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Lynn: My name is Lynn Jorde. I'm the Chairman of the Department of Human Genetics at the University of Utah School of Medicine. I'm here today with Dr. Eric Green, who is the director of the National Human Genome Research Institute.

So, we've heard a lot about the ever decreasing cost of genome sequencing, about a million fold in the last decade. Does this mean that everyone should be sequenced? Or if not, who should be sequenced?

Dr. Green: So from a research perspective, I think there's great power in getting tremendous amounts of data from as many people as possible and using this in very robust ways to try to understand many aspects of health and disease. I think your question though, is aimed more at, "Should everybody get their genome sequenced as part of their medical care?" I'm not sure we're quite there yet. That might be where we are eventually, but just because we have the technical capabilities of doing that, I think we're far away from knowing what to do with that information in a clinical context to say that this should be sort of used for everybody. Rather, I think it's most useful now in very discreet areas where there's clear evidence that having genomic information will be helpful to that patient.

Lynn: Some critics have said that the Human Genome Project, of which you and many of us have been a part, hasn't really delivered on one of the original promises to revolutionize medicine. How would you respond to that?

Dr. Green: When the Genome Project ended 13 years ago, there was incredible celebration. In fact, many of use were euphoric about having achieved the goals that were set out for the Genome Project. I think in our exuberance lots of promises were made and lots of claims were made to have this was going to revolutionize this, that and the other and lead to great medical advances. I think much of that exuberance might have been over interpreted as meaning those advances were going to take place quickly.

There was no reason to believe it was going to happen that quickly. Actually, if you look back in the history of bio-medical research, there is usually periods measured in decades between very basic discoveries, such as the discovery of antibiotics, the discovery of the basic biochemistry of cholesterol metabolism and the actual changes in medical practice that led to advances in medicine. Decades. Here we are only 13 years in to having information about our genome available to us. So we've not seen the revolution, that I think will eventually come. I think for that we've been criticized.

I think we just have to take a step back, recognize that we're 13 years in. There's some vivid examples where genomics has had a profound effect on medicine, but they're the earliest examples. Even in aggregate those don't represent a revolution, but they're highly illustrative of what is coming.

So I think, when we look back at the history of genomics, say 10, 20, 30 years from now, I think that will be the fair time to assess whether or not our claims that were made when the Genome Project ended, were accurate or not. It's just too soon to do it now.

Lynn: So we're seeing investigations now, of all sorts of traits. The genetics of IQ, people claim to have found genes that influence things like aggressive behavior, anxiety. This gets pretty controversial. Are there areas that should be off limits, at least off limits to NIH funding?

Dr. Green: Absolutely. People get very uncomfortable with some of these ideas of doing genomic studies to better understand the basis for IQ, for aggression, various other attributes. It's also controversial scientifically, so before we even think about whether or not we want to limit this, I do want to put some reality on this. I think most scientists would agree that getting an accurate assessment of intelligence is not simple. Getting an accurate assessment of behavior is not simple. I think it is scientifically controversial whether we can even make major gains in this by doing these studies. So I think that really has to temper our enthusiasm for it. But then, of course, there's the ethical and societal implications of this. Are people going to be comfortable with it?

I think we need to be very cautious. When we are going to use these new tools of genomics, especially at this early stage, to prioritize things that are going to have great societal benefit. There's so many major medical challenges, disease areas, that will benefit from using these tools first and foremost, those are the areas that should be prioritized and I think that's where we should be putting our energies. At the same time, we should be very careful looking at what some of these other studies that might be envisioned, how they'll be perceived and how practical they are. I think they're going to end up being a low priority. In some cases, one might imagine doing some studies, along those lines. I just don't think they're going to be at a very high priority.

There's a lot of controversy of whether they'll be successful. It just doesn't seem to be the thing to be emphasizing right now. So, my enthusiasm level is low. I think in general people are making decisions about where money is going are going to deprioritize them. I'm not sure I want to say there should be a ban, but there should be careful scrutiny put on these. Research dollars are precious and we need to go to things that are more practical, and things that will have a higher impact on human health and disease.

Lynn: Over the past two years there's been quite a lot of controversy about patenting human genes. So, how does patenting, or not, affect scientists and consumers? Could it affect interests on the part of the private sector in investing and genetic and genomic research?

Dr. Green: There's not simple answers. The whole intellectual property construct and the ability to get patents and protecting people's advances are very important for the private sector and their ability to invest in things and feel comfortable that they will get a return on investment and so forth.

On the other hand, there's something a little special about the human genome. It is very basic, fundamental to humankind. It is our blueprint and the potential to have fundamental information about our blueprint be used. And a fast note, any day we be restricted makes many people uncomfortable. I think one of the things genomics has done, and its sort of cultural values associated with data sharing, is making as many things available to everybody, freely, widely. I think has served us very well. I think the fundamentals of understanding how the genome works in human genes and so forth, having no restrictions on their use, I think is very, very important.

There's a vision associated with using information about one's genome to tailor their medical care. I think many of us get very uncomfortable if in the process of doing so, if too many patents were laid down they would look like tollbooths across the double helix. Every single time we would go to one to analyze one part of someone's genome, we would have to pay a toll, and that would greatly hinder advances.

So, I think many of us have taken a position that it's so basic, that information, that just raw information, which is easy to get about the human genome and about genes, should sort of be off limits for patenting. Now, if you use that information you come up with a great intellectual advance and you design things around it and you come up with something that is more than just the basic fundamental information, yes, that should probably be fair game for patenting, for getting intellectual property and so forth. I think it's that raw information about genes that has made many people uncomfortable and have said that should be off limits for patenting.

Lynn: A big part of this then is the public understanding of traits, of what it means when we say a gene is associated with a trait. This gets us to the question of genomic literacy. What can we do to increase genomic literacy among the public so that they will better understand these kinds of issues?

Dr. Green: Genomics is a relatively young discipline. It's only been around a little over a quarter century. We are fortunate that it's been wildly successful. I think we're all very proud of that, but that's actually created a bit of a challenge for us. The challenge is that this field of science is finding it's way into medicine faster than any of us could have anticipated.

As a result of that, we have some complicated concepts, but also some basic language of genomics that it's finding its way into medical care. Yet, most people don't necessarily know the basics of this. They haven't been given the opportunity to learn it. Many of the healthcare professionals weren't taught this when they were in school. So this is happening so fast and furious that our ability to educate the public, educate healthcare professionals, is lagging behind.

As a result of that, this becomes very important when patients go to see their healthcare professionals and now will start hearing, in some context, about genomics. They don't really understand those words, they don't understand that language. If the patients don't understand it, they're going to go home and talk to their family. They may not understand it. They talk to their friends, they may not understand it.

So we have a societal responsibility to increase literacy about basic language of genomics, because that is a language that will increasingly be used by healthcare professionals, as part of patient care. It's not anybody's fault that we find ourselves in this situation. We're victims of our own success. We've been successful scientifically and now we need to sort of redouble our efforts to think about how to raise genomic literacy more broadly across society.

Lynn: Looking forward to the next decade, the next two decades, what excites you the most about genomic medicine?

Dr. Green: I think what excites me more than anything is the optimism that I have that what is going to transpire over the next decade is going to be significantly greater than what has transpired over the even last decade or the last two decades. I think we're so much more poised to accelerate progress than we ever have been in the last 25 years of genomics.

So, what I anticipate, what I'm excited about, is on multiple, multiple fronts, multiple areas, whether it's cancer, whether it's rare disease, whether it's infectious disease, whether it's in thinking about how to prescribe medications in a more precise and rational way, it just seems in so many areas, the progress I anticipate over the next ten years, I actually believe will be even more remarkable than what I've seen. Yet, I've been shocked by how much we have seen medical applications of genomics begin to be realized on a timeframe that I simply would not have predicted when I got involved in this field initially. I'm even more excited about the next generation of biodmedical researchers and healthcare professionals who I think are going to be the ones that are going to truly realize genomic medicine.

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Interviewer: Imagine knowing whether or not your child is at risk for cancer. There would be the possibility to prevent the disease before it even starts. Pediatric oncologist Dr. Joshua Schiffman is part of the first initiative of its kind that promises to do just that.

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Interviewer: Dr. Schiffman, tell me about your study.

Dr. Schiffman: Right now, we've instituted a very large study through Primary Children's Hospital and the department of pediatrics to investigate every new child diagnosed with pediatric cancer in the state of Utah and the surrounding states.

Interviewer: Oh, really?

Dr. Schiffman: This program, called the Primary Children's Hospital pediatric cancer program, is one of its kind across the globe. We are doing whole-exome sequencing on every child and their parents and, when applicable and available, their siblings. This enormous unprecedented genomic sequencing effort is all to determine which children are at risk for cancer and why so that we can start to develop unique and effective prevention strategies and hopefully go on to expand this to a global population to one day hopefully prevent childhood cancer.

Interviewer: Have you started doing that?

Dr. Schiffman: We have started doing that, and we're starting to find some very interesting patterns of inheritance. Also tied into that project is not just genetic risk but trying to understand what are the long term consequences for childhood cancer in terms of late effects, what is the cost of treatment to these children, what are the immediate toxicity of these cancer therapies that we're giving, and what are the pharmacodynamics and pharmacogenetics of these therapies.
What we hope to do, going forward in the future, is take our genetic information and tie it all together to try to determine is there a genetic risk that we can identify for long term side effects, a genetic risk for toxicity, a genetic risk for drug levels in the bloodstream. There's no better place to do that type of work through the department of pediatrics with all of its collaborations and team building.

Interviewer: Yeah. I think an important point of that is this information may not just be beneficial for the patient but for the knowledge of how cancer works and the genetics of cancer.

Dr. Schiffman: Absolutely. We are in our initial phases of this pediatric cancer program, and our goal is to build this into something larger in order to take this to the globe around the world. It's not just our children in Utah that we care about. It's every child. I often say that one child diagnosed with cancer is one child too many. Through all of these different genetic efforts, epidemiology efforts, using tools like the Utah population database, we hope to reduce that number to no child diagnosed...

Interviewer: Can you give a specific example of how that information could help somebody.

Dr. Schiffman: One day if we are successful in identifying who's at genetic risk for cancer, you can imagine that it may be even possible to check a child at birth to see if they've inherited the genetic risk for cancer. If that's the case then there may be, one day, a drug we could give or a vaccine to intervene before that child develops his or her cancer, or in the very least screen closely so that cancer is identified the moment it begins. There is lots of new technology out there circulating, tumor DNA, imaging, and so on, where we can try to identify cancers at their earliest stage.

Interviewer: That's really exciting.

Dr. Schiffman: It's a very exciting time to be a pediatric oncologist. I should say that in pediatrics, which is how I'm trained, we always talk about prevention. We would rather prevent disease than have to deal with disease after it already develops. All of these genetic and genomic efforts here at the University of Utah in my mind are all to advance that mission of prevention which is so important and is our guiding light in the field of pediatrics.

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Interviewer: Maybe you've heard the term, genome sequencing; what exactly is it and should we all be demanding that we have it done?

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Interviewer: I'm with Wendy Kohlmann, a genetic counselor at the Huntsman Cancer Institute at the University of Utah. Ms. Kohlmann, describe what genome sequencing is and how it's different from say a routine genetic test.

Ms. Kohlmann: Genome sequencing refers to really evaluating the genetic code of our entire genome. We kind of think about genome sequencing, and there are two different types. One would be looking at what we call our exome. That would be analyzing the genetic code of really just the areas of our genetic material that contain genes. We have lots of filler genetic material in between all those genes, so there's a second technology called whole genome sequencing, which involves analyzing everything, including the areas that are outside of specific genes.

Interviewer: And we're learning more and more that this so-called filler DNA is actually important as well.

Ms. Kohlmann: Right, we think it is. So that's why some clinical and research applications are looking even more broadly.

Interviewer: So do you see this as becoming more common in the future, that patients will have their entire genome or their exome sequence?

Ms. Kohlmann: Genetic testing technology is rapidly evolving. In the past we used to very carefully evaluate families and try to pick the best gene that we thought fit what maybe was going on with the particular patient or a particular family history, because testing in one gene was very expensive. Technology is now making it so it's possible to sequence the whole exome or whole genome now for a few thousand dollars as opposed to the billion dollars that it took to do the first whole genome sequence. You may have heard this mentioned before, we're moving toward the idea of the thousand-dollar genome.

Interviewer: Right.

Ms. Kohlmann: But with that goes the million dollar interpretation. So actually analyzing all of that data and making meaningful sense of all the millions of variations that there are between humans and figuring out the ones that actually are providing meaningful information about that person's health, that's really where the challenge of implementing this technology into actual clinical care comes into play.

Interviewer: Is genome sequencing something that's covered by insurance at this point? Do you know?

Ms. Kohlmann: I can be in certain circumstances. The first area that was really introduced into clinical care was in a pediatric setting, where we can have very sick newborns where time is crucial in making a diagnosis. And going through this process of, well maybe it's this gene, maybe it's that gene, maybe it's that gene; that's just a luxury that those babies don't have. And so whole exome or whole genome sequencing might be an approach to trying to as quickly as possible evaluate the child to see if a genetic cause of their illness could be identified.
Coverage in general of all genetic tests is a little bit all over the board. We have some insurers who readily cover genetic testing. We have others who exclude even very well established tests. So I think with whole genome or whole exome sequencing the coverage will depend on if that's something covered by the plan, then also if a good case can be made as to why that expensive of a test is really the best approach for that situation.

Interviewer: And you would think that it could be a good thing to have your whole genome tested. After all, knowledge is power, right?

Ms. Kohlmann: I generally agree with that statement. I think that knowledge is power, but I think that there are a lot of misunderstandings about what our genetic code can tell us about ourselves. It is not if you have gene A that equals future B. It's much more complex than that. And we are still so in the beginning stages of identifying and understanding all the genetic factors that contribute to disease. What if a change is found in a gene that predisposes to cardiovascular disease? But what if you have a variation in another gene that is associated with being protective against cardiovascular disease? What does having those two results mean for any given person?
It's not that a genetic code comes with this roadmap of at 65 you'll get a colon polyp and at 70 you'll have a heart attack. It's very much more ambiguous than that. And right now it's a lot of money to spend on something that is likely to provide information that we really can't interpret or actually put into action at this point.

Interviewer: Something else you wanted to bring up is sequencing tumors. Can you explain what the difference is between sequencing a tumor and sequencing an individual's DNA?

Ms. Kohlmann: Genetic testing technology; we often think of it being used to make a diagnosis in a person or to help predict who is at risk for diseases. But genetic testing can also be used in other settings and one of the areas that we're using it more and more frequently is in the area of cancer. All cancers arise due to a series of genetic mutations. And so while we may think of something as being breast cancer or colon cancer, every cancer is actually a little bit different because of the different pathways of mutations occurred to create that cancer.
The same technology that I was describing to look at whole genomes or exomes or panels of targeted genes is now being applied to tumors to help more specifically say not just is this a breast cancer, but exactly what type of breast cancer it is. What mutations have occurred, and by looking at those mutations and knowing what role they are playing in a cell can we then pick a specific chemotherapy that may work better for this person. So this is a new area where this technology is really being applied, and an exciting area where the hope is more personalized and more effective cancer treatments.
But just like I was saying with using this testing for predicting disease risk, there are still limitations, you know. When we look at so many changes we don't necessarily know what every change is doing in the cancer cell. We don't always have a chemotherapy that may be targeting that particular mutation. But this certainly is a developing area of genetic technology.

Announcer: Interesting, informative, and all in the name of better health. This is The Scope Health Sciences Radio.