More Than Making Babies
In Vitro Fertilization is Only a Beginning
by Ruth Hubbard

Not since the expulsion of Adam and Eve from the Garden of Eden delegated the task of producing humans to our own devices did our experience of how to do it get the jolt it did on July 25, 1978, when it became public knowledge that Louise Brown had been born. The startling fact was that this baby was gestated from an embryo, produced by mixing in a glass dish an egg, removed from the ovary of an Englishwoman named Leslie Brown, with her husband's sperm and implanting the resulting embryo in Ms. Brown's womb where it was brought to term. Leslie and John Brown (with Sue Freeman) told about their experience in a trade paperback, titled Our Miracle Called Louise, published in 1979, while the embryologist Robert Edwards and the ob/gyn Patrick Steptoe, who jointly mediated the feat, described their side of the story in a 1980 paperback, titled A Matter of Life.

The embryo that developed into Louise Brown did not represent Steptoe's and Edwards's first try at IVF. In earlier attempts, however, normal-looking embryos either did not form or survive in vitro or did not implant or develop past the initial stages. Worse yet, occasionally they did implant, but in a fallopian tube instead of the uterus, which required surgery to remove the damaged fallopian tube.

Since 1978, IVF technology has become considerably more successful, but also more complex. Hormones are used to stimulate egg production and also to facilitate the implantation of the embryos in the uterus. Steptoe could introduce only a single embryo, since he was only able to collect one egg. Nowadays three embryos, and in U.S. fertility clinics often many more, are introduced into the uterus in order to increase the chances that one will implant. This practice, of course, also increases the likelihood of ending up with a multiple pregnancy, a condition most women would rather avoid.

From the point of view of its effectiveness and safety, it is unfortunate that, in the United States, IVF is offered mainly by for-profit, private fertility centers, operating with little regulation and under the loosest of supervision. In Great Britain, France, and other countries where IVF is covered by national health plans, the methods are more standardized and strict record-keeping makes long-term monitoring of the health of the women undergoing IVF and of the children born in consequence of it routine. In the United States, differences in practices at different sites would make it difficult to detect any but major disabilities or health consequences, should they occur.

Iatrogenic (meaning, medically induced) effects, detected in the past — for example, the effect of thalidomide or of DES (diethyl stilbestrol) — have usually come to attention because they involve extremely rare health problems. Sudden clusters, therefore, are relatively easy to notice. If a medical intervention merely increases the incidence of a relatively wide-spread health problem, many more subjects and much longer follow-ups are needed to suspect a causal relationship.

The currently available information about people conceived by IVF cannot provide information as to whether the method can be judged safe over the normal life-span of either the women receiving IVF treatments or the children conceived in this way. After all, the generation of Louise Brown's mother is only in its mid-forties to mid-fifties and the first generation conceived by IVF is at most twenty-five years old. Furthermore, since IVF practices tend to be more conservative in countries with national health systems, and those are also the countries that keep better health records, we are likely to know less about the health impacts of IVF, as practiced in the United States, than those in the other technologically developed countries.

I am not trying to raise needless fears, but, as will become clearer when we look at some of the practices derived from IVF, it is important to acknowledge our inability to assess the health effects of IVF itself. Fertility clinics cover themselves legally by having clients sign informed consent forms and clients may feel that they have been told what they need to know in order to be informed. But with new technologies like those we are considering here, it is questionable what being "informed" means.

The moment IVF appeared on the map, it was clear that access to human eggs and embryos would open up innumerable exciting scientific questions and medical applications, impossible to approach before. And indeed, in the last ten or fifteen years, a series of practices have grown up that use IVF as their starting point. Already in his and Steptoe's 1980 book, since it was written for a popular audience, Edwards abandons the usual scientific detachment and writes ecstatically about the sight of a human embryo under the microscope. He also right away tries to counter the objections of critics who warned that IVF will open the door to human cloning. Edwards admits that, though cloning is "a long way off,” “leading scientists regard it as a distinct practical possibility.” A "leading" scientist himself, he suggests that the future benefits from IVF would include "ultimately" being able to "produce a cohort of super-astronauts or dustmen, soldiers or senators, each with identical physical and mental characteristics most suited to do the job they have to do." Clearly, sci-fi cloning scenarios were there from the start, only waiting for IVF to become realistic possibilities.

Now that it has, in fact, become possible to clone non-human mammals, most scientists in countries with the
technical capability to attempt to clone humans disavow the intention to do so, if for no other reason, because of the minuscule success rates of efforts to reproduce non-human mammals by cloning. They also, correctly, dismiss Edwards's nonsensical projections about copying "super-astronauts or dustmen [British for garbage collectors]". But other questionable technologies have been, or are being, explored and implemented and those are what I want to discuss in the rest of this article.

The first of these to become a practical reality offers the possibility of screening embryos, produced in vitro, for genetic variants (mutations) that can result in specific health conditions, which parents wish to avoid, such as Tay Sachs disease or cystic fibrosis. Since an embryo's initial cell divisions involve only cell duplication, all the cells of a 6- or 8-cell embryo are identical. It should therefore be possible to remove one of these cells and screen it for the possibility of one or more mutations before attempting to implant the rest of the embryo and allow it to develop into a baby. A team of scientists in London (U.K.) perfected such a procedure within a few years of the development of IVF and it has led to what is now called "pre-implantation diagnosis." Since current IVF procedures usually begin with the fertilization of several eggs, parents, once they go the in vitro route, can, for an added fee, have the embryos screened. They might especially want to do that if one of the detectable conditions runs in their family. This would give them the option to implant only those embryos predicted to develop into children who do not have that condition.

Despite these practical "benefits", because of its history of Nazi eugenics, as well as for other reasons, Germany has enacted laws forbidding the manipulation of human embryos for any purpose other than their implantation. Similarly, Professor Jacques Testart, a pioneer of IVF procedures in France, by the mid-1980s, announced publicly that he would no longer perform IVF. IVF, he argued, would inevitably lead to eugenic practices of increasing sophistication, starting with pre-implantation screening for predictable diseases and going on to attempts to "improve" the physical or mental characteristics of children by genetic manipulations.

The United States does not regulate research involving human eggs or embryos. It only prohibits using federal funds for this purpose. (In Britain, France, and Germany, by contrast, government-appointed committees oversee the research protocols and results.) The U.S. position, though ostensibly based on respect for human life (including that of eggs and embryos), leaves the field wide open for scientific adventurism and its potential financial exploitation.

In one highly questionable practice, for example, the cell substance (ooplasm) of the egg, removed from a woman who has had difficulty conceiving or gestating a baby, is extruded and replaced with the ooplasm, removed from an egg of a younger and hopefully more fertile woman. The synthetic egg is then fertilized and the embryo implanted in the woman who wishes to have the child (or in another woman whom she contracts to gestate the embryo for her). This entirely unpredictable manipulation flies in the face of any number of theoretical and practical considerations. But it is justified as the only way this woman can have her "own" child, so implying that one’s DNA is the only thing that can make a child be one's own. Such procedures may, of course, offer interesting biology to explore. Since they are very expensive, there is also a lot of money to be made.

A final issue which, of late, has been much in the news is the production of so-called embryonic stem cells. Optimistic scientists promise that these cells can be made to generate, hence regenerate, all types of adult
tissues. The controversy about whether to allow the research to go forward using federal funds, to outlaw it
completely, or to let it proceed with private funds is fuelled, on either side, both by ideology and hype. Ideology comes in because the production of embryonic stem cells necessitates allowing the embryos to undergo many more cell divisions than are needed for IVF. One then removes the main mass of cells, called the inner cell mass, and uses it to culture stem cells. In other words, to produce embryo stem cells requires that one destroy the embryo. For people who believe that a human embryo is equivalent to a human being, production of embryo stem cells therefore involves murder. The hype comes in with the untested promise that embryonic stem cells will prove able to repair a wide range of health problems, from Parkinson's disease to Christopher Reeves's spinal injury.
In a rational world, it would probably be worth investigating such possibilities with mice or rats (though I shrink at the thought of inflicting the injuries which would subsequently be "cured"). Using human embryos could be put off for quite a while. What is more, the current argument involves not just the use of human embryos for stem cell research, but using cloned stem cells.

The point here is that, if one cloned embryos so that they contain the DNA of the person who needs to be treated, one could obtain one could obtain embryo stem cells that would offer an immunological match for that person. Such stem cells might work better than stem cells derived from a random embryo. Would they really? Is this a battle worth engaging at this early stage in the research? Must it so soon be tried with humans? No, no, and no. But there is a principle involved and that is that U.S. scientists fight strenuously to keep the government from regulating their research. The British government, by contrast, has for a long time regulated a good deal of biological research. For example, British scientists need to obtain a license for any experiment involving live
animals. Yet that has not stopped British research or slowed British science relative to science done in the United States.

The history of IVF and the uses to which it can be put illustrates the need to regulate biomedical research and
practice. Biomedicine is too intrusive and too expensive to allow its exploitation to be left to the market. Without
responsible, coordinated planning and regulation, potential clients who can pay are encouraged to clamor for enticing technical adventures, while those who cannot, end up doing without basic medical care.

Ruth Hubbard is Professor Emerita of Biology at Harvard University and a founding member of the Council for Responsible Genetics. She is the author of several books, among them Exploding the Gene Myth: How Genetic Information Is Produced & Manipulated by Scientists, Physicians, Employers, Insurance Companies, Educators, & Law Enforcers, co-written with Elijah Wald.