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.  

There is plenty of research on how the rapid warming of the planet is going to have growing adverse impacts on global economies, health, food supplies and natural disasters.

A new study now suggests that as temperatures continue to rise — particularly with more and more 90-plus-degree days — more fetuses and infants will experience economic loss by age 30.

“There is a growing body of evidence that finds that shocks to the fetus and young child — whether nutritional, environmental, economic or stress-related — have long-term consequences on health, education and economic outcomes throughout the life cycle,” said Maya Rossin-Slater, an assistant professor of health research and policy at Stanford Medicine and a faculty fellow at the Stanford Institute for Economic Policy Research.

Rossin-Slater published her study Dec. 4 in the Proceedings of the National Academy of Sciences, indicating early-life exposure to extreme temperatures is linked to potential losses in human capital. Her co-authors are Adam Isen, an economist with the U.S. Department of Treasury, and Reed Walker, an assistant professor at University of California, Berkeley.

The researchers used data from the U.S. Census Bureau’s Longitudinal Employer Household Dynamic Files, which contain information on adult labor market outcomes linked to county and exact date of birth. They looked at weather in counties in 24 states on any given day, and then measured how many days with average temperatures above 90 degrees a child born on that day in that county would have experienced during gestation and during the first year of life. They then compared the earnings of individuals who were exposed to different numbers of such hot days, but who were of the same race and gender, and born in the same county and on the same day of the year (but in different years).

Each day a fetus or infant experiences 90-plus-degree temperatures, Rossin-Slater and her co-authors found that he made $30 less a year on average, or $430 over the course of his lifetime. While that may not seem like a huge loss of income, the authors point out that their study is best understood from a population-level perspective rather than from an individual one.

“There is a lot of research already showing that extreme heat has immediate effects on labor market productivity and GDP,” she said. “What we are saying is that there is another wrinkle to this — that there can be consequences many years later, on cohorts who are still in the womb.”

Most Americans today only experience one day a year that is 90 degrees or hotter. But the Climate Impact Lab has indicated that if countries continue to take only moderate action on climate change, by the end of this century there will be about 43 such days a year.

So, if you multiple a $30 annual loss a day by 43 days, you come up with an average $1,290 a year — and compounded in large populations of pregnant women in hot climates.

“Prior research shows that exposure to extreme heat in utero leads to lower birth weight and increases infant mortality,” said Rossin-Slater, who is also a core faculty member at Stanford Health Policy. She said poor fetal and infant health could impact adult earnings in three ways: cognitive impairment, poor health that causes people to miss school or work, and less non-cognitive skill development such as self-control.

“With regard to exposure to heat specifically, fetuses and infants are especially sensitive because their thermoregulatory systems are not fully developed and they have less capacity to self-regulate when their bodies are exposed to extreme temperatures,” Rossin-Slater said.

Hot Zones and Air Conditioners

The obvious questions that arise from such research: What happens to the babies of women who already live in very high temperatures? And why not just ensure that all pregnant women have air conditioners, at least in the developed world where it would be more affordable?

Women in warm zones such as parts of Africa and South Asia, as well as U.S. cities like Phoenix and Washington, D.C., shouldn’t worry too much. The loss of income is relatively little and people living in hot climates may actually adapt over time to exposure to extreme heat.

“Our study is not saying that individual people should be doing something differently to avoid exposure to extreme heat,” Rossin-Slater said. “Instead, we think we are providing additional evidence for the possible population-level consequences of climate change and the projected increase in the number of days with extreme temperatures.”

And what about those air conditioners? The cohorts in the study are actually born in the 1970s, during a period of rapid expansion in air conditioning across American households. The researchers found the earning losses went away in areas where most people got air conditioners installed.

“If we think that there is something biological going on as a result of the fetus being overheated, then it makes sense that AC, which prevents the overheating, can mitigate this negative effect,” Rossin-Slater said.

But it’s important to recognize, she said, that air conditioners come with costs, both financial from the perspective of individuals and households who can and can’t afford such systems, and environmental from the perspective of the country or planet as a whole.

“So this is not a `free’ solution and any cost-benefit calculations related to climate change should take into account this adaption response,” Rossin-Slater said. “But we ought to think about what these results imply at the global level — in many countries that are much hotter than the United States and still don’t have AC. So if we are trying to understand global inequality and the impacts of climate change on developing countries, our results suggest that climate change could play a role in perpetuating global inequality across generations.”

In a shack that now sits below sea level, a mother in Bangladesh struggles to grow vegetables in soil inundated by salt water. In Malawi, a toddler joins thousands of other children perishing from drought-induced malnutrition. And in China, more than one million people died from air pollution in 2012 alone.

Around the world, climate change is already having an effect on human health.

In a recent paper, Katherine Burke and Michele Barry from the Stanford Center for Innovation in Global Health, along with former Wellesley College President Diana Walsh, described climate change as “the ultimate global health crisis.” They offered recommendations to the new United States president to address the urgently arising health risks associated with climate change.

Bangladeshi children make their way through flood waters.

The authors, along with Stanford researchers Marshall Burke, Eran Bendavid and Amy Pickering who also study climate change, are concerned by how little has been done to mitigate its effects on health.

“I think it’s likely that health impacts could be the most important impact of climate change,” said Marshall Burke, an assistant professor of earth system science and a fellow at the Freeman-Spogli Institute for International Studies.

There is still time to ease — though not eliminate — the worst effects on health, but as the average global temperature continues to creep upward, time appears to be running short.

“I think we are at a critical point right now in terms of mitigating the effects of climate change on health,” said Amy Pickering, a research engineer at the Woods Institute for the Environment. “And I don’t think that’s a priority of the new administration at all.”

Health effects of climate change

Even in countries like the United States that are well-equipped to adapt to climate change, health impacts will be significant.

“Extremes of temperature have a very observable direct effect,” said Eran Bendavid, an assistant professor of medicine and Stanford Health Policy core faculty member.

“We see mortality rates increase when temperatures are very low, and especially when they are very high.”

Bendavid also has seen air pollutants cause respiratory problems in people from Beijing to Los Angeles to villages in Sub-Saharan Africa.

“Hotter temperatures make it such that particulate matter and dust and pollutants stick around longer,” he said.

In addition to respiratory issues, air pollution can have long-term cognitive effects. A study in Chile found that children who are exposed to high amounts of air pollution in utero score lower on math tests by the fourth grade.

“I think we’re only starting to understand the true costs of dirty air,” said Marshall Burke. “Even short-term exposure to low levels can have life-long effects.”

Low-income countries like Bangladesh already suffer widespread, direct health effects from rising sea levels. Salt water flooding has crept through homes and crops, threatening food sources and drinking water for millions of people.

“I think that flooding is one of the most pressing issues in low-income and densely populated countries,” said Pickering. “There’s no infrastructure there to handle it.”

Standing water left over from flooding is also a breeding ground for diseases like cholera, diarrhea and mosquito-borne illnesses, all of which are likely to become more prevalent as the planet warms.

On the flip side, many regions of Sub-Saharan Africa — where clean water is already hard to access — are likely to experience severe droughts. The United Nations warned last year that more than 36 million people across southern and eastern Africa face hunger due to drought and record-high temperatures.

Residents may have to walk farther to find water, and local sources could become contaminated more easily. Pickering fears that losing access to nearby, clean water will make maintaining proper hygiene and growing nutritious foods a challenge.

Climate change will affect health in all sectors of society.

All of these effects and more can also damage mental health, said Katherine Burke and her colleagues in their paper. The aftermath of extreme weather events and the hardships of living in long-term drought or flood can cause anxiety, depression, grief and trauma.

Climate change will affect health in every sector of society, but as Katherine Burke and her colleagues said, “….climate disruption is inflicting the greatest suffering on those least responsible for causing it, least equipped to adapt, least able to resist the powerful forces of the status quo.

“If we fail to act now,” they said, “the survival of our species may hang in the balance.”

What can the new administration do to ease health effects?

If the Paris Agreement’s emissions standards are met, scientists predict that the world’s temperature will increase about 2.7 degrees Celsius – still significant but less hazardous than the 4-degree increase projected from current emissions.

The United States plays a critical role in the Paris Agreement. Apart from the significance of cutting its own emissions, failing to live up to its end of the bargain — as the Trump administration has suggested — could have a significant impact on the morale of the other countries involved.

“The reason that Paris is going to work is because we’re in this together,” said Marshall Burke. “If you don’t meet your target, you’re going to be publicly shamed.”

The Trump administration has also discussed repealing the Clean Power Plan, Obama-era legislation to decrease the use of coal, which has been shown to contribute to respiratory disease.

“Withdrawing from either of those will likely have negative short- and long-run health impacts, both in the U.S. and abroad,” said Marshall Burke.

Scott Pruitt, who was confirmed today as the head of the Environmental Protection Agency (EPA), is expected to carry out Trump’s promise to dismantle environment regulations.

Despite the Trump administration’s apparent doubts about climate change, a few prominent Republicans do support addressing its effects.

Secretary of State Rex Tillerson, the former chairman and CEO of Exxon Mobile, supports a carbon tax, which would create a financial incentive to turn to renewable energy sources. He also has expressed support for the Paris Agreement. It is possible that as secretary of state, Tillerson could help maintain U.S. obligations from the Paris Agreement, though it is far from certain whether he would choose to do so or how Trump would react.

More promising is a recent proposal from the Climate Leadership Council. Authored by eight leading Republicans — including two former secretaries of state, two former secretaries of the treasury and Rob Walton, Walmart’s former chairman of the board — the plan seeks to reduce emissions considerably through a carbon dividends plan.

Already an issue, malnutrition will increase with droughts in Sub-Saharan Africa.

Their proposal would gradually increase taxes on carbon emissions but would return the proceeds directly to the American people. Americans would receive a regular check with their portion of the proceeds, similar to receiving a social security check. According to the authors, 70 percent of Americans would come out ahead financially, keeping the tax from being a burden on low- and middle-income Americans while still incentivizing lower emissions.

“A tax on carbon is exactly what we need to provide the right incentives and induce the sort of technological and infrastructure change needed to reduce long-term emissions,” said Marshall Burke.

Pickering added, “This policy is a ray of hope for meaningful action on climate.”

It remains to be seen whether the new administration and congress would consider such a program.

What can academics do to help?

Meanwhile, academics can promote health by researching the effects of climate change and finding ways to adapt to them.

“I think it’s fascinating that there’s just so little data right now on how climate change is going to impact health,” said Pickering.

Studying the effects of warming on the world challenges traditional methods of research.

“You can’t create any sort of experiment,” said Bendavid. “There’s only one climate and one planet.”

The scholars agree that interdisciplinary study is a critical part of adapting to climate change and that more research is needed.

“If ever there was an issue worthy of a leader’s best effort, this is the moment, this is the issue,” said Katherine Burke and her colleagues. “Time is short, but it may not be too late to make all the difference.”

Stanford researchers have determined that more than 15 million children are living in high-mortality hotspots across 28 Sub-Saharan African countries, where death rates remain stubbornly high despite progress elsewhere within those countries.

The study, published online Oct. 25 in The Lancet Global Health, is the first to record and analyze local-level mortality variations across a large swath of Sub-Saharan Africa.

These hotspots may remain hidden even as many countries are on track to achieve one of the U.N. Sustainable Development Goals: reducing the mortality rate of children under 5 to 25 per 1,000 by 2030. National averages are typically used for tracking child mortality trends, allowing left-behind regions within countries to remain out of sight — until now.

The senior author of the study is Eran Bendavid, MD, MS, an assistant professor of medicine and core faculty member at Stanford Health Policy. The lead author is Marshall Burke, PhD, an assistant professor of Earth System Science and a fellow at the Freeman Spogli Institute’s Center on Food Security and the Environment.

Decline in under-5 mortality rate

The authors note that the ongoing decline in under-5 mortality worldwide ranks among the most significant public and population health successes of the past 30 years. Deaths of children under the age of 5 years have fallen from nearly 13 million a year in 1990 to fewer than 6 million a year in 2015, even as the world’s under-5 population grew by nearly 100 million children, according to the Institute for Health Metrics and Evaluation.

“However, the amount of variability underlying this broad global progress is substantial,” the authors wrote.

“Mortality numbers are typically tracked at the national level, with the assumption that national differences between countries, such as government spending on health, are what determine progress against mortality,” Bendavid said. “The goal of our work was to understand whether national-level mortality statistics were hiding important variation at the more local level — and then to use this information to shed light on broader mortality trends.”

The authors used data from 82 U.S. Agency for International Development surveys in 28 Sub-Saharan African countries, including information on the location and timing of 3.24 million births and 393,685 deaths of children under 5, to develop high-resolution spatial maps of under-5 mortality from the 1980s through the 2000s.

Using this database, the authors found that local-level factors, such as climate and malaria exposure, were predictive of overall patterns, while national-level factors were relatively poor predictors of child mortality.

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Temperature, malaria exposure, civil conflict

“We didn’t see jumps in mortality at country borders, which is what you’d expect if national differences really determined mortality,” said co-author Sam Heft-Neal, PhD, a postdoctoral scholar in Earth System Science. “But we saw a strong relationship between local-level factors and mortality.”

For example, he said, one standard deviation increase in temperature above the local average was related to a 16-percent higher child mortality rate. Local malaria exposure and recent civil conflict were also predictive of mortality.

The authors found that 23 percent of the children in their study countries live in mortality hotspots — places where mortality rates are not declining fast enough to meet the targets of the U.N. Sustainable Development Goals. The majority of these live in just two countries: Nigeria and the Democratic Republic of Congo. In only three countries do fewer than 5 percent of children live in hotspots: Benin, Namibia and Tanzania.

As part of the research, the authors have established a high-resolution mortality database with local-level mortality data spanning the last three decades to provide “new opportunities for a deeper understanding of the role that environmental, economic, or political conditions play in shaping mortality outcomes.”  The database, available at http://fsedata.stanford.edu, is an open-source tool for health and environmental researchers, child-health experts and policymakers.

“Our hope is that the creation of a high-resolution mortality database will provide other researchers new opportunities for deeper understanding of the role that environmental, economic or political conditions play in shaping mortality outcomes,” said Bendavid.  “These data could also improve the targeting of aid to areas where it is most needed.”

The research was supported by a grant from the Stanford Woods Institute for the Environment.