Do you remember President-elect Trump holding forth on the campaign trail about “China beating us at our own game”? Well, it’s true, as long as the game in question is editing human DNA using Crispr/Cas9. China is now using Crispr-edited cells in living, breathing human beings.
Last month, Chinese scientists at Sichuan University injected cancer-fighting, Crispr-modified white blood cells into a patient suffering from metastatic lung cancer. It was just the latest in a line of recent firsts for the People’s Republic of China, following on the heels of the first Crispr-edited monkeys in early 2014, and the first Crispr-edited human embryos last May. So there it is, Mr. President-elect: Are you going to let China win the race to edit humans?
Researchers and bioethicists worry that Trump’s political posturing could lead to a dangerous loosening of safety standards for patients. Right now, using Crispr–or any other gene-editing technique–is totally legal in the US, and subject to the same rigorous regulatory framework as other gene therapy treatments. There are even a handful of clinical trials in progress which use gene-editing, and more, including some that will use Crispr, are planned for next year.
Where it gets sticky is when you start talking about heritable changes to the human genome–what’s known as germline editing. Last December a broad coalition of leading biologists agreed to a moratorium on that until the discipline could learn more about the risks. It’s non-legally binding and anyone could buck that agreement, the problem is finding funding to do so. So what the US gene-editing community really wants to know is if Trump is going to make it possible for prospective human gene hackers to apply for big time federal grants.
Power of the purse
“There are two different and opposite things that are likely to happen,” says Hank Greely, a Stanford University lawyer and bioethicist. “The first has to do with Crispr and germline editing. Anything that looks like an embryo or sounds like an embryo will probably come under attack in the new administration.” That’s more or less the situation researchers face now. Last year’s omnibus spending bill contains a ban on all federal research dollars involving genetic manipulation of embryos, including via Crispr.
That spending bill expires December 9, though Capitol Hill Republicans plan to continue current government funding through March 31 (a short-term patch is aimed at giving the Trump administration a say in 2017 funding priorities). But don’t be surprised if embryonic editing stays taboo. The right wing’s history of opposing anything that seems like playing god goes all the way back to George W. Bush’s 2001 ban on federal funding for embryonic stem cell research.
At least one gene-editing pioneer sees that as short-sighted. “Germline editing is going to happen and to think otherwise is naive,” says University of Utah’s Dana Carroll. “And as to research on human embryos, whether or not it’s happening in the US anytime soon, elsewhere in the world it’s already started. If we want to know how to do it safely, research is going to have to provide those answers.” That may be true, but it won’t be happening on the government dollar, at least for now.
More likely is those Republican legislators will take another look at editing adult human cells–somatic cell therapies. This is the category of editing that the Chinese scientists just accomplished. The team at Sichuan University in Chengdu removed immune cells from a lung cancer patient and disabled their PD-1 gene, a brake pedal for the immune system which cancers exploit in order to proliferate. The researchers then inserted the re-engineered cells back into the patient as part of the first clinical trial to test Crispr’s safety in gene therapy applications.
The Yankee Clippers
In the US, two pieces of legislation currently in front of Congress could make it easier (and cheaper) for researchers to push similar treatments through the approval process. First is the Regrow Act, introduced in March, which would allow the FDA to bring drugs to the market for five years without Phase 3 trials (the phase where you figure out whether or not treatments actually work).
Then there’s the 21st Century Cures Act, which passed the House last year and is still waiting for a Senate vote. Actually a chimera of 19 separate bills, the proposed law would make substantial changes to the way the FDA approves drugs and devices, including streamlining of the clinical trial process. “Some provisions in there are aimed at making it easier for companies to get on the market. And while the main political thrust is stem cells, Crispr would certainly benefit as well,” says Greely.
Despite China’s head start, the international milestone still surprised some scientists–many expected the first human use of Crispr to come from a trial planned to begin next year at the University of Pennsylvania.
Whether or not you see that as a good thing depends on your politics, and what you have to gain from weaker oversight. The last few years has seen an increase in biotech lobbyists partnering with patient advocacy groups to make gene therapy and stem cell therapy treatments available to the public faster.
The Sichuan University trial received ethical approval from a hospital review board in July, after only six months of review. “To get the same thing approved in the US would take dramatically longer,” says Paul Knoepfler, a stem cell researcher at UC Davis. While study leader Lu You declined to comment for this article, others have noticed China’s reputation for moving quickly through the regulation process.
And Knoepfler says he can see how that would create a sense of urgency here in the US. “If the Trump administration buys into the idea of needing to be more competitive on gene editing, then all of a sudden there’s this pressure to allow things to move forward based on less data,” he says. “Speaking as a scientist though, we don’t tend to think along nationalist terms. None of us want to be scooped, but if it happens, we don’t care what country that person is from.”
Open the gates
The FDA, for better and for worse, is a historically cautious gatekeeper, unconcerned with international spitting contests. Clinical trials cost millions, and last for years. But George Church, Harvard University geneticist and co-founder of Editas Medicine believes it’s a necessary step to ensure new technologies like Crispr-based gene therapies really work. Even when they hold you up from making history. (Editas had been an early pick to cross the CRISPR clinical trial finish line first, in their efforts to treat a rare genetic eye disease.) “The FDA is commonly viewed as a roadblock,” he says. “But if your treatment is safe and effective it will fly through the approval process. It has nothing to do with novelty and everything to do with safety and efficacy.”
Patients are looking for answers. Biotech is looking for big bucks. Both oppose regulation. And both are at odds with scientists who think the current frameworks is appropriately judicious. “There is a real philosophical difference of opinion in Washington about whether competent adults should be able to take big risks, and whether desperate people should be offered false hope,” says Greely. He’s concerned about politicians playing up the threat of international competition to drum up support for deregulation. “That will allow trials to go forward without good data behind them. And I hope not too many people die as a result,” he says. “Elections have consequences.”
Yes they do. The consequences of this most recent one will be made clear soon enough.