On the China Covid Investigation, Take the Virus-Hunter Approach

Where did Covid-19 really come from?

The origins of the pandemic have huge importance to science, to medicine and to global security, but nearly two years after the first known infection, the search is stalled. The high-profile release last month of the U.S. intelligence community’s report to President Joe Biden only confirmed how little progress has been made: After a 90-day investigation, it offered two long-familiar theories. Either the virus originated from natural human exposure to an infected animal, or it escaped from a biocontainment laboratory. There was no consensus on which was more likely.

There’s a good reason we don’t know more: The government of China has consistently obscured the events around the early coronavirus outbreak and resisted providing key information to American investigators and even to the World Health Organization.

This doesn’t automatically mean China was a malicious actor. Its leaders may simply be worried about what else turns up along the way. Perhaps it was human error in the Wuhan lab, which would injure national pride in China’s top new biocontainment facility. And Chinese leaders are right when they complain that early finger-pointing at Beijing, and especially the accusations of bioweapon development, was nothing more than baseless political posturing.

Right now the impasse shows every sign of continuing. The World Health Organization is launching a second global investigation of Covid’s origins, this one led by more qualified investigators than the first, but China continues to reject further inquiries into what happened. In Washington, there’s now increasing pressure on the White House to play hardball with China — to force cooperation by imposing serious new penalties, like sanctions on Chinese laboratories.

There’s little reason to think these might work. And even if they did, the hardball approach would be a huge mistake in the long run. Covid-19 is only one of many pandemics we’re likely to see this century, and — given China’s vast animal and human population, extensive surveillance network, unparalleled virus sequencing capabilities and its massive biomanufacturing capability — we’ll need China in the future, both to investigate and to help fight the next one, and the one after that.

Like it or not, Joe Biden and his successors in the White House need China as a long-term partner far more than they need it as a scapegoat.

So now what? Given the current impasse, is there a way to work productively with China on the kinds of problems we’ll need to tackle in the future?

I’ve been involved in global disease outbreak operations for 22 years, isolating dangerous viruses in the field and treating infected patients, and have worked inside three U.S. federal agencies under presidents of both parties. And I can say the answer is yes. It requires, however, more than hastily assigned and executed intelligence reports. It requires more than complaining about an uncooperative China, or cooking up saber-rattling diplomatic pressure schemes.

A more promising solution would involve following the successes of a little-known 30-year U.S. government effort to root out bioweapons in dangerous parts of the world, and to secure dangerous pathogens in foreign laboratories. That effort built a field corps of U.S. experts skilled in virology, foreign biocontainment practices and the care of patients infected with highly dangerous pathogens. Their direct “glove-to-germ” experience, often in politically inhospitable settings, has generated a range of successful approaches for sleuthing out human factors that contribute to an accident, a lab infection or an outbreak.

Their experiences would expand the breadth of any renewed investigation into the origins of Covid-19 — and more importantly, their style of cooperation-building would likely preserve China’s willingness to help the West in future, possibly more dire, pandemics.

The roots of this success story lie in America’s approach to another adversarial power, the Soviet Union.

Following the fall of the USSR, the U.S became alarmed about the security of that country’s biological weapons program. The U.S. was concerned what might come out of its biological weapons facilities and stockpiles — and who might hire the 60,000 scientists trained to produce these living munitions.

Following the attacks of Sept 11, 2001, and the American anthrax attacks soon afterward, the U.S. increased efforts to prevent Soviet biological weapons, and the skills to make them, from being acquired by terrorists. Many U.S. efforts involved redirecting former bioweapons labs to peaceful purposes like vaccine production. This leveraged both the Soviets’ scientific expertise and the preexisting biocontainment infrastructure.

The risk wasn’t gone, though. These labs were still handling dangerous pathogens, and pathogen escape and infection of laboratory workers remained a concern of western security agencies. To counter the risk of laboratory leak or infection, the U.S. didn’t turn to security forces, satellites or spies. It used infectious disease experts.

The idea to develop a “special forces” for foreign lab biosecurity garnered bipartisan support in Congress. In 1991, Sens. Sam Nunn (D-Ga.) and Richard Lugar (R-In.) co-sponsored a law to counter the proliferation of chemical, biological, radioactive and nuclear weapons of mass destruction, and over the years the Nunn-Lugar programs expanded under an umbrella program called Cooperative Threat Reduction, known simply as “CTR.”

The CTR mission had 3 basic parts: to prevent the proliferation of biological weapons and the skills to produce them; to redirect foreign pathogen research to improve global health; and to prevent the escape of dangerous pathogens from foreign biocontainment laboratories. Over the next 30 years, CTR expanded from the former Soviet Union into politically unstable regions where dangerous pathogens existed alongside groups capable of weaponizing them. By 2003, U.S. biosecurity experts were deployed throughout the Middle East and Africa. In 2004, following the Bali nightclub bombing, concern that the terrorist group Jemaah Islamiyah might turn pathogens obtained from local veterinary, hospital and vaccine laboratories into crude biological weapons prompted the State Department to expand CTR into Indonesia, Philippines, Malaysia and Thailand.

The dispersed, field-based approach wasn’t just by necessity — it was also strategic. These field scientists were infectious disease doctors, veterinarians and microbiologists recruited from leading U.S. hospitals and universities such as Johns Hopkins and Harvard, as well as one of the U.S Navy’s oldest international infectious disease labs in Jakarta, Indonesia. They built partnerships in each country not just with governments, but with vaccine companies, local physicians and public health officials, many of whom had trained in the U.S. Part of the mission was to help each biocontainment facility develop a business plan to support peaceful jobs and produce valuable products. The goal was to ensure that weapons scientists weren’t tempted to wander, and to keep pathogens secure behind locks, fences and freezers.

CTR scientists were routinely the first foreigners to access some of the world’s most secretive biological laboratories — and to initiate productive collaborations in countries of concern. For example, in the former Soviet Union, State Department senior scientist Jason Rao secured $30 million in emergency appropriations to launch his novel capacity-building program, the BioIndustry Initiative. Over a four-year period, the BII secured pathogen repositories across the Ukraine and Russia, awarded grants for drug and vaccine development, assisted former weapons laboratories to develop commercially valuable services such as diagnostic tests and helped fledgling drug companies address unmet medical needs.

When the CTR playbook expanded to Asia, Rao retooled the program for the region in the form of the Biosecurity Engagement Program. Where the program in the Soviet Union focused on retraining weaponeers to peaceful professions, BEP worked to build Asian capability to increase disease surveillance, to control disease outbreaks — and to secure pathogen collections. Within 5 years, it had dramatically improved outbreak surveillance, made bird flu vaccines safer and helped to build one of world’s leading bat virus research laboratories in Bangkok.

That program continued to pay off in 2020, as the new coronavirus spread: Asia’s BEP-affiliated hospitals, universities and companies include the first public health laboratory to isolate Covid-19 outside of China. And they helped preserve communication links between American and Chinese physicians after the Wuhan cases became an embarrassment, and the risk of Chinese government censorship made communication with U.S. doctors dangerous.

The basis of the whole CTR model was collaboration, and it was built on doctor-to-doctor contacts. It paired Western scientific partners directly with local scientists to help them develop new diagnostic tests, or vaccines, or disease treatments. It prioritized working with younger scientists willing to train in the U.S. and then return to their home laboratories. It used American labs to confirm the work being done overseas, and small grants from American agencies to seed larger local investments.

This trust-building model proved extremely effective in dealing with very sensitive, and potentially very dangerous, biological programs. Examples of early collaborations include Ebola and HIV vaccine projects at a former biological weapon laboratory in Siberia, and a program to find new treatments for antibiotic-resistant bacteria at Obolensk, a lab near Moscow where weapons scientists had previously engineered anthrax to be antibiotic-resistant. These programs could have clear payoffs in the host country: In 2003, the same Obolensk team that made anthrax resistant to antibiotics in the 1990s worked with CTR to open Russia’s first insulin production facility. One partnership, the Russian Flu Surveillance program, was a triple success: It gave the U.S. critical flu surveillance in a denied area, reduced the probability of laboratory escape by centralizing dangerous flu work, and offered a local payoff by giving animal producers better diagnostic tests for veterinary diseases. (It was also featured in a Discovery documentary, Flu Time Bomb.)

Transforming biocontainment facilities into public health labs, or biotech companies, wasn’t always easy or smooth. U.S. scientists traveling in Russia were harassed by the FSB, always received the same hotel room and were required to receive Russian vaccines in order to work in Russian laboratories. Laboratories had their own dangers; a virus lab had already been suspected as the cause of one pandemic: In 1977 a flu outbreak appeared in northern China and swept the globe, killing more than 700,000 people, very likely stemming from an escaped virus from the 1950s that had existed only in laboratory freezers for two decades.

But payoffs have come both from partnerships and new on-the-ground knowledge. One key finding from CTR work, over the years, may be directly relevant to the Covid outbreak: In many cases, infections attributed to biocontainment laboratory activities actually occurred outside the lab, often during field collection of viral samples. Squirming, clawed and toothy animals bite and scratch during collection of body fluids. Teeth and talons easily penetrate the thin gloves required to maintain dexterity when handling fragile wildlife. And overhead, angry bats release a fine patina of virus-laden urine aerosols. As part of CTR field surveillance programs, I have collected viruses from Asian bats carrying coronaviruses, and from birds infected with bird flu, and can attest that the margins for personal protection during these expeditions are razor thin. The fact that researchers are not infected every time they do a field collection is a question that continues to stump us.

In cases like this, the actual point when infection occurred in the field can go unnoticed. In two Asian cases, for instance, “lab-acquired infections” among researchers were actually acquired during field collection, but symptoms were delayed for 2 and 3 days, after the researchers had returned to their home city and gone back to work in the lab. And there are other human factors at work: In China, if a researcher develops symptoms and suspects lab infection, they are inclined to hide the mistake from their superiors.

In the case of the Covid origins investigation, the timing of Wuhan Institute of Virology field collection trips, which we know occurred several times during 2019, need to be carefully tracked to pinpoint opportunities for more intensive clinical investigation. As of now, we simply don’t have enough information to know whether these might have been connected to the pandemic outbreak — and China has told its researchers not to share any data on field collection with WHO. But this scenario suggests a new target for research into Covid’s origins: Focus on hospital lab data from anyone who came in contact with the Wuhan field virologists up to 4 weeks following their return from field collections.

Given what we still need to learn about Covid-19, how might the U.S. collaborate with China on health security?

The answer may not lie with China’s leaders, who are disinclined to cooperate with the West for bigger reasons. Over the last decade, China has fueled an aggressive expansion of its domestic biotechnology research and its drug and vaccine manufacturing capacity, and keeps data and practices secret for competitive reasons. This secrecy also extends to biosecurity. I’ve been told directly by a Chinese official: The Communist Party views biosecurity — including oversight to prevent dual-use research, where biotechnology could be used to make either life-saving products or biological weapons — as detrimental to its aspirations to dominate global biotechnology markets.

Beijing’s strategic priorities help explain why U.S. health security programs do not exist in China. In fact, with the exception of a small U.S. Centers for Disease Control and Prevention presence in Beijing, there is no significant U.S. government health presence in China.

This does not mean, however, that there is no U.S. medical presence to build on. For more than 100 years, the U.S. and Chinese medical education communities have been closely linked, and their connections remain strong to this day. Yale University, for instance, has ties with China that reach back to 1835, when alumnus and medical missionary Peter Parker opened the first western hospital in present day Guangzhou. In 1917, the Rockefeller Foundation built the world-famous Peking Union Medical College, which trained numerous medical leaders in China and whose graduates have helped modernize Chinese medicine. Massachusetts General Hospital, where I work, has a relationship with PUMC that started in the 1970s, after President Richard Nixon’s trip to China.

The results of a century of U.S. Chinese medical collaborations is that members of the Chinese medical community, unlike the Chinese government, have deep relationships with their U.S. partners. And the relationships are now multigenerational and run in both directions, with U.S.-born, Mandarin-speaking scientists rotating through Chinese laboratories. These relationships prove invaluable when the U.S. needs to learn about a new outbreak in China. For example, U.S. physicians from St. Jude Children’s Research Hospital and MGH were collaborating on influenza research when H5N1 and SARS-1 outbreaks occurred in Hong Kong. Colleagues at Prince of Wales Hospital and virologists at the University of Hong Kong were first to share clinical and virologic data on SARS with their U.S. colleagues. Later, during the deadly 2013-2014 H7N9 outbreak, it was Nanjing physicians that shared disturbing data regarding the high fatality rates in Nanjing’s modern intensive care units — and the futility of treatments proposed by me and other U.S. colleagues. And in very early January 2020, the same Nanjing doctors, working with colleagues at Central Hospital of Wuhan, would share the first evidence that the novel coronavirus was spreading from person to person.

This news came as the Chinese government was vehemently denying community transmission. The information was shared at significant personal and professional risk to our Chinese colleagues: In the early weeks of the pandemic, the Chinese government was actively censoring medical data sharing between Boston and Chinese clinicians, eventually stopping the flow of data from Wuhan entirely.

Can this kind of collaboration move up the ladder from individual doctors to Chinese authorities?

To be successful, the international community must first incentivize Beijing to fully participate in the origins investigation. And although it is clear from China’s statements and behavior that such participation holds no attraction to the Party right now, that’s not the end of the story.

Discussion between U.S and Chinese drug and vaccine developers and their colleagues at Chinese medical centers suggest some possibilities. Major Chinese biotechnology companies, many with deep connections to the Party, are interested in selling products in Western markets. One option proposed to U.S. biotechnology developers, in a meeting I attended for Chinese investors, was to give provincial health authorities their own incentives to participate in the origins investigation — rewarding them, for instance, with access to medical technologies currently unavailable in China. There’s reason to believe China has data that lies outside of Beijing’s control — for instance, blood and serum samples from drug trials analyzed and stored in labs across the country, which might yield important clues about when and where the new pathogen appeared. And past outbreaks give us some hope that provincial medical leaders are willing to take modest risks in defiance of Beijing, though Covid is a different situation with more scrutiny attached.

The U.S.’s superior capability in use of immune forensics tools might be of value as well. The technologies could be shared with a reputable clinical trials research organization or leading academic medical center, where it would serve China’s future public health priorities. This could be carefully crafted to address China’s own interests: Strengthening public health through innovation has been a major pillar of President Xi Jinping’s Five Year Plans since 2010. Such an offer, designed in a way that allows China to save face, would be very hard to refuse.

There are plenty of other points of leverage. Access to American vaccine technology, especially Western mRNA vaccine technology, would give China the chance to salvage its global vaccine diplomacy efforts, currently floundering due to the poor protection provided by China’s two major exported Covid-19 vaccines. And American biocrime investigators could help track dangerous under-the-radar and controversial gain-of-function biotechnology research in Asia — which, perhaps surprisingly, is a growing concern to China as it looks across Asia’s red-hot bioindustrial marketplace.

A third incentive to encourage Chinese participation is an offer to help Chinese drug companies enter Western markets through the use of uniform drug and vaccine test and evaluation capabilities. China has realistic aspirations of unseating India as the leading global manufacturer of low-cost generic drugs and vaccines. One obstacle right now is concern about Chinese research and development methods, ethical concerns about patient recruitment into trials, dubious informed consent rules and reliance on smaller, quickly executed clinical studies. There are also concerns about the reliability of China’s large-scale drug and biologics manufacturing. The U.S. could establish a Chinese-U.S. office to help guide Chinese pharmaceutical companies seeking FDA and EMA approval to enter western markets. The example has precedent: In now-dated Russian CTR programs, former U.S. pharmaceutical executives, former FDA evaluators and other industry experts helped Russian startup companies meet regulatory milestones for testing drugs in human trials. And a 2004 vaccine training program in Moscow by scientists from Massachusetts General Hospital helped lead, eventually, to Russia’s successful development of the Sputnik V vaccine for Covid-19.

All of these approaches are built on the underlying insight of America’s CTR efforts: that biosafety is built on collaboration, positive incentives and strong scientific and public health alliances. China is a far more sophisticated, and more resistant, government than most of our previous collaborators, but that only argues for more sophisticated forms of collaboration.

There are other approaches as well. One used by CTR to promote transparency about laboratory risks was to share lessons learned from U.S. accidents. As part of my work, I’ve traveled to several high-risk countries giving biosecurity workshops on mistakes made by American researchers — a way to leaven our teaching on biosecurity practices with a dose of humility. The workshop’s philosophy is driven by insights from Matthew Syed’s book Black Box Thinking, which argues that organizations that investigate failure in objective, unthreatening ways — as the aviation industry has managed to do — can best avoid repeating mistakes. In the presentation, we discuss common laboratory acquired infections such as TB, brucellosis, coccidioidomycosis and influenza; with researchers from higher containment labs, we include a tragic case of Ebola that killed a Russian colleague, and an infection from a bacteria engineered through gain-of-function research to be resistant to all antibiotics that killed a Moscow graduate student, both in 2004. As China continues work with dangerous pathogens, its researchers will be more and more eager to hear how we assess and prevent those kinds of risks, and how we care for highly contagious patients with diseases novel to them such as Marburg, Lassa and Ebola.

The U.S. edge in technology gives us some other carrots we can use to bring to the table. For example, while China has far surpassed the genomic sequencing capacity of the U.S. in raw processing power, our systems remain better at predicting pathogen and tumor evolution and identifying escaped mutants before they actually occur. This is an extremely valuable field that is still in its infancy in China. We are also on the edge of being able to design variant-proof vaccines, while China is still chasing yesterday’s virus. Several U.S. companies are now able to construct new antibodies against targets purely on a computer. The actual manufacture of the antibody is a formality.

Some of these technologies could prove very useful in the origins investigation itself. For example, some of the most exciting new forensic immune technologies are those that decipher the history of individual and community immunity. In China, right now, human blood and serum samples from 2019 are scattered widely across both traditional and Western hospitals, as well as medical research centers and biobank freezers. Academic medical colleagues in the U.S. and other countries have suggested a number of strategies for using American technology and Chinese clinical samples to rewind the tape to find the earliest evidence of Covid infection. Since Chinese law prevents the export of human samples containing genetic information, the work could be performed in-country by a U.S.-Chinese team. If we, or Chinese partners, were to find evidence of a Covid-like infection in blood samples taken from a sick villager near a bat cave in early 2019, but none in Wuhan urbanites until December 2019, that would strongly support natural events as the cause of Covid-19. This conclusion would be great for China. Conversely, if the blood sample from villages around bat caves remained unchanged over the years, but blood samples from Wuhan citizens started showing evidence of an infection from a Wuhan Institute of Virology virus, then that data would support the lab leak scenario.

All these approaches offer a way to find common ground to work with China, not just on the Covid investigation, but on the investigations we’ll need to run after that. The alternative approach is of course some kind of hardball — whatever that means. If the U.S. did decide to cut off partnerships, or technology, or connections to Western science, we need to worry seriously about the aftereffects. Those who would be most impacted aren’t Party officials in Beijing but rather the Chinese researchers who are first to identify new and deadly viruses, our Chinese physician colleagues who teach us how to care for victims of new diseases, and the drug and vaccine developers who we need to manufacture safe, low-cost vaccines to protect the rest of the world.