In a new series for The DNA Dialogues we ask ourselves the question: is intervention in embryonic DNA necessary? We put it to Martina Cornel, professor of Community Genetics & Public Health Genomics at Amsterdam UMC, part of the consortium behind The DNA Dialogues. Cornel is both a researcher and a doctor.
About this series
In a new series of articles for The DNA Dialogues, we sink our teeth into the question: is intervention in embryonic DNA necessary? There are plenty of alternatives, right? We address this question from different perspectives.
What does a professor of Community Genetics & Public Health Genomics do?
“My chair deals with the large-scale applications of genetics and its social aspects, such as screening during pregnancy and in babies. We also investigated what parents and pregnant women think of the NIPT (this allows you to have your blood tested to see whether your child has Down, Edwards or Patau syndrome, ed.). As a doctor, I also work at a clinical genetics outpatient clinic. There I answer questions from people who have a hereditary heart disease in the family: can I get it too? And if I have that hereditary predisposition, do I already have symptoms and are preventive interventions such as medication needed?”
Martina Cornel, professor of Community Genetics & Public Health Genomics at Amsterdam UMC: “This is not a purely theoretical idea. There are really people who want this, and have good reasons for it.”
Martin Cornel
Martin Cornel
So when you have your doctor’s coat on, you are talking more to the individual, and as a professor you are talking more about the impact on society. Is there also an overlap between the two?
“Of course. If you had asked me ten years ago whether we should do something with germline modification (editing the DNA of an embryo, ed.), I would have said: ‘There are more important things in the world.’ But then I quite regularly encountered people in the consulting room and at the VSOP, the patient association of which I was vice-chairman, who said: ‘It would be so nice if you could share this predisposition, this gene, which has caused a lot of misery in our family. , can get it out in the bud.’ With the first few patients I didn’t think much of it, but when the patient organizations also started saying these kinds of things, I thought: we have to think about this more, because this is not a purely theoretical idea. There are really people who want this, and have good reasons for it.”
Do you think this technology is necessary?
“There is a small group of patients with a high risk of a serious medical condition who will indeed benefit from this. With this technique we can protect the next generation from terrible diseases. And when patients ask this question, I think you should think about it. After all, the technology is there, or at least it is being developed. But then we must first ask ourselves: why would we want it, and in what situations? What are the pros and cons? You have to identify the risks, and then perhaps investigate whether those risks are too great or not.”
It’s a small group, you say, so is it worth it?
“I don’t think the fact that it is only a small group is an argument against not working on it. In genetics we have quite a few people who are dealing with a rare disease. We are working on this, because the total sum of all rare diseases does yield a high number. Only in a small group of these rare disorders does the question of removing a disease from the embryo DNA arise. And then, in my opinion, you should start with the group that has a high risk of passing the condition on to their children, with a recurrence risk of, for example, 25, 50 or sometimes even 100 percent, where alternatives such as PGT (embryo selection, ed.) are not always successful.”
Where do you draw the line then?
“I don’t think you should ask that question to one individual doctor, but to the Dutch healthcare system. There are diseases for which people now terminate a pregnancy and there are diseases for which embryo selection is now permitted. These are included in the list of serious conditions.”
When is a condition serious?
“That is a very difficult question. There are scientific articles in which doctors try to agree with each other about what is serious and to create a system for it, but they cannot reach an agreement.”
But there is a list. And it ends somewhere.
“Yes that’s right. If you say that in your family there is a very good chance of having a sixth finger, and whether we want to remove it from the genes: no one is going to do that now. We think that is something you can easily operate on. A high risk of psoriasis, a skin condition that can be annoying, is also not an indication.”
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When the NIPT was introduced, there was the fear that people would more quickly choose to terminate a pregnancy, but that did not happen. Could that fact perhaps take away the fear of this new technology? That people appear to strive for perfection less than we think?
“There is a fear that parents will make very far-reaching choices, but many parents are often just happy that they are going to have the child they want, that they are pregnant. Every child is often welcome. But some parents feel that they cannot inflict a serious condition on a child and therefore terminate their pregnancy. We know that these considerations have not changed significantly as new technology became available. We have seen that more and more people have started using prenatal tests over the last 15 years.”
Is intervention in embryonic DNA necessary if we already have something like PGT?
“If the recurrence risk of a hereditary condition is one hundred percent, there are no embryos that do not have it. The classic example of this is cystic fibrosis: if both parents have it, they cannot have a biological child who does not have that predisposition.”
Intervening in embryo DNA could perhaps help them?
“Yes, and it is good to know that it does not always work with PGT. Embryo selection is often used in people with a high risk of a hereditary disease. Then there is not always a healthy embryo, or implantation is not successful. The chance that you will become pregnant with a healthy child with PGT is approximately fifty percent. If you apply CRISPR-Cas, all embryos would be healthy and you would increase the chance of success of such a process for more people. There is also a kind of ethical advantage to this: if you are pro-life, you might like the thought of not having to throw away half of the embryos, something that often happens with PGT because they have a certain predisposition. We don’t know whether it will take off and many people will ask for it. So for now it’s all a bit of air cycling.”
Do you have a memory that really touched you during your work at the genetics outpatient clinic?
“There was a family in which one family member had a heart transplant years ago without knowing that the disease was hereditary. As the heredity came to light and their children reached adulthood, new concerns arose. I can also remember the time that I attended a patient association on behalf of the VSOP for a group of conditions where you often have a 100% risk of recurrence. One of these was a form of blindness in which you become blind at a young age in a very short time. I came across people who had completed a course that required them to see well, but became virtually blind at the age of 18 or 19. They think about how they can prevent their children from getting this too. Some of them say, ‘Bring on all the genetic engineering.’”
What is your answer then?
“’Don’t get your hopes up too much in the short term. It’s going to take a while.’ I tell them that many things in healthcare will not change quickly, but that I will try to discuss it with them. I can’t promise them that it will be possible and allowed in five years. I can only promise them that I will put it on the agenda.”
Intervene in embryo DNA? A possible future scenario
In order for everyone to agree on whether or not interfering with embryo DNA is desirable, some hurdles must first be overcome. For example, we need to enter into a political process, says Martina Cornel, professor of Community Genetics & Public Health Genomics at Amsterdam UMC: “For this you need to talk to each other in the Netherlands, in Europe and perhaps also in other countries. It is now prohibited worldwide to modify the DNA of an embryo for the next generation.”
And then there is the question of safety. If you were to grow precursors of sperm cells in a container and you were to ‘CRISPR-Case’ them, could you really only change that one predisposition and not make any other mistakes? Cornel: “It must first be investigated whether you can make very specific repairs. In the Netherlands, this is not allowed in the embryo law, so if you ever want to investigate this, you must first allow the creation of embryos. Such a ban now stands in the way of these types of fundamental questions about safety.” Cornel does not see the lifting of that ban happening very quickly: “There are quite a few moratoriums and legal hurdles in the way: political decision-making and legal processes can take as little as ten years.” That doesn’t mean you shouldn’t think about it: “If we start thinking about this topic ethically and legally now, maybe in twenty years we can help a couple who would like to prevent a serious illness in their offspring. That is a conceivable passage of time.”
Allowing another country to renovate where the laws surrounding interference with embryo DNA are less strict feels like ‘a strange twist’, says Cornel: “We have leading reproductive doctors in the Netherlands who do a lot of research into embryos, but the things that really matter useful for health care, are not allowed. If you are there and think about the risks that exist, you can be sure that your concerns will be taken into account. So I don’t think it’s a good idea to leave that security research to China. I would prefer that we also discuss this in the Netherlands.”
Also read the other episodes in this series
2023-10-19 07:16:44
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