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.  

The sports world has been dramatically affected by COVID-19. Not only has there been a significant decline of events for the spectator—both in person and on television—but the impact on the participants themselves has also been unprecedented. Due to social gathering restrictions, organized youth sports have been almost completely shuttered. High schools and colleges have been cancelling their practices and competitive seasons. The PAC-12 recently postponed its football season. The pandemic has also had a dramatic effect on sports at the highest level. Only fairly recently have there been abbreviated attempts to reinstitute professional sports seasons such as Major League Baseball and the National Basketball Association. Even the 2020 Olympic Games in Tokyo were postponed to 2021.

SPICE is helping to develop the CoviDB Speaker Series, a TeachAids initiative which provides free online videos to educate the general public about the ongoing COVID-19 pandemic. For episode 4 of the CoviDB Speaker Series, TeachAids Founder and CEO Dr. Piya Sorcar decided to provide a glimpse into how the pandemic has impacted the lives of two of the world’s greatest athletes. Sorcar enlisted the support of Emmy Award-winning sportscaster Ted Robinson to interview three-time Olympic diver and gold medalist Laura Wilkinson and five-time Olympic gold medalist swimmer and Stanford student Katie Ledecky.

The interview can be viewed here. Robinson drew out insightful perspectives from Ledecky and Wilkinson concerning the uncertainty that they lived with while awaiting the decision about whether the 2020 Olympics would be held, and also their feelings once the decision to postpone the Olympics was made. Wilkinson reflected, “What was frustrating at first, turned out to be really special” as she reflected upon things like spending extra time with her family, including four children. Ledecky added that being able to focus more on her studies at Stanford University definitely helped to create a little more balance in her life. In response to Robinson’s question about maintaining the discipline to train in light of the postponement, Ledecky responded

During a segment of the interview that focused on advice for youth, Ledecky noted, “The work that you put in doesn’t go away… It is always in the bank… At some point in the future, you are going to be able to compete again, have those opportunities to let that work show.” Wilkinson added, “When you want something, it doesn’t matter what people say about you or what they think of you. If you think you want to do this, if this is your goal, you have to go after it because you’re capable of more than you probably think you are. And other people’s opinions do not need to define you or what you’re capable of doing. You define that.”

For each of the first four episodes in the CoviDB Speaker Series, SPICE has developed a teacher’s guide to encourage the showing of the episodes in U.S. classrooms at the secondary school level. Each of the guides includes (1) a summary of the questions that were asked by the interviewer, including terms and definitions, (2) guiding questions for small-group work, and (3) debriefing activities. In the area of debriefing activities, writing prompts such as the following for episode 4 are offered to students.

• Laura and Katie commented on how their lives have been disrupted since the pandemic. Write a diary entry about how your life has been disrupted. What has been especially challenging? What lessons have you learned from the experience?
• Write about a time when you were disappointed with the cancellation of something. How did you cope with it? Did you learn something positive from the experience? Have you ever been in limbo about whether an event was going to happen or not? How did this make you feel?

Other suggested debriefing activities involve the designing of an artistic image, writing of a poem, or writing lyrics to a song that captures the significance of quotes from the interview such the following:

• Laura: The sun is a great healer in a lot of ways, both emotionally and physically.
• Katie: The Olympics is … an opportunity for the world to come together.
• Laura: I think that it [COVID-19] has reminded us of how connected we are as a world and how we all need to be doing our individual parts to combat this.
• Ted: I have been around athletes in team sports who at some point have said that they kept playing because they wanted their kids to see them.

As TeachAids and SPICE think about their work with youth, two statements from the interview were especially poignant to the staffs. Ledecky noted, “This is history [the time of COVID-19] but you don’t have to be afraid of it. Fear is really a mindset… so if you do everything that you can do, there is no point in worrying beyond that because worrying does not help you at all. It is not going to change anything. Do what you can control. Worry about the things that you can control and things that you cannot control, you have to let those go.” Wilkinson stated, “This [challenging time] could be that gift to you. This could be that opportunity to rise to a whole new level. Don’t look at this and be sad and upset. Look at this as an opportunity of how you can get ahead.” Though the statements were intended as advice for youth, in fact, the statements seem relevant today to all of us.

The CoviDB Speaker Series is a TeachAids initiative that is co-sponsored by the Stanford Center for Innovation in Global Health, the University of California San Francisco’s Institute for Global Health Sciences, and the Stanford Program on International and Cross-Cultural Education (SPICE).

Program on Energy and Sustainable Development (PESD) Quantitative Research Associate Ian Hardman co-authored a paper as an undergraduate at the University of Virginia which was published in Science today.  The paper, “Disparities in PM_2.5 air pollution in the United States,” analyzes 36 years of U.S. air pollution data and concludes that while we may have made significant strides in pollution control, we’ve been less successful in addressing disparities of exposure between communities. Read more