Democratizing and Diversifying Access to Genetic Testing
The world of diagnostics, and genetic testing in particular, has changed enormously over the last two decades. Genetic testing and even sequencing are becoming cheaper and easier to access for patients, and options such as newborn sequencing can cut the time and costs of the diagnostic odyssey for children with rare diseases dramatically.
Madhuri Hegde, senior vice president and chief scientific officer at PerkinElmer Genomics, has seen these changes happen during her career and is now working to improve the quality of genetic testing and sequencing around the world, as well as to diversify the genetic information used to make important decisions in medical genetics.
Beginning her academic education in India at the University of Mumbai, Hegde then went to New Zealand to do a PhD in applied biology and genetics at the University of Auckland. After working for a number of years as a laboratory director at Auckland City Hospital, she moved to the U.S. and began an academic career as a postdoc at Baylor College of Medicine and subsequently Emory University.
In 2016, Hegde took up her position at PerkinElmer Genomics, a part of the wider PerkinElmer company that runs as a standalone business with labs in the U.S., Europe, China, and India. She spoke to Inside Precision Medicine senior editor Helen Albert about her inspirations, lessons learned from developing and carrying out genetic tests in many countries, and insights from her career as an academic and industry scientist.
What made you decide to make the move from academia to PerkinElmer?
When I came to Emory, I had my research lab in the department of human genetics, but I was also running the Emory Genetics Laboratory. Although it is an academic genetic testing laboratory, it was really competing in the industry with the likes of Athena Diagnostics and other labs. It really was the number one or two lab in the country at that time and we used to receive samples from all over the world.
Right around the time when I came to PerkinElmer was a time when genome sequencing was starting to become more and more prominent. The Emory Genetics Laboratory was one of the first labs to bring next-generation sequencing to clinical testing and it is also contracted by the state for second-year confirmatory testing for newborn screening.
PerkinElmer was the global leader for newborn screening …. It also had local labs in many countries. So, instead of receiving samples, I now had the opportunity to run labs in different countries. A different kind of experience, and that’s why I jumped at it.
What have you achieved at PerkinElmer Genomics so far?
We have been able to deliver genomic testing quite effectively, globally, with the awareness that needs to come around genetic testing. I just recently came back from India, presenting at the Indian Academy of Medical Genetics. I’m originally from India and it’s amazing. India has come a long way. Having a local lab there and delivering those services there has been one of my achievements.
The other important thing is bringing in genome sequencing [for newborns]. We are now the … lab, even in the U.S., to have done the largest number of clinical whole genome sequencing cases. The reason I highlight that is because today most insurance is not paying for whole genome sequencing. Very few insurance companies actually pay for it, but the impact of genome sequencing is so big.
It’s not just that you can sequence once, interrogate often. You get so much data to look at and to get answers for families. We had cases where so much serial testing was done before whole genome sequencing was attempted and if we had done that first, as a first-year test, so many dollars would have been saved.
When I came here, we started clinical whole genome sequencing, meaning a baby’s sick and testing to find the answer. At birth, a family or the parents of a healthy newborn can also choose to get the baby’s genome sequenced.
PerkinElmer is able to extract DNA from a dried blood spot (DBS) card. All 4 million babies born in the U.S. get newborn screening through a heel prick test. When the baby’s born, a DBS card is spotted. The DBS card … is sent to our lab in Pittsburgh for genome sequencing.
It is not a direct-to-consumer service; it is a physician order with pre- and post-test counselling. We have done about 600 babies now. There are a lot of funded studies, but this is the first cohort where a family has actually paid for healthy newborn genome sequencing.
Why is it important for PerkinElmer Genomics to be present in different countries?
We have labs in the U.S., U.K., Sweden, China, and India, so you can see that the spread is really good. Each country has its own regulations; we think about it like it’s “in country, for country.” The way genetic testing is done in India, versus the way we approach genetic testing in the U.S. is so different. And that’s why this having this local footprint is absolutely critical.
The rules for prenatal testing in general are very different between the U.S., India, and China. Many families, even if we give a report back saying that the baby has a defect in a gene, decide to continue with the pregnancy. Whether in India or the U.S., it doesn’t matter, but the impact of the care that is needed around it, the awareness of a particular genetic disorder, is completely different.
If it is in India, we’ll get request for free testing, because the family is trying to make a decision. In the U.S., it is largely dominated by insurance, but in India, they’re paying out of pocket. Cost considerations are so different between India and the U.S. Deciding whether to do the test or not, are there religious considerations? After doing the testing, the socio-economic considerations around what to do with the pregnancy, and then who’s going to pay for it?
I know there’s a big problem with not having enough diversity in genetic databases. Are you collecting useful data to help with this from your labs in India and China?
Having those two labs in India and China has helped variant interpretation for our U.S. lab, because the human population is not homogeneous. We all know that. Because we’re drawing data from different populations and local populations, all anonymized data, when it comes to me as a lab director doing analysis, I can actually do interpretation better.
We are actively submitting to the ClinVar database www.ncbi.nlm.nih.gov/clinvar. We have not finished, because you can only imagine how many variants we have collected now. But we are doing it in batches. We started submitting in 2021. In each batch, thousands of variants are getting uploaded. Our plan is to be up to date with all our submissions by the end of this year.
Is precision medicine changing the way you work?
We are now going from genomics to more omics-based testing, and that’s where precision medicine comes in. This is not just about doing diagnostics, or finding an answer, but actually taking a step forward in biomarker identification and testing for biomarkers.
A good part of our work in our U.S. lab, and actually a little bit in India as well, is working with the pharmaceutical industry for clinical trials and to sponsor testing programs to find rare disease patients. For example, the Lantern Project
Pompe disease is included in newborn screening, but there is a type of Pompe disease which is late onset. It goes undiagnosed for several decades till the time individuals have issues. We help identify these patients.
Once you identify the patient, they’re obviously going to go on the enzyme replacement therapy, but then you need to monitor their enzyme levels. So, we do enzyme testing as well. This is all from a DBS card. We do the genetic testing, the next-generation sequencing assay, and the same DBS card can be used for enzyme testing.
A lot of labs do sponsor testing programs for pharmaceutical industry. But what they do not have is this full-circle “closing the loop,” where we don’t just do genetic testing, but we then track the biomarkers. In precision medicine, you have to go from diagnosis to treatment, and then track whether the treatment is effective or not.
What new trends or technologies do you think we will see in this area in the next couple of years?
We are working with genetic therapies and looking at the efficacy of different technologies, such as CRISPR-Cas9. We have a number of contracts with the pharma industry to not only develop assays to monitor efficacy, but also help generate evidence for tracking something like CRISPR-Cas9. We are starting to put together some protocols around it. It’s still early days, but there’s a lot of conversations that are happening.
We will definitely make the shift from just doing genomics, and by that, I mean genome sequencing or any kind of sequencing, to omics-based technologies. I think we are going to see a shift towards, or an “ask” from physicians, to close the loop. Not just for diagnosis, but labs actively participating in monitoring and demonstrating the efficacy or the advantages of precision medicine.
I think long-read sequencing is something which is gaining more and more importance, we are going to definitely make that shift from short read to long read. That is happening quite actively right now. If you actually account for all the dollars that go into this step by step, we know that our diagnostic yield today sits around 30 to 40% [with short read sequencing]. PacBio or any long read technology is going to add about 12% more to that. If you actually do the dollar calculation, I think doing long read as the first step makes a lot more sense to me, even though it is expensive. Because overall, there’s a tremendous saving. You can also go back to the data.
What have been your biggest learning experiences at PerkinElmer?
I think one of the things I learned, coming from academia to industry, is that you collaborate in a different way. In academia, you are actively reaching out across different institutions to move science forward. Within industry, and because you’re working within a company, you have to actively collaborate and reach out internally. In a company as big as PerkinElmer, there is so much work going on, and collaboration is the key. As a lab, we sit in a very different position, because we are kind of the customer for PerkinElmer as well as a developer. We use the products, but we also serve as a testing ground before getting a product out.
Sitting in academia, there’s always this impression that when different companies are coming to you, you’re evaluating the product, asking, “Is this the best product for me?” And then we always look at it with some sort of suspicion. I now know that there is so much effort and thought put into getting a product together and then releasing it. I have learned to appreciate that a lot more. There is significant science happening in the industry.
There’s been a lot of talk about not having enough women in biotech and pharma, particularly at senior levels. What is your position on this topic? Do you think things need to improve?
I think I’ve been very lucky in my life. I would say in my career that I have had the right mentors at the right time. Even growing up in India, I was never raised to think of myself on a gender basis. My parents always said, “Go and do what you want to do.” I come from a family like that. So, I think like that too.
I think it’s two things [that] are really important. Talent has to be there. That is absolutely critical, whether it’s a woman or a man. The second thing is that, being a woman and being a mother, I know what I had to go through to come to where I am. Support mechanisms are absolutely critical. For my fellow women who are in similar positions, or getting into this career path, support mechanisms are essential. Be it by the institution, or the company, but putting that infrastructure around it is critical to help them get to that level.
I think it’s about changing the culture. How we all think about it, and also influencing the culture. It’s easy to say, “Oh, my company needs to change the culture.” But I have to actively participate in it. I have to be that agent of change as well. It’s okay to say it, but it’s different to participate in it. It starts at the ground level. If I don’t support my staff and give them the infrastructure that is needed, then it’s one thing to say it, but implementation is not going to go anywhere.
What are you doing to help support your staff?
Within PerkinElmer, and within PerkinElmer Genomics, we have created a support system for each other. To give the freedom to work the way you want to work. Look at the deliverables, and meeting those deliverables, instead of working within a frame of time.
Just as an example of how this communication goes, we have a junior genetic counsellor in India. She was getting marriage proposals. In India, there’s a lot of arranged marriages. She just wanted to reach out and talk to me about how to manage this, because she’s very career oriented.
It is about being there for them and actively participating and giving them advice. Just within PerkinElmer Genomics, we do also have a small group where we really talk about how we can support staff, and what support is actually needed, because everybody has a different situation.
What advice would you give yourself if you could go back in time to when you started your career?
I would say, because I grew up in India, you have to think about it a little bit differently; the opportunities at that time were so limited. I think I did a good job at looking around. But if I could, I would explore more and spend a little bit more time learning. The culture in India is such that you get sort of locked into becoming something, or taking a career path, so early on. I wish I had taken some time to breathe and learn more. Obviously, we are all learning through our lifetime, but there is a time in your life, before you get responsibilities, to do that more, and I wish I had done that.
Helen Albert is senior editor at Inside Precision Medicine and a freelance science journalist. Prior to going freelance, she was editor-in-chief at Labiotech, an English-language, digital publication based in Berlin focusing on the European biotech industry. Before moving to Germany, she worked at a range of different science- and health-focused publications in London. She was editor of The Biochemist magazine and blog, but also worked as a senior reporter at Springer Nature’s medwireNews for a number of years, as well as freelancing for various international publications. She has written for New Scientist, Chemistry World, Biodesigned, The BMJ, Forbes, Science Business, Cosmos magazine, and GEN. Helen has academic degrees in genetics and anthropology, and also spent some time early in her career working at The Wellcome Sanger Institute in Cambridge before deciding to move into journalism.