"We have made IVF one hundred percent"
The world–famous scientist Shukhrat Mitalipov - about the wonders of gene editing and the revolution in the fight against infertility
Anna Urmantseva, Izvestia
In the laboratory of Shukhrat Mitalipov, a method of conceiving a child from three parents was first developed and tested, allowing to get rid of rare diseases. In his laboratory, the first edited human embryos on our planet appeared. The scientist who left Russia in the 1990s became one of the most famous American biologists, he heads the Center for Embryonic Cell and Gene Therapy at the Oregon University of Science and Health in Portland. Izvestia learned from Shukhrat Mitalipov how gene therapy can completely eliminate cancer and genetic diseases, as well as make IVF absolutely successful.
– Where are your laboratories based now, where the main research is being conducted?
– Two of my labs are based in Oregon. One of them specializes in research related to human embryos, and the second one specializes in animals: monkeys and mice. We divide them because there is a law in the United States that does not allow the use of government funding for human embryo research. And since I have a lot of state funding, we have to separate these projects, so to speak.
– What projects are currently underway in these laboratories?
– We are developing two major areas: gene therapy and IVF improvement.
Chinese lawlessness
– About gene therapy. Recently, the first edited people appeared in China. How do you feel about this event?
– It's just a nightmare. If I was asked how a real scientist working on the prospect of widespread introduction of gene editing technologies could ruin the whole future of his field, I would answer: that's exactly how it was done in China. Therefore, the appearance of twins, of course, was a shock for us.
– Because the safety of the method has not been proven?
– There's a whole range of problems there. Firstly, the scientist conducting this experiment is not a geneticist, but a physicist, judging by the news in the media. Secondly, no scientific article has been published. Thirdly, the effectiveness of the implanted mutation against HIV has not been proven. Fourth, he took healthy embryos and for some reason introduced a mutation to them.
"So they weren't infected?"
– Of course not. Subsequently, of course, they could get sick. But we can all potentially get HIV infection. I think Dad was sick there. But if they did IVF, they would absolutely get healthy children.
– That is, the outrage of the world scientific community was caused primarily by the fact that he did not understand what at all?
"That's right. And technically, what he did was very simple. But, in a good way, he should have been doing this work in Petri dishes for 5-10 years, without transplantation, showing what he is doing. And he, in fact, showed how easy it is for a layman who has got a serious tool in his hands – a genomic editor, to do whatever he pleases.
– Are you probably experiencing this especially painfully because you have been trying for years to prove the safety and justification of the use of gene editing for genetic diseases?
– Yes, for years. I personally have been trying for 10 years to prove that in order to correct genetic mutations, it is necessary to edit it at an early stage: either at the stage of the egg and sperm before fertilization, or immediately after.
– In the USA, it is now possible to edit an embryo, but it is forbidden to implant it?
"That's right. We work mainly from fertilization to three- to five-day-old embryos. We bring the embryos to the eight–cell stage - these cells are called blastomeres. Then we separate them from each other, extract DNA from each and look at what happened there during editing.
Minus genetic diseases
– What diseases could be eliminated 100% now, if there were no prohibitive measures?
– All genetic diseases associated with the mitochondrial genome. There are two separate genomes in every human cell. One is nuclear, where the bulk of all genes are located, somewhere 20-25 thousand. The second one is mitochondrial – there are only 37 genes. They are inherited only through the maternal line. These two genomes are quite different, organized in different ways, inherited in different ways. So, diseases caused by improper functioning of mitochondrial genes can be eliminated.
– What diseases can be eliminated in this way?
– From 300 different mitochondrial diseases. Mitochondrial diabetes mellitus accompanied by deafness, Ley syndrome, mitochondrial neurogastrointenstinal encephalopathy and others. We have created a technology that has been successfully tested on mice and monkeys. But we cannot test it on humans, because the US Congress intervened in this matter and forbade us to bring our clinical trials to an end, although we have already started work…
– Is it more complicated with the nuclear genome?
– There are more genes and, of course, diseases associated with them. Mutations that are inherited, about 10 thousand.
– That is, it is 10 thousand diseases that can also be removed at the embryo stage?
- Yes. These mutations can be eliminated by genetic editing. If mitochondrial genes cannot be edited, then nuclear genes can. We already know which code is correct and which contains errors that lead to a particular disease. All these sections can be recoded. But the approach to each gene will need to be developed separately, although the principle of restoration is the same for everyone.
– In the same way it will be possible to rid humanity of cancer?
– Not from all types of cancer, but only from those that are inherited.
Is this Angelina Jolie's situation?
- Yes. She solved the problem by another method. But it would be possible to solve it already at the embryo stage. And what is important: it would be possible to correct this situation not only in this child, but also in all future generations, because he will pass on a normal gene. That is, to stop cancer at the root.
– The second direction of your activity is related to the improvement of in vitro fertilization technology. Is it really possible to achieve almost 100 percent results when transplanting an embryo?
– Yes, we managed to understand a revolutionary thing experimentally. After all, we have been looking at an egg for many years in a row, which looks quite normal externally, but fertilization does not occur. Why does it not develop after fertilization? We answered this question purely experimentally. It turned out that the process often does not start precisely because of defective cytoplasm.
– That is, not the nucleus, not the mitochondria, but just a "liquid" in which everything floats inside the cell?
– But in general, the cytoplasm has always been considered the most important part of the egg! A lot of maternal factors accumulate there. No one knows exactly what they are, but it turns out that they give life to the embryo. These factors program any nucleus, and sperm, and their own, and someone else's, and somatic. Now we have developed a cytoplasm replacement technology. That is, the nucleus remains mom's, the sperm remains dad's, and the cytoplasm remains donor. Now clinical trials of our technology are underway in Athens, there is a large clinic there. And now they have children, families who have tried to do standard IVF many, many times. With our technology, fertilization occurs immediately, that is, we have made IVF one hundred percent. This is a great success.
– Shukhrat, now the project "Science" has started in our country. According to it, 35 new genetic centers will appear, and the plans also include an increase in the number of scientists who own the methodology of genetic editing. Now, according to the estimates of the Ministry of Science, there are about 50 such specialists in Russia, it is planned to increase their number to 5 thousand in five years. From your point of view, is it real?
– I think so. But how and for what to use this method – it is necessary to think. Such specialists are already worth their weight in gold.
– Will you come to work with us?
– With pleasure.
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