San Diego Researchers Caught Up In Ethical Debate About Altering Human DNA

This is KPBS Midday Edition. I am morning Kavanaugh. Experiments by researchers at salt Institute are on the cutting edge of a new debate about scientific modification of the human genome AERCO in other words,, should scientists change the natural structure of DNA? There are good arguments for altering you mutator portions of DNA which can cause devastating genetic diseases. But emphasis want to put the brake on the severity research until more agreement has been reached on how far these changes may go. Joining me are all ask -- and -- to researcher Associates at salt Institute for biological studies your your involved in research to regroup strands of mitochondrial DNA in mice embryos. Alex -- welcome. ________________________________________ Thank you, thank you span Evan Snyder is here with the Sanford Bernstein medical research Institute MLA up. He was on the FDA advisory board on another method of REIT -- removing mutated ModiCon drill Ginny known as nuclear transfer or more popularly known as the parent in vitro fertilization, Evan Snyder, welcome. ________________________________________ Great, ask for being here. ________________________________________ Alex, first of all,, remind us what mitochondrial DNA is and why in mutated form it can create deadly conditions for kids to inherit it? ________________________________________ White voc. undrilled -- inside the cell and have -- they played -- play central roles in the -- one of them most known -- Sweeny mitochondrial to produce energy that is necessary for the cells. -- DNA and that the innate -- to Frank components of the mitochondrial that are essential for the energy production. We have mutations you need but undrilled DNA, you, you have a decreased level of -- -- reg muscle and heart ________________________________________ Right and these mitochondrial DNA is something that only a mother gives to her child. Is that right? ________________________________________ That is correct. There other heritage. ________________________________________ What kind of conditions does a bad mitochondrial produce? ________________________________________ The effect may need the brain, the heart and the muscle and you will have a series of different conditions -- within 200 mutations -- muscle weakness, and decreasing growth -- brain development and neurological disorders, liver failure, kidney failure so these are very -- most of the cases the kids will have a life expectancy and the teens many times ________________________________________ So Pradeep how does the research of salt try to eliminate this that ModiCon real D? ________________________________________ -- so-called what can I didn't buy the specific locations in the mitochondrial DNA so we introduce this molecule -- into the embryos from the mouse and -- specific mutations and -- so -- destroyed so by that way we can -- transmitting to the next generations and you say that you have been conducting these experiments on mice embryos, is that right? ________________________________________ Exactly. ________________________________________ Have they've been successful? ________________________________________ Yes we were quite successful, completely prevent a specific type of mitochondrial DNA from the mother to be passed on to her next generations so we -- completely eliminated so tomorrow this can be easily translated even for the human situations where we can recognize and specifically identify the mutations that are present in the human embryos and eliminate them. So by that way we can prevent them from transmitting to the next generation. ________________________________________ That was exactly the question I was going to ask next, Alex. This altered version of the mitochondrial DNA is then passed on to the next generation. Therefore, this is truly altering heritable DNA. ________________________________________ Yes. That is true. This -- way to prevent the transmission of the -- to the next generation so all the -- introduce we basically eliminate the mutated DNA and then next -- will inherit healthy DNA. Even -- not only the first -- generations after and we saw that -- so generation -- will be healthy. ________________________________________ -- part of the FDA committee, you reviewed another experimental method to get rid of mutated mitochondrial DNA, it is called nuclear transfer. Telus if you could as simply as possible how it works. ________________________________________ Yes, that technique is a true technical for us, however what involves is taking the nucleus from a diseased egg and putting it into an egg where there are healthy mitochondrial in which the nucleus has been removed. No one has an egg with the help the nucleus, the nucleus presumably of the mom who as the disease and now healthy mitochondrial. And then that egg can go on to become fertilized and give rise presumably to an offspring that has all of the traits of the mom and the dad but without the mitochondrial disease that the mom formerly had. ________________________________________ So the nucleus with this transfer is coming from a second woman, is that right? ________________________________________ The nucleus is coming from the mom who had the mitochondrial disease.. It is going into an egg -- ________________________________________ Is any of the DNA of the second woman now part of the embryo? ________________________________________ That's a becomes a scientific debate. There probably is some but I merely not. So again this is some of the gaps that we need to discuss in terms of how safe and efficacious detect and Nikki's. But in theory the DNA -- traits comes from the original mom only the mitochondrial will come from the donor eight. ________________________________________ But the suspicion that perhaps some of the second woman STNA is present and will be manifested in this child, that's why it is sometimes called three parent in vitro fertilization. ________________________________________ Correct. Plus the mitochondrial themselves will come from one woman. The traits that we believe our nucleus come from a second woman and of course the dad. It there's even a debate as to how much of the nuclear DNA is needed for the mitochondria to function. And could there be a problem with that kind of mismatch. In theory, no. But in reality, it is more complex than we recognize. ________________________________________ This nuclear transfer procedure has been given the go ahead and United Kingdom. What about in the US? ________________________________________ I think there's a misunderstanding there. That's what we do in this country is and what the committee I chair did was to simply look at the science. In fact we are instructed not to take into consideration in this particular instance the ethics or the politics what the cost or anything simply you look to see whether the science was there to enable a clinical trial to be done. What are committee came to the conclusion was that it is an interesting technique, mitochondrial diseases are clearly warble but there were gaps in our knowledge. I mentioned a few of those but we came up with the laundry list of what those gaps were. All of the United Kingdom wanted to do was to be on the same footing as the United States come have an organizational Mike the FDA back and go over and do the exact same thing for the data. In other words to make it database whether then in the legislature. What Terry co-vent of the FDA be would be that H FDA, the human fertilization and embryology Authority. It is not a go ahead. It was simply to say that the H FDA now will look at the data in the same with the FDA is and decide that are the gaps, what needs to be filled, does it make scientific sense and then of course as I like to say, good ethics comes from good science. ________________________________________ In other words there are no nuclear transfer procedures happening in the United Kingdom? ________________________________________ No. There will not be until the signs indicate that it is ready and also such a very, very difficult technique that they are probably only a few centers in the world that even have the capability to use that particular technique. ________________________________________ What are the potential risks involved in a procedure like that, Evan? ________________________________________ The risks first of all, are those that exist in any kind of assisted reproduction so IVF. We have been doing IVF are so many years now that we understand the risks. We know how to minimize them though they are still exist. The other risks are off target effects so unintended consequences. Or focusing on one gene but not recognizing that you've changed another gene or another Morgan. Or perhaps even in pairing certain functions of mitochondrial while improving one aspect you've actually impaired another function. The only to answer that question is to actually do very, very long-term follow-up, to stress the Morgan, stress the cells so the objection of our committee was not focused on the ethics ago that's a completely different issue, but just saying that there were scientific gaps in our knowledge that we really need to fill. ________________________________________ Speaking about this off target mutation, Alex, a team of scientists in China had published a paper on their research also using a method to cut out strands of DNA but they are using nuclear DNA instead of mitochondrial DNA. Their research was on unviable human embryos instead of mice. They reported a large amount of off target mutations. In other words the procedure was changing the DNA in unintended ways. What's your reaction to the results? ________________________________________ My reaction is that anything that could have go wrong actually went wrong so they have a low efficiency and -- mutation they have something that is called -- in which some -- then as you mentioned they have a very significant off target effects so -- genes you are not targeting. To me the major take is that in our case were looking at the mitochondrial versus nuclear and in your case when we make a cut and mitochondrial DNA the molecule is destroyed so it would not be -- in the way that you can have a second [Indiscernible] FX of the technology and the -- and a similar way but again as he mentioned a mentioned one is nuclear the other is mitochondrial and there are some significant differences between the two. In the case of nuclear there are technologies nowadays that would allow for healthy embryos to be selected, this is called -- diagnosis so our test that IVF clinics are doing. They can look at the embryo and select which ones are the ones that are healthy. Those -- not applicable to metacognitive resistance. There's no way the way you can predict which embryos going to be healthy and that is why we decided to focus mainly in mitochondrial ________________________________________ Pradeep, what Alexis a there is the method that you're using there's very little chance that there would be any off target mutations? ________________________________________ Exactly. In the paper we published revisit two types of -- one of them is a very specific that we are very confident so the F1 is the one out -- for each patient individual patient so for those we always try to check the off target affecting the cells of the patient's to make sure they are working in the way they have to be. If they are not we try to modify them and make them as specific as we can. Other major differences are that comparing to the -- nuclear we have only two sets of genomes. But when compared to mitochondrial we have hundreds of thousands of copies. So the chances of having this -- target effects is kind of less -- with the nuclear one. ________________________________________ Evan, the Chinese team says it stopped it is research on human embryos unviable human embryos because they believe it is too immature. The other Chinese teams are reportedly moving forward. Does that concern you? ________________________________________ They is concerning. I think even in experiments that we don't endorse and certainly the Chinese experiment that was reported would not have been performed point going ForcePad anybody in this country. One tries to pull out something that's instructive and I think what we do cleaned from that set of experiments that were published was everything we suspected as Alex indicated that every concern that we had theoretically was in fact validated in those experiments. If there were many introduced mutations, there were many off target effects and it would have created a problem and to their credit the Chinese authors on the paper said we've learned our lessons -- where not going to be doing this anymore and told the science catches up with the technology that we want to do. I would hope that their Chinese colleagues, the universities and other places would take the lesson the way that they have cautioned. This is a problem. ________________________________________ Evan you said when you are in the FDA panel you look at the science and you didn't deal with the ethical concerns. Some ethicists though and there's been some talk in the popular media as well, they are concerned is this kind of research maybe to modifications to DNA for babies eye color, forced sex, for even a letter core intellectual abilities. Could that be where we are headed? ________________________________________ That type of argumentation is called the slippery slope argument. Most ethicists to not embrace the slippery slope argumentation. I believe that we can build handrails into the slippery slope. There's no question however that if we ever got to the point where we could target certain disease mutations safely, efficaciously, selectively then still on a case-by-case basis, a gene by gene basis, we would have to evaluate what are the risk benefits and what would be acceptable and it is not acceptable, probably, to modify a normal embryo for any reason. So it would be a very, very select group of genes that would even be considered come even if we've got to the point where that became a reality. ________________________________________ Quickly, Evan there some medical ethicists a we should put a brake on this kind of research, all of it until it becomes more clear where it is headed. What we'd you support that? ________________________________________ It becomes a bit of a conundrum how to evaluate and improve the technology without actually doing the experiments so obviously the experiments need to be done but they obviously also need to be done in animals or in represented of disease models or sometimes even in a culture dish to figure out what the problems are. Fortunately I think we are the stage right now where many of these issues can be resolved just in a tissue culture dish. ________________________________________ I want to thank you all for explaining very complicated subject to us. I've been speaking with -- at -- and Evan Snyder, with the Sanford earned medical research Institute, thank you all ________________________________________ Thank you. ________________________________________ ________________________________________