In my first chapter, I mentioned that Alarmist biologist Rollin Hotchkiss from Rockefeller University predicted in 1965 that “in five years” parents would be able to order children with blonde hair, blue eyes, and fair skin.[1] Since then, a glittering parade of Alarmists, from Jeremy Rifkin to Leon Kass, wailed that earth-shaking Eugenic choices lurk right before us.
In this chapter, I discuss a new rule for analysis in bioethics, especially analysis of genetic enhancements: respect complexity. The chapter’s message is that Enthusiasts for genetic enhancement were premature, but as might be expected, not for the reasons cited by Alarmists.
To begin, consider designer babies. Much discussion of this topic is imaginary and factually inaccurate. Both champions and critics assume that simple changes could be made with relatively few risks and that the main problems are psychological, such as unrealistic expectations of parents or objectifying children as designed commodities.
On the scale of possible harms to babies, those psychological problems are minor. We don’t want to try to perfect babies and get dead ones. That’s the real ethical problem.
In 2002, Francis Collins, the head of the Human Genome Project, testified before the President’s Council on Bioethics, which then held hearings on the ethics of human enhancement.[2] It must have been a fascinating day to discuss that topic because Leon Kass, the arch-critic of enhancement, chaired that Council. The Council contained other members with similar sentiments such as Johns Hopkins political theorist Francis Fukuyama and Harvard political philosopher Michael Sandel. All three either had, or would soon publish, books claiming that human enhancement would tear apart our social fabric or (in Fukuyama’s terms) render us “post-human.”[3] They argued that we had never done anything like this before, that even the smallest improvement would put us on the slope to Eugenics.
Question: what did Collins tell this Council, and through it, most bioethicists? He first showed the Council a clip from the movie GATTACA, emphasizing what the geneticist said to Antonio and Maria, a couple planning a genetically-selected child (versus their naturally-conceived child, Vincent):
“Your extracted eggs Maria, have been fertilized with Antonio’s sperm and we have performed an analysis of the resulting pre-embryos. . . Naturally, no critical pre-dispositions to any of the major inheritable diseases. All that remains is to select the most compatible candidate. . .”
“You've already specified blue eyes, dark hair, and fair skin. I have taken the liberty of eradicating any potentially prejudicial conditions - premature baldness, myopia, alcoholism and addictive susceptibility, propensity for violence and obesity. . . ”
“You want to give your child the best possible start. Believe me, we have enough imperfection built-in already. Your child doesn't need any additional burdens. And keep in mind, this child is still you, simply the best of you. You could conceive naturally a thousand times and never get such a result.”[4]
In his testimony, Collins says about this scene:
“You can conceive 1,000 times and never get such a result.” (quoting from the scene [sic]) An interesting statement, and actually, it raises a potential problem with this whole scenario because that implies the ability, I suppose, if this was going to happen, to have 1,000 or more embryos to choose from, which is a bit of a biological quandary.
And in fact, that is one of the many ways in which this scenario begins to fall apart scientifically because if you were, in fact, to attempt to try to optimize for ten or twenty phenotypes, as the smooth-tongued counselor here was suggesting, and you consider that each of those phenotypes would probably be influenced by five or ten genes, each of which would have perhaps more than two alleles. You quickly get into a combinatorial problem where lacking a million or better embryos, the ability to actually do this in a fashion that gets you very far is pretty limited.
Of course, that’s only a small part of the scientific arguments because the concerns of trying to optimize offspring, if they are predicated on this kind of scenario, assume a degree of genetic determinism that we know is not correct, and it will not become correct just because we get smarter about genetics.
Just because we understand the nature part of the nature/nurture equation doesn’t mean that the nature part becomes quantitatively more important. It just means we understand it better.
If you understand what Collins told the Council here, you understand the foolishness of all the worries about designer babies and about choosing traits to create perfect babies.
To put this point differently, the complexity of interactions among genes, and between genes and proteins, and among all these and variable environments, is stunningly vast. So to reliably produce a beautiful, bright, genetically healthy child with an optimistic personality and musical talent would require life-long experiments in gestating and raising thousands of nearly similar embryos. Such experiments will not occur, in part because they cannot be ethically justified. And without those experiments, we won’t know what we’re doing in altering genes.
What about trying to change genes after the embryo is formed or in fetal development? This problem of insertional mutagenesis plagues most gene therapy. Because we don’t understand how to use a virus to insert genes exactly where we want, inserting genes this way often has disastrous consequences.
Even when we could prevent a child from having a devastating condition, say by deleting the genes for Huntington’s, we might inadvertently give it cancer. It is not like taking a bad brick at the bottom of a brick wall and replacing it with a good one: it’s more like taking it out and leaving a hole, making the whole wall wobble.
Once upon a time, scientists saw genes as preformed traits, with each gene containing built-in instructions for its expression. Now we know the picture is much more complex: that genes interact with each other, that DNA can be unstable, and that how they code for proteins matters greatly in their expression.
A single gene will rarely be responsible for a desirable human trait. Instead, most desirable traits will involve several genes interacting with several environmental factors. The exact features of a particular trait will depend on many environmental inputs that activate specific combinations of genes at key nodes in fetal and child development.
Human fetal development can be seen as traveling down a long road with many forks to get to the final destination, the newborn child. Embryonic development goes down the road a ways to a fork with diverging paths, going one way and not another, and then it moves to dozens of other forks, each with more diverging paths. At each juncture, it travels down only one path to a particular destination (what genetics call the "phenotype" or final characteristics).[5] At each fork, the fetus–baby–developing-child continuum is bombarded with environmental inputs that affect the expression of its gene-package.
To say we know how to order one particular destination and one particular combination of multi-gene, special traits implies that we have already gone down all these forks and paths and studied how millions of embryos each became a specific phenotype. GATTACA falsely implied that we can easily know just which embryo to select to get a hirsute male with perfect pitch and optimistic mood.
All of this should make us pause before we insert genes through viruses randomly into human cells, much less crazy talk of trying to make permanent changes in the germ line of future humans.
Were this not complex enough, let’s emphasize an important ethical fact about improving humans that makes our subject differ from research in traditional genetics: we cannot experiment on human fetuses the way animal breeders do with livestock. We breed generations of dogs for specific traits by controlling which male and female dogs breed with each other and culling unwanted pups from the line, but we cannot do so with humans.
Most human traits will begin with a biological basis in several genes and develop after complex interactions with environmental factors during gestation, infancy, and childhood. For these reasons, predicting what traits a child might exhibit, at a counseling session or from a genetic catalog, will be next-to-impossible.
Some might think the above discussion unduly pessimistic, but consider what happened in gene therapy over the last fifteen years. In 1999, in Tucson, Arizona, seventeen-year-old Jesse Gelsinger heard about experimental gene therapy at the University of Pennsylvania for his inherited disorder, ornithine transcarbamylase deficiency (OTC).
In the genetic disease OTC, the liver doesn’t properly cleanse blood of ammonia produced in normal metabolism, resulting in toxic levels. Many OTC newborns die around birth; half don’t live to age five. A new regimen of drugs and diet had enabled Jesse to live to be a teenager, but without a cure, OTC would eventually kill him.
Jesse entered the study as a healthy research volunteer. According to a friend, he “wanted to prove he was a man.”[6] Penn researchers claim Jesse was informed that the experiment wouldn’t help him and told him that it might help OTC babies. His father said Jesse wanted “to help save lives.”
So Penn researcher James Wilson sought adults with OTC whose livers still functioned. He injected them with an adenovirus that contained copies of the gene lacking in OTC patients.
Rick Weiss, the former science reporter for the Washington Post, reports the grim reality of what actually happened:
Four days after scientists infused trillions of genetically engineered viruses into Jesse Gelsinger’s liver … the eighteen-year old lay dying in a hospital bed at the University of Pennsylvania. His liver had failed, and the teenager’s blood was thickening like jelly and clogging key vessels while his kidneys, brain, and other organs shut down.[7]
The wrongful death lawsuit claimed that Wilson knew the virus had injured other OTC adults and that Wilson failed to use simple, direct language to explain his dangerous study. As University of Pennsylvania bioethicist Arthur Caplan said,
Not only is it sad that Jesse Gelsinger died, there was never a chance that anybody would benefit from these treatments. They are safety studies. They are not therapeutic in goal. If I gave it to you, we would try to see if you died, too, and if you did, OK.
If you cured anybody, you’d publish it in a religious journal. It would be a miracle. All you’re doing is you’re saying, I’ve got this vector. I want to see if it can deliver the gene where I want it to go without killing or hurting or having any side effects.[8]
Wilson only reported to the FDA 39 of 700 problems about the virus, although laws required reporting all. Researchers concluded in 2000 that adenoviruses should only be used as a last resort. After a congressional hearing on Jesse’s death, the National Institutes of Health (NIH) vowed to better monitor medical research. It soon stopped Wilson’s research at Penn and halted most research on gene therapy.
Between 1999 and 2002, an experimental gene therapy for x-Severe Combined Immunodeficiency Syndrome (x-SCID), the “bubble boy disease,” on seventeen French children restored their immune systems. Later, three of the cured children got leukemia and one died, hardly a great success, so officials halted this trial.[9]
In 2007, Jolee Mohr, a thirty-six-year-old woman in Arkansas with mild arthritis enrolled in a gene therapy experiment and died immediately. The inserted genes in the virus allowed a common fungus to grow in her abdomen, which when it became the size of a football, killed her.
In sum, fifteen years of hundreds of experiments in gene therapy have yielded little success.
So far I have stressed the failures of changing genes to cure current genetic diseases, the complexity of the tasks ahead, and as a result of these two, the huge complexity and risks of attempting to genetically enhance humans, either on a one-person basis or for all descendants.
Let’s return to the day when Francis Collins told Kass’ Bioethics Council that the “ethics community” was wasting its “energies” worrying about genetically enhancing humans. Of enormous importance, Collins testified that with neither germ-line nor somatic therapy scientists lacked the knowledge to conduct safe, human trials on genetic enhancement. Had he wanted to, Francis Collins could have also mentioned the dismal failures of human gene therapy over the previous fifteen years, but was too politically savvy to do this.
Collins delivered his coup de grace when he testified that every conceivable good use of gene enhancement for babies could be done simply, in those couples at high risk, by having them use in vitro fertilization, testing of various embryos for genetic disease (PGD), followed by implantation of healthy embryos without that disease. Nothing else, he said, would be medically needed for decades.
One then wishes one could have been a bioethicist-fly-on-the-wall when he specifically critiqued Alarmist bioethicists, saying they should expend “their energies” elsewhere. But in this case, Collins wasn’t preaching to the choir, but testifying before critics who had long since made up their minds. From their subsequent writings, none of them understood what he said.
Even if we overcame these problems and did such large-scale experiments on human children, it would be decades before we knew the results. Clearly, this is never going to happen because America will not experiment on embryos and children this way, because thousands of women will not volunteer to gestate such babies, and because thousands of parents will not agree to raise such babies in similar ways.
As Collins explained these things, it would have been interesting to know what Kass, Fukuyama, and Sandel felt. Did they think that their books had been unethically Alarmist? Did they worry about making the public worry about problems that would not emerge for centuries? Did they worry that their Alarmism might divert the public from solving ongoing, present problems? Probably not.
What we do know is that the Report issued the next year by Kass’s Council lumped together all kinds of ethical issues about human enhancement and got it terribly wrong.[10] Both the Council and its Report could have done so much better, but not only did it do nothing to help, it created unnecessary problems by tilting at windmills.
The lesson here resembles the one from the history of bioethics: separate cases by type and don’t lump everything together. By all means, keep simple cases simple, such as letting competent adults try relatively safe practices. On the other hand, appreciate complexity and do not discuss the irreducibly complex as if it were simple. The new rule: keep complex cases complex; don’t make them simple.
For all these reasons, genetic enhancement of fetuses, of newborns, of existing individuals, much less future humans, is not going to be feasible, either practically or ethically, for many decades. In this case, both Enthusiasts and the Alarmists were wrong: Alarmists to warn against things that will not be, Enthusiasts to too-eagerly embrace genetic change.
Rollin Hotchkiss, quoted by Ronald Kotulak, “And Now Your Child Built to Order: Day of Genetic Engineering Near, Biologist Says,” Chicago Tribune, August 18, 1965, 5.
Francis S. Collins, “Genetic Enhancements: Current and Future Prospects,” December 13, 2002, Transcript, President’s Council on Bioethics.
President’s Council on Bioethics (Leon Kass, Chair), Leon Kass, Beyond Therapy: Biotechnology and the Pursuit of Happiness- A Report of the President’s Council on Bioethics, (New York, Dana Press, 2003); Francis Fukuyama, Our Posthuman Future: Consequences of the Biotechnology Revolution (New York: Farrar, Straus & Giroux, 2002); Michael Sandel, The Case Against Perfection: Ethics in the Age of Genetic Engineering (Cambridge, MA: Harvard University Press, 2007).
GATTACA script, Internet Movie Script Database (IMSDb), http://www.imsdb.com/scripts/Gattaca.html
Lenny Moss, What Genes Can’t Do (Boston: MIT Press, 2002), 188.
Richard Jerome, “Death by Research,” People Magazine, February 21, 2000, 123.
Deborah Nelson and Rick Weiss, “Hasty Decisions in the Race to a Cure? Gene Therapy Proceeded Despite Safety, Ethics Concerns,” Washington Post, November 21, 1999, A1.
Center for Genetics and Society, “Gelsinger Wrongful Death Lawsuit names Bioethicist Caplan,” Genetics Crossroads Newsletter, October 16, 2009. http://www.geneticsandsociety.org/article.php?id=2857
President’s Council on Bioethics, Beyond Therapy.