Kim Tingley has a great cover story in the New York Times Magazine this week, on the slow crawl of mitochondrial gene transfer toward human trials. She does a good job of unpacking the science, and an even better job of probing the roots of our uneasiness with this prospective new therapy.
The procedure involves removing nuclear DNA from the oocyte (egg) of a prospective mother and inserting it into a donor egg whose nuclear DNA has also been removed. Any fertilized embryo produced with this egg would have DNA from two biological parents, plus mitochondrial (mt) DNA from the donor egg. Proponents say it offers hope of preventing a range of horrific conditions which are caused by mutations in mtDNA and afflict somewhere between 1 in 4000 and 1 in 250 people. Opponents say it’s basically a biotech gateway drug in that it will usher us down a dark one-way path towards — well, whatever people are afraid of science see when they envision a future overrun with unregulated experimentation. The term “designer babies” gets thrown around a lot here.
When we talk about “designer babies,” though, we’re talking about something quite different than preventing disease. We’re talking about engineering humans that are super-smart, (or super-pretty, or super-athletic). That gets us rather quickly into eugenics. At the World Science Festival in Manhattan this past May, a panel discussion entitled “Designer Babies” involved a lengthy recounting of the history of selective breeding and forced sterilization in the U.S. It’s a shameful history, to be sure. And if mt gene transfer was truly re-opening those gates, we would be right to be horrified.
But the simple fact is that we have no clue how to engineer better humans, and mitochondrial gene transfer brings us no closer to figuring it out. Yes, we’re getting much better at manipulating genes in general. We can turn adult skin cells into pluripotent stem cells by inserting the right mix of essential “factors.” And gene-therapy, the practice of replacing mutated genes with functional ones, is making a slow and careful comeback after some fatal failures in the 1990s.
Still, we know almost nothing about the relationship between genes and intelligence. We don’t know which genes impact intelligence; we don’t know how many such genes there might be, or which chromosomes they might be located on, or how exactly they might nudge us up or down an IQ point or two. We also don’t know what environmental factors might impact the expression of those genes, how their smart-making ways might be enhanced or hindered by the food we eat, or the games we played as kids, or, I don’t know, the number of times we moved before the age of 15.
In fact, most geneticists won’t touch the intelligence question with a 100-foot-pole out of fear they’ll be tarred and feathered as a neo-Nazi eugenicist. So to suggest that we’re even tip-toeing towards an era of Franken-babies feels sorely mistaken at best, and duplicitous at worst.
Another term that’s being misused in this debate is the term “cloning.” At least some opponents of mitochondrial gene transfer have likened the procedure to human cloning, an argument that conflates several terms: genetic cloning, genetic modification, and somatic cell nuclear transfer (SCNT). So let’s be clear:
- SCNT, which is used in mt gene transfer, involves replacing nuclear DNA in one person’s egg, with nuclear DNA from a different person’s egg. It does not involve manipulating that genome, getting down inside of it and changing the atcg sequence around, in any way.
Genetic modification is the direct manipulation of an organism’s genome, usually the adding or subtracting of specific genes. It includes inserting cassava genes into corn plants to make them more drought-resistant, or pesticide-tolerant. It also includes most of what we mean when we say “gene therapy.”
Genetic cloning is the production of multiple identical copies of some biological entity – a molecule, gene, or whole-organism. The most well known example of this, of course is Dolly, the sheep. Genetic modification usually involves the cloning of individual genes. But cloning humans is actually not on the horizon. In fact, it’s illegal in most states.
Again, if mt gene transfer were truly a step down the path towards human cloning, alarm bells would be justified. But it’s not. It’s a step down the path towards healthier babies and fewer intractable diseases.
There are other major criticisms of mitochondrial gene transfer. At least some opponents worry about “involving subsequent generations in an experiment to which they cannot consent,” as Tingley writes. This concern feels slightly less objectionable to me, in part because it’s not predicated on an outright misuse of scientific terminology. The problem though, is that the line we’re drawing is arbitrary. My favorite graph in the Tingley pieces sums this up eloquently:
… Ordinary reproduction is, by definition, genetic modification. The risks involved are unpredictable and potentially tragic; the subject of the experiment is a future person who cannot consent. We constantly try to control this process, to “design” our children, starting with our choice of sexual partner. During pregnancy we try to “enhance” them by taking folic acid, not smoking, avoiding stress; once they’re born, we continue the process with vaccines and nutritious food, education, clean air and drinking water. Some of these pre and postnatal environmental factors, we now know, change their biology in heritable ways. Is mitochondrial replacement, because it takes place in a petri [sic] dish, any more unnatural or morally repugnant than this?
In February of this year, the FDA held a two-day hearing to assess the state of scientific research on mitochondrial gene transfer, and to gauge public acceptance. Fertility specialists and would-be parents with defective mitochondrial genes were hoping that the hearings would lead to a green light for human clinical trials. At least two labs are poised to launch such trials as soon as regulatory approval comes through; one clinician said they had prospective participants lined up around the corner. But so far, there’s been no word from regulators, and Tingley’s account of the hearing itself does not bode well for proponents.
I spoke to Jamie Grifo a few weeks back, about what might happen next. Grifo is a physician -researcher and director of the NYU Fertility Center. By most accounts, it was his work on mt gene transfer that first raised regulatory eyebrows, back in the 1990s. In fact, when he published his initial forays (no pregnancies, but they succeeded in making an embryo) the Surgeon General called him directly. “She asked me what the hell I was doing,” he said. “And then she told me to stop doing it.” Grifo says he tried to work with regulators to move the research forward, but that the FDA had no interest. “I had numerous conversations with them,” he says. “But they just kept putting up more road blocks, hoping that we would get frustrated and quit, which is what we did. We gave all our research to China, so it wouldn’t go to waste. And then we moved on to other things.”
Mitochondrial gene transfer might be able to alleviate human suffering. But before we can find out, we need to reach an agreement on how to move forward. And before that can happen, we need an honest dialogue, one predicated on a real understanding of what, exactly, scientists are trying to do and what, exactly, worriers are worried about.
Speaking of which, there’s one more term we should talk about — one the press might well do away with altogether: “three-parent babies.” Yes, it does a much better job of drawing readers’ eyes than “mitochondrial gene transfer.” But it’s also a gross misuse of the term “parent,” even in the most purely biological sense. Mitochondrial DNA is not the same thing as nuclear DNA. It contains just 37 genes, and produces exactly one product – ATP (aka aden2osine triphosphate, aka the body’s fuel); it contains no genes for looks or behavior or personality, or for any of the other things that we mean when we say the words “parent,” or “child.”