When Legit Research is Presented as ‘Controversial’, Good Luck Expecting Science’s Help

The Print reported that there is reason to suspect an Indian institute could have conducted a controversial form of research. It didn’t mention the reason.

Bengaluru: One of the defining features of the ongoing COVID-19 pandemic is the firestorm of debate over the novel coronavirus’s origins. In its current form, there are two competing hypotheses. Zoonotic spillover posits that the coronavirus evolved naturally and then, somewhere in China, jumped from a wild animal to a human host. The lab-leak hypothesis posits that scientists at the Wuhan Institute of Virology – located in the city thought to be ground-zero of the pandemic – were manipulating coronaviruses in a controversial form of research called ‘gain of function’ (GoF), when one or some of them leaked from the lab into the outside world, and seeded a pandemic.

As investigative journalist Katherine Eban wrote, “Without knowing where it came from, we can’t be sure we’re taking the right steps to prevent a recurrence.”

This debate still rages on: either side is yet to produce clinching evidence of their being right. The zoonotic spillover team has been insisting that the possibility they’re offering is more likely. Meanwhile the lab-leak team has been contending with the proliferation of numerous conspiracy theories in its ranks, helped along in no small part by the ramblings of former US President Donald Trump and French Nobel laureate Luc Montagnier.

On June 11, The Print jumped into this fracas with a conspiracy of its own. In a 2,200-word article, it suspected that a study that researchers at the National Centre for Biological Sciences (NCBS), Bengaluru conducted in 2012-2017, and published in 2019, included elements of GoF as well. More than one tweet sharing the article has called it “detailed”, “elaborate” and a “deep-dive”. Both a tweet from @ThePrintIndia and the article’s strapline also call the NCBS study “controversial”. On both counts, the article offers zero proof. Instead, it displays the hallmark of conspiracy theorists – encouraging readers to see evidence in the absence of evidence itself.

The study

The NCBS campus in Bengaluru. Source: NCBS

The NCBS campus in Bengaluru. Source: NCBS

The NCBS study was not controversial; it was fairly straightforward. Beginning in 2012, an NCBS team obtained samples from bats and, later, blood samples from 75 members of the Bomrr clan, in Mimi village, Nagaland, after securing consent in their native language. The team also had ethical clearance from the institute’s human ethics committee, a body approved by the Indian Council of Medical Research (ICMR). It also obtained kidney, lung and spleen samples from bats that the Bomrr were hunting in a cave. As Vrushal Pendharkar explained for The Wire:

When the researchers chemically analysed filovirus strains from the humans and the bats, they found the samples from [one bat species] displayed the same reactivity pattern as that from the humans. This suggested that bats and humans had exchanged the virus but the virus hadn’t affected the humans.

Filovirus is a family of viruses that includes the Ebola and Marburg viruses. They can be deadly. And to its credit, the NCBS team had found that some filoviruses could jump from some bats in a cave in Nagaland into the bodies of the people hunting them – making the location a potential site of zoonotic spillover events for filoviruses. To echo Eban, it’s important to know where and why such sites exist around the world so that we can better anticipate, and potentially avoid, future disease outbreaks.

On February 3, 2020, The Hindu published an article, with a sensational headline at first, quoting sources in government saying the study hadn’t secured the requisite permissions. It fanned misguided speculation that Indian biological specimens and cultural knowledge had been ‘exposed’ to the influence of the Chinese government and the US Army. (The Hindu later changed the headline and its readers’ editor acknowledged the error.)

Two of the authors of the study’s scientific paper were affiliated with the Wuhan Institute of Virology’s department of emerging infectious diseases. The paper had also acknowledged funding from the US Department of Defence’s Defence Threat Reduction Agency (DTRA). And the article zeroed in on these features.

NCBS was quick to deny the allegations. It said in a statement:

Researchers from the Wuhan Institute of Virology were not directly involved in the study. They were listed co-authors ONLY because they supplied reagents critical to the study … This is standard practice for scientific authorship.

Also read: When a News Article Vanishes, We Have More Than Just a Pandemic to Worry About

The statement added that one of the paper’s authors, Ian Mendenhall, was affiliated with the Duke-National University of Singapore (Duke-NUS). The NCBS researchers had shared their test results with Mendenhall for him to compare it to his data from studies in Southeast Asia. And Mendenhall had been the recipient of a grant from the DTRA.

NCBS head of academics Mukund Thattai told The Wire at the time that “there were funds transferred from Duke-NUS to NCBS as part of the joint study reported in the … paper, and Duke-NUS also provided analytic reagents.” According to him, the Department of Atomic Energy (DAE), which administers NCBS, had approved the study and had “given security clearance to the Duke-NUS collaborator. But the ICMR brought to our notice that this still requires, in addition,” an approval from the ICMR’s Health Ministry Screen Committee. The absence of this approval could have triggered ICMR’s probe.

NCBS director Satyajit Mayor told The Wire Science today: “It has been subsequently clarified that such an approval was not required and that the DAE was the competent authority” to approve this project.

So it’s plainly possible that by disclosing Mendenhall’s participation, his source of funds and the Wuhan Institute’s help, the NCBS team was being clear about the circumstances in which its study had been conducted. This is considered good practice in scientific publishing. It doesn’t have immunity from criticism – but nor can we ignore our burden of proof. Demonising it based on vague assertions by unidentified entities – as The Print has done – will give scientists the impression that journalists are out to devalue good research.

In fact, “This is more than a fear now and pervades all engagement of active researchers with journalists,” Mayor said.

Worse, it might encourage scientists to conduct studies of the NCBS’s sort, considered important in the context of human-wildlife interactions and future pandemics, in secrecy. Or – if they lack institutional support and personal strength – they may not do it at all. We already know of scientists who have quit genetic-modification research on similar grounds.

The article by The Print picks up where The Hindu left off: with the ICMR’s probe into NCBS’s supposed lapses. The Print reported that ICMR hasn’t revealed the results of the probe (and Thattai told The Wire earlier that the institute hadn’t received a copy of its report, at the time). It also reached out to ICMR, the prime minister’s office and WHO chief scientist and former ICMR chief Soumya Swaminathan. The first two didn’t respond; Swaminathan denied knowledge of a study on bats that the ICMR funded. NCBS director Mayor responded with a statement; the secretary of the DAE didn’t respond – nor did ICMR’s current chief Balram Bhargava.

The leap

Photo: Denny Luan/Unsplash

At this point, The Print makes a gigantic leap:

The big question that has arisen – especially in the aftermath of similar questions related to SARS-CoV-2 – is whether the NCBS study was a gain of function research or had any gain of function elements.

“Has arisen”? Arisen from where? And who has raised it? Are people in government asking this question or is The Print itself considering this possibility? Either way, why?

The article does not say. It only tells us that a “big question has arisen”, and proceeds to pad it with speculation. Specifically, according to The Print, because (a) ICMR hasn’t announced the results of its probe, (b) NCBS hasn’t published a second paper arising from the filovirus samples, (c) the lab-leak hypothesis and its GoF component has received so much attention, and (d) NCBS director Satyajit Mayor has denied the study had any GoF elements, we have reason to suspect that the NCBS study has GoF elements.

Also read: ICMR Must Decide if it Is India’s Council for Medical Research or its Master’s Voice

For many months, the lab-leak hypothesis was on the margins of the conversation about the novel coronavirus’s origins. In the first half of 2021, however, it accrued enough weight to move to the centre, and demand our attention. It couldn’t have come this far – no matter how unwarranted this ‘journey’ may ultimately prove to be – without the help from some very real real-world issues. Three, for example, are the arguments surrounding the hypothesis, the consideration it has found among some credible scientists and societal issues with how people at large trust, or distrust, scientists.

The article in The Print has none of this going for it, yet it exists, and through its words, exhorts us to believe that the “big question that has arisen” is legitimate and worth our attention. If anything, the article casts the sort of needless doubt on an institution that allows political opportunists to pounce on it, to spin it to advance ideas that further weaken the institution’s ability to withstand such an assault.

Both Rajya Sabha MP Subramanian Swamy and the health ministry have done this. On January 3, 2021, Swamy tweeted that he would file a complaint with the CBI against NCBS for its “completely anti-national and illegal” study. Last year, the Union health ministry alleged that the Manipal Centre for Virus Research (MCVR) had illegally stored Nipah virus samples and that it had conducted a study with American funds sans the ‘right’ government permissions. MCVR’s then chief staunchly denied both allegations, saying the facility had kept the ICMR and the National Centre for Disease Control apprised of their work.

But effectively, as the novel coronavirus was beginning to spread faster, two top research facilities in India found themselves being suspected of ‘anti-national’ activity, and at the mercy of all the arbitrariness it brought. Today, by posing a question with no reason to consider it, The Print stands at risk of allowing the government more opportunities to escape blame for all the other things we know it is doing wrong.

Controversy and Confusion Over The Hindu’s Report of Bengaluru Scientists’ Study

The study had found that a type of virus called filoviruses could have jumped from bats to humans in the South Asia region based on blood samples obtained from individuals in Nagaland.

A controversy erupted on the morning of February 3 after The Hindu newspaper reported that the government had ordered an inquiry into a study by scientists from Bengaluru – among other places – published on October 31, 2019, implying major procedural irregularities. While the report wasn’t clear, rumours surfaced during the day that the issue may have had to do with lack of informed consent.

Later in the day, however, the National Centre for Biological Sciences (NCBS), the institute that the Bengaluru scientists are affiliated with and which is funded – among other sources – by the Department of Atomic Energy, issued a statement rejecting the unspecified allegations and elaborating on the issue.

The study had found that a type of virus called filoviruses, which includes the Ebola and Marburg viruses, could have jumped from bats to humans in the South Asia region based on blood samples obtained from individuals of the Bomrr clan in India’s Nagaland.

Every year, the Bomrr smoke a cave full of bats of two species; as the mammals exit through the mouth, they are hunted and killed. In 2017, the research group, led by the scientists from NCBS, sensed an opportunity to study bats and humans together in a limited area. They obtained blood samples from 85 members of the Bomrr, with written consent in their native tongue. They also obtained kidney, lung and spleen samples from the two species of bats inhabiting the cave.

Aside from a team from NCBS, members of the study group also included researchers from the Duke-National University of Singapore (Duke-NUS) Medical School. According to the NCBS statement, the samples the NCBS team had obtained “were tested at NCBS using technologies supplied by Duke-NUS. The test results were shared with the Duke-NUS team to compare with the data obtained from their Southeast Asian studies.”

As The Wire reported at the time, “When the researchers chemically analysed filovirus strains from the humans and the bats, they found the samples from [one bat species] displayed the same reactivity pattern as that from the humans. This suggested that bats and humans had exchanged the virus but the virus hadn’t affected the humans.”

David Hayman, a professor of infectious disease ecology at Massey University, New Zealand, had elaborated on the implications, for The Wire: “First, there may be more than one type of virus circulating in this region of Asia, but it is not clear what they are yet, because this study detected antibodies and not the viruses themselves. Second, key … groups of people can be at risk of infection.”

The study was published in the reputed open-access journal PLOS Neglected Tropical Diseases. (The Hindu report mentioned that this journal was “originally established” by the Bill and Melinda Gates Foundation; this is partly true: the journal was founded in 2007 by American paediatrician Peter Hotez with support from the Gates Foundation, under the Public Library of Science, a nonprofit publisher. As an open access journal, it levies an article-processing charge of $2,350 per accepted paper, with assistance/waivers on a case-by-case basis.)

Accompanied by a graphic entitled ‘Steeped in secrecy’, The Hindu wrote in its report, “The study came under the scanner as two of the 12 researchers belonged to the Wuhan Institute of Virology’s Department of Emerging Infectious Diseases, and it was funded by the US Department of Defence’s Defence Threat Reduction Agency (DTRA). They would have required special permissions as foreign entities.”

This special permission is provided by the Indian Council of Medical Research (ICMR), in the form of an approval by the Health Ministry Screening Committee (HMSC). Specifically, HMSC approval “is required for clinical trials and observational studies, where there is foreign collaboration and money will be transferred into India” (source).

Wuhan has been in the news of late thanks to the 2019 novel coronavirus, or 2019 nCoV, whose first recorded case of infection was registered in this city, the capital of China’s Hubei province, in December 2019 and whose spread through China and then 23 other countries has prompted the World Health Organisation to declare a “global health emergency”. However, contrary to the news report’s headline – ‘Coronavirus: Wuhan institute’s study on bats and bat hunters in Nagaland to be probed’ – the NCBS study does not concern 2019 nCoV in any way.

Also read: 2019 Novel Coronavirus: How We Got From the First Case to Today

The Hindu also wrote that the ICMR had concluded its review and had submitted its findings to the Union health ministry. Mukund Thattai, the head of academics at NCBS and a computational cell biologist, told The Wire that the institute had not received a copy.

By 7 pm in the evening, the news report had fanned rumours on Twitter about Indians being unwitting “guinea pigs” (see here and here for examples) in experiments by Chinese and American researchers.

In its clarificatory statement, NCBS wrote:

“Researchers from the Wuhan Institute of Virology were not directly involved in the study. They were listed co-authors ONLY because they supplied reagents critical to the study to Duke-NUS. This is standard practice for scientific authorship. The corresponding author of the study is affiliated to Duke-NUS. Therefore, the funding statement of the paper mentions funding obtained by Duke-NUS from the US DTRA. NCBS is not a direct recipient of research funds from DTRA.”

Thattai told The Wire that the “primary applicant” on the US Department of Defence grant “was the Duke-NUS principal investigator, with the NCBS researcher as collaborator,” and that “those funds went directly to Duke-NUS.”

However, he continued that “there were funds transferred from Duke-NUS to NCBS as part of the joint study reported in the PLOS paper, and Duke-NUS also provided analytic reagents.” He also said the Department of Atomic Energy had approved the study and had “given security clearance to the Duke-NUS collaborator. But the ICMR brought to our notice that this still requires, in addition, an HMSC/ICMR approval.”

That the research group had not obtained HMSC approval for this particular corpus of funds could have triggered the inquiry. However, The Wire couldn’t independently confirm this possibility; ICMR officials, including Balram Bhargava, the director general of ICMR, had not responded to multiple requests for comment at the time of publication.

An ICMR team is believed to have already visited the institute “and reviewed the study,” according to Thattai, and submitted another corresponding report to “the relevant authorities”. In sum, “we are fully cooperating with their recommendations,” Thattai said, adding that the institute’s ethics committee will in future flag “requirement for this permission in such cases, in addition to DAE permission”.

New Evidence That Humans and Bats Exchanged Deadly Filovirus in Nagaland

Filoviruses cause severe haemorrhagic fever in humans and primates.

Bats are reservoirs of many microorganisms responsible for infectious diseases. One such is a type of virus called filovirus, which causes severe haemorrhagic fever in humans and primates.

We know of ten different varieties of filoviruses, including Ebola, the Marburg virus and the Mengla virus.

In South and Southeast Asia, there is no historical record of filovirus haemorrhagic outbreaks. A new study presents the first evidence of filovirus exposure in humans (apart from Reston virus transmission in the Philippines) in this region. The study states that humans likely acquired the infection from bats.

“From our study we find that there is some indication of spillover disease that is happening from wildlife to humans,” says Pilot Dovih, a doctoral candidate at the National Centre for Biological Sciences (NCBS), Bengaluru, and a member of the research team.

The finding has significant public health implications as epidemic breakouts of zoonotic infectious diseases have become regular around the world.

“The ever increasing conflict at the human-animal interface and impending climate changes enhance spillover of pathogens from animals,” G. Arunkumar, director of the Manipal Institute of Virology, told The Wire. In this context, he argues it is important to understand the biodiversity and its health effects in India to identify and mitigate public health threats. “Hence this is a very important first step.” Arunkumar was not part of the research team.

Scientists undertook this work over a four-year collaboration between NCBS and the Duke-National University of Singapore (NUS) Medical School, Singapore, along with others in the US and China.

The team had earlier come to know of the Bomrr clan’s annual bat harvest in October in Nagaland. Sensing an opportunity to examine both bats and people at the same time, the team visited the cave where the Bomrr smoked out bats.

Also read: Bengaluru Scientists Find Evidence That Bats in Nagaland’s Hills Carry Rabies Virus

“These sorts of situations are quite difficult to find,” Ian Mendenhall, a principal research scientist at the Duke-NUS Medical School, said. This is because although it would be possible to screen blood for antibodies from animals at an abattoir, it would be difficult to connect exposure to a specific species. “Here we have the same individuals harvesting the same two species of bats, one day per year, every year,” Mendenhall said. “This is a very unique cohort and we are fortunate to study these interactions.”

When the clan’s members smoke the cave, they’re exposed to the bats’ blood, saliva and faeces as the hunters and the hunted come in direct contact.

The location of the cave, in Mimi village in Nagaland. Image: https://doi.org/10.1371/journal.pntd.0007733

The location of the cave, in Mimi village in Nagaland. Image: https://doi.org/10.1371/journal.pntd.0007733

 

During the 2017 bat harvest, the team drew blood from 85 willing donors. They also drew blood from 16 bats of the Eonycteris spelaea species and 30 of the Rousettus leschenaultii species. And they collected kidney, lung and spleen samples from 34 E. spelaea and 69 R. leschenaultii bats.

The team carried these samples back to their labs and screened them for filoviruses. They found five out of 85 humans had developed antibodies – which isn’t active virus but a neutralising immune response to one – against filoviruses. They also found antibodies in one and four of the E. spelaea and R. leschenaultii bats, respectively.

When the researchers chemically analysed filovirus strains from the humans and the bats, they found the samples from E. spelaea displayed the same reactivity pattern as that from the humans. This suggested that bats and humans had exchanged the virus but the virus hadn’t affected the humans.

“This may be because these viruses lack the capacity to replicate in humans and thus don’t transmit human to human, or there are ecological barriers where humans aren’t encountering bats often,” Mendenhall said. But, according to him, “the results are evidence of humans being exposed to filoviruses and generating an antibody response, so there may be an opportunity for sustaining transmission.”

Also read: The Absence of Evidence for Nipah in Fruit Bats Is Not Evidence of Absence

David T.S. Hayman, a professor of infectious disease ecology at Massey University, New Zealand, thinks the study adds two things to what we know. “First, there may be more than one type of virus circulating in this region of Asia, but it is not clear what they are yet, because this study detected antibodies and not the viruses themselves. Second, key … groups of people can be at risk of infection.” Hayman wasn’t involved in the study.

Mendenhall also argued that the geographical footprint of filoviruses is larger than previously estimated, and the genetic diversity of filoviruses greater than expected.

“This study is like a surveillance case that can lead us to find what other things are there in the bats and help us prepare for the things that are circulating in the bats,” Dovih said. “This study shows that prevention is better than cure.”

The study was published in the journal PLoS Neglected Tropical Diseases on October 31, 2019.

Vrushal Pendharkar is a freelance science writer.