What AIDS Taught Us About Fighting Pandemics

(Posted on Friday, May 15, 2020)

Thirty-five years ago, in the midst of the new and still somewhat unknown AIDS epidemic, I warned in testimony to the US Congress that we were facing another deadly episode in the long battle between humankind and microbes. If asked to testify again I would say the same thing today.

Just as it is impossible for us to control tsunamis, earthquakes, and volcanic eruptions, our ability to subdue contagious outbreaks is more limited than we like to admit. Despite what we often tell ourselves, we cannot always impose our will upon the natural world.

When it comes to other forms of natural disaster, the private and public sectors have agreed on policies to mitigate the risk. Billions of dollars have been committed to seawalls and other infrastructure to manage the threats posed by tsunamis and hurricanes, and we have long had regulations requiring that high-rise buildings be constructed to withstand tremors.

These measures were instituted to protect people from harm. They were adopted as a matter of course, and did not require debates about which country was to blame or which leaders had failed.

By contrast, in the face of the latest natural disaster, COVID-19, we have not taken a single step toward emulating these previous successes. Instead, the public-health emergency has become highly politicized. Government leaders and parties have been busy accusing each other and international organizations of willfully disregarding the danger at hand. The private sector, meanwhile, has been surprisingly silent, quietly attending to the bottom line and avoiding the costs and challenges that would come with assuming a leadership role.

The Siren Song of Denial

This is not the first time we have been paralyzed in the face of an epidemic. When I testified before Congress 35 years ago, we were in a surprisingly similar situation. In 1985, we were still learning about the virus that causes AIDS. Indeed, we had only recently developed a test that could diagnose an infection. Testing revealed that more than one million people in the United States were HIV-positive, with upward of 20 million people infected globally.

But even more troubling was the fact that we had no way to stop the progression of the disease. We anticipated that the vast majority of those infected would, over a period of ten years or so, end up with serious illnesses that would threaten their lives and tax the health systems upon which we all depended.

Although there are obvious differences between the novel coronavirus (SARS-CoV-2) and the human immunodeficiency virus, there also are striking similarities between the two crises that can inform the choices we make today.

In both cases, for example, we failed to notice the warning signs. Even when the AIDS epidemic was fully upon us and millions were already infected worldwide, there was still a widespread belief that we had nothing to worry about.

In a 1985 cover story, Discover magazine shared the “latest scientific facts” about the disease, noting that “heterosexuals are virtually risk free,” and that gay men were both the cause of the disease and the group that would suffer the most from it. We now know that this denial of reality prevented us – the public sector, the private sector, and even researchers like me – from pursuing the urgent measures needed to save lives.

As one of the few scientists researching the new disease, I had embarked on a personal crusade to enlist major pharmaceutical companies in an effort to develop a drug to treat HIV and prevent its spread. I met with the research heads for all the major companies – Bristol-Myers Squibb, Pfizer, Roche, Johnson & Johnson, and others – but I heard the same story everywhere: “Sorry, Bill, funds are already fully budgeted for this year.”

Likewise, when I approached the chairs of the infectious disease and microbiology departments at the country’s leading universities, I was told that, “It’s scientifically interesting, but we just don’t have the money.” Worse, I was even told that “AIDS will never be an important enough disease.”

In the midst of today’s pandemic, we are once again ignoring the facts and failing to mobilize the resources necessary to improve our chances against the disease. And we have behaved this way despite the fact that we have long been aware of the possibility of a highly disruptive coronavirus outbreak.

When SARS (severe acute respiratory syndrome) was first reported in 2003, the origin of the virus that caused the disease was a mystery. Scientists suspected it might have come from bats. But these findings were not confirmed until almost a decade later with the arrival in 2012 of MERS (Middle East respiratory syndrome), another disease caused by a coronavirus. On those occasions and in the years since, policymakers and the public have been warned about the potential for future outbreaks, and about the need to learn from the past.

We didn’t. While funding was made available to develop a medical solution for SARS and MERS at the height of those outbreaks, it dried up after the initial panic passed. Promising work that was underway was halted in its tracks. In a 2013 Future Virology article, virologists Shibo Jiang, Lu Lu, and Lanying Du lamented that “after the disappearance of SARS … funds were either withdrawn or discontinued because of the lack of a sustainable market of the products to be developed.”

Picking Up The Pieces

Although that previous coronavirus research came to an abrupt stop, the work done may still be enough to help us end the outbreak today, because we at least now know how the coronavirus functions. At the risk of oversimplifying, a coronavirus has three main parts: an outer shell made up of oily lipids with crown-like spikes that can attach to healthy cells in our bodies; a protective wrapping inside the outer shell that holds in place the genetic information (the most dangerous part of the virus); and the genetic information itself, along with the enzymes that enter cells, duplicate, and attack our immune systems.

In discovering the structure of the virus, researchers also opened a window onto how we might destroy it: namely, with a combination of antiviral drugs that can attack the virus’s core, where noodle-like structures prepare RNA molecules for launch. Remarkably, this solution is similar to the approach used against HIV. In that earlier fight, we combined public-health messaging with the development of multiple drugs to bring the virus to heel.

There is no vaccine for HIV/AIDS, yet, but that doesn’t mean we can’t control it. In the early days of that epidemic, our research focused on understanding the structure of the virus and how it functioned, which in turn enabled us to develop antiviral agents that would target the proteins at its center.

More important, we developed not just one antiviral drug, but rather a combination of treatments capable of targeting multiple viral proteins simultaneously. This helped to ensure that any resistance developed against one drug would be rendered impotent by the other drugs in the cocktail.

With the arrival of COVID-19 and a renewed burst of emergency funding for a biomedical solution, we must not lose sight of the insights provided by past research and public-health efforts. While work toward developing a vaccine is important, that particular solution will take significantly more time and testing than an antiviral treatment would. Previous research has pointed the way to a number of drug candidates that can inhibit the key coronavirus enzymes – polymerase, helicase, and protease. But now more work is needed to move the most promising contenders toward clinical trials.

If we do not act now to develop these drugs, we will have failed the most vulnerable among us, who are at a heightened risk from COVID-19. We also will have failed future generations, perhaps in even more significant ways, because it is only a matter of time before a coronavirus that is far more lethal and contagious than this one emerges to ravage the world’s population. When that happens, we will no longer be talking about a global death toll in the “mere” hundreds of thousands.

The Call To Action

While witnessing the collective inaction against HIV/AIDS in the 1980s, my colleagues and I knew that we needed to marshal a massive institutional response on the scale of the War on Cancer. We needed to mobilize a broad segment of the medical and scientific community, but we also needed to mobilize the government to provide seed funding and guarantee that there would be a market for any drug developed.

Only then could we get the major pharmaceutical companies to work with us on finding a biomedical solution both to treat the infection and to prevent further spread of the disease. In each case, we needed people to care.

Despite the millions infected and the thousands who had already been lost, that moment did not come until the fall of 1985, when the beloved actor Rock Hudson died of AIDS. The loss of an icon made Americans question their sense of security, and it prompted action from President Ronald Reagan, a friend of the late actor. After years of forcing cutbacks at the US Centers for Disease Control and the National Institutes of Health, Reagan approved $1 million in additional funding for AIDS research in the 1986 budget.

It wasn’t a lot, but it was enough to get us started. While continuing to warn the public about the risks of the disease, those of us who had been researching it met privately with health officials, government leaders, and industry executives, and managed to turn that $1 million into more than $300 million by the end of 1986. We succeeded because people had finally started to care.

We are in the same situation today as we were in the fall of 1985. Another celebrity of sorts, British Prime Minister Boris Johnson, was admitted in April to an intensive care unit in a London hospital for treatment of COVID-19 symptoms. Fortunately, this disease is not nearly as deadly as HIV/AIDS, and he has since recovered, though it seems to have been a close-run thing. But many other COVID-19 patients placed in ICUs have not been so lucky.

With the massive human and economic costs of this pandemic coming due, there is no excuse for ignoring the warning that nature is sending us. A much more lethal biological threat lies in wait. Whether it takes the form of a coronavirus outbreak, a more dangerous strain of influenza (like the one that killed 50 million people a century ago), or a new germ that is resistant to all available antimicrobial drugs, it will be devastating.

Evolution can crack problems that humans cannot and, as we have seen with antimicrobial resistance, it can surmount obstacles that humans put in its way. Trust me when I say that nature is the most dangerous “terrorist” out there. No border, however tightly controlled, can keep pathogens at bay. And in today’s interconnected world, the global spread of infectious diseases should be recognized as the rule, not the exception.

Taking Nature Seriously

Looking ahead, we must equip our scientists and researchers with the tools they need to fight new diseases. We should be funding a program to understand viral threats, another to create vaccines, and another to develop effective antiviral therapies that can treat coronavirus infections. All should remain in place – and receive full funding – long after the current crisis has passed.

To ensure that the necessary biomedical work is done, we also need to create the markets for these drugs. That responsibility falls to governments, which have a duty to protect their citizens. Private-sector firms cannot be expected to pour their profits into developing drugs that will leave them in the red.

SARS Inhibited (2006) stands in the center of the science city Biopolis in Singapore. The bronze sculpture by Mara Haseltine depicts the three-dimensional polypeptide backbone of the active site of the SARS protease. The paving stones represent the drug candidate that inhibits the SARS protease and stops the virus from replicating. Unfortunately, this and other similar drugs were never fully explored, and thus did not reach clinical trials. Given the similarities between the SARS coronavirus and SARS-CoV-2, following through on this work could have given us a prophylactic and therapeutic solution to the COVID-19 pandemic. Instead, we have been left playing catch-up.
In the US, I have long called on the Biomedical Advanced Research and Development Authority (BARDA) to expand the list of biomedical threats included under Project BioShield, its program for purchasing vaccines as a safeguard against biological warfare. In funding the discovery, development, and stockpiling of medical countermeasures to health-security threats, BARDA bypasses the laws of supply and demand in the name of protecting the public.

As I emphasized at the height of the AIDS epidemic, the magnitude of our response must match the magnitude of the problem. There is no greater threat to the human species than the biological weapons that have yet to be discharged from nature’s arsenal. If we don’t start preparing our defense now, we may not have time when the next pandemic strikes.

This article was originally posted on Project Syndicate (May 15, 2020).