Germline gene therapy is frightening

24 Jul 2015

Gene therapy is an array of methods where a gene is inserted into a patient's body in order to treat disease. It's a fascinating topic in biology and it holds tremendous potential for the future of medicine. There are two kinds of gene transfer. Firstly, somatic cell gene transfer is when you deliver healthy genetic material into the patient's body: a super-exciting way that could take over the realm of treating genetic disorders, like the fatal cystic fibrosis.

Secondly, there's the prospect of germline modification: essentially, let's fix a hereditary condition by changing the genetic make-up of your sex cells. That way, your child would be free of a genetic disease that you happen to carry or suffer from. For understandable reasons, some scientists, while conceding that the former carries giant pros and few cons, are upset by the prospect of the latter. There are some papers on germline gene therapy, research is being conducted, but some of the studies remain unpublished, while the ethics of germline modification are debated.

The problem with this method is remarkably frightening. It's one of those things where you can genuinely argue: this is a slippery slope. (Unlike people smoking weed and gays getting married, this is one of the genuine, dangerous ones.)

See, by changing the genetic make-up of your offspring, what you do is changing the hereditary capital they might pass on to future offspring afterwards. Not only are you fiddling with the genetics of your child; your grand-children and grand-grand-children might be affected, too. The 'new' part of their genotype might be passed on or not, but let's be clear: a tiny branch of the evolutionary tree has been altered in this scenario. Its trajectory poked a bit to the left, a bit to the right, while human intention is the operator, the one that chooses what (not which, but what) design is selected.

Now, what's wrong about this method? We use things like contraception: that fiddles with evolution, too, doesn't it? We don't live in an evolutionary world anymore, we've got hospitals, we've got vaccines, we've got homeless shelters—do I want to backtrack on the great advances of our society?

Nope. But there's a fundamental difference between cutting the branch of the evolutionary tree and somehow actively defining evolution. In Darwinian terms, we're still subject to the natural process of evolution and genetic drift: there is no creative force having steered the evolution of apes in the East African Rift valley all the way to us—we are subject to natural selection. And even if we breed dogs that drool the least and cultivate crops that yield the most, we're only choosing from what we have, and let the evolutionary process run, for the most part. (But writing the code? we've never been that creative.) And even that artificial selection of characteristics has its boundaries: I reckon we're mostly not keen on eugenics?

The point I'm making is this: just as the branching of a tree is expressed in some sort of a fractal (there's a different pattern on every scale, a complex phenomenon where if you change one parameter, the modification is projected into infinity), messing with the DNA of a potentially infinite branch of your offspring, that's a tremendously powerful imprint. And imagine someone wanted to cure baldness, splay feet or flatulence. For good.

I can't think of a red line here. Is it only fatal diseases? What if the odds are 9:1, or 1:9, of a fatal genetic disorder? What is fair to eliminate until the concept of designer babies becomes reality? And who gets the treatment primarily? Is it the most affluent people? And what about a chronically ill person who insists on having biological offspring—shouldn't it be mandatory for us to ensure that we do all we can to prevent the possibility of the child having to go through the same torment?

Even though I'm a big believer in scientific betterment of mankind, germ-line therapy is scary to me. Ethically. I've read compelling cases against germline gene transfer, as opposed to somatic cell gene therapy.

This is from an article regarding mitochondrial DNA replacement: a very potent and currently debated issue. I like it because it addresses the slippery slope argument of small changes leading to universal ethical concerns:

Supporters argue that [germline modification] concerns do not apply to modifications of mitochondrial DNA, which they characterize as an insignificant part of the human genome that does not affect a person's identity. This is scientifically dubious. The genes involved have pervasive effects on develop­ment and metabolism. And the permissive record of the UK regulatory authorities raises the prospect that inheritable mitochondrial changes would be used as a door-opening wedge towards full-out germline manipulation, putting a high-tech eugenic social dynamic into play.

—http://www.nature.com/news/a-slippery-slope-to-human-germline-modification-1.13358

And it's this 'eugenic social dynamic' that I abhor. I propose to you a rationale why germline modification should be avoided—if possible. Even, and especially, if you are leaning toward giving the O.K. on this method, I think you might agree with my premise: we're living in something of a post-evolutionary society. In this society, it is moral to abort a deeply unhealthy foetus, it is morally superior to use condoms to prevent unwanted babies and we share the notion that charity and altruism are good, regardless whether you're helping family, a friend, a stranger. The degree of relatedness is becoming an obsolete criterion for the moral imperative to help people.

Soon this logic will be pertinent to family—the concept will slowly be redefined and the genetic boundaries will be abolished. A family will become a circle of affiliations, a fellowship, a union of (dare I say it) love, compassion and shared responsibility.

In that society, the notion that one has a right to a biological son or daughter will be selfish by our intellectual standards. There are a plenty of genetically healthy individuals around the world, up for adoption. The seemingly selfless and loving (therefore morally superior) action will be to adopt a healthy child: and so the desire to imprint one's own genetics onto offspring will be phased out.

That's my thought. Being fully aware that this dynamic brings just about as many problems as it solves (it does not, in particular, solve the eugenic social dynamic as it pertains to artificial selection), it answers to the social dilemma of germline gene therapy in the present. It shows why our morality gives us certain licence to rally against this kind of medicine.

(If any of what I wrote on the science of gene therapy is inaccurate or too vague of a shortcut, I'm open to criticism.)

EDIT: As of 2017, I no longer see the prospect of biological relatedness becoming obsolete as probable. Human nature is tribalistic. It will remain such, as the powers of regression in politics and society will prevent disassociation from our evolutionary past.


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