00:00:06:05 - 00:00:30:02 Adam Hocking Welcome to The Rounds, a podcast of Marshfield Clinic Health System. I'm your host, Adam Hocking. The Rounds brings together medical experts to discuss fresh, fascinating and important topics from the world of health care. Precision medicine is an approach to providing health care that aims to tailor care as much as possible to each individual by understanding the importance of things like lifestyle, genetic makeup and the environment in which a person lives. 00:00:30:16 - 00:00:54:16 Adam Hocking Joining me today to discuss precision medicine's evolving role in modern health care is Dr. Murray Brilliant. Dr. Brilliant is a world renowned researcher in the field of human genetics. He's the director of research and the director of the Center for Human Genetics at Marshfield Clinic Research Institute. We'll discuss what precision medicine is, its evolving role in modern health care, and Marshfield Clinic's role in advancing research in this critical field. 00:00:58:04 - 00:01:01:04 Adam Hocking So, Dr. Murray Brilliant, thank you for joining us today on the podcast. 00:01:01:13 - 00:01:02:07 Dr. Murray Brilliant My pleasure. 00:01:02:19 - 00:01:18:23 Adam Hocking Precision Medicine is a topic that if you just do a new search for it, it's starting to come up more and more and news articles. It seems like it's kind of a hot topic lately. But can you help us to start with just sort of defined terms and talk about what precision medicine really is and what it means? 00:01:19:17 - 00:01:54:13 Dr. Murray Brilliant So we have different definitions for for precision medicine. Precision medicine used to be called personalized medicine, individualized medicine. Sometimes we call it genomic medicine. If we're looking at how the genome interacts with with our health. Specifically, precision medicine is a system where we utilize all kinds of information, genetic information, environmental information, dietary information to tailor your particular medical care to suit you best. 00:01:55:00 - 00:02:04:09 Adam Hocking And can you talk about how your role specifically involves precision medicine? You're the director of research and the director of the Center for Human Genetics at the Marshall Clinic Research Institute. 00:02:05:05 - 00:02:37:03 Dr. Murray Brilliant We have several research projects, some of which are designed to try to better understand how genomics interacts with with our health. We also have projects that where we take that genomic information and combine it with health care to better serve our patients. So our first and this more discovery type mechanism is that we have volunteers that help us in our research. 00:02:37:03 - 00:03:21:23 Dr. Murray Brilliant We have actually 20,000 volunteers in what we call the personalized medicine research Project, or PMP. This project enables us to look at retrospectively that is in the past as to what kind of health outcomes and health problems people have and to relate that to variations in their DNA, in their genome. That has allowed us to discover risk factors that are hidden in our genome that predict whether or not we're more susceptible to cancer or to age related macular degeneration or other things like that, or, you know, high cholesterol, those sorts of things. 00:03:22:09 - 00:03:59:09 Dr. Murray Brilliant We have used that information in a more of a prospective way to help treat some of our patients. For example, we have 750 Marshfield Clinic patients who are enrolled in our Pharmaco Genomics project. So this project looks at specific variants in DNA that predict how a person would respond to particular drug therapies. So some people on certain types of statins will develop pain in their legs, in lower limbs, and we call that peripheral myopathy. 00:04:00:07 - 00:04:23:11 Dr. Murray Brilliant We can predict who might develop such an outcome based on on their DNA variations and get that into the clinical record in a way that and do this before we ever prescribe this particular drug. So if they're at risk for this particular side effect, we know to give them a different drug from the very beginning. 00:04:23:16 - 00:04:47:16 Adam Hocking Can you talk a little bit about how you decide what the process is for, what what you ultimately study? It seems like this is such a vast potential topic, personalized medicine, and you could study so many different things, so many different medications, illnesses. How do you make the decision that we're going to study this medication or this illness? 00:04:48:08 - 00:05:12:15 Dr. Murray Brilliant That's a very good question and one that we struggle with all the time. So typically we would look at medications, for example, that have higher rates of adverse events and ones where we where we and others have found genetic variants that could influence whether or not a person on that particular drug will develop one of those adverse events. 00:05:12:15 - 00:05:43:05 Dr. Murray Brilliant So so that that has to do with a subset of drugs. Not all drugs are associated with adverse events that are related to our genes. For example, some drugs in combination with other drugs can cause adverse events. Some drugs are pretty safe for most people, and it's up to us to try to determine which ones are there are used more commonly, which ones are would put our patients at risk, for example. 00:05:43:14 - 00:06:20:01 Dr. Murray Brilliant That's just one subset of of drugs and and genes. But we also can look at at different genetic variants that we we already know are associated with risk for cancer, risk for heart disease, risk for, as I mentioned, age related macular degeneration. That's one particular disorder that we've studied in great detail. So we can predict with fair accuracy who might be at risk for age related macular degeneration. 00:06:20:09 - 00:06:42:01 Dr. Murray Brilliant And using the vast amounts of data that we have, we've actually come up with drug that we think could either prevent or halt the development of age related macular degeneration. So this is a really important topic not only for our patients but for for people all all over the world. 00:06:42:12 - 00:07:16:11 Adam Hocking As precision medicine makes its way more into the mainstream and more into the lives of of providers on a day to day basis in their approach to care. I'm curious how it would manifest itself. Let's take a maybe this is a bad example. I'm not sure a person that has a specific type of cancer in the past before precision medicine, I'm assuming perhaps the approach was, okay, we have a person, they have this disease, this is how we would normally treat this disease. 00:07:16:20 - 00:07:31:01 Adam Hocking It's kind of a standard more across the board approach. And I'm oversimplifying, but with precision medicine, you could take into greater consideration the person's DNA, biological markers, things like that. Is that accurate? 00:07:31:16 - 00:08:18:07 Dr. Murray Brilliant That's very accurate. So and that's very applicable for for cancer. So with the vast amounts of data that we have here at the Marshfield Clinic and indeed across the whole country, since most records now are electronic, we can begin to compare people who are alike. So breast cancer, for example, can affect women of all ages. But if we look at a subset of women with a particular type of breast cancer at a particular stage and with particular DNA markers in that cancer, we can then compare all the different ways that we and others treat this particular breast cancer. 00:08:18:13 - 00:08:36:22 Dr. Murray Brilliant And comparing all of these age matched and and cancer stage matched women, we can we can actually begin to see which treatment works best for that for women who who who meet those particular standards. 00:08:37:05 - 00:08:45:14 Adam Hocking Currently, if I'm wrong, the Marshfield Clinic Personalized medicine program, a precision medicine program, began in 2002. Is that accurate? 00:08:45:19 - 00:09:14:09 Dr. Murray Brilliant So, yes, we call it at that time we called it a personalized medicine research program. And this is the one where we have 20,000 local volunteers that help us in this research and that have helped us to identify genetic variants that are associated with all kinds of different diseases, and also helps us to determine what are the best treatments and outcomes to expect from different conditions. 00:09:14:18 - 00:09:36:17 Adam Hocking Can you talk about the genesis of this kind of medicine when it started to so. 22 for us. Okay, we initiated a program, but when did it start to come into the consciousness of health care in general? And people started to think, well, we have this new ability with mapping the genome and things like that. And we can approach health care in a different way because of it. 00:09:36:17 - 00:09:38:09 Adam Hocking When did that kind of start to happen? 00:09:39:01 - 00:10:21:14 Dr. Murray Brilliant It's been an evolving process. I think that if you talk to most physicians, they will say that they treat everyone differently and that that's part of precision medicine. So clearly we do differentiate different types of disorders and and treat them in different ways. But it the big push began with the Human Genome Project and the Human Genome Project, an opened up this whole vast array of data that based on genomic variants that can allow us to look at risk. 00:10:21:21 - 00:11:12:07 Dr. Murray Brilliant But one thing we also should remember is that most diseases are caused by environment, diet, whether we smoke or not, those sorts of things. Genetics plays a big role, but it's certainly not the only role. And but combining this genetic information with information that even in India on an individual basis of diet, exercise, age, all sorts of features like that, we can begin to to develop techniques where we can say that given this particular set of genes in this gene, genetic variants and this particular diet and exercise profile, that sort of thing, that this is what we might expect. 00:11:12:14 - 00:11:36:13 Adam Hocking Hmm. I had read that the influence or maybe the presence of precision medicine in health care right now is somewhat limited, I guess, in the day to day activities of the average provider. I'm wondering if you agree with that characterization and sort of if you see that changing sort of as we speak. 00:11:37:00 - 00:12:14:07 Dr. Murray Brilliant It is changing as we speak. So we shouldn't oversell this. There's still a lot of health issues that are really determined almost by chance. So that's something that we need to consider. But there are a number of of health issues that we can clearly predict. And and if we look at INDIVID atul genetic variation, for example, we do find that almost all of us will carry at least one genetic variant that could influence whether or not we get an adverse drug problem. 00:12:14:07 - 00:13:03:15 Dr. Murray Brilliant Right. But we're not all given all drugs. It's important then to test for these particular variants so that we can reduce adverse drug events. We find that over a person's lifetime, about 75% of us will be given a drug that is contraindicated by our genetics. So that's that's a large number of people. That's one of the things if we look for genetic risk that are associated with cancer, heart disease and those sorts of things that are genetic, we find about 5% of people have at least one genetic variant that could influence the rate at which they might get those particular disorders. 00:13:03:15 - 00:13:38:05 Dr. Murray Brilliant So most people could benefit from pharmaco genomic testing and a lot of and about 5% of people could benefit from other types of testing. That's just the genetics part. But we kind of use precision medicine in many ways. So there's something called a Framingham Score, which that allows your physician to determine what your risk for cardiac disease is, and that's based on your age, your body, mass index, family history, all those sorts of things. 00:13:38:11 - 00:14:03:15 Dr. Murray Brilliant And that gives you sort of a kind of equation that will tell you what your risk in the next several years is for a cardiac event. And so that's something that that's in use today currently. And and so so it's not an unusual principle. We're just applying other features, such as genetics, to to these sorts of predictions. 00:14:04:06 - 00:14:23:21 Adam Hocking One of the things sort of a buzz word you hear a lot about is big data. I wonder how much of the success of Precision Medicine is not just based on the data you collect, but how efficient or successful you are at analyzing aging and contextualizing that data. How much of the challenges is that piece of it? 00:14:24:13 - 00:14:55:05 Dr. Murray Brilliant The big data challenge is certainly real, so it requires a lot of computational time, but what comes out of that is extremely important and can be quite precise. So the human genome is is pretty big. There's 3 billion bits of information in each each of our cells and variations in any one of these might might lead to to some issue. 00:14:55:14 - 00:15:30:02 Dr. Murray Brilliant When we look at when we when we look at retrospective data, we look at medical records, for example, of a person over a lifetime. There's hundreds of thousands of of data points in that every time a person's blood pressure is measured. Every test result, every diagnosis, all of that in your medical record. But for the past 30 years, at least here at the Marshfield Clinic, those data are electronic. 00:15:30:12 - 00:15:55:13 Dr. Murray Brilliant So we use our large computing system here to relate those medical all points of data to genetic points of data. And we also overlay that with environmental data, which includes diet and exercise. And then, of course, age and sex and all those sorts of things go into this. So it is a big data challenge. 00:15:56:11 - 00:16:25:17 Adam Hocking We're talking with Dr. Murray Brilliant. He's the director of research and the director of the Center for Human Genetics at the Marshall Clinic Research Institute. I'm wondering if you've seen and maybe you don't allow yourself to do this. I don't know. But if you were to sort of dream big about what personalized medicine could mean ten, 15, 20, 50 years from now, are there any sort of signposts that you hope to get to or big innovations that you think maybe we're on the cusp of or breakthroughs, anything like that? 00:16:26:14 - 00:16:52:00 Dr. Murray Brilliant I come to this through the lens of genetics, and I don't want to again, I don't want to overemphasize the importance of genetics, but that's a new feature that we can add to all this other data that the the genetic features can be very important. As I mentioned in in a large number of people, certainly for pharmaco genomic types of data. 00:16:52:13 - 00:17:33:08 Dr. Murray Brilliant So one of the things that I think will happen is that probably when we're born or shortly thereafter, we'll have our our complete genome sequence. Those 3 billion nucleotides. And as we go through our life cycle, that that genetic information can be queried much the same way that your physician writes for a prescription now. So your physician that that data will reside someplace, your physician will query your DNA at at specific dates of your life. 00:17:33:09 - 00:18:00:13 Dr. Murray Brilliant So, you know, we we do certain things. You know, we give single shots at that to people who are over age 60. And we there's there's other immunizations that are age specific. So I think that querying your your your DNA, your genome, that 3 billion bits of information will be done at the specific milestones of a person's life. 00:18:00:22 - 00:18:28:10 Dr. Murray Brilliant And so will determine at that time what the use of that. So, for example, before you get a prescription for medication, we will check to see whether or not that particular medication might cause a bad outcome for you or if this is appropriate for you to take, for example, if you have cancer. What kinds of chemotherapeutic agents can you best tolerate? 00:18:28:18 - 00:18:58:07 Dr. Murray Brilliant And are those agents the ones that will kill those cancer cells? So those are the sorts of things that will be in your in your health information record and that will be used to determine, you know, what kind of testing we want to do, what how proactive we have to be for certain conditions and such. So if you have an average risk for cancer, we would screen you the way we normally do. 00:18:58:14 - 00:19:31:11 Dr. Murray Brilliant If you have a high risk for cancer, then that your cancer screening would be accelerated. Similarly, for for eye diseases like macular degeneration and glaucoma, we would, you know, we can look at your genetic variants and determine whether you might develop these disorders at a higher risk than other people. And so we'd want to test you for these things in advance and truly preventing disease is much better for the patient. 00:19:31:16 - 00:19:46:18 Dr. Murray Brilliant It's much better for the health care system, and it's much better for for all of us. So our goal here is to anticipate problems, prevent them when we can and treat them as best we can using all the knowledge that we have. 00:19:47:09 - 00:20:15:18 Adam Hocking I was going to say, I think prevention is kind of the word that's been lurking in the background here, because so often maybe and not so much in the medical community, but but as society at large, we hear a lot about curing cancer, finding the cure for X disease. And I think the conversation is starting to shift to, well, maybe it's easier or it makes more sense to go to the other side of that equation and say, how can we stop it from starting in the first place? 00:20:16:06 - 00:20:31:22 Dr. Murray Brilliant Correct. The paradigm that we have for for health care is that you basically go to your physician when you're sick. We'd like to change that and anticipate before you're sick and prevent that. 00:20:33:04 - 00:20:39:20 Adam Hocking What role do medical providers have in your mind in helping to advance precision medicine? 00:20:40:02 - 00:21:15:05 Dr. Murray Brilliant In terms of right now, there are several things that can be done. One is that we can continue to collect information to see again what works best. That's that's one thing. Physicians can also begin to to utilize this precision medicine. And certainly they do already in terms of many features, as I mentioned. Yeah. You know, in predicting cardiac disease with the Framingham score, things like that are already done. 00:21:15:05 - 00:21:43:14 Dr. Murray Brilliant And in practice, what needs to be added to this are the genetic variants and other environmental variation that are that's very important in your health. Again, I don't want to oversell this. A lot of our health issues have to do with our environment and whether we whether we're smokers or not smokers, whether we have a good diet or a bad diet, whether we exercise or not. 00:21:44:02 - 00:22:10:05 Dr. Murray Brilliant Those are those remain to be very important in determining your health outcomes. And so I don't want to oversell the genetics part of it, but combining the genetics with all these other features really enables us to be much more precise in predicting what risk factors you have. And once you develop a disorder, what are the best modalities? What are the best ways to treat you? 00:22:10:23 - 00:22:35:13 Adam Hocking I want to move to a bit of news. Marshall Clinic Health System. Well, Marshall Clinic Research Institute, I should say the University of Wisconsin School of Medicine and Public Health and the Medical College of Wisconsin were recently awarded $5.3 million between the three institutions to help implement in Wisconsin, the National Institute of Health's All of US research program. 00:22:36:01 - 00:22:39:17 Adam Hocking Can you tell us a little bit about what this all of us research program is? 00:22:40:08 - 00:23:24:16 Dr. Murray Brilliant The the All of US Research program is an NIH program with a goal to recruit a million Americans in a an effort to to relate their to their health care outcomes and their and predictions of health care in future relate that with their genetics, their environment, their diet and exercise and all of that. So the Marshfield Clinic's personalized medicine research project that I talked about with 20,000 individuals has been a great success in terms of research. 00:23:24:16 - 00:23:51:12 Dr. Murray Brilliant And it's it's findings that are that provided a basis for what we now call precision medicine. Indeed, we were cited by the NIH as as one of those programs that's a forerunner of this all of us program. The all of US program then intends to do this on a much larger scale instead of the 20,000 that we already have here in in Marshfield. 00:23:52:08 - 00:24:35:14 Dr. Murray Brilliant This aims to to recruit a million people. The data from a million people will again, very, very big data. Lots of data points not only if you think about it, a million people, each one of them with 3 billion variant potential variants in their DNA, hundreds of thousands of data points in their electronic health records. This is an enormous project and one that will go on for many years, but that will allow us to to advance this whole concept and whole modality of of precision medicine. 00:24:35:23 - 00:25:09:08 Dr. Murray Brilliant When I talked about before about, you know, issues with genetic variation that, for example, leads to breast cancer and how we might treat that, it's important to to note that even at a large medical center like the Marshfield Clinic, we do see large numbers of women with breast cancer, but they're all a little different one from another. Different stages of breast cancer, different ages, different genetic variants that drive that cancer. 00:25:09:18 - 00:25:30:21 Dr. Murray Brilliant So when we have a million people, we could have a thousand, for example, 1000 women that fit an almost identical profile. And then we can compare what types of treatments work best, what cures this, this disorder, what gives the best outcome and hope for these women? 00:25:31:19 - 00:25:42:16 Adam Hocking How important is the scale of having a million people? I guess I'm curious, has there been a precision medicine research project of this size before that you're aware of? 00:25:43:23 - 00:26:27:12 Dr. Murray Brilliant The United States is not the only one that is is preparing this this large group of individuals for precision medicine. The UK is recruiting a biobank of a million people as well. Other countries have done this. We're not the first and perhaps not even we may not even be the biggest in the United States. But I think that we have a unique opportunity because of the diversity of our populations, the diversity of of where people live, what they eat, how they exercise, all those sorts of things will be very important in in advancing precision medicine. 00:26:27:12 - 00:26:36:11 Dr. Murray Brilliant So this all of us program will revolutionize the way we treat patients in medical care in the future. 00:26:37:01 - 00:26:50:23 Adam Hocking I was just going to say Dr. Francis Collins from the NIH said he thought this study could alter the practice of medicine in profound ways. Obviously, you seem to agree with that. Can you talk about the type of potential this study has? 00:26:51:11 - 00:27:23:07 Dr. Murray Brilliant Well, for example, in the All of US Wisconsin program, we're going to be recruiting about a little over 8000 people over the next year. And we intend over the next five years, if the funding continues from the NIH, we will recruit 100,000 Wisconsinites for this this program. What we see developing out of this is, again, ways to to predict and and prevent disease. 00:27:23:16 - 00:28:06:17 Dr. Murray Brilliant So I think this will rapidly and substantially change medical care. Again, the most important thing is we will be able to better sort of bean people according to risk. So we can't do we can't test everyone for everything. We will continue to test the average population according to the current recommendations, specialty recommendations. So when you when you should have colonoscopy, that won't change for the majority of people, but people who are at higher risk for colorectal cancer. 00:28:07:01 - 00:28:34:11 Dr. Murray Brilliant We're going to be screening them earlier and more often this will prevent larger numbers of colorectal cancer that we wouldn't be able to do on a if we treated everybody the same. So by sort of stratifying or binning people according to whether they're at higher risk, we will be able to catch disorders earlier and and try to prevent their bad outcomes. 00:28:35:02 - 00:28:39:23 Adam Hocking I guess I'm just curious how you recruit that many people for a for a project like this. What's that process like? 00:28:40:21 - 00:29:20:02 Dr. Murray Brilliant That's a very good point. We do find certainly here in Wisconsin that people are pretty altruistic. Even if this doesn't benefit immediately, those particular people, they realize that this is something that will benefit future individuals, their their children, their grandchildren. So we've never had a real problem in in recruitment people are very interested in in helping out biomedical research, in improving the health care of others. 00:29:20:16 - 00:29:51:13 Dr. Murray Brilliant We believe, though, that this will has a has a good chance to advance the health care of of the particular participants. We haven't quite the all of us program hasn't quite decided exactly what kind of information is going to be returned to the participants. But the all of us program is is really based on having participants be partners in in this research. 00:29:51:23 - 00:30:21:18 Dr. Murray Brilliant So it's it's different from other kinds of biomedical research where people are subjects that we don't look at people who who are in the all of us program as subjects. They're really partners that help us to determine what types of research we do and and even in a way, how how we do that and how we're going to return these results to the participants and their physicians. 00:30:22:19 - 00:30:25:19 Adam Hocking Are there any parting thoughts that you'd like to share with us before we go? 00:30:26:16 - 00:31:14:02 Dr. Murray Brilliant Well, the one thing I would say is that this is a it's a grand opportunity for us to to advance medical care. I don't want to oversell oversell it too much. We have actually done a kind of, I think, a very clever experiment. And that clever experiment is some of the volunteers from our previous study have passed away and since the Marshfield Clinic has been in business for now more than 100 years, we have information on the health of some of these individuals who have now passed away that that really is their lifelong medical record from their birth until their death. 00:31:15:02 - 00:31:45:16 Dr. Murray Brilliant What we have done is to do whole genome sequencing on these 300 individuals so we know all the 3 billion bits of information, and we've compared that with with their medical record. And so we have actually found people who who we could have helped. Again, this is in retrospect and we're using techniques that aren't in use now that we hope to be in use in future. 00:31:46:02 - 00:32:18:00 Dr. Murray Brilliant But this is kind of a way of looking at at what the future will look like. So we've been able to find individuals that were at risk for cancer that indeed did get cancer that could have been prevented if we had had that information years ago. When we didn't have that information. So it's it this illustrates that this type of information can be effective and can prevent bad outcomes. 00:32:18:12 - 00:32:49:02 Dr. Murray Brilliant And so our our real goal in all of this is not to to make people live forever, but to keep them healthy until they're not. So we want to reduce the burden of disorders that are, you know, affect an individual every single day. It's quite a burden. And and we want to we want to keep people healthy for as long as possible. 00:32:49:18 - 00:32:51:21 Adam Hocking Dr. Murray Brilliant, thank you so much for joining us. 00:32:52:05 - 00:32:54:13 Dr. Murray Brilliant You're welcome. 00:33:00:10 - 00:33:26:01 Adam Hocking The Rounds is produced by Ryan Maderic and supported by the Marketing and Communications department of Marshfield Clinic Health System. You can subscribe to the rounds and download episodes via iTunes or by visiting Shine365.MarshfieldClinic.org. I'm Adam Hocking and I hope you'll join us next time on The Rounds.