Newborn Genomics: Harvard Medical School • Robert Green
Beyond Natural Selection: When Genes Are the Start, Not the Destiny
We sit down with Dr. Robert Green of Harvard Medical School and Brigham & Women’s Hospital, a pioneer in genomic newborn screening. From his early curiosity in science fiction to launching a field that’s now coming full circle, Robert shares the innovations, challenges, and ethical questions of applying genomics to healthy newborns.
2025 is a landmark year: genomic newborn screening is moving from research to real-world implementation, with Robert helping to lead the NIH’s national initiative to test feasibility in the U.S. public health system. He also recently gave a TED Talk on the topic, highlighting the significance of this moment for preventive healthcare and the future of precision medicine.
Join us to explore how genomic newborn screening is ushering in the era of precision medicine on a population scale, shaping a future where care is truly proactive, personalized, and preventive.
-
(Auto-generated by Spotify. Errors may exist.)
Robert C Green, MD, MPH, is a physician, scientist, and professor of medicine at Harvard Medical School who directs the Genomes to People research program at Mass General, Brigham, Ariadne Labs, and the Broad Institute. Dr. Green's empirical research has established the safety and feasibility of disclosing unanticipated genetic risk information in research studies and in population screening. He led the first federally funded clinical trials of genomic sequencing in healthy adults, the MedSEEK Project, and in the active duty military personnel, the MillSEEK Project, and currently leads the world's first trial of sequencing in healthy newborn infants, the BabySEEK Project. Dr. Green co-led the American College of Medical Genetics and Genomics Working Group that created the first recommendations for return of incidental genomic findings, establishing the ACMG list of actionable genes that has subsequently been used in many return of results protocols. Dr. Green leads the first grant to return genomic results in the Framingham Heart Study and the Jackson Heart Study and has led policy development for returning genomic information to research participants within the Global Alliance for Genomics and Health, the Verily Google Baseline Project, and the All of Us Research Program. He is also co-founded the telegenetics company Genome Medical and the newborn and childhood genomic screening company Nurture Genomics.
Host: Robert, it's such a pleasure to have you here. Thank you for being on unNatural Selection.
Robert Green: My pleasure, my pleasure, Nic. Happy to be here.
Host: And you know, I got this bio just about a week or two ago, and it's incredible to find that it's already outdated. That's how fast you move. So to start, I always ask this question to level set and give the listeners context in your own words. Could you please explain what need or impact drives your work?
Robert Green: Well, you know, my work is driven by the fact that the Genomic Revolution is here. We can now read people's entire genetic code. It's getting cheaper, it's getting faster, and it's becoming integrated into healthcare. But we're running ahead of the data and the evidence to figure out how to do it safely and effectively. We can generate massive amounts of information, but the biggest challenge is figuring out what's medically actionable and how to communicate that to people who may not be sick, or whose doctors may not be genetic experts. So, the core mission of our work at Genomes to People is to conduct the rigorous evidence-based research that will help guide the effective, safe, and equitable implementation of genomics into medicine and public health. We want to make sure that this powerful new information actually leads to improved health outcomes, and that it doesn't exacerbate existing health disparities.
[05:00]
Host: That's a phenomenal articulation of the challenge. And you've done pioneering work on this, particularly with the ACMG list of actionable genes that can be returned as incidental findings. Could you explain what an incidental, or what you call an unanticipated, finding is, and why it's so important to have a standardized list?
Robert Green: That's a great question. When a person has a genetic test ordered for a specific reason—say, they have a heart condition, or they're trying to conceive—the sequencing technology actually reads millions of data points across their entire genome. An unanticipated finding is one of those data points that reveals a risk for a completely separate, unrelated medical condition that the person wasn't being tested for. For example, a person being sequenced for a type of muscular dystrophy might also find out they carry a mutation for hereditary breast and ovarian cancer (BRCA1/2). This is critical information because, for some conditions, like BRCA-related cancers, early surveillance or intervention can literally be life-saving. The ACMG list was created because if you sequence the whole genome, you get so much information that it's overwhelming. We needed to agree, as a medical community, on a limited set of genes that met two key criteria: first, they must cause a severe, life-threatening condition; and second, there must be a clear action—a medicine, a surgery, a screening test—that can be taken to prevent or treat the condition if it's found early. This standardization provides a boundary for physicians and ensures that patients are getting information they can actually use.
Host: The ethical implications of that sound enormous. When you think about communicating genetic risk to someone who is currently healthy, what are the biggest psychological and ethical hurdles that your research has helped to address?
[10:00]
Robert Green: The hurdles are immense. The classic ethical concern is the "right not to know." Does a healthy individual have the right to avoid information that could cause them anxiety or alter their life plans, even if it's medically actionable? Our early research, the MedSEEK Project in healthy adults, showed overwhelmingly that the vast majority of people do want this information. We found that the psychological distress was mild, transient, and mostly tied to the initial disclosure, not long-term anxiety. Most people feel empowered and grateful for the warning. The biggest ethical issue we focus on now is equity. Who gets access to this technology? Right now, genomic sequencing is still primarily accessed by people with good insurance and high socioeconomic status. If we don't actively ensure equitable access, we're simply going to deepen the health disparities in our country, where people who already have more resources get an even greater advantage in proactive healthcare.
Host: That point on equity is so important. Now let's talk about the BabySEEK Project, which is groundbreaking. This is the world's first trial of sequencing in healthy newborn infants. What is the fundamental difference between sequencing a healthy adult versus a newborn, and what are the specific ethical responsibilities in that context?
Robert Green: The stakes are fundamentally different with newborns because it’s not the individual making the choice; it’s the parents. We call this the "pre-symptomatic dilemma." In the United States, all newborns are currently screened for about 30 or so rare conditions. BabySEEK explores whether a more comprehensive genomic sequencing that covers thousands of genes should be included in routine newborn screening. The ethical responsibility is profound. We are testing for conditions that may emerge in childhood, adolescence, or even adulthood, and we are giving parents responsibility for information that will impact their child's entire life. We have to be meticulous about informed consent, ensuring parents understand the difference between carrier status, a treatable childhood condition, and a risk for an untreatable adult condition. Our trial is collecting data on parental anxiety and whether the information leads to over-testing or over-treatment. Ultimately, we want to know: does this information lead to net benefit for the child?
[15:00]
Robert Green: We believe that for certain early-onset conditions where intervention is highly effective—conditions that can't be detected by current screening methods—genomic sequencing could offer a profound benefit. Imagine catching a lethal condition before symptoms even appear, when treatment is most effective. That's the promise we are rigorously testing in BabySEEK.
Host: You mentioned earlier that you co-founded Genome Medical and Nurture Genomics. How does your work as a scientist influence your approach to commercializing these discoveries, and how do you ensure the commercial entities maintain the ethical rigor that you've established in your research?
Robert Green: Well, there is often a tension between the pace of research and the speed of commercialization, but I believe it's essential for people who develop the evidence to be involved in the rollout of the technology. Genome Medical was created to address the massive genetics workforce bottleneck. There just aren't enough genetic counselors and geneticists to handle the demand for genomic information. Genome Medical uses telemedicine to scale the delivery of expert genetic care, making it accessible across the country. My role is to ensure that the clinical protocols are based on the latest evidence, emphasizing actionable results and comprehensive, high-quality counseling. Nurture Genomics, which is focused on newborn and childhood screening, is a direct offshoot of the BabySEEK philosophy—to proactively give parents the most evidence-based information to help their children. The ethical rigor is maintained by prioritizing transparency, avoiding the return of non-actionable or purely recreational genetic information, and ensuring that every patient receives appropriate counseling, whether it’s a healthy adult or a parent of a newborn. It’s about building a business model around responsible implementation.
[20:00]
Host: As you look forward, what is one major policy or societal shift that you believe is essential for the effective integration of genomics into global public health?
Robert Green: The major shift needed is a massive re-thinking of regulatory and reimbursement policy around genomic screening. The current system is geared toward diagnosing symptomatic people. If you're sick, insurance will often pay for a diagnostic test. But the value of genomics is often greatest when it's used for proactive screening in healthy people. The shift needs to be from a sick-care model to a wellness and prevention model. We need the FDA and major payors to create new pathways for reimbursing genomic screening as a preventive service, similar to colonoscopies or mammograms. This would legitimize the practice and finally make it accessible to the broader population. Without that policy change, the science will continue to accelerate, but the clinical utility will remain limited to niche groups. That’s the frontier for the next five to ten years.
Host: That's an extraordinary perspective and a tremendous challenge. Robert, thank you so much for your time, and more broadly, for everything you've done for science and medicine. It's been an honor working with you all these years and a true privilege calling you a friend. Thank you for being on the show.
Robert Green: I do too and I feel exactly the same way. And thank you for your support and belief in all of this through the years, and we look forward to the future together.
Host: And one thing that I've noticed, Robert, in all of this work, and you and I have known each other for a long time, and I've watched you in the field. It's a tremendous amount of work that you do, and yet you're probably one of the most humble people I know. And I think that's one of the things that I truly admire and respect about you and your approach. Because you know the work that you do is so profound, but yet you carry it so gracefully. And I think that's one of the greatest assets that you have.
[25:00]
Robert Green: Well, Nic, that's incredibly kind of you, and it's a huge compliment coming from you, who has also been a true friend and colleague and incredibly supportive of this work from the very beginning. So thank you for those words. I just believe that the science is so much bigger than any one person. The Genomic Revolution is a force of nature, and our job is just to try and channel it responsibly. That's what keeps me going.
Host: That's beautiful. And speaking of channeling it responsibly, you know, we're talking about all the proactive use of this, but of course, there's always the dark side, the kind of the dystopian aspect of this. What keeps you up at night when you think about the potential for misuse or the risks associated with this information?
Robert Green: Oh, the list is long, Nic. The misuse is something we are constantly vigilant about. First and foremost is genetic discrimination. Even though we have the Genetic Information Nondiscrimination Act (GINA) in the US, which prevents discrimination in health insurance and employment, it doesn't cover things like life insurance, long-term care, or disability insurance. So, a person could get this information, feel empowered, take action, but then be penalized financially when they try to get a new policy. That's a huge issue. The second is the misinterpretation and over-medicalization of normal life. We are all imperfect, we all carry risks. We don't want to get to a point where every common variant that causes a slight risk of something is suddenly pathologized and treated as a disease. Genomics has to be integrated into a healthy lifestyle, not used as an excuse for an unhealthy one.
[30:00]
Robert Green: And then the third is what I call the erosion of privacy. We are generating massive amounts of deeply personal, deeply private data. How do we ensure that it's protected, that it's not hacked, and that it's not used by governments or corporations in ways that we haven't consented to? That's why we spend so much time on governance and data security at Genomes to People and within our companies.
Host: That's a heavy responsibility. And when you think about that, who is best suited to regulate this technology? Is it the government, is it a medical association, or is it a coalition of industry leaders? Who's the right body to provide that guardrail?
Robert Green: I think it has to be a multi-stakeholder approach. No single entity has all the wisdom or authority to do this alone. The medical community, through organizations like the American College of Medical Genetics and Genomics (ACMG), is crucial for setting clinical standards—what's actionable, how to counsel. The government, through agencies like the FDA, the NIH, and the CDC, is essential for setting safety standards, funding research, and addressing discrimination. And industry must be at the table because they are the engines of innovation and delivery. We need a continuous dialogue between these groups, not a top-down regulatory fiat, because the science is moving too fast for that. It has to be an adaptive, learning regulatory model.
Host: That makes perfect sense. An adaptive, learning regulatory model. What about the direct-to-consumer (DTC) genetic testing companies? They've exploded in popularity. Do you see them as a help or a hindrance to the responsible integration of genomics into healthcare?
[35:00]
Robert Green: It's a complicated relationship. I think they've been a huge help in raising public awareness and engaging people with their own genetic information. They've democratized access to some degree. However, they can also be a hindrance when they sell purely recreational or non-actionable information, often without the necessary genetic counseling. Our research has shown that when patients get raw data or unverified results from DTC tests and bring them to their primary care doctor, it creates confusion, unnecessary testing, and anxiety. The ideal model is where a patient is engaged by the DTC company, but if a medically significant finding is suspected, they are seamlessly transitioned into the clinical healthcare system for confirmatory testing and professional counseling. That's the missing piece that we're trying to build bridges for.
Host: That's where you step in with companies like Genome Medical to create that bridge.
Robert Green: Exactly. We need the clinical infrastructure to handle the demand that DTC companies generate.
Host: And stepping back a little bit to the BabySEEK Project, you mentioned that parents are currently responsible for the information. What happens when the child becomes an adult? Does the responsibility transfer, and are you developing protocols for that?
Robert Green: That's a central ethical challenge. The data we generate on a newborn is relevant for their entire lifespan. Legally, the child reaches the age of consent (usually 18) and the information becomes theirs. Our protocols are designed to foster what we call "anticipatory guidance." We provide parents with a mechanism to store the data securely and counsel them on how and when to re-disclose that information to the child as they mature. The key is to avoid "informed-once-and-done." The information needs to be revisited at different life stages, such as when the child is approaching adolescence, or when they are planning a family, or when they turn 18. We are actively developing tools and policies to facilitate that generational handoff of genomic information responsibly.
[40:00]
Host: That's fascinating. And it almost sounds like a new role for the genetic counselor—a lifetime genetic information concierge, essentially.
Robert Green: That's a perfect way to put it. The genetic counselor's role is evolving from a crisis manager (diagnosing a sick person) to a lifetime genomic guide (helping a healthy person navigate their future risk).
Host: You mentioned earlier that you're working on returning genomic results in the Framingham Heart Study and the Jackson Heart Study. These are decades-long landmark cohorts. What is the significance of integrating genomics into these long-term population studies?
Robert Green: This is absolutely critical for establishing the clinical utility of genomics. These studies, particularly Framingham, have been the foundation of cardiovascular medicine for over 70 years. By layering genomic sequencing onto these cohorts, we can answer questions that we simply couldn't before: How does genetic risk interact with lifestyle factors over a lifetime? If we give someone a genetic risk score for heart disease at age 50, how does that change their behavior and their long-term outcome compared to their neighbors who don't get the score? The Jackson Heart Study, which is focused on African American populations, is equally vital for addressing equity. Much of the genomic data we have today is skewed toward people of European descent. By returning actionable results within this Black cohort, we are not only addressing immediate health needs but also generating crucial data to make genomic medicine equitable for all populations.
[45:00]
Host: So it's about validating the science within the context of a lived life, not just a snapshot in time.
Robert Green: Precisely. It moves the conversation from "Does this gene cause this condition?" to "In the real world, does knowing this genomic information actually help this person live a longer, healthier life?" That's the ultimate goal.
Host: Robert, you've painted an incredibly comprehensive picture of this field, from the lab bench to the policy table, and now to the commercial entities. What is the most common misunderstanding about your work that you encounter when speaking to the general public?
Robert Green: The most common misunderstanding is that genomics is about determinism—that your genes are your destiny. The public often hears "gene for cancer" and thinks, "I'm doomed." Our work actively challenges this. We emphasize that for almost every condition, including the most common ones like heart disease and diabetes, your genes represent a risk or a predisposition, and that lifestyle, environment, and medical intervention play a massive, and often dominant, role. Our message is the opposite of determinism: it's about empowerment. Knowing your risk is the first step toward changing your destiny. You can't change your genes, but you can change almost everything else about your life in response to that knowledge.
Host: That's a powerful message. And what about the next generation of discovery? You're on the cutting edge. What is one area of genomics that the public is barely aware of but that you believe will have the biggest impact in the next ten years?
[50:00]
Robert Green: I think it's the integration of polygenic risk scores (PRS) into primary care. A lot of the work we've talked about focuses on single, rare, highly penetrant genes—like BRCA1/2. But most common diseases are caused by thousands of small genetic variants working together. A polygenic risk score takes all those variants and creates a single score for your risk of common conditions like coronary artery disease, breast cancer, or Type 2 diabetes. We're now at a point where the predictive power of some of these scores is comparable to or even better than traditional risk factors like cholesterol or family history. Integrating PRS into routine preventive care—where a primary care doctor can see your personalized genetic risk alongside your blood pressure—is going to transform population health and prevention over the next decade.
Host: So it’s the shift from a monogenetic focus to a polygenic focus.
Robert Green: Exactly. That's the leap.
Host: And how do we ensure that those polygenic risk scores are equitable, given that the foundational data is currently skewed?
Robert Green: That is the biggest and most urgent challenge in the polygenic space. If we rely on scores trained only on European-descent data, they will systematically underperform and misclassify risk in non-European populations. That's why the work in the Jackson Heart Study and other minority cohorts is so vital. We must fund and execute large-scale sequencing in diverse populations to build equitable PRS models. The scientific community is aware of this, and there is a major global effort to correct that imbalance, but it requires significant, sustained commitment.
[55:00]
Host: Well, Robert, the breadth of your work, from the molecular level all the way up to societal policy, is truly remarkable. I think you've given our listeners an incredible amount to think about, not just in terms of science, but in terms of the ethical and societal responsibility that comes with that science.
Robert Green: Nic, it's been a true pleasure. These are the conversations that matter, and I appreciate you creating the platform for it.
Host: Well, it's a conversation that I look forward to continuing. And I want to thank you, not only for your time but for your friendship and for your commitment to responsible innovation in this field. You are a true leader, and it's been an honor having you here.
Robert Green: I do too and I feel exactly the same way. And thank you for your support and belief in all of this through the years, and we look forward to the future together.
