00:00:00: Hello

00:00:15: everyone and welcome to another episode of the Strategy & Insider podcast where we explore the future of health.

00:00:21: Today, We're stepping into one of the most exciting and fast-moving frontiers in modern medicine that truly merits the label Future Of Health.

00:00:30: talking about genome editing And more specifically The revolutionary technology known as CRISPR We will go deep, literally to the level of our DNA... ...to explore how scientists are now editing the code-of life itself.

00:00:43: To correct the root cause of diseases rather than managing symptoms.

00:00:48: And there is no one I could imagine better suited to guide us through this conversation Than our guest today who leads one of the world's leading genome editing research institutes.

00:00:58: So that said a very warm welcome to Dr Brad Ringheisen is the Executive Director of the Innovative Genomics Institute, or a short IGI headquartered at the prestigious University of California in Berkeley.

00:01:14: The IGI was founded back in twenty fifteen by Nobel laureate Jennifer Doudner –the co-inventor of CRISPR-Cas-IX which is one of THE most transformative scientific tools our era and we will surely unpack what it means in just a moment.

00:01:30: The IGI's mission is to develop and deploy innovative genome engineering tools that treat human diseases, help end world hunger.

00:01:38: And also create a more sustainable future spanning healthcare sustainability public education but also advancing Genome Engineering as a whole.

00:01:48: Brad's role itself at the IGI basically is that of a translator and accelerator, bridging revolutionary gene-editing research with affordable accessible real world solutions.

00:02:01: Before joining the IGI in twenty twenty, Brad's career already spent very remarkable range of fields from fundamental research to defense science and national security innovation.

00:02:12: He holds a PhD in physical chemistry And he also led the bioengineering and biofabrication section at U.S.

00:02:22: Naval Research Laboratory, pioneering work in bioprinting tissue engineering an early organ on a chip systems.

00:02:31: after that He joined DARPA which is the US Defense Advanced Research Projects Agency where he served as director of the Biological Technologies Office overseeing cutting-edge programs in genome editing apigenetics, neuro technology and bio manufacturing.

00:02:48: This is really a truly impressive trajectory And I'm honored to have you with me as my guest today.

00:02:53: Brad.

00:02:53: again A very warm welcome.

00:02:55: Thank You so much.

00:02:56: i'm excited to be here.

00:02:57: Hey your career has taken Really an extraordinary path even before the iti.

00:03:03: after your phd?

00:03:05: You moved into the public sector more specifically The u.s department of defense and its subsidiaries.

00:03:12: As i just mentioned What initially drew you towards the military research ecosystem?

00:03:18: And how does research conducted for defense application differ in its pace, risk tolerance and objectives from civil research such as FAMR&D let's say.

00:03:30: Yes it really is a unique career trajectory.

00:03:34: I spent five years at University of Wisconsin-Madison studying to do reactions, some of the most fundamental reactions that you can do in acid-base reactions and surface chemistry.

00:03:50: And these experiments were tremendously detailed and sophisticated.

00:03:55: I would spend some days all day long just trying to take one single measurement.

00:04:00: That was after weeks and weeks and week planning setting up experiment doing this on very sophisticated pieces machinery.

00:04:08: so when i'm looking start my career I really wanted to branch out into more application and applied research.

00:04:17: The Naval Research Lab was one of the leading laboratories in the country to look at applied research.

00:04:24: Of course, those applications are for the Department of Defense but I'd like to tell people that it didn't involve things that went boom.

00:04:32: Usually we were trying to protect people who were looking at traumatic brain injury or looking at battlefield medicine and chemical biological defense And I found it actually quite stimulating and exciting.

00:04:45: Every day you would wake up, you knew what your mission was... ...and we worked for the Department of Navy.

00:04:51: so a lot our applications were specific to either the Marines or naval seamen and officers And every day you knew what you were working towards.

00:05:01: You know, What was at stake with trying to protect those individuals and try to help those individual recover?

00:05:09: So I actually found it very excited in a very stimulated nice stayed there the lab for almost sixteen years

00:05:15: Wow!

00:05:16: And he moved on.

00:05:17: of course right and i did describe your role as the IGI somewhat informally as a translator but But of course is much more than that.

00:05:26: In a nutshell, what are your key responsibilities as executive director and what's in there motivating you to come into the office every morning?

00:05:35: Well yes.

00:05:36: I'd like to think of.

00:05:37: what i do here is exactly that...I have to translate a tremendous breadth and depth of science And talk about how it can impact The world.

00:05:48: We're working on some of the largest societal problems in the World Things Like Methane emissions from livestock, which is the largest methane emission source in the world.

00:05:59: Rare diseases where there are no cures more broadly or complex and common diseases like cancers right now that are still untreatable solid tumor cancers of the gut as one example.

00:06:13: so I think i learned how to translate science this way by going from the naval research lab.

00:06:22: DARPA is one of the crown jewel research funding agencies in The United States.

00:06:28: It's high risk, High reward Research.

00:06:30: its sole purpose Is to try To stimulate breakthrough science.

00:06:36: and In order to stimulate breakthrough Science it's not magic you have to form teams Of the best scientists in the world.

00:06:44: You Have to think about ideas that thinks about a future of ten and twenty years from now.

00:06:51: That's just the way DARPA works, it's steeped in the culture.

00:06:55: what DARPA is.

00:06:56: so by leading the biotech office at DARPA I was literally working with some of the best scientists around the world pushing them to try discover and innovate faster than they've ever done before this DARPA organization, I'm able to go to the IGI work with one of the preeminent scientists in the world and Jennifer Doudna.

00:07:24: With one of technology's genome editing that has a potential reshape almost every aspect.

00:07:31: our lives as humans interact their environment how we treat potentially prevent disease.

00:07:37: so where better philosophy, scientific philosophy of high risk, high reward.

00:07:45: Teamed multidisciplinary research to try to push the pace of research to make an impact in a world because quite honestly there are extremely important problems that I believe genome editing can be answer too.

00:08:02: This really sounds fascinating, and obviously you also have life outside the lab in the institute.

00:08:07: How do you personally stay curious knowing that you are in a very vibrant Berkeley Bay Area?

00:08:13: Are there fields or thinkers that influence how you approach your work at IGI?

00:08:19: And how did it relate to this?

00:08:21: Well I think there's two answers for that.

00:08:22: There is scientific answer Human a more human relatable answer.

00:08:27: and I'll start with the human Relatable Answer.

00:08:31: I have three children.

00:08:32: they're all in their early twenties.

00:08:34: now two of them are actually in science PhD programs here on The United States, but care very deeply about the future.

00:08:42: And yes it's personal for me because of my children But also Now that i've moved out Here to this amazing place In the Bay Area uh...I am less than A one-hour drive from some of the most beautiful natural landscapes, mountains and coastlines and cliffs.

00:09:00: And the sea creatures in whales and seals and sea lions... There's almost an unspeakable amount of beauty!

00:09:10: One thing I like to do is just go up into the hills here outside Berkeley and Oakland and walk amongst redwood trees that are there.

00:09:20: You very quickly understand there is a lot to protect here in this world.

00:09:26: And that means a lot, to me as someone who enjoys and loves being in nature.

00:09:32: so I find motivation now.

00:09:33: not you know i told you before I worked for the Department of Defense.

00:09:36: my motivation there was to help people to protect people To Help Them Heal.

00:09:42: Now Oftentimes My Mission when I wake up, is to do that.

00:09:45: To more broadly look for cures or diseases that are currently untreatable.

00:09:50: but it's also to wake-up and try to protect this amazing world we live in.

00:09:56: being part of UC Berkeley, the IGI helps me do that.

00:10:01: It really does give a purpose For my career.

00:10:05: The second aspect of that Is a scientific aspect.

00:10:08: I've prided myself throughout My entire career having a breadth of disciplines, a breadth of understanding.

00:10:14: As you had said I'm a physical chemist.

00:10:16: that was a mixture physics and chemistry.

00:10:19: i studied quantum mechanics and statistical mechanics steeped in the sort of basis how this world literally is stitched together.

00:10:29: but now for the last twenty five or twenty six years my career have been working with some most preeminent cell biologists microbiologists geochemists now molecular biologists.

00:10:42: And so I find inspiration across a number of disciplines, and-and i would not want to work in an job that did not allow me To look at cross tremendous breadth of fields.

00:10:55: I enjoy working with earth scientists Planetary scientists...I find inspiration from some new materials like metal organic frameworks That just won the Nobel Prize A year or two ago.

00:11:08: These are materials that have the potential to change the world as well.

00:11:12: And so Omar Yagi just recently was that Nobel laureate, also at University of California Berkeley.

00:11:18: So I find inspiration from Omar who i've met and worked with actually funded while I was in DARPA.

00:11:25: That's an individual entirely outside my now current field of work literally absorb water from desert environments and could provide drinking water to people around the world with a very low-cost, low energy solution.

00:11:45: It has the ability to very specifically capture CO₂ carbon dioxide out of the atmosphere at potentially store it as a carbon removal technology.

00:11:53: so I love looking across The World Of Science And finding inspiration for very interesting in various diverse areas.

00:12:01: Admittedly what you're describing both on me professional, as well as personal level.

00:12:05: This sounds really inspirational and admittedly speaking the Bay Area is one of the most amazing parts of the world And next time I'll make sure that we meet for a side visit.

00:12:16: if that's okay.

00:12:17: Yes

00:12:18: absolutely i will give you a little tour some beautiful nature.

00:12:32: So the IGI spends health climate agriculture which is remarkably broad as a mandate and CRISPR.

00:12:41: obviously, it's very foundational to all of these fields.

00:12:45: If you could pick one story kind of one patient or project this would change everything.

00:12:53: moment that best captures why the IGI exists.

00:12:57: what will be?

00:12:58: Well, I think that there's a very easy example of this from last year.

00:13:03: But I often like to first just describe what CRISPR is.

00:13:07: CRISPR actually has something that nature itself has evolved and it is a molecular tool almost a molecular scissor if you will.

00:13:17: That was evolved by bacteria And bacteria Just like humans and many other animals are constantly under attack by viruses.

00:13:27: So bacteria use this special system to be able to recognize viruses that they've been exposed too.

00:13:34: They cut some of the genomic information from that virus and stored it, that virus again, and to be able more rapidly or easily defend and deal with the virus if it was ever exposed.

00:13:59: You can imagine this system of molecular toolkit essentially being a scissor allows you cut-and-paste literally code life DNA.

00:14:11: but now breadth has been expanded both by nature and discovering more of these systems that work in nature.

00:14:19: They can work on DNA, they can work RNA.

00:14:23: you could even do something called epigenetic editing.

00:14:26: Epigenetics are not actually cutting the full single or double-strand nature of DNA.

00:14:34: it just changes the modifications so that you turn off a gene rather than actually cutting and permanently disabling the genes.

00:14:46: This toolkit now is a tremendously broad, very powerful tool kit.

00:14:50: Don't just think of it as something that cuts both strands of DNA and permanently changes them, permanently alters that DNA.

00:14:57: That's one flavor of how this tool works.

00:15:01: but there are so many different flavors from changing in single base to change in a single one-of.

00:15:06: those A's Gs C's T's make up our DNA to even being almost like a knob that can turn down gene activity or turn up gene activities.

00:15:16: So it really is, uh-a really remarkable tool.

00:15:20: but to sort of go from the theoretical to now practical we were involved with team led by children's hospital in Philadelphia last year.

00:15:30: But it was a large group of researchers across many, many different research groups from industry at a large conglomerate company called Danaher that we have been working with for the past three years to help lower costs and speed the manufacture but also that clinical team at the Children's Hospital of Philadelphia where they identified a patient.

00:15:56: That had a disease, this boy... This patient.

00:16:00: he was suffering from genetic defect in the CPS-I gene.

00:16:07: I know it is a mouthful But its the Cps-I Gene.

00:16:10: It was metabolic disorder.

00:16:12: The child wasn't able to adequately digest and process protein.

00:16:19: Can you imagine being born without the ability to be able to fully process protein?

00:16:24: It essentially ends up allowing a buildup in the body of the toxin, ammonia.

00:16:30: So this poor child was suffering from essentially a build-up of ammonia and his body but it just was one base pair difference From being healthy.

00:16:42: so we all banded together and raced to try to treat This baby who is very sick.

00:16:48: He was in the single-digit percentiles of weight, he wasn't gaining weight.

00:16:55: So we raced and within a six month period after he was born... ...we all banded together to design a base editing system.

00:17:03: We designed how to combine that with a lipid nanoparticle And were able to do it with treating physicians at Children's Hospital Philadelphia.

00:17:12: treat this child six months after he was born and He was dosed three times And now it's happy to report that.

00:17:22: He is home with his family, he celebrated His first birthday.

00:17:26: This Is a baby That would most likely be dead Now if It were not for this group of scientists and clinicians banding together so that?

00:17:34: Isn't incurable disease only A liver transplant?

00:17:38: and he did Not find a match for a liver transplant.

00:17:42: So I think that's an example of the power and humanity, what this tool called CRISPR can do for the world?

00:17:49: And listening to this is really amazing happened at The Children's Hospital in Philadelphia back in twenty-twenty five.

00:17:57: also FDA approved first CRISPR based therapy for sickle cell diseases so there was movement.

00:18:05: right we're seeing these CRISPR breaks through.

00:18:09: What, from your perspective are remaining barriers between where we're today and CRISPR becoming really kind of a true standard of care in future given those successes that were seeing selectively around the globe?

00:18:23: Oh yeah this is you know.

00:18:25: even when I was at DARPA We would go round The halls Of my office saying it's delivery stupid.

00:18:32: remember When there wasn't Bill Clinton That said It's the economy Stupid.

00:18:35: Well, in our world of developing new drugs whether that's a new small molecule or chemotherapy.

00:18:43: Or if it is a genome engineering solution like CRISPR oftentimes this how you deliver the drug which is most powerful.

00:18:53: there are so many different tools now fall under genome engineering and we believe CRISPR is the most precise accurate safe one.

00:19:03: those but you still need to be able to deliver that tool, the cells and tissues in your body.

00:19:11: To avoid those tissues where it is not needed... That's a tremendously difficult challenge.

00:19:21: It involves any of a number of different nanoparticles that can encompass the CRISPR reagents and safely deliver it to the tissues that it needs.

00:19:32: Now, the example I gave you of a baby at the Children's Hospital in Philadelphia was metabolic disease.

00:19:42: so this is.

00:19:43: But the liver is sort of the body's trash can.

00:19:49: When we drink alcohol, that's where things go.

00:19:51: if you have a toxin that you're exposed to oftentimes deliverance is what tries to clean up the system.

00:19:56: it's no different when you provide a nanoparticle into your system and that was delivered through an intravenous injection And so many, many of those nanoparticles went to the liver.

00:20:10: But if you for instance had a disease in the kidney or in the lungs and brain there are still very few difficult ways to selectively go through those tissues rather than deliver it.

00:20:27: One of the things that's holding our field back right now is how to efficiently and safely deliver all different tissues, cells in your body.

00:20:38: It's the cost.

00:20:40: This is still a very, very expensive technology.

00:20:43: all of that work That was done to be able to treat the baby in Philadelphia.

00:20:47: We had to do mouse models.

00:20:49: we had to Do an on-human primate study.

00:20:52: even the manufacturing regions can often cost hundreds Of thousands of dollars.

00:20:56: so we are working Very hard to try To one and done treatments that could help lower costs and working with manufacturers to be able to come up with ways, to be a manufacturer of these nanoparticles.

00:21:10: And the CRISPR reagents in ways that can maybe decrease cost by factors two or five.

00:21:17: I really think ultimately is way you're going see more patients treated this amazing technology.

00:21:26: Hey, there is so much to unpack and I'm sure we'll get back to the cost aspect in a second.

00:21:31: Can i just jump back because it's such a kind of fast moving area where you're active in around CRISPR?

00:21:39: When Jennifer Dautner was awarded the Nobel Prize in Chemistry Back In Twenty-Twenty for her development of CRISPR-Casinine can you elaborate a bit what CRISPR Casinine makes?

00:21:51: It's a very fundamentally different tool compared to what existed before that, genetic engineering.

00:21:58: And also given it is such a vibrant and field-wearing how far has the field actually come since Jennifer and her collaborator Emmanuel at the time first described technology back in twenty twelve?

00:22:12: Yeah!

00:22:13: That's an actual point most people do not ask.

00:22:16: so I really appreciate your question.

00:22:19: Genome engineering has been around for two decades or more, and in fact maybe it's closer to three decades.

00:22:26: It was back in the nineteen nineties I think where that term genome engineering or gene editing Was coined because there were tools That could do what CRISPR does this cutting-and-pasting of DNA before CRISPR.

00:22:41: So why was this such a watershed moment?

00:22:44: Why is it such huge breakthrough, and I think people don't understand that.

00:22:49: Before CRISPR the two tools most common to perform gene editing were zinc finger nucleases, ZFNs and talons And these tools could absolutely do what we just talked about.

00:23:03: They can find a specific part of DNA and cut and disable genes but they were flawed in a very, very specific way.

00:23:15: In order to be able switch and go into the new DNA target you had to completely re-engineer this system to do that.

00:23:24: The unique thing about CRISPR is yes it has molecular scissors That's the Cas-Nine protein enzyme that literally does sort of snipping the scissoring the cutting of the DNA, but it also is coupled to what we call a guide RNA.

00:23:47: And that guide RNA is sort of the homing beacon-it finds the right zip code for the DNA and if you go from one patient like baby in Philadelphia to another, the change in the DNA is almost guaranteed to be slightly different.

00:24:10: So instead of having to completely re-engineer the protein—the cutting protein—all you have of the guide rna and that's like modification that slight change of crisper is sort of a watershed revolutionary change of what happened with that design.

00:24:31: so that i think more than anything else.

00:24:33: you know it's a little bit more efficient.

00:24:35: its a little but more simple then those previous technologies.

00:24:39: all those things help.

00:24:40: But I think generally that's the molecular change, is the beauty of sort how nature had evolved this system to work in tandem with a very easy reprogramming element.

00:24:54: This guide RNA.

00:24:56: And CRISPR has increasingly also been used.

00:24:58: not just cut DNA but turn genes on or off without making such permanent changes, and you alluded to that epigenetic editing in the previous comments talking about CRISPR-A or CRISPR I. How significant would you deem this shift from kind of mere editing towards regulating?

00:25:20: And how does it change the risk benefit calculus for patients and regulators at the

00:25:25: end?".

00:25:25: Yes there's a lot to unpack on this question.

00:25:28: um i do agree with you this ability.

00:25:34: It almost acts more like what we would traditionally think of as a drug.

00:25:38: If you go in your medicine cabinet and take acetaminophen, Tylenol or if you take ibuprofen Advil Or any number of different drugs that people take on daily basis They're sort the therapeutic window effect.

00:25:52: Maybe this drug works for four hours maybe it's active but then turns off.

00:26:01: And so I think this concept of being able to now identify a specific gene, maybe sit on that gene and turn it off.

00:26:11: And silence it?

00:26:13: Gene silencing...and then goes into one of these new technologies which was the biggest breakthroughs in epigenetic editing where you can actually use what they call dead Cas-Nine—a nonfunctional Cas-nine takes and sits on the DNA, then activates that gene.

00:26:34: But it does not permanently change the actual underlying DNA.

00:26:39: so I think this is very powerful.

00:26:42: but those tools are really still at their infancy.

00:26:46: they work for many genes but there's sometimes up to fifty percent of genes, this technology still does not work well enough on.

00:26:55: So they're so critical deficiencies and it is also much easier to turn a gene off or suppress the activity of a gene rather than turning a gene in and creating more activity with expression for that gene.

00:27:09: Those technologies are at their infancy I think because innovation can be done.

00:27:17: then What all of this means for the FDA or global regulatory bodies?

00:27:24: Look,

00:27:24: they've approved treatment for sickle cell disease.

00:27:27: There's still much to be improved about that particular treatment but I think that the regulatory bodies in the world still have to contemplate what it means potentially to have a one and done treatment.

00:27:40: This is now potentially a cure to a disease much, much fewer of a drug or maybe in some cases it might enable patient to live without something like liver transplant.

00:27:56: So how does the FDA regulate this now?

00:27:59: How do companies form these new drugs that are not selling pills you take every day your life?

00:28:08: and what is business model?

00:28:13: We're a non-profit, we work under the University of California.

00:28:16: that's state government university.

00:28:19: You know?

00:28:20: We want to see this technology democratized but at the same time you still need an economic model that is able sustain the manufacture and development of these drugs.

00:28:32: so I don't have final answers here but I do know that this is a powerful technology and it looks like its working.

00:28:40: There are recent publications of a PSK-Nine gene again in the liver, there's epigenetic editing thats showing on the suppression of these and its responsible for generating cholesterol and uh...the low density lipids that are responsible for cardiac disease.

00:29:01: data and results now showing that you might be able to use epigenetic for suppressing, and turning off this critical gene that's involved in cardiac disease.

00:29:12: So I guess what i'm trying to say is we're seeing this technology work And regulators are trying to move quickly but the technologies actually outpacing both business model and sort of regulatory model.

00:29:26: here where maybe one thing your changing It's all of the drugs, the same.

00:29:31: The nanoparticles are the same and molecular scissors exactly the same as you're doing now is just changing a few letters in the genetic code for a guide RNA.

00:29:41: So I think regulators are thinking that maybe they can fast track these treatments compared to years-and-years-and very expensive clinical or preclinical work.

00:29:54: so and excited about the future because I do think we might be able to get these drugs

00:30:19: sick care and treating chronic diseases through known therapeutics such as a drug day or whatever it is right.

00:30:28: So rather than a preventative curative medicine in healthcare system, you alluded to that obviously the regulators like FDA and EMA might not have frameworks at hand allow for this regulate for yet full shape.

00:30:44: but also there's healthcare practitioners, nurses doctors that also need to be taken along and there is so much knowledge that needs to be transmitted around.

00:30:52: I mean can you probably also comment on that a bit?

00:30:54: That part of the system that needs been taking long in order really make such innovative CRISPR-Cas technologies more normal world?

00:31:03: Yes!

00:31:04: And i think this one these things that the IGI tries to lead because we have public impact team that thinks about patient rights, things about equity.

00:31:14: Thinks about the ethics and sort of the affordability of

00:31:18: technologies.".

00:31:19: And Jennifer likes to say...and she believes this—that she wants this technology become a standard for care.

00:31:27: But what does that mean?

00:31:28: How do you actually do that?

00:31:29: in the practicality of that?

00:31:31: we are still very far from not being the case because it takes the innovation and laboratory.

00:31:37: It takes manufacturing specialized manufacturing facilities, they can make these specialized molecules.

00:31:44: And then it takes clinicians and clinician scientists That our familiar with a technology to have The internal approvals at their universities or at there clinical sites To be able to actually perform and to actually dose the treatments.

00:32:00: so when you take all of that combined, your talking about a technology that is very far from being equitable.

00:32:06: That's very far for me distributed out to all areas of the world where they can afford the technology whether or not weather you're insured are whether you know i'm sorry part what the idea does to work with not just regulators, but work with manufacturers.

00:32:23: Work with companies and work with governments around the world to try to think about ways to be able to promote affordability.

00:32:32: We have a new program that we're calling CRISPR Commons where were trying to do protein engineering at tremendous

00:32:41: pace

00:32:41: A tremendous speed and breadth To then create new molecules can be new CRISPR systems that can be protected by the University of California and then, yes used and licensed to buy companies out here in the Bay Area or anywhere around the world.

00:33:00: To develop new cutting edge drugs and new cutting-edge technologies but at the same time That technology could potentially be licensed In low middle income countries potentially for no cost to be able create no-cost licenses, so that this technology might be more equitably distributed and developed around the world.

00:33:21: So there's a lot of work to do but I think by stimulating conversations at all stages from those administering new technologies down to innovating them a very good chance of being able to expand the access

00:34:01: and affordability.

00:34:09: comment on please.

00:34:10: If you follow the traditional playbook, You would see regional centers of excellence.

00:34:15: Texas is often one that has one or two regional centers.

00:34:19: obviously The Bay Area Los Angeles New York Philadelphia Florida.

00:34:24: This how the United States traditionally does this.

00:34:27: but look I'm from DARPA truly believe that we need innovation in manufacturing platforms as well.

00:34:37: And I'm seeing data now, showing especially for things like CRISPR these nucleases and aminases base editing the guide RNA manufacturing...I've seen data that seems to indicate there are much less expensive ways I believe that we are going to be able to generate these molecules with very, very good purity.

00:35:04: But maybe not just at the highest standards that the FDA requires to treat thousands and thousands of patients.

00:35:11: but maybe if you're making a personalized medicine for one patient or two or three different patients—I think there's ways to manufacture batches of those drugs in ways that can greatly reduce the cost burden on them.

00:35:27: And then They're new technologies that are out there, making smaller batches of these medicines and doing it in an automated way where you can actually do the QAQC.

00:35:39: The quality assurance is ways more automated than leveraging artificial intelligence to promote a more distributed manufacturing model.

00:35:49: so parts of the globe and large countries like United States where you don't have to solely depend on regional centers.

00:35:59: That's my vision.

00:36:00: And again, like I said from DARPAI want to think about a future.

00:36:03: that is the ideal scenario and i think for me The Ideal Scenario Is more of a distributed model so that rural areas could potentially get the same access that cities and these centers Of excellence can provide?

00:36:17: And I love the opportunities that are lying ahead of us For personalized medicine at scale globally and make this really accessible to many, many millions of people.

00:36:28: While I was saying the IGI is obviously not solely a health institution as said before it also works in climate and sustainable agriculture And you've published research on rights variety that emits sixty percent less methane than your exploring microbiome editing to reduce emissions from livestock and soils?

00:36:48: How do these genome editing tools translate into the climate space?

00:36:55: And what is your theory of change when it comes to addressing hunger and climate change through with the same molecular toolkit that you're using to treat human diseases.

00:37:04: Yes, I am so passionate about The Impact!and i truly believe That CRISPR and Genome Editing It's actually going to positively affect more lives in the area Of Climate & Agriculture than at will Through Medicine.

00:37:18: Think about that statement I just made.

00:37:20: When you think of genome editing and CRISPR, you immediately think like the baby in Philadelphia or new recent results on deliver PSK-Nine cardiac disease efforts going on but most likely even our wildest dreams.

00:37:37: we're probably talking thousands tens of thousands patients might be helped next decade with CRISPR.

00:37:46: what if engineer crops?

00:37:48: that are sustainable, that reduce inputs like nitrogen fertilizer.

00:37:53: Did you know that seventy-five percent of nitrous oxide the third most egregious greenhouse gas in the world?

00:38:01: Seventy five percent of those emissions are based on a way we grow and produce food.

00:38:05: rice is resulting between ten to twelve percent all methane generated globally.

00:38:11: You hear about fracking and natural gas extraction that, yes those are critically important methane sources but rice is ten to twelve percent of all global methane.

00:38:23: The largest single emitter of methane our livestock the beef production globally and those are living microorganisms that produce nitrous oxide and methane.

00:38:35: they're living microorganism.

00:38:37: guess what?

00:38:38: Those living organisms have the same DNA the humans that we were talking and human diseases.

00:38:45: The IGI has a huge investment in research right now trying to manipulate, modulate gene expression of microbes like those who create methane or use hydrogen as precursor for methane.

00:39:02: The result you mentioned earlier about nearly sixty percent reduction in methane production from rice is actually changing the way rice plant feeds the microbes that live in this soil.

00:39:16: So, roots are actually expressing and secreting molecules to feed microbes which end up using hydrogen more efficiently and they starve those organisms that are producing methane.

00:39:30: So you actually end up producing less methane, not because you're changing the organisms that have produced in a methane... You're actually going upstream from those organisms and starving them from the hydrogen that need to be able produce methane.

00:39:43: so The opportunity of this space is enormous.

00:39:47: That's one aspect reducing greenhouse gas emission footprint on the way that we grow and produce food, but at the same time climate change itself is threatening.

00:39:59: The way that We grow in produced food.

00:40:02: there are.

00:40:03: drought stresses temperature.

00:40:05: heat wave stresses their floods just based On the number of increasing numbers storms.

00:40:11: so think about the amount Of food that we produce globally That Are near or on the coast.

00:40:17: all those food supplies are now threatened by Storms being blown over and killing by flattening crops or by flooding those crops, then having salt and salinity pressures after that destroy the land.

00:40:33: So there's a number of different threats including disease and spread virus bacteria can threaten our global food supplies.

00:40:42: well I believe CRISPR is solution to help build in resiliency adaptation Oftentimes the way that nature itself would start to adapt those plants, but they can't adapt fast enough To the pressures that climate change is putting on them.

00:41:00: So CRISPR it's going to hopefully be though technology.

00:41:03: That helps rescue us continue to feed and provide food security around the globe.

00:41:10: So I'm tremendously excited about this technology in these

00:41:13: spaces.".

00:41:14: Hey, that is a great testament why actually The Nobel Prize was rightly awarded to CRISPR as a technology given the plethora of opportunities coming from it.

00:41:23: And big thanks for the vibrant also very inspirational conversation we just had.

00:41:28: Brad Thanks for sharing your insights giving us this view into a remarkable field of science and health care, climate but also in agriculture.

00:41:39: And this conversation to me has been really a genuine reminder of what once seemed like science fiction is rapidly becoming reality including medicine.

00:41:50: so big thanks for enlightening us here.

00:41:53: Thank you very much.

00:41:54: I've enjoyed the conversation.

00:41:58: Hey and to our listeners, if today's episode sparked your curiosity I really encourage you to explore other episodes at the podcast platform of Your Choice.

00:42:08: And while you're there don't forget to subscribe!

00:42:11: That said until next time take care stay curious and obviously Stay Well!