CRISPR: New Chapter in Gene Editing or a Bane?

Over the past few decades, researchers and investors have pinned their hopes on experimental gene therapies to change the landscape of disease and treatments. The most recent addition to the list: Clustered regularly-inter spaced short palindromic repeats (CRISPR), a powerful gene-editing technique that allows researchers to cut-and-paste genes and thereby altering the medical landscape with the way we are treated with medicines. CRISPR is still a long way from emerging as a one stop shop to stem disease-causing mutations from human cells. Newsclick interviews Dr. Satyajit Rath of the National Institute of Immunology about the latest technology on the block and its potentials and implications.

Rough Transcript

Prabir Purkayastha (PP): Hello and welcome to Newslclick. Today we are going to discuss the new technology of genetic engineering what is called CRISPR. We have with us Prof. Satyajit Rath to discuss the issue. Satyajit, good to have you back with us again.

Satyajit Rath (SR): Thank you.

PP: Can you explain what is CRISPR, what does it stand for, what is really doing. It seems to have taken in last three years overtaken this field and it is supposed to have created a revolutionary new set of technologies along with it. So what is it all about?

SR: That's a question that one can answer at number of level. The obvious answer is to give you the full form of the acronym, CRISPR which really is not going to mean anything at all. Clustered Regularly Interspaced Short Palindromic Repeat). Let's just treat it as CRISPER. The other way of to look at is to tell the story of the science and the third way to looking at is to simply say it's a protein and RNA engine machine that allows us technologically to do something we have not been able to do well easily or well so far in re-engineering the DNA of living organisms.

PP: Somebody has called it a molecular level scissor to cut and splice the DNA strands. Would that be a kind of close to what is being talked about?

SR: Yes and no because molecular scissors, any enzyme, any protein or RNA that cuts it's specific target is a molecular scissor. So simply calling CRISPER or more correctly a CAS 9 CRISPER system a molecular scissor under describes it. More correctly, I was thinking about this when you introduced the idea of genetic engineering it allows us to go from the broad shotgun notion of genetic engineering which is what we have been dealing with by and large so far to the idea of gene editing and that's the phrase out there in public space quite frequently. So to work it backwards we would have liked to able to do and could not do well. And here is how the CAS 9 CRISPER system seems to allow us to do well. It's not as beautiful as the descriptions are. We will come to that in a moment. So remember that DNA is a code. Four letters, four chemical entities arranged in various sequences. So you have got a sequence. The sequence is information broken up into little bit of pieces. So you want to change the information in a one little piece. In order to change the information there, in the original stretch, which is a chemical, very very long chemical you have to identify that particular sequence the particular combination of these four nucleotides and then cut and then change. So supposing you want to put something there you have to find it, cut it and put it in there. So far our ability to do this, we always knew how to do this, but our ability to do it has been statistical, stochastic. In other words we can try this on a hundred thousand targets and we will write at one and if we have a way to select it write at one, should, we can do this. So doing this in bacteria is not been impossible at all. You can't do this with mammalian cells because you don't have that kind of ease. We still do it which is how gene knock out mice, fish, flies all sorts of things have been made so far precisely, by engineering this. But that engineering is still dependent on a statistically low probability event being selected and amplified.

PP: Now the earlier genetic engineering that for instance were done may be plant sequence rectified problems also led to things like unintended consequences like cancer because that did not go to the right place and so on. So this actually will help may be doing it much better?

SR: So the earlier technologies, let us take an actual example of an immune deficiency because of a defective gene, single defective gene, children have immuno deficiency, children die and experiments, clinical trials were done where a good functional copy of that gene was put into their bone marrow, stem cells, they were given transplants of those cells and their immune systems got corrected. The problem with that is that the gene which were put in within that no where it went. Because, it were put in a few million target cells, it is quite possible that in different target cells, it went into different place in the entire genetic code. In some of those places where it inserted itself did not matter. But in other places, it inserted itself into a currently functional gene and changed it somehow. In theory, what we can now do is the same experiment which is take the bone marrow, stem cells from the children take the defective gene, cut the defective gene and precisely put the functional version of the gene back and the thought is hey presto! You now have children as good as new, you have changed nothing in them except for the defective gene. In theory, that's what the CAS9 CRISPER system does. In reality does it do so, is a good question. So a little uncomfortably, I want to bring up a Chinese study. Uncomfortably not because it is Chinese, but because it was apparently rejected as a paper by various reputable journal because it's ethicality appears to be in dispute because it used human embryos to correct a Beta Thelesimia genetic defect of very much analogous situation. They did not go further with it. This was simply a technical study to see whether in human embryo you could use CAS9 CRISPER genetic system to correct defect. They published it somewhere. The interesting thing is that they did correct the defect but they also had other changes. They also had of target changes.

PP: That brings to the next question which is that this technology is obviously going to have an impact on changing the way have next generation of babies. It is possible to get what we call designer babies. And that's a possibility if this technology now incrementally improves with say next five, ten years. So we are very much of a thresh hold of a position of what was talked about hypothetically a designer baby. Apart from creating tools which will actually change what you may call genetic defects, what we discussed just now. The second of course what happens to agriculture, what happens to animal husbandry. So before we go into the animal husbandry and the farming issues, what do you think is the possibility? Does it give us the possibility of changing ourselves? And if so how do you regulate it. What do you think are the postulates, the principles on the basis of which you can regulate?

SR: So keep in mind what I said earlier that what this technology is doing is changing the efficiency with which we can do what we could do earlier. So could we make designer babies earlier? Sure we could except that we had no clue by and large, what the outcome would be. So with this technology, in what way does that change. Sure assuming that it promises real, it changes in the prospect in that it allows us to predict that a certain change in the DNA of a baby we can bring about reliably There are two kinds of consequences to this and these are consequences that genetic scientists of the 20th century saw very clearly and these consequences are we can change single gene that has singular functional consequence. Take for example, cystic fibrosis results from an alteration in a cystic fibrosis gene. Beta Thelesimia, the immuno deficiencies that are genetically made, all of these are so called Mendelian inherited dominant genetic diseases where if you have a gene you are going to get a particular disease and quite likely only that particular diseases. These are the situations where if you can correct it, you stop the disease. I am not sure that anybody is going to argue that this is not a good thing. We may find people who... do after all, Donald Trump is a serious contender for the Presidential candidate of the Republican party, almost anything is possible to find as an opinion. But the reality is that this is a category of diseases and therefore, of genetic changes that across the board that we are likely to see is good. So what are the changes that we then think about that are a little more dodgy. So almost all of those, it turned out is likely to be genes where the relationship between the genes and the function, the visible consequence is not a straight forward consequence.

PP: The argument for instance Schizophrenia. How much it is inherited

SR: Everything pretty much, the monogenic traits, single gene control traits are few. We are not quite sure exactly how few. We don't have those science making good estimates but they are certainly few. So here is the problem, somebody tells you that here is a gene that is going to increase muscle endurance and you can make long distance runners. All these conversation about Kenyan and Ethiopian long distance runners. Are we going to make designer athletes and my guess is that we will try that in animal models and we will discover that much to our chagrin what we should have known in the beginning that one gene no doubt it contributes something to explaining the long distance endurance certainly does not confer by itself, long distance running endurance. In other words, we will have all sorts of designer attempts being made where there are no visible consequence.

PP: The question is will this be allowed at all, should this be regulated, should we allow 'forces of the market' the great god of the market and decide this, all our advertisements, people saying we can do this, give you super babies and there will be enough number of people who then fall for it.

SR: So, let us get something clear. Once you have this as a technology and as I said this is partly the reason why I brought up the financial viability as it were of this technology, once that happens, whether we regulate or not there is going to be an underground. There is going to be an illegal market and trafficking in this eventually. I hope it is not going to happen today. But certainly, the likelihood that it will happen in the near time future is very high and that's going to happen regardless of whether we say we are going to prohibit it completely, we can do all the chest thumping, that the whole point of black market is develops and thrives in the phase of regulation is against it so implementation gaps which are inevitable particularly in poor communities is always an issue. So under those circumstances it is need to happen, we need to provide in addition to thinking about what you brought up which is the issue that should we be regulating it and to what extent will be regulating it and I will come to that in moment but the point that I want to make is the point we forget, which is that the outcome of the inevitable, illegal activity with this technology are going to be babies. We need to make provision for them, we need to ensure that they have their rights. That is an absolutely critical and completely undiscussed issue. That said, should we regulate this? Absolutely. In what way we should regulate this. Let me bring up I am likely to be pilloried for this in certain sections but let me bring up a parallel debate on issue in regulation. The issue of the right to die. Do we have it? Do we have the right to assistance for killing ourselves, under what situations do we have these rights. These are debated issues across the world and across the world communities have taken different perspectives to this. There is one thing common, even to these communities who have acknowledged it as a right, who have acknowledged to right to assist even there is an extraordinarily serious public sector judicial supervision. And I suggest that this is a technology let us use the phrase despite my distaste for it the designer baby all said and done, all babies are designer babies because the parents want progeny in their own image. But technologically designed babies of this sort I think, need to be discussed regulated in this public, in this state, the society and the legal system driven supervision.

PP: Would you also extend it to animal, plants or did you say principles remain the same but the implementation may be less stringent that we would do it for humans.

SR: So my counterpart activists in the animal rights or the deep ecology arenas will take this and say this is precisely why we should not make germaline changes. In either plants or animals, we should not make germaline changes. In any non human life quite as much as human life. My response to that of the philosophical level remain unchanged from pre CAS9 CRISPER technology days namely, the ethicality of the idea of rights is alienabily a human concept. How we treat world around us, how we treat animals how we see the perceived pain is a reflection of how we treat ourselves and therefore, while human treatment sustainability are the values we need to work within they don't equate non-human life in human life in the sense our counterpart activists would like it to be said. That said, here is the issue and this issue remains exactly the same in the genetically modified lifestyle and genetically modified crop using as broad definition of crop as you would like that is are we going to use this technology to make far more precisely gene edited crops, absolutely. There is already a crop in the market or about to go into the market. It is a oil seed, I precisely forget. There is a company that has brought out or is in a verge of bringing out a CAS CRISPER modified oil seed. So clearly, it is going to happen. So is it a better technology, absolutely because it allows you in theory at least to change one gene. We should validate it but that's it some of the technological biological concerns with the older gene modifying technologies in crop agriculture would be addressed. But the core issue remains still the same and that is every time you do this you bring seeds into the market place backed by an extraordinary amount of seductive advertising and powers of the elite financial world behind to sell things at very high cost to people who is not clear to me can not afford this.

PP: Thank you very much Satyajit. We will be very happy to have you with us. We will discuss this issue in the coming days.

SR: Thank you.