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Now & Next: Gene editing: risk vs reward – in partnership with The Economist

Posted on 18 March 2022

The gene editing revolution has arrived, promising cures for terminal disease. In the last five years, we have made more progress than in the last 50. But new genetic technologies mean new risks - both in an ethical and practical sense. So how should the promise of genetic technologies be balanced against the potential dangers? And who decides what risks are worth taking?

The gene editing revolution has arrived, promising cures for terminal disease.

Dr Josh Lehrer, Chief Executive Officer, Graphite Bio
For the past five years you know we’ve made more progress than in the previous fifty.
And new approaches to fighting climate change. 

Dr Fyodor Urnov, Scientific Director of Technology and Translation, Innovative Genomics Institute
We have the opportunity to fundamentally change our relationship with nature.
But new genetic technologies bring with them new ethical and practical risks.
[Say no to GMO]

Prof Henry T Greely, Author of ‘CRISPR People’
Some of it could be terrifyingly threatening like biowarfare.
What is our responsibility as scientists and doctors?

Dr Natalie Kofler, Senior Advisor, Scientific Citizenship Initiative, Harvard Medical School
It’s really starting to bring out ideas around who belongs and who doesn’t belong.
So how should the promise of genetic technologies be balanced against the potential dangers and who decides what risks are worth taking?


Gene Editing: Risk v Reward
This is Professor James Dale.  A man on a mission to save the world’s most popular banana from extinction. 

Professor James Dale
I reckon these Williams are the ones that were most spectacular, weren’t they?  That’s incredible. 
There are thousands of types of banana in the world but all the fruit being grown and processed here and almost every banana exported around the world is one single variety, the Cavendish.

Professor James Dale
It yields very well.  It’s got quite a tough skin so it travels well but also it’s got a really acceptable taste and texture.
The problem is, the Cavendish is under threat.  A disease known as Tropical Race 4 or TR4 has spread across the world killing Cavendish bananas. 
TR4, one of the deadliest diseases out there.
They call it the cancer of the bananas.

Professor James Dale
You start to get that sort of motley colouration there.  It gets worse there but…
And now it’s reached James’ plantation. 

Professor James Dale
And what we’re looking for is the brown, which is what we call necrosis.  And then you see, bingo, that was the one that had the yellow leaves.  Just incredible necrosis. 
There is no cure for this disease.  It’s feared that in time, it could wipe out the Cavendish completely or stop it being such an economically valuable crop. 

Professor James Dale
It is a really serious problem.  There is no obvious replacement for Cavendish bananas for the export market. 
But James has a solution.  He has spent ten years engineering a genetically modified banana which can withstand TR4.  There is a big problem though. 
[Say no to GMO.  Oh no GMO]
Because James’ bananas are genetically modified, lots of consumers won’t go anywhere near them. 

Professor James Dale
It is unbelievably frustrating.  GM still has a lot of perceived negativity in the world.  Europe, for instance, is one of those areas, they import huge amounts of bananas but getting a GM crop through the regulatory process in Europe is virtually impossible. 
He believes this public resistance could block the development of beneficial new crops.

Professor James Dale
I think it’s a real problem.  We’re moving into a period of real flux, a real unknown period with climate change and we’re going to need to develop crops that have very high tolerance to drought, I’m not sure that we have all of the tools at our fingertips without the use of GM and gene editing so I think there is a real ethical dilemma in the world now of rejecting technologies that may become incredibly important over the next decade or two.
Some believe GM technology can be used to do lots of good.  So, is it right to put barriers in the way because other oppose the technology on principle?  In an EU wide poll, 70% said they felt GM foods were unnatural but that’s a very vague term. 

Oliver Morton, Briefings Editor, The Economist
The things that people actually grow in gardens and in fields are really not particularly natural and many of them have genomes that have been extensively changed over the course of human history.  If you look at what a modern ear of maize looks like compared to its ancestral form, you’ll see something very different.
Yet there is still a fear that these technologies could go astray and expose people to risks they have not agreed to.
This is Islamorada, a tropical paradise that’s on the frontline of the debate about genetic engineering.  Here, genetically modified mosquitoes are being released in the United States for the first time.  It’s part of an experiment to try to reduce the spread of Zika and dengue fever.  But some of the locals have been very vocal about their opposition to this kind of intervention into the natural world.
Our economy here is tourist based and a lot of tourists are laypeople and if they come down here and they hear that we’re turning loose some kind of weird critter, I think that there could be some impact on the economy.
As a result the mosquitoes have to be released in top secret locations away from protesters and vandals. 

Rajeev Vaidyanathan, Oxitech
We just add regular tap water.  The eggs hatch in about 24 hours.  There is already food in there and you can see these little holes on both sides, that’s where the adult males are going to come out of.
The Authorities hope this will solve the problem posed by Aedes aegypti, a mosquito which can carry Zika and dengue and, in some places, has become resistant to pesticides. 

Andrea Leal, Executive Director, Florida Keys Mosquito Control District
Aedes aegypti control is very expensive and what we find is that it takes up over 10% of our entire budget to control a very small population of our mosquitoes. 
Up till now, mosquito control here has involved going to door-to-door clearing standing water.  British company, Oxitec, might put an end to that with a genetic approach that has female mosquitoes in its sights.  Only the females bite and carry disease and Oxitec is getting to them through the males.  It altered the genes of some male mosquitoes so that when they mate with females, only their male offspring would survive, meaning the number of females should crash within a few generations. 

Rajeev Vaidyanathan, Oxitech
It’s essentially birth control for mosquitoes.  It’s a biological solution, it’s targeted against one species and it has no effect against bees, butterflies or other pollinators. 
The project is a field trial which has been approved by America’s Environmental Protection Agency, the EPA.  But the way the technology is regulated has provoked concerns.
The protocols for evaluating genetically modified organisms are way short on a lot of things.
Natalie Kofler is a Harvard-based bioethicist who has attended many of the town hall debates about this programme.

Dr Natalie Kofler, Senior Advisor, Scientific Citizenship Initiative, Harvard Medical School
What I am really concerned about is really how it’s been decided upon and developed, not the technology itself.
She says the regulation of this technology isn’t transparent enough and doesn’t require proper engagement with effective communities.

Dr Natalie Kofler, Senior Advisor, Scientific Citizenship Initiative, Harvard Medical School
It’s just blowing our regulatory systems apart.  One of the biggest challenges is the real need for community consent when we’re talking about releasing a genetically modified organism into people’s, literally, backyards.  We don’t have space that empowers community members in this process or gives them any real sort of agency.  That to me is a really, really big concern.
Failing to engage communities properly, not only risks intervening in their lives without consent but also raises another ethical concern.  The risk of turning people against the technology, meaning that they and others miss out on beneficial interventions. 

Dr Natalie Kofler, Senior Advisor, Scientific Citizenship Initiative, Harvard Medical School
By not engaging communities, we’re setting up GMO storm 3.0, where, you know, we already have so much distrust in that space.  This could just, you know, create entirely new concerns.
The emergence of new types of gene editing, is raising the stakes in this debate.  Gene editing is getting cheaper and easier, making the technology more widely available.  One of the biggest recent advances has been the development of a technique known as CRISPR, which in 2020 won a Nobel prize for its inventors, Emmanuelle Charpentier and Jennifer Doudna.

Dr Jennifer Doudna, Co-inventor of CRISPR technology
Human beings now have the ability to rewrite the code of life. 
CRISPR makes precise edits in DNA by using a special protein which can be programmed with a molecule called RNA so that when it finds a specific gene sequence, it makes a cut at that precise point in the DNA.  The technique’s combination of precision and ease of use opens up the prospects of tackling genetic diseases more effectively than ever before.
You cranked her up, jumped into the front seat and off you went with a family.

Prof Henry T Greely, Author of ‘CRISPR People’
I think of CRISPR as being kind of like the Model T Ford.  There were cars before the Model T but they were really expensive and they broke down all the time.  Once the Model T came out, everybody could have a car and so with CRISPR, it’s just faster, cheaper, easier, better.
[Mighty smooth riding now]
This ability to edit specific genes could change medicine dramatically and soon. 

Dr Fyodor Urnov, Scientific Director of Technology and Translation, Innovative Genomics Institute
There are 200 million people on our planet, our fellow human beings, who suffer from genetic diseases that are CRISPR-able in principle. 
One of the most recent advances is the ability to treat sickle cell disease, a blood disorder which is caused by a mutation in a single gene.
This new technology is already here and already changing lives.
Josh Lehrer runs Graphite Bio, a company researching CRISPR-based cures for the disease.  He was inspired by his time as a junior doctor when sickle cell treatment was basic. 

Dr Josh Lehrer, Chief Executive Officer, Graphite Bio
I was in medical school taking care of my first patient with sickle cell disease and we had really nothing to offer besides morphine and blood transfusions which were essentially the same ways that this disease was treated in the 1950’s, nothing had really changed.  What we’re hoping to find here is ways to actually kind of keep improving the efficiency.
Josh’s company is working on what he calls next generation gene editing treatments.

Dr Josh Lehrer, Chief Executive Officer, Graphite Bio
If we had an approach that could go beyond cutting and essentially find and replace, correct that defect and restore the normal haemoglobin protein, that should be a definitive cure. 
While most would be in favour of using gene editing to cure a disease like sickle cell, it gets more complicated when the technology is used to fix diseases and conditions which may be less debilitating. 

Prof Henry T Greely, Author of ‘CRISPR People’
I think what bothers people a lot about gene editing isn’t the idea of editing away terrible diseases, it’s the idea of editing traits that aren’t diseases at all, like eye colour or skin colour.  I think these are going to raise some really difficult questions.
At this lab in Moscow, scientists are engaged in one of the most controversial applications of CRISPR. 
[This is where a genome, DNA of a person is detected, or an exome]
They’re using gene editing to try to eliminate hereditary deafness.

Denis Rebrikov, R&D vice-rector, Pirogov Russian National Research Medical University
Today, we are working on a technique to use CRISPR to correct a mutation leading to the appearance or hereditary hearing loss in humans.  It’s correction could significantly reduce the incidences of deaf children being born to deaf couples.
Denis Rebrikov, who leads the research, says he has three deaf couples lined up for treatment and that this would be the only way they could have a child who can hear.

Denis Rebrikov, R&D vice-rector, Pirogov Russian National Research Medical University
If the parents have the same mutation, they are both deaf then, unfortunately, all the children here will have exactly the same pathology, a hereditary hearing loss and essentially, the only way to make a child hear is to repair the mutation at the very, very early stage of development at the first cell stage.
While Denis does not yet have approval from the Russian regulators to implant edited embryos into patients, he hopes it will only be a matter of time.  And for many deaf people and beyond, this is a deeply troubling prospect.  Teresa Blankmeyer Burke is a bioethicist who teaches at Gallaudet University, a college for the deaf.

Teresa Blankmeyer Burke, Professor of Philosophy, Gallaudet University
So, guess what, deaf people are not the first people to get this information.  Whenever we have technology that can change the world, we need to be very thoughtful about how we use it.
She worries using CRISPR to cure deafness could damage efforts to improve understanding and integration of deaf people.

Teresa Blankmeyer Burke, Professor of Philosophy, Gallaudet University
I think we are experiencing a deaf renaissance that this kind of experience, this kind of community, needs to continue but we can’t continue if we have the threat of dissolving us as a people. 
Some fear editing genes related to conditions like deafness could pave the way towards building so-called designer humans.

Teresa Blankmeyer Burke, Professor of Philosophy, Gallaudet University
The gene editing conversation is important because it’s really starting to bring out ideas around who belongs and who doesn’t belong and I think those are really important social questions that we need to reckon with.
Many rich countries already offer screening to pregnant women for disorders like Down’s Syndrome and some fear the elimination of conditions like this would simply be a logical next step and set a worrying precedent.

Dr Natalie Kofler, Senior Advisor, Scientific Citizenship Initiative, Harvard Medical School
It’s an evolution of, you know, pre-implantation genomics.  We have selective abortion, we’re already choosing potential for genetic disorders etc, it’s just one next step than just maybe being able to tailor those genomes for certain traits.
Editing embryos is especially controversial because it can cause genetic changes to be passed down through the generations via what is known as germline editing. 

Prof Henry T Greely, Author of ‘CRISPR People’
So, germline editing affects, potentially at least, your children and grandchildren, great-grandchildren and potentially until the end of the species.
[The doctor who sparked global outrage by claiming to produce the world’s first genetically modified babies]
Germline editing has already caused an international outcry.  In 2018 a Chinese scientist announced he had edited embryos using CRISPR to make them immune to the HIV virus. 

He Jiankui
Two beautiful little Chinese girl named Lulu and Lala came crying into the world as healthy as any other babies a few weeks ago. 
He said that twin girls had been born as a result, who could now pass this immunity down to their children.

He Jiankui
As a father of two girl, I can’t think of a gift more beautiful and wholesome for the society than giving another couple a chance to start a loving family.
But the scientific community didn’t agree.  His experiment was seen as premature and dangerous. 
So, I think we still need to understand the motivation for the study and what the process was for informed consent.

Prof Henry T Greely, Author of ‘CRISPR People’
The risks to these babies were enormous and the potential benefits were really quite small in a way that made it, I think, criminally reckless.
He Jiankui was imprisoned by the Chinese authorities and since then there have been calls for a global moratorium on germline editing.  This could put the brakes on Denis’s research in Russia and he says he is keen to see more debate about editing embryos.

Denis Rebrikov, R&D vice-rector, Pirogov Russian National Research Medical University
In my opinion, there needs to be a discussion on this topic within the scientific community and other regulatory agencies in order to set boundaries about what we need to achieve in effectiveness and safety checks so that this technology can be approved for use.
While gene editing of human embryos is tightly regulated, the same can’t be said about other areas.  In some countries, fruit and veg in which specific genes have been precisely edited aren’t subject to the same regulation as older genetically modified produce which typically contain genes transplanted in from other species.  And while the EU still bans gene edited food, CRISPR produce can be bought in Japan and America.  Some believe this comparatively permissive regulation around gene edited plants should give pause for thought.

Prof Henry T Greely, Author of ‘CRISPR People’
I don’t know any country that I think has a good regulatory structure for this.  It’s a lot easier to do wild experiments with non-humans than with humans.  Some of those will turn out to be good, useful, some of them could turn out to be terrible, some of them will turn out to be frivolous but if we don’t pay attention to them, we’re likely to get lots of bad results.  We need a better regulatory scheme.
But advocates of the revolution in gene edited foods see numerous possibilities for improving production. 

Professor James Dale
This is the first start of our screening process for our gene edited bananas. 
Back in Australia, James is using CRISPR to develop another disease-resistant Cavendish banana.

Professor James Dale
So, we’re setting up here the challenge protocol.
These gene edited bananas will contain no foreign DNA and so won’t be subject to the same strict regulation as his GM variety.  He hopes they could be the answer to the looming banana crisis.

Professor James Dale
We can take them out of field trial without getting any of those sorts of permissions and can take them all the way through to commercialisation, which is fabulous. 
From tomatoes which might lower blood pressure, to mushrooms that don’t go brown, gene edited foods promise opportunities for addressing the challenges facing global agriculture.

Dr Fyodor Urnov, Scientific Director of Technology and Translation, Innovative Genomics Institute
The age of CRISPR completely changes the way we think about agriculture.
Perhaps the greatest benefit of CRISPR could be in tackling the planet’s biggest challenge, climate change.

Dr Fyodor Urnov, Scientific Director of Technology and Translation, Innovative Genomics Institute
It is in making safe, nutritious, more climate-change tolerant crops for the world is where we really see as the future of the biggest impact that CRISPR can make. 
And it’s not just crops whose genes are being edited to help curb global warming, it’s animals too.  This is Pleistocene Park, site of an audacious plan to bring back animals that lived here tens of thousands of years ago and in doing so, counter climate change.  One of the more jaw dropping is the woolly mammoth.  A team of American scientist are working to recreate the prehistoric beasts by applying gene editing to elephants.

George Church
We’ve been trying to reduce the endangerment of the elephants by reviving some ancient DNA variations found in mammoths.
Scientist, George Church, hopes to use mammoth DNA to create an elephant capable of surviving cold temperatures, to repopulate Siberia with these new animals. 

George Church
We’re not creating a new species or a hybrid species so much as rescuing Asian elephant.
He hopes these animals could one day help control climate change by trampling the snow and exposing the permafrost to freezing air, which should stop it melting and releasing greenhouse gases. 

George Church
If they’re focussed on the parts of the Arctic that are richest in carbon and most at risk then it could have an impact comparable to a gigatonne of carbon dioxide per year.
It’s a bold claim and even if it worked, as he suggests, it’s effect on the overall climate would be pretty small.  Many worry that the headline grabbing nature of projects like this are diverting attention away from more pressing conservation issues.

Oliver Morton, Briefings Editor, The Economist
If it starts making people think of extinction as less of a problem, then I think that there could be severe worries.  That said, in some ways, a de-extinction and also the associated thing of being able to, as it were, re-inflate gene pools when things are close to extinct, I think that’s very encouraging, the idea of being able to bring back diversity that would otherwise be lost.
Gene editing has the potential to transform life on Earth and as scientists and society weigh the potential rewards against the risks, there is a need to tease out what is simply a fear of the new and what is a genuine, ethical issue. 

Oliver Morton, Briefings Editor, The Economist
Whenever you are talking about ethics and science, there is an innate tendency to see the science running too fast and ethics trying to pull it back.  I do think there’s also a need to look at what are the ethical things you would like to see happen in the world and how might science bring those about. 

Tom Standage
Hello.  I’m Tom Standage, Deputy Editor at The Economist.  If you’d like to learn more about this topic, click on the link opposite and if you’d like to watch more of our Now & Next series, click on the other link.  Thanks for watching and don’t forget to subscribe.

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