Raiding the CRISPR

The second installment from The Code, a series of 3 short documentaries on the internet about the origins of genetic medicine, addresses gene editing.  The current approach to this exploits “CRISPR,” or “Clustered Regularly Interspersed Short Palindromic Repeats,” DNA sequences initially discovered as a sort of bacterial immune system but very efficient at editing out undesirable genetic features, such as disease susceptibility mutations in plants or, for that matter, people.

For medicine, the CRISPR approach is one of the latest ways of approaching gene therapy.  For example, sickle cell anemia is caused by a single misplaced “letter” in the 3-billion-letter human genetic code.  (It’s actually 6 billion because there are two copies of each gene, only one of which is “read” to produce what the gene codes for.)  It’s a blood disease, one in which the red blood cells are defective, and to treat it definitively requires replacing an affected person’s blood cells with good, normal ones.  Sickle cell is inherited, and it shows up in kids, and, trust me, if you’ve ever taken care of someone with it, as I did 30-some-odd years ago in my medical training, you’d welcome a world in which people didn’t have to suffer from this.

The problem: where to get the good cells.  Answer: from a suitable donor, or perhaps by taking out some of the sick person’s bone marrow cells, editing the abnormal hemoglobin gene with genetic “scissors,” and infusing them back into the person’s vein, to take up residence in the bone marrow and flourish, normally, replacing the sick cells.  CRISPR is the genetic “scissors.”  The approach is still experimental, but promising.

Technical and safety concern: how can we be sure the scissors don’t go “snicker-snak,” as my old genetics professor used to say, in the wrong places, and change other genes?  They appear to be pretty accurate so far, but just how sure are we?

Bigger ethical concern: might we—should we—edit a human embryo—say, one diagnosed after IVF but before implantation—to nip the genetic disease in the bud, with the prospect of preventing future generations from getting the abnormal gene, and hence the disease, at all?

Hmmm…to cure—perchance to control?—that’s the rub.  Where would be draw the line?  Could we?  Why would we?  Why not try to edit as many diseases out of existence—and as many desirable traits into existence or predominance—as we could, technically?  Well, apart from the small problem that the genetic bases of most diseases are more complex than we yet understand (see last week’s video release from The Code), or the other small problem that editing multiple genes at once is, as of now, still a future prospect for genetic engineering and the field known as “synthetic biology,” is the concern that people making the decisions about what to edit become, as it were, the “actors,” or “conditioners,” to borrow C.S. Lewis’ term from The Abolition of Man, while those acted upon, and their progeny, are subjects—perhaps (unavoidably) unknowingly.  If this is in the context of doctor/patient relationships and specific diseases and informed consent (to the degree that is possible), and the like, that may be fine, but broader use raises concerns that should be obvious.

CRISPR-based gene editing is the most recent approach to gene therapy.  The bulk of the video is about other approaches.  It reviews past history, including efforts not to edit genes, but add good genes to replace missing or bad function of bad genes.  It also reviews the history of people dying from gene therapy research that was, in retrospect, charging ahead perhaps faster than it should have been.  And it mentions recent successes.  Still relatively scattered, but promising, and, if pursued under proper human subject research ethics, generally ethical.  It’s the prospect of heritable editing that gets worrisome.  And we should remember that, even for the ethical stuff, we humans can envision medical advances faster than we can make them reality.

These videos are good viewing for the general public.  Check them out.


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