No, CRISPR gene editing technology is not going to “cure” heart disease. But a New York Times story by Gina Kolata on an extremely early study in animals prominently plays up just this extremely unlikely claim.
The Times story is based on a press release issued by Verve Therapeutics, a new biotechnology company founded by Sekar Kathiresan, an influential cardiologist and genomic researcher associated with the Broad Institute, Massachusetts General Hospital, and Harvard. Kathiresan and colleagues used a novel CRISPR base editing technique to knock out either the PCSK9 or ANGPTL3 genes in 14 monkeys. They reported that LDL and triglyceride levels dropped dramatically two weeks after receiving the novel treatment.
“Cure”? “Succeeds”? The press release, by contrast, describes the study, correctly and appropriately, as a “preclinical proof-of-concept” study. Further, given that the company only reported two week data, what could be the possible justification for the Times subhead describing the reductions in LDL and triglycerides as “permanent”?
Kolata writes that “the experiment has raised hopes that a leading killer may one day be tamed.” Then she quotes an outside expert, the University of Chicago’s Michael Davidson, who says that “this could be the cure for heart disease.”
The story does eventually go on to include numerous caveats and cautions. Following the Davidson quote Kolata writes:
But it will be years before human trials can begin, and gene-editing technology so far has a mixed tracked record. It is much too early to know whether the strategy will be safe and effective in humans; even the monkeys must be monitored for side effects or other treatment failures for some time to come.
But many readers will already have been swept away by the breathless enthusiasm. Consider, by contrast, the beginning of Sharon Begley’s excellent coverage of the same story for STAT. The headline— “In its first tough test, CRISPR base editing slashes cholesterol levels in monkeys”— reports the actual promising result of the study without raising the idea of curing heart disease, the world’s number one killer.
Begley’s quote from an outsider is much more restrained than Kolata’s Davidson:
Joseph Wu of Stanford University, an expert on genome therapy for cardiovascular disease who is not involved with Verve, said the degree of LDL and triglyceride lowering in the macaques “looks good compared to statins.” But because Verve showed only a couple of weeks’ worth of data, he said, “I would be curious to know what the long-term effect is.”
In the Times story Deepak Srivastava of the Gladstone Institutes warns that “you will never be able to have no off-target effects,” and then points out that “in treating a condition as common as heart disease… even an uncommon side effect can mean many patients are affected.” Kolata reports that “so far, however, the researchers say that they have not seen any inadvertent editing of other genes,” but given the current preliminary results this should hardly be taken as any kind of firm reassurance.
Kolata also quotes Jennifer Doudna, the Berkeley scientist who is a co-discoverer of CRISPR, who says that “it is much too soon to say if it will be safe and long-lasting.”
But even if Kathiresan and Verve manage to pull off an extraordinary run of successes— and this would certainly take many years— it’s by no means clear that this would represent a “cure” for heart disease. For all the breathless hype there’s no evidence that CRISPR, the sexy newcomer on the block, will be that much better than the wide variety of cholesterol and triglyceride lowering treatments now available or under development. Of course there may be some advantages to a single one-shot delivery, but there may also be disadvantages and side effects.
It’s also important to remember that this will almost surely be an expensive treatment. So far, of course, there’s been no real discussion of cost at this point, but it seems fair to point out that if it’s too early to talk about cost then it’s also too early to talk about cure.
Let’s not forget the instructive example of the PCSK9 inhibitors, which for several years were hyped in much the same manner, when their manufacturers, and Wall Street, anticipated that they would be blockbuster drugs that, yes, were going to cure heart disease. Even now, when they are far less expensive than their original cost, their uptake has been modest at best, and financially unrewarding to their manufacturers. Is there any reason to believe any new drugs based on CRISPR technology will be substantially better?
In addition, any story along these lines needs to remain mindful of the conflict of interest issues at play. Sek Kathiresan is a serious, well respected scientist, but he also has a whole lot to gain from the fate of Verve.
Another question that in my experience doesn’t get much focus is what the word “cure” even means when it comes to heart disease. In response to the news Boback Ziaeian, a UCLA cardiologist, tweeted, sarcastically, that “it’s always a good idea to knockout evolutionarily preserved genes to cure predominantly lifestyle related disease.” It seems to me that the entire concept of using drugs or other technologies to “cure” or eliminate heart disease is almost certainly a misguided idea. This issue, the appropriate use of medical treatments versus public health approaches, is sadly missing from the discussion.
Finally, we need to address the impact of this sort of journalism, the way that it undermines scientific credibility. It brews distrust in the general public, ultimately leading to the rejection or suspicion of real medical advances, including such important things now like vaccines and masks.
It’s easy to blame the media for poor or irresponsible coverage of scientific and medical stories. Many scientists and doctors are often harsh critics of the mainstream press, but they rarely focus on the fact that they also play a key role enabling this poor coverage. When interviewed by journalists suddenly their high scientific standards deteriorate. Davidson is a serious scientist who should, and does, know better than to use the “c” word.
Davidson is not alone. On Twitter Rob Califf, a former FDA commissioner and one of the truly influential figures in cardiology, offered measured and thoughtful praise for the study:
Regardless of the ups and downs of therapeutic development to come (and there will be ups and downs), this is a remarkable translational achievement evolving from years of dedication.
But Califf and others offered no objections to the hype. This is typical. Top leaders in the field rarely criticize hype or call out scientific or other forms of misconduct within their profession. But if scientific leaders won’t do this how can they expect journalists to correct themselves? And if hype doesn’t provoke negative consequences what motivation is there for the purveyors of hype to curb their behavior?
Larry Husten was the editor of TheHeart.Org from its inception in 1999 until December 2008. Before that he was a freelance medical journalist who wrote for The Lancet, The New York Times, Discover, and a large number of other medical and computer publications. In 1994-1995 he was a Knight Science Journalism Fellow at MIT. He received a PHD in English from the State University of New York at Buffalo and drove a taxicab in New York City before embarking on a career in medical journalism.