| M A Y     1 
                    9 7 1 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 implication of this frog's 
                    existence, but fear that a 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 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 into 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 blastocyst stage may circumvent 
                    infertility, thereby allowing normal childbirth. Moreover, 
                    since the sex of a blastocyst 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 blastocyst 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 educate 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 
                    ways 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 more 
                    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 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 celebrated 
                    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 
                    increasing exposure to man-created 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 be 
                    come 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 blastocyst 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 super powers. 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 own making would carry even more weight. 
                    So, scientists like Edwards are likely to get a go-ahead signal 
                    even if, almost perversely, the immediate consequences 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 such 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 far 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 by 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. 
                    
 |