Moving Toward the Clonal Man

Is this what we want?
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The notion that man might sometime soon be reproduced asexually upsets many people. The main public effect of the remarkable clonal frog produced some ten years ago in Oxford by the zoologist John Gurdon has not been awe of the elegant scientific implications of this frog’s existence, but fear that similar experiment might someday be done with human cells. Until recently, however, this foreboding has seemed more like a science fiction scenario than a real problem which the human race has to live with.

For the embryological development of man does not occur free in the placid environment of a freshwater pond, in which a frog’s eggs normally turn into tadpoles and then into mature frogs. Instead, the crucial steps in human embryology always occur in the highly inaccessible womb of a human female. There the growing fetus enlarges unseen, and effectively out of range of almost any manipulation except that which is deliberately designed to abort its existence. As long as all humans develop in this manner, there is no way to take the various steps necessary to insert an adult diploid nucleus from a pre-existing human into a human egg whose maternal genetic material has previously been removed. Given the continuation of the normal processes of conception and development, the idea that we might have a world populated by people whose genetic material was identical to that of previously existing people can belong only to the domain of the novelist or the moviemaker, not to that of pragmatic scientists who must think only about things which can happen.

Today, however, we must face up to the fact that the unexpectedly rapid progress of R. G. Edwards and P. S. Steptoe in working out the conditions for routine test-tube conception of human eggs means that human embryological development need no longer be a process shrouded in secrecy. It can become instead an event wide-open to a variety of experimental manipulations. Already the two scientists have developed many embryos to the eight-cell stage, and a few more blastocysts, the stage where successful implantation into a human uterus should not be too difficult to achieve. In fact, Edwards and Steptoe hope to accomplish implantation and subsequent growth into a normal baby within the coming year.

The question naturally arises, why should any woman willingly submit to the laparoscopy operation which yields the eggs to be used in test-tube conceptions? There is clearly some danger involved every time Steptoe operates. Nonetheless, he and Edwards believe that the risks are more than counterbalanced by the fact that their research may develop methods which could make their patients able to bear children. All their patients, though having normal menstrual cycles, are infertile, many because they have blocked oviducts which prevent passage of eggs into the uterus. If so, in vitro growth of their eggs up to the blastocysts stage may circumvent infertility, thereby allowing normal childbirth. Moreover, since the sex of a blastocysts is easily determined by chromosomal analysis, such women would have the possibility of deciding whether to give birth to a boy or a girl.

Clearly, if Edwards and Steptoe succeed, their success will be followed up in many other places. The number of such infertile women, while small on a relative percentage basis, is likely to be large on an absolute basis. Within the United States there could be 100,000 or so women who would like a similar chance to have their own babies. At the same time, we must anticipate strong, if not hysterical, reactions from many quarters. The certainty that the ready availability of this medical technique will open up the possibility of hiring out unrelated women to carry a given baby to term is bound to outrage many people. For there is absolutely no reason why the blastocysts need be implanted in the same woman from whom the pre-ovulatory eggs were obtained. Many women with anatomical complications which prohibit successful childbearing might be strongly tempted to find a suitable surrogate. And it is easy to imagine that other women who just don’t want the discomforts of pregnancy would also seek this very different form of motherhood. Of even greater concern would be the potentialities for misuse by an inhumane totalitarian government.

Some very hard decisions may soon be upon us. It is not obvious, for example, that the vague potential of abhorrent misuse should weigh more strongly than the unhappiness which thousands of married couples feel when they are unable to have their own children. Different societies are likely to view the matter differently, and it would be surprising if all should come to the same conclusion. We must, therefore, assume that techniques for the in vitro manipulation of human eggs are likely to become general medical practice, capable of routine performance in many major countries, within some ten to twenty years.

The situation would then be ripe for extensive efforts, either legal or illegal, at human cloning. But for such experiments to be successful, techniques would have to be developed which allow the insertion of adult diploid nuclei into human eggs which previously have had their maternal haploid nucleus removed. At first sight, this task is a very tall order since human eggs are much smaller than those of frogs, the only vertebrates which have so far been cloned. Insertion by micropipettes, the device used in the case of the frog, is always likely to damage human eggs irreversibly. Recently, however, the development of simple techniques for fusing animal cells has raised the strong possibility that further refinements of the cell-fusion method will allow the routine introduction of human diploid nuclei into enucleated human eggs. Activation of such eggs to divide to become blastocysts, followed by implantation into suitable uteri, should lead to the development of healthy fetuses, and subsequent normal-appearing babies.

The growing up to adulthood of these first clonal humans could be a very startling event, a fact already appreciated by many magazine editors, one of whom commissioned a cover with multiple copies of Ringo Starr, another of whom gave us overblown multiple likenesses of the current sex goddess, Raquel Welch. It takes little imagination to perceive that different people will have highly different fantasies, some perhaps imagining the existence of countless people with the features of Picasso or Frank Sinatra or Walt Frazier or Doris Day. And would monarchs like the Shah of Iran, knowing they might never be able to have a normal male heir, consider the possibility of having a son whose genetic constitution would be identical to their own?

Clearly, even more bizarre possibilities can be thought of, and so we might have expected that many biologists, particularly those whose work impinges upon this possibility, would seriously ponder its implication, and begin a dialogue which would educated the world’s citizens and offer suggestions which our legislative bodies might consider in framing national science policies. On the whole, however, this has not happened. Though a number of scientific papers devoted to the problem of genetic engineering have casually mentioned that clonal reproduction may someday be with us, the discussion to which I am party has been so vague and devoid of meaningful time estimates as to be virtually soporific.

Does this effective silence imply a conspiracy to keep the general public unaware of a potential threat to their basic way of life? Could it be motivated by fear that the general reaction will be a further damning of all science, thereby decreasing even more the limited money available for pure research? Or does it merely tell us that most scientists do live such an ivory-tower existence that they are capable of thinking rationally only about pure science, dismissing most practical matters as subjects for the lawyers, students, clergy, and politicians to face up to?

One or both of these possibilities may explain why more scientists have not taken cloning before the public. The main reason, I suspect, is that the prospect to most biologists still looks too remote and chancy—not worthy of immediate attention when other matters, like nuclear-weapon overproliferation and pesticide and auto-exhaust pollution, present society with immediate threats to its orderly continuation. Though scientists as a group form the most future-oriented of all professions, there are few of us who concentrate on events unlikely to become reality within the next decade or two.

To almost all of the intellectually most adventurous geneticists, the seemingly distant time when cloning might first occur is more to the point than its far-reaching implication, were it to be practiced seriously. For example, Stanford’s celebrate geneticist, Joshua Lederberg, among the first to talk about cloning as a practical matter, now seems bored with further talk, implying that we should channel our limited influence as public citizens to the prevention of the wide-scale, irreversible damage to our genetic material that is now occurring through the increasing exposure to man-made mutagenic compounds. To him, serious talk about cloning is essentially crying wolf when a tiger is already inside the walls.

This position, however, fails to allow for what I believe will be a frenetic rush to do experimental manipulation with human eggs once they have become a readily available commodity. And that is what they will be within several years after Edwards-Steptoe methods lead to the birth of the first healthy baby by a previously infertile woman. Isolated human eggs will be found in hundreds of hospitals, and given the fact that Steptoe’s laparoscopy technique frequently yields several eggs from a single woman donor, not all of the eggs so obtained, even if they could be cultured to the blastocysts stage, would ever be reimplanted into female bodies. Most of these excess eggs would likely be used for a variety of valid experimental purposes, many, for example, to perfect the Edwards-Steptoe techniques. Others could be devoted to finding methods for curing certain genetic diseases, conceivably through use of cell-fusion methods which now seem to be the correct route to cloning. The temptation to try cloning itself thus will always be close at hand.

No reason, of course, dictates that such cloning experiments need occur. Most of the medical people capable of such experimentation would probably steer clear of any step which looked as though its real purpose were to clone. But it would be short-sighted to assume that everyone would instinctively recoil from such purposes. Some people may sincerely believe the world desperately needs many copies of really exceptional people if we are to fight our way out of the ever-increasing computer-mediated complexity that makes our individual brains so frequently inadequate.

Moreover, given the widespread development of the safe clinical procedures for handling human eggs, cloning experiments would not be prohibitively expensive. They need not be restricted to the superpowers. All smaller countries now possess the resources required for eventual success. Furthermore, there need not exist the coercion of a totalitarian state to provide the surrogate mothers. There already are such widespread divergences regarding the sacredness of the act of human reproduction that the boring meaninglessness of the lives of many women would be sufficient cause for their willingness to participate in such experimentation, be it legal or illegal. Thus, if the matter proceeds in its current nondirected fashion, a human being born of clonal reproduction most likely will appear on the earth within the next twenty to fifty years, and even sooner, if some nation should actively promote the venture.

The first reaction of most people to the arrival of these asexually produced children, I suspect, would be one of despair. The nature of the bond between parents and their children, not to mention everyone’s values about the individual’s uniqueness, could be changed beyond recognition, and by a science which they never understood but which until recently appeared to provide more good than harm. Certainly to many people, particularly those with strong religious backgrounds, our most sensible course of action would be to de-emphasize all those forms of research which would circumvent the normal sexual reproductive process. If this step were taken, experiments on cell fusion might no longer be supported by federal funds or tax-exempt organizations. Prohibition of such research would most certainly put off the day when diploid nuclei could satisfactorily be inserted into enucleated human eggs. Even more effective would be to take steps quickly to make illegal, or to reaffirm the illegality of, any experimental work with human embryos.

Neither of the prohibitions, however, is likely to take place. In the first place, the cell-fusion technique now offers one of the best avenues for understanding the genetic basis of cancer. Today, all over the world, cancer cells are being fused with normal cells to pinpoint those specific chromosomes responsible for given forms of cancer. In addition, fusion techniques are the basis of many genetic efforts to unravel the biochemistry of diseases like cystic fibrosis or multiple sclerosis. Any attempts now to stop such work using the argument that cloning represents a greater threat than a disease like cancer is likely to be considered irresponsible by virtually anyone able to understand the matter.

Though more people would initially go along with a prohibition of work on human embryos, many may have a change of heart when they ponder the mess which the population explosion poses. The current projections are so horrendous that responsible people are likely to consider the need for more basic embryological facts much more relevant to our self-interest than the not-very-immediate threat of a few clonal men existing some decades ahead. And the potentially militant lobby of infertile couples who see test-tube conception as their only route to the joys of raising children of their won making would carry even more weight. So, scientists like Edwards are likely to get a go-ahead signal even if, almost perversely, the immediate consequence of their “population-money”-supported research will be the production of still more babies.

Complicating any effort at effective legislative guidance is the multiplicity of places where work like Edwards’ could occur, thereby making unlikely the possibility that such manipulations would have the same legal (or illegal) status throughout the world. We must assume that if Edwards and Steptoe produce a really workable method for restoring fertility, large numbers of women will search out those places where it is legal (or possible), just as now they search out places where abortions can be easily obtained.

Thus, all nations formulating policies to handle the implications of in vitro human embryo experimentation must realize that the problem is essentially an international one. Even if one or more countries should stop research, their action could effectively be neutralized by the response of a neighboring country. This most disconcerting impotence also holds for the United States. If our congressional representatives, upon learning where the matter now stands, should decide that they want none of it and pass very strict laws against human embryo experimentation, their action would not seriously set back the current scientific and medical momentum which brings us close to the possibility of surrogate mothers, if not human clonal reproduction. This is because the relevant experiments are being done not in the United States, but largely in England. That is partly a matter of chance, but also a consequence of the advanced state of English cell biology, which in certain areas is more adventurous and imaginative than its American counterpart. There is no American university which has the strength in experimental embryology that Oxford possesses.

We must not assume, however, that today the important decisions lie only before the British government. Very soon we must anticipate that a number of biologists and clinicians of other countries, sensing the potential excitement, will move into this area of science. So even if the current English effort were stifled, similar experimentation could soon begin elsewhere. Thus it appears to me most desirable that as many people as possible be informed about the new ways of human reproduction and their potential consequences, both good and bad.

This is a matter far too important to be left solely in the hands of the scientific and medical communities. The belief that surrogate mothers and clonal babies are inevitable because science always moves forward, an attitude expressed to me recently be a scientific colleague, represents a form of laissez-faire nonsense dismally reminiscent of the creed that American business, if left to itself, will solve everybody’s problems. Just as the success of a corporate body in making money need not set the human condition ahead, neither does every scientific advance automatically make our lives more “meaningful.” No doubt the person whose experimental skill will eventually bring forth a clonal baby will be given wide notoriety. But the child who grows up knowing that the world wants another Picasso may view his creator in a different light.

I would thus hope that over the next decade wide-reaching discussion would occur, at the informal as well as formal legislative level, about the manifold problems which are bound to arise if test-tube conception becomes a common occurrence. A blanket declaration of the worldwide illegality of human cloning might be one result of a serious effort to ask the world in which direction it wished to move. Admittedly the vast effort, required for even the most limited international arrangement, will turn off some people—those who believe the matter is of marginal importance now, and that it is a red herring designed to take our minds off our callous attitudes toward war, poverty, and racial prejudice. But if we do not think about it now, the possibility of our having a free choice will one day suddenly be gone.

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