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What single event killed more Americans than any other in our history? The attacks of 9/11? The epic conflicts of World War I or World War II?

None of the above. This year, we mark the 100th anniversary of a catastrophe that killed more Americans than all of the events above combined: the Spanish flu epidemic of 1918, which took as many as 675,000 lives in this country and more than 50 million worldwide — killing nearly one out of every 20 humans then alive.

One hundred years later, it is the prospect of another such pandemic — not a nuclear war, or a terrorist attack, or a natural disaster — that poses the greatest risk of a massive casualty event in the United States. The scope of the danger is breathtaking: Bill Gates, citing epidemiologists, has said that there is a “reasonable probability” of a pandemic that kills more than 30 million people worldwide in the next two decades. A tabletop exercise run at Johns Hopkins Center for Health Security in May simulated a global flu-like outbreak called Clade X and found that 150 million people (including 15 million in the US) would die in the first year alone.

In an era with so much progress in science and medicine, how can the United States remain so vulnerable to such a pandemic? With so much money and energy being devoted to combatting large-scale terrorist attacks, nuclear proliferation, and other dangers, why has so much less attention been devoted to a threat that is arguably more likely and potentially deadlier?

We cannot totally eliminate the risk of pandemics in the near term. But a three-pronged agenda focused on mitigating that risk — pushing for better and faster vaccine development and deployment, a stronger emergency response infrastructure, and a more robust global health security system — can make us safer.

But most importantly, we need to take the risk seriously. A catastrophic pandemic is not merely the stuff of dystopian fiction. It is very much a real danger, as real today as it was 100 years ago.

The pandemic risk today

America in 2018 is in many respects safer from the pandemic threat than America was in 1918. Advances in science and medicine have given us many tools to combat a pandemic flu that we lacked a century ago. In the event that existing vaccines provide no protection from a particular new flu threat, antiviral medicines would at least pose a partial first line of defense against the epidemic until a vaccine could be developed. Antibiotics would also help combat secondary infections, which killed so many in 1918. We have made progress in 100 years.

But for every one of these modern miracles that makes us safer, there is some other element of modernity that raises our risk level from what it was a century ago. Global transportation networks can bring a virus from a remote corner of the world to one of its most populous cities in less than 24 hours. The clustering of more people into cities — especially supercities in Asia — creates fertile grounds for such diseases to spread quickly. The incursion of humans into wildlife habitats is increasing the crossover of zoonotic diseases (like Ebola) from animals into people. Climate change is expanding the reach of disease-bearing vectors like mosquitoes into new regions and putting new populations at risk.

The possibility that an epidemic could take a huge number of lives here and around the world should be no surprise, given our collective experience with the HIV/AIDS epidemic, which has killed more than 35 million worldwide. More recently, the West African Ebola epidemic of 2014-’15 (for which I served as the White House response coordinator) killed more than 11,000 people there and spread panic worldwide before it was contained.

The past two decades have seen a roll call of near-miss catastrophes. The SARS outbreak of 2002. The H1N1 flu of 2009. The MERS outbreak of 2012. And, of course, the Ebola epidemic of 2014, which at one point was forecast to take 1 million lives. They all were horrible, but each could have been significantly worse.

H1N1 offers a telling story. At a time when the world worried about a pandemic flu coming from Asia, H1N1 exploded from Mexico and California across the US. Once it was identified as a pandemic risk, an all-out effort to create a vaccine was launched — but the vaccine wasn’t made widely available to the public until after the epidemic’s peak. Even then, manufacturers were able to produce only a limited supply. Government officials gave conflicting guidance about the danger and the safety of routine actions (like keeping schools opened or air travel with infected people).

In the end, about 60 million Americans contracted H1N1 that year — which, by pure luck, turned out not to be a particularly lethal strain. Had it been even one-tenth as deadly as the Spanish flu (which was estimated to have killed about 10 to 20 percent of those it infected), even our modern medicine could not have prevented hundreds of thousands of Americans from dying in a relatively short period of time, in an event that would be more searing in contemporary consciousness than 9/11.

New political and social trends further increase our risk level. A rising tide of anti-vaccine sentiment in the US and Europe is raising the risk of a resurgence of once-vanquished infectious diseases (like measles), and increasing the likelihood of massive vaccine resistance in the event of an epidemic. The ability of social media to rapidly spread false information — painfully illustrated in the 2016 campaign — is another source of danger: Would the directives of public health officials be followed in a crisis? Would they be undermined by misinformation spread by misguided provocateurs or a hostile foreign power?

And then there is the risk factor of isolationism and xenophobia. While responsible officials in the Trump administration have responded to two Ebola outbreaks in the Democratic Republic of Congo this year (including one that is far from under control), in a more visible crisis, Trump’s isolationist instincts might assert themselves. In 2014, such views led him to tweet that President Barack Obama should not have evacuated American Ebola fighters who contracted the disease from West Africa, and instead, should have left them to “suffer the consequences” of their condition.

Xenophobic views played a critical role in the tardy response to Zika in 2015-16. Congress delayed acting on a funding package because Zika was perceived to be a “foreigner’s disease.” As I made public appearances promoting this funding, I often heard in response, “Zika isn’t a public health problem, it’s an immigration problem — just keep the foreigners out.”

Never mind that there was no evidence that it was foreigners — as opposed to Americans coming home from vacations — that were bringing the disease to our shores. The anti-Zika funds stalled in Congress, and we eventually saw transmission of the disease in Florida, and the first-ever Centers for Disease Control and Prevention (CDC) warning against travel to parts of the continental US.

More generally, a turn inward risks undercutting our best defense against epidemics: working with other countries to fight them overseas. Trump has proposed cutting international programs at the National Institutes of Health and CDC to fund his border wall. That may have political appeal to his base, but the reality is that there is no wall high enough to keep infectious diseases out of our country. (To date, Congress has rejected such proposals from the president, and boosted funding for the two agencies.)

How we can prepare for the next pandemic

Reducing our risk from these dangers is a vast undertaking, and runs the gamut from better surveillance systems to massive medical research projects to all forms of global investments. But three items should top our agenda:

1) Improve vaccine development and deployment

While the ultimate goal of a “universal flu vaccine” is still far in the future, better vaccines that cover a wider array of flu strains are coming sooner. Last year, a global public-private partnership named the Coalition for Epidemic Preparedness Innovations (CEPI) was formed to accelerate vaccine development for epidemic infectious diseases threats. Though CEPI was launched with generous support from donors like the Gates Foundation and the Wellcome Trust, it can fund work on only a handful of the highest-priority vaccines.

Even for the world’s best scientists, predicting which diseases should be prioritized is hard. I attended a conference in the runup to the formation of CEPI where scientists discussed a “top 10” list. Just a few months later, Zika — not even on the list — was a huge threat.

Moreover, inventing vaccines doesn’t save lives; vaccinating people does. Even if scientists discover promising vaccines for infectious diseases threats, the world predominantly relies on private vaccine makers to bring those vaccines to market, which is not always a certainty. (Large vaccine makers felt burned spending millions on developing an Ebola vaccine in 2014 that will never yield profits.)

Vaccines also face complex regulatory challenges — the Ebola vaccine tested in 2014 and being used now in the Democratic Republic of Congo isn’t licensed — and a hazy global policy framework on issues like intellectual property from clinical tests.

What’s more, while the US has a legal process to govern liability and compensation for anyone injured if a new vaccine is used on an emergency basis (called the PREP Act), most countries don’t, creating a substantial risk that a vaccine could be made to combat a crisis — and be left sitting in warehouses while lawyers and policymakers hash out the details.

The world has a hugely successful system, run by the amazingly efficient alliance known as Gavi, for funding and distributing well-established, proven vaccines in developing countries. Gavi — a public-private partnership of developed and developing nations, the World Health Organization (WHO), the World Bank, the Gates Foundation, and other civil society groups — has grown in scope and scale since its launch in 2000.

It has now taken on deployment of the new Ebola vaccine as a project, and it could be a vehicle for tackling many of the complex issues of funding and implementing an emergency epidemic response vaccine plan, but that would require additional funding sources and support to ensure that Gavi is not distracted from its core work of vaccinating millions against existing disease threats.

2) Strengthen US epidemic preparation and response

A global review known as the “Joint External Evaluation” gave the US some of the strongest marks among the world’s countries for being ready to cope with an epidemic. But that should provide only small comfort.

No city in America has existing capacity (i.e., treatment units within a hospital supported by trained staff and equipment) to treat more than a handful of dangerous infectious diseases patients at one time. During the Ebola epidemic, the US government distributed patients carefully so that even our very best infectious diseases hospitals — facilities in Nebraska, at NIH, and at Emory — never treated more than two patients at a time.

An outbreak of even just a few dozen cases of a deadly, highly infectious disease — let alone a few hundred — would overwhelm any city in our country. In such a scenario, death would beget death, as patients carrying the virus would stream into hospitals and infect others who did not yet have the disease.

Health care workers would be put at risk, and as word spread, people who were not infected but who had other ailments would stay away from hospitals. Death rates from heart attacks, strokes, childbirth, and other urgent care situations would spike.

After the Ebola epidemic of 2014, Congress funded a system of 10 regional “special pathogen” infectious diseases treatment centers in the US, a vast improvement from the three we had before the epidemic. Even so, these centers only have a total of approximately 100 equipped treatment beds — isolated hospital beds with necessary equipment and trained staff — and as the fears of 2014 fade in memory and our guard drops, the response time at these facilities to go from “standby” to “ready” is rising.

We need to step up our investment in facilities, training, and equipment for our domestic epidemic response — and do so now, not when a crisis comes. And we need to give a president some basic tools to cope with such a threat: a robust Public Health Emergency Response Fund to fund the early stages of a response (the perennially underfunded reserve currently holds just 2 percent of what the US spent on the Ebola response), and the same kind of disaster assistance authority under the Stafford Act for epidemics that the president now has for earthquakes or hurricanes.

We need to create a new group of federal epidemic responders, which I’ve called the Public Health Emergency Management Agency (PhEMA); barring that, we should create a specialized unit in the Federal Emergency Management Agency that is trained and equipped for the job.

But most of all, we need to stick with (and indeed, even increase) our commitment to the Global Health Security Agenda launched by President Obama, which helps other countries build up their capacities to detect and respond to outbreaks. Spending on such “foreign aid” will never be popular. But we should think of infectious disease threats the way we think of terrorism: The best way to make America safer is to make the world safer from this danger.

3) Bolster global response capabilities

It would shock most people to know that there is no elite squadron of fully equipped global epidemic responders ready to be deployed when the alarm sounds. As I often said during the Ebola epidemic, the thing that should scare people is not that the black helicopters will be landing in their backyards any minute now — it’s that there are no black helicopters coming, even if you need them.

Our current global response capacity relies on the WHO to declare that an epidemic is underway, and provide general coordination for a response. Most of the hardest work —actually treating sick patients, and engaging with locals on how to deal with the threat — is performed by a number of courageous NGOs such as Doctors Without Borders, the International Rescue Committee, and Partners in Health.

The WHO was roundly criticized for its handling of the 2014 Ebola epidemic, and new leadership was installed in 2017. Under Dr. Tedros Adhanom Ghebreyesus, the WHO’s new director general, the organization has improved its work on epidemics and is acting in a more transparent fashion.

But even so, the WHO — which was created initially to spotlight violations of international health regulations — has not been, and seems unlikely to become, an organization with the kind of personnel, equipment, or authority to power a full-scale pandemic response.

Moreover, as we are seeing in the current WHO-led Ebola response in the Democratic Republic of Congo — where the response is falling behind the disease, and the risk of spread to adjacent countries is rising — when epidemic responders encounter local violence, civil discord, or security threats, they have no protection and must sometimes cease operations. Officials complain that the violent, chaotic conditions in the Eastern Congo are a “worst case” for an Ebola outbreak, but in a truly ghastly epidemic, instability and regional violence is likely to become the rule, not the exception.

Some world leaders have backed a plan first proposed by then-German Foreign Minister Frank-Walter Steinmeier to create a multinational white helmet brigade that could provide security and logistical dimensions to an epidemic response. In 2014, the UN established a temporary unit that helped do similar work in West Africa called UNMEER, or the UN Mission for Ebola Emergency Response. That effort got mixed reviews for its uneven performance and rapidly rotating personnel in West Africa, but perhaps the UN could take another run at creating such a response unit.

But the bottom line is this: If science fiction became reality, and the world was threatened by interstellar invaders putting tens of millions of lives at risk, it’s hard to believe we would face that danger “armed” only with an international regulatory organization and a cluster of NGOs. And yet that is precisely what we will be relying on what a major epidemic comes our way.

In the end, the question we will face is not if a massive global pandemic will hit, but when. Pandemics have recurred throughout history with devastating consequences, from the bubonic plague in the Middle Ages to the Spanish flu a century ago to HIV/AIDS in our own lifetimes.

The more we do now to accelerate vaccine research and deployment, bolster the home front for the coming threat, and invest in a global health security agenda and response capacities, the better we will fare when that day comes.

Ron Klain served as the White House Ebola response coordinator in 2014-15. He previously served as chief of staff to Vice Presidents Joe Biden and Al Gore.

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