San Diego, CA—A day after the billionaire philanthropist—and the world’s fifth-richest person—divulged his hesitancy to donate his fortune to climate change, Bill Gates spoke at the Illumina Genomics Forum (IGF) as an exponent for biotechnological progress, notably in the arena of disease, both non-communicative or infectious. Gates is putting his money where his mouth is, having recently stated that he plans to give virtually all of his wealth to the Bill and Melinda Gates Foundation.

Kicking off the third day of the IGF, the Microsoft co-founder and philanthropist offered his take on the future of global health, focusing mainly on a pathway to end the cycle of panic and neglect with permanent infrastructure for pathogen preparedness, and fielded a few questions from Cande Rogert, vice president of scientific research at Illumina.

Pathogen surveillance progress requires genomics

“We don’t want another pandemic,” Gates said. “It’s 20 million lives, $20 trillion dollars, huge deficits, learning loss, mental stress. We are going to be digging our way out of this for a long time. The only way we are going to get back on track is a combination of better tools, where genomic plays a big role, and better targeting, where surveillance enabled by genomics plays a big role.”

But pathogen surveillance capabilities, according to Gates, are still somewhat limited Advocating for sequencing regularly, he pointed to the value that sequencing sewage has had throughout the pandemic and even before. “We’ve been using [sewage sequencing] for decades for polio, and it works for cholera,” said Gates. “Amazingly, you wouldn’t think it would necessarily work for a respiratory virus, but in the case of COVID, it gives you the best, almost real-time signal—not just prevalence in your community but also a sense of what the various variants are.”

For another example, Gates spoke about the Seattle Flu Study, which, by using samples of respiratory systems, is trying to characterize the populations of various respiratory viruses and discern how those are spread, which is important for quarantine techniques. But these studies can’t just be a one-off, suggesting we need ongoing respiratory surveillance.

At the heart of all this work on respiratory disease transmission and bioterrorism surveillance lies genomics. “Having genomics data about respiratory disease transmission will help identify the initial outbreak and warn people,” said Gates. “The actions you take at the very beginning make a huge difference because otherwise, you get exponential growth and geographic spread. Those tools are getting to the point where it will eventually be common sense to come up with countermeasures.”

With so much open source information being put out, Gates thinks we will be able to have genomic libraries of pathogens that improve our ability to intervene, whether with antivirals or antibodies.

“Genomics is how we get the information, understand what these antibody populations, what does this breakthrough look like, and feeding that into these shape space tools that will only get better after the pandemic,” said Gates. “The gene sequence is the basic starting point that we have to have both the non-pharmaceutical interventions but also the starting line of building the interventions.”

Genomics was critical for work that gave rise to the SARS-CoV-2 vaccine and ongoing pharmaceutical disease measures, such as developing proteins to block viral transmission. Although today’s vaccines have saved countless lives, Gates thinks that we still have a long way to go to produce the ideal vaccine. “They don’t protect for decades or block infection, and they’re not universal in the sense of taking the entire coronavirus family in creating antibodies that broadly protect,” said Gates.

To this point, he discussed the potential of mapping proteins and protein shapes with programs like RoseTTAFold and AlphaFold2 for drug design, as well as a project at the Institute for Protein Design at the University of Washington School of Medicine working on the breadth of vaccine protection.

Nixing malnutrition with NGS

In addition to developing new tools and strategies to reduce the burden of infectious disease, Gates spoke about another leading cause of child mortality in developing countries —nutrition. To exemplify our lack of understanding of the topic, he noted that even if twins get the same diet, one of the twins will have stunting and never fully develop mentally and physically. This research can potentially have a tremendous impact, as over 30% of African children develop into adults with malnutrition. By looking at the microbiome of infants, we can sense what good gut health looks like.

But Gates says we are gaining understanding by looking into the microbiome and understanding the complex interactions between the immune system and this microbiome. “Understanding these bacteria, it’s something we’ve been blind to,” said Gates. “There are trillions of microorganisms living inside of us, and [we’re just beginning to get a] statistical sense of which ones are associated with good outcomes and which ones are associated with inflammation and bad outcomes. We couldn’t do this without cheap sequencing.”

The Bill and Melinda Gates Foundation is doing nutrition interventions to give kids foods that encourage the good part of the microbiome and discourage the bad part. “That is very promising because, in the case of nutrition, we’re seeing that these interventions could be very cheap,” said Gates.

Equitable access to genomics

The conversation’s final segment pertained to the importance of equitable genomics. “You do need to make sure, as we’re going about all this genomic work, we’re doing it in an equitable way,” said Gates. While Gates has advised his friends to get the $950 Galleri test —a blood test that can detect 50 different types of cancer from the lab Grail, which is owned by Illumina—the Bill and Melinda Gates Foundation does not prioritize developing novel therapies for cancer and genetic illnesses that can cost patients hundreds of thousands or even millions of dollars.

Instead, Gates is focused on making sequencing equitable across the globe. During the pandemic early on, most of the viral sequencing was done in rich countries. So, there was a lack of understanding of exactly what was happening in Africa. Gates says that understanding the variants coming out of Africa has importance beyond the continent and helps the world know what’s going on. This inequity is further affected by the limited existing genomics data on Africans.

“First, [the African] genetic background is more diverse than any other population,” said Gates. “In terms of understanding and dealing with their particular health challenges, we need to do better in getting that information to the databases, which today are only about 1% of the information. So, equity’s got to guide what we’re doing here. That’s where our foundation has a priority—finding exactly where those gaps are and finding the right partners to solve those things.”

Gates closed his talk on the duality of many of these global health issues. “The current health circumstances post-pandemic are not what we want them to be, but on the other hand, we have this innovation, much of it underpinned by genomics. So, I’m very excited about how we can take that capability and use it for traumatic improvements in human health all over the world.”

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