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Genome Giants: Heidi Rehm – Chief Genomics Officer, Mass General Hospital

Heidi Rehm is the Chief Genomics Officer in the Department of Medicine and at the Center for Genomic Medicine at Massachusetts General Hospital (MGH), the Medical Director of the Broad Institute Clinical Research Sequencing Platform and Professor of Pathology at Harvard Medical School. Rehm is a leader in defining standards for variant interpretation and developing standardised approaches. She is a Principal Investigator of ClinGen and the Broad-LMM-Color All of Us Genome Center. She is also a strong advocate and pioneer of open science and data sharing.

Please note the transcript has been edited for brevity and clarity.

FLG: Hello everyone and thank you for joining me today for the latest Genome Giants as we take a look at some of the most influential people within the genomics field. Today, we are joined by Heidi Rehm, geneticist and leader in implementing genomic medicine. So, Heidi, if you could introduce yourself?

Heidi Rehm: Sure. I’m Heidi Rehm. I consider myself a Clinical Genomicist, but I wear a few different hats. I am the Chief Genomics Officer at Mass General Hospital, and I’m Institute Member and Medical Director of the Broad Institute’s clinical laboratory, and a Faculty Member of the Centre for Genomic Medicine at Mass General Hospital.

FLG: So, if we just take it back to the beginning. You spent most of your childhood in Lake George, would you describe what are some of your fondest memories from growing up?

Heidi Rehm: Yes, so Lake George is in New York, although it’s up in a more rural part of New York in the lower Adirondacks. I grew up on the side of a mountain – my parents owned 40 acres of land; they still live there actually. And so, you know, we had a pool and lots of space to play outside. So, I think my fondest memories are just playing outside in the woods, in the streams, and hiking through the forest and things like that, playing with friends. That’s sort of my fondest young memories.

FLG: What were you like as a child and when did you think “I see myself getting into a science career”? Because I know that a lot of people start off and they’re interested in something completely different, and then they end up in science.

Heidi Rehm: Yeah, my school was small, there was only 80 students in my whole class. So, it was a fairly rural area. I did lots of stuff in school. I was into sports – I played volleyball, field hockey, basketball and softball, eventually focusing more on volleyball and softball. I was a good student – I was valedictorian of my class, and I had a lot of close friends. So, I did a lot of different things in high school. But as much as I was social with friends and sports and things, I also was pretty diligent in studying, getting good grades, and graduated valedictorian of my class. I always had an interest in science, my father was actually a high school Biology teacher. The interesting thing was, I had no desire to be a teacher, in part because the side of teaching that I saw was his frustration with the public-school system and coming out of work and being very frustrated with the principal and policies in the school. And so, I wasn’t attracted to wanting to be a teacher at that stage in my life, due to observing my father, and his frustrations from teaching. At the same time, all of the snakes and reptiles and amphibians that he would bring home for the summer, that would be at our house, exposed me to a lot of biology. And that might have influenced, I’m sure it did, my continued interest in science and maths as I entered college, and so on.

FLG: Is that something that you bonded over? And then as you got older, you carried on bonding over your love of Science and Biology?

Heidi Rehm: Yeah, I mean, I always loved the subjects of maths and science. And the more it was relatable, the more interesting it was to me. So, biology, I felt was more relatable to the human world around me, and so I think that was more of interest. I also am a very type A personality; I like to organise the world. I remember in probably ninth grade biology, starting to learn about genetics, and to me, the genetic code was very simple and straightforward and elegant in how the DNA sequence encoded genes and proteins that made up what the body does. And that sort of ability to logically understand how the human body works to me was interesting and fascinating. But also, over time, to see how disruption of it would lead to human disease and I wanted to study the impact of disruption of genes, as I saw that process break down and have effects on people. And so over time, my interest in biology and genetics turned to the clinical impacts of that as I got further on in my career.

FLG: You attended Middlebury College, what made you want to do a BA in Molecular Biology and Biochemistry?

Heidi Rehm: Well, again, that was the sort of field of science and math that was most tangible to me, most relevant to the world around me. So, it was very natural to pick that field, it was the field of biology that most encompassed genetics, which I was fascinated by. It was a brand-new Major, I think I was just the first or second class to be able to take this particular Major at Middlebury College, which is a small liberal arts school in Vermont. And I also really enjoyed one of my professors, Bob Cluss, who I still am close colleagues with to this day. He is the director of that Major, and I did my thesis under him studying lyme disease Borrelia burgdorferi.

FLG: Then you went on to Harvard, what was your experience like there? And how did that compare to your experience at Middlebury College?

Heidi Rehm: Yeah, you know, I remember applying to graduate schools. I applied to Harvard, Dartmouth, Princeton and MIT. And there was a part of me that sort of saw Harvard as this stuck-up school that maybe wasn’t as down to earth as something that I wanted, and it wasn’t actually my first choice because of the impression I had about going to Harvard. But then I went and spent the weekend at a retreat for new, incoming, accepted students, and just really had an awesome time. I met professors and other students, and everyone was friendly and down to earth, and intellectually stimulating, and it was just an incredible experience and dispelled my impression of this snooty school. Immediately, I was wanting to attend, and so that was a fairly quick decision to go to Harvard Medical School in the PhD programme.

FLG: What did you work on during your time at time Harvard?

Heidi Rehm: I continued to have an interest in genetics, and particularly human disease. So, when I got to Harvard Medical School, I looked at laboratories that were studying human diseases: Cynthia Morton, Lou Kunkel, Geff Duyk – these were all human geneticists that studied different diseases. Within the two rotations that I had done, I quickly decided to stay at Cynthia Morton’s lab, and her lab studied hearing loss. I was fascinated by the inner ear organ, the cochlea. It has this elegant anatomy, where just understanding the anatomy, you can really understand how hearing happens and works, and how disruption of the different structures can lead to hearing loss. I got very interested in studying hearing loss and was actually studying this family with a genetic disease that included hearing loss but also included blindness and peripheral vascular disease, and I ended up ultimately going down to Costa Rica to study this disease in this family.

FLG: After your time at Harvard, what was your early career like, and how did you transition? What kind of challenges did you experience at that time as well?

Heidi Rehm: Yeah, after I finished my PhD, or as I was nearing the end, I continued to be very interested in the genetic basis of hearing loss and I’d been in a lab that studied the story of human genetics, the molecular biology side of it, and I wanted to stay in the field of hearing loss. I really liked the clinical relevance of understanding the causes of a disease like that, but I wanted to broaden my scope of experience and tools and techniques. So, I went to David Cory’s lab in the Neurobiology Department at Harvard Medical School. He was more focused on neurophysiology and understanding physiological basis of hearing, and so the goal was to sort of broaden my base of research skills and tools, but to stay in the field of hearing loss. However, after a couple years in his lab, an opportunity arose to get involved in a new centre that was being created. It was originally called the Harvard Centre for Genetics and Genomics, and Raju Kucherlapati had been recruited to start up this new centre and I was asked to start a clinical lab as part of that centre. As I mentioned earlier, I was always interested in the human and the clinical side of science and genetics, and so to me the opportunity to be involved in a clinical lab that could do genetic testing for patients with diseases and figure out what was the underlying cause of their disease, was just really amazing. So, I ended up agreeing to take this job and to start to build this new clinical lab as part of this centre, the Harvard partner Centre for Genetics and Genomics.

I was employee number one and I started to hire. I had to simultaneously enrol in a training programme, a two-year fellowship, to become board certified as a Clinical Laboratory Geneticist, which is the credentials needed to actually be a director of a clinical lab. So, I enrolled in that while I was starting to build this lab. I’d rotate at a lab, figure out how they were doing X and then apply that as I was building up a team and a lab, and getting the regulatory requirements to be able to actually offer genetic testing. Raju had brought his team from Einstein that was involved in the Human Genome Project, so they had scalable approaches to DNA sequencing, really scalable at the time. It was still based on the original Sanger sequencing methodology. But we ended up working with that team to apply, what was at the time, originally high throughput Sanger sequencing platform to genetic testing and launching some of the first genetic tests for lung cancer treatment, for diagnosing hypertrophic cardiomyopathy (which is one of the most common monogenic diseases that kills individuals, particularly professional athletes is when you hear about it most – Reggie Lewis and Hank Gathers both died from hypertrophic cardiomyopathy). And we launched the first clinical test for that disorder to be able to diagnose the cause, and also identify family members and prevent sudden cardiac death in individuals in those families.

FLG: What was it like being approached to launch that? As you said, you were the first person, employee number one, how did you feel during that time? What were the challenges around that as well?

Heidi Rehm: Yeah, I mean it was both fascinating and daunting. I remember taking on this job and had to simultaneously enter this training programme. I remember asking “Okay, where is the instruction manual for how to launch a clinical lab? And what are the regulatory requirements that I have to meet? Where is the book? The guidance? The tools?” Basically, the answer was, there are none – you just sort of figure it out. You talk to colleagues, and so I became friends with the clinical labs and the hospitals to understand how they were doing things. Rotating through the labs that I was rotating through as part of my training programme allowed me to see the operations and approaches and the regulatory requirements that were happening there, and I just learned it on the fly. I mean, I remember I had to buy refrigerators and gel rigs and pipettes and freezers, there was nothing there, it was all from scratch. I hired my first technician when I was pregnant with my first child who was born two weeks after my first technician started. So, five days after I gave birth, I started coming back to work a half day a week just to meet with her and review what she had done for the past week and help guide her what to do for the next week. Then I came back mostly full time after five weeks, so I wouldn’t recommend it as how you should take a maternity leave. It was hard in the beginning. I had no idea what it was going to take to launch a clinical lab and it took over a year to do that.

FLG: How did that kind of experience shape the rest of your career? The stuff that you learned from the experience, how did that drive the rest of your career?

Heidi Rehm: I dove into that clinical lab – there’s a part of me that felt like I was leaving science and research to become more focused on the clinical application, the clinical side of things. And to some extent, I absolutely did that for a while. I was entirely focused on launching this clinical lab, developing novel genetic tests, running operations. We built the lab from me up to a 50-person team. So, for a number of years, I was very focused on just launching this lab and launching novel tests and the clinical care side. Now, over time, as you run a clinical lab, all those samples are coming, you’re doing genetic testing, you’re identifying novel causes of disease in terms of new genetic variants and determining which are pathogenic and which aren’t – determining which phenotypes have underlying disease causality and which don’t, and it really became a ripe foundation for writing papers on the work that we’re doing. I started being able to publish on our work in the clinical lab, being part of research studies that were using the results of our work. Then over time, NIH became more interested in genomic medicine as a primary field of research, and so I started working with colleagues, Robert Greene and others, where we had studies to look at introducing genomics into the practice of medicine. Studies like MedSeq, BabySeq and other programmes. So, I started to get back into the research realm, having spent a bit of time launching this clinical lab, but then really using it as a platform to study the introduction of genomics into the practice of medicine.

But along the way, I also realised the sheer inefficiency of some of the things that we were doing. We would identify novel variants, or variants that we had to search the literature and find bits of evidence and information, and it was extraordinarily labour intensive to find information on variants that might be in some embedded paper somewhere. And as the technologies began to scale, and we converted from Sanger sequencing to next generation sequencing, we generated lots of data, lots of variation, and the ability to manually interpret these variants became a huge bottleneck. That was when I started to think there’s got to be an easier way to do this, and instead of all these clinical labs operating in silos, what if we work together? What if we shared our own efforts in researching these variants that we needed to report back to patients? That’s when I started to communicate with other clinical labs and started to think about shared approaches for how we could share the work we’re doing. We were also realising that different labs were interpreting variants differently, and so patients were not getting accurate results. So, by coming together as a community, we could not only reduce the labour involved in the work we’re doing, but we could also improve the accuracy of the work we’re doing, and that’s what I sought out applying for – my own grant funding to build a consortium of laboratories that would share data and classify variants with rigorous standards. That ultimately developed into the ClinGen programme that we now run today.

FLG: What was your experience like of launching ClinGen? What kind of challenges were there at the beginning? What are the challenges that still exist today?

Heidi Rehm: In the beginning, the question was whether all of these laboratories were truly willing to voluntarily share their data. And I remember talking to many companies, that had all sorts of interesting financial models for how to get laboratories to share their knowledge and their various interpretations. There were all these complex models, for every variant you share, every time anyone uses that variant in its interpretation, you will get paid a small amount of money. And there’d be this whole financial network – I just said, it’s never going to work. No one will ever share data if they can’t get money for it, and that just fundamentally isn’t how this this field should work. There should be a pre-competitive space where we can share the knowledge base, the evidence, and then laboratories can make profits on services on top of the shared knowledge base. And so, I abandoned these financial models that people were convincing me was the way to go and went down the route that we could convince them to voluntarily share this data, but it was a big risk. We weren’t sure that it was going to work, and we tried a couple different approaches, because the question was – where was this data going to go? In the beginning, we partnered with a colleague who had an involvement with a company that was going to make a database, that anyone who donated to the database would have free access, but others would have to pay for it. It was still a little bit of a mixed model, and I was concerned.

Then, a group of us approached NCBI at NIH about their willingness to develop a database to house this information. NCBI had, at that point in time, been a really trusted resource and Institute for creating highly valuable genomic resources for our field and sustaining them. In my mind, a much better model was something that wasn’t tied to commercial entities and had a reputation for sustaining things that were useful to the community that they had built. So, we thought that that was a much better model, and we began working with NCBI on what ultimately became the ClinVar database. They built this database with the input of all of these clinical labs coming together, saying ‘We are willing to share our data in that database’. The first grant, that we wrote included funding for about seven or eight clinical laboratories to really help provide the bioinformatics resources and covering some of the staff that could spend time really figuring out how to do this. What were the fields that we needed to share? And how do we get that data out of their systems and submit it? They were the guinea pigs of this process. So, we actually funded not a lot of money, but enough to justify some time and effort in helping build this platform. In the second round of funding, we ultimately didn’t find anyone for the actual sharing of data, and it became part of their operational expenses and that is how it works still to this day. The funding that we have now really funds the expert panels that can resolve differences between laboratories and really apply it as another level of expertise to the process.

FLG: You mentioned data sharing, and I think over the past year, we’ve seen that accelerated in terms of the pandemic. Do you think that we’re on the right path? What are the challenges that exist now that we need to resolve in terms of data sharing?

Heidi Rehm: I think that the major challenges in data sharing today are several fold. One, the most valuable data that we need to share is really individual level data from patients, from research subjects, from individuals, where we can get both genomic and other omic data and their health information and correlate it. But when you’re getting patient or individual level data, the privacy and security of that data becomes a big factor. Having consent and permission to share, not wanting to compromise the identifiability of those individuals and risk loss of their privacy. So, there’s constant tension of really helping these individuals share their data to advance medicine, to advance our understanding of human health and disease, yet also do our best to ensure that their privacy is upheld, and that we’re not compromising anyone’s willingness and what they want to share. So that’s one major challenge that we have to overcome. And I think transparent engagement and consent of individuals is how we can best tackle that, as well as ensuring we have platforms that can protect this data appropriately, yet still share it robustly, which is also a challenge.

The other critical aspects are really thinking about the standards – how do we collect this data? What are the fields? What are the standards for annotating it? Because if we really want to learn from it, we have to bring data from every corner of the globe. But if everybody’s collecting it with different standards and file formats, and methods of access, then it becomes very difficult logistically to share that data and make use of it. So that is one of the reasons that I’ve spent a fair bit of time over the last few years involved in the Global Alliance for Genomics and Health, really working with that organisation to instigate standards and policy frameworks that are applicable across the globe. They can really engage major driver projects and other efforts across the globe. So, we can get everybody working in the same sort of dialogue and language and standards. So, we can do this as a global community.

FLG: You were involved in the ACMG/AMP guidelines for interpreting variants. Are there any plans to update this?

Heidi Rehm: Yes, we are actually in the process of updating those guidelines. So, a new committee was convened with a number of members from the original guideline that we published back in 2015. It’s co-chaired by Les Biesecker and Steven Harrison. I’m involved and so are a number of other individuals. We’ve been working on this for over a year now, so we’re hoping towards the end of this year, or early next year, to come out with the next version of that guideline. It will be more quantitative – it will be a point-based system that’s aligned with a Bayesian framework. And so we’re really working to continually move variant classification to a more objective and quantifiable framework from a less expert opinion and subjectivity. So that’s the shift we’re making, and we continue to refine and evolve the rules for variant classification to make them as objective as possible.

FLG:  What has it been like this time around compared to when you initially released the guidelines? What has the process been like this time?

Heidi Rehm: Yeah, I think the process has been really thinking hard about how we can use evidence to guide the rules. So instead of it being “What do we think is strong evidence?”, “Oh, segregation and families is strong evidence – will we give that strong, or supporting or moderate?”. But instead to actually use the statistical framework to say, “What is the statistical likelihood that a variant in that location of the genome is actually causal for this disease?”. And a LOD score is a statistical framework. So, we can use certain types of evidence that are more quantifiable, to then code them with scores that are based on their actual statistical evidence. The same would be true of a functional assay, where you validate it against known variants that are either pathogenic or benign and based on the accuracy of those functional assays against variants that have been classified without functional assay with other genetic evidence, for example. We can validate those assays, and then based on their performance, in a quantitative way, apply a Bayesian point-based scoring system to that evidence. So, as we dissect these different types of evidence, instead of using expert opinion, we can really use the data itself to drive how much evidence each of those pieces of data is worth.

FLG: Well, I look forward to reading it when it comes out. If we just go back to your career, and I’ve had to write this down because it’s a long list. You’re currently the Medical Director of the clinical research sequencing platform at the Broad Institute, as well as the Chief Genomic Officer at Massachusetts General Hospital, and also a Professor of Pathology at Harvard. How do you it? How do you do all of that?

Heidi Rehm: On the one hand, I do wear a lot of hats. I’m involved in a lot of different projects and programmes. On the other hand, they all coalesce around a common theme. So, my research is really around building resources to support the community in the application of genomic medicine. So, my involvement in ClinGen, in gnomAD, in our Rare Disease Centre that Anna O’Donnell-Luria and I co-lead, where we’re working to discover novel causes of genetic diseases. These are all projects that contribute to improving clinical genomics. Then my role as Medical Director in the Broad’s clinical lab is ensuring that we have a way to take the high throughput genomic sequencing performed at the Broad and allow anyone access to that technology at a scalable level and at low cost. And then my role in Mass General Hospital as the Chief Genomics Officer is really about delivering genomics to patients, and so in that role, I’m working with the clinicians to understand the barriers to ordering genetic tests for their patients. I ran the Mass General Brigham Laboratory for Molecular Medicine for 17 years before I took on this Genomics Officer role, and in that laboratory environment, we developed and launched every test there was from single gene sequencing up to whole genome sequencing. Yet still, there were so many patients not getting testing, for various reasons like – no genetic counselling, physicians not knowing how to order genetic tests, or not knowing how to interpret the results, insurance not paying for it – various barriers. So, my decision to take on this Chief Genomics Officer role is really about working on the frontlines to improve the ability for patients to get these tests. So yes, there’s a lot of different things that I do, but they all come back to a central theme – providing genomic medicine at the end of the day, and every tool and resource we need to get there.

FLG: How do you feel your previous career and experience has put you in this position? And do you feel like you’re in your happy place? Is this the perfect job? Do you feel it suits you?

Heidi Rehm: Yeah, I think what I found the most satisfying from the early stages of my career was recognising that you can accomplish so much more working as a team. So very early on, being very thoughtful about who I recruited into my lab and making sure they were talented and capable and driven, but then, enabling them to be independent and not be a micromanager. I bring talented people in, make sure they have basic guidance, but then allow them to really flourish and develop their own skill set and capabilities, and that continues throughout my career today. The only reason I can get half the things done that I do is because I have just an amazing team of people that work with me, that each and every one of them are entirely capable, skilled, and very productive. It is a global team, across both global organisations like GA4GH, but also local teams that are doing that work, and we all work together. It’s really a teamwork environment, and it is that teamwork that is the most critical thing. The things I enjoy about my job is being to interact with all these just amazing people that do the work of the whole organisation. That brings me the most satisfaction in my career.

FLG: In your experience, what has it been like being a female in such prominent roles? Have you experienced any challenges, particularly in your early career and also now?

Heidi Rehm: I mean, overall, in my career I haven’t experienced significant challenges in being a woman. There’s probably one position that I ultimately did achieve but wasn’t put in that role for a number of years after when I probably should have been. So maybe there was one career step in the ladder that might have been affected by that. But overall, I work with people that respect the work that I do and are willing to recognise that work. I think the two things that I focus on are, finding those people that are team players and will respect you for your contributions, and it doesn’t matter what your gender or your race or your background is, but really respect you for your contributions. And aligning myself with those individuals, and also adhering to those same standards myself and how I think about my team and the work that they do. The other thing I have always done is gone towards the things that I enjoy day to day.

When I mentor younger individuals, I say to them there are two key things that you want to do. One, go into a field or career that when you’re at a cocktail party, and someone asks you what you do, that you feel proud of whatever it is, that you can talk about it with excitement. And feel like you’re contributing to society and that you feel good about what you say you do. But then equally important, is that you’re in a job where the things you actually do all day long, when you show up at work, you enjoy. For myself, I’m in meetings and phone calls all day long. It’s like 40 hours of zoom and meetings, particularly in the pandemic, it’s literally all on zoom! But I’m a people person, I enjoy that. I enjoy the teamwork, I enjoy problem solving as a group. That’s what drives me and so, day to day that’s what I enjoy doing. Whereas someone else who’s not a people person, in my particular role would not be happy, even if they thought that there was an important job to be done. I think those are the two things, finding something that you enjoy doing day to day, in terms of what you’re actually spending your time doing, but also feeling good about it, and then the advancement will happen. Because if you enjoy your job and you do it well, then you’ll be productive, and you’ll flourish.

FLG: That cocktail party thing is good advice. You’re also involved in the All of Us Research Programme. Would you be able to just discuss that a little bit and the purpose of that programme?

Heidi Rehm: The goal of the programme is to recruit individuals to be part of a large cohort, where we can gather as much information as we can about those individuals, both from medical records and personal surveys. And also generate data – genomic sequencing, other metabolomic, proteomic. Over time, there’ll be lots of data generated on these individuals, as well as information collected, and then we will be able to use that as a rich resource for learning about human health and disease, that can continue to power our understanding of genetic diseases, and not just genetic diseases, but environmental influences on health and disease and other factors. So that’s the overall premise. A key goal was really making sure that this cohort was incredibly diverse, even more diverse than our own US population. So, a lot of emphasis has been on recruiting individuals who are underrepresented in biomedical research. That’s not just race and ethnicity as factors of diversity, but also age and demographics and socioeconomic status, gender – all different factors that allow us to have an incredibly diverse cohort that we feel will be most important to learn information about that will become applicable to all individuals from any background.

Now, part of that programme and generating data on these individuals is to think about return of value. So, these individuals are contributing their own data to this programme, what are ways that we can return value back to them? So, since we’re generating sequencing data, one decision was, well, let’s return both traits of interests, ancestry and some of the fun traits e.g., we can return eye colour and different things like that. But then also, if we find information that is actionable to those individuals and could improve their health by intervening, we want to return that information as well. So, the three funded genome centres, and we are one of those genome centres at the Broad Institute in partnership with Color and the Mass General Brigham Laboratory for Micro Medicine, as a team we’re participating in generating the sequence data and also interpreting those results so that they can be returned back to participants when we find clinically actionable information.

FLG: What are some of ethical issues associated with that? Because I think one of the main things that comes to my mind is that when you get your genetic data, you’re not just learning about yourself, you’re obviously learning about things that could be in your family as well. So, what other kind of challenges are there? And how are they being addressed?

Heidi Rehm: Yeah, you’re absolutely correct. You know, when we think about genetic data, it is sometimes unique in that it has impacts for other family members. So that’s a factor. At the same time, there are very few examples where if you find a genetic variant in one individual that you can say, with 100% certainty, that their family member also has it. Usually, it’s 50% likelihood, for example, for a dominant trait. There are some exceptions related to mitochondrial variation and other things, but most of the time, you still cannot  say for certain that a relative, even a first degree relative, has the variant. So, while on the one hand, their risk of having a variant would be much higher if that first individual has it, it’s still not a guarantee, and it still allows some autonomy of those family members to decide what they want to do, and whether they want to learn that information as well. But at the same time, we have saved the lives of individuals by identifying, actionable information early on, so that we can prevent the onset of serious disease. On the one hand, you can say, well maybe somebody doesn’t want that information, but in our experience, in the course of offering this information to individuals in both clinical and research context, most individuals do want to learn this information – they would want to take action to improve their health. So, I think, on the net, we certainly feel that the benefits outweigh the risks, but each person makes their own decision, whether they want this information back or not. Then, each family member of those individuals also gets to make their own decision if their family members share their personal information.

FLG: I think it’s a really exciting time for genomics, particularly with all the research projects that are emerging and ongoing. Is there anything in the field that you’re excited about and interested in watching evolve?

Heidi Rehm: Yeah, for the last few years we’ve been focused on knowledge sharing, you know, ClinVar, and all the labs, sharing their interpreted variants. I’m now involved in the gnomAD database and getting allele frequency data out to the general community. But I think what I’m excited about now, which has been a struggle over the years, is really getting these rich resources of case level data accessible in broader environments, and the All of Us research programme is one example of that. But there’s cohorts being launched all around the world that are recruiting individuals into Biobanks and other research studies. The UK Biobank is a great example – their decision early on to make that resource accessible to the global research community has fuelled so much discovery and an understanding of human disease from that. But even now we would consider it as a small resource compared to some of the others being launched. What we really need to think about is the global collection of these biobanks and cohorts. So, I’m most excited about the potential for what we can learn by a federated network of global cohorts around the world that will just fuel another level, an exponential level, of our understanding of human health and disease.

FLG: That is definitely going to be exciting. If you were to take a look back at your career, and obviously your career still going, but are there any kind of missteps in your career that you learned from and built your character?

Heidi Rehm: Yeah, it’s a great question. I don’t think there’s any major missteps, perhaps I could have been smarter about getting more computer training early on in my career. I have a lot of software engineers and computational scientists in my team, and it does challenge me because I don’t have a really strong fundamental training in computational science and software engineering. I have to really heavily rely on the managers of those individuals to oversee those teams and to explain to me different factors, so that I can put budgets together and understand what our cloud compute costs are going to be and what are the best technical solutions. So, maybe if I was to go all the way back to college, instead of minoring in physiological psychology, I would have minored in computer science. That’s probably one of the only missteps that I can think about right now.

FLG: Are there any notable people throughout your career that inspired you and helped you along the way?

Heidi Rehm: I wouldn’t say there’s one single person or even a small handful of people. But lots of people along the way that I interact with that are just good people, who really taught me that doing things for financial gain doesn’t necessarily bring you more happiness than doing things for the good of society. I think watching the excitement in my scientific mentors. My own parents, and their incredibly strong work ethic that I learned from as a child and continued throughout my career. I think there are people along the way that I observed, and I thought were role models for showing me the joy that you can have from just building things that are useful for the community, and the joy you can have from just being part of teams that are doing really amazing stuff. I wouldn’t say that there are particular people that were that critically instrumental, but just in general, my interactions with so many different people that showed me the joys of what could be accomplished.

FLG: Outside of your career, what do you like to do in your spare time?

Heidi Rehm: In terms of the personal side of me, so of course I have two amazing children, who I spend as much time as I can (as they will allow me to) watching them grow and develop. But beyond my own children and my husband, I also enjoy lots of stuff outdoors. I ran a mountain club in graduate school for a number of years and we did backpacking, canoeing and mountain biking, wilderness first aid. Lots of trips that we went on. I still do to this day – we camp every year, sleeping in tents, and using outhouses, and so on. So, I love the outdoors. I also play Ultimate Frisbee, my husband and I both play. Unfortunately, the season got cancelled due to the pandemic last year, but we’re hoping this year to be able to get back in the groove of playing, that’s one of my sort of side hobbies. In addition, just in general, trying to spend as much time outside riding my bike or hiking in the woods, those sorts of things.

FLG: Who’s better at Ultimate Frisbee, you or your husband?

Heidi Rehm: It was actually my husband, who introduced me to the sport when we were in graduate school. Right after we got married, his team needed some extra women – it is largely a co-ed sport and they needed women. I’d never played before but had experience in field sports, so I joined their team. It was called Sudden Death, and I played with them, and they were some of the most amazing Ultimate Frisbee players. They were part of the group that started the sport in the 70s, so I learned from some of the best players. I actually even continued after my husband sort of left frisbee playing for competitive cycling for a while. I continued playing on my own on various teams in the Boston area as a club sport. Then eventually, my husband came back after he gave up competitive cycling for the most part, and he joined the team that I’m on today called Toads. So, we’re a club team in the Boston area and I continue to play with them, as does my husband.

FLG: I only recently realised how competitive Ultimate Frisbee is.

Heidi Rehm: Yeah, it’s a huge sport and can be incredibly competitive. Actually, an interesting story was that my boss at the Harvard partner Center for Genetics and Genomics, Raju Kucherlapati, his son was an ultimate frisbee player. And Raju and his son started the professional league in the US and ran that league for a while. David, his son, and I actually played frisbee within some of the pick-up leagues in the winter when we were just keeping ourselves active over the winter season.

FLG: All these scientists seem to be really good at Frisbee! This is a bit of a silly question to end on, but if you could turn your life and career into an autobiography or a film, what would the title be? I have thought of one for you during this as well.

Heidi Rehm: It’s good that you might have come up with one because this is a hard question. You know something silly like “teamwork makes the dream work” or something.

FLG: I was thinking something along the lines of like “many hats” or something like that. You said that you wear many different hats and I think that’d be kind of cool.

Heidi Rehm: Yeah, that would be a good one. I definitely wear a lot of hats throughout my career and the different jobs I do today. So that’s a good one, I like that one.

FLG: Thank you so much for joining me today Heidi. It’s been really interesting and also inspiring just to listen to you. Especially you having a child and going back to work so early!

Heidi Rehm: Not the advice I give to my young female pregnant members of my team, come back after five days is not the best work life balance advice. But you know, I learned from my mistakes along the way as well.

FLG: Thank you so much. It’s been great.

Heidi Rehm: Well, it’s been a pleasure to speak with you.