The Magazine

The False Promise of "Therapeutic" Cloning

Moral considerations aside, human cloning is not going to lead to useful medical treatments.

Mar 11, 2002, Vol. 7, No. 25 • By WESLEY J. SMITH
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THE SENATE will shortly take up one of the most pressing moral, ethical, and scientific issues of our time: the Brownback proposal to outlaw human cloning. Two alternative proposals would ban only "reproductive cloning," which would mean explicitly legalizing human cloning but not the implantation of a clone embryo into a womb. Pro-cloners are willing for the most part to outlaw reproductive cloning (for now) because it isn't safe and it gives the appearance of a reasonable compromise. But they oppose a ban on cloning for research and experimentation--euphemistically known as "therapeutic cloning"--arguing that such a cloning license is necessary to the development of future medical treatments for terrible human ailments.

The case against cloning, including therapeutic cloning, has mainly been argued on grounds of morality. Opponents have warned that creating embryos through cloning for the purpose of research (with the full intention of destroying them later) is a breathtakingly radical enterprise. For the first time in history, human lives will be created for the explicit purpose of exploitation. Such considerations have led activist Jeremy Rifkin to opine that the cloning debate is to the 21st century what the slavery debate was to the 19th.

Unfortunately, we live in a time of widespread and extreme non-judgmentalism, an era when many Americans simply do not respond to moral arguments in public policy debates. For these folk, what counts is not right versus wrong, but whether it will or won't work--in a word, utility.

Does this mean that the public policy amoralists among us must end up by default on the pro-cloning side? Not at all. There is increasing evidence that therapies based on cloned embryo cells would be so difficult and expensive to develop and so utterly impractical to bring to the bedside, that the pie-in-the-sky promises which fuel the pro-cloning side of the debate are unlikely to materialize. Not only is human cloning immoral but it may have negative utility--in other words, attempting to develop human cloning technologies for therapeutic use may drain resources and personnel from more useful and practical therapies.

To understand why therapeutic cloning fails the utility test, we must take a quick look at the significant difficulties facing embryonic stem cell research. Embryonic stem cell researchers hope to create medical treatments that would use undifferentiated cells--known generically as stem cells--extracted from 5-to-7-day-old embryos known as blastocysts. During natural gestation, these stem cells eventually "differentiate," that is, they transform into bone, neurons, muscle, organs, blood--indeed, all of the more than 200 different tissue types in the body. Researchers hope to learn how to harness this ability by extracting stem cells from embryos, transforming them into specific tissues, and then injecting the tissues into patients to treat medical ailments.

In their enthusiasm for embryonic stem cells--and in an effort to assure ample funding for the research--some advocates have all but promised that such therapies are just around the corner. But that isn't even close to being true.

Writing in the scientific research journal Stem Cells, editor in chief (and advocate of embryonic stem cell research) Curt I. Civin admitted that "scientists have exaggerated the immediacy of the prospects of clinical therapies using stem cells." Moreover, Civin believes that "clinical application" of stem cell therapies is actually "a long way off." Why? Primarily two reasons: First, embryonic cells may cause tumors in patients; and, second, the body may reject embryonic tissues in the same way the immune system rejects transplanted organs.

A recent experiment involving rats, reported in the January 8, 2002, Proceedings of the National Academy of Sciences, illustrates the tumor problem. Researchers at Harvard Medical School and McLean Hospital in Belmont, Massachusetts, injected mouse embryonic stem cells into rats to relieve Parkinson's disease-like symptoms. Of the 25 rats receiving the embryonic stem cells, 14 showed modest improvement, 6 showed no benefit, and 5 died of brain tumors caused by the stem cells. In other words, the therapy actually killed 20 percent of the recipients of the embryonic stem cell therapy. And this occurred even though researchers tried mightily to prevent tumor formation by injecting only 1 percent of the number of such cells that have been used in other experiments that led to tumor deaths. It is becoming clear that overcoming the problem of tumor formation--if it can be done--will be a very difficult, time-consuming, and expensive undertaking.

Contrast that decidedly mixed result with a similar but far more successful experiment involving adult stem cells in rats reported by the Proceedings of the National Academy of Science, December 19, 2000. Researchers at the University of California, Irvine, reported that they were able to stimulate the growth of (adult) neural stem cells in rats suffering from Parkinson's-like symptoms. These cells then migrated to the damaged area of the brain and differentiated into the types of neurons needed to replace the missing/damaged brain cells. An encouraging 80 percent of the rats in the experiment--more than in the experiment using embryonic cells--received therapeutic benefit. Moreover, none developed tumors. The experiment was so successful the scientists reported that their research presented "significant implications with respect to the development of treatments" for both brain injuries and degenerative diseases. They further predicted that their approach could offer "an alternative strategy" to using embryonic cells to treat such ailments.

Tissue rejection presents nearly as high a hurdle to surmount. Unless researchers find a way to prevent the body's immune system from attacking embryonic cells as "foreign," patients receiving embryonic stem cell therapies will require a lifetime regimen of strong drugs to suppress their immune systems. These medications often produce serious side effects such as problems with wound healing, a propensity to suffer opportunistic infections, skin malignancies, and drug-related toxicities.

Researchers have endeavored mightily to solve the problem of tissue rejection, so far without success. One seemingly promising approach--removing from the cells the molecules that stimulate rejection--did not prevent rejection in animal skin graft experiments. So now, back at their drawing boards, researchers contemplate inserting desired genes into the embryonic stem cells to fool the body into thinking that the injected cells are its own. Whether this can be done is not known, but learning how to manipulate embryonic stem cells genetically to thwart rejection is clearly a problem that is also going to take a very long time to overcome--assuming that it can be solved at all.

THE TISSUE rejection conundrum brings us back to human therapeutic cloning. Cloning advocates argue that they must be allowed to legally clone human embryos in order to overcome the rejection problem described above. This is how the process of therapeutic cloning would work: A patient requiring embryonic stem cell therapy would donate his own genetic material, say from a skin biopsy, which would then be used to clone an embryonic identical twin of the patient. The clone embryo would be developed to the blastocyst stage and then destroyed and harvested for the stem cells. The harvested stem cells would then be transformed into the type of tissue required for the patient's treatment. Researchers expect that the clone's virtually identical genetic makeup would fool the patient's immune system into perceiving the injected tissues as "self," thereby overcoming the rejection problem.

That is the theory, and it has been swallowed hook, line, and sinker by many in the media, government, and patient advocacy groups. But a close look at the realities of this scenario shows that it is smoke and mirrors. Even if scientists are ever able to develop a human clone to the blastocyst stage (not a given), and if these clones are not genetically defective (most mammalian clones created to date have had serious genetic anomalies), human cloning will still not be able to help the millions of patients who desperately hope to benefit from clone stem cell therapy.

Here's why: Cloning involves something called nuclear cell transfer. In humans, this is accomplished by removing the nucleus from a human ovum and replacing it with genetic material removed from a cell of the clone donor. The genetically modified egg is then stimulated with an electric current. If it works, a new human organism that is virtually identical to the clone donor comes into being and begins embryonic growth.

There are two absolutely essential ingredients to successful nuclear cell transfer cloning. One is a somatic cell from the clone donor. No problem there. The other is the egg. And here is where therapeutic cloning hits a brick wall: We can only create as many patient clones for therapeutic use as there are eggs available. Thus the entire utility argument over therapeutic cloning boils down to one crucial and unavoidable question: Where are we going to get the eggs we would need to treat the millions of patients who would supposedly benefit from clone embryonic stem cell therapy?

The simple answer is: We aren't going to get them. Assuming that therapeutic cloning researchers could overcome the genetic defects problem, and assuming that they could also control the growth of the new cells so as to prevent tumors, and even assuming perfect clinical conditions, there is no way around the fact that at least one human egg would be required for each patient. Now, consider the number of patients in this country alone with medical conditions for which embryonic stem cell therapies are being promoted as promising--people with Parkinson's disease, stroke, Lou Gehrig's disease, multiple sclerosis, spinal cord injuries, Huntington's disease, and more. According to a National Academy of Sciences estimate, there are more than 100 million such patients in the United States alone, meaning that even in a perfect cloning world, we would need at least 100 million human eggs to treat them. The only possible way out would be to use cow eggs. But few researchers speak publicly of wanting to go there.

And that isn't the half of it. As daunting as that number is, for the foreseeable future it will take many eggs to successfully create just one clone embryo. This means that the actual number of eggs that would be necessary for clinical application of therapeutic cell cloning is some unknown multiple of the figure above--an utterly staggering number.

David Prentice, an expert in stem cell research at Indiana State University and an opponent of human cloning, has done the math for just one patient group: diabetics. The results are devastating to the prospect of ever seeing therapeutic cloning take pride of place in medicine's armamentarium. There are some 16 million diabetics in the United States. Prentice assumed that 20 percent of cloning attempts would succeed in reaching the blastocyst stage of development. This number is based on published reports on successful production of blastocysts from animal cloning. The number is more than fair since cloning a genetically sound human embryo would be more difficult than cloning an embryonic mouse, sheep, or cat.

He next assumed that stem cells would be successfully derived from 10 percent of these clone embryos. This figure is also fair. It took 36 embryos for James Thomson of the University of Wisconsin to create 5 human embryonic stem cell lines, a 13.8 percent success rate. The Jones Institute used 110 embryos to get only three stem cell lines, a 2.7 percent success rate. And these embryos were created through fertilization, which does not pose the genetic defect problem found in clone embryos.

Using these figures, Prentice computed that it would take 800 million eggs just to treat the 16 million American diabetics with a therapy involving cloned embryonic stem cells.

Obtaining human eggs for this purpose would involve stimulating the ovaries to hyper-ovulate, which generally produces 7-10 eggs. Assuming a liberal 10 eggs harvested from each procedure, 80 million women of childbearing age would be needed as donors.

Considering the number of people in the United States with other diseases who have been promised they will benefit from therapeutic cloning, the actual number of women that would be required to donate eggs just to treat patients in this country can hardly be imagined.

Now, consider the difficulties involved with hyper-ovulation. The procedure is not exactly a walk in the park. After the ovaries are stimulated to release multiple eggs, the eggs are surgically extracted. A partial list of potential side effects from the procedure include rupture of the ovaries, severe pelvic pain, accumulation of fluid in the abdomen as well as around the heart and lungs, bleeding into the abdominal cavity, acute respiratory distress, and pulmonary embolism. That being so, how many American women are going to be willing to provide eggs for use in cloning?

Of course there are billions of women in the developing world who could provide eggs. But that would require creating a market in human ova in which poor women would submit to hyper-ovulation for pay without any personal therapeutic benefit. And even assuming a thriving market in eggs, the number that could realistically be obtained would not even scratch the surface of the actual therapeutic need.

The "egg dearth" is a mathematical certainty. This means that if clone embryonic stem cell therapy were ever successfully developed, it would have to be either severely rationed or available only to the very rich. But therapeutic cloning is being held out as a panacea for the many, not as a rare procedure available to the very few. That's a false hope. The real "promise" of therapeutic cloning is this: millions of Third World women being paid to submit to operations for the benefit of rich Americans.

Researchers already realize that therapeutic cloning will not be a generally available medical treatment, although they don't speak about it too loudly for fear of aiding the anti-cloning effort. Still, some cloning advocates rise to the level of public candor. For example, a year ago biotech researchers Jon S. Odorico, Dan S. Kaufman, and James A. Thomson admitted the following in the research journal Stem Cells:

"The poor availability of human ococytes [eggs], the low efficiency of the nuclear cell procedure, and the long population-doubling time of human ES cells make it difficult to envision this [therapeutic cloning to obtain stem cells] becoming a routine clinical procedure even if ethical considerations were not a significant point of contention."

Other researchers have made the same point privately. Peter Aldhous, Nature's chief news and features editor and a man with a reputation for giving the straight story, reported in the December 20/27, 2001, edition of Nature, "the idea of 'therapeutic cloning' seems to be on the wane. By creating cloned human blastocysts, some experts have argued that it should be possible to derive ES cells perfectly matched to individual patients. But most now believe this will be too expensive and cumbersome for regular clinical use." Or to put it another way, there just aren't enough human eggs.

Be that as it may, some readers might be thinking, why not go forward with research into human cloning anyway? The answer to that question brings us back to the issue of utility. If our goal as a society is to fund research into cellular technologies with the best hope of providing viable medical therapies in the shortest period of time, human cloning is the last thing we want to fund. After all, medical research dollars are a finite resource, and research into human cloning is very expensive. (It took $3.7 million just to clone one cat.) Thus, money poured into human cloning is money that will not be available for other areas of medical research.

Moreover, when it comes to the issue of stem cell therapies, the evidence is becoming overwhelming that our limited resources are most wisely spent pursuing research into adult stem cells as our best and quickest hope for developing efficacious new medical treatments. Adult cells don't appear to lead to tumors. And since the patient's own cells are used, tissue rejection is not an issue. Moreover, adult stem cells are already used to treat human ailments such as heart disease and auto immune deficiencies--which even the most optimistic proponents of therapeutic cloning admit are many years away using embryonic stem cells. In this regard, it is worth noting that the American Red Cross recently refused a National Institutes of Health grant to work on embryonic stem cells in order to focus more intensely on research involving stem cells found in umbilical cord blood. Why concentrate on umbilical cord blood and exclude work on embryos? The Red Cross representative could not have been clearer: "We really need to focus our resources, our attention, on those areas where we could most likely provide, in the shortest period of time, some therapies for our patients."

To pour money into human cloning embryonic stem cell research is to risk drilling one dry hole after another. The moral policy thus also turns out to be the pragmatic one. The United States Senate should vote to ban all human cloning now.

Wesley J. Smith, a frequent contributor to The Weekly Standard, is the author of "Culture of Death: The Assault on Medical Ethics in America."