This interview by Bruce Goldman was originally published by the Stanford School of Medicine.

On May 13, the journal Science published a letter, signed by 18 scientists, stating that it was still unclear whether the virus that causes COVID-19 emerged naturally or was the result of a laboratory accident, but that neither cause could be ruled out. David Relman, MD, the Thomas C. and Joan M. Merigan Professor and professor of microbiology and immunology, spearheaded the effort.

Relman is no stranger to complicated microbial threat scenarios and illness of unclear origin. He has advised the U.S. government on emerging infectious diseases and potential biological threats. He served as vice chair of a National Academy of Sciences committee reviewing the FBI investigation of letters containing anthrax that were sent in 2001. Recently, he chaired another academy committee that assessed a cluster of poorly explained illnesses in U.S. embassy employees. He is a past president of the Infectious Diseases Society of America.

Stanford Medicine science writer Bruce Goldman asked Relman to explain what remains unknown about the coronavirus’s emergence, what we may learn and what’s at stake.

1. How might SARS-CoV-2, which causes COVID-19, have first infected humans?

Relman: We know very little about its origins. The virus’s closest known relatives were discovered in bats in Yunnan Province, China, yet the first known cases of COVID-19 were detected in Wuhan, about 1,000 miles away.

There are two general scenarios by which this virus could have made the jump to humans. First, the jump, or “spillover,” might have happened directly from an animal to a human, by means of an encounter that took place within, say, a bat-inhabited cave or mine, or closer to human dwellings — say, at an animal market. Or it could have happened indirectly, through a human encounter with some other animal to which the primary host, presumably a bat, had transmitted the virus.

Bats and other potential SARS-CoV-2 hosts are known to be shipped across China, including to Wuhan. But if there were any infected animals near or in Wuhan, they haven’t been publicly identified.

Maybe someone became infected after contact with an infected animal in or near Yunnan, and moved on to Wuhan. But then, because of the high transmissibility of this virus, you’d have expected to see other infected people at or near the site of this initial encounter, whether through similar animal exposure or because of transmission from this person.

2. What’s the other scenario?

Relman: SARS-CoV-2 could have spent some time in a laboratory before encountering humans. We know that some of the largest collections of bat coronaviruses in the world — and a vigorous research program involving the creation of “chimeric” bat coronaviruses by integrating unfamiliar coronavirus genomic sequences into other, known coronaviruses — are located in downtown Wuhan. And we know that laboratory accidents happen everywhere there are laboratories.

All scientists need to acknowledge a simple fact: Humans are fallible, and laboratory accidents happen — far more often than we care to admit. Several years ago, an investigative reporter uncovered evidence of hundreds of lab accidents across the United States involving dangerous, disease-causing microbes in academic institutions and government centers of excellence alike — including the Centers for Disease Control and Prevention and the National Institutes of Health.

SARS-CoV-2 might have been lurking in a sample collected from a bat or other infected animal, brought to a laboratory, perhaps stored in a freezer, then propagated in the laboratory as part of an effort to resurrect and study bat-associated viruses. The materials might have been discarded as a failed experiment. Or SARS-CoV-2 could have been created through commonly used laboratory techniques to study novel viruses, starting with closely related coronaviruses that have not yet been revealed to the public. Either way, SARS-CoV-2 could have easily infected an unsuspecting lab worker and then caused a mild or asymptomatic infection that was carried out of the laboratory.

3. Why is it important to understand SARS-CoV-2’s origins?

Relman: Some argue that we would be best served by focusing on countering the dire impacts of the pandemic and not diverting resources to ascertaining its origins. I agree that addressing the pandemic’s calamitous effects deserves high priority. But it’s possible and important for us to pursue both. Greater clarity about the origins will help guide efforts to prevent a next pandemic. Such prevention efforts would look very different depending on which of these scenarios proves to be the most likely.

Evidence favoring a natural spillover should prompt a wide variety of measures to minimize human contact with high-risk animal hosts. Evidence favoring a laboratory spillover should prompt intensified review and oversight of high-risk laboratory work and should strengthen efforts to improve laboratory safety. Both kinds of risk-mitigation efforts will be resource intensive, so it’s worth knowing which scenario is most likely.

4. What attempts at investigating SARS-CoV-2’s origin have been made so far, with what outcomes?

Relman: There’s a glaring paucity of data. The SARS-CoV-2 genome sequence, and those of a handful of not-so-closely-related bat coronaviruses, have been analyzed ad nauseam. But the near ancestors of SARS-CoV-2 remain missing in action. Absent that knowledge, it’s impossible to discern the origins of this virus from its genome sequence alone. SARS-CoV-2 hasn’t been reliably detected anywhere prior to the first reported cases of disease in humans in Wuhan at the end of 2019. The whole enterprise has been made even more difficult by the Chinese national authorities’ efforts to control and limit the release of public health records and data pertaining to laboratory research on coronaviruses.

In mid-2020, the World Health Organization organized an investigation into the origins of COVID-19, resulting in a fact-finding trip to Wuhan in January 2021. But the terms of reference laying out the purposes and structure of the visit made no mention of a possible laboratory-based scenario. Each investigating team member had to be individually approved by the Chinese government. And much of the data the investigators got to see was selected prior to the visit and aggregated and presented to the team by their hosts.

The recently released final report from the WHO concluded — despite the absence of dispositive evidence for either scenario — that a natural origin was “likely to very likely” and a laboratory accident “extremely unlikely.” The report dedicated only 4 of its 313 pages to the possibility of a laboratory scenario, much of it under a header entitled “conspiracy theories.” Multiple statements by one of the investigators lambasted any discussion of a laboratory origin as the work of dark conspiracy theorists. (Notably, that investigator — the only American selected to be on the team — has a pronounced conflict of interest.)

Given all this, it’s tough to give this WHO report much credibility. Its lack of objectivity and its failure to follow basic principles of scientific investigation are troubling. Fortunately, WHO’s director-general recognizes some of the shortcomings of the WHO effort and has called for a more robust investigation, as have the governments of the United States, 13 other countries and the European Union.

5. What’s key to an effective investigation of the virus’s origins?

Relman: A credible investigation should address all plausible scenarios in a deliberate manner, involve a wide variety of expertise and disciplines and follow the evidence. In order to critically evaluate other scientists’ conclusions, we must demand their original primary data and the exact methods they used — regardless of how we feel about the topic or about those whose conclusions we seek to assess. Prior assumptions or beliefs, in the absence of supporting evidence, must be set aside.

Investigators should not have any significant conflicts of interest in the outcome of the investigation, such as standing to gain or lose anything of value should the evidence point to any particular scenario.

There are myriad possible sources of valuable data and information, some of them still preserved and protected, that could make greater clarity about the origins feasible. For all of these forms of data and information, one needs proof of place and time of origin, and proof of provenance.

To understand the place and time of the first human cases, we need original records from clinical care facilities and public health institutions as well as archived clinical laboratory data and leftover clinical samples on which new analyses can be performed. One might expect to find samples of wildlife, records of animal die-offs and supply-chain documents.

Efforts to explore possible laboratory origins will require that all laboratories known to be working on coronaviruses, or collecting relevant animal or clinical samples, provide original records of experimental work, internal communications, all forms of data — especially all genetic-sequence data — and all viruses, both natural and recombinant. One might expect to find archived sequence databases and laboratory records.

Needless to say, the politicized nature of the origins issue will make a proper investigation very difficult to pull off. But this doesn’t mean that we shouldn’t try our best. Scientists are inquisitive, capable, clever, determined when motivated, and inclined to share their insights and findings. This should not be a finger-pointing exercise, nor an indictment of one country or an abdication of the important mission to discover biological threats in nature before they cause harm. Scientists are also committed to the pursuit of truth and knowledge. If we have the will, we can and will learn much more about where and how this pandemic arose.  

1. Can you give us an overview of your research and the topics you’re investigating?

My research addresses the following question: Why are some authoritarian regimes more responsive to social unrest than others? While it might seem counterintuitive to think of authoritarian regimes in this light, repression and responsiveness often occur in tandem under authoritarian rule. Centered on a comparison between Vietnam and China, I document the steps that each has taken to address social discontent fueled by pervasive government seizures of rural land. In response to societal input between 2003 and 2017, Vietnam enacted comprehensive and programmatic reforms to reduce the permissible scope for government land expropriation whereas those enacted by China were relatively marginal and piecemeal. At the subnational level, this difference has had important implications for land rights and the security of villagers in both countries. In summary, despite their many similarities, the manner and degree of their responsiveness have varied. My research then traces the historical origins that undergird the political development and institutional character of Vietnam and China’s divergent responsiveness to social unrest. 

2. How did you first become interested in these topics?

My interest in the repressive-responsive character of authoritarian regimes stems from my preoccupation with questions of political legitimacy, societal resistance, and institutional dynamics in authoritarian contexts. One particular experience that stoked my interest was my visit to Wukan, Guangdong in 2016. Wukan was once hailed as an emblematic case of grassroots democracy and accommodation by the Chinese state, when villagers’ outcries against the local government’s seizure of their land resulted in the re-election of the village committee in 2012. Yet, when I visited in 2016, villagers expressed that nothing had changed, and that “everything that could be done has already been done.” This experience led me to question what responsiveness means in authoritarian contexts.

3. During the last year, the world has changed significantly because of the pandemic and fluctuating politics in many nations. Have these changing global situations given you any new insights into your research?

The pandemic has underscored the need for a nuanced and contextual understanding of democracies and non-democracies. For instance, the variation in state responses to COVID-19 suggests that there is no clear correlation between responsiveness or the effectiveness of government responses to COVID-19 and regime types. Consider Vietnam’s proactive approach and success at containing the pandemic as opposed to the US. Other recent developments such as the crackdowns on pro-democracy protests in Thailand and mass protests against the recent military coup in Myanmar showcase how quickly state responsiveness to social demands can erode, even in multi-party states.

4. What has your experience as one of our Shorenstein Fellows been like during this unusual period of time when we haven’t physically been together at APARC?

My fellowship has been remote, and I have therefore needed to be much more proactive to stay as engaged as possible. I have consulted with my mentor often over Zoom, and reached out to other scholars for their feedback and advice on my research. I have also especially appreciated the chance to participate in the China Social Science Workshop, where I've shared my work and learned from other presenters. Other postdoctoral fellows at APARC and I have also gotten together virtually to exchange stories and to share our experiences from this unusual year.  

5. What are some of the things you've done during this past year to give yourself a break from work and have some fun?

Due to the pandemic, I have been living back home to Austin, Texas, since March of last year. The last time that I was home for this long must have been after I graduated from college. So, for the first time in a long time, I've planted tomatoes, eggplants, and sunflowers in our garden, and I've really enjoyed watching them bloom and ripen. With everything growing, it feels like I've spent most of my break in our backyard defending our flowers, fruits, and vegetables from squirrels and bunnies! But luckily I also have our two dogs, Wishie and Sushi, to help me!

6. As the state of the pandemic changes and things in academia and our communities, what are some things you are looking forward to both professionally and personally?

I'm certainly looking forward to having conferences in person again! I'm also still not sure when it will be possible and safe for me to visit Asia again, especially Vietnam and China, but I have missed these places. I'm also learning Khmer this summer, and I'm excited to eventually visit Cambodia to pursue my research there.

This commentary by Kiyoteru Tsutsui and Charles Crabtree was originally published in The Hill.

The recent White House summit meeting between President Biden and Japanese Prime Minister Yoshihide Suga signaled to the world, and especially to China, that the U.S.-Japan alliance is strong and ready for intensifying competition in Asia.

For the first time in more than 50 years, the Japanese and American leaders mentioned Taiwan in their joint statement. China immediately responded with strong words, as expected, but since has moderated its tone. Furthermore, Chinese leader Xi Jinping participated in the U.S.-organized Leaders Summit on Climate the week after the Biden-Suga meeting and took a collaborative stance, a hopeful sign that competition will not eliminate the possibility of some collaboration and that climate change is an area where Beijing, Tokyo and Washington can work together.

But the U.S. and Japan still have at least three concerns about China: Beijing’s continued posturing on Taiwan and the Senkaku Islands; its significant leverage in economic relations; and its repression of human rights in Xinjiang, Hong Kong and beyond. How should the alliance handle these important issues? 

On the security front, America’s return to multilateralism under Biden is a welcome development for Japan and other like-minded states in the region. The U.S.-Japan alliance is obviously central in the coalition of democratic nations concerned about China’s ambitions. The primary goal of these countries ought to be walking the thin line between demonstrating their resolve to counter any aggressive behavior by China with force and avoiding any unnecessary provocation against China. 

Toward that end, the most promising framework is the Quad that includes India and Australia in addition to Japan and the U.S. The first-ever leader-level meeting in March elevated the Quad’s status significantly. While it still is a long way from becoming a NATO-like security apparatus — and it’s not even clear if that’s the consensus goal — it could help stabilize the region by creating a credible counterweight to check China’s territorial ambitions.

Beyond the Quad, the inclusion of other like-minded stakeholders such as South Korea and ASEAN countries on security matters is important. With South Korean President Moon Jae-in’s visit to Washington planned in late May, a good first step for the Biden administration would be to invest some diplomatic capital in mending fences between Japan and South Korea. A full-scale reconciliation between the two regional powers is unlikely this year; Suga faces elections in the fall, for which he needs to consolidate the conservative base, and Moon is a lame duck with limited political power. But some reconciliation would be welcome for the U.S. as it seeks to resurrect the trilateral alliance with Japan and South Korea to complement the Quad in deterring China’s ambitions and addressing the threat posed by North Korea. 

In the economic domain, China is arguably even more difficult to contain, being the largest trade partner for virtually all the countries in the region. Decoupling from China was a key theme at the Biden-Suga summit, but this is a task that has proven much easier said than done. From semiconductors to rare earth minerals, the battle for key materials for the 21st century economy will only intensify, and China’s grand scheme in the Belt and Road Initiative needs to be countered by a similarly grand long-term strategy that would flesh out the Free and Open Indo-Pacific vision.

In this regard, the U.S.-Japan Competitiveness and Resilience Partnership can be quite consequential. In addition to pledging cooperation on “sensitive supply-chain” issues, it outlines the agenda for technological innovation that cuts across security and economic domains, making it a critical tool in the competition with China. This is because whoever develops an edge in transformational technologies — such as artificial intelligence, 5G infrastructure, and outer space development — will enjoy diplomatic and military advantages as well as economic profits. The combined $4.5 billion investment in the partnership is a good first step to ensuring that the U.S. and Japan retain an innovation advantage. Additional expenditures likely will be necessary, though, considering China’s commitment in these areas.

On human rights, Japan and America take different approaches. While the U.S. has called the situation in Xinjiang a genocide and imposed sanctions there, as well as in Myanmar following the military coup, Japan has taken a more subdued stance. This is a standard approach for Tokyo, which prefers to emphasize engagement with violating governments.

The Biden administration seems to accept Suga’s strategy of engagement, and perhaps the diplomatic channel that this approach provides can be useful in negotiating some kind of settlement. However, the strategy of engagement that has produced some benefits in countries such as Thailand and possibly Myanmar is unlikely to be as effective with China. Furthermore, several Western corporations are facing boycotts in China for taking a stand against forced labor in Xinjiang. If Japanese corporations avoid paying the price and continue business as usual, Tokyo might face greater pressure to take some action. Given the central importance of the Chinese market for Japanese businesses, this could give rise to significant tension between Tokyo and Washington. 

On all these dimensions, for Japan and the U.S. to be effective in countering China, both Biden and Suga would have to consolidate domestic support. Biden’s first 100 days generally were seen as successful, with COVID-19 vaccine distribution going smoothly and Congress passing ambitious spending bills. Besides, Biden has at least until the midterm elections in November 2022 to move things forward.

The timetable is less friendly for Suga, who needs to win the Liberal Democratic Party (LDP) presidential election in September and hold a House of Representatives election by October. His fate will be shaped in large measure by his government’s pandemic response and how that influences economic fortunes, and to a lesser extent the success of the Tokyo Olympics. Most Tokyo insiders predict that he will remain in office past October, citing weak opposition both in and outside of the ruling LDP. If, however, COVID-19 vaccine distribution does not move forward by the fall, as projected by the government, and the economy continues to slide, that could still trip him up.

Only with domestic political stability and economic prosperity can Tokyo and Washington take the next steps in projecting strength vis-à-vis China, and that is the best deterrent against China’s expansionist ambitions and toward ensuring peace and stability in the Indo-Pacific area.