Jennifer Doudna | Four ways that CRISPR will revolutionize healthcare

Jennifer Doudna | Four ways that CRISPR will revolutionize healthcare

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It’s an extraordinary, I think, moment in science where we're seeing a technology that came from fundamental curiosity-driven science turning into a technology that can be used widely for treating diseases that previously were, were frankly not treatable and certainly not curable. We are all here today because we are really united by our common mission to make all of science open so that scientists, us, so that we can collaborate better and faster and deliver solutions that enable everybody out there to live healthy lives, on a healthy planet. And here at the Frontiers Forum, we actually like to select visionary scientists to present exactly these types of breakthrough solutions that will enable human and planetary health. And today's speaker represents this mission just beautifully.

She actually needs very little introduction, thanks to the huge impact she's already had on science and society. So it is my great pleasure to welcome Professor Jennifer Doudna of UC Berkeley today. Professor Doudna is the pioneer behind the revolutionary CRISPR-Cas9 gene editing tool and CRISPR has completely transformed all of gene editing.

It allows researchers now to rewrite the genetic code of almost any organism in a simpler, in a cheaper, and in a far more precise way than any previous technology. And for her work on developing this technology, Jennifer was awarded the Nobel Prize in chemistry in 2020, alongside her long-term colleague, Professor Emmanuelle Charpentier. They're actually as well the first all-female team to ever win a Nobel Prize, which I guess makes this even more of a historical achievement. Jennifer is also the author, as well as the subject, of several best-selling books. In 2017 she, for example, wrote "A Crack in Creation" which is more of a personal account behind the CRISPR story. And just last year, Walter Isaacson wrote a best-selling biography about her.

It's called “The Code Breaker,” and it debuted at number one on the New York Times bestsellers list. Great book, recommend both highly. Now thanks to CRISPR scientists can now repair human genes to treat diseases, they can wipe out pathogens, they can design better crops to feed a growing population. It is really an incredibly powerful technology, which is probably only comparable to the invention of the steam engine or the birth of the internet, because of the huge impact it has on all of our lives. So it is my really great pleasure to hand over the microphone right now.

Jennifer the floor is all yours. I think CRISPR will revolutionize health care for everyone, and I want to just point out four different ways that we see this coming about. First of all in the future, it's going to provide treatments for many diseases – I don't want to say all, but certainly it's a technology that is going to impact I think many diseases, not just a rare genetic disease in the future. And this comes about partly because there's a lot of ongoing innovation with CRISPR, new CRISPR enzymes that are being uncovered all the time, new ways of improving the activities of these CRISPR proteins and making them even more precise for genome editing, and then engineering new ones. There's a couple of examples here, with different versions of these CRISPR Cas proteins that have different chemical properties –including, I want to point out on the right, this family of proteins known as Cas13 that are naturally capable of targeting RNA molecules, which is very interesting and is already being used diagnostically, for example. And that's research that is very much ongoing, as well as a lot of clever engineering that takes advantage of the RNA guided platform of CRISPR Cas proteins and adds on to them other kinds of enzymatic activities, such as some of the examples shown here.

That includes being able to alter individual nucleotides in a process called base editing; activate or silence genes without making a permanent change to the genome, or to create changes to the epigenome – in other words the modification state of chromosomes that can affect the output of genes. These are all things that are already happening very rapidly, in some cases there are already publicly traded companies that are developing these types of approaches. And for all of this, I think right now, one of the challenges ahead is figuring out delivery of CRISPR molecules. In other words, how do we make sure that the CRISPR proteins and their guide RNAs get into the cells where editing is needed? It's a challenge that again many academic and corporate groups are addressing through a combination of using viral based delivery vectors, as well as nanoparticle-based systems, and lots of other types of innovations that are ongoing currently. So the second aspect of CRISPR for the future is the possibility that it can be a technology that will usher in an era of what we call off-the-shelf therapeutics.

So one of the great things about cell and gene therapy right now is that it can be personalized, which is awesome; on the other hand we want to make sure, and I think that you know one of the goals of the medical community in the future, is to ensure that these types of therapies are widely available. One of the ways that will happen is to standardize the production of modified cells, figure out how to make cells that are more if not universally applicable in different people, at least more widely useful in different individuals, and again this will definitely involve manipulation of the genome and CRISPR is going to be a tool that will help usher that in. Number three is faster diagnostics and drug discovery. So this speaks to the both the utility of CRISPR as a research tool, but also as a very much a cross-cutting technology. It's not just useful as a genome editor, but it's also useful as a detector, and that's where some of the diagnostics come in.

Already there are CRISPR-based diagnostics that have been approved, given EUA approval by the food and drug administration in the US, that allow CRISPR to be utilized in a fashion that can detect viral nucleic acids. For example, the SARS-CoV-2 virus that has been so much front and center over the last two years, but certainly for other kinds of pathogens as well. So this is an example showing a point of care test that's based on a CRISPR strategy, and actually at our research institute, the Innovative Genomics Institute, we run a clinical lab that does a standard PCR test for SARS-CoV-2.

We actually now run a high throughput CRISPR test for SARS-CoV-2 in parallel, so we're working with a company to test their technology in that regard. And then I just also want to point out that, as I mentioned earlier in the talk, CRISPR is revolutionizing research and I think one of the the exciting directions that is headed is coupling that kind of production of large-scale data sets. CRISPR is widely used now for screening large numbers of genes to figure out which genes are involved in a particular pathway or process, whether it's a natural process or a disease process. And one of the tools to help analyze all of those data is going to be machine learning and AI based approaches for analyzing those data sets. So I think CRISPR combined with AI is certainly poised to revolutionize drug discovery. And then fourthly, and this is more forward-looking, is thinking about CRISPR as a preventive tool.

So how do we think about that? Well I think CRISPR, because of its ability to alter genes precisely, could in principle be utilized to provide people with protective genes. And there are increasing examples of diseases –Alzheimer's for example comes to mind, as well as cardiovascular disease – where there are genes that make individuals more susceptible to those diseases over time, but where CRISPR in the future could be used to provide a protective allele of the of the disease and of the gene in question to protect people from disease. And then this is just also pointing out that it may be possible to work in the agricultural sector with CRISPR, to create crops that are more nutritious, more resilient in the face of climate change, dealing with challenges of food production, as the environment is changing around us. And that's it. I just want to thank all of you and I’m really excited about to hear from the other speakers and of course to entertain your questions when we have time for that.

Thank you very much. Thank you, thank you very much the presentation was clear, it was inspirational, and it was very comprehensive also, so thank you very much for giving us a sort of a broad view of everything, what it's all about and what it can do. But first we're going to open the floor to the three people that we've invited as panelists today, and we're going to start with Professor Andrea Crisanti.

Professor Crisanti is a Professor of Molecular Parasitology at Imperial College in London and Professor of Microbiology at the University of Padua. He is the world's leading expert on developing gene drives to reduce mosquito populations, as a way to stop malaria transmission. The groundbreaking work that he has led has implications beyond malaria, such as for controlling agricultural pests that threaten human food security and eliminating invasive species in fragile ecosystems.

So Andrea over to you for more about one of these important potential applications of CRISPR gene drives. Thank you very much for this invitation. I’m really honored to being amongst you and I thank you for the opportunity and thank Jennifer for giving us this fantastic technology that has been really instrumental for moving a bold concept into something that will probably have an impact in eradicating malaria. Jennifer has explained very well how a gene drive works so I will not spend a single word on it, but I will tell you that we've been using this technology, we have developed this technology, to solve the problem of malaria. Malaria has been eradicated in around the middle of the 20th century for most of the western world, but in resource-poor countries it's still a huge problem.

Every year about 200 million people are infected by malaria and we still have about half a million children that die of malaria every year. And malaria is closely linked to poverty. Resource-poor countries do not have the logistics and the capability to implement measures that have been proven effective in the western world – like insect control, drug treatment, and breeding site reduction. Our gene drive technology offers a viable alternative of a conventional approach in terms of sustainability and cost effectiveness.

We have seen, as Jennifer has explained, that in sexually reproducing organisms this element, gene drive, can transmit a gene inherited by one of the parents to 100% of the progeny, and not just 50% like a normal gene. So this means that generation after generation, they can spread to an entire population. Gene drives can be engineered with an objective to introduce a variable trait, like for example, developed mosquitoes are refractory to malaria, they are immune to malaria they cannot transmit malaria, or we can engineer them with genes that interfere with the ability to reproduce.

And so we can drive this population to extinction. The project started about 15 years ago with the idea to exploit the capability of a kind of a selfish parasitic genetic element that have this property, that we're first discovering yeast, that we call these genes orbiting endonucleases. This just reminds me that they are nucleases, so they are enzymes, like CRISPR, they cut DNA, but unlike CRISPR, they do not have the flexibility of being engineered where we want them to cut. And so when CRISPR technology was introduced, we were able to test this technology much, much quicker, and as well this translated in time reduction, time to results, and allow parallelism, this means that we could test many options and many solution in parallel rather than one by one, after the other one. So using CRISPR, we demonstrated the gene drive targeting a key gene involved in sexual development of mosquito, we could completely suppress caged mosquito population in a span of 6-8 generations, which translates into three months.

You know this is, we believe, this is a revolutionary achievement. This is the first time that by manipulating a genetic makeup of a species, you can bring that to complete extinction or to complete suppression. The same time double sex play a key role in all insect species in regulating reproduction, so this means that this approach can be used for other insect species that function as a vector for disease other than malaria – for example, dengue, yellow fever, zika, or cause important agricultural damage. Of course, this technology has a lot of challenges, it is difficult to conceptualize for lay person, is invisible, requires some background level of genetics and reproductive biology. There is a widespread prejudice by the public and GMO organisms, and we face a complex regulatory framework that is not up to technology development.

So what we learned so far, it is crucial to a competent and motivated colleague in the field where the technology has to be delivered. Main challenge is political instability represent a key factor. You need to be sure that you're able to make technology transfer training and communication are key factor for success. Two years ago, however, we were able to release in Burkina Faso the first GMO, which and the gene drive, which was incapacitated but at the same time it was done as a proof of principle, as well as to test the capability, and a week ago we shipped in a laboratory in Burkina Faso a self-limiting, bias sex bias GMO line. And we aim to obtain regulatory framework for approval regulatory approval for DSA – double sex gene drive for suppression – by the end of 2024.

And thank again, Jennifer, for giving us such a fantastic tool. Thank you so much for that for that quick overview, just is there a reason for Burkina Faso? Was that because of…? As I said, it's very crucial they have competent scientists there that are able to take up the technology. They have the political and scientific credibility. This is really key for success. You really need a champion that has the scientific and political credibility. All right, and this is linked also to a problem who, who has a say in this technology.

I think we should – and this is more an ethical issue – but I think the people that have the problem are the one that should decide whether the technology has to be applied or not. I mean, it's very easy to judge the technology sitting comfortably overlooking the Bay of San Francisco, but it's another fact being in the middle of the savannah with a problem there and without the resource to solve it. OK and Andrea, would you have a question for Jennifer? Yeah, yeah I do have a question for Jennifer. Jennifer, clearly this technology really pushed the boundary of what human being can do really over the limit, for the first time we are able to manipulate the evolutionary trajectory of multicellular organisms, and clearly there is a clear need and let's say also an ethical reason for doing this for disease vectors.

How do you feel about applying this technology for agriculture pest or for, let's say a small rodent or rodent or other species. Well first of all I'd just like to acknowledge your incredible work on gene drives, it's really been exciting for me to see how CRISPR is being applied in this type of application for controlling you know, mosquito spread disease. And I think you're right, that there are opportunities to use it also in the control of agricultural pests and to, you know, to do that both by directly editing the pest itself, as you're doing in the mosquito vector, but also to think – one thing that we're working on currently with a lot of collaborators at the Innovative Genomics Institute is the opportunity to use CRISPR in microbial populations that support agricultural outputs that could help control, for example, carbon release during a large-scale agriculture. So these are the kinds of things that we're looking into and we'll have to, you know, be following the kinds of leads that you and your colleagues are taking in terms of environmental protections, right, ensuring that CRISPR is used safely as it starts to be applied more widely.

Thank you very much. Thanks Jennifer, thanks Andrea, and so we'll just keep the discussion moving forward. Our next panelist is Françoise Baylis. She is University Professor at Dalhousie University in Canada. She is a philosopher whose work on bioethics aims to develop more effective ways to understand and tackle public policy challenges.

So she's helped to develop public policy in a number of issues around bioethics, and is very active in helping the public to understand these types of scientific and bioethics issues. Now these include the ethics and governance around human genome editing. She is on the Committee of the 3rd International Summit on Human Gene Editing, and she helped to develop the World Health Organization's governance framework and recommendations on human genome editing. And she's the author of a book, entitled "Altered Inheritance: CRISPR and the ethics of human genome editing." So it's, we're very much looking forward to Françoise, to hearing your contribution and your perspectives on some of what we've already heard during the event today.

Françoise over to you please. Great thank you very much. So one of the things that I think is really important, is the summary that Jennifer provided for us at the end about the potential for CRISPR and a number of domains. And one of them that I think is particularly interesting and important is disease prevention. Now in the context of the work that I do, it's widely recognized that this goal would most effectively be pursued by using CRISPR technology to edit gametes and embryos. For a number of reasons this is controversial.

So since 2015 I and others have been arguing pretty consistently that we should not be editing human gametes and embryos, unless and until two conditions are met. Those conditions are safety and efficacy, which people might think of as the science, and then broad societal consensus, which people might think of as the ethics. That's a pretty crude description, it's not accurate in important ways because it relies on the fact value distinction, which people in philosophy like myself don't actually endorse. But let's think about this ethics framework for a minute.

Safety and efficacy, broad societal consensus. Well let me tell you this is probably one of the simplest ethics frameworks you'll ever hear about. Why? Because there's only two elements. Trust me, most ethics frameworks have a lot more than two elements! But the other thing that's actually really complex is, I would say to you that we don't actually know what either of them entail, so that makes it actually a very difficult and easily contested ethics framework. So what do I mean when I say that? Well, safety and efficacy are actually value-laden concepts. It will never be 100% safe, it will never be 100% effective or efficacious, and what that means is someone actually will have to make a decision, someday, that it's safe enough.

It's efficacious enough. We're good to go with a clinical trial. Well who gets to decide what that threshold is and when that threshold has been met? And I think in this arena we really need to think about this in the long term, as well as the short term, and how do we do that? So there's actually a lot of work to be done just around this concept of safety and efficacy. And then there's the second element, broad societal consensus, and I would say to you that that's widely misunderstood – and because it's misunderstood, it's easily contested.

So one of the things I try to emphasize is consensus is about unity not unanimity. It is not that 100% of people agree. You can have a functional consensus without that – and the most obvious and related example is the 14-day rule for human embryo research. We have had a consensus around this for nearly 40 years.

That doesn't mean that everybody agrees with it, but it is in fact what's working in the scientific community. It's under pressure, it may well change, and in the near future it may well change – but if it does, that doesn't undermine the fact that we had a consensus for some 40 years. If it's not consensus, it's not 100%, I'd also say it's not majority rule.

Why? Because in ethics we know might doesn't make right. So what I’m saying, what makes sense is to try to build together a broad societal consensus that's based on respectful dialogue, and interestingly and importantly in the context of current historical moments, a lot of this work comes from work in the 1980s by the women's encampment for peace and justice in Seneca at the army depot in the US, who were there advocating against the deployment of NATO missiles. The women who came together had to find ways to make decisions as a group and they articulated, if you will, criteria for respectful dialogue: responsibility, self-discipline, respect, cooperation, and struggle –and in my own work I've added to this inclusivity and benevolence. I unfortunately in the time I have I can't elaborate on that, but if you're interested, I would encourage you to look at my book “Altered Inheritance,” which actually tries to meaningfully unpack this. But the summary, the bottom line is a consensus is not where everyone agrees, it's not about all persons, it's about all ideas, it's about having confidence in the belief that all positions have been heard and understood before a decision gets made.

So bottom line: most scientists, and I’m sure that includes Jennifer, agree that heritable human genome editing should not proceed unless there's evidence of safety and efficacy. And I’m saying there's much more at stake than just safety and efficacy. We also have to think about broad societal consensus, and I think this commits us to public education, engagement, and empowerment – all of which are deeply embedded in the WHO guidelines in this arena. So that's kind of where I’m coming from, and with that I have a question for Jennifer as well. Jennifer and I were both on the planning committee for the 1st International Summit on Human Genome Editing in 2015, and at that time the planning committee in fact articulated this ethics framework of safety and efficacy and broad societal consensus as being the grounding for moving forward with any proposed application.

Since then, thanks to the work of a number of scientists around the world, advances in CRISPR technology have brought us closer to the day when we could consider permanently removing disease-causing genes from the human population. So I’m asking you Jennifer, if you could share with us today your current view on what it means to go ahead with heritable human genome editing for this purpose, disease prevention, and your ideas about achieving societal consensus. I think that at some point we may, as a society, decide that that the benefits outweigh the risks for some uses of human germline editing.

I don't think we're there today, and I think you articulated that very nicely, and I also want to point out for this audience that I continue to feel that the most impactful uses of CRISPR, certainly that will impact people globally, continue to be in editing somatic cells, so in individuals, as well as applications in agriculture and in the control of the spread of disease, as we heard from Professor Crisanti. So you know, I think that's an important point to make. That being said, as you just pointed out, there's a there's a very important need to be considering the other types of applications of CRISPR, including in the human germline. So I’m an advocate of continued education definitely, continued transparency on the part of scientists globally about the type of research that's going on in that area. There's a lot of, I think, intersecting technologies that are being developed right now that probably will impact the use of CRISPR in the germline in the future. For example, being able to create germ cells and to cultivate germ cells in ways that are being done increasingly in animals, not really yet in humans, but we can see that day is probably on the horizon.

So all the more important to be having the kinds of conversations that you and your colleagues are leading. Thank you very much Jennifer for the reply, and thanks Françoise for your comments. I think you know we will have the third panelist Soumya step up and give her comments, and then I think we're gonna open it up to the audience and try and, try to mix some of these ideas together. So, our next panelist is Dr Soumya Swaminathan. She became the first Chief Scientist of the World Health Organization in 2019. She has 30 years of experience in clinical care and is known internationally for her research on tuberculosis and HIV.

Her role at this new division at the WHO includes publishing norms and standards and guidelines that are about scientific excellence, about relevancy for the public, and about timely publication. This includes the WHO's Governance Framework and Recommendations on Human Genome Eediting published last year, whose development was led by Soumya. As well as a revised Guidance Framework for Testing Genetically Modified Mosquitoes, also published last year. Both very relevant to today's discussions. So, she has been quite outspoken about the need to ensure global and equitable access to the fruits of biomedical research, and so we're all very much looking forward to her thoughts and insights on exactly this issue. So Soumya, over to you for this important issue.

Thank you very much Fred and I’m delighted to be at this really very, very exciting discussion, you know following Jennifer's absolutely brilliant talk, and the other comments that we've just heard. So I think we've heard a lot about the word equity when it comes to COVID. We've talked about equity in vaccine access mostly, but also an access to diagnostics and drugs, and seen how the inequity in the access to these products has really hampered, I think, our control of the pandemic.

And this is something that WHO thinks about all the time, that we think about all the time, including things like access to insulin, which you know was a drug discovered over 100 years ago, and did not have a patent and yet people around the world today don't have access to insulin. And so when we think about these new technologies and the amazing applications that are possible, particularly with the somatic gene editing there could be immediate applications – and we already saw examples of HIV and sickle cell disease and other genetic diseases, where you can actually cure people, and, and save them from suffering. But we also know that the burden of these diseases is quite often in low and low middle income countries, and therefore we need to start thinking about access. Equitable access right from the beginning, because we've seen far too many examples of the world developing treatments which are then only accessible to a few and particularly to those who can afford them.

So we need, I think thinking about these things right from the outset and particularly the scientific community advocates for this, and finds the solutions then it will be possible, I think that there shouldn't be insurmountable barriers to, to addressing this. And particularly I think when we talk about diseases like sickle cell disease, we know the burden is very high in sub-Saharan Africa, and we really need to ensure that if a cure can be developed that it be accessible to people there. I just want to switch for a minute to the committee that was set up, and that deliberated for 2 years, and Françoise was a member of that committee, to make recommendations on the regulatory and governance considerations and the oversight mechanisms for human genome editing. And the committee focused mainly on somatic, but at the same time you know the statements that were put out by several organizations and including the DG of the WHO clearly said we're not at the point where we can do, or anyone should be doing, experiments on human germline editing that lead to pregnancies.

And so there was a sort of agreed moratorium on that, but this obviously needs to be revisited from time to time to see where we are progressing with the safety and efficacy as mentioned. But on the somatic gene editing there were a number of recommendations made including that WHO should set up a registry, so we actually have a registry now with 130 or so clinical trials registered. We don't yet have a registry for the basic and pre-clinical work on gene editing – that might be something that another organization takes on. There was recommendations on why countries need to develop policies. Yes sometimes laws and why regulatory agencies around the world need to work together and with the WHO, as we've done very effectively for COVID, on aligning on the kind of regulatory mechanisms that need to be put in place. We've seen a lot of unethical work going on, particularly around medical tourism and advertisement of cures which really don't have much of an evidence base, and it is big business around the world, and therefore I think countries also need to pay attention and not allow these, you know tourism-related treatments of unproven remedies to continue without putting in place strong local laws and and regulatory mechanisms.

We also need a mechanism I think globally for stakeholders – or anyone to really – to flag unethical or unsafe research that may be going on that they've heard about, and we will convene an expert group soon to think about what that mechanism could be, should it be WHO that receives those types of complaints, or, and it has to be obviously handled with a lot of sensitivity. We have issues around intellectual property, and again I think the parallels with COVID where many people have – including the WHO – have been calling for sharing of know-how, sharing of technology, making sure that we are also transferring technology to countries and building that capacity to make these products in the countries where it's really going to be needed. So I think addressing that with obviously agencies like WTO and WIPO, where these discussions take place, but I think scientists have an important role to play here in advocacy. And then finally they made a very strong pitch for education, for training, for empowerment, for involving civil society and others, patient groups in these discussions –which need to happen at the regional level, at the national level, really addressing their own local research priorities.

So finally, I'd like to say that we have set up a Science Council, this was you know something that followed the creation of the science division in the WHO, with a goal of looking ahead exactly at emerging technologies that can have big impacts on public health. On the one hand we know that to have that impact, you need wide access to the new technology and on the other hand you also need to be prepared to mitigate any risks that might arise from the use of these technologies, either those which can be predicted or those can which cannot be anticipated. And the first report of the Science Council happily is going to be on genomics, looking at all aspects and telling countries why it's important to invest in genomic technology today.

You know everything from surveillance of pathogens, all the way to the kind of treatments and prevention of disease that that we heard about. And so that report I think is very timely, it should be out in the next couple of months and hopefully that will also help to advance the discussions that that have been happening globally. In terms of the question that I have it's, it's also related to equity, and the use of this technology: what should we be focusing on, you know given that this is such a powerful technology that can be used in in human health basically is what I want to focus on, but clearly in agriculture as well which impacts human health through nutrition. But just if we stick with the health aspects, what should we be focusing on now to ensure that we can have as equitable access as possible to the fruits of this emerging this new technology.

And I think that will also have an influence on other emerging technologies that are bound to come in the future. Thank you. Right, first of all I want to thank you for your work at the World Health Organization. It's been really exciting to see the development of the international forum, the report that is out already, and the one that you referenced that will appear shortly. So thank you for that. I also think that like you, that for CRISPR to have real impact around the world rather than just affecting a few individuals, we do need to be focusing on ways to ensure that there is going to be broad access to it.

How do we do that is a big challenge! At my organization, the Innovative Genomics Institute, we're a non-profit, and our major reason for being is, is really to try to achieve this. So we have projects focused in health care and in climate change, both with an eye towards ensuring widespread international access in the future. So I'll give you just one example, and that is that I’m very proud that we're the only non-profit that I’m aware of that's running a clinical trial with CRISPR. So we have an ongoing phase one trial to treat patients with sickle cell disease.

It's a three-way collaboration between the three campuses of the University of California, Berkeley, San Francisco and UCLA, and the purpose of that trial, so there are other trials being conducted already with the commercial organizations, but in the example I showed you with Victoria Gray in particular, that treatment costs close to 2 million dollars a patient right now. So if we want that type of therapy to be available widely, of course the cost needs to come down dramatically. So we're taking a two-pronged approach – we have our trial running, which will allow us to work directly with patients and de-risk a particular approach with CRISPR that we've developed at the institute that we can then partner with commercial organizations from a position of, we hope, technological advance, and work with them to have a tiered structure for pricing. And then the other thing that we're doing, of course, is to focus on the technology of delivery, because having an approach that avoids the need to conduct a bone marrow transplant for each patient, for example, would definitely be broadly enabling and would reduce cost as well. So that that's one example, but we have other initiatives in the climate area that also involve partnering internationally and working directly with farmers so that we can ensure that they have the knowledge about what CRISPR is and what it can do, and secondly that they can actually be working on applications that make sense, depending on where they're located around the world. The light motif that keeps on coming up has to do with education, you know educating the public and to what extent is that a blocker for broad access? Is something just as simple as the public understanding what's happening? I mean it ties back to Françoise's consensus question, but I don't know, to me, is that really a major blocker? Is that comparable with the technology? The technological sort of the delivery, let's say aspects, is it possible to weigh these things at some point? OKI can start Fred, I think that the major block really is the technology, and I think the cost of the technology, as Jennifer pointed out.

I mean if you look at sequencing of the SARS-CoV-2, when you look at a world map, you find that there are huge areas that are gray, and it's because they don't have the capacity to do sequencing, and now I think countries have started investing because they see how critical it was to really monitor the course of the pandemic and to track the virus. And that's one of the, hopefully, the outputs of this genomics report that the Science Council will really make a case for investing in this, but we need a good economics case. But on the other hand I think the public education is so critical, because particularly we've seen now with the misinformation that circulates, especially on social media, that can highlight absolutely falsehoods and spread myths and rumors – and that's why it's so important I think for scientists and scientific organizations to engage – and I love the idea of your, the journal for children. We have to start with science literacy for children, and young people, but I don't think that would be the major barrier just now for access. I think it's the technology, the training, the know-how, and of course the infrastructure and the funds available to run this kind of program. If I can maybe just expand on that briefly, I think one of the things that's important both in my work individually as an academic, but in the WHO report, is this commitment to education engagement and empowerment, and I think what's important about that locution is that it's not just education in terms of starting with the knowledge deficit model – with the idea that people don't understand, and that's why they aren't as enthusiastic as we think they should be.

Education is really important in terms of making sure that people understand the science, but the goals and the objectives – and I think most people are motivated by really good goals and objectives. But I think what's important is moving from education to engagement and seeing that people outside the scientific community also have things to contribute to that process –and that's what you're starting to see with citizen juries, democratic conversations, and it's not just what knowledge does the scientific community have but what knowledge does civil society have that they can contribute. And part of that contribution is to the priority setting and I think that's what's really important because if you want to get to the priorities that WHO has as its core mandate, things like equity and access, you have to get to the point of empowerment where society can tell you "these are the things we need in terms of being able to really have a flourishing community." Thank you Françoise and I just wanted 30 seconds back to Andrea just on this on the same theme. How were the local populations informed about your experiments in Burkina Faso? Did you engage with them? Yes and this has been a priority of the project, actually, this is one of the major activity of the project – outreaching and communication.

So we have done this at different a different level. We have done on the people on the field, so we have translated all the material in local language, we involved with a chief administrator there, and we also with the help of the scientists there we also have approach political authorities. So I mean in principle you have to have a bottom-up and a top-down approach, otherwise it doesn't work.

So in principle and of course we made sure that the scientists on the field were really the champion, they were motivated and they have the capability to and the credibility like the scientific credibility, and the integrity ability to deliver the message. I mean that's the most important thing – the trust is really the currency that makes the things moving. Thanks Andrea, and just Jennifer do you want to just sort of wrap it up with before we we have a whole series of questions coming from the floor? So I want to make sure we have time for that but maybe you can just sort of give your, a final round of comments on what's just been said? I think that the science is going moving very quickly, it goes, seems to go faster all the time. I personally think as a scientist that the work that you just heard about and you know thinking about access is probably, you know, dating right now, it's not really going to be the science. So I think it's incredibly important to be thinking about how we're going to disseminate this technology safely.

How we select the right applications, as Françoise has talked about, and then of course how it gets regulated, and how resources are applied over time. So I really am grateful for all of the work that we heard about just now. Thank you, thank you so much. So without any further ado, let's just jump right to the questions from the floor. The questions are open to any of the panelists, or to Jennifer. I would like to ask Laure Marignol to step up and take the microphone please, and ask the first question.

My name is Laure Marignol and I’m in Trinity College, Dublin in Ireland, and I’m a radiation biologist and I had a great interest in CRISPR, because of the ability to generate double strand breaks. And my question is for you Professor Doudna is, how do you address the specificity of a strategy, or how do you make sure that you only edit these cells, if your target sequence is common to disease and non-disease cells –and in particular I come from a cancer biology background. So my question is, do you solely rely on the delivery agent, or are there anything that you can maybe suggest that can be tweaked in a system to perhaps address this tumor specificity? Thank you. Thank you for the question. You mentioned the delivery strategy, so that's one certainly one approach, is attempting to get the editors into just the tumor cells, for example.

But there are some other really clever ideas that people are exploring. For example, using proteins that control the activity of CRISPR Cas enzymes and some of these are made naturally in bacteria and even in bacteriophage, you know the viruses that infect bacteria. So these are called anti-CRISPRs and there's been an effort to deploy them and use them as regulators of CRISPR Cas proteins. So that would be one idea for ensuring, you know, some kind of a cell type selective activity or being able to turn off the activity of CRISPR Cas proteins in particular cell types. Again, that just maybe just pushes off the challenge of getting the regulatory protein into the cells where you need it, but again you know that this is something that can be done in some cases at least with viruses that have selectivity for particular tissue types.

And then there's also the approach of in cancer, which I think is very interesting, is actually looking at cancer specific DNA, you know, sequences that are found uniquely in cancer cells whether they are highly amplified, you know, sequences, there are these circular RNAs that get made at least in some tumor types. So there's a number of people that I’m aware of in the academic world who are looking into that type of approach for ensuring selectivity of cancer based targeting with CRISPR. Thank you very much. Thank you so thank you Laure, thank you Jennifer, and I think what we'll do now is, I see that Sangwon has his hand up… So we have been talking mainly about the health problem the disease prevention and agricultural productivity for the use of CRISPR applications, but I would like to kind of broaden this up to you know slightly different topic and see how you know we perceive this as an issue.

So increasingly more, we are realizing that the all the good things, not the good things, and the ugly that humans are committing to one another, and to the environment are not only about our knowledge institution or technology, or the lack of them, but more fundamentally about human conditions. So you know our nature and the behavior derived from it. So for the sake of an argument, I’m not necessarily advocating or not you know opposing to something, but for the sake of an argument let's say that there is a particular human behavior that puts the humanity and its sustainability into a grim danger. So be that an extremely aggression violence, a desire for expansion, or destruction now, you name it and suppose that we scientists found the linkage between the particular behavior and the gene expression. In that case, can or should we consider using CRISPR to induce positive social changes or prevent a catastrophe, and if that's the case how the society can come up with a collective decision on what can be changed or what cannot be changed? I know that this can be a, you know, kind of worm, but I think for the sake of our argument I'd like to kind of pose this question to Jennifer.

Thank you. Well, I’m actually very curious to hear what my colleagues would say to that, as again speaking scientifically I can tell you that what you propose is clearly very solidly in the realm of, of science fiction right now, because we know that behavioral traits in animals and certainly in humans are multi-genic and probably involve hundreds of genes, with a lot of environmental influence that we don't understand yet. So I think you know it's it's, it's really clearly a your question is, is really a theoretical question. I’m curious about, about what Françoise and Soumya would, would say to that. Well, from an ethics point of view we always think it's important to exercise the moral imagination, and so I want to start by you know emphasizing what Jennifer's just said that we really anticipate that this is something very far-fetched, in terms of what might be possible, partly because it's not just one gene but also because the kinds of traits you're alluding to are very complex.

But having said that, I think one of the things that would be very important if we were to engage in this sort of science fiction, is that it's relatively easy to imagine scenarios where we would say well look, you know what, humans keep waging war. It's a pretty stupid thing to do. We haven't seen to be able to stop this through things like education, so why don't we find the gene for anger and aggression and you know edit that out and in the abstract that sounds laudable, but I think what's really important to appreciate is that we don't actually necessarily imagine that that's the way in which any activity, any behavior is actually determined. And I think that that's one of the things that these behaviors point to, that it's also environmental and we don't talk a lot when we talk about CRISPR, and I’m guilty of it too, we don't talk as much as we should about gene environment interaction that gets us into these sort of thorny places, and I think that that is really important. But I also want to highlight that this kind of imagining for many of us brings up the specter of eugenics, and here all I want to say is that we have to understand that goals and objectives are again value laden and what one person thinks is a positive change, other people might think is a negative change, and we're already seeing in the context of things that seem to fall under the sort of treatment and disease category a fair bit of tension and disagreement.

And one of the examples that's often brought to the fore is that of eliminating deafness, and the deaf community is quite adamant about the fact that we don't see this as a disease or a limitation we see this as a very rich community, and part of the reason I use that example is that we do have a scientist, Dennis Replicov in Russia, who has said that he's ready to go. That he has a number of couples who are interested in using this technology in order to ensure that they would not have a hearing-impaired child. And so I think in that context as we get from the science fiction to closer to reality you can already see how it raises a lot of concerns about what are legitimate priorities, whose understanding of disease, or a negative or a positive trait counts, and would direct you know decision making. And that's why I think it's the priority setting, it's the values that ultimately are going to make or break this technology.

I have all the confidence in the world that scientists will do great things, but what will we as a people do with this capacity. Thank you so much Françoise, I think that was an ex exhaustive answer to the question, and so I think we're gonna move right on to the next. We have a long list of people - we'll try to get in two or three more questions before we be before we close today. There's another question that's come up from Mukteswar Mothadaka.

My question is antimicrobial resistance is a serious problem, so using CRISPR how we're gonna tackle it? Well, CRISPR is naturally in found in bacteria of course, and, and utilized there as an immune system so you know, on the one hand it has promise I think for controlling infectious disease, on the other hand a challenge there is that and this we see this in our you know in in the in the research that's been done on CRISPR systems is that they evolve rapidly, and that that reflects the fact that they're you know they're, they're constantly having to, you know, address they're constantly evolving to deal with the evolution of viruses as well. So I think that's that's going to be a challenge in applying them in for human infectious disease. I personally think that probably the more fruitful direction there is using them as a diagnostic, where I have a lot of hope that they will be effective as a point of care diagnostic that can quickly detect and report on the presence of an infectious agent. We're going to take one more question and I’m looking on the list.

I think Sotorios, Sotirios Zarogiannis are you still with us? My question is a bit more interstellar I'd say. So are you aware of any experiments taking place, since so many expeditions are planned for space and colonization of other planets. So I think if CRISPR Cas technology is stable in space, then that can be a catalyst for speeding up adaptation of plants and humans in in other planets.

So are you aware of any experiments in NASA, European Space agency or the international space station, using Cas in order to see how it performs? Thank you. Thank you for the question I’m not aware of such experiments, but I think you're right, that I've certainly heard conversation about, about that application of CRISPR. That as human beings increasingly want to explore off of our planet that it will be necessary to have a technology that enables more rapid adaptation to those new environments and CRISPR could provide that for sure. Thank you. I think what we're going to do is we've gotten to the end of the session thank you so much to the panelists, to Andreas, Soumya and Françoise. Thank you very much to to Jennifer for for her talk, and thank you for all the people who raised questions and contributed to the show this afternoon.

And thanks everyone who attended. I hope you enjoyed the session we will keep you informed about the next Frontiers Forum session. So keep an eye out for more information, which will be coming soon.

So until we gather again for the next Forum, a warm goodbye to you all and thank you so very much for being here today. Thank you very much. Thank you. Thank you very much.

2022-05-27 07:06

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