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Transcending Boundaries with Synthetic Biology
Episode 349

Omar Abudayyeh and Jonathan Gootenberg, McGovern Institute Fellows at Massachusetts Institute of Technology

Transcending Boundaries with Synthetic Biology

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Transcending Boundaries with Synthetic Biology

Episode 349

Recommended Book:

Originals by Adam Grant

Medical Detectives by Berton Roueché

Best Way to Contact Omar & Jonathan:

LinkedIn-Omar

LinkedIn-Jonathan

Mentioned Link:

McGovern Institute

Transcending Boundaries with Synthetic Biology with Omar Abudayyeh and Jonathan Gootenberg, McGovern Institute Fellows at Massachusetts Institute of Technology | Convert audio-to-text with the best AI technology by Sonix.ai

Saul Marquez:
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Saul Marquez:
Welcome back once again to the podcast. Today have a special privilege to invite two guests. First we have Omar Abudayyeh. He is a an M.D. Ph.D. student at Harvard Medical School in the lab of Feng Zhang at the Broad Institute. Omar is a six year M.D. Ph.D. student at this program. He received his B.S. in Mechanical and biological engineering from M.I.T. where he was awarded the top prize in engineering school. He's a graduate studies at the lab at the Broad Institute. He has Colette studies reporting the discovery and characterisation of novel crisper enzymes. We all know these are the headlines of papers today. Ways to tackle diseases that we struggle with like cancer including the first single enzyme RNA targeting crispr cast systems. We'll talk more about that during the podcast interview today. He later developed the cas 13 A system into the Sherlock platform for nucleic acid detection with his colleague Jonathan Gootenberg which I'll do his intro here in a second. His work has resulted in 20 research publications in journals such as Nature Science and Cell and has been funded through the Paul and Daisy Soros Fellowship, National Defense Science and in junior and graduate fellowship and the NIH National Research Service Award. We also have Jonathan Gootenberg. He's currently a Ph.D. candidate at the Harvard Systems Biology program. Co-advised by the Feng Zhang and Aviv Regev of the Broad Institute of M.I.T. in Harvard. Jonathan's research combines computational and molecular approaches to discover and characterize new biological tools with a specific focus on crispr cas proteins as Omar is doing, their partners in crime in this effort. These tools have diverse basic science and translation applications including nucleic acid detection genome scale screening and live cell. So with that introduction. Needless to say these are some brilliant minds working on crispr technology and it's a privilege to have you both on the podcast. Help me fill in any of the gaps of the intros that I gave to you guys and we're giving you here a warm welcome on behalf of everybody listening.

Omar Abudayyeh & Jonathan Gootenberg:
Yeah thanks for having us. Thanks for the opportunity. Yeah those bios are pretty spot on. We both recently graduated so I guess candidates no longer.

Saul Marquez:
Congratulations.

Omar Abudayyeh & Jonathan Gootenberg:
Thank you.

Saul Marquez:
That's awesome.

Omar Abudayyeh & Jonathan Gootenberg:
But yeah it was great. School is a great time to learn and discover a lot of different things.

Saul Marquez:
Absolutely.I'm glad that you guys made time to be on and thanks for the correction there. Congrats on finishing that. So you know we'd love to hear, what got you guys into the health space to begin with?

Omar Abudayyeh:
Yeah. So I think you're growing up when you study all the subjects. Physics, math, your chemistry, biology. I was somehow drawn to biology because it's the processes that are happening inside of physics. It's like you described stating that you might be familiar with everyday like bouncing a ball or throwing in a paper plane like you started learning about polymer races and viruses and how they can talk into cells and how T cells can obliterate other cells in your body and it's really like a warfare evolution that's happening inside of you and you never notice it. You never see it and yet it's incredibly fascinating and so I think ever since I was a kid I kind of got hooked on the invisible molecular world. And as I started getting diving more and more into that world you start realizing that all of these interesting things play a huge role in disease and so you know biology is really this foundation that starts and form medicine. It's like biology is kind of like learning how to walk but medicine is being able to run and so I started realizing that all these interesting things that happen and you can go awry that can cause disease and the more knowledge you have about the cell the more of a blueprint you have that you can start to actually design fixes and come up with medicines and I think that's kind of really fascinating and I think even your biology has come a long way since I was a kid. We have synthetic biology and we have pools where you can actually program cells you can program how to cut DNA and change DNA. I think the tools are you know getting more and more advanced every year to the point where you can really think about biology as an engineering discipline and you can actually start designing it which I think is just really cool and fun.

Saul Marquez:
Yeah now for sure it's definitely a fascinating place to to plan, the evolution has been pretty stellar in the last few years. Great to hear your story, Omar. Jonathan, how about you?

Jonathan Gootenberg:
Yeah I think that I was pretty lucky to grow up in a family. My parents were practicing physicians and so for me a very early age I was kind of in that environment of medicine and biological discovery and I also grew up in Bethesda Maryland so I was literally a kind of a subway…

Saul Marquez:
Backyard. Yeah.

Jonathan Gootenberg:
Yeah from my house. But I think beyond that both Omar and I are very lucky to kind of come into biology and it's kind of medical science at a time when there's becoming to be so much more possible because the discovery of new tools is those based on instrumentation but my cross-check you better DNA sequencing. But also based on molecular tools where we can start to take the elements of life these proteins that are surrounding us and turn them into things that allow us to edit genome or cure diseases. I think that's so rapidly accelerating right now. So it's just such an exciting time to go into this really thrilling field where these days you can write something down your computer, a gene sequence and ship it off to a company and in three days you can get a two with that DNA of that gene in it. So I think it's seeing the advances and we're really at the cusp of something really amazing where we can start to take this biology diversity and this is what Omar and I've been doing our graduate careers and turn them into tools to the biological community but also these really new approaches for doing medicine for diagnosing and treating disease. It's just a really thrilling time and seeing that and seeing how things are kind of evolving that way. I really couldn't resist being in biomedicine.

Saul Marquez:
Yeah it's really phenomenal what we've been able to accomplish. Like you said and from like computer code to actual like DNA code is pretty insane.

Jonathan Gootenberg:
Yeah yeah. And it's just gonna become more and more accessible. So I think it's something that will be really transformative in the next decades.

Saul Marquez:
For sure. So let's dive in guys, what do you guys feel is a hot topic that needs to be on health leaders agenda today. And how would you guys approach it?

Omar Abudayyeh:
Yeah I mean I think you know we think about every day is gene therapy and how to drive that forward and make it a reality for the adults five thousand or more plus genetic diseases that we can pinpoint a specific genetic mutation to and know how that sort of causes the progression of disease and I think there are outstanding challenges to making that happen that many layers. I think by now even if you had the perfect genome editing system which crisper is almost that it's not quite there has some limitations. There's still problems with cell deliberate and so one of the biggest problems in sort of gene therapy spaces. How do you target the tissues you want and how do you get into the cells you want without causing off targets and hitting tissues you don't want to correct. How do you know what you're injecting is actually safe for the patient. I think the past year there were a string of papers showing that crisper casting itself enzyme there's a certain faction population actually has pre-existing immunity to these proteins likely because crispr actually comes from bacteria that are normally in humans or humans can become exposed to them for example strong powers. This is actually a pathogen for humans so they might be exposed to it and then about immunity. So you know immune toxicity is one issue and then of course there is the cost which I think is not something you know. JOHNSON I deal with every day because we're just in the lab developing these things. But the costs for these types of therapies is getting larger and larger every year. You know immuno cancer therapies that were announced a year or two ago were a few hundred thousand dollars like Tamara. And one of the latest JPM conferences I think there were at gene therapy announcements were two or four million dollars a piece. So these are some of the largest prices ever in the drug industry and drug companies I think justify it because it's a single of curative dose. You know it's not something you take every year for a long time but that's also becoming a big consideration. It's like who pays for it. How what happens if your insurance doesn't pay for it have you afford it. And you know those things have not really been worked out yet.

Saul Marquez:
Now some really great insights there and in some of the limitations that you call out as well. I think it's really fair. And the promises is large and the limitations are also there. So we'd love to hear an example of what you guys are seeing and how results have been created by doing things and thinking differently.

Jonathan Gootenberg:
Yeah I think that it's really important as these new technologies are developed and you know our role is really at the kind of very early technological inception. It's important to have a dialogue right now between those really early technologies and the people who will be eventually adopting them because it's in when we develop these gene therapies. And when we think about ways that you know maybe we can treat certain diseases it's important to think of the whole process and how you know as Omar alluded to how will these be paid for. How can create a structure that they can be efficiently adopted and really taken to their actual realization. So I think this is kind of a broader question throughout all of these technological disruptions, gene therapy and crispr but also the emerging role of artificial intelligence and machine learning and medicine how to best adapt that while maintaining good herds of patients and not having issues with patient privacy or risks with false predictions of certain genetic information. So I think all of these things, there needs to be a discussion between the technology developers and the people who actually use the technology and because we're so early we don't often have to get a chance to have these discussions but through work you mentioned with Sherlock which is a diagnostic platform that we helped develop in the lab our graduate work and is now in the process of you know hopefully being translated. We've had the opportunity to attend things like TED MED where we can have these conversations to use technologies have such potential but where can they first be applied where can they make the biggest difference and where can they given their price points are they very cheap but easy to deploy or are they very expensive but more difficult to deploy where they can best be used by medical professionals. So it's really the take home I think is how can we start developing new tools in the lab with the end in mind where they'll actually end up and not just drop these things on patients saying oh this will cost two million dollars and more discussions more planning would really be a great way to do that for.

Saul Marquez:
Totally. Love that insight and you know we'd love to hear a little bit more about Sherlock. What is it and how are things going?

Omar Abudayyeh & Jonathan Gootenberg:
Yeah. So Sherlock is and I'm sure most people listening are aware of sort of the story of the detective Sherlock but in our work it's an acronym for I believe Specific High Sensitivity Enzymatic Reporter Unlock and lock, lock step for unlock.

Saul Marquez:
I love it. That's great.

Jonathan Gootenberg:
But the technology does and the reason you chose Sherlock as acronym is it's essentially you know a detective nucleic acid. So the technology. Yeah. It's able to very sensitively and specifically pick up DNA or RNA signature, viruses, bacteria, diseases like cancer, even single mutation. So if you want to genotype someone for mutation that increases Alzheimer's risk or a mutation that gives you norovirus resistance it's able to do that. And we've been able to create this platform using the power of crispr. So we discovered a few years ago a set of enzymes that instead of being useful for gene correction as is most popular with crispr gene therapy it's actually much better for reporting on the presence of nucleic acid. So what these enzymes do which is specifically in their name is Castor gene and test twelve when they bind a nucleic acid they start becoming permanently active and start chewing up everything in the solution. And so if there is a reporter molecule that when chewed up becomes fluorescent essentially these proteins will turn that fluorescence to the detection of a specific nucleic acid. So what that allows for is because these enzymes are very good at picking up nucleic acids we can a single molecule of DNA in a sea of millions of other molecules and because they're a super specific to the sequence they're able to pick up that single base pair. So it's a really enabling set of underlying proteins that enable the whole platform. And what's even better is they're very cheap to produce. It's very quick. It happens in less than 10 minutes. And we've been able to deploy this platform on paper strip so you can actually see the fluorescence on a paper strip using a simple device or even by allowing it to be deployed in resource poor settings where person running it might not be skilled or they might not have like an actual instrument. So that's kind of the promise of the technology and almost a series of papers around it. And now we're trying to think about how do we really deploy it in the real world. And so we've done that through some collaboration. There's another group here run by somebody at the broad that's been running Sherlock workshops in the developing world and Honduras and some other countries in Africa. They are trying to track epidemics of different viruses like Lassa virus but we've also been thinking about maybe how to spin this technology out of academia to go after diseases for example like sepsis. So a big issue in the medical world is you know someone has bacteria growing in their blood and it present to the E.R. And you know new blood cultures it takes you know a day or two. Usually it's it's hard to diagnose what's going on. You have to give broad spectrum antibiotics which is not really good for the patient. They have bad side effects and that also promotes antibiotic resistance. So the promise of a technology like ours you can have a test either in the E.R. directly or in the hospital lab that within an hour to tell you what specific bacterial strains are in someone's blood. And then you could actually treat this sort of exchange using the exact antibiotics that are appropriate. So it's an example of how you know a simple nucleic acid test can sort of change workflows happening right now in the hospital.

Saul Marquez:
And super interesting.

Omar Abudayyeh & Jonathan Gootenberg:
Yeah.

Saul Marquez:
That's definitely interesting. Yeah. Thinking about you know the sepsis deal it's definitely something that does take time. You know you go you see. Perhaps you know some repertory compromise will get a lactic acid test that takes a while and this is a very interesting approach. So appreciate you sharing that obviously tip of the iceberg folks. So at the end of the podcast we'll share some links where you could learn some more and get in touch with these folks if you're interested. Omar and Jonathan. So let's dive into some of the things that maybe haven't gone as well. Maybe you guys could share a setback and what you learned from that setback to have made you guys better.

Omar Abudayyeh:
Yeah I mean it probably honestly easier to talk about a time that we haven't made a mistake. Science the process of science is really about embracing failure.

Saul Marquez:
Yeah.

Omar Abudayyeh:
You know in lab every day we'll do 10 things and seven of them will fail on a good day. But I think that maybe one specific instance of failure was well it comes actually back to a lot of this early work that we were doing with a lot of these crispr enzymes and the characterization is enzymes is a pretty comprehensive process. We run a bunch of different assets to try to figure out you know how they like to cut nucleic acid their molecular scissors right and how what different sequences they prefer. So back in this was would be about late 2015 or early 2016. Omar and I were characterizing this enzyme task 13 back then called it C2 which is a little bit more of a mouthful and we are running a lot of different ends assays to figure out exactly how it like to figure out which nucleic acids like to come. And we're doing this a couple different ways one we would put it into bacteria and we would have a kind of a big soup of bacteria each with a different sequence in it and some of bacteria would grow and some of them wouldn't. And they told us that you'd like to copy a certain sequence and that was very cool. You know we had expected that and we were trying to repeat the experiment in a test to kind of you know take everything out of bacteria and just have it as you know these nucleic acids that a tube. And we knew that the proteins would work to work outside of bacteria but every time we read out the assay and this would take about a week and costs a couple of thousand dollars and it would be fair amount of work we got nothing. So what we found that the enzyme was actually kind of everything independent of its sequence and it was actually a little disheartening that we were like What are we doing wrong. What are we doing wrong or something. I mean there's so many things that can go wrong experiments. So we had to debug from every angle you can get contamination that can cause things to chew up you know problems with amplification. You can have other enzymes go bad. So I think we read in the paper about five times over the course of probably a month and a half and did we still didn't get anything.

Saul Marquez:
That's tough.

Jonathan Gootenberg:
Yeah. It was disheartening but that made us think you know how is this enzyme working in this test too. And maybe it's working differently than we expect. So one thing you have to chew see when you see data over and over again is there is a part where you have to trust the data when you've eliminated every other possibility. You have to stop going with your gut sometimes and say what are my governing assumptions. And maybe those governing assumptions are wrong. So we were thinking that this enzyme too juicy to custard TNA was working like past night and glomming onto us to pick sequins and cutting it. But what really was happening was that it was glob into one sequence in other sequences in the solution. It was actually this collateral activity that Omar discussed this mechanism that's at the heart of the Sherlock technology that was causing this experiment to fail over and over again. And it made us think Man we should test for this explicitly if we trigger it with one piece of RNA. Will it cut another piece of RNA. And that led us to actually think this is the first time that we have this really new activity of this enzyme we had not predicted it at all and explained the result perfectly. That was actually come back between everything up and that's what made Sherlock so.

Saul Marquez:
Where were you guys when you sort of like came up with this conclusion?

Jonathan Gootenberg:
I think we were probably I mean we're done in the lab. I think we're either at the bench or at our desks but it was like you know we're like man maybe it's doing this crazy thing you know he's set up a experiment to test this hypothesis and you know we ran it and now by golly that's exactly what would be expected if he was having this activity. And I remember seeing as like oh man we wasted so much of our time. But really I mean it's not wasted because we could be confident that it wasn't some other part of this really complex procedure of gait analysis and everything you know, Omar did the experiment I did the experiment we both did it and it was all always failing and then eventually you know you just realized man I've really been latching onto this core foundational axiom that was incorrect. So to take that away from that I mean of course we learned a lot of lessons about how the enzyme worked and that was incredible for so many applications. But more broadly you have to learn how to identify where you're really making assumptions because they happen all the time and usually they're incredibly important. But to be able to know that you've made assumptions and then go back and say "oh man this is what was really the wrench that destroyed everything later on" then you can see entirely new perspective. And that's the most important thing.

Saul Marquez:
That's a really great story Jonathan and appreciate you sharing that. You know it's you've said latching onto core foundational axioms that are incorrect. Usually they're important right. And sometimes we've got to really kind of take a look at these things when things aren't working and question them. I think something listeners you could apply to the business world in a really great way. Maybe you've been trying to achieve the results and also to the clinical world maybe you've been trying to achieve a particular outcome. Well are there assumptions that you have a question. Now's the time. So great insights there guys. What would you say one of your proudest experiences has been throughout your work to date?

Omar Abudayyeh:
Yeah it's a good question. There's maybe multiple answers to this question. I would say I think one of the things that makes coming into work every day is actually the people. Jonathan was saying earlier that probably most things every day fail. And so if you're just you know writing your emotions and your happiness like the outcome of your experiments for a given day you're really in for a rollercoaster. Being in science. And so I think one thing that's been really fun over the past few years is having you know trainees and mentees that you know really helped drive the science forward. But you really get to seek row during the course of the research and the projects. And so I think over my time in the Broad Institute the best fear is through all these papers we've probably had a few masters students if you research associates and I think some of the proudest moments is really seeing them go from you know maybe never having fun stuff like that before having done some research in undergrad to becoming really effective. You know budding scientists and going off into the world. You know he'd go to medical school or get P.hD's. One of our most recent students really helped drive our last science paper forward for the past year and then ended up doing into UC program at the University of Cambridge. So that was really exciting to see his growth. So I think I would say it. So my proudest moments have really been the people around us succeeding and doing great science at the same time.

Saul Marquez:
Now that's outstanding. You guys definitely have to build each other up because of all of the failures and the stones being thrown and just kind of beating your head up against brick walls. It's certainly important. So kudos to you for building that legacy of future scientists there as you continue your discovery of these amazing insights. What about an exciting project that what you guys want to share with the listeners about an exciting project you're working on today?

Jonathan Gootenberg:
Yeah I mean I think that we're truly thinking about how we can take the discoveries that we've made in foundational just microbial diversity discovering these new enzymes and how we can apply them to new applications and new directions. So one thing that we're working on pretty actively right now is a field called RNA editing and that's about using some of the enzyme we've discovered to actually change the information in RNA instead of DNA. So DNA is in molecular dogma of biology. DNA is kind of like the blueprints. It's this foundation. But RNA is really what the information is turned into. It's where you can actually see which proteins are going to be made in that particular cell. So it's more transient and it's more abundant but it's kind of a more closer proximity to the actual machinery of the cell. And what we think is really cool about this is that DNA editing is so powerful. We now have this ability with crispr to kind of to a first a first approximation go into a cell and make a change but there is a lot of questions about you know do you want to make permanent changes. Because of course there's a question about should we make changes to the genome. Or will there be off target effects that could make changes somewhere else that will be permanent and problematic or you know what if that's passed down to cell. So by changing RNA we're having a more temporary change potentially which actually allows us to not have to worry about those problems as much but it also allows us to have much more flexibility with what we can do so we can use the precision of this really single base resolution where we can change a single letter and know exactly what that will do to the biology of a cell but join a temporary level so we can change a protein temporarily and alter the inflammatory state of immune cell or alter how a nerve cell is expressing a certain receptor or channel so it behaves in a temporary fashion. And because most medicines you don't want permanently right. You don't want a painkiller. Take a painkiller and not be able to feel pain for the rest of your life. So I think the power of gene editing taking that to more broad way and saying "Now we have control over how we can express proteins and how these different biology. But also have temporal control we can turn it off then permanence." I think that's going to be a really large field going forward. I mean there are of course tons and tons of caveats with how we actually implemented and deliver it. But once you pass all those it's kind of this general larger thread of medicine being able to have very very precise control over the states of the biology most foundational level in our bodies which as therapies develop will be to one miraculous things because control of cell states control of different pathways. It's a totally new approach to being able to do medicine and I think it'll be a really fertile area.

Saul Marquez:
Yeah. Now that's really really fascinating insights there and yeah makes everybody wonder what is next then. And temporal control. Wow I mean being able to affect RNA in that way never crossed my mind. I mean this is definitely going to give me something to think about after I interview you guys. So you're exploding my brain here. You guys are definitely awesomely smart and insightful. I know the listeners are probably really enjoying this right now but all great things also have to come to an end. So in the next few minutes that we have here Jonathan and Omar, got a lightning round so I'm gonna asked you guys five questions. It'll be rapid fire answers and then we're gonna follow that by a book recommendation from both of you guys. So you're up for that slamming up?.

Omar Abudayyeh & Jonathan Gootenberg:
Yeah that's right. Good.

Saul Marquez:
Awesome. All right. So what is the best way to improve healthcare outcomes?

Omar Abudayyeh:
I think obviously better diagnostics. We need to have more information and real time information so that you know what's wrong with the patient and actually have all the data to build proper hypothesis.

Saul Marquez:
What is the biggest mistake or a pitfall to avoid?

Jonathan Gootenberg:
Yeah I think it's really being super attached to an idea but what it can do to your time if you are pursuing it too hard and not question yourself but also to be emotionally attached to it and not be open to criticism.

Saul Marquez:
Love that. How do you stay relevant despite constant change?

Omar Abudayyeh:
I think at least in our field stay on top of the literature continued to push the limits of thinking and creativity, brainstorming. I like to think of what we do as an art and trying to really bring that creative process to how we think of ideas and combining new ideas to come up with innovative solutions to the problems of medicine.

Saul Marquez:
Some good advice. What's an area of focus that drives everything in your work?

Jonathan Gootenberg:
I think we're both really inspired by kind of the diverse in complexity of biology both as kind of this natural beauty but also about how we can really transform and take it to make these really useful therapies and diagnostics.

Saul Marquez:
Yeah so interesting and totally agree I mean just the conversation with you guys right now I'm like super jazzed and inspired by your enthusiasm. So definitely is contagious. So keep up the enthusiasm, the great work that you're up to. The final question here is a two part question and I'd love to hear from both of you on it. One of them is what is your number one health habit and then the second one is what is your number one success habit? So whoever wants to go first.

Omar Abudayyeh:
I'll have it. I mean I think the most important thing is getting… maintain your sleep. It's becoming more and more clear every day of their papers coming out of the effects of poor sleep on all these different processes at the molecular level even and you can see how it affects your mood. So I try to get a good night's sleep every night and if I can't the next night I prioritize moving on that. So yeah I just…

Saul Marquez:
Love it.

Omar Abudayyeh:
take care of yourself.

Jonathan Gootenberg:
Yeah. So for success habits. I'm not sure. I think actually, now that's a tough question. I think organization is actually the key. So when we're running I mean when you're working by yourself in science it's really easy to just do your own thing. I think as we've grown out scientific teams it's been really key to have organization for protocols for you know reasons we generate like plasmids. We generate thousands of plasmids over the course of a year and it's easy to lose them. So having like a scheme where you can keep track of everything and essentially like a limbs model where people know exactly where something is is so key to success. Yeah. Yeah that's I. So Omar and I mean we're obviously working pretty close together involves a lot of alignment. So like every day we basically meet up in the morning and kind of go over what we need to do for that day and figure out you know what the experiments, what are the right and what's the outline for the week. So just so we can stay on top of these different things. And that extends I think to every area. We're just kind of knowing what's going on allows you to not have to keep it all in your brain so you can feel that kind of mental capacity with other thoughts and designs.

Saul Marquez:
Yeah some great shares guys. I mean I feel that way about journaling too right I'm a big fan of journaling just you know thoughts in business and in clinical affairs work and you know it's so important to stay organized but also to go back and learn from insights that you gain that maybe you forgot about. So the reviewing of this stuff. How often do you guys go back and review the stuff that you've done?

Jonathan Gootenberg:
So we recently switch electronic or not recently but like four years ago we switched the electronic lab notebooks. It's incredibly easy to just go back and find stuff that you maybe like wrote down three years ago whether it's ideas or notes about a protocol that needed more get better. And the best thing is without trying advisable the book you can just control the search.

Saul Marquez:
So great.

Jonathan Gootenberg:
Yes I have like 10 notebooks.

Saul Marquez:
That is amazing. And then now you guys could probably even run some machine learning over if you want to right?

Omar Abudayyeh:
I mean kind of like how we have changed the way that we've done experiments and in the future hopefully you will be able to say oh let's experiment fail and then you can look that over of course thousands of experiments there aren't really these new rules of science and It'll be entirely new area very exciting.

Saul Marquez:
Yeah oh man that is so cool. That is so cool. Well thank you for sharing that guys. What book would you recommend to the listeners? And you guys could both do one.

Omar Abudayyeh:
Yeah I think for me I recently read Originals by Adam Grant and it's this sort of organizational psychology both about basically how to champion new ideas and effectively reorganizations to pursue new ideas and continue to innovate. And I think it totally changed how I think about my own work even though most examples of this are like in business and tech and sports. But like his advice applies to sort of any field but I think one of the main pieces of advice about like channeling new ideas that still sticks with me is that when you're presenting a new idea to someone or a group of people the first for people as they think about ways that the idea will fail or like you know they'll think of ways to tear it down and it makes it harder to get people to sort of see something that's totally new and challenges the way they think. And so I'm better way the present and I guess to actually present the idea and actually directly address all the problems of that. So I actually put the problems up front and have people sort of think about those and what it does is a one builds trust because it doesn't seem like you're just pedaling an idea and trying to sell someone something and two, when someone sees all the problems front they start to say "Okay how do we solve those problems?" And they start thinking out how to make the idea better than actually how to tear down that idea. I thought that was just a brilliant way of trying to bring new energy to Keynes and groups of people in an organization.

Saul Marquez:
Very practical. A great one great one.

Jonathan Gootenberg:
Good one the one book that I kind of always liked is a Berton Roueché's Medical Detectives and it's a series of short stories about different studies and epidemiology where there's these kind of crazy things happening. I think the most famous ones up is a few blue men. It's about these different people who turn blue and what the cause of these things and for them it turned out to be that it was I think of the salt that was contaminated some other interesting aspect that led to kind of an anoxic conditions. But it has all these different kind of weird medical curiosity. Another one is somebody who had a kind of really horrible noxious smells so it can be run anything it turned out to be a sick deficiency. And it's it's kind of cool which just seemed like you know there's so much interesting stuff out there in biology. There's this kind of crazy things that happen in the human body but also throughout life and be able to appreciate that. But there's the fact that you know it's just life is so weird in biological sense but also how it really directly impacts you know human health and kind of our existence is really a nice thing to kind of think about. So it's a fun read is it. He's a very good writer so. But it's just all these crazy.

Saul Marquez:
That's very cool. That's very cool and the way to get you to think outside the box too. Now it's a great recommendation and folks you get you can get all of our interview, synopsis in the show notes or a full transcript. Just go to outcomesrocket.health and in the search bar type in either Omar or type in Jonathan you'll find it there. Type in crispr too. We have a nice little search engine on the website It'll help you get this podcast and any other podcasts that we record. But I think this is one you want to listen to again because it's been a lot of fun interviewing these guys. So what I'd love to do here Omar and Jonathan is ask both of you to leave us with a closing thought and then the best place for the listeners could get in touch with or learn more about your work.

Omar Abudayyeh:
Yeah. So I think my closing thought would be everything we've worked with all these enzymes all these technologies have come from nature. We sequenced bacteria from all over the world from the deepest seas to you know mountains and thermal vents and these bacteria spent millions hundreds of millions of years evolving these protein machines did you really interesting things that now we're starting to leverage for human health and so are these just really incredible all the advances that we can develop to make our society better. And it just comes from the things that are all around us that are invisible to us. And I think that's really inspiring.

Jonathan Gootenberg:
Yes it's a good one too. I think the important thing is you got to have fun with it. You got to look at your day to day and see what you enjoy and what you don't and really be able to kind of justify yourself why you're doing what you're doing. And I think a lot of that comes with how you enjoy it. And a lot of that comes from the people you work with. So you know Omar and I we've got this great working relationship and I think we're really lucky to have that. And it's almost unique in a way but just in science in a lot of ways in life it can be really tough and need to have good people that can support you. One person we haven't talked about much at all during the past our mentor, John. And he's just incredible mentor. So I think we've both been lucky enough to be surrounded by great people and find those ways to work with them and find good people and enjoy working with them. And that is and that just makes the whole process so amazing.

Saul Marquez:
Some great great takeaways guys. Absolutely absolutely some takeaways for our listeners today. And apart from your LinkedIn profiles which we'll leave in the show notes what would be the best way for listeners to keep up with your work?

Jonathan Gootenberg:
So we're going to actually… we mentioned to begin the show graduated. So we're actually going to be starting a lab together on MIT in well it technically started. So they'll be at the McGovern Institute of M.I.T. and there should be a website fairly soon. It's McGovern. So if you just google that – MIT we should have a live website and personal websites. I couldn't kind of describe what we're doing and we can send you those links when they're up.

Saul Marquez:
Yeah that sounds great. So folks you're listening by the time this goes live, these guys will be up and running on their on their website as well. But it's the McGovern Institute at M.I.T?

Omar Abudayyeh & Jonathan Gootenberg:
Yeah that's it.

Saul Marquez:
So Google that folks but will also go to the show notes just go to outcomesrocket.health look up Omar and Jonathan you'll see the two guys there. Click on the show notes and we'll share the links that they'll provide so you could keep up with the awesome work that they're up to. So again Omar, Jonathan I just want to say a big thank you for sharing your insights with us on these really cutting edge science topics and looking forward to keeping up with your work myself. So thanks again.

Omar Abudayyeh & Jonathan Gootenberg:
Yeah thanks. Thanks so much.

Thanks for listening to the Outcomes Rocket podcast. Be sure to visit us on the web at www.outcomesrocket.com for the show notes, resources, inspiration, and so much more.

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