Gene editing: Bring it on
There has been a lot of excitement lately over the new gene-editing technology, CRISPR. How does it work?
Gene editing is snipping out a targeted DNA sequence and replacing it with another. It used to be time-consuming and imprecise, but now you can edit any living genome, using your computer to target a stretch of DNA. Guides made of bespoke RNA lead the CRISPR molecular machinery to the target, where an enzyme makes a cut. This either destroys the function of the DNA in that location or allows you to change its functioning by manipulating how the cells repair the cut, for example by inserting a genetic sequence of your choice.
What will we be able to do with CRISPR?
It could enable gene therapies that would allow physicians to fix genetic diseases, including some types of blindness, the blood disorder beta thalassemia and the neurodegenerative disorder Tay-Sachs disease. It could also mean new approaches to treating cancers and viral infections, including HIV.
Other techniques could allow helpful DNA to spread through wild animal populations – which may allow us to eliminate infectious diseases like malaria.
Earlier this year, there was controversy when a team in China attempted to use CRISPR to edit the genes of non-viable human embryos. For some people this still crossed an ethical line. What are your thoughts?
In the early days of any field, if you mess up enough, you don’t just mess up your lab, you mess up all the labs. I don’t think this brouhaha will kill gene editing – they didn’t hurt any patients. But they were incautious.
From a technical point of view, there are several widely known techniques that have been proven to improve the specificity and efficacy of CRISPR gene editing, some of which were developed in my lab. The Chinese group must have known that their work was going to get a lot of attention, so it was disappointing that they chose not to use these techniques. They may have felt that if they waited to do it the right way, another lab would have scooped them. In practice these other labs, mine included, are not doing CRISPR research with human embryos, so I don’t know what they were worried about.
Mediocre science is not the same as evil science – after all, the experiments they did are legal in most countries.
So you’re not worried about the ethical issues that have been raised?
For me, the safety issues are the ethical issues, and the safety issues are not fundamentally different from those of any new therapeutic. Gene-editing techniques are being tested in animals extensively, in primates as well as rodents, and will eventually move into people.
I’m a professional worrier. But the form that my worry takes is action. As soon as somebody expresses something to me that they think is wrong with the world or with research, I say “let’s work on this”. We can innovate on safety measures.
Some people are against any tinkering with the gene pool – summoning the ever-present spectre of designer babies.
We humans already tinker with the gene pool with inherited diseases such as Tay-Sachs: genetic counselling before or after conception can help parents to decide on the health of their future children.
We tinker with the gene pool every time we fly at high altitude, which increases random mutations in developing sperm and egg cells. These things are allowed. If you don’t like the concept of tinkering with the gene pool, then ban it across the board. Don’t be exceptional about CRISPR.
“People worry that gene editing is irreversible, but that notion is a straw man”
Then there’s the issue of what we value. Do we value long life, intelligence, athleticism, beauty? We are already making our children more educated than their ancestors, and typically we do that without the permission of the children. People pay for products that improve beauty and athleticism. If you don’t think those are good values, then ban tinkering with them. But be fair. Don’t ban a particular form of it – unless it’s unsafe.
Gene editing: Bring it on
Enzymes (pale blue) cuts target DNA (red), guided by RNA (yellow) – it’s CRISPR in action (Image: Bang Wong, from source material provided by Feng Zhang)
Should unborn children have the right not to have their parents genetically dictate who they become, or is it the parents’ choice?
Parents owe it to their children to provide them with a good start. Education, chores, nutrition, dress code, faith and curfews are often dictated by parents for the good of the child. And parents already use genetic counselling to guide pre-conception and prenatal choices, to dictate that the child will not be burdened by serious genetic disease. Once those children grow up, they can choose different dictates for their own children as new information about genetics and child rearing becomes available.
There are also concerns that genetic modification affecting sperm and eggs will produce changes that are irreversible and that can be passed down through the generations.
The irreversibility argument strikes me as a straw man because, clearly, gene editing is not irreversible on a population-wide level.
If the population is changing because individuals are making decisions, it can change back if governments or individuals make alternative decisions. In fact, it can change back more readily because the technology is improving all the time and the costs are reducing. Now, it could be that people won’t want to reverse the changes, but that’s telling you that the change is valuable in some way.
If humanity doesn’t take the opportunity to advance genetic engineering in people, are we doing ourselves a disservice?
Absolutely. This question should come up more frequently. With seven billion people and growing, sitting still is not really a great option. For example, we could wipe out malaria using a gene drive – a technique that would allow a malaria-resistance gene to spread through a population of mosquitoes extremely rapidly.
That could be risky.
Some of us may say that gene drives are too risky in general because of unknown unknowns – like perhaps causing the extinction of a mosquito species. But if you did, it’s unlikely that that is going to kill any other animal. And every year that we hesitate, 600,000 people die of malaria unnecessarily and another couple of million get sick and miss days at work. That’s a pretty big price to pay.
You’re also interested in what’s called genetic augmentation. Isn’t using gene therapy in that way, whether for physical or mental enhancement, controversial too?
It’s less controversial because it would be in consenting adults. If a majority agrees that adults can be augmented – using a new drug, device, or gene therapy – then as long as it passes the usual safety and efficacy rules of the US Food and Drug Administration (FDA), in my view it’s not controversial enough to prevent rapid adoption.
You’ve famously come up with a list of 10 particularly protective but rare gene variants that we might all benefit from.
Yes. For example, PCSK9 protects you from cardiovascular disease, and it’s “superhuman” in the sense that people who have it are well beyond the average human in terms of low cardiovascular risk. Three others on the list – MSTN, LRP, APOE – will probably lead to therapies to prevent muscle degeneration, osteoporosis and dementia.
What about genes unrelated to disease? If we go in for editing such genes, what kind of society will we end up with?
It comes down to what societies value, and then what individuals want.
I don’t think everyone will want the same thing: we won’t all suddenly become exactly 5 feet 10 inches tall, with blonde hair and blue eyes. I think augmentation will actually increase diversity.
Some of it will be driven by need or ambition. People who want to go to space may want super-strong bones to protect them from osteoporosis in low gravity, while people who go to live at the bottom of the ocean will want a different set of modifications. And people who want to be super bankers are probably going to want a different set than the people who want to be super athletes. There isn’t a best kind of human, just like there isn’t a best kind of car.
If you’re going to worry – which I do all the time – I would worry about adult augmentation, because it will spread fast. If I were to augment a child, an embryo, it will take 20 years before they have any significant impact on society.
But if I come up with an augmentation that improves adult intelligence, news of that will go through the internet at light speed and a lot of people will try it. And then if it’s successful in the first million people who try it, then there could be a billion people who try it.
In 2012 you published a book entitled Regenesis, and you have talked about your lab as a centre for new technology aiming to rebuild creation to suit humans. Set that alongside your appearance and your name, and is it any wonder people accuse you of playing God?
It’s certainly not my intention. But we’re engineers – making our world suit us is what we do. It’s what humans do. The term “playing God” is mainly used to imply that you are doing something beyond your means.
I agree that we need to be cautious and I actually feel that humanity generally does move forward in steps. It can seem very fast and can, ultimately, happen in gigantic leaps – like landing on the moon and eliminating smallpox – but these things are done cautiously.
Yet technology is advancing at a blistering pace.
Einstein said our technology exceeds our humanity. I don’t buy that. I think that even when technology is going very fast, we have tried-and-tested traditional ways of reining it in. We don’t need special bans or a moratorium – we have the Environmental Protection Agency, we have the FDA. We need to think big, but also think carefully.