Biotechnology

Petri Dish Politics

Biotechnology will make it possible for us to live longer and better. So why are some people dead set against it?

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"Death to death," declares Gregory Stock, director of UCLA's Program on Medicine, Technology, and Society, at a conference on life extension. "Aging itself can be considered to be a disease," says Cynthia Kenyon, the biochemist who last year discovered genes that quadrupled the life of the nematode C. elegans.

"This is the first time that we can conceive of human immortality," William Haseltine, the hardheaded CEO of Human Genome Sciences Inc., the largest genomics company in the world, tells The Washington Post. Francis Fukuyama, the man who famously asserted that "The End of History" had arrived, declares that History is about to begin again, and its motor is biotechnology. "It is no longer clear that there is any upper limit on human life expectancy," writes Fukuyama. That, he argues, changes human nature and thus restarts History.

The biomedical revolution of the next century promises to alter our culture, our politics, and our lives. It promises to extend our life span and to enhance our mental and physical capacities. The closer those promises come to reality, however, the more they incite opposition and, in some cases, horror. And they are becoming more real by the day.

In September, Princeton University neurobiologist Joe Tsien announced that he had boosted the intelligence of mice by inserting extra copies of a gene that produces a type of receptor in brain cells; the receptor enhances long-term memory and learning. The "smart mice" did considerably better than normal mice on a battery of six rodent intelligence tests. The mouse gene Tsien manipulated is 98 percent identical to the one found in humans. In the short term, Tsien's work could lead to drugs that will boost the memory capacities of adult humans. Over the long run, these genes might be introduced into human embryos who, once born, would have an easier time learning and retaining new information. It was the prospect of making smarter people, not just curing Alzheimer's, that made global headlines.

On the horizon are artificial chromosomes containing genes that protect against HIV, diabetes, prostate and breast cancer, and Parkinson's disease, all of which could be introduced into a developing human embryo. When born, the child would have a souped-up immune system. Even more remarkably, artificial chromosomes could be designed with "hooks" or "docking stations," so that new genetic upgrades later could be slotted into the chromosomes and expressed in adults. Artificial chromosomes could also be arranged to replicate only in somatic cells, which form regular tissues, and not in the germ cells involved in reproduction. As a result, genetically enhanced parents would not pass those enhancements on to their children; they could choose new or different enhancements for their children, or have them born without any new genetic technologies.

Already, a Vancouver company, Chromos Molecular Systems, makes a mammalian artificial chromosome that allows biotechnologists to plug in new genes just as new computer chips can be plugged into a motherboard. These artificial chromosomes, which have been developed for both mice and humans, offer exquisite control over which genes will be introduced into an organism and how they will operate.

Meanwhile, the prospect of substantially extending the human lifespan is growing, as biomedical researchers investigate promising technologies to diagnose and treat the various ways the body breaks down with age. EntreMed Inc. of Rockville, Maryland, and Cell Genesys Inc. of Foster City, California, are working to deliver a gene-based drug that will cut off a cancer's blood supply and kill it. Human Genome Sciences, also of Rockville, is developing a heart-bypass-in-a-shot using the VEGF-2 gene, which produces a protein that encourages the growth of blood vessels around blocked arteries. In Silicon Valley, Santa Clara-based Affymetrix Inc. has created a "biochip"–a silicon wafer that analyzes thousands of genes in a single test, diagnosing all sorts of diseases. Combined with the full sequence of all human genes, which will be available in a couple of years, the biochip will enable doctors to do a full genetic physical with a simple blood test.

Late last year, Geron Corp. of Menlo Park, California, announced that scientists whose work it had supported had isolated the grail of human cell biology: embryonic stem cells. These remarkable cells are capable of growing into any of the 210 types of cells found in the human body. Suffer a third-degree burn? Grow some skin cells in a petri dish for a skin graft. Heart attack? Replace the damaged tissue with made-to-order heart cells. Broken back? Fix that right up with a skein of new nerve cells.

Repairing broken bodies, extending life, and improving individuals' capabilities may sound like good things. But the promises of biomedicine increasingly attract opposition. A chorus of influential conservative intellectuals is demanding that the new technologies be crushed immediately, and many in Congress are listening. These "luddicons," as one observer has dubbed them, see in biomedicine the latest incarnation of human evil. "In the 20th century, we failed to stifle at birth the totalitarian concepts which created Nazism and Communism though we knew all along that both were morally evil–because decent men and women did not speak out in time," writes the British historian Paul Johnson in an article in the March 6, 1999, issue of The Spectator. "Are we going to make the same mistake with this new infant monster [biotechnology] in our midst, still puny as yet but liable, all too soon, to grow gigantic and overwhelm us?"

The most influential conservative bioethicist, Leon Kass of the University of Chicago and the American Enterprise Institute, worries both that our quest for ever-better mental and physical states is too open-ended and, contradictorily, that it is utopian. "`Enhancement' is, of course, a soft euphemism for improvement," he says, "and the idea of improvement necessarily implies a good, a better, and perhaps even best. But if previously unalterable human nature no longer can function as a standard or norm for what is regarded as good or better, how will anyone truly know what constitutes an improvement?"

Kass argues that even "modest enhancers" who say that they "merely want to improve our capacity to resist and prevent diseases, diminish our propensities for pain and suffering, decrease the likelihood of death" are deceiving themselves and us. Behind these modest goals, he says, actually lies a utopian project to achieve "nothing less than a painless, suffering-free, and, finally, immortal existence."

What particularly disturbs these conservatives is biomedicine's potential to overthrow their notion of human nature–a nature defined by suffering and death. "Contra naturam, the defiance of nature, used to be a sufficient argument for those who were not persuaded by contra deum, provoking the wrath of God," writes historian Gertrude Himmelfarb in The Wall Street Journal. "But what does it mean today, when we have defied, even violated, nature in so many ways, for good as well as bad?" She goes on to suggest that cloning, artificial insemination, in vitro fertilization, and even the pill might be "against nature." Himmelfarb continues, "But the ultimate question is how far we may go in defying nature without undermining our humanity….What does it mean for human beings, who are defined by their mortality, to entertain, even fleetingly, even as a remote possibility, the idea of immortality?"

Himmelfarb insists that she doesn't disdain all improvement. "To raise these questions is in no way to reject science and technology or to belittle their achievements," she writes. "It is not contra naturam to invent labor-saving devices and amenities that improve the quality of life for masses of people, or medicines that conquer disease, or contrivances that allow disabled people to live, work and function normally. These enhance humanity; they do not presume to transcend it."

It is hard to see how a genetically enhanced memory, a faster mental processing speed, or a stronger immune system "undermines our humanity." After all, many full-fledged human beings already enjoy these qualities. Nor is it clear why "contrivances" that let disabled people cope with their physical problems are acceptable, while genetic cures to avoid the problems in the first place are not.

Nearly all technologies–agriculture, literacy, electric lighting, anesthesia, the pill, psychoactive drugs, television–affect human nature in the sense that they change the rhythms of human life and widen the range of behavior in which people can engage. We are no longer tribesmen living in family bands of 20, hunting and gathering on the plains of Africa. Surely there have been significant changes in human psychology as a result of the development of civilization. In fact, changing human psychology might be said to be the whole point of civilization; some anthropologists speculate that civilization is a set of social institutions that exist to tame human, especially male, violence.

Himmelfarb and Kass accuse those who favor biomedical progress of seeking immortality, as though that were a self-evident evil. But "immortality" is, in a sense, just a longer lifespan. Since 1900, lifespans worldwide have doubled, and most people think that achievement has been a great moral good. Using genetic techniques to increase human lifespans is not any different ethically from using vaccines, organ transplants, or antibiotics to achieve the same goal. Kass and Himmelfarb assert that human beings have been "defined by their mortality." But human beings are perhaps even better defined by their unending quest to overcome disease, disability, and death.

Indeed, all of the things on Himmelfarb's list of acceptable enhancements are "contra naturam." Is it not more natural to tear our meat with our hands rather than with stainless steel forks? Is it not more natural to die by the hundreds of thousands of tuberculosis, smallpox, or ebola? And is it not more natural for the lame, the blind, and old to die beneath the claws and teeth of predators? Himmelfarb does not make it clear how trying to "transcend" the dirty, nasty, brutish, and short lives of our ancestors undermines our humanity. Oh sure, a lower infant mortality rate–down from 300 or 400 deaths per 1,000 live births in the 18th century to only seven per 1,000 today–has deprived us of the chance to contemplate the tragic fleetingness of life and the poignancy of innocent death. But who among us really minds?

In an ironic linguistic twist, the pro-death opponents of substantially extending human lifespans have found their greatest allies among the pro-life opponents of abortion. The reason lies in genetic essentialism: the reductionist view of human beings as nothing more than meat puppets dangling from the strands of our DNA. Nowhere is this strange alliance more important, or its philosophical underpinnings more apparent, than in the debate over stem cell research.

At the very earliest stages of development, an embryo is an undifferentiated mass of cells, rather than blood cells, neurons, skin cells, muscle cells, etc. These undifferentiated stem cells can develop into any type of tissue. Isolated stem cells could one day be used to grow new heart, nerve, pancreatic, or liver cells that would replace tissues damaged by disease. Such replacement parts could extend human lifespans by decades, with significantly improved quality. They are just the sort of ambitious, "unnatural" technologies the luddicons fear.

Currently, biotechnologists investigating stem cells use embryos donated by couples who have had infertility treatments. The embryos are grown in laboratory cultures until they reach the blastocyst stage at four to seven days after fertilization. At that point the embryo consists of about 100 or so cells. A blastocyst is a hollow sphere of cells whose outer layer would develop into the placenta while the inner cell mass grew into a fetus. Once the inner cell mass is extracted from the blastocyst, those stem cells can no longer develop into a complete organism.

Stem cells removed from the blastocyst are grown in a culture on a layer of feeder cells that provide the necessary environment to keep them alive and in an undifferentiated state. Researchers are still trying to learn exactly what molecular signals will cause stem cells to develop into specific tissues. Those signals hold the key to using stem cells to develop replacement tissues which would be part of a universal tissue repair kit.

Once those signals are understood, using stem cells will depend, at least in the near future, on technology originally developed in cloning research. As we know from Dolly the lamb, factors in egg cytoplasm can reset an adult cell nucleus, giving it the ability to grow into an embryo as a source for stem cells. Using cloning technology, doctors might one day take the nucleus of one of your skin cells, put it in a human egg from which the nucleus has been removed, and allow that cell to divide to the blastocyst stage. They would then take out the stem cells from its inner cell mass and dope them with the appropriate hormones and proteins to turn the stem cells into, say, heart tissue, which could then be used to repair your ailing heart. Using your own cells in this way would mean that your immune system wouldn't reject the newly engrafted tissues, since the tissues would be a perfect match.

This research obviously promises to significantly advance human health and longevity. And just as obviously, stem cell research is completely entangled with the politics of abortion. It involves the use of embryonic tissues and, eventually, the creation of fertilized eggs that abortion opponents consider full-fledged human beings. To abortion opponents, a blastocyst used to duplicate your heart tissue isn't an extension of your tissue. It's another human being–the equivalent of your identical twin. As Judie Brown, president of the American Life League, told the Los Angeles Times about research on embryonic cells, "It doesn't matter if it's done in the womb or a petri dish, it's still killing."

After Geron scientists announced in November 1998 that they'd isolated human embryonic stem cells from donated embryos and aborted fetuses, President Clinton asked the National Bioethics Advisory Commission to look into any ethical issues associated with stem cells. In January, the U.S. Department of Health and Human Services ruled that the National Institutes of Health could fund research using already derived embryonic stem cells. This ruling provoked 70 anti-abortion House members, including Majority Leader Richard Armey (R-Tex.), Majority Whip Tom DeLay (R-Tex.), and Republican Conference Chairman J.C. Watts (R-Okla.) to sign a letter of protest to the president, declaring that the HHS ruling violated the congressional ban on funding research on human embryos. The congressional ban, adopted in 1996, outlaws the use of federal funds for the creation of human embryos for research in which they are "destroyed, discarded or knowingly subjected to risk of injury or death."

In January, however, HHS General Counsel Harriet Rabb artfully concluded that Geron's embryonic stem cells "are not a human embryo within the statutory definition." She based her decision on the fact that the cells "do not have the capacity to develop into a human being, even if transferred to the uterus." Consequently, destroying them in the course of research would not constitute the destruction of an embryo.

NIH scientists, whose work depends on federal funding, are eager for the ban to be lifted. NIH Director Harold Varmus correctly claims that federal funding also brings federal oversight, which he argues will protect the public interest. Of course, Varmus and other researchers curiously overlook the point that it was precisely federal oversight that led to the ban on federal support of this important research in the first place.

As it became clearer that the National Bioethics Advisory Commission was going to recommend that some stem cell research be federally funded, opponents turned up the heat. In July, Sen. Sam Brownback (R-Kan.) sponsored a Capitol Hill press conference featuring a group of bioethicists, religious activists, and physicians who oppose human embryonic stem cell research. "Human embryos are not mere biological tissues or clusters of cells; they are the tiniest of human beings," asserts the group's July 1 press release.

At the press conference, Edmund Pellegrino, a bioethicist at Georgetown University's Kennedy Bioethics Center, took aim at even private research efforts like those sponsored by Geron. He urged that a congressional ban "should be extended permanently to include privately supported as well as federally supported research involving the production and destruction of living human embryos." Although the current debate centers on federal funding, the real issue is whether the research should be done at all.

According to an NIH spokesperson, the NIH's draft guidelines for embryonic stem cell research are likely to be issued before the end of the year, and Congress will take up the subject in February. Sens. Arlen Spector (R-Pa.) and Tom Harkin (D-Iowa) are the two leading proponents of human stem cell research. Opponents include DeLay, Brownback, and Rep. Henry Hyde (R-Ill.).

The opponents argue that biotechnologists should concentrate on isolating and using stem cells known to exist in adults instead. Such adult stem cells are the precursor cells that renew tissues like skin and the linings of the intestines, and they likely could be used to regenerate these tissues. But many researchers believe that adult stem cells won't be as protean as embryonic cells–that they won't be able to turn into as many different types of cells.

One day it may be possible to take any adult stem cell back to the embryonic, and hence protean, stage. But the research to figure out how to do that depends on work with embryonic cells and the resulting cells, of course, would themselves be embryonic. People who oppose stem cell research on the ground that any cell that can become a human being already is a human being are essentially arguing that every cell in your body is another person.

"What happens when a skin cell turns into a totipotent stem cell [a cell capable of developing into a complete organism] is that a few of its genetic switches are turned on and others turned off," writes University of Melbourne bioethicist Julian Savulescu in the April 1999 issue of the Journal of Medical Ethics. "To say it doesn't have the potential to be a human being until its nucleus is placed in the egg cytoplasm is like saying my car does not have the potential to get me from Melbourne to Sydney unless the key is turned in the ignition." Since nearly every cell in the human body contains the complete genetic code of an individual, it is logically possible using biotech to turn every one of a person's cells into a complete new human being. If one doesn't turn on the ignition of a car (or one doesn't strip the suppressor proteins from a nucleus and put the cell into a womb), then the car won't go (or the skin cell won't grow into a human being). In other words, simply starting a human egg on a particular path, either through fertilization or cloning, is a necessary condition for developing a human being, but it isn't sufficient. A range of other conditions must also be present.

"I cannot see any intrinsic morally significant difference between a mature skin cell, the totipotent stem cell derived from it, and a fertilised egg," writes Savulescu. "They are all cells which could give rise to a person if certain conditions obtained." Those conditions include the availability of a suitable environment like a woman's womb. A petri dish is not enough.

"If all our cells could be persons, then we cannot appeal to the fact that an embryo could be a person to justify the special treatment we give it," concludes Savulescu. "Cloning forces us to abandon the old arguments supporting special treatment for fertilised eggs."

The DNA content of a skin cell, a stem cell, and a fertilized egg are exactly the same. The difference between what they are and what they could become is the environment in which their DNA is found. Thus, Savulescu argues, the mere existence of human DNA in a cell cannot be the source of a relevant moral difference. The differences among these cells are a result of how the genes in each are expressed, and that expression depends largely on which proteins suppress which genes. Does moral relevance really depend on the presence of the appropriate proteins in a cell? Trying to base moral distinctions on this level of biochemistry seems a bit quixotic.

So, asks Savulescu, is it immoral for you to take one of your skin cells, put it into an enucleated egg, and begin to grow it in a petri dish with the intention of making new brain cells to cure your Parkinson's disease? The cell was your tissue, with your genes. The transformed cell would not exist except for your intention–it would simply have flaked off and gone down the drain. "It's important to remember that essentially every cell in our body has a full complement of genes and in that sense is potentially totipotent," Varmus, the NIH director, reminded the National Bioethics Advisory Commission. That a cell contains a complete set of human chromosomes, yours, surely does not make that cell the moral equivalent of a baby. But as Savulescu and Varmus point out, if one is committed to the sort of genetic essentialism relied on by many opponents of cloning and embryonic stem cell research, then one is also logically committed to maintaining that the only difference between your skin cell and your twin is which proteins decorate their DNA strands.

The next step in stem cell research will occur when biotechnologists learn how to strip off the suppressing proteins from a mature cell's genes and transform it directly into a stem cell without having to use enucleated human eggs. That advance will take human eggs out of the discussion. Once it is possible to make stem cells without eggs, perhaps the moral intuition of many people will shift.

"It may eventually become possible to take a cell from any one of our organs and to expose it to the right set of environmental stimuli and to encourage that cell to return to a more primitive stage in the hierarchy of stem cells," explains Varmus. "Under those conditions, one might in fact generate the cell with as great a potential as a pluripotent cell [capable of becoming many different, but not all, types of tissues] from a very mature cell. One might even in fact imagine generating a cell that is totipotent in that manner." (Again, a totipotent cell is one that could develop into a complete organism if put in the right circumstances.)

Stem cells produced this way would be identical to the human embryonic stem cells that currently must be harvested from embryos. A cell whose suppressor proteins have been stripped off could become a nerve stem cell, a liver stem cell, or a baby–depending on the intentions of the patients and doctors. Researchers are experimenting right now to see if new embryonic stem cells could be formed by introducing the nucleus of an adult cell into an already existing enucleated embryonic stem cell, thus bypassing the need to use human eggs.

One final consideration is that those committed to claims that individual human beings are defined by their DNA must take into account the fact that up until the eight-cell stage any one of an embryo's cells could become a separate embryo and, under the right circumstances, develop into a baby. So until that point are there several persons, or one, in a fertilized human egg? It is now possible after a fertilized egg has first divided into two cells to take one cell and use it to test for genetic diseases. The tested cell could have developed into a baby if placed in a woman's womb. Has the genetic test killed a twin?

Stem cell research opponents might respond that these arguments are just splitting hairs. But there are quite a lot of biochemical hairs to split. And just how you split them determines how you regard the moral status of all types of cells.

Does human uniqueness really reside in our genes? Try this thought experiment. Imagine that transplant surgery has so improved that it is possible to remove your brain and place it safely into another body. So after your brain transplant, is your original body "you"? Or are "you" residing now in a different body? A new body could certainly change "you" in certain ways, since your senses and biochemistry would be different. But humans already affect the operation of their brains by giving themselves different drugs. When people take therapeutic drugs, say Prozac, L-dopamine, or even steroids, we do not believe they become different people.

"The human mind, of course, is a dynamic entity, but genes are static," explains Princeton biologist Lee Silver. A person's genes provide the instructions for building his or her brain, and the mind which comes out of that brain can respond to the environment. Unlike genes, a mind can change. "The human mind is much more than the genes that brought it into existence," concludes Silver.

What makes us distinct and unique is not our genes but our brains and the minds they contain. Persons generally have brains that are capable of supporting enough mental activity to give rise to a mind. As one of my old philosophy professors once put it, "I have never seen a mind that was not located in fairly close proximity to a brain."

The point that brains, not genes, are the source of our uniqueness is further underscored by the fact that no one argues that natural clones, otherwise called identical twins, are the same person, even though they share an identical set of genes. They have two different brains and experience the world from two different points of view. Human brains–malleable, fluid, flexible, changing–not static genes, are the real essence of what defines us as people. We are not mere meat puppets at the mercy of our genes. In fact, with biotech it might better be said that our genes are now at the mercy of our minds.

Leon Kass is disheartened by this prospect. "We triumph over nature's unpredictabilities only to subject ourselves, tragically, to the still greater unpredictability of our capricious wills and our fickle opinions," writes Kass in the September issue of Commentary. In other words, he is against human freedom because he doesn't think we can handle it. Ultimately, Kass wants to preserve the "freedom" of some portion of humanity to be miserable, sick, and unhappy. But if they were truly free, would people choose to suffer or to subject their children to such suffering? Not likely.

Kass does have a point, however, when he writes in Commentary, "Even people who might otherwise welcome the growth of genetic knowledge and technology are worried about the coming power of geneticists, genetic engineers, and, in particular, governmental authorities armed with genetic technology."

There is a threat of government control. Some intellectuals are already succumbing to the temptation of government-supported and mandated eugenics, lest the benefits of genetic engineering be spread unequally. "Laissez-faire eugenics will emerge from the free choices of millions of parents," warns Time magazine columnist Robert Wright. He then concludes, "The only way to avoid Huxleyesque social stratification may be for government to get into the eugenics business."

Clearly we must be on guard against any attempts to harness this new technology to government-mandated ends. But a Brave New World of government eugenics is not an inevitable consequence of biomedical progress. It depends instead on whether we leave individuals free to make decisions about their biological futures or whether, in the name of equality or of control, we give that power to centralized bureaucracies. Huxley's world had no "laissez-faire eugenics" emerging from free choice; Brave New World is about a centrally planned society.

A biological future without a plan is exactly what scares critics on both the right and the left. "Though well-equipped [through biotech], we know not who we are or where we are going," Kass fearfully writes. If we know not who we are, surely advances in biotech are helping us to understand more completely who we are. As for where we are going, the fact that we don't know is why we go. Over the horizon of human discovery Kass sees a territory marked, like the maps of yore, "Here be monsters." To avoid the supposed monsters, Kass wants humanity to stay quietly at home with its old conceptions, technologies, traditions, and limited hopes.

If we use biotech to help future generations to become healthier, smarter, and perhaps even happier, have we "imposed" our wills on them? Will we have deprived them of the ability to flourish as full human beings? To answer yes to these questions is to adopt Rousseau's view of humanity as a race of happy savages who have been degraded by civilization. The fact is that previous generations have "imposed" all sorts of technologies and institutions on us. Thank goodness, because by any reasonable measure we are far freer than our ancestors. Our range of choices in work, spouses, communities, medical treatments, transportation–the list is endless–are incomparably vaster than theirs. Like earlier technologies, biotech will liberate future generations from today's limitations and offer them a much wider scope of freedom. This is the gift we will give them. Like all technologies, biotech could be abused, but using it is not, as Kass and Paul Johnson would have us believe, the same as abusing it.

Scientific facts will not resolve these issues. On the one hand, people who see human genes as the defining essence of humanity will object to stem cell research and a good deal else in the coming biotech revolution. One the other hand, people who see human beings as defined essentially by their minds will have fewer moral objections.

At a hearing earlier this year, Edward Furton, who works at the National Catholic Bioethics Center, asked the National Bioethics Advisory Commission to "please remember in your deliberations that millions of your fellow citizens hold that the human embryo is a human life worthy of the protection of the law." He added, "As a result of the tainted origin, many Americans who have deeply held moral objections to embryo destruction may choose not to receive any benefits from this new research."

No one is suggesting that people should be forced to use medicines that they find morally objectionable. Perhaps some day different treatment regimens will be available to accommodate the different values and beliefs held by patients. One can imagine one medicine for Christian Scientists (minimal recourse to antibiotics, etc.), another for Jehovah's Witnesses (no use of blood products or blood transfusions), yet another for Roman Catholics (no use of treatments derived from human embryonic stem cells), and one for those who wish to take the fullest advantage of all biomedical discoveries.

In a sense, the battle over the future of biotech –and, if Fukuyama is correct, the future of humanity–is between those who fear what humans, having eaten of the Tree of Knowledge of Good and Evil, might do with biotech and those who think that it is high time that we also eat of the Tree of Life.