As the Covid-19 pandemic spread across the globe in January 2020, virus hunters pushed for funding to uncover more “yet-to-be-recognized deadly viruses.” They believed that cataloging viruses in wildlife could help prevent future pandemics.
“In China alone, we sampled >10,000 bats and ~2,000 other mammals, using PREDICT protocols to discover 52 novel SARS related-CoV’s, including the closest relative of the Wuhan nCoV [SARS-CoV-2],” boasts a University of California, Davis letter to Senator Dianne Feinstein requesting federal support for programs like PREDICT, the government’s flagship virus-hunting program.
However, the letter didn’t mention the risks of collecting and studying SARS-related viruses, which have the potential to be lethal or highly transmissible. The U.S. Energy Department, Federal Bureau of Investigation, and the World Health Organization now recognize that a research accident with SARS-CoV-2 may have sparked one of the biggest pandemics in history.
Indeed, the entire chain of virus hunting work entails risks that can lead to accidental infection, from handling animals to experiments in the lab. The risks can even extend beyond the program: published virus genetic sequences allow other groups to perform high risk research, and can even give terrorists instructions for bioweapons.
The U.S. Agency for International Development (USAID), which spent hundreds of millions of dollars funding virus-hunting work, is attempting to address biosafety loopholes that existed in previous programs. However, new documents obtained by U.S. Right to Know show that their latest precautions center around lab work. The risks involved in handling wildlife and publicly publishing sequences of potential pathogens remain.
Unfortunately, these risks are inherent to virus hunting, calling into question the necessity of such programs, and whether their purported benefits justify the risks of triggering a pandemic.
“The programs pose potentially existential risks and provide no–zero–civilian practical benefits.” says Richard Ebright, a molecular biology professor at Rutgers University. “The only applications are bioweapons-agents discovery and bioweapons-agents threat assessment.”
USAID is currently reviewing DEEP VZN, the government’s newest virus-hunting program, after the White House National Security Council and Office of Science and Technology Policy expressed concerns that data from the program could be exploited by foreign actors to develop bioweapons.
The House Committee on Energy and Commerce also requested an investigation into the risks and benefits of programs like DEEP VZN. The committee expressed concerns that such programs would not be able to predict which viruses pose a threat to human health, and that collecting and studying viruses would increase the chances of an accidental outbreak. A key question in their letter is whether methods safer than field sampling can be used to achieve the program’s goals.
“Logically, it makes sense to inventory threats we have out there and get ahead of it. But in the process of trying to find out how to stop a pandemic, are you creating one?” Senator Lindsey Graham told Josh Rogin of the Washington Post. Sen. Graham wanted to suspend funding for DEEP VZN until the proposed work and safety protocols were more transparent.
“USAID, in consultation with our colleagues across the Administration and with Congress, is undertaking a comprehensive review process to make sure the most rigorous safeguards are in place before field research under DEEP VZN can begin. Because field implementation research has not yet started, there are not further details to share at this time,” wrote USAID in response to questions about DEEP VZN’s safety protocols.
DEEP VZN — short for Discovery & Exploration of Emerging Pathogens Viral Zoonoses — is a 5-year, $125 million USAID project that aims to discover and study novel viruses with pandemic potential. Launched in October of 2021, the program is led by Washington State University in collaboration with the University of Washington, Washington University in St. Louis, PATH, and FHI 360 (Family Health International).
Both PATH and FHI 360 are U.S.-based organizations that aim to address health challenges, primarily in low or middle-income countries.
DEEP VZN follows PREDICT, USAID’s $200 million viral discovery project that lasted from 2009 to 2020. Led by UC Davis, EcoHealth Alliance, and Metabiota, PREDICT sampled more than 160,000 animals and people in over 30 countries looking for virological threats. The program discovered nearly 1,000 novel viruses, including over 100 coronaviruses and a new ebolavirus.
The premise of these projects is simple: Finding and studying deadly pathogens before they spill over from animals to people may allow governments to respond to, predict, or even prevent future pandemics.
Yet some scientists worry that viral discovery programs like PREDICT and DEEP VZN risk causing the pandemics they aim to prevent, either by exposure in the field, an accident in the lab, or by providing malefactors with the information they need to synthesize a pandemic-ready pathogen.
Concerns ran deep enough that White House National Security Council and Office of Science and Technology Policy officials suggested ending DEEP VZN in December 2021.
New U.S. Right to Know documents give an unprecedented look into DEEP VZN’s safety precautions.
The documents show DEEP VZN is trying to address risks associated with its predecessor PREDICT, but these measures do not assuage critics’ fears that the program could lead to a new pandemic.
The DEEP VZN proposal recognizes that “>80% of novel virus characterization can be performed in the absence of virus isolation.” It was amended to state that “ there will be no isolation of and studies using novel coronaviruses, paramyxoviruses, or filoviruses”, and that they will inactivate all viral samples as soon as possible.
The new precautions also “strictly prohibit Dual-Use Research of Concern with a focus on Gain of Function Research,” research on live animals, and ranking viruses according to their risk of starting a pandemic.
DEEP VZN’s precautions contrast with PREDICT, whose funds were used to isolate novel coronaviruses, create chimeras, and analyze and publish which viruses posed the greatest risk of infecting humans. PREDICT may not have inactivated about half of its collected samples, and did not expressly prohibit gain-of-function research with newly discovered viruses or dual use research of concern.
The newest safety precautions seem designed to prevent the kind of research some scientists worry could lead to a pandemic.
Yet though the proposal for DEEP VZN appears to prohibit gain-of-function research, the term isn’t clearly defined by the scientific community, and isn’t described in more detail in their proposal.
The definition is murky enough that the NIH did not apply rules restricting gain-of-function research to experiments that constructed chimeric viruses more pathogenic than the parent virus in humanized mice.
“Razor thin” safety margins when handling wildlife
While DEEP VZN’s precautions may mitigate risk in the lab, the risk of exposure in the field remains.
Bites and scratches can cut through gloves, and fluids like blood, urine, and saliva have splattered into researchers’ faces.
Standard safety gear like Tyvek suits may offer inadequate protection. “In our experience Tyvek easily tears and allows exposure to undergarments or skin,” EcoHealth Alliance stated on a January 25th 2017 PREDICT team call.
They also noted that “gloves make handling animals difficult in hot/humid areas due to perspiration…”, which could tempt virus hunters to remove them.
Virus hunters can become infected even if they use all appropriate safety gear and have no obvious exposure to animals or their secretions.
“Workers who collect viral samples in the wild will be exposed to viruses they otherwise would not be exposed to,” said Justin Kinney, an Associate Professor at Cold Spring Harbor Laboratory and co-founder of Biosafety Now, a non-profit that advocates for increased regulations on pathogen research. “There is a risk that some workers could become infected with previously undiscovered viruses, could transmit those viruses to others, and could potentially trigger a new pandemic.”
According to virus hunter and infectious disease specialist Michael Callahan in Politico, “…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.”
However, documents obtained by U.S. Right to Know show that PREDICT thought the risk of infection during sampling was minimal.
“It is highly unlikely that PREDICT team members, as part of their routine activities, are at increased risk of exposure to pathogens from the animals being sampled above the background level of the local community who actively hunt and consume many of the animal species being sampled,” one document reads.
Viral sequences pose information risk
Some scientists and biosafety experts worry that other labs will use viral sequences published by DEEP VZN to perform high-risk experiments, even if DEEP VZN doesn’t.
These concerns are not unfounded, considering novel coronaviruses like swine acute diarrhea syndrome coronavirus (SADS) discovered by PREDICT have been recovered and studied outside of the project.
Publishing the sequences of potential pathogens could even give bad actors the “blueprints for an arsenal of plagues,” according to Kevin Esvelt, a biologist and professor at the Massachusetts Institute of Technology.
“Virologists will almost certainly use other funds to resurrect some of the newly identified viruses from knowledge of the viral genomes. And unless stringent new biosafety regulations are adopted by the US and other governments, dangerous gain-of-function experiments will almost certainly be performed on the newly identified viruses that have the greatest potential to trigger a new pandemic,” said Kinney.
Unfortunately, there are barriers to adopting stringent biosafety regulations. No agency is empowered to create and oversee globally-accepted biosafety standards. In the U.S., safety regulations primarily apply to institutions receiving federal funding.
Richard Ebright echoes Kinney and Esvelt.
“Virus-discovery poses information risks by providing information on the sequences and properties of new potential pandemic pathogens,” Ebright said. “Publication of the sequences provides information that can be used by a rogue nation, organization, or individual to construct a new potential pandemic pathogen and release it to cause a pandemic.”
According to Ebright, this does not mean that virus discovery work is safer if the results are classified.
“The work should not be done. Period.” he said.
He further cautioned that research can deviate significantly from what is written in a proposal.
“There almost always are differences, usually large differences, between the research proposed in a grant application and research performed under a funded grant,” he said.
Indeed, DEEP VZN’s proposal states that no viruses will be isolated “at this time,” leaving the possibility open for the future.
Despite potentially catastrophic risks, civilian benefits are ‘very unclear’
In spite of significant time and funds invested in viral discovery, scientists remain split on the benefits of such programs.
Ravindra Gupta, a microbiology professor at the Cambridge Institute for Therapeutic Immunology and Infectious Diseases, says that programs cataloging viruses are essential.
“Many of those viruses may have human benefit, and so it’s critical that we do understand what’s out there,” he stated at the Pathogens Project Conference, referring to the Global Virome Project, a virus-hunting offshoot of PREDICT.
Increased knowledge of mammalian viruses can also help “rapidly contextualize where, how, and why new human viruses originate in wildlife, ” wrote Colin Carlson, an assistant research professor at Georgetown’s Center for Global Health Science and Security.
He described how PREDICT helped categorize SARS-CoV-2 at the beginning of the pandemic.
“PREDICT-funded work has contributed to the sequence libraries (along with rapid isolation of the virus, and global data sharing) that allowed taxonomists to rapidly classify SARS-CoV-2 and propose candidate origins,” he said.
Opponents of viral discovery programs note that they haven’t predicted any pandemics yet, and any benefits can be achieved by safer means.
“Monitoring of virus in humans, livestock, crops, and wastewater poses little or no risk and provides much greater, and much more immediately actionable, practical benefits,” said Ebright.
Any such viruses have already infected humans or are poised to do so. Early detection can prevent widespread transmission without the risk of introducing novel pathogens to human populations.
Prominent virologists have also argued that an easier, cheaper, and more effective way of preventing pandemics is to monitor people, screening those with a predefined set of symptoms. Indeed, the sheer number of viruses, many of which mutate rapidly, make prediction expensive, time consuming, and maybe even impossible.
Finding animal reservoirs of human pathogens can be challenging even during or in response to an actual outbreak.
“It seems all previous efforts around outbreaks have failed,” wrote Andrew Clements, PREDICT’s USAID senior scientific advisor, in a 2018 email discussing whether PREDICT should sample animals to find the reservoir of an Ebola outbreak.
“The benefits of the research that will be funded by DEEP VZN are very unclear.” said Kinney.
Indeed, only one novel PREDICT virus posed a potential threat to humans. This virus was sequenced from a patient rather than an animal, and only spread to a handful of people.
“Although PREDICT almost certainly discovered hundreds of potential zoonoses, their true zoonotic potential is almost impossible to assess, leading to the surprising statistic that the programme only led to one conclusive discovery of a zoonosis, the Bas-Congo virus,” wrote Carlson.
Steven Salzberg, a biomedical engineering professor at Johns Hopkins University, goes further than Kinney, stating that there are no benefits “whatsoever” to programs like DEEP VZN. He also disagrees with claims that PREDICT-funded work may have helped respond to the pandemic, or shed light on COVID’s origins.
“It’s true that we had a few viruses from animals that told us perhaps where it originated (e.g., from bats) – but 3+ years later, we still don’t have an answer to that question. So it’s simply false to say those sequences helped us identify things at the beginning of the pandemic,” said Salzberg.
“The risk-benefit ratio is extremely unfavorable,” said Ebright. “In particular, virus discovery research in wildlife is not needed for, and does not contribute to, the development of vaccines and drugs.”