The CRISPR Revolution in Science, Religion and Ethics

Ray Pickett: This lecture was established through a generous gift by Harvey and Elizabeth Mohrenweiser to address moral and ethical points between the practice of faith, science and religion. And by the way, I’m cherry-picking. I’m the rector here at Pacific Lutheran Theological Seminary.

So today we are very pleased to have Dr. Arvin Gouw give the lecture on the CRISPR revolution and the various uses of CRISPR, which is a powerful gene editing tool. I was just talking to Dr. Gouw about this. I didn’t know this, but he was actually the TA to Dr. Jennifer Doudna here at UC Berkeley, whose pioneering research in RNA is what set this whole revolution in motion. So this was when he was a Master’s student.

So, and then Dr. Ted Peters is here, who Arvin has also known since he was an undergraduate. So Dr. Doudna, some of you know, won the Nobel Prize for that research. And so that’s for this gene editing technology, which has tremendous potential for good in terms of gene therapy and other uses in health care, but also raises significant ethical and religious questions regarding the use of genome editing for reproductive purposes and the limits of human intervention. We were just talking about — recently, I just saw an article this week of a doctor whose name I’ve forgotten – Dr. Gouw will know – who was just released from prison for actually doing that. So it’s a real kind of interesting challenge.

Dr. Gouw is currently working in the field of theology and Science at the University of Cambridge Faculty of Divinity, and I think is uniquely qualified to speak with us about the moral and religious significance and implications of CRISPR, as well as the science. He’s also a scientist who until recently, was at Stanford University School of Medicine. And he has also done research fellowships in science and religion at Harvard Divinity School and Princeton Theological Seminary. And I just learned this morning that he’s living in Virginia now, but he’s actually doing a second PhD in theology there. So again, uniquely qualified.

Dr. Gouw received his doctorate from Johns Hopkins University School of Medicine, a Master’s degree in Theology and philosophy from the University of Pennsylvania and a degree in theology from SMU Ecumenical Institute of Theology, and in endocrinology and neuroscience from UC Berkeley. So, very diverse background.

And so we’re also pleased to have this morning Dr. Ted Peters, who’s Emeritus professor of Systematic Theology here at Pacific Lutheran Theological Seminary, so we welcome him, and he will give a response to this. They are working together. They edited, recently, a book called Religious Transhumanism and Its Critics, and then they have a book they are finishing together. Dr. Peters and Dr. Gouw are finishing an edited book to be published this summer, called The CRISPR Revolution in Science, Religion and Ethics. So please join me in welcoming Dr. Gouw, who will give the lecture, and then after the lecture Dr. Peters will give a response, and we’ll have some time for a Q&A. So welcome Dr. Gouw.

Arvin Gouw: Thank you so much, Dr. Ray Pickett. And first I’d like to thank the Mohrenweiser for this opportunity for this invitation. I’m very, very glad to be here. Of course, whenever we get an invitation, I would check. You know, what is this lectureship all about? When I saw that it’s about the moral implications of inventions in science and medicine, and how it relates to faith, I thought, “This is awesome. You know, every seminary or every university should have this kind of lecture.” And I thought, “But who would deliver the talk?” (laughs)

So I’m very grateful for the opportunity. But this is one of those things where, you know, as a scientist, I’m trained to focus on just one gene amongst 20 or 30,000 genes, and here I’m forced to talk about general ideas and how it relates to religion and ethics. This is not my comfort zone. This is a gracious invitation that I’m here to tackle the challenge and sin boldly. So that’ll be that’ll be the task today. And I’m glad that it’s also at PLTS. This is home for me, Berkeley. I grew up in the Bay Area, I went to undergrad here. So PLT has always been a campus that’s very engaged with science, thinking of the luminaries from the Lutheran tradition, even from Pannenberg, Phil Hefner, Ted [Peters]. It’s very, very sensitive to the need of the public in engaging scientific advances. So I’m very happy to be to be back here.

All right, so this is the title of the talk. Again, it’s very ambitious. I decided for most of it to be science, because I know the audience will be more qualified to talk about the theology and ethics than I am. So the talk will be in four parts: the CRISPR mechanism – maybe only two slides or so. Some applications, a lot of applications, the dangers, and regulations, because I usually get asked about “how is this thing regulated?”

So CRISPR was discovered as a bacterial immune system, right. And what that means is, if we get sick by COVID, you know, we have white blood cells to fight off the pathogens, the virus, the bacteria. But if you’re a bacterium and you get attacked by a virus, what can you do? You’re by yourself, as a single celled organism, and you don’t have white blood cells. You are a cell, right? So this was the research – this was Jennifer’s research. And she found that, well, you have this kind of CRISPR CAS system. Basically, with foreign DNA, a viral DNA comes in, gets chopped off, and the bacteria knows that the next time it comes around, it’ll send that RNA along with a CAS-9, a scissor, to basically degrade the virus, DNA. Okay, so that’s how it works. And they discovered this a while back, a decade or so before Jennifer realized that well, “Hey, you know, this sequence, what if we put our own guide RNA, then it’s not just going to target the viral genome, but it can target any gene we want in the DNA?”

And that’s a simple idea. It looks simple, but they get a Nobel Prize for it, right. So this is them in October 2020 – Nobel Prize. And this is the crystal structure that she just published two years ago in Science. Of course, the blue part is the DNA, and the white part is the Cas enzyme, the scissor that clips things off. And the red part is the deaminase that can do the nucleotide switch for genome editing. So this is the actual crystal structure, which is very nice. So it can be used from bacteria to humans.

So what are the applications? The applications are very broad. In agriculture, now people are genetically engineering plants so that they can grow under warmer temperatures, they can grow with less water, and more productive, longer shelf life, and so forth and so on. So a lot of industry and research behind CRISPR and plants.

So one of the initial CRISPR experiments were done on dogs, making the skinny dog to be more buff. Micropigs – these are these are pets. You make pigs that are smaller so that you can keep them as pets. 1500 bucks, very cute. Hypoallergenic eggs, probably a lot more useful than micropigs. And anti-malaria mosquitoes. And we’ll talk about the mosquito issue soon.

Now, I want to highlight Hercules, the buff dog here. I think you can you can realize that the potential of myostatin deletion for causing increased muscle mass. You can help human cases, for example, with patients where you have a loss of muscle mass. That’s a therapeutic use of CRISPR, right, but it’s dual use. You can also theoretically make a Captain America, from Captain Rogers to Captain America. That’s what that would be enhancement to this. So therapy and enhancement are dual uses of CRISPR, and we will talk about this more later.

Species and Gene Drives

Now, what are CRISPR gene drives? This is an interesting invention. So the idea is, if you remember your Punnett Square from high school, which I don’t, you have Mendelian inheritance, one allele from mom, one allele from dad. If you get one from dad, it’s a 50% chance. But with CRISPR, you can make it says that well, the one allele you got that’s edited, you’ll double it to the other allele, so that you become a homozygote. So that way all your progenies will get edited. That’s one way to design it.

So in a normal mosquito population, if you have a mutant, not many of them will be mutant, but with a gene drive, because it’ll copy itself to the next allele, within a few generations you’ll have all the mutations in the mosquito population. So what you can do is that, because these mosquitoes that carry diseases, right Zika virus, malaria, dengue fever, you name it. And because of that, you can design mosquitoes such that if you made with the [mutation], they cannot have progeny. They might not be able to fly, or you know, people will do different modifications on the mosquitoes. So you can drive species extinction using this method.

The first U.S. open-air test of genetically modified mosquitoes [was] deemed a success. The mosquitoes were released in the Keys in Florida, though I saw in the LA Times they’re also in California. So they deemed this a success. There are ways to control this so that they don’t mutate. You can reverse the gene drive, you can kill them off, and so forth and so on. There are many technologies to control these CRISPR mosquitoes. Also maybe they can drive away the New York rats, poor New York pizza rat, because this CRISPR CAS-9, this gene drive, had been shown to be able to be done in mice as well. So this is expandable in terms of what you can do, not just in “lower” or simpler organisms such as mosquitoes.

So what are the issues surrounding gene drives and species extinction? Right. So these are some ethical reflections, theological, ethical reflections. The Laudato Si reminds us that we are part of nature, not above nature. Who are we to do these things to other species? We need to consider the environmental effects of gene drives. That’s Lisa Fullam, that’s also at GTU.

“All creatures, even microbes, have their intrinsic value”  – the intrinsic value argument. Independent of the relationship to us? Lynn White has brought this up, Chris McKay as well. There’s a kind of counter-argument that this intrinsic values of other species are always relativized to humans when it comes to reality. In other words, – like, mosquitoes have their intrinsic value, but they’re killing many people and causing diseases. So, guess who wins? We win, right? So there is always, when, when the tire hits the road – this intrinsic value argument often goes out the window. We’re back to instrumental ethics. And the problem with instrumental ethics is that well, circumstances, values, change depending on the circumstances, right? You can have an E. coli that would be bad for your agriculture but good for humans as a microbiome. So you can’t just drive it to extinction, for example.

So it’s very complicated. You don’t have a strict guideline if you don’t have intrinsic value. So I think Ted, for example, has published on responsibility ethics, trying to maybe get away from this dilemma and try to see, well, what is our responsibility, in terms of a protectionist model  to protect ourselves and all of creation? It’s a different way of approaching the problem.

And my approach is to say that “Well, you know, whenever we try to value these other organisms, other species, whether intrinsically or environmentally, we need to look at their original context, and their own microbiome, and how they are related to the space that they occupy.” This is coming more from my liberation as some kind of postcolonial, because organisms are usually tied to that land, tied to the seas, in that specific environment. Science will oftentimes harvest, colonize and mine these organisms for our own use. So there is an imperialistic aspect of science that we need to be mindful of. We cannot divorce them from their land.

So are genetic models helpful? Yes, they are, I think. Even if not being applied to humans, genetic mouse models are very, very helpful. So this is an added value, for example, of the use of transgenic mouse models for rare-disease research, because if you can copy the disease of a patient – the single mutation in the patient that causes the disease – you copy it in the mouse. Then you can experiment on the mouse, find the drug, develop a new drug, and then test the drug, and see if it works on the mouse, before you go back to considering using it on a human. So CRISPR is a very powerful research tool.

And which one would we target first? And I published this in 2018. I would say, “Well, the monogenic diseases.” There are about 4,000 monogenic diseases. “Monogenic” just means you can pinpoint the cause of the disease to a single gene, genetic mutation. That’s all. I mean, CRISPR technically can edit multiple genes at the same time because it’s so easy to use. But when it comes to humans, let’s just fix one at a time, right? But fixing one at a time, there are 4,000 of these diseases that are monogenic, so the opportunity is huge. This is about 200 million people globally, that have these diseases. Many of them are actually rare diseases. So rare diseases are not so rare. There are 7,000 rare diseases out there. And combined total that’s 300 million globally. So rare diseases are not so rare. The problem is it’s difficult to get funding to do research on rare diseases because your impact score in your grant application won’t be so great thing. “Well, it didn’t help too many people.” Developing this drug for companies, as well, will be very expensive.

So how do we go about, then, to do this CRISPR gene therapy? In general, there are two ways. One is called ex vivo, outside of the body. You take some blood cells from the patient, you CRISPR him outside and lab, inject them back in. Simple. Ex vivo – you do the CRISPR outside. Or you can send the CRISPR into the body, then you would use viruses or nanoparticles to do the job.

And you hope – of course, you’ll design the virus to go to the specific target in the body to deliver the CRISPR CAS-9 system. That’s in vivo gene therapy. That’s how you do it, in one slide. This is a timeline in terms of history. I love these timelines, because this is a way for scientists to reconstruct history. So it was identified, CRISPR, [in 19]87. Rhey studied a bunch of structural functional relationships, and in 2012 was the publication of CRISPR CAS-9, and you have the first CRISPR clinical trial against HIV in 2017. And now we have a lot more. And 2020 was the Nobel Prize.

If we look at CRISPR clinical trials, you might think, “Well, do people really do this?” Yes, yes, they do. So over a dozen CRISPR clinical trials, you can go to clinicaltrials.gov if you want to update your status, if you want to check how many CRISPR clinical trials [there are], maybe. That’s what I do for fun. (laughs) And then you can get a list. You can see the drugs, the mechanism, whether it’s ex vivo or in vivo  – we talked about that, right – and what clinical phase it is. Most of them are clinical phases 1 or 2. One of them is in phase 3.

CRISPR applications and problems

Now, how broad is this gene therapy? Is this new? If you look at gene therapy in general, not CRISPR, CRISPR is just one of the newer tools that we can play with. There were other genetic tools that are more difficult to use, but they were already made, right. So according to this paper, for example, as of 2017, there were already about 2,600 [clinical trials of] gene therapies globally. There’s a lot. In 2021, [there were ongoing trials for] 131 gene therapies , of which a dozen of them were CRISPR. By December 2022, a few months ago, about 27 cell and gene therapies were approved in the US by the FDA. This is kind of the landscape in terms of what is going on. Of course, a lot of them are in the US and Europe.

We can cure disease by editing a person’s DNA. Why aren’t we? “Why aren’t we doing it more often?” This is an opinion article in the New York Times by my previous professor, Fyodor Urnov, who’s here at Berkeley.

There are dangers, right? So let’s talk about some of the dangers – scientific risks. These are well known off-target effects. Just like any drug, you send the guide RNA, it might bind elsewhere, not where you intended it to bind. So that’s one possibility. 3 billion base pairs, 23,000 genes, how do you know it’ll bind in the right place? On-target effects – just because you reach the destination, you delete that gene, it might have unintended consequences that you didn’t know about before.

So a classic example would be sickle-cell anemia. We might get rid of sickle cell anemia, but then you will get rid of the resistance to malaria, which is a worse disease than sickle cell anemia. So we have to think of the on-target effects as well. Chimerism is probably more technical. If you send the CRISPR in, but not all of them get edited, then you end up with a chimera. And how will this chimera be? You know, will it render the CRISPR modification useless, or will it be partially useful? Will it be overcome by the non-CRISPR cells? And so forth and so on.

Epigenetic factors, I think, are very important. “Epigenetic” just means anything that’s non-genetic. So if you think of our DNA, it has to be tightly wound to fit in the little nucleus. Because it’s tightly wound, it’s not always wound open, accessible. So you can’t put in a gene that will make you smart, it doesn’t exist. You can put a gene like that. But if the DNA is bound closed, it’s not going to be able to be activated. It’s not going to work. So it’s rendered useless. So just because you have the gene, you have to also consider the epigenetics. And nature has a way that usually epigenetically, if it doesn’t want it, it’ll repress it. I can talk more about that. It has tendencies.

So there are strategies to overcome all the problems that I’ve talked about. So these risks were from early guidelines from 2015. But people have been working on fixing these problems. So delivery issues – people were worried about viruses coming to our body. Well, what if the virus has gone wild? Just kidding. What if our body reacts to the virus and has an immunogenic response? And this did happen in a gene therapy case in 1999, where a teenager passed away because of immune reaction. This is a serious concern. Now we can use nanoparticles. Nanoparticles are a lot safer, it’s been discovered I think people are shifting to nanoparticles. They’re lipid balls, basically, that you deliver in.

In terms of off-target, we can kind of anticipate what the off-target [effect] is using bioinformatics tools. There are also CAS-9 Nickases. This is one of those things where you will need usually CRISPR CAS, they’ll come in, they’ll cut double strand DNA, but you can make it such that they’ll cut only one strand. That means you need two CRISPR CAS nickases to make the cut. In other words, if you’re going to go wrong, off target, you have to have two CRISPR gone wrong, the same exact wrong side, which is highly unlikely. Because if you only have one of them gone wrong, it’s just going to cut a single strand, nothing happens. The DNA will fix itself. Okay. So so this makes it a lot safer. The downside is it’ll be less efficient, because then that means you have to send in a lot more CRISPR CAS for the targets that you actually want, because now you’re going to need two CRISPR CAS instead of one. Right so that’s the drawback but you can address the off target effects with.

The immune response the other the other way to deal with it is you do the CRISPR modification early, in babies, so that your your tolerate it, your immune system will tolerate that modification, so that you don’t have an immune rejection. So these so there are many ways to overcome these problems. And I think we’re getting more and more confident in experimenting with CRISPR and using CRISPR.

All right, that’s the science stuff. What about the non-science stuff, the application? “Obama Advisors Urge action Against CRISPR Bioterror Threat,” in 2016. When I first saw this, I thought, “Who’s going to think of bioterrorism? You have to be pretty smart.” No CRISPR how it works? Well, I was wrong. I watched an episode of Designated Survivor – it was on Netflix already – where some biohacker made a CRISPR against people with dark skin. So you get the gene for dark skin, and the CRISPR will knock out certain genes and make it harmful for that person. So that was on Netflix. So much for ideas floating around.

And this is actually an idea put in practice. This is what Dr. Pickett mentioned. He Jiankui, a biophysicist from China, he decided to do the human experiment modifications of twins, nicknamed Lulu and Nana, to make them HIV-resistant, or AIDS-resistant. So his thinking is, “If I can design” – CRISPR designer babies by definition,” as you design imply that if you do modification X, it’ll cause a change in X. His idea is, HIV needs this receptor, this hook on your cell, CCR-5, in order for it to attach. Well, if you get rid of the hook, the HIV can’t attach, voilá, you’re AIDS-resistant. It doesn’t work like that, of course. And the problem is that CCR-5 have their natural functions, right. So some studies in the mouse show that CCR-5 might be good to protect against General herpes simplex, you might get rid of HIV but you might be more susceptible to HSV. Right. So again, this is kind of the on-target unintended consequences that I talked about before.

More papers were published. Well, maybe the CRISPR twins might have shortened lives because of the CCR-5 knockout. And others will say, “Well, CCR-5 suppresses cortical plasticity, which means flexibility in learning.” So maybe the twins will be smarter, because they don’t have CCR-5. So we don’t know what will happen. People speculate of what the possible unintended consequences are.

Have we traded theological determinism for biological determinism, perhaps? We think, “Well, genes don’t do everything.” But if we know the environmental context, we can predict what will happen. That’s kind of the spirit. If I just know your genomic makeup, what causes those 4,000 diseases? I have to CRISPR everything, I have to make sure it’s perfect, and then you have a healthy diet, wear your Fitbit watch, walk 10,000 steps a day, and you should live up to 120, as long as you didn’t get hit by a car. That’s some kind of a you know, socio-biological determinism as well. So are we truly free or are we simply unconscious of our gene-environmental predetermination?

The Simplicity and Spread of CRISPR

Regulations – how are these things regulated? There are several bodies that have tried to provide reports on this. American College of Medical Genetics and Genomics talked about the same scientific risks that I’ve discussed before, off-target effects and unknown, epigenetic kind of consequences. The National Academies of Science, Engineering and Medicine also did a report. They understood that there are advantages in prevention of inheritance of genetic diseases, advancements in sort of basic science research, but again, you have the same four major concerns. And I think they were also there was also a WHO report on this as well, more recent.

But should someone decide to do this, who’s going to stop them? That’s the question. Right? And this technique is easy to use. So gene editing tool went from labs to middle school classroom. Eighth graders, learning how to do CRISPR and being able to do it. It’s simple. That’s why CRISPR is powerful. This biohacker Josiah Zayner – he regrets it later, but he publicly injected himself with CRISPR. And so this is the term biohacker. So this is something that you can do in your garage – poorly. You can you can do CRISPR very easy if you don’t care about doing it properly and correctly. That’s what I should say. It’s easy in the sense you just want to get it done dirty and quick. That’s easy. But it’s not clinically prudent.

So, CRISPR kit, 180 bucks on Amazon – just to edit the bacterial genome, though. It arrives in two, three days. Not Prime yet. And all you need I love this. You don’t need anything else but water and a microwave. That’s all you need. That’s fine. So, so yes, this is easy to use. I’ve argued this – I think this is one of these technologies that are very powerful, but easy to use. We are always concerned about access, right, but this is not like the race to the moon, where we need billions of dollars and a lot of technical expertise. This is something that’s a lot easier for the public to access. With just some basic science and some protocol understanding, you can do CRISPR.

So, America’s first CRISPR law in California (laughs), “Do not change your DNA at home.” So that’s the first law on that other than the patent dispute. So, Sheila Jasanoff, who was contributing to our upcoming book, has promoted this idea of “CRISPR democracy“– gene editing and the need for inclusive deliberation. This is Benjamin Hurlbut, who did a PhD in STS at Harvard. That’s how they’re connected. But yes, this becomes a democracy, because everybody will be affected by this, and should be mindful, and should know about this technology. That’s why I think a platform like this is very useful, where the public is also engaged. This is not just something that scientists can tell you what to do. This involves everybody.

So this is a more elaborate diagram that I like, from a recent paper. This is a way to think through on whether you use CRISPR or not in humans, you can ask the question, “Does this disease that you want to fix have a known and monogenic cause? Does it have a single gene as a cause?” If no, do something else. If yes, well, “Is this disease bad enough? Is the mortality high, the morbidity high?” If yes, then you consider the ethical and legal considerations. Is there a societal consensus on this? Have measures been taken to reasonably reduce the risks? Is there consent? This is also very important, the idea of autonomy beneficence diagram, autonomy and beneficence. Is there a suitable long-term monitoring of the patient? And are there any conflicts of interests? The legal aspect ethical aspect, the scientific aspect had this done? Have this been done in animals? Are there other treatments? If yes, are the other treatments better than CRISPR, or the same? If yes, then why are we doing this? Right? If there is, and it’s not as good, well, is CRISPR, a lot more expensive? Is that treatment more expensive – cost-benefit analysis?

So these are the kind of the scientific input, technical input. And if you say “yes” to all these things, then maybe we can consider CRISPR as a therapy, but still not enhancement.

Playing God?

All right, so several themes to consider. Natural versus modified, therapy versus enhancement, somatic versus germline. Okay, so we’ll talk about the first one first. Are we playing God? Of course, I think this is one of Ted’s book titles. Should we alter nature. Is this a Promethean, Frankensteinian hubris, like according to Leon Kass, who picked up on Hans Jonas on this issue? “There’s a reason why nature is the way it is, don’t tinker with it,” says Rifkind. So these people would say, “No, do not do that. We’re playing God. Do not alter nature.”

But there’s a counter-argument: well, you’re assuming that the way nature is is the way it should be. This is Hume’s Guillotine, the “is/ought” distinction. Maybe with G.E. Moore it becomes a naturalistic fallacy, right – is nature how things should be? Or as being refined by Lebacqz: “Does nature define what is good?” That’s also a form of naturalistic fallacy. Maybe we’re not playing God necessarily. Maybe we’re playing with God. As co-creators. We’re given this tool, we might as well be active and consider how this tool can be used for the greater good.

It’s also the idea that nature is incomplete. There’s an openness from Terry Deacon here, but also from Ted, that the future is open. So we can participate in design of that.

And I think there is a blurry distinction, even in science, I would say. You know, we often think, “Well, you’re doing this CRISPR modification, this is unnatural.” Fixing mutations are natural if you put CRISPR in, but nature fixes mutations on its own. It’s called “preferred mutations.” So this is a disease. Originally, it’s GC, the first mutation, you have a disease, but sometime you have a second mutation that put you back into the first one, and you get better, okay. So isn’t CRISPR just helping Mother Nature to fix herself? Is the question. So this “natural versus artificial,” I think is a blurry line.

And what is nature anyways? This is more of a question for you, not for me. Should we alter our DNA? What about identical twins? They have the same DNA, but are obviously different persons. Well, they’re different persons — is it because of their brain? So maybe the personality is in the brain. We tinker with the genes of the neurons, then we’re tinkering with human nature? Or are we nodes within social infrastructure, the brain is controlled by interactions with the environment? So maybe it’s okay to tinker with everything that’s in our bodies, it’s society that kind of defines who you are. Maybe this is more of a Marxist analysis, or to be theological, to be Barthian. Are we how we respond to God? So there are different ways to look at this question, and I think we have to be holistic in assessing this question.

Therapy versus enhancement. I’ve been saying this for a while because this is an issue that bugs me a little bit. What is “normal”? If we think of what is normal, the normal is usually kind of like the mean. If you’re below the mean, you’re sick. If you can’t walk, for example, you’re sick. If you can run very fast, well, that’s great. You’re very healthy and you’re enhanced. So a treatment to push a person’s capability from below the mean to mean is considered therapy. A modification to push a person from the mean to above the mean would be considered enhancement, right. But the problem is, of course, if you provide therapy – therapy is allowed, enhancement is not allowed – well, if you provide therapy, the mean’s going to move. The average human height is 5’ 10”. You do CRISPR for people who are shorter than 5’ 10”, then of course the mean shifts six feet. I mean, you can’t do this, but that’s the general idea.

This therapy/enhancement distinction is either nonexistent, as some philosophers have argued, or at least a moving line – kind of my position. I think there is a line. We do have some sense where certain things are enhancement; I would even call them cosmetic. There are certain things that are also therapy, that’s very obvious. But the line does get blurry.

And not only thinking of a line, but we need to think of what kind of population and context are we talking about. So for example, if there’s a genetic modification on me, to make myself radiation-resistant, that’s an enhancement. I’m resistant to nuclear bombs. But for an astronaut who needs to fly to outer space, being exposed to radiation, that’s not enhancement. That’s a preventative therapy. They need that for their job. That’s an essential genetic modification. So it’s ideas, also, from Conrad and Braden [Molhoek], who are writing in our book. So the context also alters what we mean by therapy. Enhancement cannot be universalized to everything. We need to look at specific context as well.

All right – somatic versus germline. Germline basically just means you can do the CRISPR modification either in your sperm or your egg. If you do that, then basically every cell in your body will have that genetic modification, which also means you’ll pass it on to the future generations, right? This is one of those things that change your whole descendants, your generation. Somatic mutation is if you do CRISPR on me now, just not on my gametes, then it’ll stay with me. If you do CRISPR on my liver, then it will stay in my liver. That’s it. So this is the distinction. And right now the guideline – well, we can talk about the guidelines, in general, germline, you have to be more cautious, somatic, that’s fine. Okay. For obvious reasons. Maybe not so obvious. According to Eric.

Yes, even in germline therapy, there are very constant risks. It’s a slippery slope, enhancements, right? We don’t have the consent of future generations. We’re tinkering with our genome. allocation of resources – maybe we can do other things, and integrity of genetic patrimony, the future generations have the right to inherit the original genome, not the one that we modified and want to give to our kids. But there are “pro” arguments as well. Utility – the germline gene therapy, maybe it’s offering a true cure for diseases. Maybe it’s essential. Maybe that’s the only cure the only way to fix it is if you if you do it germline.

Maybe prevention, in terms of germline therapy, is less costly than a lifetime of treatment. This would be a “pro” argument for germline. We talked about the autonomy and the consent of the future generation, but what about parental autonomy? What about scientific freedom? These are kind of pros and cons that have been posed.

So this is a very important paper that the Canadian philosopher thinker and philosopher Françoise Baylis published in The CRISPR Journal in 2020. They survey many, many countries, 96 countries, policies on human germline genome editing, not for reproduction, and you get 19 countries prohibiting, 11 permitting. US is green – it permits germline genome editing, but not for reproduction.

Now what about for reproduction? No, everybody says no. Then you have 70 countries prohibiting, five countries are making exceptions. That would be Belgium, Colombia, Italy, Panama, and United Arab Emirates. That’s interesting.

All right, so should we enhance our children? That is the question, right? Will we be blamed if we edited their genome, because they want their original genome? Will we be blamed if we did not edit their genome. “Why didn’t you do it, Dad, and now I’m shorter than everybody else”? I think as parents, we’re going to be blamed either way by our children. (Laughs) If the technology is available, we are responsible to decide. To not act is to have decided.

On the other hand, there’s this past history of possibility of eugenics that we have to be mindful about. And John Slattery writes a book chapter on that in our upcoming book. And there’s the issue of commodification of children. When we’re editing our kids, was it really for them? Or is it for us? Well, our kids are smarter, our kids are healthier, and so forth and so on, right – then we probably have commodified our babies. If gene editing goes wrong. Do we get a discount? Or do we then make another kid, the perfect child syndrome? Well, modified X is brilliant, but not good in sports – let’s modify X and Y , have a second kid, have a third kid, so forth and so on. And I would say at what point is the enhanced child no longer my child? My son looks like me. But if I had edited him to be 6’ 5”, blond with blue eyes. How is that my kid? Right. So the parental aspect of it is still important, as it has been pointed out.

All right, some theological reflections. It usually comes in within the framework of dignity, benefica. So in some cases, for example, from Austriaco – he’s a Dominican priest and also scientists, he did his PhD at MIT. He said something like “Maybe it is okay to do germline modification – if it is done safely, and it’s preventative therapy, not enhancement, and it still does not undermine their dignity, that could be acceptable.” People are more open to this idea. Lisa [Fullam] points out that in terms of the dignity that we can’t think only of the dignity of the embryo that we’re crossbreeding, but someone has to carry out the pregnancy. And these are women. It’s more of a feminist perspective. We need to think about what is the impact of such CRISPR therapy in the mom? So dignity can go in many different directions.

All right, concluding remarks. CRISPR applications are very broad. These are the scientific dangers, off target, on target effects, and epigenetic factors. The CRISPR regulations are there but they’re not enforceable. And they are somewhat unclear on where to draw the line, or on what the line means. And by “line,” I meant natural versus modified, and the therapy versus enhancement. The somatic versus germline – that’s pretty clear. And I think CRISPR democratization, because it’s so easy to use for everybody, really calls for a public engagement and a platform such as this, where CRISPR applications and regulations can be discussed with the public. Thank you.

Ted Peters: Well, thank you, Arvin, very much for that. What I would like to do here in a couple of minutes of responses is raise the question: why is knowing something about this kind of science important for the pastor, the pastors of today and the pastors for tomorrow? I just have to say that I really appreciated hearing Arvin here today. It was some years ago, when Arvin was studying genetics at Cal across the street, that he showed up in a doctoral seminar on systematic theology, and he’s been on two tracks ever since. He didn’t mention, or Ray didn’t mention either, that he’s a cancer researcher, and up until recently had two laboratories going, one at Stanford and one Cal. And I’m hoping that there will be a day in which he’ll receive the Nobel Prize for curing cancer — you know, you gotta hope, right?

Why might CRISPR gene editing be important for a pastor to know about? Well, there are two areas. The first one is pastoral care. Over recent decades now, families who are expecting children will frequently go to a genetic counselor, the OB-GYN will recommend one. And then they show up in the pastor’s office with what they have learned. Amniocentesis tells them something about the genome of the child that’s about to be born. And for a long time, the question was, “Should we abort or not?” Why? Well, they found one of those monogenetic genes that are responsible for disease, and do you want to get rid of the child before the child is born, because they’re going to suffer? Certainly in Jewish families, with Tay Sachs, lots of rabbis find themselves counseling people in that circumstance.

There was a graduate of PLTS some years ago named Martha, and she became a pastor up in Oregon, and she and her husband decided to go with in vitro fertilization, and their baby was born. And then upon birth, they discovered the child had Williams Syndrome, due to a malfunctioning allele on chromosome seven. Well, the symptoms were that he’d walk down the hall and he’d bump into the walls, and he would have a shortened lifespan, and a few things like that. So here they are using exotic reproductive technologies. Had they known that the child had a gene for Williams Syndrome, would they have aborted – or, if it were to happen now, might they have been able to alter chromosome seven using CRISPR gene technology? And if so, “Pastor, what should I do?”

Well, it’s good if the pastor has a little knowledge of, of what’s going on here, in those kinds of, of circumstances. One of the issues that’s almost always on our minds, as Arvin had mentioned, is this relationship between nature and altering nature. The romanticism in us tends to say “If it’s natural, it’s good.” And when we get into the human genome with wrenches and screwdrivers and trying to change it, are we playing God? Are we violating nature? Are we risking Frankenstein or Prometheus or something of that particular nature? Those questions hover around our consciousness and, you know, sometimes a pastor is a good person to ask about this kind of thing. And so having a little bit of knowledge and actually having already formulated some opinions is a good idea for pastoral care.

The other item, near the end of our presentation, has to do with public policy. When in China this researcher Arvin mentioned decided to go ahead and bring into the world two babies whose genome had been altered by CRISPR because he wanted to prevent them from contracting the AIDS virus. And he was very proud that he had achieved this technology, and the whole world of ethicists and genetic researchers rose up in anger at this. Why? Well, the first thing is that those who oppose this bringing children into the world with an altered genome, the first problem is that genes work in systems – Arvin used the word “context.” One gene can make four different proteins, depending on his interaction with the other genes. And if you just alter a gene like that, and you don’t know the context, you don’t know how it works systematically with other DNA, you could throw things out of whack. And that’s what happened in this case. The critics were able to show that the lifespan of these children can be shortened now, because of the even though the work was on target, the consequences are such.

And so my experience with geneticists is they’re saying, “We don’t know enough yet. And so let’s not experiment on a human being – a human being has dignity – until we’ve got all of the factors in hand.” And the geneticists don’t at this particular point. And so you heard Arvin saying, towards the end there, that if you and I engage in somatic therapy – that is to say, if you’ve got a liver that’s a problem, CRISPR gene therapy can lead to healing, if not regeneration – good, go right ahead. But even though that affects you therapeutically, it’s not going to affect the children you bring into the world. That’s where for the most part, ethicists and geneticists have the big concern. So the traffic is going to be slow on this technology, even though the technology is easy. But as Arvin was saying, the easiness of it may turn out to be a difficulty, because any teenager in a garage could start altering the genomes of the dogs and cats in the neighborhood. And we don’t know if chaos is going to be the result of this. So if you’re a pastor, check the neighborhood (laughs) and see if the dogs and cats are starting to look different because of this.

It’s also the case that in many communities, pastors are asked for their opinions on policy matters. And so having some level of keeping up to date with the science is always good, for just that level of sophistication that pastors have to offer the community. Now, as an aside, I was working yesterday on a movement that you probably don’t know about called Don’t Trust Your Pastor. And in noticing that, the Gallup Poll reports that trust in pastors has dropped to 36%. Who’s lower than pastors? Telemarketers are lower. Who’s higher? Nurses, doctors and pharmacists. What’s wrong? Why is it that the public does not trust the ethical profile of the clergy? I would just say that in some of these areas, such as we’ve been talking about today, upping the scientific knowledge and the ethical discernment on subjects like this might be a way of actually improving the professional contribution our average pastor can make to the wider community.

Well, those are my thoughts, and I want to thank Ray and PLTS and the Mohrenweiser family for their farsightedness, because this interaction between faith and science should not be dominant, but it is a way of enriching the ministry of the pastors and leaders of our church. So thank you very much.

Ray Pickett: Thank you, Ted. First, of all, I want to thank you, Arvin, for an incredibly clear presentation, and, and a very balanced presentation, where you look at the pros and cons and they’re almost equal on each one. So you’ve definitely raised more questions than we can answer. And I mean, I have a lot of questions, and I’m going to invite people to ask questions and come up, but the thing I think most about from this is just, you know, our, our inclination to want to control things and then and we all know this from our experience, the unintended consequences of trying to control our lives or anybody else’s life. So, again, it’s a lot to think about, and I appreciate, as Ted said, you sort of educating us as theologians and pastors, because this stuff is out there, and I’m not sure how much people are aware of it, but I mean, it raises all kinds of questions about even what it means to be human, as you say, so thank you so much.