A Straight Dope Classic from Cecil's Storehouse of Human Knowledge

Is CRISPR the big deal everyone says it is?

December 30, 2016

Dear Cecil:

I keep hearing about the bright future of gene editing, specifically involving something called CRISPR. I've seen claims that it could cure cancer and most genetic diseases, maybe even prolong life to infinity and beyond. Is this kooky futurist crap, or maybe something that'll be too expensive for mass distribution?

Cecil replies:

The experts predicting cancer cures are the relatively sober, realistic ones, Julia — we’ve got CRISPR teams living the sci-fi dream, sticking preserved mammoth genes into elephant cells. The CRISPR-Cas9 editing process still looks like the revolutionary development it’s been touted as over the last four years, and research hums along at a remarkable pace. Still, some of the more dramatic projections surely won’t pan out, and those that do will have to overcome all kinds of stumbling blocks — biological, ethical, legal, ecological, and, yes, financial.

Let’s catch everyone up on what we’re talking about. The immune systems of certain bacteria use DNA sequences called CRISPR (clustered regularly interspaced short palindromic repeats), containing genetic material collected from viruses the bacteria have been exposed to. When one of these viruses attacks again, the matching CRISPR segment gets copied to an RNA molecule (remember from bio class? Like DNA, but just one strand?) that tracks down and binds to the virus’s own DNA, allowing a specialized enzyme called a Cas (CRISPR-associated) protein to cut the DNA and disable the virus.

So in CRISPR-Cas9 editing, researchers create guide RNA sequences that match parts of whatever gene they want to alter and use them to essentially program Cas enzymes to go make cuts at the desired spots, adding or removing DNA as needed. This turns out to be easier, cheaper, more precise, and more flexible than previous gene-editing methods, and since late 2012 scientists everywhere have been putting CRISPR to ambitious use. Researchers in Pennsylvania used it to cure hemophilia in mice, with major implications for other genetic disorders. At UC Davis, they’re getting ready to create a modified pig that will grow a (presumably transplantable) human pancreas inside it. Just two months ago, in the first such test on an actual person, Chinese oncologists introduced CRISPR-edited immune-response cells into a lung cancer patient.

As one might guess with such a pervasive and powerful new methodology, critics have raised concerns about the safety of performing CRISPR editing on human genes. Chief among cited risks is what's called off-target effects, in which the guide RNA gets confused by multiple similar DNA strings and the wrong gene gets edited; even when the enzyme finds and cuts the correct DNA, it can still dart off and snip some other segment too. The resulting potential for cellular mayhem is serious: a mistargeted edit could activate (e.g.) a gene causing cancer. Efforts to identify and minimize off-target trouble spots are complicated by the fact that each person’s genome is different and may contain more repeated segments than is typical.

The field of embryonic gene editing is both more promising and more ethically troubling. We may soon be able to correct genetic problems or add immunities in utero, but such prenatal tinkering refuels perennial fears of creating designer babies, customized for attractiveness or intelligence. CRISPR-edited genes may also head out into the ecosystem: scientists anticipate being able to quickly wipe out pest species (mosquitoes being the classic) using something called a gene drive, which would cause a sterility mutation to spread through the population much more quickly than ordinary heredity could manage.

The low cost of CRISPR research democratizes the research process but thereby increases the likelihood of error by a careless team, and it’s not like there’s much regulation to keep mavericks in line. There are more restrictions on the embryo-modification front: some countries ban it outright, or permit it only for research; others have spelled-out but unenforceable guidelines. A year ago, scientific bodies in the U.S., the UK, and China called for a moratorium on making any heritable changes to human DNA. Since then, though, Swedish and British biologists have begun CRISPR-based research on healthy human embryos; the understanding is that these won’t be brought to term, but given such obvious potential for clinical benefit this may be a tough door to keep closed.

With scientists predicting that competition between China and the U.S. for CRISPR supremacy will become the fiercest scientific rivalry since the space race, it’s unlikely that either government will want to set up too many regulatory hoops for scientists to leap through. On the other hand, there’s existing intellectual property law. Wherever billions of dollars are at stake, lawsuits proliferate — competing researchers are now battling over CRISPR-related patent claims in U.S. federal court, and they won’t be the last.

And though the research itself may be cheap, any resulting medical treatment likely won’t be. In recent SEC filings, two CRISPR research firms stated that their investors’ profits will hinge on the availability of insurance coverage for their still-developing procedures. That’s no hypothetical concern — insurers have been reluctant to cover medical procedures tailored to individual patients. The biggest obstacle to the life-altering breakthroughs that CRISPR may yield could well be our kludgy healthcare system. Those designer babies ain’t gonna pay for themselves.

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