndings can also be misleading. Take thecase of men and women and sex chro-mosomes. Females have two X chromo-somes, while males have an X and a Y.The Y chromosome makes up perhaps 1percent of the dna. But there is very lit-tle correspondence between the Y andthe other chromosomes, including the X.In other words, the dna of a humanmale differs as much from that of afemale as either does from a chimpanzeeof the same sex. What does this mean?Simply that dna analysis, which hasgiven us a revolutionary new under-standing of genetics and evolution,doesn’t give sensible answers to somecontemporary questions that society isinterested in.

Most of the differences that we noticeare caused by a very tiny fraction of ourdna. Given six billion base pairs percell, a tiny fraction–1/1000 of six billionbase-pairs–is still six million differentbase pairs per cell. So there is plenty ofroom for genetic differences among us.Although we differ from each other in a

very tiny proportion of our dna, we dif-fer by a large number of dna bases.

Some noteworthy evolutionarychanges in human beings have occurredrelatively rapidly, despite the slow over-all rate of change at the dna level. Thedifference between the skin color ofAfricans and Europeans probablyevolved in less than ½fty thousand years,an adaptation to differences in climate.Still more rapid were changes in genesthat confer resistance to malaria inAfrica and Mediterranean regions; itonly took between four and eight thou-sand years for the new genes to evolve.What genetic analysis reveals is thatsome of the genetic changes that seem sosigni½cant to us depended on a very tinyfraction of our dna.

But, as I said, this tiny fraction is still avery large number of bases. No twohuman beings are alike in the traits theypossess. Some are tall, others are short;some are stocky, others thin; some aregifted musically, others tone deaf; someare athletic, others awkward; some areoutgoing, others introverted; some areintelligent, others stupid; some canwrite great poetry or music, most can-not. And so on.

To understand our differences, weneed to consider not just dna, but itscellular products as well. This area ofstudy is new, but it is progressing rapid-ly. The emphasis is changing from dnasequences to genes. A gene is a stretch ofdna, usually several thousand base pairslong. The function of most genes is toproduce proteins. The genome sequenc-ing project has revealed that we humanshave thirty to forty thousand genes. Butsince a gene often produces more thanone kind of protein, sometimes produc-ing different kinds for different bodyparts, the number of kinds of protein ismore like one hundred thousand.

We share a number of genes with


Unequalby nature

chimpanzees, genes that make us pri-mates rather than elephants or worms.Evolutionary scientists believe thatmany of the differences that we observebetween ourselves and chimpanzeesinvolve changes in the amount ratherthan in the nature of gene products.Human beings and chimpanzees shareproteins that produce body hair andbrains, but in chimpanzees these pro-teins produce more hair and less brains.Why this should be so is still far frombeing fully understood. But this is aresearch area that is advancing very rap-idly, and there are good genetic leads tobe followed up.

Of course, not every human differencehas a genetic cause. Many are environ-mental, or are the result of interactionsbetween genes and environment. Evengenetically identical twins develop intodistinct individuals.

The ability to learn a language is large-ly innate, built into the nervous systemof all normal people, as demonstrated sobeautifully in the effortless way in whichyoung children learn to speak. But theparticular language any individual learnsobviously depends on the social setting.Mozart was a great composer partlybecause of his genes and partly becauseof his training. Ramanujan had a greattalent for mathematics, but without hisbeing exposed to a textbook–not a verygood one, by the way–he could neverhave made his astounding discoveries.Michael Jordan has a talent for basket-ball, but it would never have developedhad he grown up among the Inuits.

Just as there are great differences amongindividuals, there are average differ-ences, usually much smaller, betweengroups. Italians and Swedes differ in haircolor. Sometimes the differences aremore conspicuous, such as the contrast-ing skin color and hair shape of Africans

and Europeans. But, for the most part,group differences are small and largelyovershadowed by individual differences.

Biologists think of races of animals asgroups that started as one, but later splitand became separated, usually by a geo-graphical barrier. As the two groupsevolve independently, they graduallydiverge genetically. The divergences willoccur more quickly if the separate envi-ronments differ, but they will occur inany case since different mutations willinevitably occur in the two populations,and some of them will persist. This ismost apparent in island populations,where each island is separate and there isno migration between them. Each onehas its own characteristic types. In muchof the animal world, however, and alsoin the human species, complete isolationis very rare. The genetic uniformity ofgeographical groups is constantly beingdestroyed by migration between them.In particular, the major geographicalgroups–African, European, andAsian–are mixed, and this is especiallytrue in the United States, which is some-thing of a melting pot.

Because of this mixing, many anthro-pologists argue, quite reasonably, thatthere is no scienti½c justi½cation forapplying the word “race” to populationsof human beings. But the concept itselfis unambiguous, and I believe that theword has a clear meaning to most peo-ple. The dif½culty is not with the con-cept, but with the realization that majorhuman races are not pure races. Unlikethose anthropologists who deny the use-fulness of the term, I believe that theword “race” can be meaningfully appliedto groups that are partially mixed.

Different diseases are demonstrablycharacteristic of different racial and eth-nic groups. Sickle cell anemia, for exam-ple, is far more prevalent among peopleof African descent than among Euro-



peans. Obesity is especially common inPima Indians, the result of the suddenacquisition of a high-calorie diet towhich Europeans have had enough timeto adjust. Tay-Sachs disease is muchmore common in the Jewish population.There are other examples, and new onesare being discovered constantly.

The evidence indicating that some dis-eases disproportionately afflict speci½cethnic and racial groups does not ordi-narily provoke controversy. Far morecontentious is the evidence that someskills and behavioral properties are dif-ferentially distributed among differentracial groups. There is strong evidencethat such racial differences are partlygenetic, but the evidence is more indi-rect and has not been convincing toeveryone.

To any sports observer it is obviousthat among Olympic jumpers andsprinters, African Americans are farmore numerous than their frequency inthe population would predict. The dis-proportion is enormous. Yet we alsoknow that there are many white peoplewho are better runners and jumpersthan the average black person. How canwe explain this seeming inconsistency?

There is actually a simple explanationthat is well known to geneticists andstatisticians, but not widely understoodby the general public or, for that matter,by political leaders. Consider a quantita-tive trait that is distributed according tothe normal, bell-shaped curve. iq canserve as an example. About one personin 750 has an iq of 148 or higher. In apopulation with an average of about 108rather than 100, hardly a noticeable dif-ference, about 5 times as many will be inthis high range. In a population averag-ing 8 points lower, there will be about 6times fewer. A small difference of 8points in the mean translates to several-fold differences in the extremes.

Asian Americans represent about 12percent of the California population, yetthey represent 45 percent of the studentbody at the University of California atBerkeley. Asians have only slightly high-er average sat scores than Caucasians,but the university’s policy of admittingstudents with the highest sat scores hasyielded a much larger proportion fromthe group with the higher mean.

Two populations may have a largeoverlap and differ only slightly in theirmeans. Still, the most outstanding indi-viduals will tend to come from the popu-lation with the higher mean. The impli-cation, I think, is clear: whenever aninstitution or society singles out individ-uals who are exceptional or outstandingin some way, racial differences willbecome more apparent. That fact maybe uncomfortable, but there is no wayaround it.

The fact that racial differences existdoes not, of course, explain their origin.The cause of the observed differencesmay be genetic. But it may also be envi-ronmental, the result of diet, or familystructure, or schooling, or any numberof other possible biological and socialfactors.

My conclusion, to repeat, is thatwhenever a society singles out individu-als who are outstanding or unusual inany way, the statistical contrast betweenmeans and extremes comes to the fore. Ithink that recognizing this can eventual-ly only help politicians and social policy-makers.

These are times of very rapid change inour understanding of biological process-es. The genome project is but one exam-ple. At the same time, we are gettingmuch closer to a deep understanding ofthe nervous system and of human be-havior. Medical knowledge improves, asdoes data collection and computer


Unequalby nature

analysis. All of these tell us more aboutindividual and group differences. Whatwill be the impact of this new knowledgeon societal issues? What are the politicalimplications of modern biology?

We have seen that the dna sequencesimilarities revealed by the genome proj-ect, valuable as these are for answeringmany interesting and important ques-tions, are misleading in regard to impor-tant human differences. But this situa-tion is rapidly changing. The currentemphasis goes beyond simple dnasequences to identifying the individualgenes, their products, and their complexinteractions. At the same time, not onlythe kinds of gene products (usually pro-teins) but their relative amounts arebeing investigated by much sharper newtools. Genes differ greatly in their pro-ductivity, including differences in activi-ty in different parts of the body.

In the near future, biologists will beable to tell us much more than we nowknow about the genetic and environ-mental causes of human differences. Themost obvious and immediate humanbene½ts will be in medicine. We canforesee the time when many–we canhope most–of our individual suscepti-bilities to disease will be understood, sothat the disease can be predicted inadvance, allowing doctors to anticipateand tailor treatments for the particularperson. Small steps in this direction havealready been made. New treatments areunder development. As a result of ourgenetic understanding, we also now bet-ter understand how to manipulate theenvironment in order to help preventdisease.

At the same time, the study of geneproducts and their regulation is beingextended to normal traits. We can expectthat the molecular biology of the future,perhaps the quite near future, will pro-vide precisely the kind of information

that in the past has depended on obser-vation and statistical analysis of oftenvaguely de½ned traits. We shall be able,as individuals, to know a great dealabout our own genetic makeup.

The magni½cent advances in molecu-lar biology will bring new depths ofunderstanding of human differences,normal and pathological, and the extentto which these are genetic or environ-mental–or, as usually will be the case,both. Whether society will accept thisknowledge willingly and use it wisely Idon’t know. My hope is that gradualprogress, starting with small beginnings,can lead to rational individual behaviorand thoughtful, humanitarian socialpolicies.

It is important for society to do a betterjob than it now does in accepting differ-ences as a fact of life. New forms of sci-enti½c knowledge will point out moreand more ways in which we are diverse. Ihope that differences will be welcomed,rather than accepted grudgingly. Whowants a world of identical people, even ifthey are Mozarts or Jordans?

A good society ought to provide thebest kind of environment for each per-son and each population. We already dothis in part. We give lessons to musicallygifted children. We encourage athletesand give them special training (andsometimes dubious drugs). Studentselect courses according to their abilitiesand interests. We have special classes forthose with disabilities, and such classesare becoming more speci½c as the causesof the disabilities are understood.

We cannot, of course, tailor-make aspecial environment for every individ-ual, but we can continue to move in thisdirection. Finding a genetic basis for atrait doesn’t mean that environment isunimportant. Indeed, more environ-mental influences on the human organ-



ism are constantly being discovered,often through genetic studies.

A test of our democratic institutionswill be the degree to which people canaccept all our differences and ½nd waysto ½t them into a smooth-working, hu-manitarian society. And I argue that weshould strive not only for maximum per-sonal satisfaction but for maximum con-tribution; each of us owes society thefruits of our special gifts. I believestrongly that research into the geneticand environmental causes of human dif-ferences should continue and be sup-ported. The newer procedures broughtabout by molecular advances and com-puters will greatly accelerate discover-ies.

I believe that knowledge, evenunpleasant knowledge, is far preferableto ignorance. I hope that American soci-ety can be less fearful of learning thetruth about biological inequalities andmore courageous in using discoveries inways that are humanitarian and pro-mote human welfare.

The question of equal opportunityversus equal outcomes becomes particu-larly vexing in those occupations andprofessions for which only a small frac-tion of a population can qualify. I havealready mentioned the gross overrepre-sentation of African Americans amongOlympic runners. This is closer to a truemeritocracy than anything else I canthink of: a stopwatch is color-blind. Inthis case, there seems to be no socialpurpose in demanding equal racial rep-resentation.

In some important professions, suchas physics and engineering, Asian Amer-icans are overrepresented and AfricanAmericans underrepresented. We pre-sumably get better research because ofthis. This may or may not outweigh theinequity of unequal group representa-tion. That is a social decision.

What about physicians? There maywell be social considerations, perhapstemporary ones in our society, thatwould make race more important thantest scores in selecting students for med-ical schools.

To achieve political and social equalityit is not necessary to maintain a ½ctionthat important human differences donot exist. The great evolutionist Theo-dosius Dobzhansky said it well: “Peopleneed not be identical twins to be equalbefore God, before the law, and in theirrights to equality of opportunity.”

I have emphasized that people differ,and differ greatly. They differ not only inshapes and sizes, but also in abilities andtalents. They also differ in tastes andpreferences. As Shaw said, “Do not dounto others as you would that theyshould do unto you. Their tastes maynot be the same.” Society’s business, Ithink, is not to minimize individual dif-ferences. We shouldn’t try to ½t peopleinto one mold.

While I expect that science will con-tinue to provide us with further evi-dence of human variability, and while Iwelcome such variability as a source ofsocial enrichment, there are some kindsof human variability that we could welldo without. I refer to serious, painful,debilitating diseases. Many of these arethe result of an unlucky throw of thegenetic dice. Already there are ways ofdiscovering, preventing, and treatingsome of them. More treatments are sureto come. I hope they will be acceptedwillingly and used responsibly. I for onewould be content if the genes for Tay-Sachs disease and Duchenne musculardystrophy were to become extinct, alongwith the malaria parasite and aidsvirus. I hope the great humanitarianbene½ts that could come from geneticresearch will not be held up by fears ofpossible future misuse.


Unequalby nature

Let me leave the last word for JimWatson, co-discoverer of the doublehelix and a major ½gure in the genomeproject:

If the next century witnesses failure, let itbe because our science is not yet up to thejob, not because we don’t have the cour-age to make less random the sometimesmost unfair courses of human evolution.



james f. crow unequal by nature: a geneticist's perspective on

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