Dr. Jonathan D. Glinstein (Internal precision medicine) We will be interviewing Galatea’s bio CEO and Venezuelan-born founder Carlos Bustamante (Stanford University School of Medicine). He explains how a 10 million genome biobank can guide Latin America’s drug development and treatment.
[Jonathan D. Grinstein, PhD, the North American Editor of Inside Precision Medicine (IPM), hosts a new series called Behind the Breakthroughs that features the people shaping the future of medicine. With each episode, Jonathan gives listeners access to their motivational tales and visions for this emerging, game-changing field.]
Imagine a future in which your ancestors not only tell stories about your past, but also hold the keys to your health. It is a vision that drives Dr. Carlos D. Bustamante, a population geneticist and the founder of Galatea Bio. He embarks on an ambitious mission. Building a 10 million genome biobank to transform drug development and healthcare across Latin America.
Latin America is a gold mine of genetic diversity, as thousands of founders are scattered throughout the region, from the Valley of Medellin to the Caribbean islands. But up until now, it has been largely overlooked in genomic studies. Behind the breakthrough episode, Bustamante explains why mapping this diversity reveals genetic insights that lead to better treatment of diseases that disproportionately affect these communities. [. . .]
IPM: What motivates you to establish a bio of Galatea and create a new biobank?
Bustamante: We will inform you of observations regarding EGFR mutations in lung cancer. This means that Asian populations have more EGFR-positive lung cancer than the European population. Why does that happen? It could be environmental or fundamental genetics. I don’t know yet. How do you start thinking about that issue and on the way to develop new drugs?
The opportunity to learn something new in a biobank that has not yet been sequenced is higher than that already sequenced with a genotype. If you build it, you may have the opportunity to learn new things due to these differences in population prevalence.
We started in Latin America for two reasons. One is that we have a great belief in the founder group. In the United States, there are over 1,000 founders. [Latin America] Many islands include Puerto Rico, the Dominican Republic, Cuba and fewer Antilles. Then there are islands between the mountains, as each of those valleys is a separate island. If you’re thinking about the people of Paisa around Medellin, Colombia. In that case, they know it from a population perspective, as they have a different set of genetic founders’ alleles than the coastal population of Balanquila and Kali.
So, how do you use it to make discoveries on a large scale? We set bold goals to really move the needle, and said it would be interesting if you reached an interesting case of 100,000 people because of these bundles of chronic diseases. Still, there are only 100,000 random controls – many such others. So we need a lot of cases. If you reach a large group, 10 million people can mix case and controls, and you can also find some of these protective alleles.
Ultimately, you want to build a pharma consortium that can get traction and take on this sequence, so we work closely with instrument manufacturers to figure out how to do it. In the US, there is also a global range of functional insurance-based clinical genetic testing. If there is a risk of breast cancer in this country for genetic reasons, it can be covered. It is either covered by one of the state-funded insurances, such as Medicare or Medicaid, or covered by private insurance. [. . .]
What did you learn from people who came before you in “DNA business” like IPM: 23andme?
Bustamante: Given my roots as a corporate researcher and advisor, I always remember the differences between research and clinical. It sometimes blurs people’s minds. But in general, we tend to have a fairly clear line when you’re talking about research, or when you’re talking about clinical research, and you need to allow clinical testing on a scale that identifies people at risk based on authentic and well-understood science and public health. It has accumulated over time.
If someone is looking at a doctor who believes that a condition may have a genetic origin, or if they think understanding genetics can improve management, order a genetic test. [. . .] Data is more sensitive, so I try to be thoughtful by getting an IRB and being taught what data should and shouldn’t be. [. . .]
I think there should be a market where you can take off your Galatea biohat, wear your fellow citizens’ hats, and have a variety of products available. I was very excited to help my ancestral DNA start my DNA business. They discovered that some people like genealogy and would like to spend their time learning it online. We discovered that DNA is a useful tool in that regard. [. . .]
IPM: What about population genetics that keeps you so fascinated?
Bustamante: Population genetics provided us with a theoretical framework for understanding genetic data. Without population genetics, we cannot do many gene mappings that have led to a genuine understanding of the genetic basis of disease. That’s not the case in other areas. There is no true theory of gene expression that gives a null hypothesis to compare some. But that is very different from population genetics. Here is authentic mathematics that drives evidence of choice, movement, mutations and all of its understanding, coordination, and imbalance. So, for a long time, it’s beautiful science that has been merely a theory until we have data. That was very appealing to me. [. . .]
See for the full interview https://www.insideprecisionmedicine.com/multimedia/podcasts/behind-the-breakthroughs/from-medellin-to-caribbean-latin-american-diversity/
