Print BCTV: Genome Revolution -- NHGRI's Eric Green on social quandaries in 2d decade of genome revolution

Genome Revolution

Transcript of BioCentury This Week TV Episode 152




Dr. Eric Green, Director, National Human Genome Research Institute (NHGRI)




Smithsonian Museum of Natural History

Henrietta Lacks

The Human Genome Project

Genome: Unlocking Life's Code


Air and Space Museum





Steve Usdin, Senior Editor




STEVE USDIN: The Human Genome Project was completed a decade ago. This week, possibilities and perils from genetic science, an interview with Dr. Eric Green, head of NIH's Genome Institute. I'm Steve Usdin. Welcome to BioCentury This Week.


NARRATOR: Your trusted source for biotechnology information and analysis, BioCentury This Week.


STEVE USDIN: The Human Genome Project, the first map of the genes of a single person, was completed a decade ago. It was a historic scientific advance, achieved at great cost. The first human genome cost a billion dollars. And using the same technology, it would have cost $100 million to create a second genome. Over the last five years, the cost of sequencing one person's genome has taken an astonishing plunge.


It's about $5,000 now, and the $1,000 genome is within sight. Just as the shift from expensive mainframes to cheap personal computers had profound economic and social consequences, the reduction in gene sequencing costs has transformed biology and medicine. Gene sequencing has changed the way we think about and treat disease, even our ideas of what it means to be human.


We've had to rewrite the story of evolution and human origins, even learned that modern humans carried Neanderthal genes. At the same time, the genomics area is fraught with ethical quandaries over anonymity, autonomy, and privacy.


What doors will genetic technology open in the next 10 years? To discuss the possibilities, positive and negative, I'm pleased to be joined by Dr. Eric Green, Director of the National Human Genome Research Institute.


Dr. Green, there has been a lot in the news recently about privacy in a lot of contexts. But the ultimate issue about privacy really is the privacy of our own genetic information. Are we going into an era where everything that's known about us personally and about our relatives and descendants is just going to be out there in the public domain?


DR. ERIC GREEN: Hopefully, it won't be ominous, in the way some people might interpret what you just had to say. But at the same time, what we have to recognize is that to really take advantage of these genomic advances that we've seen of late and really be able to apply them to better understand human health and disease and eventually improve human health, we need to do studies that are going to involve understanding people's genetic material, their genomes, and having that information widely shared with other scientists so that you could, in aggregate, infer things about the basis of disease in our blueprint, our genome.


STEVE USDIN:  And so one of the things, one of the tools that has been used in the past is to make that data anonymous. So the genetic data is out there, and some data about people's phenotype, what their diseases are, for example, are out there, but not their names. But some researchers have said now that really that's just a sham, that you can go back and figure out who the person was, in many cases, to de-anonymize that data.


DR. ERIC GREEN: And some people have used the phrase, it's almost illusionary to believe that we could truly make this genomic information completely anonymous. And so the context to think about this in, of course, is these two precious values that biomedical researchers have as they do these kinds of studies, where, on the one hand, we value so much the participation of individuals in biomedical research, which includes being able to have them share genetic information with scientists and also information about what diseases they have. But at the same time, we recognize, especially in recent years, that we need to share that data widely so that we can have studies that are large enough to be able to make inferences about the basis of disease.


And yet those things become in conflict when we begin to realize that we can't completely guarantee privacy when it comes to genomic information.


STEVE USDIN: So what we're talking about today are people who hopefully have given informed consent. They've made a decision. But there are a couple of interesting angles on that. One is, of course, that their descendants haven't and their living relatives haven't necessarily given consent, and information that they share will shed light on their relatives. The other thing is that we've got some data from people from before the era of informed consent.


The most famous one is Henrietta Lacks. She had cells that were taken from her cancer that were used for cancer research -- still are. There's a lot of controversy about that. Can you describe that and where it's going?


DR. ERIC GREEN: In the case of the second story, the Henrietta Lacks story, it's exactly as you described, where she had cervical cancer. And before the era of informed consent, some sample of that tumor was taken. And it happened to make a incredibly valuable cell line for scientists. They could grow in their laboratory for cells over and over again.


Worldwide, that cell line has been used for decades now for some very important biomedical research studies. But at the same time, what has come out, of course, is the identity of her family. She's now long deceased, but her family -- and now there's lots of genomic information about that cell line, including some recent studies where the complete genome was sequenced, completely elucidating that blueprint of Henrietta Lacks' cells.


And the questions were about the privacy of that family, because there might be information in there that they wouldn't want widely shared. And since this was done before the era of informed consent, protections were not put into place about what to do with that data.


STEVE USDIN: So there's another circumstance that probably is going to become more usual. There have been isolated incidents reported where families who are trying to undergo in vitro fertilization, who are trying to have a baby, do genetic sequencing on the embryos to select them. In the past, they've looked at embryos to see if they have a particular genetic defect. But now you can do a whole genome sequence, and you can decide this embryo might have an enhanced chance of getting breast cancer when she's 40, or this one might have an enhanced chance of getting Alzheimer's or something.


Is that something that's going to be in our future?


DR. ERIC GREEN: So there's no question these issues are coming up, and they reflect a whole host of societal issues we need to think about as the technologies put us in a position where we can ask very simple questions about embryos we may or may not want to have couples use because they would have devastating diseases. And then you can start moving down a path where some of them are less devastating or occur much later in life. And of course, you could even get into other characteristics that may not even be disease-specific and more about other characteristics or other features of an individual.


And as a society, we need to grapple with this. We need to think through this. We need to research this. One of the things we do at our Institute is actually support programs to investigate these things.


STEVE USDIN: Do we have a forum? Is there a way besides the pages of the newspapers and the tabloid TV shows to discuss this in an honest and reasonable way?


DR. ERIC GREEN: We certainly do. And one thing I think that's unique about the field of genomics is essentially from the inception of the field, we've always dedicated a fraction of our budget to studying the ethical, legal, and social implications of the work that we're doing, hand in hand with the research. And we've been grappling with some of these questions for many years and in fact are looking at them.


So it's not just the newspaper that this is being discussed, but we have real data, real science behind some of these decisions which help guide policy makers and healthcare professionals as they implement these exciting new tools.


STEVE USDIN: We've been talking about the ethical implications of cheap gene sequencing -- but how cheap? Moore's law predicts the rapid decrease in computing costs. But the plummeting cost of gene sequencing makes it look sluggish by comparison.


NARRATOR: You're watching BioCentury This Week.




STEVE USDIN: We're talking about the human genome with Dr. Eric Green. Dr. Green, when the first draft of a human genome was published, there was a lot of enthusiasm. And maybe even hype. People thought that the mysteries of life are going to be unfolded right away. We're going to have breakthroughs just around the corner. That didn't happen, but we have had some concrete medical advances as a result of the human genomics, haven't we?


DR. ERIC GREEN: We certainly have. I meant the past 10 years has really brought spectacular advances, the 10 years since the end of the Human Genome Project. Much of this was aided by significant efforts to actually understand that sequence, because the Human Genome Project was just about determining the order of the letters of our blueprint. We still are intensely studying it to understand all the intricate choreography that takes place.


But the second major thing that happened which is really helping these kinds of advances are new technologies for being able to read out human genome sequence, read out that DNA sequence. In 10 years, we've now dropped the cost of genome sequencing a million fold. And that puts the cost of sequencing the human genome into the bin that's like other diagnostic tests used in medicine.




DR. ERIC GREEN: Exactly.


STEVE USDIN: So can you talk about some of the things that have happened in medicine that are happening today -- later in the show, we're going to talk about things that are going to happen in the future -- things that are happening today as a direct result of our advances and knowledge about human genomics.


DR. ERIC GREEN: I can give you some immediate examples. One's a big word -- pharmacogenomics, pharmacology and genomics brought together. We've learned in addition to what genomic changes might result in a disease, we've also learned which genomic differences among people make them either a good responder or a bad responder to certain medications. And as a result of it, we now have, for a number of drugs, sort of standard of care being doing a genomic test to determine whether you are the right person to get that drug or not.


And so that's here and now for a number of medications. I predict between now and the end of the decade, it'll be dozens more medications where that's done.


STEVE USDIN: And so for example, for cancer, we've done shows about new melanoma therapies, where in order to know whether you can get that therapy, you have to have a genetic test that tells you that you might respond to that drug.


DR. ERIC GREEN: Of your tumor. But it's not just cancer therapies. It's also psychiatric medicine. Standard of care now for major medication use for treating AIDS is a genomic test to determine whether you're going to be a good responder or not a responder to a particular medication.


STEVE USDIN: Another area where it seems like some of the low hanging fruit was rare diseases that are particular ones that have an obvious genetic component.


DR. ERIC GREEN: Exactly. Especially ultra-rare genetic diseases. And we certainly see this where these cases come in to places like the National Institutes of Health, but we're seeing this sprinkling out across the country, where the medical care system has failed to deliver a diagnosis to this, oftentimes a child. And there's clearly something likely genetic wrong.


And these patients have had many, tens of thousands, hundreds of thousands of dollars of workup clinically and have not yet yielded a diagnosis. At that point in time, for a few thousand dollars, sequence that individual's genome, read out their blueprint. And not always, but quite often, you will find what the genetic defect is that's causing that disease. Sometimes that gives us clues about new treatment.


Sometimes it gives us clues about new diseases that have never previously been discovered. And sometimes it just puts us in an arena where we need to continue to study that patient and look for other similar patients with similar genetic defects.


STEVE USDIN: So I wonder if gene sequencing is going to become -- it is becoming less expensive -- it is going to become more common. What has to change both in the way that physicians practice medicine and maybe even the way that patients think of their own role in their care as a result of this cheap gene sequencing?


DR. ERIC GREEN: Well, both of these are incredibly important. And it's things we're absolutely thinking about in the field of genomics. The field has moved so quickly that most physicians, including my medical classmates, never saw this coming when they were back in medical school. And yet they're in the mid part of their career practicing medicine. And patients are walking in the door more and more asking questions about their genomes and even being able to think about tests they want to get.


And we need to be educating current physicians as well as future physicians. And then similarly thinking about these patients. Lots of people are becoming more and more aware. I think in areas like cancer, like you mentioned, they're going to jump on the web. And they're going to read about this for the particular cancer that they're affected with or a family member's affected with. And they're going to see genomics more and more featured in what they read about, and patients are going to want to be able to understand much more what these genomic nuances are associated with their disease.


STEVE USDIN: And that's happening already to the extent where people are getting access to direct to consumer genomics services, like 23andMe and some others like that. What do you think about those in general as tools for people to be able to manage their own health?


DR. ERIC GREEN: So one thing they've done is they've made much more aware of genomics in everyday life. And that's been a good thing. I think people have gotten much more engaged in the notion of genomics, and curious about it. The truth of the matter is we have to realize where we are now in 2013.


We have the technologies for being able to see these genomic differences among people and some of the earliest information about what it means medically. But we're in the early days. And so for many of the variants, people detect, and they know about we can't say for certain what that clinically means.


STEVE USDIN: As we've heard, one of the first medical applications of the human genome has been pharmacogenomics, changing the way drugs are used based the patient's genetics. Here's some data on pharmacogenomics.




NARRATOR: Now, back to BioCentury This Week.


STEVE USDIN: We're talking with Eric Green about the future of genomics. Dr. Green, soon, as we've been talking, the cost of a human gene sequence is gonna be the same as an MRI. What's that gonna mean for the future? What are the things we're going to see in the next 10 years as a result of that?


DR. ERIC GREEN: Well, certainly by the end of the decade, I would always say that I think the greatest change would be in clinical applications. Would be in the arena of cancer. Cancer is fundamentally a disease of the genome. A tumor's genome has picked up typographical errors, mutations that has turned it into a cancer cell.


And we are now opening up those cancer genomes as part of research, reading it out, and cataloging all the differences. And from that, we're learning a tremendous amount about cancer. We're so naive about so many aspects of cancer now, and we're really taking down those drapes, and seeing a lot more to understand what cancer is all about.


We're going to start to see increasingly, as part of cancer care, a much more rigorous diagnostic procedure of sequencing the genome of that tumor, and then making decisions about treatment. And also, making decisions about exactly what kind of cancer that really is.


STEVE USDIN: So it's going from a pathology where you're standing cells and doing what they could undermine the 19th century to looking at the genetic basis of tumors. There's also going to be advances -- it's not actually going to always be sampling of a particular tumor, right? There are going to be new technologies -- there are new technologies under development where you can actually find tumors circulating, or cancer circulating in the blood.


DR. ERIC GREEN: Well, absolutely. And again, it's this ultra-sensitive nature of these DNA sequencing methods that allow us to now just take blood samples to learn about various clinical problems. The one you just mentioned. Tumors that, especially a patient who has cancer and you want to know if the tumors come back, it's metastasized, and it's come back.


Instead of looking all over the body for one approach that we've now demonstrated, at least in research studies might work is draw blood from that patient, and constantly be looking at the DNA that's floating around in their bloodstream, and seeing whether or not you could detect that tumor, which you characterized months earlier, or years earlier, to see whether you're detecting it.


That's one example of sort of free floating DNA. Another one, changing sort of clinical situations completely, are pregnant women. Routinely now, many women get amniocentesis, chorionic villus sampling to do prenatal genetic testing, or genomic testing. That might go by the wayside. It may now be a blood draw, because in every pregnant woman, in her bloodstream is floating around a teeny bit of fetal DNA, and we can now detect that using these methods.


STEVE USDIN: And that kind of raises the other question, which is how far away are we from every baby having their full genome sequenced as a newborn?


DR. ERIC GREEN: Well, let's keep in mind, of course, and I'm sure you're aware of it, virtually every newborn in a country like the United States, at birth, or --


STEVE USDIN: There's a blood draw.


DR. ERIC GREEN: There's a little bit of blood stick, and they take a little bit of blood from the heel. And that baby, depending upon what state you're in, gets two to three dozen or so genetic tests done. But you raise a great issue. Instead of just looking at 20 or 30 different broken genes, why don't we look at a bigger battery?


And of course, it makes sense because we now know for about 5,000 genetic diseases, what the mutation, what gene is broken in that child's genome, and why are we only looking at two or three dozen? It may come to pass it'll be easier just to sequence the full genome, and get a much better appreciation?


STEVE USDIN: And then that begs the question of who gets that information, and who gets to release it? I mean, do the parents find out everything? Do they want to find out everything? Do they tell the child everything? Is that all made public? We've only got a few seconds left, but it's a very complicated.


DR. ERIC GREEN: Well, it's very complicated. We need to study it. In fact, we're starting some major studies to look at that. We see a future where perhaps people will want to have their newborn child's genome completely sequenced, and have that as part of their medical record. But there's a lot of practical and ethical issues that need to be understood and dealt with before we see that reality.


STEVE USDIN: Dr. Green, one of the things that genomics has allowed us to do, which is really fascinating, is to learn more about really, what does it mean to be a human? About human origins.


And one of the things that fascinates me the most is that we've learned that all humans, actually, or many humans have genes from Neanderthals. Before, we thought that modern humans and Neanderthals didn't mate. What did we learn about that, and how did we learn it?


DR. ERIC GREEN: Well, how we learned it is particularly cool, because these powerful new methods for sequencing DNA that we've developed in the last 10 years are so exquisitely sensitive that you can take fossil materials, like Neanderthal bone, which you can just recover teeny bits of DNA from, but it's enough DNA to sequence the genome of that Neanderthal, for example.


That gave us insights about an ancestor. And when you read out that sequence and you compare it to the current human genome sequence, you can see teeny patches where it's very obvious that there was some inter-mating between the two, and so there's a little bit of Neanderthal DNA in many of us.


STEVE USDIN: And we've learned other things about human origins from genomics also, haven't we?


DR. ERIC GREEN: Well, absolutely. We are much more precisely able to trace human origins and the migration of humans as a species out of Africa, and different relationships among different populations across the world. Many things that we had suspected for a long time, but you bring genomic data and superimpose it on top of all the other data that's available, and it just solidifies sort of our understanding of human migrations.


STEVE USDIN: And we've also learned about humans by studying other creatures, by studying other genomes of, what, hundreds of other, thousands of other kinds of animals, and doing comparisons, and seeing what's conserved among mammals, for example.


DR. ERIC GREEN: Absolutely. Because in every animal species, or every living creature on Earth, if you open up that genome and you read it out, it's like looking at evolution's notebook. Lots of notes have been kept about what did and did not work, or what had a change to make an organism different from another organism.


And the same tools we use for sequencing human genomes, we can sequence other animal genomes, take the data, line it up in a computer, and you can absolutely see the DNA basis for biological innovations, what makes us different from animals.


STEVE USDIN: And we also see, when you look at human DNA, you can see that there's bits and pieces of DNA from, what? From bacteria, from--


DR. ERIC GREEN: Absolutely.


STEVE USDIN: Viruses that are in there. People think of humans as being somehow distinct, but we're not. We're part of the whole kind of kingdom of animals, aren't we?


DR. ERIC GREEN: Correct. It's called evolution.


STEVE USDIN: And what are some of the other kind of different things, or surprises that we've learned about evolution, human evolution in particular from genomics?


DR. ERIC GREEN: Well, I think some of the surprises is just how much we really share with creatures that are far away from us. Other vertebrates, for example, that it really reinforced this idea that some of the most basic biological processes are shared.


STEVE USDIN: And next we're going to talk about increasing public awareness of genomics. More in a moment.


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STEVE USDIN: We're talking about bringing the public up to speed on genomics with Dr. Eric Green. Dr. Green, as we've been talking about, a lot of these issues are going to involve the need for public consensus. And you can't really have public consensus unless the public is informed and knows something about genomics. What are you doing at the Genome Institute at NIH to try to promote that?


DR. ERIC GREEN: Yeah, we regard genomic literacy, as we call it, a high priority. Many things we're doing, many outreach efforts -- including social media, Facebook, Twitter, a very sophisticated web page, and we take advantage of every educational outreach opportunity that we can. But I would think the thing that we're particularly excited about was a major collaboration that our Institute formed with the Smithsonian Institute, and in particular, the National Museum of Natural History. And after a couple years of rapid planning, just this year, to commemorate the 10th anniversary of the completion of the Human Genome Project, a major exhibition opened in the National Museum of Natural History called Unlocking Life's Code.


STEVE USDIN: Well, that's really cool because if you go down to the Mall, as you are mostly living in Washington, as I have, you go to the Air and Space Museum. And it's all about NASA's accomplishments, as well it should be. But before this, there really hasn't been anything about NIH. What do you expect people can come away from this, in different ages -- what are they going to learn from this exhibit?


DR. ERIC GREEN: Well, first of all, what we try to accomplish in this exhibition is to just make people aware, what is a genome, and some of the most fundamental aspects of genomics. But sprinkled throughout the exhibition is an appreciation for genomics important for individuals as patients, and all the clinical applications, for their place in the living world, recognizing genomics is so relevant for so many societal issues, and we sprinkle in as well, asking many questions to make them think about all these tough issues we've been talking about today.


STEVE USDIN: So we've got just a few seconds left. But how do you justify NIH's expenditure on education in an era where sequestration, where the budgets for research, for cutting-edge research, are being cut back. Are you going to be able to justify and maintain this kind of work?


DR. ERIC GREEN: So I should stress that the exhibition at the Smithsonian was completely put on with funds we raised privately, or that were raised on our behalf privately. So that wasn't using research funds. Actually, the amount of money we're spending, actually, I don't think is particularly high. We do it really in their spare time. And in some ways, certainly, the Smithsonian exhibition was a lot of hardworking people doing it on top of their day jobs.


But at the same time, I think this is a responsibility. If we really want to see genomics be applied clinically and change the way we practice medicine and improve health, we need the general public to be literate about genomics. This is going to become part of their everyday interactions with their healthcare professional. So we view this is as a responsibility that goes hand in hand with the research mission that we have.


STEVE USDIN: So we've got just a few seconds left -- two or three things that you want -- take-homes that you think are the most important things for the American public to know about genomics.


DR. ERIC GREEN: I think the thing to recognize about genomics is that, once upon a time, this was mostly about research. But fast forward, 10 years after the Human Genome Project, this is increasingly becoming relevant for all individuals as patients, and friends, and family of patients, which means all of us -- and increasingly, between now and the end of the decade, more and more genomic concepts are going to become part of standard discussions with healthcare professionals.


STEVE USDIN: Well, that's this week's show. I'd like to thank my guest, Dr. Green. Remember to share your thoughts about today's show on Twitter. Join the conversation by using the hashtag #biocenturytv. I'm Steve Usdin. Thanks, for watching.


NARRATOR: Dr. Christian Jobin, the microbiome expert featured on BioCentury this week, is now a professor in the College of Medicine at the University of Florida.