Editing Your DNA, with Nobel Prize Winner Dr. Jennifer Doudna

There is a microscopic technology that now gives  us the power to edit our own genes while we're. alive to cure certain diseases, possibly prevent  others, maybe boost what our bodies can do, or even. one day give our kids abilities that nobody has  ever had before, effectively putting evolution. into our hands. And this is not some sci-fi  future. We are already using this technology. in real medicines in plants to grow new crops  in animals to create new species. It's called.

"CRISPR" "CRISPR-Cas9" and Jennifer Doudna won the  Nobel Prize for discovering it. "It's incredible! It's extraordinary." So deciding how we should use  this new superpower will be one of the greatest. challenges we have ever faced and one of the  biggest opportunities to reduce human suffering. So in this video we're going to use specific  examples to help you see how gene editing is. already affecting your life and help  you decide: How should we use it? When.

is it wrong... and when is it wrong not to?  This is Huge Conversations. Genetics! Secret of life! DNA. What does it mean  that we have this new power? To eliminate. diseases like hemophilia, sickle cell, Alzheimer's,  Huntington's, it would almost be unethical not to use it... It's great to be here! Thank you so much for doing  this I'm really looking forward to it My goal for.

this conversation is to work together to explain  how this new power to edit DNA might really impact. this audience's lives What's possible and how  can we help this gene editing future go right. the audience that you're talking to is great. They  are smart and optimistic and also because we cover. so many different things this might be the first  time they're ever hearing about CRISPR. For myself.

I have now done months worth of research for this  conversation but I'm no expert. Our bigger goal. for this show Huge If True is to explore better  futures because we believe that when people are. able to see them, they help build them. What's your  goal in this conversation? Why do this interview? I share your goals! I think CRISPR is such an  exciting technology and it's the beginning of what. will be possible in the future with genome editing  and how we can manipulate our environment and our.

bodies to maximize our health and maximize our  experience in life and and to really understand. our role in the world. So I'd love to share that  with everybody in the audience. And I imagine. incredible insights and science coming from all  of them in the future. I love that. That's Huge If True! To explain why this is a huge moment in human  history we need to explain why CRISPR-Cas9 was.

such a big leap. My understanding is that we've  known for over a century that there are specific. molecules inside our cells that carry information  in a four-part code. And then our cells use groups. of that code as a blueprint for how to make the  proteins that govern so much about us. From how. we look to how we think to how we get or fight  disease. But for most of that century we could only. read this genetic code. We couldn't change it. Could  you help me understand how what you pioneered. with Emmanuelle Charpentier was different from the gene  therapies and other gene editing systems that.

came before? What was the big insight and why is it  so important? CRISPR is a technology that came out. of fundamental science. The very first tool that  was used for gene manipulation really was coming. from the natural world and that was viruses. Some  viruses naturally insert into the human DNA in. our cells, HIV is one example of a virus that  does that. By studying how viruses manipulate.

DNA and how they get into DNA there were a lot  of insights about how we could potentially as. scientists change DNA sequences but we didn't  have the tools to do it. And so what happened next. was that there were a series of tools developed to  find a particular set of letters in the DNA of say. a human cell and alter them using tools that  were generated for that specific purpose. For the. the the wonkier folks in the in the audience  these include Zinc-finger nucleases and TALEN.

proteins. These showed that DNA manipulation  was possible and also could be very powerful. But what was challenging with those tools is that  they were bespoke meaning you had to make one of. them for every single change that you might want  to produce in a cell for example. And that meant. that they were expensive. They took a long time to  produce and then to to deploy. And this is where.

CRISPR comes in because what viruses and bacteria  over eons interacting in nature had figured out is. that they could use proteins that were directed  by molecules of RNA which are chemical cousins. of DNA. They interact with DNA So they look at  the DNA sequence on a letter by basis but they. allow easy recoding. And so scientists once we  understood how that recoding works with RNA we. could easily manipulate and change the sequences  in DNA that CRISPR can recognize. And that's.

really the crux of the technology. It becomes  a a programmable tool that can be directed to. essentially any DNA sequence where it can make  a change in a targeted way and in a way that is. easily controlled in the lab. So the big change is  that within the last few decades we've gone from. observing our genes to trying to change them but  slowly and with one-off tools to now with CRISPR. we have quick precise editing like a text editor  for the instruction manual of life. What does it.

mean for us that we have this new power? What  are the stakes here? Well it's kind of profound. I think because if you if you start imagining what  you can do when you have that kind of capability. to manipulate DNA sequences it's everything  from changing the ability of crops to resist. drought or to produce more tomatoes to changing  sequences in a human embryo that alter heritable.

traits that get passed on for future generations.  And so especially the latter application has truly. profound implications. It means that if you think  about it now as human beings we have in our hands. the technology to change chemically fundamentally  who and what we are. It's quite extraordinary. Huge. if true! Huge! Yes! Thank you. You talk in your  book about you say, the question is not whether.

we can change our genes anymore it's how should  we? My understanding is that within that debate. there's a big divide between whether we're editing  cells that are not involved in reproduction so. the change would end with us versus cells  that are in which case they would get passed. down to our kids and our kids' kids and maybe  even a whole population depending on the gene. Why is that distinction so important? It goes back  to concepts like eugenics and thinking about.

even even the Mary Shelley's Frankenstein you know  thinking about what we can do when we have the. power to alter who we are fundamentally And to  me it's and I think in general it's just. very it's a very different set of concerns  when you're thinking about changing DNA in an. individual which of course has safety and ethical  considerations but nothing like if we're changing.

DNA in a heritable way in embryos. The embryos  can't make that decision for one thing and once. that change is made it's permanent and it gets  passed on to all future generations. And so you can. imagine starting to change the you know the the whole genetic makeup of human populations if. this were to go far enough. If I'm imagining this  as you know two columns, one is somatic and one. is germline then there's also the type of change  itself sort of with a spectrum between treating.

diseases that we would all agree are diseases to  prevention of future diseases to what some people. might call enhancements or moving someone or their  descendants into a new part of what is possible. for humans... And I've even because this is a show  called Huge If True heard people talk about changes. that might move people out of what is now normal  for others. So super enhancements. And in fact in.

order to keep us grounded I have prepared some  specific examples. I'd love to use each of these. examples and get your help to understand where  do they fit into this debate? How real or not real. are they scientifically, how could they actually  impact the audience's lives or not? And what gets. you most excited in these different categories?  Okay so my first example is curing sickle cell.

in one individual. Could you tell me the story of  Victoria Gray and what's happening with CRISPR. right now in sickle cell disease? Well this is a  big success of of the CRISPR field. In the I think. late fall it was November and December of 2023  the food and drug administration in the US and the. their counterpart in UK approved a crisper-based  therapy for sickle cell disease patients So these. are people that have a single genetic um mutation  that gives them a very severe blood disease that.

results in frequent you know requirements for  frequent blood transfusions and if they don't have. those they have organ failure over time They have  u very um severe crises that happen frequently. that are very painful for them So you can imagine  extremely disruptive to their lives And with this. CRISPR-based treatment it's a one and done therapy  that doesn't exactly cure the disease at the.

genetic level but what it does is suppress  the effect of the disease-causing mutation. And it does that by turning on the production  of a protein normally only made when we're. uh developing in the womb which is a protein  called fetal hemoglobin that when turned back. on using crisper can suppress the effect of the  disease-causing mutation in adult hemoglobin And. as a result people like Victoria Gray and she was  the first US patient to receive this therapeutic.

have not had another sickle cell crisis since  receiving this one and done therapy. So it's. incredible! It's extraordinary and having talked to  her and a couple of other folks that participated. in that very first clinical trial I've heard  their stories about being just you know their. lives being completely transformed by this and  their ability to then function in a way that they. never imagined to be possible given their previous  disease experience. So it's amazing I would put.

this in the category of I'd call it a treatment  and I'd call it a treatment for an individual. Right now we're not using it in the human germ  line but it's it's a clearly a a very exciting. advance for the field with some caveats Right now  this therapy is very expensive meaning that most. people who could benefit from it globally can't  get access to it. It also requires hospitalization. because they have to go through a bone marrow  transplant And that's something we're working very.

hard on here in our institute to overcome We'd  love to have this therapy ultimately deliverable. in a in an easy format that doesn't require  hospitalization How should I think about the fact. that this treatment for cickle cell is based on  the fact that cickle cell is related to one gene. Well you put your finger on a really good point  Cleo That's that's exactly right So this is a. disease that results from one gene that's gone ary  and right now crisper is is well suited to treat. that type of disorder It's a lot harder to think  about how you would treat a disease like let's say.

schizophrenia which almost certainly results from  maybe hundreds of mutations in the human genome. So those are going to be a lot harder to treat And  as I understand it castvi requires removing blood. from the patient making those changes in a lab  and then putting blood back in If we wanted to use. crisper for single gene or maybe very small number  of gene changes for treatments in individuals but.

those treatments needed to be in our lungs or our  liver or our brain how would that work yeah it's. that's a lot harder It would work with difficulty  We don't have a good uh strategy in general for. getting the crisper molecules into particular  cells in the body Although again that's something. that's changing quickly It's an area to really  keep an eye on over the next few years because. many many uh scientists appreciate that this is  an important challenge not only for crisper by.

the way but also for any kind of human therapy is  how do you do the therapy in the right cell type. or the right tissue in the body how do you get it  there in in a safe and effective way and that's. clearly a challenge with crisper I think that  over time what we're going to see is increasingly. uh sophisticated technologies for doing exactly  that We're already at a point where for a disease. like cickle cell uh I think we're you know maybe  within a few years of having that capability to.

deliver in the body and safely and I think at  a cost that would make this therapy much more. widely available and I can't tell you how excited  I am about that Me too just to be even more um. nerd out on this point a little bit more because  I know that delivery is a big interest area for. a lot of people that are working on this um what  what are the actual challenges with the delivery. is it that our immune system attacks it well let's  think about how the body is put together We have a.

lot of different kinds of cells that make up our  bodies and even within one particular organ like. let's say our brain many different kinds of cells  are required to form the human brain But when we. have a disease that affects our brain like let's  say Alzheimer's disease that disease is primarily. affecting only some of the cells we think not  all of them And so ideally what one would like. to be able to do is you'd like to get the genome  editor into just those cells where a change to the.

DNA sequence could have a positive effect on the  patient and not bother any of the other cells in. the body But doing that as you can imagine is very  tricky And that's partly because the cells are all. growing together So you have to have a sort of a  chemical mechanism of distinguishing one cell type. from another Fortunately cells often have little  zip code molecules on the surface that mark them. as different cell types but so far science is  still trying to figure out what they are and.

figure out which zip codes go with which cell  types So that's something that's very much work. in progress And even once we know that then the  challenge is how do we recognize one particular. set of molecules on certain cells and ignore  all the others That's something that viruses. are actually very good at doing So one of the  motivators and and and sort of inspirations in the. delivery field right now is looking at how viruses  do that kind of recognition and delivery and then.

taking advantage of it for delivering other  molecules rather than delivering a virus Can we. deliver our our crisper cargo i know you've used  the analogy of we now have the ability to cut and. paste DNA like a text editor And so I'm imagining  if I play this analogy out a little bit it's like. I we now have the ability to cut and paste and  create new letters but we are still inventing. the postal system We're still trying to figure  out how to send the letters Exactly Interesting. That's right Got it Yep My second example is  curing Huntingtons or al removing Huntingtons.

from all your future descendants What do I need to  know about this example and this general category. well Huntington's disease is a is an interesting  example because it often does run in families and. as some folks in the audience may know it's a  neurodeenerative disease So it causes severe. degeneration of the brain over time It often uh  doesn't begin until somebody is in their midlife.

somewhere Uh so 20s 30s 40s depending on the  exact uh detail of the mutation they have It's an. interesting target for crisper because like cickle  cell disease it's a single gene that causes the. disorder that's very well defined And furthermore  we know of families in the world where this. disease gene is inherited by by by kids you know  from their parents And so it's a it's terrible in. the sense that they can see what's coming and know  that they have this genetic dis predisposition.

but they can't do anything to prevent it So  it's you know it's really sort of a horrible. thing to contemplate And with crisper one could  imagine at some point being able to remove that. disease-causing mutation from an embryo such that  not only does the individual once they're born not. bear the Huntington trait but they also don't pass  that trait on to their kids It would be amazing. and change a lot of people's lives It could change  a lot of people's lives and and I I certainly.

think that if and when that capability is in our  hands that it would almost be unethical not to use. it for that purpose But we're not there yet And  the reason is that it's very tricky to control. the way that DNA repair which is really part of  the whole editing process The way that that is. conducted uh especially in embryos is still very  much under uh you know investigation And so I. think until we have a good handle on how it works  and then how to do it safely it will remain a you.

know future aspiration but not something that  I think should be done today That brings us to. my third example which is preventing something  like HIV in your future descendants There was. a scientist in 2018 that edited human embryos and  those embryos were born into babies who as far as. I can tell are still alive and many scientists  including yourself opposed that decision My. understanding from your book is that you opposed  it because you felt the risks to those kids were.

greater than the rewards Um could you explain  why that was the case in that example but also. more generally what are the other options besides  crisper for many of these diseases and how should. we think about when a use of crisper is actually  necessary and and therefore potentially has a much. greater incentive to use it i think with any  therapy you have to ask yourself do the risks. outweigh the benefits or not and with crisper and  especially if we're using it in embryos or the.

germ line um the risks are are quite significant  in the sense that any change that gets made is. is permanent and it gets passed on to future  generations So you want to be very confident. that those changes are going to have a positive  impact and have the desired outcome And so in. the example that you cited yeah it was a very you  know very um kind of alarming case because it was.

a situation where a scientist informed parents  that they were uh going to receive a treatment. for their unborn children that would prevent HIV  transmission to those kids during birth and later. in their lives and furthermore that that trait  would then be transmissible to their kids But I. don't think from what I understand that the those  parents in the trial really understood the risks. of the technology and that for example it had  never even been tested in in animals prior to.

putting into into people which you know is one  really big ethical concern Furthermore with the. the example of HIV there already are well-known  treatments that can prevent transmission in kids. even if they have an HIV positive parent as was  the case in that situation So given that there. was already a you know very wellested and safe  way to prevent transmission arguably it's pretty.

unethical to then apply an untested un untried  uh new technology to to do this in in people And. um and then the third uh issue kind of gets in  a little bit more in the weeds of what actually. happened that when it was revealed how the genome  editing was done in those embryos it was clear. that it wasn't a clean edit In other words it  wasn't a uh a way of making a a very precise.

manipulation to the DNA That instead what probably  happened was that multiple different kinds of. edits happened in the cells of those embryos  So that those kids were actually born chimeas. meaning they had a mixture of different kinds of  uh genetic makeup in their cells Would that be. harmful or not the answer is we don't know because  it had never been tested before So these are all. things that I think are are really um important  to understand when people evaluate whether a new.

technology especially something to be used  in embryos would be allowed to to go forward. It seems like a really hard challenge especially  as someone who's a pioneer in the field because. we talk a lot on the show about how the status  quo the world that we live in right now is sucks. in all kinds of ways right like it is just as bad  to you know allow the existence of a huge amount.

of suffering when you could change it as it is to  you know cause that suffering by changing it Right. this is a classic human problem that we deal with  in so many different ways And one of the things. that I found incredibly powerful in your book  there's this quote... this is Charles Sabine a. victim of Huntington's And he says "Anyone who has  had to actually face the reality of one of these. diseases is not going to have a remote compunction  about thinking there is any moral issue at all.".

And the reason why that has really stuck with  me is because I think it's one thing to talk. about these weights and counterweights in  theory and then you talk to someone whose. life could actually be changed and you come away  feeling like "Holy cow how can we how can we help. as quickly as we can in the way that you know  keeps them safe and keeps the rest of us safe?". What's that actually like for you when you hear  from people who are experiencing diseases that. you feel crisper could be really good candidates  to help solve it's really getting to the heart of.

what it means to suffer from a disease like that  and then to have the opportunity to have a a cure. for it something that might have been unimaginable  even a few years ago And you're right I hear from. people uh pretty much now it's probably at least  once a week that write to me about diseases in. their families that are of genetic origin Often  it's disease affecting kids and asking you know.

when and how will Crisper be able to make a change  and it's a it's a really big challenge I I feel. um I'm I'm humbled by it I'm honored that people  share their their personal uh stories with me And. I I have to admit I sometimes feel a little  bit helpless because I I I realize the the. challenges still that lie ahead scientifically and  technically to make it possible But at the at the. same time I feel an incredible sense of motivation  and passion because you can see how especially.

with the cickle cell story how it can be so  positive and so beneficial So it's a you know it's. a real motivator getting out of bed every day Yeah  I bet Speaking of good health I want to show you. something I'm wearing the Whoop MG It just came  out and I've been testing it over the last month. So let me show you what I find most interesting  My goal is to just feel great I want to wake up. and I want to have energy and I don't want to feel  tired and I want to be able to make this show and. learn and I want to feel strong and I want to feel  that way for as many days as I can for the rest.

of my life So I use Whoop to set a goal to feel  better and then to keep track of my daily habits. It uses these sensors to measure among other  things nine biometrics that have a long-term. impact on my health outcomes And it combines them  into what Whoop calls my health span And that. helps me understand how my habits right now affect  my long-term ability to have as many healthy days. as possible One thing I found helpful is the Whoop  AI coach Today for example I was feeling tired so. I just asked it I'm feeling tired Why then it  analyzed my real data from the last month and.

helped me understand a couple things that I could  do especially around hydration and workouts And it. also has sensors that measure electrical activity  from my heart through my skin So I can do an ECG. All of this just helps me feel better dayto-day  and hopefully longterm too So if you want to try. it go to this link right here or click the link  in the description Now back to gene editing As. someone who is lucky enough not to be currently  struggling with disease when I think about how.

crisper might most directly impact my life I think  about the genes that correlate to future disease. and how we might prevent future disease I think  about reducing Alzheimer's risk which I understand. relates to APOE4 or heart disease um and PCSK9  or cancer and BA um that would completely change.

my life and I'm curious what what are the most  interesting relevant examples in this category. that you think about i think those are three  great ones And in fact it's probably worth. pointing out that there's already a clinical trial  running for people uh who have the gene that makes. them susceptible to high cholesterol buildup and  hence to cardiovascular disease Yes many of us do. uh have this and um and the idea in that clinical  trial is to use crisper as a preventative So can.

you make edits in the DNA of the liver that would  prevent cholesterol accumulation in people that. are otherwise susceptible to this if it works  it would be incredible because again it's a you. know it's a one-time therapy that avoids the you  know the need to take drugs daily or weekly or or. monthly to control cholesterol levels and would  give people freedom from worrying about you know. heart attacks at a young age if that would  be otherwise something they might experience.

So I think that's really exciting It also you know  raises uh the bar I think for what we would demand. in terms of safety because probably none of us  would want to you know if we're not currently. ill we don't want to take something that might  make us ill and and we want to take something. only if it can really improve our health Does  that study that you just mentioned relate to what. we talked about with the challenge of delivery  because if they're delivering it to the liver. that implies that they are they editing it in a  lab in the liver are they also trying to find a.

delivery mechanism that works amazing They are  Yeah Amazing Right now here's the thing So the. liver is an organ that naturally filters toxins  in our body So a lot of molecules will end up. in the liver quite naturally So it's a bit of a  unique organ in that regard And so it means that. for a lot of the interest in crisper at least  in the very early days before there were many. strategies for delivery it was you know people  kind of recognized that the liver would be a great.

uh organ to target because it's it very naturally  accumulates molecules including crisper So that's. been um the the basis for this ongoing trial And  they're actually using uh little greasy blobs. that are known as lipid nano particles These are  known to any of us that have had the COVID vaccine. because that's the the basis for delivering the  the COVID vaccine is using these little lipid. nano particles And those particles will naturally  traffic to the liver in the body and they'll carry.

along other molecules like crisper So that's been  the basis for for that trial Cool Yeah Um okay So. now we're getting into the category that I think  people would call enhancements Here people talk a. lot about eye color and height and things like  that but there are also and these are the ones. I find most interesting genes that might relate  to enhancements for health that are not related. to disease So genes for example like the MSTN  gene associated with building larger muscles.

or and this one I get very excited about uh DEEC2  which I understand is associated with needing less. sleep What examples do you think about in this  category that are most genuinely interesting and. what should people know about what's realistic  here well I think those two you brought up are. are interesting There's also a gene that was  identified by a colleague of ours at uh UC San. Francisco In fact he won the Nobel Prize for that  work that is involved in pain perception And so.

you could imagine you know in in fact there are  natural uh variations of that gene in the human. population And people that have a certain type  a certain format of that gene are naturally uh. pain tolerant And so you could imagine ways that  you might use that type of genetic manipulation to. remove experience of pain in you know say cancer  patients or you know people that have a chronic. uh uh pain uh causing disease and so um I think  those are all extremely interesting and yeah do.

we you know it's a little bit this starts to get  into to me a bit of a gray area those enhancements. like if we're talking about pain perception that's  you know it's really a health related thing but It. it's an important uh aspect of of thinking about  genetic manipulation because it forces us to you. know to really ask ourselves where do we draw that  line and I argue that it's very hard to do that I.

think it's you know there's a kind of a continuum  and uh there's certain certain modifications. that some of us might call enhancements and the  rest of us might call health related So who who. decides and I think those are those are some  of the real issues that we're grappling with. This is the area if I'm honest I started to  struggle with a concern that came up a lot and. I'm sure is coming up right now for the audience  as they're watching this is that we move into a. world more like the movie Gatka that there is  a divide between what people can and can't get.

um maybe based on wealth maybe based on other  factors that that harms society because there. is a a gene gap as you call it at the same time  I've and I think everyone has witnessed over and. over again an expensive technology becoming less  expensive over time as it's used by more people. Um a sort of sub subsidy maybe of that technology  early on that then ends up benefiting the rest of. us because it gets time to develop and exist  and and just sort of comes into the world Um.

and I have a hard time with the argument that we  shouldn't use something because only a few people. could use it in the short term when the the hope  right is that everyone can use it And I I wonder. you know why do we care about this when it is a  huge opportunity to reduce human suffering but. not when it's our iPhones how do you think about  something like that i think I'm with you Cleo I I.

really it it doesn't sit right with me to argue  that we shouldn't develop a technology because. today it's only available to a few And as you said  that's that's often true When new technologies. come along they're not easily uh distributed early  on typically and they often are expensive in in. the early days I mean think of even personal  computers kind of went through that transition. And so I think that we have to be very forward  thinking and we have to be imagining what could.

be possible in the future I'm highly motivated for  example by the idea that crisper although today as. a therapy it's only available to a few That's  not going to be true forever It's clearly not. And also I'm I'm a big believer in you have to  you have to imagine the future to create it You. have to think about where you want to go and then  work to get there Me too My understanding is that. one of the ways that people can get some of these  all the above prevention enhancements treatments.

um is through selection of the embryos that  they actually end up using in the first place. PGD Could you explain how that works and how the  existence of that option influences how we might. or might not find it appropriate to use crisper  so one thing that's important to point out with. crisper when we think about using it in embryos is  that it would be done in the context of in vitro. fertilization Maybe that's obvious but you know  in vitro fertilization or IVF technology has come.

a long way from you know where it started And  uh today it's possible to for people that are. are having a child using invitro fertilization  to actually conduct embryo selection if they. want to They can identify embryos that have  certain traits or avoid certain traits that. they otherwise might inherit And so that's been  a great way uh for families to screen out uh. disease-causing mutations For example I think  that with crisper you could imagine using it.

similarly where you could use it to remove a trait  and then screen embryos for the ones that have uh. you know where you've successfully done that Yeah  And also the key difference would be that crisper. can actually make changes that might be present  in all embryos for that specific couple Chris. work could edit whereas PGD merely selects Correct  Yeah I also think an important thing to talk about. with respect to PGD is none of this is easy I did  the egg freezing process and I can tell you that.

getting that number of eggs out is hard That's the  first step in IVF It's difficult and timeconuming. and expensive no matter what And so you know  we're we're dealing with a lot of different. weights and counterweights about what might be  easy or difficult for people in different ways. Yeah absolutely You know I think there going to be  some interesting changes over time Again I don't. think they're happening you know immediately but  I do think that there's a lot of work being done.

on human reproduction um about gameamtes you know  eggs and sperm that are you know going to probably. change the landscape of what's possible in the  future And I'm talking about over the coming. decades right so you know for folks that are you  know very young kids right now you know this might. be something that would be become possible in  their lifetime or something they would want to. consider doing Um so that's an area definitely to  keep an eye on because I do think there's a lot of. activity Before we move into plants and animals  which I really want to get to because I think.

it's one of the biggest ways crisper might impact  people's lives Um there is one additional category. here um within humans The final category and this  is a show called Huge If True is as we understand. more about our genes there could potentially be  ways to move people beyond what is possible for. anyone right now Helping you heal faster extending  your life beyond what's normal giving your kids.

abilities that seem like superpowers I don't  know what's possible How do you think about. this i had a call years ago now from a reporter  at Sports Illustrated They wanted to do a story. on enhancements or maybe even you could call  them super enhancements that would create. super athletes You know imagine basketball players  that were eight feet tall or you know could jump. uh jump unreasonably high or uh people that  had and I guess this is already one thing that. is theoretically possible having you know very  very well-developed muscles and muscle structure.

I think these are are fascinating I think for  the most part they're not really realistic at. the moment Mostly because we don't understand  the genetics well enough to understand how. manipulating those genes would affect our health  in other ways And we know for sure that you know. our genes are interconnected So when you tweak one  thing you're probably not just changing one effect. you're you're changing lots of other things So I  think that for any of those kinds of manipulations.

clearly a lot of research would need to be done  But um but I'll just mention that since I know. we're going to get to plants and animals in the  plant world we're already seeing just incredible. advances using crisper to create the type of  plants that you know certainly breeders have. never had success in creating and that if you  tried to do it with traditional breeding would. take inordinate amounts of time probably  decades that increase the yields of crops.

that increase the nutritional value of crops  in ways that could be incredibly uh valuable. and exciting for probably all of us and probably  not in the distant future So I think that's an. example of the kinds of super enhancements in  organisms that we're going to see with crisper. So play that out for me What happens next in  the world of plants and animals using crisper. i've thought for a long time that that uh  that the the extraordinary global impact of. crisper will probably happen first with plant and  animal manipulations And the reason is when we're.

talking about making changes in human beings that  obviously requires a lot of testing to make sure. that it's safe We have to do a lot of research  so we understand how a genetic manipulation. will affect our health Whereas uh if we're do if  we're making changes in let's say a plant you know. we can conduct that as an experiment and many of  those can be performed at the same time and with. crisper you now have a tool that allows the kind  of precise manipulation that plantreeders could.

only dream of in the past So maybe just to explain  how traditional plant breeding works for people. Traditionally plantreeders would introduce random  changes into the DNA of plants And they would do. it by um using chemicals that would change DNA  sequences randomly or even exposing seeds to. radiation that would also lead to random genetic  changes then planting the seeds and allowing. them to grow up and looking for plants that had  changes to their traits that were desirable and.

then picking those and breeding them and you know  and so you can start to think about that There's. a there's a few issues there right first of all  it takes a long time Secondly the changes are. are really random So if you wonder why is it that  we have roses that are thornless which might be a. desirable trait but they've lost their nice smell  Well it's because you know traits are coupled. right and so you you tweak one thing and you you  get something that comes along with it that maybe. you don't didn't want but you now can't get rid  of And we see that over and over again So with.

crisper we truly now have an opportunity to make  targeted precise changes that only alter one trait. and don't affect other things So I think that's  really exciting And another uh aspect of crisper. in plants that is just truly mind-blowing for me  is that you can use crisper in multiple genes at. one time Now you could do that in humans too and  I'm sure that will come But today in plants it's.

already possible to change 5 10 15 genes at  a time And that means that we can make really. quite sophisticated alterations to to plant traits  in one shot and do it safely and do it precisely. And the more that we learn about the genetics  of plants and that's a whole separate area of. research for sure but you know it it just they  kind of go hand inand We learn which genes we can. tweak and then we have the tool to tweak them Is  that happening right now in a way that I might not.

notice when I'm at the grocery store am I eating  plants that have been edited with crisper or not. yet only if you're in Japan Interesting Well  in Japan there's a there's a tomato that's been. approved that has a crisper change that makes it  are they argue more have higher nutritional value. Um will that happen in the US oh yeah I mean it's  certainly coming and already there are changes in. um plants like well fungi like like mushrooms  where there are non-browning mushrooms that were.

created using crisper and um a colleague of ours  has created tomatoes here in in his lab in in the. US that are much higher yielding than uh normal  unedited tomato plants but they don't have any. other differences in the taste or the look or the  you know the the sort of properties of the tomato. So again something potentially very exciting and  very desirable Right now um there's a there's an.

ongoing uh sort of debate in different countries  around the world about how those types of crops. will be regulated And here in the United States  the US Department of Agriculture has re has ruled. that when changes are made to the DNA of plants  that could be done by traditional breeding if. you took the decades to do it but are sped up by  using crisper Those are not considered genetically. modified and they're not regulated Whoa Which is  so interesting right yeah So I think absolutely.

in that regard at some point in the notistant  future we could see these types of of crops in the. grocery store Fascinating I al I also know the two  other categories that I want to talk about here. are related to climate change and related to human  health by virtue of editing other animals So on. climate change the example that I have is making  cows fart less methane Could you tell me about. that one yeah that's a good one That's a good  one So the uh yeah this is this is a a project.

that um you know a lot of scientists have come  to recognize that one of the most uh significant. contributors to global carbon emissions in the  form of methane which is a powerful greenhouse. gas is the um is the farming of animals and in  particular is cattle And they produce a lot of. methane and they produce it primarily from bugs  in their gut that are methane makers and that uh. that uh you know produce this this gas instead of  using food that the cattle are eating to make more.

milk or more meat So wouldn't it be great if there  were were a way to alter the metabolism of those. organisms those bacteria we call it the microbiome  in these cattle that are producing methane dial. that down and turn up the ability of their of the  these metabolic pathways to uh generate nutrients. that are actually valuable to the animal and and  valuable to the farmer and to the consumers of.

of these products That's exactly what we're doing  now with crisper because again crisper is a great. tool for this It's a tool that has the ability to  go into the DNA of just one type of bacterium to. one gene in that type of bacterium and make the  kinds of changes that will alter their metabolism. permanently We've got some of the best uh cattle  biologists in the in the world who are working at. Davis and they had already shown that if you  change the cow microbiome by altering their.

diet that you could have a very profound effect on  methane production So that's very exciting We know. this is an approach that can work The challenge  there is that altering the cow diet is not an. approach that's inexpensive and it's not easily  deployed to farmers around the world Whereas if. we had a very easy let's say it was a pill that  you could give once to cows when they're born. that would edit their microbiome in a way that  was sustainable over their lifetime You could.

imagine that type of change being incredibly  profound and also easy to deploy And that's. exactly what we're working on And again you're  editing the microorganisms inside the cow not. the cow itself So it's a different category of  assistance for the animal That's right Yeah How. can we do that in humans and how might that help  us without editing us editing the microorganisms. in us This is such an interesting as uh area of  medicine I think it's it's early days but I think. there's a lot of evidence pointing to our own uh  microbiome the human microbiome having a profound.

impact on our health in ways that we're only  starting to appreciate Now we have a colleague. uh at University of California San Francisco  who has shown that in people especially in. kids that are susceptible to asthma they tend to  have molecule produced in their own microbiome. that's not present in people that don't have  asthma And she's shown a correlation between.

the concentration of that you know microbiome  produced molecule and disease susceptibility. So again we see a really exciting opportunity to  use crisper to turn down the production of that. molecule and potentially prevent asthma in kids  So that's something that we're currently testing. with her laboratory in animals and if it works  then we hope to test it in humans Wow What are. the other examples that you think about often that  I haven't asked you about there are areas of sort.

of um understanding microbial human health biology  where I think there's a lot of a lot of exciting. potential and one is is really understanding the  connection between our microbiome and our brain. and another is thinking about the connection  between our microbiome and our immune system. So imagine that you know when when when we're  born we have our our immune system is developing. we're also becoming uh you know hosts to lots of  different kinds of of microbes So there has to be.

a an interplay there And we know that uh there's  a relationship between inflammation in the brain. which often involves microbial activity and  and activity of our our immune system and later. susceptibility to diseases like Alzheimer's So I  think as the genetics of those interactions become. better understood over time and by the way that's  something that crisper can help with is really. dissecting the the genes that are involved in  those interactions we now have the ability to to.

change those uh those genes whether it's changing  them in the microbiome uh of of an affected person. or as we talked about with prevention potentially  doing it before we're susceptible to disease. If someone is coming to the end of a story about  crisper what do you want them to know well we've. talked about a lot of great applications of  crisper I guess I I want to circle back to. maybe where we started in the conversation because  I find that a lot of students today will ask me.

um the questions about you know how did I get  interested in this area of science or how did. I how did I you know how did I start working  on on crisper in the first place did I know. that it was going to be you know a really exciting  technology when we got started and the answer is. no And I I think it's important to to emphasize  a couple of things here that are are I feel and. especially at in this moment that we're in and in  our country and in the world that that I think has.

been perhaps missed by a lot of people and that  is that you know science is really a it's a it's. a process and it's a process that's very very much  a human endeavor Now maybe AI will change that at. some point I'm I'm sure it will will assist us  But fundamentally my experience is that it's. very much driven by human curiosity It's a person  or a few people wondering I wonder how something. works and then digging in to figure it out And  if you look at the fundamental breakthroughs.

that have happened over time in the biological  sciences certainly the vast majority of those. have come about from that type of question and  answer And crisper is very much in that category. So I think it's great for people to appreciate  that that's kind of how science works And so I I. I always encourage students to think about what  they're curious about what they're interested. in what do they find fascinating what's so  what's something that they've experienced. in their lives where they have no idea how it  works and they wonder what the heck right and.

and they want to figure it out because that's  always how I've I've directed my research And. um there's real value to that and that's really  how fundamental breakthroughs are made So I I. think we have to first of all appreciate that  and secondly I hope agree that we're going to. continue to support that kind of curiositydriven  science for the next generation hopefully who are. listening to this I hope so too What are some  of the what the heck curiosities for you right. now feel free to get as nerdy and specific and  maybe don't explain like just what are some of.

the things that are that feel what the heck to  you well I mean I'm curious about all kinds of. crazy things like I heard about a great project um  to investigate how bipeedalism emerged how how it. evolved You know why are we bipedal whereas our uh  ancestral apes were originally not bipedal and so. uh there's actually a scientist that I know  who's using crisper to try to figure this out.

in rodents because there are related rodents  some of which are bipedal naturally and some. of which are not So she's trying to figure out  the genetics of that So there's a that's a kind. of a cool one What the heck uh what the heck um  in our own research I'm you know very interested. in well as we discussed this connection between  microbiomes and our health So there's a there's. a number of things that we're investigating  there by tweaking the genes of microbes and. then asking how does that affect the behavior of  human cells So I think that's a you know that's a.

an area that there continues to be lots of kind  of curiosities to to explore And then the third. thing is more applied but a big area that we're  focused on in my own laboratory and here at our. institute is this question of how we deliver  molecules specifically into cells because that. that's really going to be transformative when  we have that that capability more broadly And. so I'm curious about how this happens in nature  and of course viruses do it But it turns out so.

do bacteria You know certain bacteria have the  capability to get into particular cell types. So we continue to investigate those fundamental  processes hoping that we can uh you know learn. from them and and learn how to do it ourselves  What the heck what the heck can I ask you what. does it feel like to have been such an important  part of bringing this new power into the world. humbling I guess is the first word that comes to  mind I feel grateful too I feel so excited to be. part of it You know I feel um uh you know when I  was a kid growing up I just could dream of doing.

science in the future and imagine myself as a  scientist but I had no idea really what I would. work on or where where I would end up I could have  never in a million years and you know imagined. um all of this coming to pass But it's been  such an incredibly interesting journey and I. also feel that I'm always learning you know so  it's a it's it's given me great opportunities. to learn new things My last question for you  is could you read this you wrote it That last.

paragraph few technologies are inherently  good or bad What matters is how we use them. And when it comes to crisper the possibilities of  this new technology good and bad are limited only. by our imaginations I firmly believe we can use  it for the former and not the latter But I'm also. cognizant that this will require determination  from us individually and collectively As a. species we have never done anything like this  before But then again we've never had the tools.

to do it The power to control our species  genetic future is awesome and terrifying. deciding how to handle it may be the biggest  challenge we have ever faced I hope I believe that. we're up to the task Thank you so much for your  time I really appreciate it Awesome Yeah Oh this. is very fun Thank you Boy I'm really impressed  You did a you clearly did a lot of homework. and uh you had great questions Thank you We got  more deeply into this than is usually possible.

in this type of a conversation So that's great  Really means a lot to me Yeah for saying that.