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Genetics and AI

My message to America’s top scientists

How two technologies can benefit the world’s poorest.

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People often ask me which technologies have the most potential to change our lives in the decades ahead.

AI is always near the top of the list. It can help us make sense of complex biological systems—like the microbiome in the human gut—and give us new insight into tough problems in global health, such as premature birth.

Gene-based tools are another technology that I always mention. For example, advances in that field are giving researchers powerful new tools to investigate potential cures for AIDS, sickle-cell disease, and other conditions.

These tools can also give us key insights into new diseases, such as the novel coronavirus that recently emerged, so that we can develop diagnostic tests, treatments, and vaccines faster.

Thanks to these and other breakthroughs, science is giving us the opportunity to improve lives more rapidly than ever. But we’ll only make the most of that potential if we ensure that these tools reach everyone who needs them, including the poorest people in the world.

That’s the focus of much of our work at the Gates Foundation. Today I’m honored to be giving a speech on this subject at the annual meeting of the American Association for the Advancement of Science. Here’s what I plan to say:

Remarks as prepared
Seattle, WA
February 14, 2020
American Association for the Advancement of Science

Thank you. It’s great to be here today.

The Coronavirus

I want to take a few minutes to talk about the novel coronavirus, which I know is on everyone’s mind.

Our foundation has committed up to $100 million to address this new coronavirus because we believe it poses a serious threat to global health. This money will support efforts to detect, isolate, and treat confirmed cases, help countries in sub-Saharan Africa and South Asia take steps to prepare for the epidemic and protect their most vulnerable citizens, and accelerate the development of vaccines, treatments, and diagnostics.

We believe that multilateral organizations and national governments must make every effort to stop this outbreak, but we also want to help the world be better prepared if it becomes a global pandemic. Above all, we believe that the world will need to be guided by science, not fear, in the weeks ahead.

The Diseases of Poverty

A few blocks from here is the foundation that Melinda and I started in 2000. When we decided to focus on philanthropy, we knew that the core of our work would be eliminating the gross inequities in health that we had seen a few years earlier on our first trip to Africa.

One area where we believed we could make a difference was investing in R&D to address diseases of poverty. Today, I want to talk about several exciting and important tools of modern science that have the potential to help us solve some of the biggest health problems—not only in low- and middle-income countries, but everywhere.

To be sure, health in lower-income countries has improved. Over the last 25 years, we’ve nearly eradicated polio. Child mortality has been cut in half. And we’ve significantly reduced deaths from HIV, TB, and malaria.

But there is still room for a lot more improvement.

This year, more than 5 million children under the age of five will die. HIV, TB, malaria, and other diseases still kill millions of people every year. And nearly a quarter of a billion children are malnourished. Almost all of this disease burden is carried by people in the poorest countries on the planet.

Innovation with Equity in Mind

To make further inroads against the diseases of poverty, we need every sector to engage. Governments need to continue funding of basic research; partners like our foundation need to nurture the best ideas through discovery and translation; and the private sector needs to develop solutions that are commercially viable, affordable, and scalable in countries with limited resources and fragile health care systems.

The private sector has much to gain from pursuing breakthroughs that benefit people in lower-income countries. Over the next few decades, developing economies will continue to expand. By 2050, the population of sub-Saharan Africa will more than double to almost 2.5 billion. That’s more than twice the forecasted population of the Europe and North America combined.

Yet, today, the overwhelming percentage of investments in health R&D reflect market opportunities in rich countries. If we stick to this model, market forces will continue to prioritize development of costly products designed to meet the needs of the few and unaffordable to most. Imagine if we turned this traditional market model on its head and committed to designing new vaccines, therapeutics, and diagnostics with equity in mind.

Today, we have an opportunity with the evolution of tools like AI and gene-based technologies to develop a new generation of health solutions that can benefit everyone, everywhere. This is what really excites me about the future.

The Potential of AI and Gene Therapy

As a 7th grader at the Lakeside School here in Seattle, I became fascinated not only with computers, but also with Shakey, the Mobile RobotLife Magazine called Shakey the “first electronic person.” That might have been overstating it a bit, but Shakey was an early example of how artificial intelligence could be applied. It had a limited ability to perceive objects in its environment and adapt its movement. It could plan simple travel routes, and it had the ability to rearrange simple objects. For its time, Shakey was really cool.

Since Alan Turing laid the groundwork for artificial intelligence in 1950, AI has gone through a kind of boom-and-bust cycle—enthusiasm would grow and then expectations weren’t met.

But we are finally beginning to realize the potential of AI. The computational power available for AI applications is doubling every three and half months—far surpassing the historical metric of Moore’s Law. This processing capability is being coupled with troves of new data, and we are learning to annotate this data in smarter ways. That’s enabling us to realize some of the promises of AI: the ability to synthesize, analyze, see patterns, gain insights, and make predictions across many, many more dimensions than a human can comprehend.

This data revolution will apply to virtually all of the disciplines represented here today. What I’m most excited about is how it can help us make sense of complex biological systems and accelerate the discovery of therapeutics to improve health in the poorest countries.

And, with recent breakthroughs in gene-editing technologies like CRISPR, we are on the verge of a new era of precision diagnostics, therapeutics, and vaccines that has the potential to improve health—not only for rare genetic disorders, but also for diseases that predominately afflict people in poor countries.

It’s amazing to think how far we’ve come since Crick, Watson, and Franklin laid the foundation for modern genetics. It was only 15 years ago that the Human Genome Project gave us the ability to read our DNA and identify specific sequences that cause or contribute to disease. It was only 8 years ago that CRISPR gave us the ability to edit DNA precisely.

Now, with the latest CRISPR gene-editing approaches, it’s believed that up to 89% of genetic variants known to be associated with human disease can be corrected.

Last year, researchers began using the molecular scissors of CRISPR in clinical trials to remove, edit, and inject people’s cells back into their bodies.

In short, artificial intelligence and CRISPR have emerged as powerful tools with the potential to revolutionize healthcare and many other fields.

The Product Pipeline for Global Health

I’d like to share a few examples of innovations in the pipeline that make me optimistic about the future.

Our foundation is working with the National Institutes of Health to develop affordable, gene-based cures for sickle cell disease and HIV. The goal is to move these solutions into clinical trials in the next 7-10 years. This would be a huge breakthrough.

Of the 38 million people worldwide living with HIV, 95 percent live in lower-income countries and one-third aren’t receiving treatment. Imagine if we could cure every one of them.

Sickle Cell Disease is also a major health burden in lower-income countries. Fifteen million babies will be born with sickle cell disease in the next 30 years, the vast majority in Africa. Although exact numbers are hard to come by, at least half and maybe as many as 90% of these children will die before their fifth birthday.

In recent years, we’ve seen gene-based therapies introduced for some rare genetic diseases as well as for sickle cell disease. Ongoing trials are promising, with early results showing clinical benefit to more than a dozen people with sickle cell disease. But the treatments are prohibitively expensive—likely to cost $1 million or more per person.

And they require highly trained doctors and state-of-the-art hospitals to administer the cures—which involve in vitro editing of bone marrow stem cells for reinfusion, and toxic bone marrow conditioning regimens.

The focus of our work with the NIH on sickle cell disease is to develop effective, durable, safe, and affordable gene-based cures that don’t require costly hospital stays.

We hope to create in vivo gene editing techniques that can be delivered with a single injection using vectors that target and edit blood-forming cells in the bone marrow—with high efficiency. This approach could reach millions of patients in primary care facilities at a fraction of the cost.

Similarly, with HIV, the purpose of our collaboration with the NIH is to investigate the use of in vivo gene editing and other technologies that could drive a functional cure for those infected with HIV in an affordable, scalable way. A high bar, for sure, but it’s the kind of bold approach to designing therapeutic innovation with equity in mind that excites me.

Gene editing shows great promise for our work in malaria, too. The world has made huge progress against malaria in the past two decades. Since 2000, deaths have dropped from about 1 million per year to 400,000 per year. But further progress requires new tools and strategies.

Researchers are exploring the use of CRISPR to create “gene drives” that suppress the handful of mosquito species most responsible for malaria transmission. They are also working on introducing genes that could eliminate the parasites as they pass through a mosquito’s gut on their way to its salivary glands.

Newborn Health

One area where I see great potential for progress is newborn health. As you’ll see on this chart, nearly half of the 5.3 million children under age 5 who die this year will die in the first 28 days of life.

Deaths from complications associated with premature births account for the single largest percentage of neonatal mortality. The reason the number of deaths is so high is that there is still so much we don’t know about the root causes of prematurity and neonatal mortality. We are funding several studies to help solve this mystery.

First, by applying artificial intelligence to a range of complex data sets, we are learning about the biological pathways leading to prematurity and low birth weight.

Second, we’re combining clinical data with information from low-cost devices like a hand-held ultrasound and wearable sensors—and using AI to identify indicators that a pregnant woman may be at risk of giving birth before full term. We can do something similar to look for signs that newborns may be in trouble.

Third, researchers are exploring the associations between maternal undernutrition, the maternal microbiome, and premature birth. By distinguishing abnormal changes in the microbiome during pregnancy, we may be able to give pregnant women microbial therapeutics—as well as nutritional interventions—to improve fetal growth and reduce the risk of pre-term birth.

The Microbiome

It is increasingly clear that the gut microbiome and nutrition—and the interplay between the two—are also big factors in child health and development.

An estimated 225 million children worldwide are severely malnourished—and malnutrition is an underlying cause of more than 40 percent of under-five child mortality. Children who are malnourished often have underdeveloped microbiomes that make them more vulnerable to disease and to cognitive impairments that last a lifetime.

There is also evidence that children in wealthy countries who grow up in super-hygienic environments – with an abundance of processed foods and antibiotics—have poor gut health that may make them more susceptible to obesity, diabetes, allergies, and maybe even auto-immune disease.

But there’s still a lot we don’t know about the microbiome—including which bacterial species are most critical for health and whether augmenting these species can reduce malnutrition. Deciphering the human microbiome is not an easy task. It contains more than 100 trillion organisms and 200 times more genetic material than the human genome.

Using artificial intelligence, scientists hope to analyze the composition of the trillions of microbes in our body and identify the patterns, interactions, and changes we can't see that indicate a higher risk of disease—or, conversely—a protective shield against disease.

One tool that’s helping us understand how to optimize the gut microbiome is technology called “organs-on-a-chip.” In simple terms, this technology allows in vitro modeling of human organs in ways that mimic how organs perform normally . . . and when they are diseased.

Linking different organ chips together—for example, intestine, liver, and kidney chips—can enable researchers to model human drug kinetics.

Culturing a human intestinal microbiome-on-a-chip can enable researchers to probe the complex interactions between microbiome, host, nutrients, and pathogens in a systematic way.

Researchers are using this technology to study the vaginal microbiome and therapeutics that could reduce the incidence of pre-term birth and risk of HIV infection. We’re also supporting other “organ-on-a-chip” studies, including one that’s using lymphoid organoids to understand vaccine responses.

This technology has the potential to shave years off the time it takes to evaluate the safety and efficacy of new drugs, vaccines, and other therapeutics—and save hundreds of millions of dollars associated with research and clinical trials.

Climate Change and Agricultural Adaptation

I’ve been talking about the innovation we need to build on recent progress in global health. Many people are surprised when I say that progress in global health also depends on the fight against climate change.

There are two parts to addressing climate change. Mitigation and adaptation. Mitigation is about what we need to do to get to zero on greenhouse gases that are warming the climate.

Adaptation is about helping people cope with the changing climate. It’s unfortunate, but true, that the people who are most affected by climate change today account for a tiny amount of the world’s greenhouse gasses. Specifically, the 2 billion smallholder farmers and their families who rely on the food they grow to survive.

Increasingly, climate change is putting their livelihoods—and their lives—at risk. More extreme weather conditions mean more floods, more droughts, and more plant pests and diseases that can wipe out a crop.

When smallholder farmers lose their harvest, their kids may not have enough to eat and that makes them susceptible to the effects of malnutrition.

To adapt, farming families need seeds and livestock that have been bred to thrive in the more extreme conditions caused by climate change.

The world’s largest agriculture research group, CGIAR, has developed dozens of new varieties of maize and rice that can withstand drought—including one called “scuba” rice that can survive for two weeks under floodwaters.

A team of scientists led from the University of Cambridge is using evolutionary genomics to help maize and other cereals partner more effectively with microorganisms in the soil to capture nutrients and water.

For farmers with poor soils and no access to fertilizer, this process could supply the nitrogen needed to increase production. That’s good for food security, farmers’ livelihoods, and the environment.

Conclusion

Earlier this week, Melinda and I released our 2020 annual letter. It’s something we’ve done every year for the last 10 years. This year, we reflected on the progress in global health since we started our foundation 20 years ago and the challenges that remain. And we talk about where things stand with the primary focus of our work in the US—improving K-12 and postsecondary education.

These issues share one very important feature in common. They are both key to a healthier, better, and more equal world. Disease is both a symptom and a cause of inequality, while public education is a driver of equality.

When we first started our foundation, we were optimistic about the power of innovation to drive progress. Looking at progress in global health over the last two decades and the amazing advances I talked about today, I’m more optimistic than ever that we are closer to the goal of giving every person the opportunity to live a healthy, productive life. Thank you.

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