Robin Lovell-Badge, embryologist

With the power to edit human genes within our grasp, this researcher wants to help society reach responsibly. Interview by Lindzi Wessel

April 04, 2016

Embryologist Robin Lovell-Badge in his lab at the Francis Crick Institute in London. Credit: The Francis Crick Institute at Mill Hill

In December 2015, experts in biomedical sciences, ethics, and policy from around the world descended on Washington D.C. to attend the International Summit on Human Gene Editing. New technology, called CRISPR-Cas9, has given scientists the ability to alter a cell by removing genes, adding genes, or swapping one gene for another. When Chinese researchers attempted to do this in human embryos, a once-fantastical piece of science fiction became an inevitable reality. During the three-day summit, experts weighed human health benefits of gene editing against potential risks and ethical concerns, working to create international guidelines governing the science.

To Robin Lovell-Badge, an embryologist at the Francis Crick Institute in London and one of 12 experts on the summit’s organizing committee, the gathering was one of many attempts to help society navigate the increasingly complex terrain of advancing medical technology. Lovell-Badge was first thrust into the public limelight in the early 1990s when he co-discovered the Y-chromosome gene that orchestrates male development. He then used this gene to make a genetically female mouse develop as a male. As stem-cell sciences took off at the turn of the century, the British Parliament called upon him for advice in revising the U.K. Human Fertilisation and Embryonic Act. Since then he has regularly given scientific counsel in areas of public engagement and policy.

Back in Washington D.C. for the February 2016 meeting of the American Association for the Advancement of Science, Lovell-Badge recapped key points of the summit for conference attendees. After his presentation, he sat down with SciCom’s Lindzi Wessel to discuss the science, policy, and ethics of tinkering with the human genome.

Do you use CRISPR-Cas9 in your research?

Absolutely, yes. As soon as it became obvious that this was an easy-to-use technique, we started using it. It's been incredibly valuable for our own research, which is mostly in mice. It’s been very powerful.

What does CRISPR bring to gene editing that we didn’t have before?

The CRISPR-Cas9 methods are simple to use, quick, precise and very efficient. They make the change [in a gene] just where you want it. They are also inexpensive and can be used in seemingly any species.

Is there any chance your research would be affected by the international regulatory questions being discussed today?

I'm not doing any work with human embryos at the moment. I wasn't doing any anyway, but I had to promise that I wouldn’t for this year because I'm on this National Academies study committee.

There’s been a lot of international debate about editing genes in human embryos. What are some possible reasons to do this research?

By manipulating the genes using gene editing, you can see which pathways are important in embryonic development. Most of what we know about early mammalian embryos comes from studies in the mouse. People have realized that there are many differences in the activity of genes in human and mouse embryos, and some of those differences are in genes which we know are essential in embryonic development. That means we don't really understand much about how early human embryos develop at all. Just being able to study these early events might actually reveal critical things about many different aspects of health.

When it comes to the potential for using gene editing to treat disease, you mentioned Huntington's disease as one good candidate. What makes a good candidate for potential treatment by CRISPR?

For people who know there’s a risk of having a child with a genetic disease, like Huntington’s, there’s already a technique called preimplantation genetic diagnosis (PGD). You do [in-vitro fertilization] and then test the early embryo to see if that embryo is likely have the disease. Then, in theory, you only transfer the disease-free embryo back into the mother. But there are some individuals for whom that method either would be very inefficient or won't work at all. There are rare individuals [with genetic mutations that would cause all of their children to have Huntington’s]. If they wanted to have their own genetic child, then the only way would be to correct the genetic defect. That would be an ideal case for using the gene editing methods of CRISPR-Cas9.

"If it were doing something like [blending human and animal genes] or the end of humanity, what would they do?"

What about someone who already has Huntington's? Could gene editing help them?

Huntington's disease is a big problem because it affects many neurons in the brain. It would be very difficult to introduce the CRISPR-Cas9 components into sufficient numbers of brain cells in a way that would provide benefit. Moreover, as neurons do not divide, the DNA repair mechanisms required for the gene editing to work might not function well. This [kind of treatment] would require new methods to be developed. 

Other things may be treatable. Sickle-cell disease is a mutation in the beta globin gene. In theory you could take out bone marrow, do your gene changes, and then put the bone marrow cells back in the patient. It’s very disease-dependent. If you can access the diseased tissue relatively easily, or if there are good stem cells or regenerative cells you can use, you have a relatively good chance of having a good therapy. But in the brain, it's really hard.

Another thing you mentioned is a concern over rogue clinics. What do you mean by that?

In the stem-cell field we've seen this proliferation of rogue clinics around the world, even in the United States. They offer treatments for diseases like multiple sclerosis and Huntington’s that sound like miracle cures to people who don't understand the details. Desperate people pay large sums of money for treatments that have no benefit and can even be dangerous. That scares me. I'm afraid that in the U.S., the in-vitro fertilization industry is not well regulated.

In the U.K. there's recently been an approval to allow gene editing in the embryo for research purposes only. You've mentioned that you feel confident in the U.K.'s regulatory system of IVF clinics and research. What makes you feel that way?

In the U.K. we have the Human Fertilisation Embryonic Authority, which is empowered to enforce. They regularly inspect all IVF clinics, which must have records of essentially every embryo that's gone through. Monitoring lets you catch people who are doing things they shouldn't. There's this famous [U.S.] case of the Octomom, the mother who had eight children. That should never be allowed to happen. That's so dangerous for the mother and the children.

Are there other U.K. regulations of PGD that might be important to consider for gene editing?

There are some potential uses that would be considered trivial—meaning non-life threatening. You wouldn't be allowed to use PGD to choose an embryo with blond hair and blue eyes, for example. And some members of the deaf community want to have a deaf child. In the U.K. you're not allowed to deliberately choose to have a child who's going to be deaf.

That's a really interesting ethical question.

Yeah. So again, I think regulation is needed.

In your talk, you mentioned you hate the term "designer baby." Why?

It’s been used as a general catch-all for anything you do, whether it's correcting a genetic defect and reducing disease risk, or making some elaborate enhancement that people would find either trivial, dangerous, or just ridiculous because you can’t do it.

Some people might be excited by the prospect of editing out genes that confer enhanced risk for a disease, like the APOE4 gene that increases the risk of Alzheimer's. In your talk, you mentioned the potential for unforeseen consequences. What could go wrong?

Whenever a particular gene variant is present at quite high frequency in a population, you have to think: Is it there at high frequency because it actually confers an advantage in some situations?

So how sci-fi can we get with CRISPR?

You can let your mind wander and think of all sorts of things you could, in theory, do with the technology. You could make changes to genes representative of something that already exists in the human population, but you can also contemplate introducing genes from other animals or plants into humans. We know that some animals have photoreceptors that detect UV light or infrared. If you wanted your children to be able to see in the dark, you could put infrared-sensing cells in. Now that sort of sounds silly, and you probably wouldn't want to do that unless the environment changed radically so it would be useful for humans to see in the dark. But think of all the horrible things we are doing to the environment and all the things that might happen with climate change. Could you modify humans so they could digest [different kinds of plants]?

Do you see that as a positive aspect of gene-editing technology?

Well it would give humanity a way out, a way of surviving something cataclysmic. Obviously it would be a slow process, but yeah.

I think some people might find that to be ethically questionable, the blending of the human and the animal.

Oh, of course people do. But if it were doing something like that or the end of humanity, what would they do?

Is there a line for you personally of what we should and shouldn’t do?

Well, I think the trivial we just shouldn't do. We are duty-bound to do the best for our children, so you'd only want to do things that you felt your children would be happy that you did. If you make them glow green, that's not going to necessarily make them very happy. But I think it's for society to decide how far you should take it, not for me, not for scientists and clinicians.

Who should be making these decisions if not scientists?

Not scientists alone. Scientists should be involved in the decision, but you want public support—you want people to have thought about it carefully. Of course not everyone is going to agree. So clearly it would have to be a political decision, but hopefully one based on an informed public giving their views as well.

How long do you think it will be before we actually see people who have had genetic “corrections”?

Well I hope it's not right now, because I think we still need to understand how to use the methods properly. But at the rate things are going in this field, particularly with the CRISPR-Cas9 technology, you can imagine it could start happening within just a few years. I would much rather it happen in a properly regulated way. It certainly should not be just a free-for-all because that would be horrible—that would be crazy.


© 2016 Lindzi Wessel. Lindzi maintains a crisp portfolio of work at