Jennifer Kuzma Interview Transcript

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Bruce McCabe: Welcome, Jennifer Kuzma, to FutureBites, my little podcast …

Jennifer Kuzma: Thank you.

BM: … and a way of exploring the future with luminaries such as yourself. Let me do a brief intro. You're a distinguished professor in social sciences, and you're a co-director of the Genetic Engineering and Society Center at NC State, that gorgeous University that I just visited not so long ago. And you've been there 10 years, something like 10 years?

JK: Yeah, almost 10 years, correct.

BM: Alright.

JK: I was at the University in Minnesota before that.

BM: And is that equally beautiful in Minnesota?

JK: Of course, it gets cold in the winter, but it's very beautiful.

BM: We could start some sort of dispute up right now by doing that. Okay, so I look at your amazing bio and you've been into this area of ethics and governance, particularly around the biotech industry for a long time, you've been commenting quite prolifically, which is how I found you and spotted you when I was coming to NC State. But I'd love to get a little bit of insight into just how you ended up on that governance side of things, the responsibility side of things, because you got all these distinguished awards for your Social Science and your research, and now you've jumped into, in my view, one of the hardest areas, one of the most important areas, but also one of the hardest areas. How do we actually impose some responsibility on this space? [chuckle]

JK: Absolutely. Well, I had always been interested in science as a teenager and a young college student, but I also had a lot of broader interests about how science interacts with society. And just at the time I was in college where really when the first genetically engineered organisms were coming to be. And it fascinated... I also had a minor in philosophy at the time, so it kind of...

BM: Oh, really?

JK: Yeah, so questions about whether we should genetically engineer the natural world and how we should and the ethics of it, always really intrigued me, but I ended up getting... My dirty little secret is that even though I'm a distinguished professor in the social sciences, my PhD and my degree, formal training is, in biochemistry and molecular biology. So I spent a long while in the lab working ironically on ... My very first project in graduate school was on the ice-nucleating bacteria, which was the first genetically engineered organisms proposed for field releases. And so I was very fascinated by how these bacteria could... The displacement of them could potentially prevent frost damage on plants by using genetic engineering. And so I spent some time in the lab doing biochemistry work on, not only ice-nucleating bacteria, but plants that emit isoprene. I ended up getting a patent on the discovery of isoprene emission from bacteria, which was then licensed to make rubber out of a bacterial source of isoprene instead of cracking petroleum.

But to make a really long story fairly short, I actually am not a very detail-oriented person. And so the lab work, although I totally admire people who can do it, the very narrow focus on one gene or one pathway or one problem was not for me. And so I started looking for alternative careers and sort of really stumbled into the world of science and technology policy, which I didn't even know really existed before I stumbled into it.

BM: Yeah, interesting. And this philosophy side is really interesting. My personal experience was similar in that I did a science undergrad degree with Computer Science, as major in physics, and other things. But I ended up, just to fill in enough units to get my degree, I did a subject called the History and Philosophy of Science, and it turned out...

JK: Yeah, wonderful.

BM: To be the subject I learned more... I learned more in this subject, which is worth like half points in my degree, more in that than I think, every other subject combined. It was most wonderful. It's the most wonderful broader set of learnings about the place of science, the weaknesses and strengths, and the evolving Philosophy of Science, and therefore the fallibility of our observation and all that. So, it's really, really important. And probably...

JK: Absolutely.

BM: Just by luck, I strayed into that as well, so maybe that's why I'm talking about the future and you're talking about governance now. [laughter]

JK: Maybe maybe. And I think... And I'm really proud, I don't know if we'll get to this at some point, but I'm very proud of the programs that we built here at our center at NC State, because what we're trying to do is train these graduate students and undergrads to a certain extent, we have more grants on the graduate training side, in this kind of interdisciplinary space, bringing together the natural and the Social Sciences and Humanities to think about these issues.

BM: Yeah, well, I definitely want to talk about that. And I want to talk to you a little bit about priorities first, because it seems like this is a monumental space in terms of the challenges of imposing... Or not imposing, maybe a strong word, but getting governance into this and responsibility into this. And so I'd like to talk a little bit about that first, and then maybe move into what we can do and what you're doing. And I'm sure what you're doing will also act as an example to others as well, what you're learning and what you're trying to do. Because policy, and actually directly writing government policy, there's so many things you're doing or have tried to do. But before we get to that, yeah, priorities. Because I look at the conversations I had with one of your colleagues, Rodolphe Barrangou, about food editing, amazing person. There's everything going on, of course, in medicine, all the debates around germline editing, and then there's gene drives to eradicate parasites. [chuckle]

JK: Absolutely.

BM: And so it's everywhere. CRISPR as an instrument, as a technology is... If you had to name just three technologies, for example, the top three changing the world, it would be one of them, there's no question about it.

JK: Yeah, I agree.

BM: Yeah, what do you think are the most urgent priorities?

JK: Yeah, well, and this involves governance as well, governance isn't just all about safety and top-down regulation, but also how do we direct our resources to the most pressing societal needs. And my personal... I think, obviously, climate change mitigation is high on the list. Prevention and mitigation. And unfortunately, there's not top dollars often going to that. And so, generally, you'll see that these emerging technologies are often directed towards... I don't want to say extremely important diseases, but they're diseases that we care about in the US and Europe and so forth, like cancer and obesity and diabetes and things like that. Very important to find solutions to that, but that's where a lot of top dollars go, to begin with. So my preference would be, how do we see this technology directed towards things that receive less funding proportionately, like climate change and public health, pandemics, of course. And not only pandemics in the US, but elsewhere. So I do think some of the gene drive community, and maybe we'll get into that later, but I do think that the focus on mosquito-borne diseases from a public health perspective is a pretty appropriate focus.

I also think that some of what the gene drive community is doing in the area of conservation biology and the potential protection of endangered species is also a high priority. So those would be my... I would like to see governance systems not only talk about regulation and safety, but also how best to steer the technologies in the absence of... I guess in the absence of a market, a free market that's going to choose those directions, how do we create a governance system that can help society direct resources towards those problems? Because capitalism and the market isn't going to cut it in some ways.

BM: Well, this is already interesting, because I was expecting you to dig into the dangers and the governance around protecting ourselves from some of the mis-management of the diseases, but you're already talking about really the governance of where we direct resources and how we should prioritize our effort. And Rodolphe was particularly strong on that as well. He pointed out to me, it was a very interesting lesson, if we look at all the biomass on planet earth, 90% of people working at CRISPR are working on human editing, which is really wonderful. They're going to save perhaps 100,000 lives or whatever the numbers are, and yet the vast preponderance of biomass is out there in plant matter. If we get that right, we can save many billions of lives and certainly improve the prospects for many billions of lives in future. So, it was a completely disproportionate allocation of effort. [chuckle]

JK: Yeah, I think we agree on that part. In fact, we wrote an article in 2014 before gene editing was really even being called gene editing. Actually wrote it probably a bit earlier than that, I think it was published in 2013, so we probably wrote it in 2011, 2012, where we did an analysis of all the articles and we called it targeted genetic modification at the time, because CRISPR wasn't really even around, but these TALEN-based gene editing and zinc-finger based gene editing was starting to merge. And we did an analysis of the funding and the research portfolio, bibliometric, mining, text-mining analysis, and kind of showed how all these projects were starting to go towards these major Western, if you will, diseases, and how there was a need to steer them in the direction. So that was 20 years ago or 10 years ago. Yeah, so I couldn't agree with him more that we could use a lot more resources and energy directed towards climate change and public health crises.

BM: And what about the, I guess the dangers that come up? Every time I give a talk about CRISPR, my focus as a futurist is trying to show people better pathways to the future, where are the opportunities, so I'm very positive and I'm always opening people up. And it might be the food industry, or it might be a healthcare conference, and I'll be saying, "Well, here's 15 opportunities perhaps you haven't even thought about yet. But it's all about the opportunities. We all get excited together, but whenever we get to the questions, of course, people start talking about dangers and they talk about edits that... inadvertent edits, for example. We all get on to germline editing and what happened in China with He Jiankui going ahead and editing some human babies and making that heritable. And in the natural world, when we talk about plants and crops, the thing that comes up is very much the same stuff that came up with GMO the first time around. People worry about, "Well, hang on, what if we're changing the natural balance of things in nature? What if one species ends up taking over another?" Maybe there are unintended consequences. What are the things that worry you most? What you think, again, we need to most work on in those areas? Do you have a priority list?

JK: Well, I think there are several types of risks that one can think about either with GMOs or gene editing. The question that always comes up is, are they any more concerned with those technologies versus conventional breeding? And I'm not sure. I think it depends on the traits, it depends on the context. But some of the types of risks are things like you mentioned, these off-target edits that sometimes will occur with whatever kind of gene editing you're using. Where you can't be assured that you're not raising the levels of an endogenous allergen or toxicant in the plant or the animal. And then whether or not that's safe for someone who consumes it, whether it's a human or another species in the environment. With things like biological introductions, we always have to be careful if we're adding an organism with a gene drive in the environment, in the open ecosystems, that we can actually make sure that we have an ability to control it or recall it, because there have been a number of biological control introductions that have gone awry when we've tried to use biological... There have been many that have been very successful with sterile insect technology and screwworm, that's been very successful for the eradication.

But there are some that have really gone awry. And so I think my biggest concern is not necessarily on any of those individual risks, but do we have a system in place that respects those kinds of things that we should be looking out for? Do we have the ability to reverse it or recall it? And can we tamper down the techno-optimism and take some of these concerns seriously? I think the biggest danger is kind of our fragmented regulatory and governance system, and that there's not one place where we're looking at these technologies holistically in an ecosystem context.

So regulatory agencies tend to have authority for very few direct risks, like the FDA will screen for toxins or allergens, the EPA will look at non-target effects for pesticides, the USDA will look at plant in Agricultural Health. But who's looking at kind of the ecosystem scale effects on biodiversity on whether we're increasing or decreasing land use or water use, and whether or not some of these technologies may go awry in a broader ecosystem sense, and that's where we're missing that. And we don't also have a place to compare them to the non-engineered version. And we don't have really good risk science developed in order to do that. How do we move from a smaller scale field release of a gene drive to a medium scale release, to a large release, and right now with gene drives, most of our regulations are set up to confine or contain GMOs. With gene drives, really the purpose is to do quite the opposite and to get it to spread, get the gene drive organism to spread that gene drive system throughout the population, and that might cause the population to crash or it might immunize it, or what have you.

But you're moving from more of a laboratory scale to almost a full release, if you're talking about a gene drive. So in that case, I think we need to be a bit more precautious about really looking at all these potential risk pathways, if you will, prior to release. So I guess I'm not overly scared or concerned about any particular individual risk but just that we don't have a really good comprehensive system in place.

BM: Interesting, and if...

JK: And that the market, all the incentives and all the political power is all targeted towards a techno-optimist mindset, and so that's what scares me most is that it's not a very popular place to talk about governance of genetic engineering or gene editing. You're not usually the most popular person in the crowd when you go to these scientific meetings, and so I think a healthy respect for what could go wrong is something that would be nice to see in a comprehensive place to look at it holistically.

BM: We want techno-realism, don't we? We don't want...

JK: Yeah techno-realism, right. Because the public. [overlapping conversation] Yeah, go ahead, I'm sorry.

BM: No, no, I was just going to say, I often encounter techno-pessimism as well, not in the business community necessarily, but just especially around AI and CRISPR, you come across individual people who have been worried to death about everything, and so you do get the opposite too, but we should always be trying to train ourselves to be realistic and not let the emotions run away on the other side.

JK: Yeah, yeah. The techno-pessimism is interesting, you do hear it pop up, but in the technology governance space, I don't think that's the particular group that has either the political or economic power, so although it has maybe a populist power, it's not necessarily the ones that have the political or economic power, so.

BM: That's really, really important actually, when you say that. I like that very much because in terms of affecting change going forward. .. Yes, it's Silicon Valley driving things, it's the biotech players driving things, it's the connections between them and government, which drives change, whereas the individuals who are fretting about it at home, feel rather powerless and disengaged. Yeah.

JK: And if you study the dynamics of that, sometimes they have to swing in such a polarizing position, sometimes they have to take that just to counteract the forces on the other side, and so they have to use things like the media or social media in order to change the policy process, because that's where... That's the only place where their power lies, and so sometimes they'll take more extreme positions than may even want to, in order to counteract with the other side. So I'm not often a fan of calling those people luddites or they just don't get the science. I think that they have real concerns and in some cases, yeah, their job is to swing in the other direction in order to counteract some of the other forces that are occurring. Yeah.

BM: Yep, yeah. Yes, I one-hundred percent agree. And just rewinding, there's quite a few points out of what you've said that I want to explore a bit more. When you talk about this fragmented governance landscape, what are we pointing towards there? Say the federal level, it would be nice to have a central organization or a central way to point to that crosses healthcare, agriculture, all of those sorts of things, that's kind of the nirvana here? What that be much better?

JK: Well, I think that may be the case. To get into the weeds, we've been formally regulating biotechnology under something called the Coordinated Framework for the Regulation of Biotechnology, which was put in place in the mid '80s when the ice-minus kind of tested that framework for the first time. And what it did is it assigned the federal agencies, it didn't create any new laws, and it said, Let's use existing old laws in order to regulate the products of biotechnology. So for example, genetically engineered animals are regulated as new animal drugs by the FDA. So you're fitting a genetically engineered animal into an old statute that is a drug statute. And because the idea was that the gene changes the physiology of the animal, so therefore it acts like a drug, and so... But it's a bit of a mismatch when you're talking about regulating an animal as a drug, but yet that animal might be released into the environment. Does FDA really have the environmental scientists, the ecosystem thinkers there in order to capture those issues? And then the two main things you're looking at, at drugs, is safety to the animal and efficacy.

And those are the two main regulatory hooks that the FDA has. Whereas the most appropriate hooks for a genetically modified fish or a genetically modified insect would not... You wouldn't necessarily be that concerned about the safety to the animal, especially if it's... Well, in the case of mammals and fish, probably, but in the case of insects, you're actually looking to kill the insect sometimes. And the efficacy is important, but that's usually something industry is going to test prior to bringing it to the FDA, so we kind of have... In some cases, not all, but in some cases, we have a mismatch between the actual regulation that we're using and the risk that we care about, in some cases, risks are... Certain risks are falling through the gaps because of these various jurisdictions, and in other cases, in other cases, some products are over-covered, like there's two agencies looking at them when maybe there doesn't need to be. So we've taken up some of these issues. The National Academy sciences has written reports on this. I was a member of one of the committees, and I think it at the very least, we should get all the agencies coordinating on some of these products that are highly novel, highly complicated, and where the statute doesn't necessarily fit the actual product very well. So that's sort of what I'm talking about.

The case with genetically engineered plants is also interesting because USDA was given primary authority for them under the Plant Pest Act or Plant Protection Act. So the main risk that USDA looks at is how well a genetically engineered plant harm other plants. How can it be a plant pest? And so for a while, we were engineering genetically engineered plants with Agrobacterium, which you used to use it as a tumor causing bacteria, and you used to use that to insert genes into the plant. And so it was a plant pest. And so because there were little tiny pieces of genes that ended up in the genetically engineered plants from this Agrobacterium, that was their regulatory flow. So then when people started using gene editing, they were no longer using Agrobacterium sequences.

And so there were dozens, and I think it ended up being about 100 kind of gene edited plants or ones that didn't use Agrobacterium anymore that were largely exempt from regulation on the USDA side because they didn't contain plant pest sequences. And so that was a case where there might have been a gap in regulation, at least from 2010 to 2020. Well, the law has changed since then, but there was a period of about 10 years where these products would not undergo USDA oversight because of that antiquated regulatory book, 'The Plant Pesticides'. So, that might have been getting too much in the weeds for this conversation, but it's interesting, in some cases, these older laws don't really fit the technology, and the governance system doesn't keep pace very well with the pace of the technology.

BM: Well, you use the word ecosystem and you really open my eyes with that word, because as you're going through those examples, the complexities, you quickly start to appreciate all the complexities and all the nuances, there are so many. So in a sense, everyone has taken a narrow focus because that's the historical trajectory. And that's no longer good enough, because we're in an area of biotech where the impact or potential ramifications are far broader than these narrow focuses on safety or medicinal sort of approvals ... They just keep going, they’re much bigger. Do you think... It's so hard in government to get all the people with the right talent and skills and convince them to work in government as opposed to private sector. Do we have enough of those skills or are there... Is this sort of a bit of a danger now with just not having the appreciation within government, or not having the capacity to appreciate, or do they have the right people inside the system?

JK: I think there are many of the right people inside the system, I do think that there's always been a lack of capacity, and again, one of the National Academies Reports I was part of did try to account for what are the capacities and how could they be bolstered in government regulatory agencies for sure. But I wouldn't say it's the people who lack the expertise, I think it's the numbers and the resources. The people I know in government are very savvy about these issues, and they're often the experts, because I've worked in government a little bit... It was a long time ago, but I've since worked with a lot of regulatory agency folks, and they know their stuff. I don't think that's the problem. I think the problem is that they're constrained by resources, but they're also constrained by legal authorities. They can't take on a scope that's bigger than their authority, they can't step out of their boundaries. Congress will eventually get word of it, and is kind of interesting, because every time that... In fact, this USDA regulation was contested in the late 2000s, early 2010s. And Congress put a lot of pressure on them saying, "Well, how can you even regulate these at all, because you have this plant pest statute, it doesn't make any sense why you're regulating biotech crops under this."

And so whenever regulatory agencies try to go, even use some authority or go beyond it, you'll have industry groups contacting Congress, lobbying Congress and say, "Hey, put some constraints on these regulatory folks." Right, so there's that cycle that... So they're always kept in check by Congress and by the interests out there. So they try to do the best they can. I do think they could use more resources. But I really respect the expertise of our people who work in a federal government.

BM: Yeah. Totally get it. And when I look at... Are there any international exemplars of what we could do in terms of governance, because, I mean, look at the EU and it's almost the opposite. They've really, really constrained the level of innovation there and the possibility... And I don't know. Or maybe there are models within the EU? Have you seen someone doing it really well?

JK: Well, yeah, I actually think in a lot of ways, Australia's had a permissive approach to biotechnology, but yet they have a more concentrated regulatory authority. They have a specific act for genetic technology, they have really good risk assessment capacity there in Australia. I've seen a lot of nice things come out of C-S-I-R-O, CSIRO or whatever you guys say it. As far as...

BM: We sometimes say it ‘sci-ro.’ But CSIRO is perfectly good, yeah. [laughter]

JK: Are you Australian?

BM: I am Australian.

JK: Yeah, okay. I was just picking that up with the accent. So I've seen some nice things on the risk assessment side come out of there, and they've been permissive, but yet I've seen some nice governance there. Now, this is on a... Some people might argue with this because Norway is not a big player in at least the plant biotech space, but I really like... Some of their statutes are, there's a mandate to consider the broader socio-economic and ecosystem risks, so they have some nice language in there where they have to engage the public and consider social, economic and ecosystem parameters when it comes to genetic technologies. So I think there's some good things going on there. I think that some of the countries that are members of the Convention on Biological Diversity, the biosafety protocol, like in Latin America, have set up systems where there's a particular biosafety law. And so they still have plenty of biotech products out there, like Brazil, for example, but yet they have a particular biosafety law and pathway where you can consider some of these broader ecosystem concerns. So I think there are some examples out there. I don't think the USA is doing a horrible job. We've managed to avert major health concerns or major ecological concerns from GMOs in the first 30 or so years that we've done this. But I do think that there's room for improvement here.

BM: Yeah, for sure. Well, it's a very complex environment in the US, and you're sitting on the greatest innovation engine in the world, which is a great force to be reckoned with in its own right.

JK: I mean, I would like us to be a member of the Convention on Biological Diversity. I think we're one of the few countries that hasn't ratified it, and a member of the Biosafety protocol, the Cartagena Protocol on Biosafety, because that's where a lot of these international negotiations on how we deal with gene-drives in synthetic biology and GMOs are taking place. However, the US, that particular convention or protocol, the biosafety protocol has used the word precaution a little bit too much for the US's liking. It's imperfect as well, in the way that things get negotiated there, imperfect, but I would like us to at least be a part of that, and you're part of the international community when it comes to these things.

BM: Yeah, well, international... And one of the questions I want to ask you, it's always so hard, but when you're trying to do this, talk about herding cats, when you try and do this across Japan, China, the EU, the US, and ultimately, if it does go wrong somewhere it goes wrong for all of us. So it's one of those classic things like climate mitigation, and climate action. It's just so horrendously difficult, which is why it's so important and why you are so important at what you're doing.

JK: And I think especially with gene drives and wide scale ecosystem releases of genetically engineered organisms, they're not going to stay in a particular country, they're going to move across borders. And so I think it's especially important. And a pest... Let's say you're using a gene drive to get rid of a past in one area that could be an important species in another area, you just... You've got these cultural differences, right. And so I think those need to be respected and the UN... This Biosafety Protocol, the Nagoya Protocol, the liability and redress, these are important frameworks that I think we need to be engaging in. And they may be imperfect, but it's what we got right now, so.

BM: Yeah, yeah, so another thing I really want to ask you was examples of where it has gone wrong. As I dig around in the food industry, we're editing fish to make them more resistant to diseases in fish farming. We're doing trees, we're doing crops. Now, the great fear is something that perhaps gets out of the box and impacts other organisms, species, ecosystems beyond expectations, unexpected consequences. Are there any significant examples that we can point to and learn from and read up on?

JK: Well, I think one that illustrates the point that I was saying about taking in these broader ecosystem concerns is really the herbicide tolerant crops. And so those were approved in the US, and they are virtually almost completely penetrated corn, soybean, cotton herbicide tolerant traits, genetically engineered or now gene edited traits. So that led to a lot of the use of Roundup, which is the companion herbicide. So you made the crop resistant to that herbicide using genetic engineering, and then you sold the herbicide with it. Now, Roundup was a safer herbicide than many others, so at the time, it kind of made sense. But if you look at the data on that, there's really the growing use of that herbicide. And now, we're starting to see a bunch of different weed species resistant to Roundup or glyphosate. And now, we're having to use even more potent, dangerous herbicides in order to get rid of the weeds that became resistant to Roundup.

JK: And so there was an overuse of the genetically engineered crops that were resistant to it, and therefore an overuse of the herbicide, which is now leading to a transition back to more dangerous herbicides. And a lot of problems for farmers. So that's one example where... Yeah, we might have covered the toxicity of the plant under FDA. There might not have been a food safety risk, there wasn't necessarily a plant pest risk under USDA, [chuckle] but there was certainly this broader risk of overuse of the herbicide, leading to more problems down the road.

BM: Yeah. Secondary and tertiary effects and... Yeah, wow.

JK: Yeah, yeah. And that's just one example. There have been other mishaps in the US of cross-contamination of food... Excuse me, plants that have been only approved for industrial use or animal feed that have gotten co-mingled in the human food supply. But it didn't lead to any... That we know of, any real adverse effect. They were able to detect it and remove it from the shelves. One of them was the StarLink corn, in that episode.

So I think we learned from that, that was a pesticidal protein from a bacteria, Bt, that was put into corn, was only approved for animal feed because it had sequence homology to an allergen, allergenicity, potential allergenicity. But it ended up getting into the human food supply. And ironically, some of the activists groups found that out by testing taco shells off the shelf back in 1999, I think it was. So that's an example of an almost mishap, and... Something that could have...

The other one that was an almost mishap is that there were some studies back in the late '90s about Bt crops, and particularly pollen being harmful to monarch butterfly larva. And it turns out that was demonstrated, and it wasn't a risk that was caught prior to approval of these crops. And so however, the varieties of Bt crops that we ended up using didn't quite have high enough concentrations in the pollen.

However, there was this one variety that did in order to cause harm to monarchs, but it ended up not being ones that farmers adopted. So we kind of got lucky in that regard. Because there were other reasons why that particular variety wasn't adopted. So we've had a couple things that have come close to saying, "Hey, we definitely have to have shown some gaps in the regulatory system." But nothing that caused a great catastrophe, which is why I say we haven't done a horrible job at looking out for risk, but we could be doing better. And as these technologies proliferate and kind of overwhelm the system and become more common in nature, I think it's even more important to make sure that we're covering those gaps.

BM: Well, those examples are really important, because they're illustrative. And I for one can use them to at least illustrate the potential and the reality of the potential. And... Gosh, it's kind of scary now, because it's not just about state actors, it's about the ability to get a credit card out and order your CRISPR toolkit. Yeah. We are going to get ‘proliferation,’ if you like, we're getting proliferation now, of this technology into all kinds of hands. So yeah, so there's that element as well.

JK: Yeah. Well, that's an incredibly wicked problem, and I really don't have as many solutions on... Or ideas for solutions [chuckle] and maybe solutions. But I don't have as many ideas on that front, because you're right, this is something that eventually could be disseminated by an individual actor, who could perhaps... We're far from that yet, because making a gene drive and spreading a gene in ecosystem is still pretty darn tricky. But I can certainly see us in 20, 50 years, it being quite easy to do for people. Now that people are able to tinker with biotechnology in these DIY labs or at home even, I can see it getting to the point where you have some sort of kit that can make a gene drive organism in the future. And that is frightening. I should say though, we've been worried about bioterrorism for a long time. In fact, I used to work on bioterrorism as a study director at the National Academies, right around 9/11 actually. I have more stories in that regard, but I won't go into that. But we've been worried about agricultural bioterrorism and ecosystem bioterrorism for a long time. And to our knowledge, nothing major has occurred yet. So it might be more difficult than we think it is to actually get it to work.

JK: And that's the one consolation that I have. And there might be more incentives for bad actors to do other kinds of things. I mean, what you can do with a gun is enough really, to cause terrorism.

BM: Absolutely. In my mind, there's a middle ground of dangerous territory, where we've got people pursuing edited crops, for example, in all kinds of countries at a very small scale outside the system, don't care about regulation, because they're, "Hey, we've got droughts in this little part of Africa, and we're just going to do it," or, "We've got floods in this part of Asia, and we're going to do something resistant." So you could see this proliferation...

JK: I see what you're saying.

BM: In the middle... No, no, no, I was talking about terrorism as well.

JK: Okay, okay.

BM: So yeah. But I'm also thinking about the middle ground and some proliferation down to small businesses doing CRISPR.

JK: Yeah. So not necessarily...

BM: Not individuals necessarily.

JK: Bad actors, but careless actors or overly optimistic actors.

BM: It could be both. I get asked all of time, "Toxins, people could make a super toxin or a bacteria." Of course, that's the bad actor terrorist individual. And then on the other hand, there's just the commercially irresponsible actors, let's call them, that at a small scale might just go, "Hey, we just want to make this thing ..."

But we can't solve that, so let's spend the last few minutes on the things that we can do more actively now and sort of learn from what you've learned. Because the people listening to this and watching this, they're typically business and government decision makers at all levels though. So what can we do, what can we learn from you and what can we do as individuals to help as we go further?

JK: Well, maybe I'll start at more the... Well, I guess everything I really... The ideas I have mainly are at the policy level. But at the individual level, I think we can just at least try to create and foster a healthy respect for responsibility and safety and anticipation of what could potentially go wrong. We can try to educate more students or people going into the field about those dimensions of biotechnology. So I think that's kind of on the more micro- or meso-level scale. I think that's the first thing we can do. I tend to have small-ish conversations with biotech developers, and many of them are becoming interested in this responsibility space. Maybe for the wrong reasons, because they want to convince the public that they're good, as opposed to really wanting to be good, [chuckle] but that's okay, as long as they jump into that space and dip their toe in it, that makes me happy. They want to avoid more of the public backlash from the first generation of GMOs, as more consumers are avoiding GM foods. That's just... According to the surveys I've seen. So they want to avoid that, and they're starting to dip their toe into these waters. So I think cultivating that healthy respect, becoming trustworthy, not just wanting public trust.

I hate to say, when people say, "Oh, we have to convince the public," or, "We have to get the public to trust us." No, you have to focus on becoming trustworthy, I think that's the most important thing. And I'm not trying to preach, it sounds a little preachy. I'm not... I am imperfect as well, but I think that could be one thing we could do on the micro level.

On the policy level, I really do think that we need... And actually, the Biden administration right now is looking for comments on the federal regulatory biotech system. And they just had a listening session the other day, and public comments are due beginning of February. And they're looking for ways that they can bolster the... They're looking for comments on how they can bolster the bioeconomy, but they're also looking for comments on how they can improve the regulatory or oversight system as well. So I think they're thinking about this, and I think they could be steered in a direction of maybe just a unified kind of place where we have a more holistic look at the risk-benefit issues... Not only risk but benefits. And so can we create... And I don't want to create another Department of Homeland Security, for example [laughter] But can we create a smallish agency that can bring the different regulators and funding agencies together to think more broadly about governance as a first step? And probably under the Office of Science and Technology policy would be the ideal home for it, of the White House. So that would be kind of a second policy thing we can do.

I think on the research side, further upstream from when a product is being presented for market release, we could... For every project we fund on the technology development side, could we set aside a portion of the funding for social scientists, humanities scholars, stakeholders with concerns, various publics, to also engage and do more of a real-time integration of the societal concerns? So let's say 80-20 split, and the technology development gets 80%, the social societal aspects gets 20%, or something like that. For every particular technology development project, we would have a concurrent governance development project. That's another thing.

Those are just a few of the ideas that I think could put us in a step in the right direction. And it would be costly, but wouldn't cost so much money. It's not going to cost as much one... It's not going to cost you as much as probably a few clinical trials. So...

BM: Yeah, yeah. And the risk management science, you mentioned that right at the beginning, this idea that we've got to get better at the science of getting... Of understanding the risks. Is that... I'd like... Yeah, can you expand on that a little bit?

JK: Absolutely. There's very little funding that goes to risk assessment, real risk assessment and risk science. The USDA used to have these Biotechnology... And they still do, have these Biotechnology Risk Assessment Grant Programs. But it's a very small program, and it... When you look at it, it's not really necessarily funding risk assessment on different aspects of the technology, it's more... I could get into it. Some of it is directed at risk assessment, but a lot of it is directed more at technology development to maybe lower some risks as opposed to actually doing the risk assessment, bringing together loads of information, doing the safety try... Testing in independent venues. Right now, most of the time, these risk assessments are done by the industry itself, and I think there would be more public confidence if there were more independent agencies that had the resources to do risk assessment and risk science.

BM: Yeah, yeah. Well, we're going to need a lot more [chuckle] of all of it, because it's going exponential, isn't it? It's not just this gold rush mentality for therapies in particular, and foods and so forth.

The one recently that really made me think much more broadly was what Verve Therapeutics is doing with cholesterol. That first patient, to do a modification to lower their LDL cholesterol. And it's like at the moment, that's on a therapeutic basis, there's the particular patient needs it desperately. But the pathway is 100% towards a pill that anyone could take to lower their output of LDL cholesterol. So it's not a therapy, it's a modification. It's not a cure, it's a... Yeah. And that's a whole new era [chuckle] of ethics.

JK: Yeah, yeah. And back in the late 1990s, the gene therapy community was set back for a decade, from the death of Jesse Gelsinger, was one person who died from a gene therapy trial. And I would hate to see that happen to the gene editing community as well. There was a trial just a couple weeks ago I heard that got halted on CRISPR based technology for sickle cell anemia. It had significant adverse event happen, and I... And so I think, you know, that's good it was caught early, in the early stages of a clinical trial, but I would hate to have this whole field set back because of the few early mishaps that we didn't necessarily catch early enough.

BM: Yeah, yeah. Jennifer, I'm very conscious of your time. We've used up everything allocated ... Look, as with so many things, it's one of the hardest things, and that's also one of the most important things, they tend to go together. So, um, very inspiring to spend time with you, because you're working on one of those incredibly hard but important problems. I don't envy you, we need a thousand of you, I think. [chuckle] We need to start cloning you, right? [chuckle]

JK: We're trying to... There are more coming out of programs like the one we have and others. And there are more academic programs now that are bringing together these areas and getting the natural scientists to think about governance and incorporate responsible innovation really into their work, life-long. So I think the next generation is going to be... There's going to be more people trained in these spaces. So there are... And there are a good couple dozen of me out there too, so thank you for your kind words, so... [chuckle]

BM: Well, my pleasure. And we'll try and spread the word a bit further and make some more Jennifer Kuzmas out there.

JK: Well, thank you so much.

BM: And... Yeah, try and keep it real. We want techno-realism, don't we? That's our goal. I like that. I like that.

JK: Yeah.

BM: Thank you again, Jennifer. I appreciate the time.

JK: Take care. Bye-bye.

BM: Bye-bye.

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