CRISPR

When news broke that Chinese researcher He Jiankui allegedly used CRISPR to genetically engineer twin girls, it stirred controversy on a subject that’s been heated since it started making headlines five years ago.

The technology, Clustered Regularly Interspaced Short Palindromic Repeats, is science’s most efficient methodology to modify chromosomes to express different properties through the genes that carry information. But using it on humans is illegal in the United States and in many other places. 

It also elicits fears, rational or otherwise, of a science-fiction world filled with “designer babies.” But, according to Penn medical ethicist Jonathan Moreno, that will never be the reality. Penn Today spoke with Moreno about CRISPR and where he predicts the future of the technology is headed.

Q: Can you briefly explain CRISPR?

A: The first technology to move genes around systematically in the lab, called recombinant DNA, was created in the 1970s. There have been various advances at making it more efficient to get those chromosomes to express different properties, and CRISPR is the most efficient way that’s been developed.

In the lab, you might try to understand which proteins genes produce in different environments. You might be able to obtain new characteristics from those DNA molecules, or reduce the incidence of certain characteristics created by that genetic material. So, if you want to see whether a certain gene is associated with a certain physical property or behavior, you can modify those cells using the chromosomes, perhaps put them in an animal, and see what happens. Those models could then tell you something about what might be used in cells in the human body or in human embryos. 

Q: What has Dr. He claimed to have done?

A: Dr. He claims to have targeted and disabled a particular gene associated with HIV, a particular strain of HIV. In targeting that gene, the hope is you produce a baby who is resistant to HIV, and in this case, he did modify the embryo—two of them in fact. According to his report, one of the twin girls appears to have been made resistant to this particular strain of HIV and the other one probably not. He also reported in Hong Kong that he created another pregnancy with a third modified embryo. 

Q: For him to have done this, the parents must have given consent, right?

A: There’s consent, and there’s consent. We don’t know what they really knew. And the mother and the father, we don’t know who they are; we don’t know how much they really understood. According to some sources, they were told it was like a vaccination. It’s not really like a vaccination at all. 

We’re still waiting for Dr. He to publish his data. He hasn’t published a paper, and in science that’s the gold standard. There’s debate about whether any journal would accept his paper because now it comes under this ethical cloud. He may have to publish it independently, but, either way, at least then people would be able to look at it. The bottom line is we don’t really know the quality of the consent. And by the way, in some ways, these issues about gene editing in embryos are eclipsing some other, more critical issues about the use of CRISPR.

Q: Can you explain what you mean?

A: Recently, there’s been a series of international meetings about gene editing in animals. In insects, for example, the effect of gene editing for subsequent generations is minuscule in a human population but really big in rapidly propagating populations like mosquitoes. One of the big questions is whether it’s acceptable to lab-produce millions of mosquitos that, when they mated, would have sterile offspring. Then in theory, you could reduce the risk of mosquito-borne diseases like malaria. But are you changing the environment when you do that? Can you build those mosquitos in such a way that doesn’t permanently undermine them? 

And there’s not only the public health problem but issues about agricultural pests, too. You could reduce a rodent population by editing genes and sending them into the wild, but then what are we doing to the population in the long term, as well as to other populations that depend on them? It’s not nearly as sexy as the story about editing human DNA, but in terms of implications for the natural world it’s much more important. 

Q: In your estimation, what’s the future of a technology like CRISPR? Why does it provoke such strong emotions? 

A: People are concerned that damage will be done not only to individuals who are produced using technologies like this but to the science, too. People are saying this is a failure of science to police itself, but there are no science police created by the science academies. There’s a certain symbolism in the human genome and the fact that we’re millions of years into evolution. So, I think the main concern is that this somehow could undermine human dignity in ways we don’t yet understand. 

Then there’s the bigger worry that we’re headed into some science-fiction world with designer babies. That’s just not going to happen. That’s not how biology works. There are relatively few traits that you can really manipulate. Gender is one, and you can vastly up your chances of having a male or female baby through fertility technologies, but the big things that people really want aside from health for their children you can’t build in. That’s because there is something called epigenetics, the way the environment enables certain qualities to express themselves, certain traits. Basically, for each of us, the genome creates a range. I’ll never be Einstein. Sadly for me, I’m only somewhere within the mean for human cognitive function. But within that range, I get to flop around.

Q: Where does the international scientific community go from here?

A: The international community has spoken about this before this whole event happened. There are international standards, from the National Academy of Sciences and the Nuffield Council on Bioethics in the U.K. Undoubtedly, they need to be revisited, maybe made more specific and improved. But there are standards, and, as I said before, there are no science police to go into labs and make sure people are doing what they’re supposed to be doing. These are voluntary standards for people who are presumed to have good intentions.

 

Penn Integrates Knowledge professor Jonathan Moreno is the David and Lyn Silfen University Professor at the University of Pennsylvania. He is a professor in the Department of Medical Ethics and Health Policy in the Perelman School of Medicine and in the Department of History and Sociology of Science in the School of Arts and Sciences.