 Well welcome everyone to this session which we're calling rewriting human genes. I'm Joe Palca couple of pieces of housekeeping to start with Please Turn the ringer off on your cell phone Someone suggested to me that if your cell phone goes off during this session. It means you have a burning question I'll ask you to come up on stage Stand in the middle and say it out loud And then sing your college Alma mater So but we do want you to leave your phones on because you're welcome to Tweet questions up to me. I have a pad here, which I'll be getting them. The hashtag is global health And anybody who's out there who would like to ask a question feel free to tweet them at Hashtag global health. I have a pad here that will receive them and That's really about it. We're gonna have a 45 minute discussion about Genetics after which there'll be a quiz. So Please be sure and take notes. No, there's no quiz This is just an attempt to catch up with some of the most interesting Science that's being done in the world right now and two of the people who are directly or ten Indirectly directly involved in it are with me on the panel first. There's Jennifer Doudna from the University of California Berkeley She has been very popular lately for a technology that I'm sure we'll start to talk about Called CRISPR and we'll let Craig mellow tell you exactly what that stands for. No, I'm only teasing him We also have with us Craig mellow. He's done some interesting things in biology including working with a something called arnie interference which is an interesting way of silencing genes and Some committee in Sweden decided that that was a very interesting Piece of research and awarded him the Nobel Prize for doing it. So They have credibility I'd say you should believe everything they say but they have credibility. So I thought Craig made the interesting point that Rather than launch right into rewriting genes. Let's let's do a little biology 101 and talk about What we're talking about So Craig, what what do we mean when we talk about rewriting genes? What are genes? Okay, great. Thanks Joe It's great to be here and and welcome everybody I've I've had a lot of experience in the last few years. I'm talking to lay audiences about science and one of the things that You realize is is that you know our vocabularies don't mesh up very well People I've given whole lectures and then at the end had people say well R&A is protein is someone has a birdie question Are you know things like that R&A and protein, you know, what are those words mean? These are really jargon jargony terms if you will so I'm gonna just give you very quick brief introduction to gene expression so Gene expression is really really simple. There's an alphabet that has four Different letters just four letters in the entire alphabet and there are basically 20 different words that can be spelled In a series of you know What our three letter words can spell each of these different amino acids which make up the 20 different building blocks of protein So you have in every cell your genetic material your DNA your genome Which is billions of nucleotides long the nucleotides are the letters and wherever there's a G nucleotide it pairs up with a C Wherever there's an a it pairs up with the T So those are your four things and that's basically the structure that forms into this beautiful spiral double helical structure and Explains so much about for example how your DNA replicates because when your DNA unwinds each strand can encode By through this very precise mechanism of base pairing can encode for the other strand So you always can template a new strand using either of the two strands of your genome. It's really simple stuff It's really basic and then when your DNA genes are expressed It's transcribed into RNA, which is another four letter Type of nucleic acid is another form of the genetic code It gets processed into what we call messenger RNAs Then those are decoded by reading the sequence of nucleotides in the genetic code three at a time and each of the three letters of code Specify a different amino acid that's then assembled by this amazing machine called the ribosome Into proteins by assembling the amino acids that are called out the 20 different amino acids Which have all these different chemical properties are then assembled into a linear chain that make your proteins So gene expression is incredibly simple. Everybody should know this It's a starting point for this discussion because you know your genome is made up of this Organization of letters that specify all the different types of proteins that your body can make so that's my sort of bio 101 Introduction and we can sort of spring off from there And now I'm going to repeat it to make sure that I've got it right But also to say one of the things that boggles my mind always is that you can with from these four letters That combine in various various orders It describes everything. I mean everything in a living human being and I think that's kind of an amazing concept But transcribe I just want to make sure and express those are two words and protein Those are three words that have different meanings in a non-technical sense So I just want to say transcribe is sort of just reading the code, right? Something that comes along says oh, here's what this is and then express means to build The protein or or turn it on essentially. Yeah, I think I again I slapped into jargon So transcribe is just copying right DNA into RNA, right? And then the that where the code gets read is by the ribosome which reads each Three-letter word assembling a different amino acid to match each of those as it goes along with the mRNA sequence, right and then finally the Protein is a word so protein is also it's not the meat that you get in fish, you know the stuff in fish No, but it's a serious It's one of those were it is but it's one of those words that scientists use in a slightly different way than the public Thinks about it Proteins are the stuff that does the things inside the cells inside our body So if you want to change I mean if you want to make insulin right insulin is a protein So you have to have a gene that has the instructions to make Insulin and the cell has the machinery to read the instructions in the genome Trant and transcribe them to turn them into a protein that makes insulin that does something in ourselves, okay? Are we I think okay it went by fast see that's what happens you gonna do? This is the we have to start here because otherwise It's the rest of this talk isn't going to make any sense you have to understand that the genes have the instructions To make things they can either make them properly Which is health and good balance or they can make them in properly in which case something bad happens It could be cancer. It could be diabetes. It could be neurodegenerative disease It could be a lot of things but just keep in mind that the genes Make the proteins which do things Okay, and the steps are of classically DNA RNA Protein so if you ever get confused those are the all that's that's the basics, right? DNA she's notting so I feel good DNA RNA protein Instructions transcribe into proteins that do things okay Jennifer What what part of that world do you focus on in your research? well, I My lab has always worked on RNA so trying to understand the function of this molecule that a Lot of people thought for a long time was less interesting than DNA or proteins It's kind of the molecule in the middle and so we've always had an interest in understanding what it does and I think one of the exciting things that's happened in biology and certainly Craig can speak to this over the last well really couple of decades is that there's command kind of this Appreciation of the incredible diversity of RNA molecules and the importance of their function in cells And and really for human health right and and the and one of the keys that we're gonna get to is that You can change the DNA and that does something to the protein But if you do something in the middle step that also can do something to the protein so maybe Craig you could talk about Where your work? Fits in this work and and just a couple of more points that I think are relevant one one is that you know You're not really an organism your your body is a colony Right so you hear you've heard about the human genome. Well, there's this microbiome that lives in you And you can't live without it. You would not be here without your your flora and fauna that are part of you It's really amazing. So Information in the form of nucleic acid sequences such as DNA and RNA is moving around in the environment. That's what viruses are Bacteria have DNA in them They're constantly exchanging information There's benefits and their costs when you get infected you can get sick But believe it or not There's a lot of evidence that viruses can actually help organisms sometimes so Information can move and be a positive thing sometimes but a lot of times of course It just makes you sick and it's bad because it'll take over the viruses will take over the machinery inside your cells and kill you now cells have evolved mechanisms to combat or to control nucleic acids that are Inside them or infecting them both and one of the ways they do that is they use Proteins of service search engines just like you would search on the worldwide web. They have proteins that use short query made out of RNA Nucleic acid sequence information is used to search for matching information in the genome because the four letter Alphabet is so simple, right? If you have an RNA guide molecule, we call it Or query molecule that's loaded onto one of these search engines It will then go through the genetic sequences inside the cell and look for matching information where the G's A's T's and C's or all line up perfectly so that When the guide sequence matches up it'll it'll form this helical structure with the target and when that happens the cell knows That it's got a perfect match. It's found a perfect match target. So back in 1998 Andrew fire, and I discovered what turned out to be an artificial way of Entering queries into these search engines that exist in every one of our cells. We wouldn't be here without them They're very like imagine you had the worldwide web, but you couldn't search it. What good would it be? Cells figured this out billions of years ago that they needed to have really rapid ways of searching through and Handling information inside them. So they use these search engines to do all kinds of things. They they destroy viruses with them they control their own gene expression with them and then we discovered a way to make an artificial query that We could then give to the cell and it would enter into this searching machinery And that's very powerful because that allows us to use the cells own Searching mechanism to carry out gene regulation and we by by doing this we called an RNA interference We could block the expression of any gene by interfering with the The the translation of the messenger RNA into protein we could destroy the messenger or cut kill the messenger So it turns out that that this has turned out to be a very useful approach for both studying genetics and Biology and also there's there are therapeutics that are now in clinical trials in humans So it's an exciting field, but the interesting thing is this is not Rewriting genes right that's something about that the RNA level. We're intervening After the DNA has been copied into RNA. So remember you can Change the code and change what the protein does or you can do some to that middle guy and have that middle guy Do something that changes what the Protein does or how it works or whether it switches on This is a funny concept too because if you think about it all the cells in our body have all the well Oh, let's leave lots of germ cells All the cells in our body have all the instructions for all the things that we need to stay alive, but the cells in your liver Don't have aren't using the same Proteins as the cells in your brain or the cells in your skin. So some of those genes have to be turned on or expressed while others are not and so if you Suddenly find that there's something in the liver that's turning on that shouldn't be or that you want to turn off this thing to see What it does to make the liver function properly. Well, you come along with Craig's probe and you send it into the cell and it goes and Turns that gene off and then you say oh wonder what that did and you look and see and that's sort of how the research works But Jennifer you're actually doing something a little different than that because your lab has come on to this Well, maybe actually it's a version of that. It's not quite that yeah, I guess you could call it a version of that I mean, I think one of the interesting things when When Andy fire and Craig mellow made this discovery about RNA interference one of the curiosities I guess at the time was that that bacteria which is a very as you know many many different types of bacteria on the planet None of them seem to do this and people could not find the molecular machinery for RNA Interference in those types of cells and so the question that we had was You know, we were sort of interested in how these these RNA molecules do this this searching and we're studying that and then a in around 2005 There were a few sort of obscure Observations about about bacterial systems that looked like they might be Aligned or similar at least to RNA interference. There was no experimental data for this at the time. It was basic based on looking at the genomes of bacteria and realizing that Many bacteria have a way of stealing little pieces of DNA from viruses that they get infected with they they They integrate or they incorporate those pieces of DNA into their Genomic or genetic material and then they make an RNA copy of that information and just like Craig described They use those pieces of it of information in the form of RNA to search the cell for matching Sequences that might come from a virus and if they find a match then they have proteins that can Engage with that at that point that piece of DNA that has been identified as foreign and And lead to its destruction and so that That was a hypothesis and and we started Investigating it thinking that it would be very interesting to just you know, we were just curious basically wanted to understand You know if bacteria really were capable of that sort of Activity and you know you can if you think about it. It's really like an acquired immune system, right? You acquire information from your your invader and then you use that in the form of RNA to protect the cell So that was the idea that we set out to test and so in the course of doing that that research And of course other labs Started to investigate this as well and over the next few years it emerged that in fact this is exactly what happens in bacteria They have this ability to acquire Sequence information and then use it in the form of RNA so a very interesting parallel I would say to RNA I and But I'm a you know I'm a biochemist and a structural biologist So I'm very interested in the molecules that do this How do they work and that's the question that we really wanted to address that led to a Technology that is now really taking off for for genome engineering. So explain okay So explain why so people this isn't a people have been manipulating genes and doing things with genes and rewriting genes and There's genetically modified organisms and there's all this stuff But yet what you've done this new idea this thing It's called CRISPR, which again, we won't tell you the acronym because we're both Somebody will get it wrong and then if somebody else will laugh and but CRISPR allows you to do something that's different Even though it's doing some of the same things. So what's different? Well, I guess I would say what's different is that I guess the way the way that I think about it is It's like a molecular scalpel It's a very precise tool that can be used to identify a particular place in Genome and you think about you know the vastness of the human genome for example and imagine being able to imagine Knowing that there is a single change in the Four-letter sequence of the genetic code in a human cell that is giving rise to a defective protein I could you know many examples of this cystic fibrosis is an example You know sickle cell anemia is another example lots of genetic diseases that are caused by a known mutation or change in the DNA that creates a Bad or ineffective protein and so what if you had a precision tool like a scalpel to go in and Actually make the change correct that exact site in the DNA and not Effect anything else in the DNA very very powerful, and that's basically what this CRISPR technology enables Is that kind of precision change to the DNA? Can I Jennifer's lab has Been working again on the structures of these proteins that do this so in in RNA interference the search engine searches through the Messages that are out in the cytoplasm And sometimes in the nucleus as well, but it's basically searching single-stranded Sequences for matching information, but this enzyme this Bacterial enzyme and this is really basic science because when Jennifer and others started working on this there was no Glimmer really that this would actually be useful in humans are in human cells But basically what this enzyme does is it searches the same sort of the same way in a similar way For perfect base pairing interactions, but it opens up the DNA it unwinds the DNA and it searches both strands of the whole genome Billions of nucleotides of information it searches through all that information somehow In a scanning the whole genome for a match when it finds a precise match It actually allows this base pairing interaction that's highly specific and then it cuts Not only the strand that's base pair to but the other strand as well. It has two enzymes It's so beautiful in the structures that Jennifer's lab has made are just mind-blowing Showing how this enzyme can engage the DNA and make these very precise cuts So it is just like like Jennifer said like a scalpel that you can direct towards any part of the genome to make these Extremely, but that's a very important point So something that to appreciate about this that that helps you understand It's I think the power of this technology is that we figured out how to program this. Okay, so it's programmable so you take the ability to program the scalpel and you combine that with the genetic information that we have for the human genome we know the sequence of Many human genomes now, but other other genomes from other organisms as well and so you have that information and You can now program this CRISPR tool with it's a protein called Cas9 to actually Recognize a site that you know is defective in the genome to make a break in the DNA And then after that occurs the cell can repair that break by Incorporating new genetic information at the site and there are various ways to control how that repair Happens and so you put all of those Technologies and and and information together and it creates an incredible Opportunity in biology and this is what we're seeing right now. It's just an incredible explosion of research that's using genomic information from humans, but also from other kinds of organisms combined with the technology to now make changes very precise changes in that information and Do it quickly and also very importantly do it simply right? So it might maybe it sounds complicated, but turns out that for for anybody that has a basic knowledge of molecular biology This can be done Easily and quickly and effectively so we've had we've had high school students come to the lab and within a few weeks of training They're doing this type of precision genome editing and And I was just thinking one final analogy that may help a little bit in kind of getting your head around this is it's a little bit like First we had the book or like think of it as a word processor First we could write all these words down and then we had this function that was allow you to find so you could search For words and then the next step was search and replace or search And so you get that extra step of not only finding things and maybe taking them out But now you can find them take them out or put something new in in a very powerful way and So as long as you know the book and you know that Instructions to use the word processor You're good to go sort of now Craig you started out by talking about Diseases human diseases that that might be Them and that they're already therapeutics that are based on your the RNA interference technique And when we first were kicking around ideas for how to name this session we were thinking about okay The end of genetic diseases and that made you uncomfortable. So I want to talk about Why that is I mean where are we realistically in terms of Applying these tools into something that people say oh well, that's great. I'm glad you discovered that My aunt is alive because that's a great question Joe and I to answer it up I'll just sort of go back to the last night. We had a discussion at dinner About you know, what are the major gaps in knowledge? that we face and I may be analogy of my old friend Neil Shubin who went up to Canada and Hike Canadian Arctic and found this amazing fossil of a fish from 350 million some years ago That had these vestigial forelimbs and when he came back and everybody was celebrating his colleagues congratulated him for creating two new gaps in the fossil record But in genetics that's exactly what's happened with genome sequencing so when you sequence a genome like the human genome You it create a great deal of new knowledge, right? But as with all science all new knowledge actually creates more questions than answers and so with human genetics now We have very personal gaps in knowledge because we as individuals may know that we have a genetic You know, we have a an a lesion or a polymorphism in a gene that may be linked to a disease Something terrible like Alzheimer's or a neurodegenerative disease like Huntington's disease and yet Knowing what's wrong with your DNA doesn't mean that we have a therapy doesn't mean that we can fix it And increasingly now your when you go to get a health checkup in the hospital Or if you unfortunately get cancer or someone in your family does then all of a sudden you have this additional burden of new information Right your dad might have cancer and then you start to wonder well if he has the gene Do I have the gene that that predisposed him to that cancer my dad had prostate cancer? so right now there's no genetic test for that but You know these are the kinds of burdens and gaps in our knowledge that are affecting all of us now when it comes to health care so genetic Genetics in humans is now driving Laboratory science because we can take a genetic lesion that's known to be linked to disease in a human and using crisper We can model that disease now in an organism where we can study it much more effectively a fruit fly or a worm or a mouse We can now incorporate exactly the same lesion that causes a disease in a human and then study it in the animal And that's that's very powerful So probably more important than actually developing a therapy based on fixing the human disorder We can now study in an animal setting where we might be able to find a small molecule or some other Biological approach by you know an antibody or something that would would have a therapeutic effect for that that patient So the era of genetics and human genetics is Absolutely upon us. It's it's you know There are potentials for applying this technology to directly correct human genetic disorders in human cells So there's that but there's also this reverse flow where we used to model Or try to understand biology in a model organism and then try to extrapolate from the human increasingly we're taking information from the human genetic information from the human and now trying to model that in organisms and so there's a huge need for Additional research because there are thousands of human disease related genes now and it's really exciting time right now in genetics Just to remind people the the hashtag global health if you have a question that you want me to see on this iPad or if you're out in The worldwide web land and you want to ask questions, please do But that's it brings me to question Jennifer 30 years ago probably just about when we had The gene that causes cystic fibrosis we knew what it looked like and we knew some of the places where it went wrong and Could cause disease because that's another problem with genetics They gave names for genes that are necessary and make people think they're bad the cystic fibrosis gene is a gene We all have to have for ourselves to work properly. It's only when that gene is incorrect that we get the disease Bad genetics if they had asked me I would have stopped them from using that terminology a long time ago Anyway, they do it doesn't matter But that was in a day 30 years ago when we had gene therapy. Oh, we know the sequence of the gene We can make a proper copy and scoot it back in 30 years ago and there is no gene therapy I mean there's the beginnings of gene therapy in some places. I'm not I'm not saying What's different? Why is CRISPR? Are we in are we gonna say it 30 years ago? We thought well CRISPR was gonna give us the answer of how to fix these genes, but now we don't I mean What's different do you think? I think 30 years ago, you know to do an experiment like you're describing would require using for example a virus to deliver a normal copy of the gene and the viral The way that the virus works is to go, you know, it gets into a cell using a sort of an infection pathway and And then depending on the type of virus either it integrates into the genome But it integrates where it wants to integrate not where you want it to go Or it stays inside the cell, but doesn't actually Replicate or get you know copied into the genome of the cell so Yes, you could introduce the the normal copy of the gene using those sorts of approaches, but You know it was very difficult to control the way that gene would then be Express or you know would be used to produce the correct copy of the protein in those cells I think the difference now is that with a precision tool the CRISPR system allows Scientists to if you know and we do in this case Where that gene is located and you know the sequence of the gene and you actually know the sequence of the gene mutation in the gene you can design this system to go in Recognize it cut it out and then allow the cell to repair it with a normal copy of the gene and now you have in principle at least you have now a corrected Genomic sequence that can allow the cell to function normally So Craig do you think? CRISPR or that technology is going to Accelerate the path to therapies it's certainly going to accelerate knowledge about how Cells work and how and allow scientists to do interesting experiments But and what do you think about the therapeutic potential? I think there's a great therapeutic potential for especially for cells that can be taken from patients and Manipulated in the laboratory So if you can take a stem cell population from a patient that has a genetic disorder and repair the genetic lesion in the laboratory where it's safe and you can make sure that you've Affected the change you want and made no others then you can reintroduce those cells in a in a setting Where they'll then provide that function now to the person what where it's harder to do is to Take someone let's say who has a muscular dystrophy or down syndrome or something like that and actually try to affect a change Globally throughout the body of the individual or throughout all the muscles or in a tissue type right brain Yeah, so there it's very difficult again the delivery Problem is the real problem and another thing that you know I think one reason everyone has to know about CRISPR is you can rewrite the human germ line with CRISPR Very tell them what that tell them what the germ line. That's the sperm in the egg lineage. So It used to be you know really hard to do that kind of manipulation on an animal like us But now people have done CRISPR on other primates already on lots of different types of livestock You know cows pigs People are doing this and it's really a powerful tool because breeders when they used to breed animals together would have to Cross them together and then segregate all the traits away But now with CRISPR you could move one trait at a time very rapidly for multiple traits at a time Multiple traits at a time. Yeah, it's it's really powerful tool for changing the genomes of organisms Permanently by affecting what's called the germ line And so that's that's something that everybody really needs to sort of understand because first of all You know, there are ethical implications there a lot of them And it's something that's you know much more likely to happen now that it's so easy to do So it's important that people be aware that that is something that's Before we leave that Jennifer, can you can you sort of sketch out? I know you've been thinking about this What are some of the ethical implications of modifying the sperm or egg of an organism? Well, I think Craig, you know sort of sketched, you know the the fact that this is now something that it's a technology That's easy to employ to do this the challenge is that that you know, yes, we have Genomic information But we don't understand or at least I don't understand all of that information. We don't know What will really happen if you make a change at one place in the genome? Does it really only affect that one? you know Protein that gets encoded there if it's a if it's a change that's made in a gene or are there other effects that we can't predict later on Right that might happen So I think that that's a really important challenge and then I think that you know the question always comes up You know if you if you if this type of thing were to happen with humans You know where where do you do you draw a line or and if you do where do you draw a line? It's okay to correct the mutation that causes cystic fibrosis But is it okay for someone to say well, I'd like my child to have blue eyes and not brown Right and you can go on from there So I think that you know, it's just a it's a very important Conversation that needs to happen and one of the things that I would like to do and we have a new initiative at UC Berkeley and UC San Francisco called the innovative genomics initiative and one of our goals is to educate people about this technology and also to to really try to You know foster the conversation about bioethics that comes up around this We do have a question from the Internet or from the Twitterverse This is from someone who says he's in Indonesia or I think it's he how can we cure cancer with genetic engineering? Is it a possibility to cure cancer great? Well, you know, there are lots of different therapies for cancer that are extremely successful You know the war on cancer, you know the scientists sort of always sort of overpromise I guess or get misinterpreted Enthusiasm gets misinterpreted, you know like the title that was proposed for this session the end of genetic disease It's really just the beginning of understanding Genetic disease not even close to the end But there are therapies for cancer now that are very effective and there will be more therapies Some of them probably will employ CRISPR and genome editing There's a new type of therapy for cancer called immunotherapy, which I think is absolutely beautiful where a patients own immune system is essentially Used or adapted so that it will attack the cancer and then you can re-infuse the The cells modify the cells so that they'll recognize the cancer cells and they'll go and then kill the cancer cells So your immune system that normally fights and destroys infected cells can be Educated so that it will attack cancer cells specifically and there's an opportunity to use CRISPR to help Make the that type of attack even more precise so that you can try to Engineer the immune system to do this and some of the the clinical trials of this new therapy are look very promising where individuals for example with inoperable brain tumors are showing What looks like complete remission with the without need need of a surgery, you know So those cells go into the brain find the tumors and destroy them so yeah, there's some really exciting applications in that area I You know that's the one that comes to mind But I'm not sure that you'd really be able to use this to engineer the cancer in order to kill itself And it's probably not going to work because evolution is working against you there Right, but there's an interesting point also to make here And that's the difference between a genetic disease in the sense that it's inherited and a genetic disease in the Sense that something's gone wrong with the genetic machinery inside of a cell and that's really what's happening a lot of the times in cancer It's not that necessarily that you inherited something bad. That's going to cause cancer It could be something that changes over the course of a lifetime In the way the genes are functioning inside of a cell that can cause the cancer is that do I have that right? Yeah, yeah, and so Does CRISPR I mean? Once you make a change with CRISPR like if you took out Cells from me these may be bone marrow stem cells that Craig was talking about like they do bone marrow transplants now And you made some change In those with that change persist if you put them back in me And they would they keep having that over and over again as they populated Yes, if they're if they are what what are called stem cells, you know cells that can proliferate Over many generations in the body, right one example of a therapy like that is the therapy to create for people with HIV to create resistance to HIV by mutating the CCR 5 receptor on the cells that the HIV needs to get into the cell so if you take a patient that's already infected You get bone marrow cells from the patient that are not in fact Infected cells make that correction put those cells back Then those cells will not be able to get infected So the the patient will then those cells are now under positive selective pressure Because the other cells are being destroyed by the virus and they take up residents Populate the immune system of that individual and then hopefully you've affected a therapy So we are already know that people who have that mutation are resistant to HIV So those are there's their clinical trials for for doing that using another version of a genome editing tool Jennifer you alluded to this earlier, but I want to Sort of hammer home this point that when you were Doing your research over the last couple of decades you weren't sitting in your lab thinking, okay How can I cure human diseases? It was sort of like oh that would be a nice consequence But but you are asking a very very kind of basic question about how cell machinery works What's the connection there? I mean how how do scientists both work on something basic but have their minds open to something that might have a Therapeutic potential well I think a lot of the important technologies that have come out for Manipulating DNA in particular, but other things as well have really come from this sort of curiosity driven research By scientists who are you know not not going after a new technology in particular But are just investigating how how things work and in the course of doing so they Stumble across something and or realize that something can be harnessed for a As a technology and that's you know you there are many Interesting examples of this actually a lot of them have come from bacteria You know so something called the polymerase chain reaction, which is a way that we can amplify or make many many copies of just a particular Segment of DNA that's something that came from the bacterial world and again was from curiosity driven research not not necessarily to create a technology and You know the something called green fluorescent protein, which is used for labeling cells another Idea that came from just under you know wanting to understand you know how do certain types of organisms have Are able to turn their bodies green From jellyfish right so you know just very very interesting so I think I think To me this really underscores the value of doing that kind of research and I mean Craig also his laboratory Also does research that I would say is of a very fundamental nature trying to understand the basics of biology and again You know his research came across something where you know They realized in the course of doing their experiments that this could actually be really interesting and really exciting technology Yeah, you know the the basic science really is so important and so powerful in You know when you're trying to understand something extremely fundamental about how cells work We still have a lot that we don't understand But the thing that people don't realize is that the genetic code is the same in bacteria and humans the same four letters the same three letter words And the same amino acids assembling the protein so you can learn a huge amount in fact the genetic code is deciphered using bacteria and bacteria phage bacteria viruses to study the human You know to figure out the genetic code and later on we realize that that it's the same in humans so there are really really fundamental questions that we need to answer and Like Jennifer's field of protein structure one of the huge unknowns right now is how can from a primary sequence of Amino acids could you or how can you predict how a protein will fold? Because there's all kinds of even though. There's only 20 different amino acids 20 different words if you will they have a really Really intricate chemistry associated with each of them and they assemble in three dimensions So you get these emergent properties when proteins fold and we don't understand that even the fastest computers We have are really lousy at predicting structure So you have to actually determine the structure of these proteins you can't just read the sequence and say oh I know what that protein would look like And I think one of the best ways to think about the importance of basic research is if you think about the work that was being done in the 1950s on trying to understand what to do about polio There were a lot of people who were designing better iron lungs Because that was a really concrete thing you could do to help polio victims survive longer But the real breakthrough polio came from a basic understanding of the virus That caused polio and suddenly instead of building better iron lungs We were designing a vaccine that prevented polio in the first place So you sometimes say well, what's the connection between basic research and where does it get us? And the answer is it takes us it's almost this quantum step forward That you know applied research sometimes only gets you small baby steps anyway just saying we have time for one quick question It's a big question, but I wanted to take it. It's from the internet and it says who owns this new genetic tool And I don't know whether you want to take that craig it's bearer Well, but maybe you can just sketch out a little bit about the fact that there is some issue about that Yeah, and it's certainly it's not something to tackle in a couple of minutes, but Jennifer and and her co-workers filed some of the original intellectual property around how to Essentially design Guide RNA molecules that will enter into this search machinery Which I think is a really fundamental piece of intellectual property But there's a lot of intellectual property that is coming along as people figure out other ways and better ways maybe of Designing guide RNAs and to modify the enzyme itself. It's really I mean that's another thing You know this investment in basic science does lead to any big economic impacts RNA interference is a multi-billion dollar industry You can order a guide RNA for doing an RNA I experiment and have it delivered here by FedEx tomorrow if you want it I don't know if they have same-day delivery, but seriously you can knock out any gene in the human genome With a guide RNA from from the you know ordered off the web So, you know these these there's a lot of intellectual property There's it's still being sorted out and there'll be a lot more But that's good for the economy because it's start leads the startups Jennifer and I are both involved in different startup companies that are they're commercializing this technology All right Well, I'm afraid we're gonna have to leave it there There will be an opportunity to comment on this session if you enjoyed it on the way out And so we'll end simply by asking you all to give our speakers a round of applause