Reprinted from BioScience, Vol. 17, No.7, 1967, pp. 461 - 464
Editor's Note: This article appeared in a somewhat different form in the Bulletin of Atomic Scientists, (Ornstein, 1967). The editors of BioScience asked Dr. Ornstein to allow its publication in this journal as well because they felt it deserved the attention of a larger audience of biologists.
Crow's essay (1966) on "The Quality of People: Human Evolutionary Changes" posed a number of important problems concerning the evolutionary future of the human species. Particularly important are the problems resulting from the slow increase in frequency of mutant genes in human populations which must inexorably follow in the most obvious democratic and humane termination of the population explosion.
Among knowledgeable biologists, much confidence is placed in our current understanding of the broad outlines of the evolutionary process in populations of sexual organisms. Evolution is seen to result from the interplay of the genetic endowment of the members of an interbreeding population with that population's environment.The genetic endowment is continuously subject to recombination as a result of processes associated with sexual reproduction. Occasional random physical rearrangements, duplications, etc, provide opportunities for linking together of especially adaptive recombinations. Rare random point mutations of the coded genetic message provide the seeds for adaptive inovation. Those mutations and rearrangements that provide their carriers with some adaptive advantage will, on the average, gradually replace the parental stock. Those mutations which, on the average, confer a selective disadvantage to their carriers are generally eliminated--or held at a low incidence--in competition with the parental stock. Thus, evolution results from balanced interaction of random mutation and selection (Dobzhansky, 1951).
In the absence of mutation, a non-human species would ultimately be expected to become extinct if its fixed genetic resources were inadequate to permit it to adapt to the kinds and magnitudes of environmental changes to which it might be exposed to over periods of millions of years. In contrast, man, with his unique ability to revamp his environment, now depends upon cultural and technological mutations to provide even greater plasticity for coping with natural environmental change than that provided by the adaptive innovations which are sparked by random genetic mutation. Therefore, the absence or elimination of mutation in humans need not constitue a biological threat.
In the absence of selection, however, any species (including Homo sapiens ) would be expected to degenerate gradually through a process closely related to genetic drift (Dobzhansky, 1951). The resulting increasing accumulation of mutations would produce wider and wider departures of the individual phenotypes from one another and from the parental type. The mechanism is quite simple. The overwhelming majority of mutations which occur in a selective environment are deleterious and are therefore eliminated, tending to keep the population relatively monotypic. Selection plugs the multiple leaks that are forever occuring in the genetic dyke and channels the flow of life thermodynamically uphill along adaptive paths. In the absence of selection, the dike would slowly crumble and the flow would dissipate down a multitude of exentropic gulleys, producing a vastly refashioned species. The only directions or styles that would be apparent in this kind of evolutionary process would be those which reflect changes in those genetic code words which for whatever reasons, mutate at the highest rates--and these mutations will almost always represent phenotypic departures from the parental type. And later generations of mutations would represent still further departures from this more heterotypic base.
Now what can reasonably be meant by "in the absence of selection"? If death were eliminated and fertility maintained indefinitely, there would be, at least initially, no selection--however, in an extremely short period of time, a species would exhaust any "real" environmental resources--and this hypothetical kind of "elimination of selection" thus would be too short-term to be relevant to our present discussion. But there are two other ways to eliminate selection: (a) a mechanism which maintains a stable population size, in the presence of random fluctuations of fertility, by random elimination of offspring, independent of the genetic endowments of the individuals; and (b) a mechanism which maintains a stable population size by uniformly and randomly limiting fertility of individuals, independent of their genetic endowment.
If the elimination of offspring occurs before birth (e.g., abortion and some forms of birth control), it is essentially equivalent to a limitation on fertility, or what is commonly called birth control.
With this frame of reference, we will now consider two facts of life which, although in and of themselves are quite encouraging from a humanistic point of view, nonetheless conspire to generate the next great threat to humanity.
There is a growing agreement that some form of birth control will provide the only reasonable solution to the population explosion and the limited resources of our planet. All efforts to increase food production to relieve, at least temporarily, population pressures should be encouraged. But no one supposes that exponential population growth can be matched by food technology. Therefore, in the long run, enthusiasm for such efforts is not likely to be permitted to reduce attempts at population control. Those who divert attention from the real and pressing problem by appeal to science fiction--expecting "to reap the resources of the universe"--will hopefully soon begin to appreciate the sobering cost estimates of even a trip to a nearby star (von Hoerner, 1962).
The ranks of those who at least pay lip service to the principles of equalitarianism and classless or open-class societies are swelling rapidly both within bona fide democracies and in major totaitarian states. It seems not only undesirable from a humanistic point of view that this trend should be reversed, but reversal is also unlikely.
The expected solution, if any, to the population explosion therefore will probably involve the almost universal application of birth control and voluntary (although socially and/or economically rewarded or coerced) individual commitment to the maintenance of a reproductive rate of two offspring per pair of adults, independent of the genetic (or other) endowment of the parents. If such a program is successful in maintaining a stable population and avoiding racial, class and individual biases in the rates of reproduction (and therefore in the composition of future generations), the human species may eliminate selection and thus be on the road to ultimate biological degradation and probable extinction!
Is there a democratic way out? Lederberg (1966) has stated that "It would be a tour de force to demonstrate any change (increase) in the frequency of a specific harmful gene in a human population that could be unambiguously traced to relaxation of natural selection against it. In comparison to the pace of medical progress, these exigencies are trivial." Crow also has pointed out that "An increase incidence [of homozygotes for a rare recessive harmful gene] of 2% per generation would mean about 40 generations for the incidence to double. This is more than a thousand years. The genetic consequences of the successful treatment of diseases caused by rare recessive genes are slight." The tone of such remarks is calculated to lull the reader into a state of evolutionary complacency. Yet, on the following page, Crow's tone turns. "However, I must introduce two cautions in this perhaps over-optimistic discussion of simple examples. One is that the increase is geometric, not arithmetic, and over a long period will become important" (itallic supplied).
Effective tools for recognizing the human cariers of recessive genes (the great majority of new mutations are recessive and harmful) have only been discovered within the past few years. Changes in the frequency of such genes due to mutation in large breeding populations (the human population now is effectively a very large breeding population) occur very slowly. Therefore an extremely large random sample of each of two successive generations would probably be required to demonstrate a change unambiguously. Lederberg's first statement is therefore correct.
His second statement, however, requires more careful examination. "Trivial" by what standards? Examine the case of a disease such as diabetes. Assume that diabetes is due to a recessive gene in the homozygous state. Prior to the discovery of insulin, a large fraction of diabetics died before reaching sexual maturity (or soon enough thereafter to lower the probability of the survival of their offspring). The human efforts, in terms of research and medical care, and the economic and other social costs of the production of drugs which control diabetes clearly are trivial when compared to the suffering of millions of diabetics and their families that was endured before the development of such drugs. Medicine has, in this case, effectively begun to neutralize the harmfulness of diabetes genes. Their frequencies and the frequency of afflicted carriers will therefore automatically increase among future generations due to unapposed mutation pressure (Dobzhansky, 1961). In a similar way, eye glasses, artficial kidneys, and all the devices, transplants, and drugs of the coming euphenic revolution will reduce or eliminate the harmfulness of many genes. But the genetic base from which harmful mutations arise has until now been kept relatively homogenoeous by selection. Therefore, the numbers and kinds of mutations that at present can occur are constrained by the homogeneity of that base. As this special variant of genetic drift slowly takes over, the base will become more and more heterogeneous, and euphenic correction of each new mutation will become more and more a problem of the custom engineering of individual medical or biochemical crutches or prostheses. Insulin solves the problem of a very large number of diabetic individuals and the social cost per individual is very small.*
*The production of insulin has been coupled with, rather than competitive with, food production. It is, however, perhaps instructive to note that until very recently, the maintenance of an average diabetic over a 30-year period required the production and destruction of about 1000 head of cattle.
This is likely to gradually become less and less the case for the correction of newly arising mutations. It may not be possible to predict, with any accuracy, the relative rates of progress of medical and euphenic research as compared to the rates of increase of problems with which medicine will have to deal as a result of the elimination of selection. In the short run, the benefits from the development of crutches will clearly outweigh the costs, but in the long run (and how long is problematical) the costs are likely to become prohibitive. It takes little effort to conjure up glimpses of the bizarre brave new world--a world of enormous individual variability, each individual (human?) uniquely wired up and supported by his own special set of transplants and external biochemical plant. A glimpse into a relatively modern hospital will convince one of the rapidity with which this vision is being realized at present, although admittedly for a relatively tiny fraction of the world population. But later, a major portion of technology and virtually all of society's resources would be consumed by that technology. An individual that would be recognizable as a member of Homo sapiens would be rare indeed. Are such exigenicies "trivial"?
The cultural relativist might argue that provided such a culture does not exhaust its resources in trying to keep itself alive, its values and way of life may be just as good for its members as ours are for us. I would counter that if we can now, by judicious planning, provide greater adaptive flexibility and fewer biological and economic burdens for our descendants, as judged by our standards of value, then we cannot entertain the relativist's rationalization with a clear conscience.
What alternatives exist? Lederberg (1966) states "Eugenics is relatively inefficacious since its reasonable aims are a necessarily slow shift in the population frequencies of favorable genes" (italics supplied). He and others (e.g., see Dobzhansky, 1962) have rightly emphasized the problems of defining "favorable" genes in our present state of genetic ignorance. The problems of defining "unfavorable" genes may often be equally difficult. If the genes for schizophrenia were responsible, in the heterozygous state, for attributes of the kind of intelligence which we believe we value, eugenic attempts to reduce the frequency of schizophrenics from their present levels of 1% to 2% might reduce average intelligence of the population as a whole. This might produce an undesired and unexpected by-product which would outweigh the desired reduction in human misery and in the social burden that elimination of schizophrenia should represent. Would schizophrenia genes average out as favorable or unfavorable? And would we want to increase or decrease their frequency? Because of the difficulty in defining "favorable" genes as well as "unfavorable" genes, I question Lederberg's implication of the absence of other reasonable (short-term, i.e., within the next 10,000 years?) aims of eugenics.
In discussing the evolutionary process, Crow reminds us "...that for many, and probably most traits there is little selection toward systematic change in a fixed direction. Most natural selection is not changing things. Rather it is acting to remove deviants in both directions from the mean, or adjusting to fluctuations in the environment, eliminating recurrent harmful mutations, or maintaining polymorphisms. Considerable selection is needed to maintain the genetic status quo, even without any progressive evolutionary changes" And later on he asks, "...must we soon begin genetic steps if the human phenotype is not to deteriorate? And should we be content merely to keep ourselves from getting worse?"
I believe we must begin by being "content merely to keep ourselves from getting worse," and that perhaps the only reasonable short-term and conservative aims of eugenics, taking into account the impending reduction in natural selection and our present state of ignorance of human genetics, are: (1) the approximate maintenance of the present distribution of gene frequencies and frequencies of "linked" combinations of genes, and (2) the reduction of the frequency of those rare mutations which clearly confer severe phenotypic disabilities that are not easily compensated by present medical technology. Such conservative aims should be vigorously pursued, provided that the individual and social costs are not excessive.
If we had methods for decoding and reading the complete set of genetic messages of each and every individual and for recording this data in a central computer file, it would be possible, in principle, to examine the message sets of any two prospective mates to compute recommendations as to the number of offspring they should have in order to help to contribute to the maintenance of the genetic status quo. For most couples, the recommended number of children would be two; for many, one or three; and in rare cases, none or more than three. As Crow (1958) previously demonstrated, variances in reproductive rate of this sort can provide very "considerable selection". The computer would be programmed to take past frequencies of both intentional and accidental departures from the recomended values (continuously updated from birth records) into account in formulating recommendations. Some such program of conservative eugenics is probably the only kind of eugenic program that would have a chance to start to function successfully in democratic societies.
Some reasonable eugenic measures have begun to be put into effect to hold down the frequencies of rare genes that produce severe disabilities. Those with the highest natural mutation rates pose the greatest threat, and it is just those which tend to be among the first to be singled out for attention. This is the kind of genetic counselling program to which informed and humane physicians are often privately committed.
It is clear that the evolutionary process itself has selected, in some cases, for reduction of effective mutation rate to compensate for increase in generation time and decrease in number of offspring per mating. We are now beginning to understand something of the workings of some mutation-rate control mechanisms such as excision of nucleotide codons which constitute coding errors and replacement with correct codons (using an unmutated complementary strand as a model?). Increased redundancy in the genetic code (e.g., polyteny and polyploidy and gene duplications) may have provided natural means for reduction of effective mutation rates through the action of such genetic reading and editing mechanisms. And in so far as we can discover artificial means to reduce natural mutation rates, the rate of genetic drift can be slowed.
New high-resolution electrophoretic techniques for the separation of proteins (which are the direct translation of genetic messages) and techniques for fingerprinting of the peptide digests of pure proteins begin to permit us to collect significant amounts of data on gene frequencies. These techniques more often than not permit the identification of heterozygous carriers of otherwise pheotypically recessive genes. Routine cataloguing of the accessable proteins of blood cells and serum and other body fluids of each individual (to be followed up later by routine analyses of the proteins of samples of tissue biopsies or cultures from such biopsies) will begin to lay a foundation for the kind of genetic analyses of human populations that is required to guide conservative eugenics.
Although the pace of genetic drift in large populations is initially very slow, the development of the kind of biomedical information-retrieval system and genetic decoding techniques required to stem the tide of drift may also be very slow, and attempts to discover practical means for reducing mutation rates may be even slower in reaching fruition. Therefore, the sooner a very much more substantial social commitment is made to the pursuit of such ends, including making adequate genetic education a required part of all high school curricula, the more secure will be the future of humanity.
Removing the spectre of suicide by nuclear, chemical, or biological warfare and putting a damper on the population explosion (which includes world-wide democratic application of birth control and the elimination of poverty) come first and second on my personal list of social priorities. Attending to our evolutionary future comes a very close third. Learning to live with leisure and computers follows. A 1000 BEV Alternating Gradient Synchnotron, trips to the moon and planets, listening for messages from outer space (Project OZMA), etc., all seem trivial by comparison. As for large-scale application of "algeny" and positive eugenics to the improvement of mankind, I believe, with Lederberg (1966), Dobzhansky (1962), and Hotchkiss (1965) that these must wait at least until we are both technicallyt more proficient and genetically vastly more knbowledgeable.
Crow, J.F. 1958. "Some possibilities for measuring selection intensities in man" Human Biology, 30: 1.
Crow, J.F. 1966. "The quality of people: human evolutionary changes". BioScience, 16: 863-867.
Dobzhansky, T. 1951. Genectics and the Origin of Species. Columbia University Press, New York.
Dobzhansky, T. 1962. Mankind Evolving. Yale University Press, New Haven, Conn.
Hotchkiss, R.D. 1965. "Portents for a genetic engineering". J. Heredity, 56: 197.
Lederberg, J. 1966. "Eperimental genetics and human evolution". Bull. Atom. Sci., 22: (10) 4.
Ornstein, L. 1965. "Subnuclear particles: a question of social priorities". Science, 149: 584.
Ornstein, L. 1967. "The population explosion, conservative eugenics and human evolution". Bull. Atom. Sci., 23: (6) 57.
von Hoerner, S. 1962. "The general limits of space travel". Science, 137: 18.
In the interim, the gel electrophoresis methods which I co-invented have been successfully extended (by others) to the resolution of nucliec acid fragments that differ by single nucleotides, and serve as the main analytical tools for reading the genetic code. The multi-year, 3-billion dollar Human Genome Project is well on the way to sequencing the "complete set of human genetic messages" and the first generation of the required kinds of computers and computer programs to do the job already exist. To make execution of my recomendations practical will require methods that reduce the 3-billion dollar cost by about five more orders of magnitude, and the years to at least days, that appears feasible to me within the life-time of the next few generations. It hasn't been my priorities that have driven this revolution, but curiosity and the wide-spread belief in the power of the new technologies for euphenic (mainly medical and agricultural) applications and the possibilities for "gene repair" (algeny). But for the long run, conservative eugenics still warrant the higher priority.