Two years ago, scientists quietly developed a technique known as CRISPR/Cas, which allowed them to edit DNA more cheaply, more quickly, and more precisely than ever before. At the time, few people were paying attention.
Now, however, lots of people are talking about CRISPR — particularly after a group of researchers in China recently used the technique to edit nonviable human embryos. Though the embryos would never turn into humans, this was the first time anyone had ever tried to edit the genetic material of homo sapiens, and the April 18 publication of the results sparked a massive outcry.
One of the leading voices speaking out against editing human DNA was Francis Collins, the director of the National Institutes of Health. In an NIH statement, Collins took a firm stance, saying, "The concept of altering the human germline in embryos for clinical purposes has been debated over many years from many different perspectives, and has been viewed almost universally as a line that should not be crossed." He went on to explain that the NIH would not fund such research, mainly for ethical reasons.
I called Collins to talk further about the ethical problems CRISPR raises, and why he thinks this genetic editing technique is both hugely promising and, potentially, very dangerous.
Julia Belluz: What were you thinking when you first saw the results from China — that scientists had finally edited the genes of a human embryo?
Francis Collins: There had been a lot of rumors, so I wasn't shocked to see [the study] when it appeared. But obviously the details were of interest in terms of the experiment they did. I was relieved they had done this experiment with [nonviable embryos that were] impossible to re-implant.
JB: In the experiment, as you know, only a fraction of the embryos survived, and only a tiny fraction of those survivors were successfully modified with the new genetic material. What did you make of these results?
FC: Some of the breathless responses suggested we had never previously considered what might happen if someone tried to target the germline of human beings. But we have had those discussions intensively over several decades.
What is new: it's a technology that had the promise of the kind of surgical precision you might imagine be applied [to humans] without immediate unpredictable harm to future generations.
In that regard, [CRISPR] sort of failed the test. In [the Chinese scientists'] hands, at least, it was way short of anything you could contemplate would be acceptable, simply on the basis of safety, much less other ethical concerns. They missed the target a fair amount of time and hit a lot of other targets. We have a ways to go to even begin to contemplate doing this in a fashion that would not have all kinds of unintended consequences.
JB: Can you take me through the major ethical concerns about editing the human genome?
FC: I'm concerned about a circumstance where an embryo is manipulated, then intentionally re-implanted, with the goal of having that turn into a human being.
In terms of research that doesn't do that — i.e., what the Chinese did with flawed embryos — a different set of questions, in the line of slippery slope, arises. Most prominent is safety, doing something that affects not only that individual but their offspring for generations to come. Experimenting on individuals who cannot give their consent. How can you be sure they’re not doing something harmful? Designer babies make great Hollywood movies. They make really bad science, and I think they are really bad ethics.
On top of that, any time you’re contemplating doing something this drastic, you must ask about benefits and risks. A lot of conversation hasn't reflected that.
It's also very hard to identify the need for this kind of embryo manipulation for human purposes. If you're talking about genetic disease, we have pre-implantation genetic diagnosis, which gives couples at risk for genetic disease a chance to avoid that risk without any manipulation of the germline.
Last, there are deep concerns of a philosophical sort, about what it means for human beings to intentionally manipulate their own genomes. If applied broadly and widely, does that result in us being changed into something other than homo sapiens? I don't think we even have to go to that one to say this is something we shouldn't do. The safety arguments and lack of medical need trump [these concerns].
JB: Do you think we should ever do this kind of research on human embryos?
FC: There's a strong consensus — not just in the US but by other ethical bodies that have looked at the potential of modifying the human germline with intent to produce pregnancy — that that is a line we should not cross.
That's what I tried to cover in my statement — to remind people of all the prohibitions that are already in place. It was not my personal opinion that the government should or should not do this. Prohibitions have arisen over the course of many years. One of them is the amendment — Dickey-Wicker — from the 1990s. Congress said public federal funds will not be used for research involving derivation on human embryos. That says — no matter what I think — this type of research will not be supported by NIH.
JB: But, theoretically, people could do work on human embryos here — just without federal funding — since there is no outright ban?
FC: You’re correct in saying that people who don't have that kind of [federal] support are not bound by Dickey-Wicker or the [Recombinant DNA Advisory Committee, a federal advisory committee that provides recommendations to the NIH director and also advises against editing human DNA].
But scientists are bound by a strong tradition over several decades of thoughtful people weighing in saying, "When it comes to manipulating the human germline with the intent to pass that on to other generations, it's not right to go ahead." While there is no legal prohibition, there are lots of ethical constraints.
JB: What most excites you about the CRISPR/Cas system? What do you think it'll be useful for?
FC: It is an enormously powerful way to make changes, not in the germline of humans, but to other tissues. You see how it is applied to HIV/AIDS: you have the ability to go in and create immune cells that are no longer possible for the virus to invade and give those back to people whose cells those are. That's [research] being done in Philadelphia right now. They could use this approach to cure sickle cell disease, correcting the mutation, and expanding the cells and giving them back.
When you go to research, [CRISPR/Cas] makes so many things exciting and quickly possible that would otherwise take years of work, like understanding how each gene does what it does and developing new ideas about future treatment.
If we want to understand the application of CRISPR/Cas to embryos, lots of that is being done in animals and quite usefully to create animal models for disease.
Let's not lose sight of fact that this is an incredible advance — scientists can go faster and more powerfully than we could with previous methods of modifying the animal germline.
But when it comes to the humans, the question is what is the need to also try this out to human embryos? Is there information here we need to desperately have? If we have at the moment the strong sense we shouldn't be using this in a way that results in a successful pregnancy, what’s the reason for doing these preliminary steps toward that goal? I think this is more an argument about the use of resources and slippery slopes.
This conversation has been lightly edited and condensed for clarity.