There’s a questionable notion floating around out there in the numerous discussions over heritable human genetic modification and CRISPR.
This idea goes that if germline human gene editing goes awry for any number of reasons, scientists could simply reverse it by applying genetics again.
The reversal notion does not fit with the reality of science as we know them today and could be harmful in giving false reassurance of the safety of genome modification.
To put it another way, you can’t retract a designer baby or its genetic modifications if they are later proven to be problematic.
If human modification were done in the germline (sperm and eggs or in a 1-cell embryo), then for better or worse every one, barring chimerism, of the trillions of cells of the resulting genetically modified (GM) baby would have that genetic modification. How would you effectively reverse an unexpectedly deleterious hard-wired change in all of those cells? The reality is that it would be impossible. Trying to do so would also raise the very real possibility of introducing yet more problems as well.
If the reversibility notion of human genetic modification is meant instead in a broader population sense such that within the larger human population that accidentally harmful genetic changes could be reversed or at least their transmission stopped, what would that entail? Forcing people who carry such unexpectedly “bad” genetic changes not to reproduce? We need to consider social justice issues.
Or is reversibility only implied in the context of gene drive-based genetic modification introduced into organisms in a natural ecosystem rather than humans? Even there I’m doubtful reversal attempts would work and others are also skeptical.
Overall, scientists and others should use greater caution in discussing the notion of reversibility of genetic modification. It would not be as simple as portrayed sometimes. Other notions such as genetic “off switches” for modifications in organisms (while elegant systems in the laboratory setting) could also prove in the real world to be impractical amongst heterogeneous cells in an organism within a population of organisms.
This doesn’t mean that people should stop working on or thinking about reversal strategies or conditional approaches to genetic modification. Quite the opposite as that work is important and should continue, but the notion that one could “simply” reverse an introduced genetic problem is misleading and downplays legitimate concerns over safety. It also potentially exaggerates human control of genetics in the real world.
As some of you readers know, I’ve written a new book on human genetic modification including on possible use of CRISPR in people. In the book I discuss the potential upsides and risks of CRISPR’ing people. The book is called GMO Sapiens. In it I discuss something called “reproductive quarantine” where humans with unexpectedly negative genetic outcomes from modification attempts are prevented by governments from reproducing.
While CRISPR’ing people would be an experiment, if something goes wrong with it then unlike a bad experimental outcome in a test tube or in a dish, or even a profoundly flawed paper that can be retracted, I don’t see how you undo the harm at the very least to individuals.
More broadly this raises the point that in these kinds of hypothetical human genetic experiments, the person becomes the experiment, necessitating a higher level of discussion that includes bioethical and social justice considerations.
The same thing could be said about de novo mutations in conventional babies.
@pat You are correct, of course.
One would hope that all scientists would understand the concepts of growth and saturation and be able to distinguish quality from quantity and have the courage to speak plainly to the mathematical fact that optimizing quantity sacrifices quality…
We are a small group animal. Or, more accurately, we evolved as a small group animal. Large groups of humans always become pathological. (Observe how the large “American Group” subdivides into so many subgroups in largely failed efforts to find a small group that individuals can be comfortable within. Observe how the “family small group” is still “important” and observe how it is destroyed by bringing to the table a world-wide-web of electronic communication devices. Observe…)
Long before CRISPR, Huxley explained how the human animal could be remodelled (The Department of Predestination) and conditioned (subliminal messaging in sleep and elimination of the family) and standardized (Bokanovsky’s Process) and placated (soma) so as to live as a large group animal — like ants. Of course these are all the sorts of things that we do to the domesticated species that serve us. Observe how GMO is much touted as a tool for manipulating domestic species.
Domestication is an interesting process. Consider the dog. Derived from a wolf, it’s skin has become loose and sagging. It’s brain is much smaller than a wolf. It’s analytical ability is nothing compared to a wolf but the dog greatly exceeds the wolf when it comes to “emotional intelligence” — which is to say, being compliant, being docile, being domestic.
Now I I ponder for a minute. What is the most domesticated species? I’d say that it is the human species.
Roll out the CRISPR babies…
I really do not understand why we as a society need CRISPR babies at all. What is the justification for taking the risk? Our world is overpopulated as it is. Homo sapiens is one of the few non-endangered species on this planet. If someone with obvious genetic disease very badly needs to populate the world even more, then preimplantation genetic screening should solve any “bad genes” problems for now. Let’s not create GMO babies just because we can.
About re-editing badly edited breast or any other tissue – this is such an impractical idea! We are talking millions of cells and they would have to be re-edited with 100% efficiency – remember that a SINGLE cell can give rise to cancer.
Paul – I think you’re being insufficiently imaginative here.
First, for reversing the heritable effects, one would “just” edit the eggs or sperm of the recipient of the edited gene back to wild type (or edit any embryos that person had a gonad in the production of). Note that this only works if it is the substance of the DNA change that is the problem; if the process of making the DNA change is the problem, this won’t solve it – but such a problem might also not extend past the first generation anyway. And I would note that such transgenerational effects of the process should show up in preclinical work with non-human animals. It might not – reproduction is often quite species specific – but there’s no particular reason to think it will.
Second, for reversing any harmful effects on the person who was the product of the gene editing (on the soma, not the germ line), somatic cell gene therapy should be an option. It would need to be better than it is now, but it is now on the edge of clinical use, at least in some applications. If we get good enough to edit embryos (or gamete cell lines) we are likely to continue to make progress on the somatic side. And, note, we probably don’t need to edit all roughly 5 trillion nucleated human cells (turns out 90% of human cells are red blood cells, without DNA – who knew?). Many genetic diseases are (largely?) tissue specific. Re-edit breast and ovarian tissue in women who got an inadvertently “bad” edited version of BRCA 1 and you fix most, though not quite all, of the problem.
None of this is to say we should do human germ line editing without great caution. Extraordinary preclinical work should be required and, if it is successful, the subsequent human trials should be quite limited and carefully controlled. But the repair option is, I think much more promising than you think it is.
I do agree that reversal is likely to be harder in any non-human release into the environment, though even there not necessarily impossible – and certainly worth investigating and planning for.