by Isaac Asimov
(But, as often happens when biological systems are studied, behavior does not follow the rules as rigidly as scientists are sometimes inclined to suppose. In the 1940s and afterward, the American biologist Barbara McClintock, carefully studying the genes in corn, and following them from generation to generation, came to the conclusion that some genes can shift rather easily and frequently from place to place on the chromosomes in the course of cell division. This idea seemed so out of line with the results obtained by Morgan and biologists who followed him that she was ignored—but she was right. When others began to find evidence of gene mobility, McClintock (now an octogenarian) received the Nobel Prize for physiology and medicine in 1983.)
From such chromosome maps—and from a study of giant chromosomes, many times the ordinary size, found in the salivary glands of the fruit fly—it has been established that the insect has a minimum of 10,000 genes in a chromosome pair. Hence, the individual gene must have a molecular weight of 60,000,000. Accordingly, the human’s somewhat larger chromosomes may contain from 20,000 to 90,000 genes per chromosome pair, or up to 2,000,000 altogether.
For his work on the genetics of fruit flies, Morgan received the Nobel Prize in medicine and physiology in 1933.
Increasing knowledge of genes raises hopes that the genetic endowment of individual humans might someday be analyzed and modified: either preventing seriously anomalous conditions from developing, or correcting them if they slip by. Such genetic engineering would require human chromosome maps—clearly a tremendously larger job than in the case of the fruit fly. The task was made somewhat simpler in a startling way in 1967, when Howard Green of New York University formed hybrid cells containing both mouse and human chromosomes. Relatively few human chromosomes persisted after several cell divisions, and the effects due to their activity was more easily pinpointed.
Another step in the direction of gene knowledge and gene manipulation came in 1969, when the American biochemist Jonathan Beckwith and his co-workers isolated an individual gene for the first time in history. It was from an intestinal bacterium, and it controlled an aspect of sugar metabolism.
THE GENETIC LOAD
Every once in a while, with a frequency that can be calculated, a sudden change occurs in a gene. The mutation shows itself by some new and unexpected physical characteristic, such as the short legs of Farmer Wright’s lamb. Mutations in nature are comparatively rare. In 1926, the geneticist Hermann Joseph Muller, who had been a member of Morgan’s research team, discovered a way to increase the rate of mutations artificially in fruit flies so that the inheritance of such changes could be studied more easily. He found that X rays would do the trick-presumably by damaging the genes. The study of mutations made possible by Muller’s discovery won him the Nobel Prize in medicine and physiology in 1946.
As it happens, Muller’s researches have given rise to some rather disquieting thoughts concerning the future of the human species. While mutations are an important driving force in evolution, occasionally producing an improvement that enables a species to cope better with its environment, the beneficial mutation is very much the exception. Most mutations—at least 99 percent of them—are detrimental, some even lethal. Eventually, even those that are only slightly harmful die out, because their bearers do not get along as well and leave fewer descendants than healthy individuals do. But in the meantime a mutation may cause illness and suffering for many generations. Furthermore, new mutations keep cropping up continually, and every species carries a constant load of defective genes. Thus, more than 1,600 human diseases are thought to be the result of genetic defects.
The great number of different gene varieties—including large quantities of seriously harmful ones—in normal populations was clearly shown by the work of the Russian-American geneticist Theodosius Dobzhansky in the 1930s and 1940s. This diversity makes evolution march on as it does, but the number of deleterious genes (the genetic load) gives rise to fears justified anxiety.
Two modern developments seem to be adding steadily to this load. First, the advances in medicine and social care tend to compensate for the handicaps of people with detrimental mutations, at least so far as the ability to reproduce is concerned. Eyeglasses are available to individuals with defective vision; insulin keeps alive sufferers from diabetes (a hereditary disease), and so on. Thus they pass on their defective genes to future generations. The alternatives—allowing defective individuals to die young or sterilizing or imprisoning them—are, of course, unthinkable, except where the handicap is sufficiently great to make the individual less than human, as in idiocy or homicidal paranoia. Undoubtedly, the human species can still bear its load of negatively mutated genes, despite its humanitarian impulses.
But there is less excuse for the second modern hazard—namely, adding to the load by unnecessary exposure to radiation. Genetic research shows incontrovertibly that, for the population as a whole, even a slight increase in general exposure to radiation means a corresponding slight increase in the mutation rate. And since 1895 we have been exposed to types and intensities of radiation of which previous generations knew nothing. Solar radiation, the natural radioactivity of the soil, and cosmic rays have always been with us. Now, however, we use X rays in medicine and dentistry with abandon; we concentrate radioactive material; we form artificially radioactive isotopes of terrifying radiant potency; we even explode nuclear bombs. All of this increases the background radiation.
No one, of course, suggests that research in nuclear physics be abandoned, or that X rays never be used by doctor and dentist. There is, however, a strong recommendation that the danger be recognized and that exposure to radiation be minimized: that, for instance, X rays be used with discrimination and care, and that the sexual organs be routinely shielded during all such use. Another suggested precaution is that each individual keep a record of his or her total accumulated exposure to X rays so as to try to avoid exceeding a reasonable limit.
BLOOD TYPES
Of course, the geneticists could not be sure that the principles established by experiments on plants and insects necessarily applied to humans. After all, we are neither pea plants nor fruit flies. But direct studies of certain human characteristics showed that human genetics does follow the same rules. The best-known example is the inheritance of blood types.
Blood transfusion is a very old practice, and early physicians occasionally even tried to transfuse animal blood into persons weakened by loss of blood. But transfusions even of human blood often turned out badly, so that laws were sometimes passed forbidding transfusion. In the 1890s, the Austrian pathologist Karl Landsteiner finally discovered that human blood comes in different types, some of which are incompatible with each other. He found that sometimes when blood from one person was mixed with a sample of serum (the blood fluid remaining after the red cells and a clotting factor are removed) from another person, the red cells of the first person’s whole blood would clump together. Obviously such a mixture would be very dangerous if it occurred in transfusion, and it might even kill the patient if the clumped cells blocked the blood circulation in key vessels. Landsteiner also found, however, that some bloods could be mixed without causing any deleterious clumping.
By 1902, Landsteiner was able to announce that there were four types of human blood, which he called A, B, AB, and O. Any given individual had blood of just one of these types. Of course, a particular type could be transferred without danger from one person to another having the same type. In addition, 0 blood could safely be transfused to a person possessing any of the other three types, and either A blood or B blood could be given to an AB patient. But red-cell clumping (agglutination) would result when AB blood was transfused to an A or a B individual, when A and B were mixed, or when an O individual received a transfusion of any blood other than O. (Nowadays, because of possible serum reactions, in good practice patients are given only blood of their own type.)
In 1930, Landsteiner (who by then had become a United States citizen) received the Nobel P
rize in medicine and physiology.
Geneticists have established that these blood types (and all the others since discovered, including the Rh variations) are inherited in a strictly Mendelian manner. It seems that there are three gene alleles responsible, respectively, for A, B, and O blood. If both parents have O-type blood, all the children of that union will have O-type blood. If one parent is O-type and the other A-type, all the children may show A-type blood, for the A allele is dominant over the O. The B allele likewise is dominant over the O allele. The B allele and A allele, however, show no dominance with respect to each other, and an individual possessing both alleles has AB-type blood.
The Mendelian rules work out so strictly that blood groups can be (and are) used to test paternity. If an a-type mother has a B-type child, the child’s father must be B-type, for that B allele must have come from somewhere. If the woman’s husband happens to be A or O, it is clear that she has been unfaithful (or there has been a baby mix-up at the hospital). If an O-type woman with a B-type child accuses an A or an O man of being the parent, she is either mistaken or lying. On the other hand, while blood type can sometimes prove a negative, it can never prove a positive. If the woman’s husband or the man accused is indeed a B-type, the case remains unproved. Any B-type man or any AB-type man could have been the father.
EUGENICS
The applicability of the Mendelian rules of inheritance to human beings has also been borne out by the existence of sex-linked traits. As I have said, color-blindness and hemophilia are found almost exclusively in males and are inherited in precisely the manner that sex-linked characteristics are inherited in the fruit fly.
Naturally, the thought will arise that by forbidding people with such afflictions to have children, the disorder can be wiped out. By directing proper mating, the human breed might even be improved, as breeds of cattle have been. This is by no means a new idea. The ancient Spartans believed this and tried to put it into practice 2,500 years ago. In modern times, the notion was revived by an English scientist, Francis Galton (a cousin of Charles Darwin). In 1883, he coined the word eugenics to describe his scheme. (The word derives from the Greek and means “good birth.”)
Galton was not aware, in his time, of the findings of Mendel. He did not understand that characteristics might seem to be absent, yet be carried as recessives. He did not understand that groups of characteristics would be inherited intact, and that it might be difficult to get rid of an undesirable one without also getting rid of a desirable one. Nor was he aware that mutations would reintroduce undesirable characteristics in every generation.
Nevertheless, the desire to “improve” the human stock continues, and eugenics finds its supporters, even among scientists, to this day. Such support is almost invariably suspect, since those who are avid to show important genetic differences between recognizable groups of human beings are sure to find the groups to which they themselves belong to be “superior.”
The English psychologist Cyril Lodowic Burt, for instance, reported studies of intelligence of different groups and claimed strong evidence for supposing men to be more intelligent than women, Christians to be more intelligent than Jews, Englishmen to be more intelligent than Irishmen, upper-class Englishmen to be more intelligent than lower-class Englishmen, and so on. Burt himself belonged, in every case, to the “superior” group. His results were, of course, accepted by many people who, like Burt, were in the “superior” group, and who were ready to believe that those who were worse off were the victims not of oppression and prejudice but, instead, of their own defects.
After Burt’s death in 1971, however, doubts arose concerning his data. There were distinctly suspicious perfections about his statistics. The suspicions grew; and in 1978, the American psychologist D. D. Dorfman was able to show, rather conclusively, that Burt had simply fabricated his data, so anxious was he to prove a thesis that he deeply believed but that could not be proved honestly.
And yet, even so, Shockley, the co-inventor of the transistor, gained a certain notoriety for himself by maintaining that blacks are significantly less intelligent than whites, through genetic factors, so that attempts to better the lot of blacks by giving them equal opportunities are bound to fail. The German-British psychologist Hans J. Eysenck also maintains this view.
In 1980, Shockley laid himself open to some ill-natured jests when he incautiously revealed that he had contributed some of his then seventy-year-old sperm cells for preservation by freezing in a sperm bank designed for eventual use in the insemination of women volunteers of high intelligence.
My own belief is that human genetics is an enormously complicated subject that is not likely to be completely or neatly worked out in the foreseeable future. Because we breed neither as frequently nor as prolifically as the fruit fly; because our matings cannot be subjected to laboratory control for experimental purposes; because we have many more chromosomes and many more inherited characteristics than the fruit fly; because the human characteristics in which we are most interested—such as creative genius, intelligence, and moral strength—are extremely complex, involving the interplay of numerous genes plus environmental influences—for all these reasons, geneticists cannot deal with human genetics with the same confidence with which they study fruit-fly genetics.
Eugenics remains a dream, therefore, made hazy and insubstantial by lack of knowledge, and vicious because of the ease with which it can be exploited by racists and bigots.
CHEMICAL GENETICS
Just how does a gene bring the physical characteristic for which it is responsible into being? What is the mechanism whereby it gives rise to yellow seeds in pea plants, or curled wings in fruit flies, or blue eyes in human beings?
Biologists are now certain that genes exert their effects by way of enzymes. One of the clearest cases in point involves the color of eyes, hair, and skin. The color (blue or brown, yellowor black, pink or brown, or shades in between) is determined by the amount of pigment, called melanin (from the Greek word for “black”), that is present in the eye’s iris, the hair, or the skin. Now melanin is formed from an amino acid, tyrosine, by way of a number of steps, most of which have now been worked out. A number of enzymes are involved, and the amount of melanin formed will depend upon the quantity of these enzymes. For instance, one of the enzymes, which catalyzes the first two steps, is tyrosinase. Presumably some particular gene controls the production of tyrosinase by the cells and, in that way, will control the coloring of the skin, hair, and eyes. And since the gene is transmitted from generation to generation, children will naturally resemble their parents in coloring. If a mutation happens to produce a defective gene that cannot form tyrosinase, there will be no melanin, and the individual will be an albino. The absence of a single enzyme (and hence the deficiency of a single gene) will thus suffice to bring about a major change in personal characteristics.
Granted that an organism’s characteristics are controlled by its enzyme make-up, which in turn is controlled by genes, the next question is: How do the genes work? Unfortunately, even the fruit fly is much too complex an organism to trace out the matter in detail. But, in 1941, the American biologists George Wells Beadle and Edward Lawrie Tatum began such a study with a simple organism which they found admirably suited to this purpose: the common pink bread mold (scientific name, Neurospora crassa).
Neurospora is not very demanding in its diet. It will grow very well on sugar plus inorganic compounds that supply nitrogen, sulfur, and various minerals. Aside from sugar, the only organic substance that has to be supplied to it is a vitamin called biotin.
At a certain stage in its life cycle, the mold produces eight spores, all identical in genetic constitution. Each spore contains seven chromosomes; as in the sex cell of a higher organism, its chromosomes come singly, not in pairs. Consequently, if one of its chromosomes is changed, the effect can be observed, because there is no normal partner present to mask the effect. Beadle and Tatum, therefore, were able to create mutations in Neurospora by expos
ing the mold to X rays and then to follow the specific effects in the behavior of the spores. If, after the mold had received a dose of radiation, the spores still thrived on the usual medium of nutrients, clearly no mutation had taken place, at least so far as the organism’s nutritional requirements for growth were concerned. If the spores would not grow on the usual medium, the experimenters proceeded to determine whether they were alive or dead, by feeding them a complete medium containing all the vitamins, amino acids, and other items they might possibly need. If the spores grew on this, the conclusion was that the X rays had produced a mutation that had changed Neurospora’s nutritional requirements. Apparently it now needed at least one new item in its diet. To find out what that was, the experimenters tried the spores on one diet after another, each time with some items of the complete medium missing. They might omit all the amino acids, or all the various vitamins, or all but one or two amino acids or one or two vitamins. In this way, they narrowed down the requirements until they identified just what the spore now needed in its diet because of the mutation.
It turned out sometimes that the mutated spore required the amino acid arginine. The normal wild strain had been able to manufacture its own arginine from sugar and ammonium salts. Now, thanks to the genetic change, it could no longer synthesize arginine; and unless this amino acid was supplied in its diet, it could not make protein and therefore could not grow.
The clearest way to account for such a situation was to suppose that the X rays had disrupted a gene responsible for the formation of an enzyme necessary for manufacturing arginine. For lack of the normal gene, Neurospora could no longer make the enzyme. No enzyme, no arginine.
