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May 1971
Moving Toward the Clonal Man
by James D. Watson
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.
Volume 227, No. 5, pp. 50–53
