Posted on March 27, 2015 at 10:54 AM
An article in the New York Times last week suggests that the genetic engineering of humans is only just around the corner. A recently developed gene editing tool known as CRISPR/Cas9 has finally made it possible to easily and accurately make genetic alterations to human cells, which could make it possible (according to the Times story) “to cure genetic diseases, but also to enhance qualities like beauty or intelligence.” Moreover, the tool could be used to alter germline cells (that is, eggs, sperm, and any cell that gives rise to them), which would mean that the alterations were encoded permanently in the human population, generation after generation. This prospect has motivated a group of prominent genetic scientists and bioethicists to propose a professional, self-imposed moratorium on any attempt to make clinical use of tools for editing human germline cells. Another group, whose members have helped develop an alternative gene editing tool (zinc-finger nucleases), has proposed an even broader moratorium, one that would proscribe research into germline modification as well as clinical applications.
The moratorium is a good idea, and in fact similar pauses should probably be considered for some other potential applications. CRISPR/Cas9 is both less powerful and more powerful than the Times story suggests: it does not have us right on the doorstep of editing the human genome, but it may well have us on the doorstep of some other very significant forms of genetic engineering.
There have always been two big challenges confronting anyone who wants to edit the human genome: making the genetic changes correctly (getting them into cells and then into the genome at the right location) and making the correct genetic changes (actually achieving the results without accidentally creating new problems). CRISPR/Cas9 makes tremendous headway on the first problem, although the scientists behind its development don’t think the problem is fully solved. Sometimes, for example, the genetic modification is still made in the wrong spot. Such problems provide one reason for supporting a moratorium on clinical use.
The second problem – identifying the correct genetic changes – is the real issue, though, and CRISPR/Cas9 doesn’t even address this problem. In fact, no gene editing tool can solve the second problem, any more than a word processing tool can by itself solve the problem of how to write the next great American novel. To identify the “correct” genetic changes, we need to understand what the targeted gene does, but also how it interacts with other genes, and also how the genome interacts with environments. We’re not there. As Baltimore told the Times, “I personally think we are just not smart enough — and won’t be for a very long time — to feel comfortable about the consequences.” This is the second and bigger reason that the moratorium is a good idea.
CRISPR/Cas9 can be turned to many other uses than editing the human germline, however. One of the most extraordinary is the possibility of using it in “gene drives” that could be make genetic modifications to sexually reproducing populations of microorganisms, animals, or plants. Sexually reproducing organisms have two sets of gene—one from each parent. A gene drive is a set of genes that, if it is inserted into one set, will get itself copied to the appropriate location on the other set, replacing any competing genes and also ensuring that all of the organism’s offspring receive the drive. Within those offspring, the drive will again replace any competing genes, ensuring that all of the next generation receives the gene. If a species reproduces rapidly, it might be possible to quickly alter the whole species. Mosquitoes could be altered so that they can no longer transmit malaria or dengue, for example.
Depending in part on how they are constructed, gene drives might go awry. Possibly, for example, another gene could somehow get added into the drive, so that not an unintended genetic change was being driven through the species along with the desired one. This is a version of the first problem above – that of doing the edits correctly.
The second problem – that of finding the “correct” genetic changes – also arises with gene drives to alter wild species. In one respect, to be sure, good changes might often be easier to identify. There might be changes to mosquitoes that would be straightforwardly desirable, from a human perspective, and could achieved with a simple genetic change – perhaps by editing a single gene, sidestepping some of the complexities of gene-gene and gene-environment interactions that stand in the way of editing the human genome so as to enhance beauty or intelligence.
In another respect, though, finding “correct” changes remains difficult. Depending on how the drive is constructed, there is some possibility that a mosquito species targeted by a drive would evolve a workaround of some sort, probably introducing some slight risk that the newly evolved mosquito could be worse than the original in some way. Also, sometimes (but not always) modifying a species means modifying an ecosystem, insofar as other organisms are affected by the target organism, and ecosystem engineering could be as complicated as engineering beauty in the human body. Some modifications may well be pretty straightforwardly desirable (from some human perspectives); imagine a gene drive that prevents the wooly adelgid, a kind of aphid that has been accidentally introduced into the United States, from destroying the eastern hemlock population. Such a genetic intervention might be desirable from a preservationist standpoint (somewhat paradoxically). Many other cases of ecosystem engineering could be more complex.
We want to move forward with gene drives, and we may want to move forward with editing the human germline. Nonetheless, a moratorium on these applications, if not on research into them, is probably desirable for now. We need to make sure we’re smart enough to do these things.
Gregory E. Kaebnick is a research scholar at The Hastings Center and the editor of the Hastings Center Report. He is the author of Humans in Nature: The World as We Find It and the World as We Create It. (Oxford University Press 2013).