production funding for qed with dr b is provided by american electric power foundation boundless energy for brighter futures and by viewers like you thank you i'm dr fredrick berkley immunologist and educator science is everywhere and for everyone and it's all around us shaping our lives every single day in this series we'll look at cutting edge research talk to the scientists who are charting new frontiers and solving today's problems to make all our lives better when a scientist or mathematician demonstrates the proof of concept in their work they often use the term q e d quad demonstratum that roughly translates to quite easily demonstrated welcome to qed with dr b [Music] hey dr b how are you doing today good how you doing dana what are we going to talk about today today we're going to talk about genetics and this whole new landscape of gene editing now a lot of times when we hear about gene editing we hear this name crispr what is that and how has it revolutionized genetics crispr is one of the greatest discoveries in the last 10 years of molecular biology and genetics stands for clustered regularly interspaced short palindromic repeat now what's really cool about this you remember when we talked about viruses how we said that viruses can even infect not just people and animals but also bacteria well bacteria have evolved an immune response called an adaptive immune response which actually helps them protect themselves from these viral infections and the piece that actually helps them is this thing called crispr so crispr was discovered by biologists in 1987 but most recently dr jennifer doudna and dr carpentier they modified this gene to make it a scissor cutting tool to replace a negative or mutated gene and put in a correct gene in this place if you've ever used word processing you know what we're talking about if you use that find and replace you're finding a word that's misspelled and you putting in the proper spelling of a word or replacing it with a different word that's exactly what crispr caspase-9 offers for us and it's revolutionizing molecular biology and genetic engineering that's phenomenal and i know that there is a lot of debate around this whole idea of the ethics of changing your dna but today our guests are really going to shed a lot more light on all of these things and it's a really fascinating yet very complex area of study that's right diana and our first guest is a world leading expert in genetics dr george church dr church developed the first direct genome sequencing method and helped initiate the human genome project in 1984 and the personal genome project in 2005. he currently leads synthetic biology at the weiss institute and is a professor of genetics at harvard medical school a lot has happened over the last 30 years from the human genome project in 1984 then the personal genome project in 2005 which you actually played a significant role in both of those what are the importance of those studies the most important one is kind of the project in between those which is technology development called next generation sequencing which brought down the price from three billion dollars to three hundred dollars which is getting close to the point where everybody can afford it almost all of medical research depends on those genome sequences the biggest secret sauce is the concept of molecular multiplexing that's the main reason that that these methods are 10 million times cheaper than they used to be and 100 000 times more accurate and in the molecular multiplexing you have a droplet of water and that droplet normally contains one kind of molecule and you process it at great expense but now with multiplexing you can put in millions or billions of different kinds of molecule in that same droplet because the molecules don't take up much space it's mostly water anyway and they're all barcode tags and boom now it's uh you know 10 million times cheaper just because there's 10 million molecules in that same droplet so the same instrument is being used the same reagents are being used the same hundreds of steps each droplet goes through but instead of treating one molecule as one molecular type at a time you're doing a million or a billion that sounds like a miracle but it is is simply the bar code is has so many bits of information in it you just can't confuse it's just like barcodes in the supermarket this is exciting the technology is advancing incredibly fast that our knowledge base is continuously being built upon let's talk about some genetic engineering and the future of genetic engineering specifically are we looking at bringing back species i'm part of a international group called revive and restore that is working on restoring ecosystems that have been damaged by either modern humans or in some cases ancient humans you can read out the ancient dna into the computer and then you you don't have to recover the entire genome just the parts that would be helpful to increasing the diversity of modern uh species so that they can either tolerate the climate change or other environmental changes fragmentation of their herds migration paths and so forth so you you're really building a slight variation on on modern species so that they can thrive and in some cases restore an ecosystem that is in the best interest of humanity for example restoring the grasslands to the arctic would increase carbon capture and retain the 1400 gigatons of carbon that could otherwise be released as methane i'm really glad you said that because a lot of times when people talk about genetic engineering and the dna technology and bringing back extinct species they're always talking about at least in hollywood the wooly mammoth or it's always an animal but i love the fact that you're talking this is much bigger this is the ecosystem this is plant life this is all kinds of other living forms and and a cold resistant elephant could be a part of that solution they're a keystone species but it's not just about the endangered elephant species say more about where we really will get to with curing illnesses especially genetic illnesses how close are we to identifying a genetic mutation that's causing a serious phenotypic disease and a patient in our loved ones and going in there with some genetically engineered tools and fixing that we already have effective gene therapies at least five have been approved by the fda for general use and many are looking very promising clinical trials including some crispr editing for sickle cell anemia and also for retinal diseases so we might have a handful of gene therapies that are approved but there are thousands of genetic diseases that can be avoided simply via preconception genetic counseling so this is much less invasive than either in vitro fertilization or gene therapy much less research and development has to be done because each it's just one method which is looking at your genome potential spouses [Music] so if we look at kind of the genetic ecosystem on the one side is counseling that's an education thing let's just keep promoting that getting people to understand that these are options to learn about it and make choices um and then as you said it's really exciting the fda has approved already i think you said five gene therapeutics on that side of it because there's thousands of diseases genetically based diseases how fast do you see that ramping up it's not so much we can't find the cures the cost of getting them through clinical trials will be a burden almost all of biomedicine is going exponentially faster once you figure out how to do it for one it's very quick to do it for others but in general preventative medicine is cheaper than than these expensive therapies so we need to practice preventive medicine even if it's even if the companies can't figure out how to make much money on it we still have to think think about it at a governmental and uh citizen point of view are the other applications that you see this great technology that the average person doesn't hear about are not headlining and youth it can also be used for agriculture to make more efficient tastier vegetables that taste more like meat say and provide protection against various serious diseases like vitamin a deficiency and impoverished nations that kill about a million people a year i think that we should have the equivalent of weather maps i call them bio weather maps so that we're constantly monitoring emerging of resistance to drugs and vaccines emergence of diseases from from animal zoonotic diseases that are coming in we want to be monitoring all potential pathogens and we should be at least as interested in the morning bio weather map is in the weather map the weather map prevents us from falling down and breaking your hip and the bio weather map will stop us from getting you know allergens and pathogens listen dr church it was an absolute pleasure to have you on the show with us today thank you for your time thank you wonderful being here so to kind of summarize what dr church was talking about is that crispr cas9 is really changing the way that scientists can study genetics but dr b this is really complex he also talked about molecular barcoding can you unpack that just a little more yeah molecular barcoding is really cool so if you've ever gone to the grocery store and you have seven to ten different red apples they're all different but on them there's a specific barcode differentiating each one well similarly that's what they're now doing with this molecular barcoding instead of putting a barcode actually putting a dna sequence tag on a specific amount of dna that they want to analyze and what this does is it revolutionizes how fast we can process dna for example you have to take a sample of dna one at a time and process it but now you can put these little clones on each section and throw them all together process them at the same time infinitely cheaper from a cost perspective and super fast now you get a lot more information in a short amount of time at a significantly reduced cost and scientists are using all of this data to further the field of medicine and that actually leads us to our next guest that's right dr maya buchen professor of genetics at the pearlman school of medicine at the university of pennsylvania has been studying genetic diseases that involve more than one gene tell us a little bit about your research and the underlying genetic basis of developmental and psychiatric disorders i felt that it would be very helpful to work in parallel on two disorders a very early neurodevelopmental disorder such as autism that's usually diagnosed in second or third year of life and then bipolar illness um illness that has very different characteristics and much much later onset it's family-based approach so we basically collect families we perform very very extensive phenotyping and then we generate whole genome sequence and based on analysis in extensive analysis of whole genome sequence we're trying to see if we can somehow subdivide families with autism into a groups that carry mutations in a particular gene what did you find at the genetic level that differentiates those kinds of populations of autism we see something that's at the beginning it was very discouraging there is no a particular gene so many of us are familiar with huntington's disease or cystic fibrosis or maybe anemias where we can identify particular gene that's disrupted in vast majority of cases with autism it's not one gene that's disrupted there are many many mutations in different genes so although we don't have one particular gene still knowing this gene so-called genetic architecture knowing that many different genes lead to autism is extremely important not only that but each gene can have different kinds of mutations we find that some of these mutations are inherited in parents but it turns out that in many families these are new mutations that arose during formation of sperm in the father or formation of the egg in the mother many of these genes are critical for so-called synaptic transmission communication between neurons so we do have very good insight into pathways that are disrupted a major really surprising finding for me is that so many of these genes play very important role during embryonic development so as we know autism is usually diagnosed in second or third year of life on the other hand the action of these genes is much much earlier and this is also very important when we think about possible environmental factors that it's not at a time when child is diagnosed but maybe there are some environmental factors during embryonic and fetal development so it sounds like over the last 20 years or so the autism field has significantly grown in terms of our understanding of the genetics the genes involved and then how they're expressed where do you see kind of our understanding of autism and bipolar disorders 50 years from now wow 50 years from now wow that's a very very tough question in 5 or 10 years a child we will get a whole genome sequence for a child the minute this child is born that is something that is going to be happening very soon second and here i may be jumping to 50 years from now and not 10 years from now we know that complex disorders are not only genetic environment plays very important role so heritability of many complex disorders is 50 to 70 so we are basically right now uh ignoring we geneticists are ignoring environmental factors and in my view we will know much much more about these environmental factors actually i have here i forgot to put it on my feedback you can imagine that many of us are going to have many different sensors not only how much we walk or how much we sleep but also what's happening with our metabolism so if you have whole genome sequence and you have all these phenotypes many many different phenotypes by putting that together we will be in a much better position to make predictions and based on predictions to go with interventions we know for instance in autism diagnosing a disease early it means early intervention and with different behavioral therapies a child can really significantly improve so my answer to your question environmental influences and this genotype phenotype association that will allow us to make predictions so let me get this right in the future my fitbit may not only be able to track my blood pressure and my heart rate but it may also store my genome sequence what are the possibilities that adults can even know their genome sequence there are so many possibilities and one very effective low-cost way is through genetic counseling when we couple that with cutting-edge technology we could significantly reduce the amount of time and collect much more information to lead to better diagnosis and ultimately prevent disease and that has a lot of implications for family planning and actually our next guest is going to talk a little bit more about that she is an expert in bioethics that's right i talked with dr alta charo emerita professor of law and bioethics at the university of wisconsin-madison law school about the ethics of genetic engineering so genetic engineering has been with us for decades but now we're hearing the catchphrase gene editing in your opinion what are the important ethical issues around gene editing well let's first divide it up into categories because gene editing or genome editing is something that could be used either to for example change plants and animals in the world of agriculture it could be used to treat an illness that you or i have it could be used to edit an embryo in which case you're actually going to affect a future child so each one of them has a slightly different set of concerns right the public's fascination has been around a designer baby and that's going to be the least likely or at least least frequent use of this technology for the foreseeable future its biggest use is going to be in agriculture it's going to be about changing animals or plants so that they can better survive in a changed climate or where they emit fewer things that are problematic environmentally we've already used other forms of genetic engineering to create a pig that releases less phosphorus in its waste which would improve runoff to our legs there's a salmon that was changed so that it could be grown faster and in enclosed tanks so you don't have to ship it across the country and use all those transportation resources for adults like us this technology has enormous potential we've already seen it now treat sickle cell disease and this is a terrible disease because it creates incredible pain and in past years has led to early death and because it's mostly in the african-american community it's also hitting people that are disproportionately already disadvantaged in the healthcare system we now have the ability to correct the problem and the person with sickle cell disease no longer suffers from these things but there's a huge dilemma here it is incredibly expensive and it takes sophisticated facilities and tremendous amounts of money and that leads to several things it's very hard to get insurance to want to step up and pay for these incredibly expensive therapies second problem is in west africa the situation is even more dire and it's almost impossible to imagine in many of those countries being able to mount this kind of technological and economic feat so one of the ethics issues is should we go ahead and continue to develop therapies that are going to be out of reach for most people and if we are how much should we be devoting ourselves to finding a way to make them accessible to everybody despite that farmers essentially have been cross breeding and that is actually genetically engineering and we've been doing that for millennia and people are comfortable with that and so you talked about science and technology and the tools today allow us to do that at a more efficient rate and so is there is there a double standard that are kind of antiquated farming techniques going back thousands and tens of thousands of years those are okay but now instead of using a shovel and and putting your hands in the dirt and you're using these genetic tools in the lab that's somehow bad yes absolutely part of it is familiarity i do a biotech brunch for my students every year where i have them come to my home and have a brunch made of biotechnology affected kinds of foods and i serve them things like cheeses and yogurts because fermentation is a form of biotechnology as well as trying to find some genetically edible actually most of the corn we have is genetically engineered and so i serve them something that has corn in it so yeah some of it is is a double standard just based on familiarity and not recognizing how much of this has already happened part of it i think though is efficiency sometimes we use technology in a fashion that makes it possible for us to do things so much more easily that many more people think to do it and now what used to be a personal question becomes a societal question and that's because of the efficiencies and i think that's part of what happens with genetic engineering as we get better at it and it gets easier and genome editing has certainly been a leap forward in our capacity and the ease we suddenly begin to worry much much more about how many other things we might want to change and are we really comfortable with changing that many things you know and and suddenly that question becomes much bigger for us and part of a larger set of concerns about human control over ourselves and the environment and not just a question of a single lab or a single product talk to us a little bit more about what are the issues around designing babies should i have the right to choose what my baby can and should look like how tall he or she could be how smart if we could figure out what gene codes for that you said do i have the right to control how my child looks or any other trait and i'm going to tell you that you already have that right and you already use it when you pick a partner with whom to have a child you are also picking something about what that child is going to be when you use a sperm bank and you pick a donor you're already making some decisions about that child it's probabilistic but what if you could really be absolutely sure of what you're gonna get does that mean everybody rushes forward and said well let me do it now that i know there's no risk that's the fear the reality is that there'll never be no risk first editing is not 100 perfect and there can be unintended effects on other parts of the genome second when you edit an embryo which already has multiple cells you may succeed in editing some of the cells but not all of them and finally editing one thing doesn't tell you how it's going to manifest in a live born child because it's against a backdrop of a whole other set of genetic traits and so-called epigenetic traits the things that affect how the genes operate so genome editing is nowhere close to making it possible to truly design a baby so the phrase itself gives people the impression of a power we don't have and we are nowhere near having the question for the moment has not been about whether it should be forbidden to use the technology to choose a child with the traits that you like you know the height the complexion it's really about whether or not it should be used when you know that there's a genetic trait that is highly penetrated it will express itself against almost any other genetic background and it's truly devastating results in incredible pain and a very short life there are some genes like that they tend to be relatively rare but there are thousands of them and if you've got parents who know that they are at risk of passing this on or they know that an embryo has the trait and they still want to bring that embryo to term or they still want to have children for themselves that are genetically related this provides an option to delete that devastating trait i think of technology as a force of good it needs to be controlled but science is an avenue to improving our lives and improving the neighbors lives and improving the health of the planet i can't get past that optimism time for takeaways so my takeaway is that this whole idea of gene editing and what it can do is really exciting and i cannot wait to see the breakthroughs we make in medicine and also in other areas absolutely i mean think about books and libraries and then what google as a search engine has done for us to access information similarly crispr caspase 9 and next generation gene sequencing is a similar tool to expand our capacity to really impact healthcare in better ways and that's quite easily demonstrated qed with dr b join us on facebook instagram and twitter and we'll see you next time [Music] [Music] [Music] production funding for qed with dr b is provided by american electric power foundation boundless energy for brighter futures and by viewers like you thank you you
2021-07-10