From Skeptic vol. 7, no. 2, 1999, pp. 48ff.
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How Close Are We To Cloning Time?
An Introduction to the Science and Ethics of Human Cloning
"The Commission concludes that at this time it is morally unacceptable for anyone in the public or private sector, whether in a research or clinical setting, to attempt to create a child using somatic nuclear transfer cloning."
Report on Cloning Human Beings, National Bioethics Advisory Commission.
"What nonsense, what utter nonsense, to think we can hold up our hands and say, 'Stop.' Human cloning will take place, and it will take place in my lifetime. I don't fear it. I welcome it."
Senator Tom Harkin, Senate Committee Hearings on Human Cloning.
The very phrase "genetic technology" linking genetics, "the science of heredity," with technology, "the practical application of knowledge, especially to engineering purposes," is the stuff of which horror stories and science fiction are made. For most of human history, life has been seen as a gift, perhaps the greatest gift, of God or the gods. But since Mendel first started breeding peas and especially since Watson and Crick determined the molecular structure of DNA, the mysteries of life have become increasingly demystified. The emerging field of genetic technology has given us new forms of life, the ability not only to detect but to cure genetic disorders, and even the ability to build even more sophisticated biological weapons, including the spectre of ethnically targeted bioweapons. The cloning of Dolly the sheep suggests we are close to cloning a human. To many that means "taking a major step into making man himself simply another one of the man made things" so that "human nature becomes merely the last part of nature to succumb to the technological project which turns all of nature into raw material at human disposal" (Kass, quoted in National Bioethics Advisory Board [NBAC], 82).
Who should control human reproduction, God, society, tradition, the state, the individual? Is cloning a human next? If so when? What are the reasons for human cloning and what are the risks? How close are we to cloning time? This special issue of Skeptic on cloning, genetic engineering, and genetic theories of human behavior begins with this overview of the science behind cloning and ethical questions it raises. It is followed by my interview of Dr. Richard Seed, "the man who would be cloned," who has become the point man for human cloning ever since he announced he plans to clone himself. Next, Michael Shermer examines how the ethical issues provide the latest test of our ability to navigate the nexus between science and morality. Then Richard Dawkins demonstrates how natural selection generates an increase in information content in the genome. Nicholas Thompson considers the implications of group selection for evolutionary explanations of moral behavior. Finally Kari Konkola and Glenn Sunshine compare and contrast evolutionary and religious explanations of human behavior.
From Cuttings to Cloning:
Getting at the deeper issues involved in cloning and genetic engineering requires brief overview of the ever growing field of genetics. The structure of the DNA molecule as a twisted ladder with AT and GC base pair bonds as the rungs has provided a completely materialistic basis for the defining properties of living things: a self-directing information code that has a structure which is maintained in stable form and so is able to serve as a model to replicate itself yet is susceptible to change that is transmissible.
Some Scientific Background
Sexual reproduction, differentiation, and development into the various cells of a complex organism, growth from single cell to fetus to newborn to adult, disease and repair, even senescence and death, are each day proving more understandable in terms of the underlying biochemistry. An important point is that the duplication of DNA is not always exact. The sequence of base pairs occasionally contains a "typo," which provides for the introduction, accumulation, and transmission of mutations. The on-going frequency of such typos is actually rather high, about 1 per 100,000 base pairs. We now know that the DNA code acts like a program which contains its own "spell-checker" that detects most of these errors and corrects them (Weaver and Hedrick, 183). In fact, the spell-checker itself has evolved so as to regulate the number of errors it lets through. Feed that controlled variation into the Darwinian selection machine and we can understand not only the biochemical basis of the life of an individual, but the evolution of more complex life forms over time.
Viewed from this perspective, the bodies, sensory organs, and behaviors of complex organisms appear as vehicles for transmitting what Richard Dawkins so aptly dubbed "selfish genes." The distinction between non-living things and living things becomes a matter of increasing information, organized complexity, not categorical difference. Crystals mark the end point on the non-living side, viruses the living side, with the area in between becoming increasingly gray and muddled.
In discussing cloning it is especially important to remember that:
(1) The complete genetic code for each and every cell in our bodyłthe genomełis contained in the DNA that composes the chromosomes of every cell of our bodies.
(2) There are 23 chromosomes in each of the human germ line cells (sperm or eggs), and 23 pairs of chromosomes in each of the somatic cells.
(3) We now have the technology to recognize, remove, or replace sequences of DNA base pairs, to use them as a trigger to stimulate biological processes that are linked to them in some manner, to duplicate them, or to use them to restart the process of development and gene expression.
All Clones are Not the Same
The word "clone" derives from the Greek for a twig, and horticulturists have been taking cuttings and growing new plants from them for centuries. The word came into current usage when the renowned British biologist J.B.S. Haldane suggested in 1963 that it would soon be possible to create genetic duplicates of plants, animals, and even humans. Nobel laureates Joshua Lederberg and James Watson also discussed the prospects of future cloning (Kolata, 70-73; Pence, 1998, 1-11). Numerous science fiction books and movies then took up the term and popularized it. The two best known to the general public are David Rorvik's In His Image, and the legal brouhaha that followed its publication of as a work of non-fiction, which resulted in the publisher (but not the author) stipulating to its being "a hoax and a fraud," and Ira Lewin's novel The Boys From Brazil, about Dr. Josef Mengele's program to clone Adolf Hitler, later made into a movie starring Gregory Peck and Sir Laurence Olivier.
According to the National Bioethics Advisory Commission (NBAC), a clone is "a precise genetic copy of a molecule, cell, plant, animal, or human being" and cloning refers to any of a number of "established technologies that have been part of agricultural practice for a very long time and currently form an important part of the foundations of modern biological research" (25). Regenerating complete plants from cuttings is commonplace in agriculture. Simple animals such as flat worms can regenerate completely from a small segment, and even vertebrates such as lizards regenerate tails and limbs. While this type of regeneration does not take place in mammals, millions of human clones, identical (monozygotic) twins, walk the earth today. Each pair of twins developed from a single ovum that was fertilized by a single sperm and then at some point during the pregnancy split into two (or more). If the split is not total, it produces conjoined (what used to be termed "Siamese") twins. Identical twins are usually very similar in their bodies and their behavior, but they are not "identical persons." Conjoined twins certainly aren't, and Dolly-type clones wouldn't be either.
The biotechnology revolution has brought four new types of cloning: (1) Molecular Cloning; (2) Cellular Cloning; (3) Blastomere Cloning, the technique used to clone the monkeys, Netty and Ditto, born in 1997; and (4) Nuclear Transplantation Cloning, i.e., Hello Dolly!
Molecular cloning uses a host bacterium to duplicate a segment of DNA that has been found to produce a biologically important substance (e.g., insulin for treating diabetes). Cellular cloning makes copies of particular somatic (not germ line) cells. It is extremely useful in testing the effects of new drugs on the cells of a particular part of the body. (An example would be cloning kidney cells to test the effects of EPO, which is used to treat the anemia associated with kidney dialysis.) Neither of these methods, which are commonplace in the biotechnology business and a vital part of modern medicine, produces anything like the sci-fi clone that grows from a fertilized egg into a complete genetic but time-lagged duplicate of a sheep, goat, or another Hitler.
Figure 1 shows how we make babies the "good old fashioned way." The chromosomes in the sperm of the father join with those in the egg of the mother to produce an embryo that develops into a baby sheep, goat, or human. If however it splits during development, identical twins are produced.
Biotechnology now allows us to perform the fertilization in vitro, induce splitting, and then implant the offspring into surrogate mothers. That technique, termed blastomere separation, has become an effective method of producing two or more genetically identical sheep or goats (which is particularly valuable when used on genetically engineered animals that produce important biochemicals). As shown in Figure 2, however, the separation must be induced early in the development sequence. Once what is termed the blastocyst stage (in which the inner cell mass has developed) is reached, it is no longer possible to produce clones.
While blastomere separation is a long way from the clones of sci-fi, it illustrates the concept of totipotency, which is critical not only in producing clones of adults, but to Richard Seed's Holy Grail of human rejuvenation. The blastomeres in Figure 2 are totipotent, that is, they have the potential to generate a complete new organism; the blastocysts in Figure 2 are not. The key scientific issue that underlies the entire technology of cloning is the question of how long the DNA remains totipotent. From the moment of conception, the fertilized egg begins to divide and develop into different types of cells and tissues, such as the muscles in our arms and legs, the liver, kidneys, and especially the neurons in the brain.
How far in the developmental process does our DNA retain totipotency? DNA in the germ line cells (sperm and eggs) remains totipotent throughout life. But what about the somatic cells? All the somatic cells contain the same DNA, but the particular genes that are activated determine which type of cell develops. A potential neuron, for example, must turn on the neural genes, but turn off the genes that activate the development of other somatic cells. Likewise for a liver cell or a muscle cell.
How long does the DNA in a cell in the liver or the kidney or the brain retain the ability to repeat the entire developmental sequence and produce not just another liver, kidney, or brain, but a complete genetically identical delayed twin? Is the duration of totipotency the same for all somatic cells? Does it vary among species, decreasing with biological or neural complexity? Does it vary among individuals within a given species? Is it itself genetically determined? Is it subject to selective pressure? The answers to those questions will determine whether human cloning remains science fiction or becomes science fact.
Experiments with tadpoles as far back as the 1950s and 1960s demonstrated that, at least in some amphibians, somatic cells retained totipotency. As shown in Figure 3, if the nucleus of a somatic cell could be injected into a recipient ovum in which the nucleus had been deactivated, a small number would develop into adult frogs.
Other experiments successfully transplanted the nuclei of adult frogs. A very small number (4%) developed into tadpoles, but none of these became adult frogs, which suggested that potency might be declining as a function of donor age (or degree of cellular differentiation). The state of knowledge circa 1978 suggested that cloning a man from an adult somatic cell was a long shot at best. So Rorvik's In His Image had to be science fiction, not science fact.
Research in the 1990s, however, demonstrated that most somatic cells do retain some degree of totipotency. Then with the technique of using an electric pulse to fuse nuclei of somatic cells with unfertilized eggs, the door for cloning a human suddenly and loudly swung open. Figure 4 shows the method by which Ian Wilmut produced Dolly. Donor cells from the mammary gland cell cultures of an adult sheep were placed next to an egg cell from which the nucleus had been removed. A shot of electric current fused the donor and recipient cells. Most importantly, it set the DNA differentiation program back to time zero.
Of 277 successful fusions, however, only 29 (11%) developed to the blastocyst stage. When these were transferred into surrogate mothers, only 1 produced a live, bleating little lamb.
Scientific Questions Raised by Dolly
Dolly marked the first time a fully developed mammal had been cloned by somatic nuclear transfer. She was a one in 277 shot, not good odds at any race track. And a number of important scientific questions remain before human cloning becomes a sure thing:
- Was Dolly really produced from a fully differentiated mammary gland cell or from a less differentiated mammary stem cell? Wilmut's experiment might not really have proven that it is possible to turn back the program to time zero for fully differentiated cells.
- Just how old was Dolly at birth? Somatic cells age each time they divide during the normal course of life. This is probably because the ends of the chromosomes, termed telomeres, are truncated on each cell division. For germ line cells, the enzyme telomerase helps the telomeres restore their full length. But this is not the case for somatic cells. While there is telomerase in the recipient nucleus, will it protect and restore the ends of the donor chromosomes? Were Dolly's cells really those of a newborn little lamb or were they already those of an old ewe when she emerged from the womb? Recent evidence says that Dolly (or at least her genetic material) was 6 years old at birth, because her chromosomes are shortened.
- Normally, mutations in somatic cells affect only that cell and the cells it produces when it divides. Any mutations that occurred in the mammary cells were transmitted into Dolly. Are somatic cells more subject to mutation or to more lethal mutations than germ line cells? Was Dolly born with a heavy genetic load?
- Embryonic gene activation occurs at the 8-16 cell stage in sheep, but at the 4-8 cell stage in humans. Is the window of opportunity in humans too narrow for successful somatic nuclear transfer? Would the success rate in humans be substantially below Dolly's 1 in 277?
- By definition, cloning reduces genetic variation. Reduced genetic diversity has already produced problems in inbred strains of wheat and corn, leaving them dangerously susceptible to killer strains of viruses and bacteria. Purebred dogs, while remarkable not only in their physical attributes, but also their behavior, are subject to a host of genetic disorders. (The solution is to breed back to other strains, which agriculturists, but not dog fanciers, realize and practice). Clones would all share the same genetic risk factors. A nation of clones could be wiped out by a single virus.
- While the thought of cloning another Michael Jordan or Albert Einstein may be appealing, a little reflection shows that neither of them (or anyone else of prominence) was produced by cloning. The whole evolutionary advantage of sexual reproduction is that it increases genetic variability by continually throwing up new combinations of genes to face new environmental challenges. Whether investing in the stock market or descendants, diversification is a wise long term strategy in an uncertain world.
Religious, Ethical, and Medical Concerns
Before reaching its conclusion urging a moratorium on human cloning, the NBAC examined not only the scientific, but also the ethical, legal, and even religious implications of cloning. Virtually everyone agrees that the degree of medical risk involved needs to be considered when human cloning is contemplated. But they disagree on the extent to which they believe that risk will remain above that associated with other, acceptable methods of reproductive technology (such as in vitro fertilization), or even ordinary reproduction.
The religious arguments against human cloning are as varied as the religious doctrines from which they derive. Their only consistency is that those religions or religious persuasions (e.g., Roman Catholicism) that have adamantly opposed other means of giving individuals control of reproduction adamantly oppose cloning, while those that have been more open to such methods (e.g., Reform Judaism) are more open to cloning. The NBAC could only conclude that "the wide variety of religious traditions and beliefs epitomizes the pluralism of American culture, there is no single 'religious' view on cloning humans, any more than for most issues in biomedicine." (72) The Commission also weighed ethical arguments, as opposed to purely religious arguments against cloning, including the possibility of a diminished sense of individuality and personal autonomy, degradation of the quality of parenting and family life, whether parents would be tempted to seek excessive control over cloned children, and the re-opening of the door to eugenics. They compared these arguments with those in favor of cloning, including protecting personal choice, maintaining privacy, freedom of inquiry, and encouraging the development of powerful new technologies. They concluded that their efforts were hamstrung by the fact that "neither moral philosophers nor religious thinkers can agree on the 'best' moral theory; indeed, they often cannot even agree on the practical implications of any single theory." (76-77)
The most ardent academic opponent of human cloning is bioethicist Leon Kass, of the University of Chicago. Kass testified before the NBAC and elaborated the anti-human cloning position against political scientist James Q. Wilson's measured defense in the "opposing viewpoints" book, The Ethics of Human Cloning (Kass and Wilson, 1998), published by the American Enterprise Institute think tank. Kass, himself a former molecular biologist, builds his argument against human cloning on the "wisdom of repugnance": "the emotional expression of deep wisdom beyond reason's power fully to articulate it." Kass concedes that "some of yesterday's repugnances are today calmly accepted" although he qualifies the concession by noting: "though, one must add, not always for the better." (18) It should come as no surprise, then, when Kass places the specific issue of cloning within the broader conflict between societal and individual control of reproduction:
Cloning turns out to be the perfect embodiment of the ruling opinions of our new age. Thanks to the sexual revolution, we are able to deny in practice, and increasingly in thought, the inherent procreative teleology of sexuality itself. But, if sex has no intrinsic connection to generating babies, babies need have no necessary connection to sex. Thanks to feminism and the gay rights movement, we are increasingly encouraged to treat the natural heterosexual difference and its preeminence as a matter of "cultural construction." But if male and female are not normatively complementary and generatively significant, babies need not come from male and female complementarity. Thanks to the prominence and the acceptability of divorce and out-of-wedlock births, stable, monogamous marriage as the ideal home for procreation is no longer the agreed-upon cultural norm. For that new dispensation, the clone is the ideal emblem: the ultimate "single-parent child."
Thanks to our belief that all children should be wanted children (the more high-minded principle we use to justify contraception and abortion), sooner or later only those children who fulfill our wants will be fully acceptable. Through cloning, we can work our wants and wills on the very identity of our children, exercising control as never before. Thanks to modern notions of individualism and the rate of cultural change, we see ourselves not as linked to ancestors and defined by traditions, but as projects for our own self-creation, not only as self-made men but as man-made selves; and self-cloning is simply an extension of such rootless and narcissistic self-re-creation. (emphasis in the original, 8-9).
Compared to Kass, James Q. Wilson provides only the most qualified defense of controlled human cloning in the AEI volume. Much stronger cases are made by such cloning advocates as the philosopher Gregory A. Pence in his book Who's Afraid of Human Cloning? and Lee Silver, a professor of Molecular Biology, Ecology, Evolutionary Biology, and Neurosciences at Princeton University, in his book Remaking Eden: Cloning and Beyond in a Brave New World. Pence had already begun his book before the NBAC was convened. Attending the meetings, Pence was disappointed that none of the commission members "was willing to defend human cloning in any way" and that "professionalism in bioethics meant that each side had to be defended with logic and passion." (xi-xii) Pence shows that the very same arguments, including medical risk, have all been made against other reproductive technologies, most recently, in vitro fertilization. Technical advances and market acceptance have disposed of all of them.
Pence also edited the opposing viewpoints reader, Flesh of My Flesh. It includes essays against by Kass; by theologian George Meilander that cloning cheapens God's gift of human reproduction (39); and by bioethicist George Annas that cloning is replication, not reproduction, and would therefore cross a natural boundary of kind rather than degree. Annas opined against the NBAC and other government commissions that "popular notions of cloning derive from science fiction books and films that have more to do with cultural fantasies than actual scientific fact" and that they were "wrong to disregard the lessons from our literary heritage on this topic, thereby attempting to sever science from its cultural context." (80) The book also includes an essay by philosopher Philip Kitcher, who would only allow cloning when there is no other way to produce genetically related offspring, as for example for a lesbian couple; as well as essays by Stephen Jay Gould and by Richard Lewontin, debunking fears of genetic determinism.
In Remaking Eden Silver argues that rather than a technological curse, genetic engineering will provide all the cures for cloning, as well as ordinary reproduction. He points out that good old-fashioned reproduction produces plenty of errors and has a lower overall success rate than some modern reproductive technologies. Critics of cloning and other forms of reproductive technology can't have it both ways. If medical risk is a serious enough moral concern to demand banning a given reproductive technology, then the existing risks of ordinary reproduction must produce an equal and opposite need to develop methods of reducing or eliminating those risks.
Pro-cloners dismiss the concerns about reduced genetic variability by pointing out that cloning will no more replace "making babies the good ole fashioned way" than has any other reproductive technology. As Richard Seed notes in the interview, the applications to his human cloning clinic have come from infertile couples, not influential billionaires. Further, Seed argues that advanced reproductive technology opens the door for unlimited genetic variability. He dismisses all the ethical and religious objections against human cloning, and considers the medical risk the only valid argument. Increasingly, however, that risk is proving to be real. Cloning experiments on mice, goats, cows, and monkeys, while admittedly still in their infancy, nonetheless already have produced some serious medical problems.
Reuters (1999) summarized a report published in the May 1st issue of the British journal The Lancet on the sudden death of a cloned calf that led French researchers to suspect the cloning process itself causes long-term health problems. From birth, the calf's white blood cell count fell rapidly. There was a quick decline in hemoglobin, the oxygen-carrying pigment found in red blood cells. Iron supplements did not improve the calf's condition, and it died of severe anemia at the age of 51 days. Postmortem examination revealed a seriously underdeveloped thymus, spleen, and lymph nodes, organs that play a key role in the immune system.
The report noted that "cloning has a relatively high rate of late abortion and early postnatal death," with current neonatal death rates among cloned animals approaching 50%. The researchers concluded that cloning may pose an inherent risk to long-term health, noting that their observations ōshould be taken into account in debates on the effective application of reproductive somatic cloning to human beings.
The Oregon Regional Primate Research Center produced Netty and Ditto through the process of blastomere cloning. But they have not been able to clone a monkey successfully by somatic nuclear transfer. Their attempts have resulted in death of the clones and sometimes even their pregnant mothers. The Oregon team's experiments have produced placental abnormalities, abnormal swelling, three to four times the normal rate of umbilical cord problems, and severe immunological deficiencies. These abnormalities are similar to those found in experiments on disrupting the phenomenon of gene imprintingłthe switching on or off of genes based on whether they come from the mother or the father. Since clones have only one parent, faulty imprinting may be the cause (Weiss, 1999).
Recent evidence from the Roslin Institute (Chronicle News Service, 1999) shows that Dolly's telomeres are 20 percent shorter than is normal for a 3-year old sheep. Cloned from a 6-year old ewe, Dolly's shortened telomeres suggest she was biologically six at the time of her birth. Each time the DNA unwinds, the telomeres (a small piece at the end of the chromosome that may help to seal and then release the two strands) are truncated. Like a barber or a loan shark, the aging process always "takes a little bit off the top." Eventually, like Humpty Dumpty, the double helix can't be put back together again. But are telomeres the mechanism of aging, or just one of its products (like grey hair), or its markers (like worn-down molars)? To complicate matters further, Dolly has given birth to two lambs. If Dolly was prematurely aged at birth were her offspring as well? Only time and continued observations will tell. But the latest research on sheep is baaaaaad news for Richard Seed's goals of human cloning and rejuvenation. Instead of a fountain of perpetual youth, the result of repeated DNA reprogramming may be to turn out the techno version of the Struldbruggs of Swift's Gulliver's Travels, they live forever, but continually age, ending up a bunch of blind, deaf, slobbering invalids, surely new grist for the sci fi clone mill.
A Matter of Prudence
The issues of cloning and other reproductive technologies cannot be decided by religious or ethical argument because there simply is no agreed upon religion or ethical system. Experts reach totally opposite conclusions. Kass, an esteemed bioethicist who is knowledgeable in the biosciences, argues vehemently that cloning is but the last step in the breakdown of the protection given by society to the normal family. Kitcher, an equally distinguished and erudite ethicist, is troubled by human cloning but thinks it would be justified for the purpose of building what Kass would find a most un-normal family. Pro-cloners Silver and Seed have faith that greater knowledge and technical expertise will solve all problems.
Human cloning is really a matter of prudence, defined as "proceeding from caution and good judgment." Ian Wilmut and the Roslin Institute originally conducted their sheep cloning experiments as a way to decrease the costs to support the institute's other ongoing biogenetic research. When the media raised the issue of human cloning, they backed away because they saw the subject as only getting in the way of advancing scientific knowledge and future profits. The NBAC moratorium was an attempt to assuage the public fears raised by that media coverage. As human cloning advocate Richard Seed points out, the NBAC prohibition on human cloning has no teeth. Congress has taken no binding action. Even it if did, how could they ban all forms of cloning? The slightest change in procedure could legally qualify as being something other than somatic nuclear transfer. If banned in the U.S. (and elsewhere), it would only go to countries eager to attract capital and technology.
The opening quotations from the NBAC and Senator Harkin are both correct. Given the medical risks and the scientific unknowns, human cloning "just wouldn't be prudent at this time," as former President George Bush used to say. Seed's Human Cloning Clinic or some other group may announce that they have cloned a human, even before you read this article. But if so, it will only be like landing a man on the moon, a sensation rather than a scientific breakthrough. The latter will come from innumerable experiments, large and small, some ballyhooed, most unreported by the mass media, that explore the underlying issue of genetic development, how does the DNA code direct itself? Before Richard Seed's goal of rejuvenation becomes reality, we will have to answer that question precisely for each and every organ in the body, or at least the master genes that code for them.
Chronicle News Service. 27 May 1999. "Sheep clone was born old, study says" p. A-1
Kass, L. and J. Q. Wilson. 1998. The Ethics of Human Cloning. Washington, DC: AEI Press.
Kolata, G. 1998. Clone: The Road to Dolly and the Path Ahead. NY: Norton.
National Bioethics Advisory Commission (NBAC). 1997. Cloning Human Beings: Report and Recommendations. Rockville, MD.
Pence, G. E. (ed.). 1998a. Flesh of My Flesh: The Ethics of Cloning. New York: Rowman & Littlefield.
Pence, G. E. 1998b. Who's Afraid of Human Cloning? New York: Rowman & Littlefield.
Reuters Health News. 30 April 1999. Summary of article in The Lancet, Vol. 353: 1489-1491.
Silver, L. M. 1997. Remaking Eden: Cloning and Beyond in a Brave New World. NY: Avon.
Weaver, R.F. and P. W. Hedrick. 1997. Genetics. Chicago, IL: William C. Brown Publishers. 3rd Edition.
Weiss, R. 1999. "Clone Defects Point to Need for 2 Genetic Parents." Washington Post. May 10, 1999, P. A1.