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.