Shattuck Lecture Innovation for Pandemics

Bill Gates
Boston, Massachusetts
April 27, 2018
AS PREPARED

Thank you, Dr. Drazen, for that kind introduction. It’s an honor to be invited to deliver the Shattuck Lecture.

Most of the speeches I give on global health are about the incredible progress and exciting new tools that are helping the world reduce child mortality and tackle infectious diseases. Thanks to better immunization and other interventions, child mortality has been reduced by more than 50 percent since 1990. We are on the verge of eradicating polio. HIV is no longer a certain death sentence. And half the world is now malaria-free.

So usually, I’m the super-optimist, pointing out that life keeps getting better for most people in the world.

There is one area, though, where the world isn’t making much progress, and that’s pandemic preparedness. This should concern us all, because if history has taught us anything, it’s that there will be another deadly global pandemic.

We can’t predict when. But given the continual emergence of new pathogens, the increasing risk of a bioterror attack, and how connected our world is through air travel, there is a significant probability of a large and lethal, modern-day pandemic occurring in our lifetimes.

Watching Hollywood thrillers, you’d think the world was pretty good at protecting the public from deadly microorganisms. We like to believe that somewhere out there, there is a team ready to spring into action – equipped with the latest and best technologies.

Government agents like Jack Bauer in 24. Harvard professors like Robert Langdon in Inferno. And WHO epidemiologists like Dr. Leonora Orantes in Contagion – who even risked getting kidnapped as she pursued “Patient Zero.”

In the real world, though, the health infrastructure we have for normal times breaks down very rapidly during major infectious disease outbreaks. This is especially true in poor countries. But even in the U.S., our response to a pandemic or widespread bioterror attack would be insufficient.

Several things in the last decade have made me pay closer attention to the risk of future pandemics. One was the outbreak of Swine Flu in 2009. While H1N1 wasn’t as lethal as people initially feared, it showed our inability to track the spread of disease and develop new tools for public health emergencies.

The Ebola epidemic in West Africa four years ago was another wake-up call. As confirmed cases climbed, the death toll mounted, and local health systems collapsed. Again, the world was much too slow to respond.

And, as biological weapons of mass destruction become easier to create in the lab, there is an increasing risk of a bioterror attack.

What the world needs – and what our safety, if not survival, demands – is a coordinated global approach. Specifically, we need better tools, an early detection system, and a global response system.

Today, I’d like to speak with you about some of the advances in tools – vaccines, drugs, and diagnostics – that make me optimistic we can get a leg up on the next pandemic. And I’ll talk about some of the gaps we must address in preparedness and response.

Interestingly, the first Shattuck Lecture – given back in 1890 – focused on a pandemic . . . the Russian flu that struck Massachusetts the previous year. The Russian flu was not especially deadly. But it was the first flu pandemic to spread across continents connected by rail travel – and between continents connected by fast ocean liners. The virus circled the globe in just four months.

But the world was soon in for much worse. Less than 30 years later, the Boston area was one of the first places in the U.S. to feel the deadly effects of the 1918 flu. Military personnel getting off and on ships at the Commonwealth Pier – near where we are meeting today – helped carry the pathogen across the U.S. and back to the battlefields of World War I.

This animation shows how quickly the virus spread across the United States. It took five weeks and killed 675,000 people.

The death toll was so great that average life expectancy in the U.S. for that period dropped by 12 years.

Worldwide, the 1918 flu killed an estimated 50 million people, perhaps more.

We have better tools today than we did a century ago. We have a seasonal flu vaccine, although it’s not always effective, you have to get one every year, and most people in the world never get the shot. We also have antibiotics for secondary infections of bacterial pneumonia.

Despite these advances, this animated simulation by the Institute for Disease Modeling shows what would happen if a highly contagious and lethal airborne pathogen – like the 1918 flu – were to occur today.

Nearly 33 million people worldwide would die in just six months.

That’s the sobering news. The good news is that scientific advances and growing interest on the federal level, in the private sector, and among philanthropic funders makes development of a universal flu vaccine more feasible now than 10 or 20 years ago.

Our foundation is involved in a variety of research partnerships, including a collaboration between the Icahn School of Medicine at Mount Sinai, GlaxoSmithKline, and PATH.

Their work focuses on several vaccine candidates that did well in animal trials and which are now in human trials.

We are also supporting efforts by others, including the National Institute of Allergy and Infectious Diseases, whose vaccine candidate is expected to advance to human safety trials in about a year.

To broaden efforts even further, today we are launching a $12 million Grand Challenge in partnership with the Page family to accelerate the development of a universal flu vaccine. The goal is to encourage bold thinking by the world’s best scientists across disciplines, including those new to the field.

Lucy and Larry Page are also supporting efforts by the Sabin Vaccine Institute to encourage innovative approaches that eliminate the threat of a deadly flu pandemic.

However, the next threat may not be a flu at all. More than likely, it will be an unknown pathogen that we see for the first time during an outbreak, as was the case with SARS, MERS, and other recently-discovered infectious diseases.

The world took an important step last year to begin addressing this risk with the launch of a public-private partnership called the Coalition for Epidemic Preparedness Innovations (CEPI). With funding commitments of more than $630 million, CEPI’s first order of business is advancing the development of vaccines for three of the priority diseases on the WHO list for public health R&D: Lassa fever, Nipah virus, and Middle East Respiratory Syndrome.

CEPI is also working on rapid-response platforms to produce safe, effective vaccines for a range of infectious diseases – almost as quickly as new threats emerge. Later this year, CEPI will announce grants to several companies working with a variety of technologies – including nucleic acid vaccines, viral vectors, and other innovative approaches. The goal is to be able to develop, test, and release new vaccines in a matter of weeks or months, rather than years.

I’m a big fan of vaccines, but they may not be the answer when we have to respond immediately to rapidly spreading infectious disease pandemics. Not only do vaccines take time to develop and deploy; they also take at least a couple of weeks after the vaccination to generate protective immunity. So, we need to invest in other approaches like antiviral drugs and antibody therapies that can be stockpiled or rapidly manufactured to stop the spread of pandemic diseases or treat people who have been exposed.

Earlier this year, the Shionogi pharmaceutical company received approval in Japan for a new influenza anti-viral, Xofluza This single-dose drug stops flu in its tracks by inhibiting an enzyme that the virus needs to multiply.

And PrEP Biopharm, a development stage biopharmaceutical company, has demonstrated in human challenge studies that pre-activating the innate immune response through intranasal delivery of a double-stranded viral RNA “mimic” can prevent both influenza and rhinovirus.

Since the host’s innate immune response is non-virus specific, such an approach has the potential to offer protection against other types of respiratory viruses as well.

Monoclonal antibody therapies have also made incredible advances in the last couple of decades, leading to several products for cancer and autoimmune diseases. During the Ebola outbreak in West Africa several years ago, researchers were able to identify and test a promising combination of monoclonal antibodies to treat infected patients.

And a growing pipeline of broadly neutralizing antibodies are being discovered in some individuals exposed to infectious diseases. For example, a small percentage of people infected with HIV develop antibodies with high potency and breadth of coverage sufficient to protect against many strains of the virus. The same is true for some people infected with the flu. Different sets or cocktails of these exceptional antibodies may protect against a pandemic strain of a virus even if it has genetically evolved. It is conceivable that we could create libraries of these antibodies, produce manufacturable seed stocks, and have them ready for immediate use in an outbreak—or ready to scale up manufacturing if a pandemic ensues. If we can learn how to use RNA or DNA gene delivery effectively, we may not need to make the antibodies at all.

Rapid diagnosis is also critical, especially at the beginning of an outbreak when quarantine, treatment, and other public health measures are most effective. To that end, researchers at the Broad Institute and at UC-Berkeley have developed a highly-sensitive point-of-care diagnostic test that harnesses the powerful genetic engineering technology known as CRISPR.

But instead of using CRISPR to edit DNA, they have programmed an associated protein called Cas13 to hunt for specific pieces of RNA. When Cas13 locates the relevant genetic sequence, it releases a signal molecule that indicates the presence or absence of the target.

In a paper published yesterday in the journal, Science, the Broad researchers highlighted the field-use potential of this new diagnostic. Using paper strips similar to a pregnancy test – and with minimal sample processing – the diagnostic can check a patient’s blood, saliva, or urine for evidence of a pathogen.

What’s more, it can test for multiple pathogens at once. It could, for example, identify if someone is infected with Zika or dengue virus, which have similar symptoms.

There are also some interesting advances that leverage the power of computing to help predict where pandemics are likely to emerge and model different approaches to preventing or containing them.

Over the last few years, researchers at the Institute for Health Metrics and Evaluation at the University of Washington have developed a sophisticated computer model that combines data from dozens of sources with geospatial mapping to predict the pandemic risk of infectious diseases.

They recently looked at the pandemic potential of four viral hemorrhagic fevers in Africa – including Ebola. Their analysis confirmed that Guéckédou prefecture in Guinea – where the West African Ebola outbreak originated – was indeed one of the most likely places where an individual Ebola case could lead to a widespread epidemic.

The research also pinpointed dozens of other African communities that are at high risk of outbreaks of hemorrhagic fevers.

Meanwhile, researchers at the Institute for Disease Modeling are pushing the boundaries of computational epidemiology to provide a deeper understanding of both the spread of infectious diseases and the effectiveness of different control and eradication strategies.

In the effort to eliminate malaria, for example, IDM is combining surveillance data with computational modeling to tailor antimalarial efforts to unique local conditions. They are also using quantitative analysis and modeling to evaluate various control strategies for HIV, TB, and to eradicate polio. This kind of research could provide valuable information to help predict disease transmission and identify prevention measures and intervention tactics for epidemics and pandemics.

At the Munich Security Conference last year, I asked world leaders to imagine that somewhere in the world, there is a weapon that exists – or that could emerge – that is capable of killing millions of people, bringing economies to a standstill, and casting nations into chaos.

If this were a military threat, the response – of course – would be that we should do everything possible to develop countermeasures. In the case of biological threats, that sense of urgency is lacking.

The world needs to prepare for pandemics the way the military prepares for war. This includes simulations and other preparedness exercises so we can better understand how diseases will spread and how to deal with things like quarantine and communications to minimize panic.

We need better coordination with military forces to ensure we can draw on their mobilization capacity to transport people, equipment, and supplies on a mass scale.

We need a reserve corps of trained personnel and volunteers, ready to go at a moment’s notice. And we need manufacturing and indemnification agreements in place with pharmaceutical companies –with expedited review processes for government approval of new treatments.

Last month, Congress directed the administration to come up with a comprehensive plan to strengthen global health security – here and abroad. This could be an important first step if the White House and Congress use the opportunity to articulate and embrace a leadership role for the U.S. in global health security.

No other country has the depth of scientific or technical expertise that we do – drawing on the resources of institutions like the NIH, the CDC, and advanced research organizations like DARPA and BARDA.

Our biopharmaceutical industry is the global leader in biomedical innovation. And, on the world stage, the U.S. is an influential member of international forums like the UN, the WHO, the G7, and the G20.

The point is that the U.S. can and should play a leadership role in creating the kind of pandemic preparedness and response system the world needs.

As I said at the start, I’m fundamentally an optimist, and that gives me hope that we can get prepared for the next big pandemic.

The global community eradicated smallpox, a disease that killed an estimated 300 million people in the 20th century alone.

We are on the verge of eradicating polio, a disease that 30 years ago was endemic in 125 countries and that paralyzed or killed 350,000 people a year.

And today, nearly 21 million people are receiving life-saving HIV treatment, thanks primarily to the support of the world community.

America’s global HIV initiative, PEPFAR, was the catalyst for world action on the AIDS crisis. It’s an example of the kind of leadership we need from the U.S. on a broader effort to make the world safer from other infectious disease threats. With strong bipartisan support, PEPFAR has saved millions of lives and shown that national governments can work together to address pandemics.

Somewhere in the history of these collective efforts is a roadmap to create a comprehensive pandemic preparedness and response system.

We must find it and follow it because lives – in numbers too great to comprehend – depend on it.

Thank you for the opportunity to address you today.