 Welcome back, everyone, and good morning, afternoon, or evening, depending on what time zone you're in. My name is Wei Shu, I'm a professor at Texas A&M University, and I'm a member of the standing committee. I am a former physicist like the distinguished speaker in the previous session and now in computational toxicology and risk assessment and I'm very pleased to moderate the session on enhancing the dialogue between environmental health and precision medicine. So the objective of this session is to have a dialogue about what new frameworks people approaches are needed to address the opportunities and challenges in precision medicine as it integrates with environmental health and exposure data over the next 10 years. The idea is to both look forward in the next 10 years, in which we will have, you know, access to all types of new types of data and how we best utilize it, and also looking backwards from 10 years from now how will we get to that point. So the science is needed to, in order for us to achieve that, that goal, and who needs to be involved, how do we get them involved, as well as discussing policy and ethical considerations in moving towards that integration. We have a distinguished expert panel to discuss this scenario. Each panelist will first give a five minute short introductory talk to provide background on their work and their perspectives, after which I will describe a particular scenario as a launching point for discussion. So our first speaker is Julia Brody from the Silent Spring Institute. Dr. Brody. Hello everyone, I'm delighted to be here. I do have a few slides so give me a moment to get them up. So I'm coming to you from Boston. And last week was the 50th anniversary of women being officially allowed to run in the Boston marathon. That led me to thinking that it was still another 20 years before Congress directed NIH in 1993 to include women in clinical research. And the idea that we need data for women as well as men could be thought of as perhaps a small step towards precision medicine. Same year, 6,000 people gathered in the Government Center Plaza in downtown Boston to call for environmental research into women's health, specifically studies of environmental factors and breast cancer to inform prevention. And Mass Breast Cancer Coalition founded Silent Spring Institute to be a scientific team that would take on this work in partnership with activists, clinicians and policymakers. I'm the director, I've been the director for more than 25 years. And that has led me to a preoccupation drawing on their vision about precision environmental medicine that focuses on advancing primary prevention, community engaged partnerships, and equity precision medicine has the potential to be a counter force against each of these goals. I appreciate the chance to discuss a more positive vision. Very much consistent with comments that you heard earlier today. To focus on prevention, we needed a decision framework that reflects the influences on health of exposures across the life cycle. And we need to remember that recommendations will rarely come from clinical trials, observational epidemiology is also quite limited. And then the environmental report of the President's cancer panel called for a new environmental health paradigm, scientific approach that would support action without definitive proof. And Silent Spring Institute proposed a model that focuses first on understanding biological mechanisms. That is what do chemicals do along pathways to disease. And second, when chemicals are identified as potentially harmful, how are people exposed. And when we know those two things, we have a basis to reduce exposures. Translating this model for precision environmental medicine the first step is to identify chemicals that are important in a particular context to achieve this chemicals testing becomes part of precision medicine. The second step is to integrate exposure measurements into routine care across the life cycle. And the third step means using those results for personalized exposure reduction targeted medical monitoring and public health surveillance and policy. Community partnerships and equity considerations will be vital to set priorities and put results into action. For example, of step one, my colleagues recently used data from an EPA talks cast assay to publish a list of 300 chemicals that increase production of estrogen or progesterone chemicals that are strongly associated with breast cancer. These chemicals are in common exposure sources including pesticides, a hair colors and other dyes and products of combustion. To advance step two, there's been a great deal of innovation in exposure measurement and communicating those exposure results in a right to know right to act context is one of the tools for engagement and equity. And that's the focus of my own work so I'm going to turn to some examples. To make it possible to impractical to return results in bio monitoring projects of any size. We developed Derby the digital exposure report back interface, which uses decision rules to personalize results and offer individuals contact contextual information about what's what they can do. This is this could be integrated into electronic medical records and it includes tools that could be useful for clinicians to evaluate patterns of exposure. It uses a personalized headlines to highlight key results, it can compare results to national the national exposure report from NHANES or to other benchmarks. The headline format is makes it easy to integrate information across individual measurements so it can handle mixtures and it can integrate genes and environmental genes and environment together. It includes individual and community level strategies to reduce exposure. We developed a smartphone prototype to expand access in low income communities where this is the primary access to the internet. This is an example of the data visualization tools that would allow a clinician to look at exposures for a patient across many different chemicals to think about patterns mixtures highlight high exposures. Think about clues to exposure sources. Reports could also include resources for medical monitoring for exposed patients. This is an example for developed for communities with PFAS drinking water exposures. So, consistent with the scenario that we're, we're talking about today. I wanted to talk in particular about the green housing study of children with asthma living in public housing. We've interviewed hundreds of participants in exposure studies and interviewed them after they received their reports and in this particular study. In all of these studies we see participants brainstorming about exposure reduction, and in the green housing study parents for example reported actions such as avoiding pesticides, switching from pesticides to sticky traps, and switching to products that were fragrance free. They took their results to clinicians, and some said that they got more attentive medical care for their child who whose symptoms had perhaps been ignored. In conversations with participants we, we were able to discern sources of high exposures that hadn't been anticipated for example burning incense, or cooking with a broken kitchen fan, again really personalizing the recommendations for how to reduce exposures for these kids. As an example of how exposure monitoring for precision environmental health can work as a public health surveillance system in the northern California household exposure study. We surprisingly discovered high levels of flame retardants in California compared with the US. And this was due to a unique state flammability standard. Once these measurements were revealed, the flammability standard was revised to reduce exposures without sacrificing fire safety. So precision medicine could contribute to this kind of analysis being widely available and important for public health policies. These are the examples of reports from a variety of different studies on our website. And I'm very grateful to my very transdisciplinary team and multi institutional from Silent Spring Institute northeastern UC Berkeley, Harvard and the studies that have helped us feel these results reports and learn how people respond to them. Thank you very much. Thank you, Dr. Rody. Our second panelist is Dr. Brandon Pierce. Dr. Pierce, please go ahead. Thank you. Good morning afternoon evening everyone. I am my name is Brandon Pierce, and I am a genetic and molecular genetic and environmental epidemiologist working at the University of Chicago. And my research is really about me and my research is really focused on understanding gene environment relationships that are relevant to cancer. So so there's there's a two, two aspects of the research one is studying the inherited genome. So the variation, you know, in the human genome that we inherit from our parents, and how that, you know, modifies our susceptibility to the effects of environmental exposures. And then sort of the other angle that I work on is studying the impact of environmental exposures on the human genome sort of focusing on dynamic features of the genome not not the variation that we inherit from our parents but features like, you know, the, the length of features like the epigenome which which isn't genome sequence but features the genome that affect how the genome is packaged and how how genes are turned on and off. And as well as acquired mutations in the genome like mutations that can contribute to cancer. And so by studying, you know, the, the interactions of the relationships between genetics and environment. You know, our hope is that we can better, you know, understand that the biology of what exposures do, you know, under the skin, have better understand susceptibility to exposures and the mechanisms underlying that susceptibility. You know, potentially the ability to identify individuals who are might be at higher risk for, you know, higher risk for exposure effects toxicity, and potentially identify biomarkers that reflect the effects of exposures on health. And so a lot of this type of work we have pursued in Bangladesh in particular, which is a unique place where there's a unique exposure. Arsenic being sort of naturally occurring in the earth and Bangladesh and a lot of the ground water there being naturally contaminated with arsenic so you know, the sort of sad story in Bangladesh is over the past, you know, 50 or so years. The motivation to eliminate or to reduce surface water as a drinking source and promote the use of packaging free ground water has resulted in this fairly widespread exposure to arsenic across across that country. And you know arsenic is a metal is a known it is a known carcinogen. It has effects on multiple body system it's a multi system toxic and this sort of exposure to arsenic was discovered in Bangladesh. You know several decades ago, you know, studies followed your cohort studies, you know we're set up in Bangladesh to study these effects and you know that I think one of the primary goals of these studies was to was to first and foremost reduce exposure. And then you need to sort of assess exposure in the area and by collecting all this information on exposure levels and health were able to set up fairly unique cohort studies that study that they're really, you know, designed to assess the effects of arsenic on health. And some fairly unique work and those studies in part because they have really high quality exposure data and genetic data is available on large numbers of people. And some of these, these studies in Bangladesh so we've been able to have a kind of unique mission that we've been able to study the genetics, how in heavy inherited genome influences susceptibility to arsenic. So the strong focus on understanding how people differ in their ability to metabolize arsenic and eliminate arsenic from their body so we've been able to identify, you know, regions of the genome where the variation you inherit impacts your ability to deal with arsenic that you're exposed to, at least in this study, you know, through drinking water. And so, we've also done work in this area to think about, you know, returning those types of results to to research participants so similar to what Julie was saying in the prior talk about, you know, returning information to to exposed individuals so, you know, in addition to, you know, informing our research participants about, you know, their exposure level actions they can reduce to reduce their exposure we also have the possibility of returning information on their genetic susceptibility to exposure. You know, if they're interested in that to potentially further motivate them to, to take action to reduce their exposure. You know, on the other side, we've also studied arsenic in relation to the dynamic genome features I mentioned in relation to telomeres and epigenetic somatic mutations with the hope we can potentially identify. And I've had a health effects but also maybe biomarkers of exposure effects signatures that you know someone has been exposed, you know, to to arsenic or other or other environmental exposures. And one front where we're sort of pursuing now is trying to extend that work beyond blood samples which is what we typically deal with an epidemiological research and human studies and try to look at, you know, using data sets of that contain multiple types of tissues that came from tissue donors and ask, oh, can we look at exposure effects on, you know, lung tissues and other tissues that are much harder to get in human studies so that's sort of a growing area of our work. And I'll stop there I think I talked about five minutes so pass it on to the to the next speaker. Thank you very much. Our next panelist is Dr. Elena Rios from the National Hispanic Medical Association. Hi, it's an honor to be here. I'm Dr. Rios with the National Hispanic Medical Association. We started in 1994 representing 50,000 licensed Hispanic physicians in the United States. And our mission is to improve the health of Hispanics and other underserved. And we primarily do national conferences we've developed chapters and infrastructure that includes doctors who are very interested in, in educating their communities, they are looked at as leaders from their communities. And we also have developed mentoring programs such as our college health scholars program to reach to the pre health Hispanic students funded by the Office of Minority Health program has been around for five years but we've actually been recruiting since 2005 at our national conference. So with the Office of Minority Health we started focusing on areas in the country where there are more Hispanic students, namely California and Texas. We also started our own foundation, the National Hispanic Health Foundation, we changed the name from NHMA or medicine, because we wanted to focus on providing scholarships to students that we're going into, or into the careers by being medical students nursing public health pharmacy dental and physician assistants. We have a corporate advisory board, and we are establishing through this last few years, a national center for Hispanic health research. So what I wanted to talk about just briefly why Hispanic community is so important to this topic, and how we can be of service, and what we've done with environmental activities. So Hispanics are 60 million or 19% of the population are projected to be one out of four Americans, you know, by the year 2035. Many live in poverty face social determinants of health course in a long history of discrimination unequal treatment, accumulation of social and environmental disadvantages and high prevalence of health disparities in all clinical diseases and conditions. But they're also very hard working essential workers with large families, close social networks. So a lot of opportunity for educating, you know, young people and they'll get to everybody in the family. But they live in close proximity to carbon plants truck routes areas with poor air water housing with high levels of chemicals that are detrimental to them. And from research we know that the history of living with inequality and discrimination leads to toxic stress and chronic disease prevalence, which is really what has led to health disparities in our country. And I also think the most important thing that we have to think about is that many of our communities live in medically underserved areas or health professional shortage areas with less less access to health care and services and also it's Hispanics are the group that is the largest group without health insurance. And I have to say that without very many Hispanic, or people that look like them, talk like them, Hispanic health professionals at all levels, just for doctors. We're still only 5% of the total doctors in the country. We've been pretty much flatline since 1970s. So in terms of precision medicine and environmental health, we've been a partner with the all of us research program at NIH since started in 2017. And I think what's very important is some of the key findings that started the program was that, you know, Hispanics make up 16% of the population but only 1% of clinical trial participants, same with African Americans 12% of the population but only 5% of clinical trial participation, and pretty much all of our research, you know, has been based on white Caucasians, and it was very important for the country to embark on a precision medicine initiative that includes environmental health and for Hispanics There was a major report done by the Natural Resources Defense Council on the Hispanic population, and that they found more than half reside in states with the highest levels of climate change threats, such as air pollution, extreme heat and flooding. Many Hispanic communities face serious health risks by air pollution again, but also oil and gas with toxic air emissions, including asthma rates that that affect asthma rates, extreme summer heat, especially in outdoor occupations. And then of course we know all of our seasonal agricultural workers also are faced with many many pesticides, low income Hispanic communities more likely to live in areas most vulnerable to impact by climate change natural disasters. And of course there's a major psychological impact. And then I think there's just a few things that are people don't think about but one and a half million Latinos live in unincorporated communities, especially the US Mexico border, where there is a lack of potable water sewage treatment that contributes to waterborne diseases, more than a third of us Latinos live in the western states, where arsenic industrial chemicals and fertilizer residues, often contaminate local drinking water, 80% of farm workers in the country are Latino. Twice as many Hispanic children as non Hispanic white children have led in their blood at levels higher than the action level established by the CDC and approximately 66% of us Latinos are 26 million people live in areas that do not meet the federal government's air quality standards. So there's a lot to be done in terms of the National Hispanic Medical Association and our work with environmental justice. We've worked with the National Natural Resources Defense Council EDF environmental justice green Latinos and climate action campaign on several advocacy issues, running the gamut I think advocacy is something that's needed, very much so and policy impact what we work with the tri caucus and the Hispanic and black nation caucuses, as well as the White House with Gina McCarthy. And we've also been very much involved in mentoring and getting younger people involved to all our programs with the all of us research program we've been able to get to our chapter levels in work with getting more people involved in research. And I'll just make one last comment here about the importance of our national Hispanic health foundation developing a national center for Hispanic research, where we've had PCORI funding and health services research funding to be able to develop a cadre of research researchers at the senior level, working with the junior level. And we've learned I think what's most important is that Hispanic are trusted Hispanic doctors and researchers are trusted by the community, and we need to develop more policies and support for having younger people in in K through 12, not only understand STEM math and science, but understand research, and the importance of community designed research the PCORI center, you know centered patient centered outcomes research and clinical research. We're actually working to find clinical investigators that are in the communities in the clinics, community health centers working with academic faculty, and also private practice doctors because there's so few Hispanic doctors that have the opportunity to do more research, because they're always caught in a million committees in the hospitals or in our medical schools, you know doing minority admissions or interviewing or what have you. And we've learned as an organization how important it is to focus on developing that next generation of through our pipeline efforts are mentoring in our leadership development programs. So I'll stop there. Thank you very much. Our speaker has hasn't joined yet. Dr. Carla Sherman welcome so we'll move on to our final panelist, Dr Alicia so from color health. Thank you. Thank you and thank you for the opportunity to part of this panel today I'm very excited to be speaking with all of you. So my name is Lisa Joe I am the chief science officer for color health. My background is that I'm a molecular biologist by training and a cancer researcher. Very similar to Brandon. I work on the clinical genetic side of the world thinking about how your genes hold information that might affect what types of traits you might exhibit later on in your life. I'm going to give a quick introduction to myself as well as color so that folks have an understanding about that. Please let me know if you can't see my slides otherwise we'll just go ahead and charge forward so color is been working for the last seven years on really being able to do scale decentralized healthcare delivery. So we started out in the field of clinical genetics really thinking about access to gene testing like BRC one and two sequencing that could be very useful and predicting a woman's chance of having breast or very cancer in her lifetime. The last two and a half years have actually spent a lot of our time responding to the COVID pandemic by delivering more than 75% of the COVID testing here in the San Francisco Bay Area. Recording stopped have been recording in progress have been doing the skilled vaccine delivery for the state of California as well as multiple other states. We have worked with large research programs and actually as Elena mentioned we are part of the all of us research program as well which I'll go over very briefly as well, but really the way we think about it is our goal is to bring scaled infrastructure for healthcare program delivery so thinking about what are the interventions and the care that you want to bring to community and how can we make sure that you get equitable access to those interventions across the full population. We started in the world of clinical genetics and really the way we thought about it is to always do a patient centered way of delivering clinical genetics results so we think about how we can make sure that the patient is a piece and a part and a partner in the delivery of their results so there is a patient facing the interface for the results delivery. On the back end we do have our own CAP CLIA lab for next generation sequencing samples are collected by either saliva or or blood and the nice thing about saliva is that it does allow us to have this shift to home modality, meaning that you don't necessarily need to be in a clinical setting in order to provide your biospecimen but rather you could provide a saliva sample from your own home. We've actually changed a lot of the way that we are able to extend access to genetic testing. This is a room temperature stable biospecimen that can be mailed through the standard USPS mail, and has been one of the ways in which we've been able to reach a lot of the individuals who traditionally have access to clinical genetics. Those samples are then sequenced here at our San Francisco based lab, and then we're able to do the interpretation of those results and return those results back to the patient, and their provider through a web based interface, and then, importantly, figuring out how to integrate that data into the recovery system such that that data is actually used longitudinally by the provider and the care team to actually improve and hopefully change the care for that patient. Underlying the work that we do is really this ability to have all these different pieces of the infrastructure as I mentioned so we think about all the way from recruitment all the way through to the return of genetic results. Having a patient centered view on that. So, of course, there's the ability to collect biospecimen in the first place as I mentioned using saliva or blood collection, and the generation that data is important, but it's also important to understand the participant's point of view, making sure that they have the ability to consent into the return of results that they would like to get that they have a view into where their sample is at any given time. And then when their results are ready that there is a patient supported workflow in which they can get their results back. So as part of that, we also have started offering or since the beginning have offered a genetic counseling as part of our workflow. I think when it comes to the return of these types of results which are relatively new still for patients and providers, it's important to have the right specialist to help support that return of results. So genetic counseling is a huge component of the return of these results. And actually, as I talk a little bit more about the all of us research program I can talk about the way in that program we've thought about genetic counseling as well. So, one of the things I do want to emphasize here is that I think we are shifting into a different framework and mindset when it comes to the use of genetics for precision medicine. I think we started in a world where we very much thought of it as phenotype first phenotype being the observable characteristics of an individual. And we thought about identifying individuals who had rare phenotypes who had abnormal phenotypes and then having them be undergo genetic sequencing to try to identify the cause of that rare or abnormal phenotype, and in doing so we're searching for that molecular diagnosis. This has been really useful and helpful for the identification of rare diseases, and certainly has been very instrumental for diagnosing many of these genetic linked high diseases that we know about today. But I think where we are now is that we are moving into this genotype first world, where now that getting whole genome sequencing done getting genetic testing done is becoming much more accessible and affordable. It does mean that you're going to have many more folks who are getting their genome sequence first getting the next testing done first. These individuals don't necessarily have anywhere or abnormal phenotypes. Now we have all of this rich genetic data that now we can use to try to predict how that genetics might impact their eventual phenotype, and then hopefully use that data to improve health outcomes. Now of course what's really important in this then is to understand that as well as having genotypes and genetics being influencing your eventual phenotype, the environmental factors are going to be quite important here as well. And as Brandon spoke to earlier, these things will interact with each other. And so understanding what's in your genetics but also understanding what your environmental exposures are are ultimately going to be the combination of these two things that help us to determine what types of health outcomes you might have. So, this is the type of genetics today that we typically are able to return there's a set of actionable monogenic findings these are relatively rare in the population but an example of this is, if you have a pathogenic variant in the BRCA one gene. This causes a greatly increased chance for hereditary breast cancer and ovarian cancer, very famously Angelina Jolie has a mutation in this gene, which has resulted in her in her taking action, early to prevent breast and ovarian cancer for herself. There's pharmacogenetics, which is the way that our body interacts with and metabolizes drugs. This can be quite important for environmental factors as well. And understanding how your body reacts to different external compounds can be very important and to Elena's point of a lot of this information has mostly been collected in European and Caucasian individuals and being able to understand a better diversity of these individuals is going to be the best way for us to be able to integrate this this kind of data into care. And then there is now the recent use of polygenic risk scores, and this is really thinking about all of the risk that you harbor across your entire genome. There's not a specific one mutation that's causing risk for disease, but if you sum up all of the genetic factors across your whole genome, everybody is on a different spectrum of risk and this is where environmental factors can play a huge role in changing your outcome eventually. And the last thing you want to touch on is the all of us research program, in which we are the genetic counseling resource, our job here is to help return the genetic results back to all the participants in this study. Elena already mentioned this but the all of us research program is this landmark study that's being conducted by the NIH. The goal is to recruit 1 million participants across the United States over the course of 10 years. Specifically to recruit these individuals from populations that are underrepresented biomedical research. And what that means is that the goal of the study is to achieve a recruitment goal that we 70% of its participants to be individuals who are traditionally underrepresented biomedical research. That's not just on ancestry or race but it's actually also age diversity, it's gender diversity, it's also world versus urban diversity, socioeconomic status diversity, and I think, ultimately it is these types of resources that going to help us understand and get the right data to really understand how we integrate environmental factors with genetic factors to predict this new era versus medicine. Thank you very much. We will now go on to our discussion and I want to sort of paint the scenario picture that it's sort of the main topic or launching point for this, this panel discussion. This is a patient from a community business a primary care physician in complaints of difficulty breathing occasional rashes constant headaches. Her family has a history of cancer. Another close relative was recently diagnosed with cardiovascular dementia and grandchildren living nearby suffer from asthma and was recently diagnosed with a learning disability. The patient wants to know if all these are connected and if the environment to play a role, and we're thinking, you know, 10 years from now where physicians may have access to not just the genomic data that we're just talking about but also environmental exposure data that Julia was talking about and you know, behavioral factors as well that a number of you have touched on. So, how, how will we actually utilize this, all this data to try to provide some actionable information for the for this patient and want to start. I'll just start with an understanding that a doctor has to be able to communicate with their patient have a an understanding of where the patient lives and and the social determinants of health especially. And also the environmental factors. And I think the family and patient history of that can be expanded with genetic testing, and I'm sure the, the experts here can talk more about specifics, but I just think that the precision medicine tools for the future are going to have to be able to correlate the exposure times and the, you know, the, have an understanding of where this the grandchildren, the family, where they live where they've grown up where they spend their time. The work history, especially the occupations. And where is the, where is the community in terms of, I'll say a climate frontline community, or first line or essential communities that that we would look at, in terms of, you know, our environmental grading, if you will. So I'll just start there. I've jumped in since the green housing study conducted by CDC and HUD, focused exactly on asthma and the role of various environmental exposures in asthma. And so I think you, you could start there with talking about pesticide use with thinking about air pollutants from both indoor and outside the home. Some of these could be readily assessed with questions asked to the parents. But 10 years from now. They're also, or there's also been just a proliferation of new exposure measurement devices so that you could send home a passive air sampler or ask a child to wear a wristband for a week and you could get a much clearer picture of what might be the exposure to viruses that are relevant to asthma and think about fragrances and consumer product chemicals that maybe haven't been on doctors minds as much, although I think asthma doctors are pretty, pretty up on fragrance as a potential trigger. And then thinking about the question of whether those other diseases are linked raises for me, the, the issue that we need to share the information that we know, and also let people know what we don't know. And so, I, in this particular scenario there's not enough information to make maybe make connections but in the case of actual patient care you might know more about those other cases and whether they seem likely to be linked for example by high air pollution which could cause other kinds of outcomes, but you could also be, it's also important to be transparent that we don't make one to one connections between an exposure and a particular disease, and that we, we don't necessarily know. We might have lots of evidence that these things can cause an illness but but the, the correspondence isn't one to one. One of the things that when I think about 10 years from now what we hope to have I think a huge component of this is the ability to have collected that data in some way that informs this clinical decision. And I think Julia you made a really great point which is that hopefully in 10 years from now there is going to be empirical data that can be collected from devices that can be integrated into that care, but also there should hopefully also be standard surveys and questionnaires that all clinicians use and can be coded for us to be able to understand what are the environmental exposures that this family these individuals are facing. I think this is actually really interesting because early on in so the introduction genetics into into care we we face the same issue where a lot of the care was being done in a very specialized way. And then you would have all of these sort of unstructured clinician notes that were maybe in the medical record, but probably weren't. And instead you really just had this sort of one clinician who really understood this case understood the molecular diagnosis of this case. In order for us to have really scaled to and we're still struggling to to really bring precision medicine with genetics to large populations. And then it has to be that that data is integrated into the EHR in some way that every clinician can view. And then also there's a shared understanding from the expert standpoint in terms of what are the factors that are going to influence this kind of a disease. And so I hope that 10 years from now that there is regular sort of normalized collection that data, both from the survey side as well from the device side, but then also some way for all that data to go into a shared public common database for clinicians and researchers to be able to derive insights together off that data because I think ultimately without that, it will be very hard to get out of the world in which you're doing so this is spoke one to one diagnosis. And so at least I wanted to probe on a couple of things from your presentation. One was the genetic counseling. Are we going to need essentially environmental and gene environment social determinant counseling services as part of the healthcare delivery precision medicine environmental health nexus. Maybe start start with that is that is that a model that can be scaled to this complete level of complexity. And this is a really great question I think one of the things that we are trying to do in the in the clinical genetic space is actually to teach more primary care physicians, how to counsel especially some of these more common genetic areas. I think that at the end of the day genetic counseling is going to be quite useful, especially when you're talking about counseling full family and talking about individual specific case, but for common genetic disorders when I say common there's still relatively one to two percent of the population, but hopefully a primary care physician should understand the implications of a BRCA one mutation and be able to counsel you on that. In terms of that sort of scale delivery, especially as you put into creation of environmental factors, I can think this is an area I'm sure Brandon has a lot of experience in having done this in Bangladesh so I'd love to hear what his point of view is. Yeah, I mean, I guess, you know, that my mind was on sort of the first question of, you know, does the primary care physician have the basic knowledge base, you know, to be able to connect these dots right does does the physician have, you know, you know, complete knowledge of the, the environmental exposures locally that wherever the patient is from that the key environmental exposures that are concerned, and can the position, you know, having does they have a knowledge base to link those exposures to the symptoms that are being reported to the common exposures with symptoms are, you know, maybe it's it's straightforward. But they're, you know, you know, obviously that there's government agencies that do monitoring of water and air, you know, EPA US GA, you know, to build that knowledge base of what exposures are, are a particular concern where but you know some of those might not be on everybody's radar, which actually brings to mind this, this, this new this app this sort of phone app that's been developed by, you know, colleagues of mine in Chicago as a part of an environmental health center here. We have people developing an app that can be used by people in the community to report, you know, environmental concerns that they have and put them on a map right because some of these maybe sort of, you know, micro exposures that are not a huge people, a number of people are exposed to. So I guess that, you know, first understand the local exposures. And then, you know, I like all of your ideas about how to gather additional information on that whether it's gathering, you know, data on air samples at home or through wristbands, or through, you know, collection of participants, you know, or collection of patients, blood and urine samples that can be used to directly measure, measure the exposure. So I guess, you know, start with we need, you know, the position to have to have the right knowledge base to connect all these dots. And so that was the first thought I had. So, Alicia, I'm returning returning to what you asked me could you could you sort of restate that. Yeah, I am. I think at the end of the day it is, you do have to figure out how to integrate all of those data into into care and I feel like this is probably an area where we could use specialists but the scalable solution is going to be to use primary care physicians. Do we do we believe that primary care physicians will have that ability or is there going to be the need for specialized tasks for specialized profession for for the region of these types of results. Before I get to Julia later I think this reminds me of some of what you were saying about how a lot of the doctors in these communities are already overburdened because they're they're medically underserved and they don't need to, you know, put put another layer of sort of continue education or in terms of really, or maybe that 10 years is too short to really build capacity for the next generation but longer term well, maybe you want to comment upon that. Let me comment on so I'm a general internist by training and actually went to public health school before medical school to learn about small area analysis and planning communities. And honestly, I think that now we know with genetic counseling and also with social determinants of health. There are some concepts that are much broader than just looking at a disease that primary care doctors do need to understand the broader context of medicine and and the inclusion of public health with medicine, especially having gone through this coven 19 pandemic. I think that the future primary care physician is the still the gatekeeper if you will, you know, to refer to consultation for for special, you know, whether it's pulmonologist for the asthmatic asthmatic or what have you. The extra burden is because there's so few doctors for Hispanic patients that we also need to understand the importance of training those doctors and providers who work in a predominantly Hispanic community. How to better interact with the Hispanic population and that's the concept of cultural competence and the class standards. So I think that that's part of this scenario is that there has to be an understanding that we're never going to have enough Hispanic doctors for the Hispanic population or the black doctors for the black population. And in our national health service core model, I think just needs to be has to has to have more of a career focus instead of just a revolving door where doctors go to work in a clinic to, to get their loans repaid for three years and then leave. There will be a new, a new association of, of how the doctors that take care of a community need to really understand that community to understand the, how to educate the community to change their behaviors and adapt to the behaviors of the climate change. And, and to better, you know, to better take advantage of the opportunities of new technology. And I also think it's going to be a huge push for artificial intelligence within the, within these communities that have not had that data before, to be able to understand how to use data in in our communities of color and disparities communities to, to make changes. Well, I want I wanted to add about this problem that I love the vision of the gene environment counselor sometime in the future. One of the goals of Derby is to automate the knowledge base so it has a content library that physicians as well as patients can use so that when you get a result it's in the context of what's known about health, health effects and it's link to about exposure reduction so that an individual doctor doesn't have to know all the things that we, we really can't realistically expect them to know about environmental exposures and instead they have this library that's, that's linked to the, to the measurement so that they're, they have the content library is being being served to them in relationship to the particular result that they're dealing with. And that kind of segues into one of the q amp a questions that you know what research on communication of science and social science is necessary for advancing the translation of this sort of technical knowledge that we hope will be will be gaining. Is there any additional sort of science that needs that's needed to make this information sort of applicable to the physicians and decision makers and, and you know what what are some some potential ways to accomplish that. Yeah, I think that there this at the end of the day I think you have to really think about the researchers and their role in sort of bringing this future to fruition and I think that the researchers need to work together as a community and start to understand how to sort of, what are the, what is the nomenclature for the environmental exposures that they all agree on so that physicians can to use the same words. And this is actually something that in the genetics community that we had to figure out as well because if the researchers can't agree about what it's called and and how much, how much of it, how much exposure results and what kind of disease risk if the researchers can't do those things then it becomes very hard then for the physician to deliver that information to a patient, especially what you don't want to happen is for a patient to go to two different physicians or two different specialists and get very different information or different recommendations, or even be told completely opposite things about whether that environmental exposure actually has contributed to their disease risk or not. And part of that is it is on the research community to start to understand what is the shared nomenclature and the shared sort of classic risk that that that we want to use, how do we then educate the clinical community about using using that that framework, and then thinking about then what are the, how to educate and work with the patient community to make sure that the words that we're using are actually understandable to them I think that's something that in the genetics community that we, we kind of are learning how to do that. So, for example, in genetics community, we often say you have a positive result if you have a disease causing variant in your genome, and the word positive, of course, has these connotations of something good has happened in normal speak. And we've learned that telling somebody that they have a positive result in this way can actually not be that useful and for the all of us research program we actually did a bunch of coverage and testing and realize that we can't even use that word when we return that that result we need to immediately address that there is something significant for their health that was found in that report. So I do think there's a lot of this sort of communication that has to communication, sort of iterations on nomenclature and verbiage that has to be done. I think first, I think the researchers and clinicians need to agree about what they want. What is the framework in which they want to classify these exposure risks. And I do think there should be, you know, continuing medical education. Again that that brings this into fruition for the future of learning. And I think there should be more learning communities like you said and honestly there's so much that policy can do with the Medicaid population for example the Medicaid waivers that states have states that have large rural populations could could do more for rural health education with the environment about heat and pesticides, etc. or the, you know, the water communities on the water. There's just all kinds of things I think that the policy could do when you think about reimbursement to states for education it's not just about diabetes or for heart disease chronic diseases but actually looking at environmental impacts and adding that to the I guess to the to the learning community at large. So I guess one of the other questions that is of great interest to the sponsors is what, what type of research is needed that you know in terms of funding or, you know, what type of grants or what subject areas need to be addressed. You know, in order to just actualize this type of vision, are there are there specific areas that are currently under under resource that need to be emphasized more. Are there things that, you know, just people haven't really thought of or things that are more multidisciplinary that that are in the current environment difficult to, you know, difficult to get funding for you know what are some particular suggestions for for how do we move, move in this direction. I would say I multidisciplinary especially was brought up about women's health, for example, and I know women's health in the environment is very important, but also the, when you talk about. And I'll just go back to the Hispanic health or if you want to call it health disparities work, Office of Minority Health and at HHS, working with all of the different agencies that that have, you know, EPA for example and agencies that have more direct policies that can change where they can show direct impact of health and how they need to change policies in the environment. You know with auto emissions, that's the Department of Transportation so they're definitely need for a more a broader, you know, collaborative effort for policies. And I also think and I'll just put that plug in again that I think there needs to be a real focus on the next generation of researchers. And, and having students learn about the importance of these types of careers, not just think about climate change as something you know what a fad to get involved with because other young people are involved, but that there really is an impact that's needed from a research perspective, and public health researcher if you want to call it you know whatever you want to call it, we get there's so much importance related to public health. I really like to reiterate from my earlier remarks that we need to know a lot more about what chemicals do biologically. Yeah. And what, what do mixtures do when you were not exposed to one chemical at a time what what is the combination of exposures do what are the early effect markers that we can use to say that short of full flow disease which is not a preventive to, to health so I think we still have a really big knowledge gap in understanding what the effects of chemicals are in the body. Yeah, I definitely agree with that I think in addition the other thing that we have to really start to understand is the acknowledgement that these environmental factors play a role in our health and I think Elena and Julie you mentioned that. I have a question about what kind of funding needs to be put in place I do think, probably breaking it down by disease area can be helpful, especially the areas where we know environmental factors have a huge impact today. I think the analogy is an area where I think we've already talked about in the case study was was the example as well. You know, are there are there already areas in which there's clear environmental impact on disease risks that we can use as the first case to show why taking into account environmental factors is going to be very important. I think the other thing that Elena has said a couple of times I think is very important and is and people are beginning to understand is social determinants of health. And also with social determinants of health. I feel like we're using a very sort of crude measure for that right now where we're thinking about sort of zip code level data, or thinking about social economic status as a proxy to things that are in social determinants of health. I do think ultimately we really need to think about what it means, you know, access to a safe home environment, this food security, you know, being able to access care when you need it. It's kind of tied under social determinants of health. And so I do think that having more research in that area being able to break down all of those subcategories and understanding what that actually means is going to be very important for us to sort of realize this vision that's 10 years from now. Another thing is really the communications needed by the messengers that you know that that are trusted by the community to change communities behavior. You know, I mean I grew up in the 50s and 60s when people in Los Angeles, I grew up in Los Angeles, everybody had an incinerator in their backyard and burn their own trash. I mean, can you imagine. So now California is going into composting, and everybody's going to have to learn how to compost, and it's going to be against the law in California not to come compost your own track your own food waste. So we have to think in terms of policies that can help with changing behavior and not being afraid of taking tests not being not being afraid of the government and and trusting. And that's one of the best things about all of us the all of us research program has allowed everybody that lives here whether you're a citizen or not to become a participant in the program. Yeah, I can. I like to pop on Julia mentioned about, you know, understanding, understanding exposures their biology their effects what is going on and since the session is sort of focused on, you know, future thinking sort of technology will have access to it. We should at least mention, you know, these sort of exposomic technologies right that can take a biospecimen and do some sort of, you know, global or quasi global measurement right of exposure content in that sample and I realize and I don't really work in that area with those those types of mass spec technologies. It's a very rapidly developing area where there's a lot of work to be done I think I think Bob right is on this call you may talk you may have a session on this later right. But it's an area that I'm excited about me in park because there's you know, probably interesting genetic studies we could do to understand differences amongst people. You know, in terms of their profiles of you know various metabolites for exposures measured globally. You know, these technologies, you know, if they if the technology is developed to the point where we can, you know, feasibly apply them in large studies like all of us. You know, is that is sort of a big data approach, you know, a good way to learn about exposure effects. I think remains. I'm hopeful it can be but I guess remains to be seen. And in this clinical setting like could a technology like that be helpful for understanding. You know, the environmental exposure concerns that this that this patient is having, you know, you know, you know, could we get to the point where we could have, you know, somewhat automated ways of analyzing that data to pull up, you know, a list of exposures of potential concern that might potentially be, you know, useful to that patient so let's focus on this a little bit because I feel like I mean the way currently we're doing we're doing this is is analogous to the modern genetic diseases right we're doing one chemical at a time and it's actually even worse for just the just that because chemical exposures have different levels, whereas the modern genetic diseases is more of an on off kind of thing. And then on the, you know, Lisa, you showed that for pharmacogenomics we have 14 genes, but how long have we've been working on that we only have 14, right, in which there's an interaction with drugs that, and one of the other things that maybe if there's time to get to was about whether those 14 genes also might be relevant for environmental chemical ADME, right. But like, weird, like, it seems like there's a there's a long way to go perhaps to get from you know the monochemical exposure relationships to the polychemical and then polychemical plus social determinants and and genetics like how how are we going to try to pave a path there that won't take 100 years I guess. Yeah, I think, I think one thing that we certainly have now that we didn't have before is that we've learned a lot about how to handle and derive insights from large amounts of data. There's a huge amount of improvement in that field that has that has been seen over the last 1020 years, the ability to analyze large amounts of data, multiple sources of data and being able to actually derive insights about causation correlation from that data. We've greatly improved all of those methodologies in the past 15 years or so. I do think that for that reason I actually do feel like this is a surmountable problem. If we can have a way to store that data collect that data and have that data across a diverse and large set of individuals. I think that's one of the things about when you're trying to do this sort of, you know, all these inputs, having all of these risk factors for disease. At the end of the day, the only way that you can really derive good and solid insights from that is to start from a place where everybody has the same input data right so I do think being able to invest now in the data infrastructure for how are we going to do this, make sure it's not just, you know, notes in the, in the EMR that are completely unorganized and unstructured, but actually have structured ways to be storing that data and to, and to get the buy-in from the community that everybody's going to use this database is going to be really important. And I think, yeah, the point about pharmacogenics is interesting, right, the pharmacogenics and actually genomics in general, what we've learned is there are, you know, all of these genes across the human genome but at the end of the day we actually only understand really a handful of them in terms of how they really, really interact with your disease phenotypes. I do think that we are moving to a place now where we're able to consider polygenic considerations for disease and that's actually a huge step forward for the genetics community. So it is going to be another large step forward for us to be able to integrate environmental signals as well. But it all comes down to you got to start with collecting that data across a large population in a structured way, so that we can start to really derive the correct insights from that. And I think the other thing is key to all of this is going to be risk, the risk involved and risk management, but also looking at what communities or what environmental exposures have the highest risk. I'll just say the Flint, Michigan case, water quality, I mean it's horrible, but I mean, I'm sure that it's everywhere. But we have to look for it and have a way of for policy and funding to go to those highest risk to take care of those, you know, to cut the kind of nip it in the bud, if you will, even though these environmental exposures have been there forever. As we find ways to handle and treat that we do take care of it, we don't just let it, you know, get worse. And I could see that with with policies. There's another question from the Q amp a about following up on the big data, what, what kind of investments in, you know, data science, maybe research needs to be made in order to sort of, you know, prepare us for that, for that future on the on the data infrastructure and you know data and big data analytics methods and things other particular areas that you see is as as there being a need. Oh, absolutely I think data science has a huge role in all this and I think that all of the improved technology improved techniques that we have for data science, you know from machine learning should just being able to make a linear regression model for multiple, you know, role sort of inputs for disease risk I think it's going to be important underlying that though is the data infrastructure and that's, that's actually costly right posting all this data and putting it all in a single place for folks to access it and analyze it. I think one of the things that oftentimes is underestimated is the cost of simply maintaining all of that infrastructure. And what's interesting is in all of us research program, there's a specific award that was given just for the data center right just for the data centers and host all this data and make it available for researchers to use. And so when I think about sort of the funding that could help in this area, or, or areas in which, you know, the NIH or other federal agencies could have an impact. Being making available this common data base and and the underlying data infrastructure to support that could be a huge investment that could be very, very important for the ability to really derive strong insights from this and then definitely training our data as a basis of the future to understand that they have to have this multidisciplinary approach that they need to understand the biology but they also need to understand the statistics and being able to bring that together is going to be incredibly important. Yeah, on the training I was wondering whether, you know, training grants might be a method to, as opposed to just, you know, our one or, you know, research individual research grants or training grants might have more flexibility. So, you know, promoting that kind of multidisciplinary, you know, training essentially, and I don't know whether you all have any, any thoughts on that. Yeah, I think one thing with the coven 19 pandemic we realize that NIH could become a little bit more focused on collaboration outside of the recent individual researchers and looking at coalition building. And I would say, for the future the coalition should include the data users and, and the, you know, having the data infrastructure can connected to each, let's say grant around certain, like asthma or certain diseases, and just like and it could be connected but I think that, but I think that the importance of having researchers connected to the communities that they do the research in with some type of collaborative effort with say if it's agricultural area that the US Department of Agriculture get involved in the EPA, and that there, there be more cross cutting policies, we in a HHS we called it when I was at HHS before health and all policies, and in this case it's environment policies and environment genetics, I think, there's a lot to be done. I think one of that multi disciplinary training I happened to co lead with Phil Brown, a T 32 training program that trains environmental health scientists in social science and vice versa, the attention being to facilitate community based research by cross training across these fields. We run a program CDC actually on having leadership development of physicians involved in public health, because, you know, even just public health and medicine are never connected. So it has to be more training cross training. I do feel like that these days trainees need to be armed with just basic knowledge of how to handle large data science problems that really that means that, you know, instead of, you know, you need to take your molecular biology and your cell biology and your human biology, but then you also need to take your, you know, statistics course you have to understand your basic, you know, maybe even understanding how to handle sort of that bioinformatics side of things that the data that flows through the pipe how you how you use it. I think it's going to be really important and I do think these days a lot of training programs are including data science and machine learning and computational biology as parts of the of the curriculum. I think it has to become sort of required curriculum rather than optional. And I feel like that will help a lot in terms of arming the future generation with the right tools to actually handle some of these problems. I think we should sort of close with discussion of, you know, sort of privacy ethic, ethical equity access to data kind of issues and how, and how you see those playing out in, you know, the kind of genomic plus real determinants, plus, you know, all of these, all these things together, like how, what are some of the barriers and challenges in terms of the, you know, ethics equity and privacy security space. I can just say one of the biggest barriers is the our own biases, and especially those who do not come from a certain community and go there to do research and may look down on the community or you know have microaggressions or some other discrimination and I think that's the worst thing that could happen. I think people need to be trained before they go into a community they're not from and to understand the importance of those ethical considerations. Yeah, I think the other piece of that is just to make sure that there is unbiased collection that data across the board I think to Julia's point to the extent that we can use empirical measurements using devices to measure you know air quality in areas, etc. You know having those devices actually be available and that data available across all of the geographies is important and not have them be super concentrated in more affluent areas or more enlarge metropolitan areas and then all of a sudden we have this huge gap in from more of our rural communities that that that kind of that kind of unconscious bias is the reason why we currently have a lot of gaps in our data today and so making sure that we are able to collect that data. Equally across all of our communities is going to be important. And then also just understanding that. Yeah, to Linus point that the researchers don't go in and just say we're here to answer research question and in doing so might actually sort of harm the relationship with the community between the clinicians in the community. You know you have to work together on that and make sure that the participants feel like they have a part in that research, rather than feeling like they are being studied by a researcher I think those are those are really important. In terms of getting towards several people mentioned that a normalized data collection and the data infrastructure me even the, you know, building that infrastructure. It seems like it has the potential to be biased from the start just by how what's it what is included in it, how it's coded, you know what it what's missing. And so does that mean we kind of need to do a lot of this kind of community based work before we decide on what the ultimate, you know, normal, you know normalized data collection tool or or data infrastructure are. Yeah, I, the community based research is most important here and I do think that our research enterprise has really been focused on the academic researchers inside and you know, a bubble if you will, of the academic health center. Again, COVID-19 showed us the importance of doing research with community input and having more community at all levels at the design phase that the implementation phase, you know the questionnaire phase, etc. To lessen that as much as possible to lessen the bias. And Brandon, do you have any final thoughts or we close. I mean, I echo those comments on community based research that, you know, we should really ideally be speaking with the community. You know, first to see what their interests are and their, you know what they would like to see in terms of research and environmental problems addressed in their community and let that guide setting research agenda. Julia, last word related to your question about privacy I think we haven't yet grappled with the potential. Privacy risks associated with environmental data and that is going to be important to community trust and to using the data for good and not stigmatization and genetics is ahead of us in that regard and we have some catching up to do. All right. Hi everyone, I thought it was a great robust discussion of the intersection and precision medicine environmental health. And thank you all for your participation. And now I'll turn it over to back to Kristen. Hi, thank you everyone thank you so much for this really, really wonderful discussion and thinking about the ideas of where we need to move forward both the science the funding and sort of a dealing with the ethical issues. We'll be back in. I think we'll be back at around at it's 1215 here. So we will be back at 130 on East Coast time 1230 central time. Yep, we'll be back at 130. I want to remind people if you want to add questions there on the on the link below the dialogue that we're having there's a space for you to submit questions, longer questions detailed questions and comments. A goal of this workshop really is to gather all of these diverse voices so I really really thank this panel and all of the different perspectives that were brought to this discussion and we will have another engaging discussion starting at 130 so please join us.