Summer 2006

Ethics and Morality

Small Concerns

Dan Cloer

The illumination of the human genome has opened the door to a vast range of medical therapies. The promise of drugs and interventions tuned to the individual patient’s genetics holds persuasive advantage over the one-size-fits-all generic remedies we count on today. Further progress in this booming field of molecular medicine, however, relies in part on continuing research using the stem cells of human embryos. Although the cells themselves are microscopic, their use in medical research leaves many with not so small concerns.

Dr. McCoy looks with sympathy at the old woman languishing from kidney disease. Recalling that he’s traveled back to the 20th century from the 23rd, he grimaces and mutters, “Dialysis? We’re in the Dark Ages.” He snaps open his medical bag and slaps a pill into the woman’s hand. “If you have any problems, call me.” She slips the pill into her mouth as the doctor disappears down the hospital hall. Only moments later a phalanx of interns parades her wheelchair through the ward, the woman exuberantly exclaiming, “Doctor gave me a pill, and I grew a new kidney! Doctor gave me a pill, and I grew a new kidney!”

If only organ replacements were as easy as they are in Star Trek movies. Thousands today are on waiting lists for kidney transplants. Many more desperately hope to obtain lungs, hearts, livers or corneas from the ranks of unfortunate accident victims or terminal patients who have consented to be organ donors. What a miracle it would be to have the ability to stimulate repair from within our own bodies! We may not be there yet, but it is nevertheless increasingly difficult to stay up-to-date with the rapid developments in medical practice: the medicine of Star Trek is clearly a target toward which we are steadily moving.

For example, recent news from the 21st-century medical world reports the manufacture of human urinary bladders. While bladder tissue is one of the simplest structures of the body, the surgical restoration of patient function with a new organ grown outside the body is remarkable. New techniques that print a so-called bio-ink composed of cells onto a synthetic scaffold are being pioneered by biophysicists. The developers believe that, in principle, they can “print” any desired structure, including blood vessels and organs.

Successful genetic interventions are becoming increasingly common as well. In early 2006 two patients with inherited immunodeficiency (a kind of bubble-boy syndrome) were successfully treated using their own blood stem cells, which had undergone genetic engineering to replace the defective gene. Such cell-based cures give great hope to those suffering from other degenerative diseases such as Alzheimer’s, diabetes and Parkinson’s.

The concept in these cases and others, including muscle repair after heart failure and spinal-cord trauma, is to design or train cells to regenerate or replace the damaged tissue of the patient. While there appears to be reliable evidence from animal studies that repair is achievable and not merely theoretical, human clinical trials are only now ramping up. However, although increasing numbers of trials are being undertaken and researchers are optimistic, a problem remains: even when successful, researchers often remain in the dark as to the biochemical and genetic mechanisms that are actually coming into play.

The senior editor of the journal Regenerative Medicine, Stephen L. Minger (a stem cell researcher at the Wolfson Centre for Age-Related Diseases at King’s College, London), enthusiastically notes that “the field of regenerative medicine and stem cell biology has become one of the hottest areas in contemporary science.” Still, Minger told Vision, much of the potential for “personal medicine” and the timeline for actual cures is being exaggerated. Right now, he says, “it’s all alchemy, not science at all,” because many fundamental processes have yet to be unraveled.

The important questions revolve around understanding how tissues and organs form in the first place. Researchers believe that if they could fathom the nuanced developmental history of the body, they could find better ways to stimulate repair when things go wrong. But how far will they go in attempting to make these discoveries? The means of moving from alchemy to biochemical understanding is a point of significant ethical controversy.

Dis-Counting the Cost

Though by no means carte blanche for harvesting the organs of human clones or creating new species of humans, current laws nevertheless allow procedures that are troubling to many. The lengths to which researchers will go to solve these puzzles and develop clinical applications often seem too utilitarian for comfort. Huseyin Mehmet of the Weston Laboratory at London’s Imperial College, for example, is investigating the use of stem cells to repair brain damage in premature infants. Most would call this a heroic endeavor.

His investigative technique, however, involves the extraction of brain cells from freshly aborted fetuses. At least this gives a pregnant woman the sense that “it’s not a total waste,” Mehmet told Vision. Later-term abortions are the best candidates, he noted, because “naïve stem cells are not good for therapy.” In his research, the extracted human cells are injected into embryonic mice; when the mice are later born and sacrificed, the human nerve cells have successfully incorporated into their brains. “They have the correct morphology,” Mehmet remarked, “but to be truly therapeutic, we would have to know that they function as well.”

Stemness

Such cell swapping may appear grotesque, yet there is method to the seeming madness. Understanding function requires understanding the engine of the cell: genes. If one is to control the development of tissues and the fate of cells, one must understand how cells come to know their place in the body—how they come to know which genes to use.

We can imagine the genes of our genome as file folders in a cabinet. When cells grow and divide, they duplicate the whole cabinet; cells are not different because they contain different sets of genes but because they are using different subsets of genes. At fertilization, when sperm meets egg, a human genome is reconstituted and complete. The trick, then, like rearranging one’s files in the proper order for the tasks of the day, is to turn on the genes in the correct sequence in order to build all the various tissues, organs, systems and structures of the body. It’s a complex dance of communication and chemical procedure, somewhat akin to maneuvering the Queen Mary 2 as opposed to a motorbike.

As the body forms, cell fate becomes solidified. Biologists call this differentiation—the progression that limits a cell to a particular future. Liver cells are restricted to reading liver cell files, for example; muscle cells, nerve cells, and all of the more than 250 cell types in the body take on and stick to their unique genetic files, while the other files are sealed and locked away. Some cells, however, even in the adult body, retain the ability, or potency, to reproduce several cell types. These are called stem cells, because a variety of cell-type branches may stem from them.

The original stem cells that create an individual are, of course, found in the embryo. Until recently stem cells in the adult body were believed to be limited to areas where constant growth is necessary: skin, blood and intestinal lining, for instance. But further study has discovered stem cells scattered throughout the tissues of the body, from brain to fat, from liver to nose. Adult stem cells have the ability to create several other related cell types but, importantly, not all cell types. Little if any controversy surrounds the use of these cells, because they are not embryonic: they cannot be used to clone an individual, nor is the creation of an embryo necessary to obtain them.

The utility of such cells for body repair is under close investigative scrutiny. Animal research has shown that many types of adult stem cells do indeed have the capacity to aid in the regeneration of damaged tissues. Still, without a thorough understanding of the biochemical nature of the interactions between stem cell and damage site, translating the animal research to human use and benefit remains distant. No one wants to start moving stem cells from one point in the body to another without a thorough understanding of what they do and why they are doing it. The basics of the biology is still, well, embryonic: Are the stem cells responding to calls for help from the damage site? Are they acting like engineers surveying and commanding other cells? What happens when these cells locate themselves in nontargeted areas? If they carry the same defective genes as the malfunctioning cells, will they, too, degenerate?

To tease out answers from the complex web of ongoing cellular interactions within an adult system is extremely difficult. Thus, regardless of the future of adult stem cells, the relative simplicity of the early embryo and its embryonic stem cells will remain an important research platform. Even if stem cell therapy is one day found to be possible without the creation of embryos, the embryo will remain a focus of developmental and medical science.

Supply and Demand

Just as the Human Genome Project was just the starting place for many new fields of investigation, research using embryonic stem cells is also likely to expand. But while DNA is not in short supply, human embryos are. It is the further production and use of human embryos for scientific research that concerns many. Even researchers who find no moral difficulty using them as source material for stem cells—whether those embryos are “leftovers” from fertility clinics or newly created in the lab seems to make little difference—are quick to admit to the need for oversight.

Ethical concerns related to use of human embryos for the derivation of human embryonic stem cells, . . . the rush to translate stem cell research to clinical application and the unreasonable hype that surrounds this area of research all threaten to undermine a fast-moving field with important potential for treating human disease,” writes Wolfson’s Minger. “Therefore it is important to highlight yet again, how with appropriate regulation and committed involvement of the scientific community, a stable and pragmatic research agenda can be put forward.”

Such regulation in the United Kingdom includes laws of Good Manufacturing Practice and licensing agreements that allow U.K. laboratories to create embryos for research. The law also establishes a communal stem cell bank, a sort of clearing house into which new stem lines may be deposited and traded between research groups.

Permissive science and high regulation is the ideal model,” Minger told Vision at a Cambridge Healthtech Institute stem cell conference in San Francisco. Noting that “the U.S. population doesn’t buy into regulation,” Minger extolled the more hospitable European environment. “The U.K. represents one of the sanest and most pragmatic environments in which to pursue stem cell research.”

As we descend into an instrumental use of human life, we destroy the very reason for which we were undertaking our new therapies; we degrade the humanity we were trying to heal.” 

William B. Hurlbut, “Altered Nuclear Transfer”

But it is just that sort of pragmatism that worries Stanford bioethicist William Hurlbut. A member of the President’s Council on Bioethics, Hurlbut is pushing hard for a rethinking of scientific (or what he calls “instrumental”) use of human embryos. In an article in the Spring 2005 issue of Perspectives in Biology and Medicine, he wrote, “At this early stage in our technological control of developing life, we have an opportunity to break the impasse over stem cell research and provide moral guidance for the biotechnology of the future. . . . Any postponement of this process will only deepen the dilemma as we proceed into realms of technological advance unguided by forethought.”

Hurlbut is not trying just to throw sand in the stem cell gears—gears that he readily admits will not stop turning. His solution, called “altered nuclear transfer,” would provide a means of creating the genetic equivalent of embryonic stem cells without creating the embryo. He writes, “Using the techniques of nuclear transfer, but with the intentional alteration of the nucleus before transfer, we could construct a biologic entity that, by design and from its very beginning, lacks the attributes and capacities of a human embryo.”

The Cost of Convenience

The most interesting aspect of the human embryonic stem cell controversy is that there is controversy. Although some continue to claim loudly that “an embryo is like an IKEA bookcase”—just parts awaiting assembly—our increasing understanding of the developmental process says otherwise. It is becoming increasingly difficult to insist that a human embryo, however early in its gestation, is simply tissue. To the question of whether the embryo is a human being, Hurlbut’s simple response is unequivocal: the “moment of meaning” is conception; an embryo is in the process of “becoming what it already is.”

To the question of whether the embryo is a human being, Hurlbut’s simple response is unequivocal: the “moment of meaning” is conception; an embryo is in the process of “becoming what it already is.” 

Yet it seems likely that embryo-based research will continue, simply because it is easier than the alternatives. Minger puts it plainly when he says, “IVF [in vitro fertilization] embryos are available and being discarded; why bother with altered nuclear transfer?”

Medical science is often a cruel business. Over the centuries it has advanced through the study of the sick and the dying. Countless patients have suffered greatly as the practice of medicine has been refined. In return, many have not only lived longer but have also contributed to the great pool of clinical knowledge that continues to carry medicine forward.

But embryonic stem cell research is different. As medical researchers seek a multitude of cures, the embryo has no say in its own destruction. The “informed consent” that has always been at the heart of human-based research gives way to the perceived needs of the investigator’s prerogatives and the economic hopes of sponsors. It is an approach that easily morphs into one where the ends justify the means—the harsh rationalization that “you’ve got to crack a few eggs to make an omelet.” The fruit of curative medicine should not be cultivated through a neglectful disregard for the materials it employs. Good fruit is not borne from poor practice. What we are seeing today could be described as hybrid fruit from the proverbial tree of the knowledge of good and evil.

However high our intentions, the realities of the human embryo—realities that science itself has revealed—should inform and moderate further progress. “Anything short of affirming the inviolability of life across all of its stages from zygote to natural death leads to an instrumental view of human life,” Hurlbut warns. “The reversal of such a basic moral valuation will extend itself in a logic of justification that has ominous implications for our attitude and approach to human existence.”

Hurlbut concludes that the situation is more dangerous than just a “slippery slope,” where a hope of traction still exists. Rather, we are building on a “crumbly cliff,” a ledge without foundation, where the crucial underpinnings—timeless moral principles regarding human life—have been dispensed with for the sake of convenience. “The subsequent descent is simply practice catching up with principle,” he writes. “As we descend into an instrumental use of human life, we destroy the very reason for which we were undertaking our new therapies; we degrade the humanity we were trying to heal.”

Focused Attention

Science fiction is notable not so much for its fiction as for its science. When Star Trek’s Dr. McCoy returns from the future and offers a regenerated kidney in a stimulatory pill, we want to believe that we are seeing a glimpse of a future reality. Our desire for such healing and remission of suffering easily leads to suspension of disbelief. But the quest to relieve suffering is not itself a painless trek, and the lessons that come from it often reveal more than we expected to discover, telling us more about ourselves than about the diseases that plague us.

In the rush of trying to heal, we find it increasingly easy to ignore fatal flaws embedded in our own motivations. These are flaws of spirit, flaws of pride, which lead us to believe that the solutions we seek for controlling degeneration and disease are worth any cost that might be incurred. These costs are indeed dear and, like interest on debt, inherently degenerative.

It is unfortunate that the movies don’t explain the reality of the transitions and the choices that must be made to reach the ends depicted. As genomic and developmental science continues to fortify the understanding that human life exists in the first cell of the embryo, we will be increasingly challenged in the ethics of our treatment of that creation.

To move ever closer toward realizing the medical potential that the Star Trek scene inspires, we will be forced to come to grips with greater issues concerning our collective definition of human identity and purpose. Such a definition, which includes all we can fathom from the potential of the cell to the vastness of the universe, will surely challenge our sense of what life is and the sacrifices we will make to control it.

Sometimes it is the smallest steps along the path that require our closest attention.