The Moral Imperative of Human Embryonic Stem Cell Research

by Sanford M. Goodman

Delivered before the congregation of the First Unitarian Church of Omaha

January 25, 2004

Thank you for the opportunity to address you today. When Vicki called me earlier this week and proposed that I speak on stem cell research, I was in the midst of preparing and distributing material for the then-upcoming legislative debate on a proposal to criminalize an entirely new direction for that work. I am pleased to be able to report today that, due to the efforts of a few committed and courageous State Senators and numerous other individuals, this legislative threat has been put off for another year; more on that later.

But, first, what is “stem cell research” and why is it under legislative threat? To answer these questions we must delve briefly into developmental biology for some basic facts.

Stem cells are body cells that have two primary characteristics; they can both replicate themselves and become, or differentiate into, more specialized body cells, such as nerve, skin, bone or blood cells. They are further classified according to their potential for differentiation and development. A totipotent stem cell is a cell that can develop into a completely new organism, given the proper environment and nourishment. This describes a fertilized egg, or zygote, from which all cells and structures necessary for development derive, including the placental support system. A pluripotent stem cell can differentiate into all the cells of all the body cell types, but not the placental system, and, therefore, not a completely new organism. A multipotent stem cell can differentiate into multiple kinds of cells but only within a particular cell type such as blood or nerve system cells.

The zygote, or totipotent stem cell, begins its transformation to a multicellular human being by beginning to divide. After about five days the cells have increased in number to approximately 200 to 250 and are organized in the form of a hollow ball with a knot of 30 to 34 cells jutting from the inner wall. This structure is a blastocyst and the cells in the knot, the inner cell mass, are generally thought to be pluripotent stem cells, although some recent work suggests they may be able to differentiate into placental cells after all, which would make them totipotent. Researchers can extract these cells and induce them to replicate themselves repeatedly in culture in the lab, thus creating stem cell “lines” that can be divided and stored frozen for later research, whereupon they will resume their replication. In extracting these cells, the blastocyst is destroyed. While this technique was developed with mouse cells over 20 years ago, it was first done with human cells only in 1998.

As the organism completes its development through continued cell division and differentiation, the stem cells that remain are multipotent. These multipotent stem cells comprise a very small percentage of the cells of the body. Their primary function appears to be to regenerate replacement cells in certain systems. We know the most about those which form the various types of blood cells. Over the last 15 years or so, researchers have learned to isolate these hematopoietic stem cells and utilize them in leukemia therapy in what is commonly known as a bone marrow transplant. (Researchers here at UNMC played a vital role in that work.)

While researchers have identified stem cells for other systems, such as the nervous system and the skeletal and muscle system, they have not yet identified the characteristics of these cells to the same level of specificity as hematopoietic stem cells, and they do not yet have the techniques to isolate them in large quantities. Recently, some researchers have reported discovering they can induce multipotent stem cells to differentiate into cells that have characteristics of different systemic families beyond that into which the particular multipotent stem cells normally develop. This suggests that these cells may, in fact, be more pluripotent than previously thought. Independent labs have not been able to reproduce these results, however, and other studies raise serious questions that need resolution. In addition, multipotent stem cells do not seem to be able to reproduce indefinitely in culture like pluripotent stem cells.

So what, you might be asking; what’s the big deal about stem cell research, anyway? Well, it’s a really big deal. What has been discussed most frequently in the press is the prospect of learning how to induce stem cells to differentiate into specific cell types, which will repair or replace damaged cells when transplanted into a patient. Researchers have achieved some repair of spinal cord injuries in mice in this way. Others are pursuing similar research to regenerate insulin producing cells to cure diabetes, among other efforts. This approach is often referred to as “regenerative medicine.”

More and more, however, it is becoming apparent that the real payoff in stem cell research is the fundamental knowledge of developmental biology and cell development and differentiation that we will develop. If we can determine what causes a cell to differentiate, we may be able to determine how to make it de-differentiate and then differentiate into another cell type. We may be able to discover how to induce latent stem cells in the body to turn on and repair damaged tissue, such as that incurred during a heart attack, created in the brain by Parkinson’s or Alzheimer’s or suffered during an accident. We may be able to determine what turns a normal cell into a cancer cell and discover targets for drug development to reverse that process. We may be able to identify the specific genetic configurations that make some people susceptible to early death from heart disease. The list is as long as the creative imaginations of those at work in labs around the world; some of whom we are fortunate to have sitting among us today.

But why do people have any problems with stem cell research if it holds such medical promise? The dispute arises over the fact that, as previously stated, the only source of pluripotent stem cells is extraction from a blastocyst. Recall that the blastocyst is destroyed to extract the pluripotent stem cells that constitute the inner cell mass. Of course, both the zygote and blastocyst are technical terms for what is commonly known as an embryo during the initial stages of development, roughly the first two months in humans. These pluripotent cells are commonly known as embryonic stem cells. The multipotent cells in fully developed organisms are known as adult stem cells, although they exist in children and even blood removed from the umbilical cord at birth.

Despite assertions to the contrary by embryonic stem cell research opponents, we must study both embryonic and adult stem cells in an integrated framework in order to develop a workable understanding of stem cell characteristics and development. This view was reinforced earlier this month in a report issued by the President’s Council on Bioethics. While it is possible that we could determine how to make an adult stem cell become truly like an embryonic stem cell, and thereby be able to create all the cell types we require, by studying adult stem cells alone, studying both together will undoubtedly hasten the work. To illustrate this, imagine you came upon the microprocessor in your computer and wanted to know how to make it. Even if you had comprehensive knowledge of materials science, electronics and computer systems, it would be a lot faster to figure out the manufacturing process for you to go visit the Intel factory (or IBM factory for the Mac users in the audience) and watch them being made, rather than trying to reverse engineer it through trial and error.

What would be the consequences of delay associated with restricting research to adult stem cells only? Clearly, we would not be preventing the use of known or even imminent cures and therapies. But just as clearly, even though the point in the future at which we will develop workable cures and therapies is unknown in any event, by walling off the direct source of knowledge from study, we would be pushing that point out well beyond what it otherwise might be. For those suffering from disease whose time comes to an end during that window, that delay would be deadly. And of course, those who do not die would suffer needlessly during that time.

Now, let’s talk briefly about the forestalled legislative threat I mentioned at the beginning. I have described how human embryonic stem cells are derived from roughly 5 day-old embryos; but where do these embryos come from? Over 100,000 excess embryos reportedly remain frozen and destined for disposal in in vitro fertilization clinics around the country. Those few embryonic stem cell lines that are currently approved for Federally funded research under the Bush Administration policy announced on August 9, 2001 came from such surplus embryos. As you may recall, President Bush declared that Federal funds could be used to fund research only on lines derived from extractions that occurred prior to the time of his speech.

It turns out that there are only about a dozen such lines that are readily available. As you can imagine, these lines reflect very little genetic diversity. One of the country’s leading researchers in the field, Dr. Irving Weissman of Stanford University, described them as the genes “of a few wealthy, white, infertile couples”. during a visit here in early January. Even were all 100,000 excess embryos available for study, the genetic diversity they represent would still be severely limited. In addition, to the extent that future therapies and cures involve cell transplantation, such transplants would likely require patients to take immunosuppressant drugs to prevent rejection of the transplanted cells.

There is a way to overcome these challenges of limited genetic diversity and transplant rejection. By removing the nucleus of an unfertilized egg, or ovum, and replacing it with the nucleus of an ordinary skin, or somatic, cell, scientists can create pluripotent stem cell lines that are genetically matched to the skin cell donor. They do this by stimulating the ovum with the skin cell nucleus to begin to divide and then extracting the pluripotent stem cells from the inner cell mass at the blastocyst stage. This procedure, somatic cell nuclear transfer to create pluripotent stem cell lines, is popularly known as therapeutic cloning. Utilizing this and related techniques, Dr. Weissman and others are beginning to develop research programs more carefully targeted to understanding the very biomolecular processes underlying diseases.

But cloning is a very highly charge word. The live birth cloned animals produced to date, such as Dolly the sheep and CC the cat, were produced using somatic cell nuclear transfer to create the pre-implantation embryos that were implanted in the animal’s wombs. In reviewing those animal reproductive cloning efforts, a National Academies of Science panel chaired by Dr. Weissman, determined that the success rate was less than one-tenth of one per cent. Frequently, the mother died when the fetus miscarried, which happened even more frequently. There is no question that the scientific and medical facts justify a legally enforceable ban on human reproductive cloning.

In contrast, the scientific and medical promises of therapeutic cloning create a moral imperative to proceed with such work. Yet the proposal before the legislature this past week would have made it a crime to utilize somatic cell nuclear transfer with human cells. That proposal fell only one vote short of obtaining the 33 of 49 votes necessary to cut off debate.

How is it that almost two-thirds of Nebraska legislators could vote to criminalize medical research that has such incredible promise? The problem arises among those who view the destruction of the blastocyst as deliberate destruction of human life. They object on this basis even to the use of the excess IVF embryos destined for destruction, and recoil from the prospect of therapeutic cloning. They often cite the Kantian principle that each of us has a dignity above price and that we should never treat humanity simply as a means, but always as an end, as one moral philosopher describes it. This commentator goes on to point out that the problem with this viewpoint, at least insofar as it rests on a Kantian foundation, is that the basis of dignity for Kant was autonomous reason, and embryos are not rational.

This view, that the destruction of the blastocyst is the taking of innocent life often also rests on the position that the zygote is a human being with equivalent moral status (and Constitutional rights) to born, breathing human beings, a position otherwise known as zygotic personhood. Some argue this from the position that conception is the only non-arbitrary milestone in human development at which to establish personhood. Each of us, they argue, began as a single cell zygote, which embodies within it the complete genomic code for each individual. Looking to any other point, they fear, provides too much leeway for gradual shifting over time as familiarity removes our initial caution along each step of the way, the infamous “slippery slope.” Of course, we live our lives on such slippery moral slopes. We rely on the institutions and traditions of our open, democratic society to manage those challenges, as we must in this instance.

Time does not permit a complete review of all the arguments put forth in debate over these issues. The aforementioned report of the President’s Council on Bioethics, Monitoring Stem Cell Research, provides an excellent overview. It is available online, for those who are interested. I would also direct you to the web site of Nebraskans for Research, an organization with which I am affiliated.

But there is one remaining source of objections pertinent for discussion among us today that I would like to address in closing. I refer, of course, to religious beliefs. Such beliefs underlie the objections of the vast majority of embryonic stem cell research opponents. “Human life is a gift from God who breathes a soul into every human being at its single-cell stage,” declares one of the definitions of the Nebraska Coalition for Ethical Research, a local group organized by the Pro-Life Office of the Nebraska Catholic Conference to argue for a ban on embryonic stem cell research. “The human being is, at once, body and spirit,” these definitions go on to state, “Therefore, any external intervention on the human body is an intervention on the entire human being.” Clearly these are religious and philosophical positions that are a matter of individual conscience. Yet, as this group’s very name, and their presentation of these propositions as “definitions,” suggest, they seem to think that they are in sole possession of the truth.

“It is a terrible and dangerous arrogance to believe that you alone are right: have a magical eye which sees the truth: & that others cannot be right if they disagree,” noted the British philosopher Isaiah Berlin in 1981. “This makes one certain that there is one goal & one only for one's nation or church or the whole of humanity, & that it is worth any amount of suffering (particularly on the part of other people) if only the goal is attained,” he also stated.

I will close with the words of Michael Shermer, author and editor of Skeptic magazine who elaborates on this theme; “As long as it is understood that morality is a human construction influenced by human cultures, one can become more tolerant of other human belief systems, and thus other humans. But as soon as a group sets itself up to be the final moral arbiter of other people's actions, especially when its members believe they have discovered absolute standards of right and wrong, it is the beginning of the end of tolerance and thus, reason and rationality.”

Thank you.