Tag: Covaxin

The BHU Covaxin study and ICMR bait

Earlier this month, a study by a team at Banaras Hindu University (BHU) in Varanasi concluded that fully 1% of Covaxin recipients may suffer severe adverse events. One percent is a large number because the multiplier (x in 1/100 * x) is very large — several million people. The study first hit the headlines for claiming it had the support of the Indian Council of Medical Research (ICMR) and reporting that both Bharat Biotech and the ICMR are yet to publish long-term safety data for Covaxin. The latter is probably moot now, with the COVID-19 pandemic well behind us, but it’s the principle that matters. Let it go this time and who knows what else we’ll be prepared to let go.

But more importantly, as The Hindu reported on May 25, the BHU study is too flawed to claim Covaxin is harmful, or claim anything for that matter. Here’s why (excerpt):

Though the researchers acknowledge all the limitations of the study, which is published in the journal Drug Safety, many of the limitations are so critical that they defeat the very purpose of the study. “Ideally, this paper should have been rejected at the peer-review stage. Simply mentioning the limitations, some of them critical to arrive at any useful conclusion, defeats the whole purpose of undertaking the study,” Dr. Vipin M. Vashishtha, director and pediatrician, Mangla Hospital and Research Center, Bijnor, says in an email to The Hindu. Dr. Gautam Menon, Dean (Research) & Professor, Departments of Physics and Biology, Ashoka University shares the same view. Given the limitations of the study one can “certainly say that the study can’t be used to draw the conclusions it does,” Dr. Menon says in an email.

Just because you’ve admitted your study has limitations doesn’t absolve you of the responsibility to interpret your research data with integrity. In fact, the journal needs to speak up here: why did Drug Safety publish the study manuscript? Too often when news of a controversial or bad study is published, the journal that published it stays out of the limelight. While the proximal cause is likely that journalists don’t think to ask journal editors and/or publishers tough questions about their publishing process, there is also a cultural problem here: when shit hits the fan, only the study’s authors are pulled up, but when things are rosy, the journals are out to take credit for the quality of the papers they publish. In either case, we must ask what they actually bring to the table other than capitalising on other scientists’ tendency to judge papers based on the journals they’re published in instead of their contents.

Of course, it’s also possible to argue that unlike, say, journalistic material, research papers aren’t required to be in the public interest at the time of publication. Yet the BHU paper threatens to undermine public confidence in observational studies, and that can’t be in anyone’s interest. Even at the outset, experts and many health journalists knew observational studies don’t carry the same weight as randomised controlled trials as well as that such studies still serve a legitimate purpose, just not the one to which its conclusions were pressed in the BHU study.

After the paper’s contents hit the headlines, the ICMR shot off a latter to the BHU research team saying it hasn’t “provided any financial or technical support” to the study and that the study is “poorly designed”. Curiously, the BHU team’s repartee to the ICMR’s makes repeated reference to Vivek Agnihotri’s film The Vaccine War. In the same point in which two of these references appear (no. 2), the team writes: “While a study with a control group would certainly be of higher quality, this immediately points to the fact that it is researchers from ICMR who have access to the data with the control group, i.e. the original phase-3 trials of Covaxin – as well publicized in ‘The Vaccine War’ movie. ICMR thus owes it to the people of India, that it publishes the long-term follow-up of phase-3 trials.”

I’m not clear why the team saw fit to appeal to statements made in this of all films. As I’ve written earlier, The Vaccine War — which I haven’t watched but which directly references journalistic work by The Wire during and of the pandemic — is most likely a mix of truths and fictionalisation (and not in the clever, good-faith ways in which screenwriters adopt textual biographies for the big screen), with the fiction designed to serve the BJP’s nationalist political narratives. So when the letter says in its point no. 5 that the ICMR should apologise to a female member of the BHU team for allegedly “spreading a falsehood” about her and offers The Vaccine War as a counterexample (“While ‘The Vaccine War’ movie is celebrating women scientists…”), I can’t but retch.

Together with another odd line in the latter — that the “ICMR owes it to the people of India” — the appeals read less like a debate between scientists on the merits and the demerits of the study and more like they’re trying to bait the ICMR into doing better. I’m not denying the ICMR started it, as a child might say, but saying that this shouldn’t have prevented the BHU team from keeping it dignified. For example, the BHU letter reads: “It is to be noted that interim results of the phase-3 trial, also cited by Dr. Priya Abraham in ‘The Vaccine War’ movie, had a mere 56 days of safety follow-up, much shorter than the one-year follow-up in the IMS-BHU study.” Surely the 56-day period finds mention in a more respectable and reliable medium than a film that confuses you about what’s real and what’s not?

In all, the BHU study seems to have been designed to draw attention to gaps in the safety data for Covaxin — but by adopting such a provocative route, all that took centerstage was its spat with the ICMR plus its own flaws.

On Agnihotri’s Covaxin film, defamation, and false bravery

Vivek Agnihotri’s next film, The Vaccine War, is set to be released on September 28. It is purportedly about the making of Covaxin, the COVID-19 vaccine made by Bharat Biotech, and claims to be based on real events. Based on watching the film’s trailer and snippets shared on Twitter, I can confidently state that while the basis of the film’s narrative may or may not be true, the narrative itself is not. The film’s principal antagonist appears to be a character named Rohini Singh Dhulia, played by Raima Sen, who is the science editor of a news organisation called The Daily Wire. Agnihotri has said that this character is based on his ‘research’ on the journalism of The Wire during, and about, the pandemic, presumably at the time of and immediately following the DCGI’s approval for Covaxin. Agnihotri and his followers on Twitter have also gone after science journalist Priyanka Pulla, who wrote many articles in this period for The Wire. At the time, I was the science editor of The Wire. Dhulia appears to have lovely lines in the film like “India can’t do this” and “the government will fail”, the latter uttered with visible glee.

It has been terribly disappointing to see senior ICMR scientists promoting the film as well as the film (according to the trailer, at least) confidently retaining the name of Balram Bhargava for the character as well; for the uninitiated, Bhargava was the ICMR director-general during the pandemic. (One of his aides also has make-up strongly resembling Raman Gangakhedkar.) In Pulla’s words, “the political capture of this institution is complete”. The film has also been endorsed by Sudha Murthy and received a tone-deaf assessment by film critic Baradwaj Rangan, among other similar displays of support. One thing that caught my eye is that the film also retains the ICMR logo, logotype, and tagline as is (see screenshot below from the trailer).

Source: YouTube

The logo appears on the right of the screen as well as at the top-left, together with the name of NIV, the government facility that provided the viral material for and helped developed Covaxin. This is notable: AltBalaji, the producer of the TV show M.O.M. – The Women Behind Mission Mangal, was prevented from showing ISRO’s rockets as is because the show’s narrative was a fictionalised version of real events. A statement from AltBalaji to The Wire Science at the time, in 2019, when I asked why the show’s posters showed the Russian Soyuz rocket and the NASA Space Shuttle instead of the PSLV and the GSLV, said it was “legally bound not to use actual names or images of the people, objects or agencies involved”. I don’t know if the 2019 film Mission Mangal was bound by similar terms: its trailer shows a rocket very much resembling the GSLV Mk III (now called LVM-3) sporting the letters “S R O”, instead of “I S R O” ; the corresponding Hindi letters “स” and “रो”; and a different logo below the letters “G S L V” instead of the first “I” (screenshot below). GSLV is still the official designation of the launch vehicle, and a step further from what the TV show was allowed. And while the film also claims to be based on real events, its narrative is also fictionalised (read my review and fact-check).

Source: YouTube

Yet ICMR’s representation in The Vaccine War pulls no punches: its director-general at the time is represented by name and all its trademark assets are on display. It would seem the audience is to believe that they’re receiving a documentarian’s view of real events at ICMR. The film has destroyed the differences between being based on a true story and building on that to fictionalise for dramatic purposes. Perhaps more importantly: while AltBalaji was “legally bound” to not use official ISRO imagery, including those of the rockets, because it presented a fiction, The Vaccine War has been freed of the same legal obligation even though it seems to be operating on the same terms. This to me is my chief symptom of ICMR’s political capture.

Of course, that Agnihotri is making a film based on a ‘story’ that might include a matter that is sub judice is also problematic. As you may know, Bharat Biotech filed a defamation case against the Foundation for Independent Journalism in early 2022; this foundation publishes The Wire and The Wire Science. I’m a defendant in the case, as are fellow journalists and science communicators Priyanka Pulla, Neeta Sanghi, Jammi Nagaraj Rao, and Banjot Kaur, among others. But while The Wire is fighting the case, it will be hard to say before watching The Vaccine War as to whether the film actually treads on forbidden ground. I’m also not familiar with the freedoms that filmmakers do and don’t have in Indian law (and the extent to which the law maps to common sense and intuition). That said, while we’re on the topic of the film, the vaccine, defamation, and the law, I’d like to highlight something important.

In 2022, Bharat Biotech sought and received an ex parte injunction from a Telangana court against the allegedly offending articles published by The Wire and The Wire Science, and had them forcibly taken down. The court also prevented the co-defendants from publishing articles on Covaxin going forward and filed a civil defamation case, seeking Rs 100 crore in damages. As the legal proceedings got underway, I started to speak to lawyers and other journalists about implications of the orders, whether specific actions are disallowed on my part, and the way courts deal with such matters – and discovered something akin to a labyrinth that’s also a minefield. There’s a lot to learn. While the law may be clear about something, how a contention winds its way through the judicial system is both barely organised and uncodified. Rahul Gandhi’s own defamation case threw informative light on the role of judges’ discretion and the possibility of a jail term upon conviction, albeit for the criminal variety of the case.

The thing I resented the most, on the part of sympathetic lawyers, legal scholars, and journalists alike, is the view that it’s the mark of a good journalist to face down a defamation case in their career. Whatever its origins, this belief’s time is up in a period when defamation cases are being filed at the drop of a hat. It’s no longer a specific mark of good journalism. Like The Wire, I and my co-defendants stand by the articles we wrote and published, but it remains good journalism irrespective of whether it has also been accused of defamation.

Second, the process is the punishment, as the adage goes, yet by valorising the presence of a defamation case in a journalist’s record, it seeks to downplay the effects of the process itself. These effects include the inherent uncertainty; the unfamiliar procedures, documentation, and their contents and purposes; the travelling, especially to small towns, and planning ahead (taking time off work, availability of food, access to clean bathrooms, local transport, etc.); the obscure rules of conduct within courtrooms and the varying zeal with which they’re implemented; the variety and thus intractability of options for legal succour; and the stress, expenses, and the anxiety. So please, thanks for your help, but spare me the BS of how I’m officially a good journalist.

Something more foolish than completing phase 3 trials in 1.5 months?

That the Union government and the Indian Space Research Organisation (ISRO) had entered into a more intimate, but not necessarily more beneficial, relationship became evident in 2019 when then ISRO chairman K. Sivan trotted out a series of dubious claims to massage the fate of the Chandrayaan 2 mission, whose lunar surface component had obviously failed. Anyone who follows Indian spaceflight news is familiar with the adage ‘space is hard’ and all of them abide by it (there’s an argument that we shouldn’t extend the same courtesy to more mature space programmes). Yet Sivan was determined to salvage even more, going so far at one point to call the whole mission (orbiter + lander) a “98% success”.

Shortly after news of the lander’s fate became clear to ground control, Prime Minister Narendra Modi, who was present as the chief guest, consoled Sivan with his customary hug even as ISRO at large withdrew into a shell of silence, offering only the occasional scrap of what it knew had happened to the lander. The vacuum of information allowed a trickle of speculation, but which was soon overwhelmed by a swell of conspiracies and, as is inevitable these days, a virtual barrier erected by right-wing commentators and bots that suppressed all questions asking for more information in the public domain. This ISRO, and the attendant public experience of India’s spaceflight programme, was markedly different from the ISRO of before – a feeling that Sivan deepened with other claims about the amount of time ISRO would need to realise its ‘Gaganyaan’ human spaceflight mission, which has already been delayed by three years. Sivan had unknowingly underestimated the amount, had deliberately communicated a shorter duration, had communicated the actual time but to which government officials couldn’t agree, or something else happened. The first possibility would’ve been unlikely were it not for the COVID-19 pandemic – but then it would seem that even if Sivan’s successor, S. Somanath, were to push back and ask for more time, the government has made up its mind: New Indian Express reported on December 8 that ISRO had received “instructions from the government” to send Indian astronauts to space on its GSLV Mk III rocket before the 2024 Lok Sabha elections! This has to be the second most unintelligent decision the government has made in the limited context of large-scale undertakings involving science and the lives of people, after Balram Bhargava’s subsequently rescinded threat in mid-2020 for researchers to complete the Covaxin phase 3 clinical trial in time for Prime Minister Modi’s Independence Day address less than two months away. It’s not clear if the government will rescind its demand of ISRO; the report itself is brief and doesn’t mention any resistance from the spaceflight mission team. But how this squares with minister Jitendra Singh’s statement in parliament last week, that the first crewed mission will only liftoff in late 2024 and that “crew safety is paramount”, is unclear. Assuming that the government will continue to push ISRO to launch in the first half of 2024, a flight based on a schedule modified to accommodate the demand may surpass the foolishness of Bhargava’s ask.

Every human spaceflight mission is inordinately complex. ISRO will have to design and test every component of the launch vehicle, crew capsule, mission profile, ground systems and crew management beforehand, in different conditions. It has to anticipate all possible failure scenarios and arrange for both failure-avoidance systems and failsafes. The timeline may have been more flexible in the early days of the undertaking, when the systems being tested were less composite, but not so today. When the government “instructs” ISRO to launch the ‘Gaganyaan’ crewed flight before the 2024 Lok Sabha elections (which are around 18 months away), it’s practically asking ISRO to devise a testing schedule that will be completed – irrespective of the tests’ outcomes – in this period all so it can use the mission’s outcomes (developed with government funds) as part of its election campaign. It’s effectively asking ISRO to sideline science, safety standards and good sense. Imagine one safety test going awry, and which ISRO might in other circumstances have liked to fix and redo. With “instructions” like those of the government, it won’t be able to – jeopardising the mission itself as well as the lives of the astronauts and the reputation of the Indian space programme in the international arena. The government simply shouldn’t make such a frighteningly asinine demand, and instead allow ISRO to take all the time it needs (within reasonable limits) to successfully complete its first human spaceflight mission.

ISRO has of late also embarked on programmes to increase its commercial revenue, even though it’s a “space research organisation”. If a crewed mission fails because the organisation let itself be cowed by the national government into trimming its testing process, all so a political party could use the launch as part of its poll propaganda, all of the organisation’s other rockets will confront doubts about their safety and whether they won’t threaten satellites worth hundreds of millions of dollars. A lot of ISRO’s work on ‘Gaganyaan’ has also happened to the exclusion of other launch vehicles and scientific missions, including (but not limited to) the reusable launch vehicle, the semi-cryogenic engine and the Aditya L1 space-probe. Its low rate of production of new rockets recently forced it to postpone the Chandrayaan 3 mission to accommodate the OneWeb satellites (in a commercial contract) in its launch manifest. Setting aside questions of ISRO’s relatively low funding and internal priorities, even if ‘Gaganyaan’ succeeds out of luck, the prospects of all of these adversely affected projects will suffer at least further reputational consequences. If ‘Gaganyaan’ fails, the future will be a lot worse.

Just as the Covaxin incident opened a window into how the Indian government was thinking about the COVID-19 vaccination drive and the role of science in shaping it, a demand of ISRO to launch realise its human spaceflight mission with a hard deadline opens a window into the Indian government’s considerations on ‘Gaganyaan’. The BJP government revived ISRO’s proposal for a human spaceflight mission in 2014, approved it in 2017 and allocated Rs 10,000 crore in 2018. Did it do so only because of how the mission’s success, should it come to pass, would help the party win elections? It’s desirable for a party’s goals and the country’s goals to be aligned – until the former crimps the latter. But more importantly, should we be concerned about the government’s heuristic for selecting and rejecting which spaceflight missions to fund? And should we be concerned about which publicly funded projects it will seek more accountability on?

There have been standing committee and audit reports calling ISRO out for slow work on this or that matter but the government at large, especially the incumbent one since 2019, has taken pains to maintain a front of amicability. It might be mildly amusing if a political party promises in its pre-poll manifesto to get ISRO in shape, and then in line, by readying a reusable launch vehicle for commercial missions by 2025 or launching five scientific missions in the next four years – but standing in the way of that is more than a knack to translate between public sentiment and technological achievement. It requires breaking a longstanding tradition of cosying up to ISRO as much as granting it autonomy while simultaneously underfunding it. We need the national government, most of all, to pay more attention to all ISRO projects on which there is evidence of dilly-dallying, and grapple honestly with the underlying issues, rather than poke its nose in the necessarily arduous safety-rating process of a crewed mission.

Featured image: A GSLV Mk III rocket lifts off on its first orbital flight, July 2017. Credit: ISRO.

The biopolitics of Covaxin

In a new investigation, STAT has reported fresh problems with Covaxin’s approval process in India, including the phase 2 trial dropping its placebo arm in favour of one preordained to make Covaxin look good and Bharat Biotech – the maker – commencing phase 3 trials based on results from animal studies. I’m also filing the report under “yet another instance of a pro-government Indian entity responding to the foreign press but not the local press” (following this). Krishna Mohan, one of the company’s directors, responded to STAT by admitting to a wrongdoing, massaging other similar actions, and pointing a finger at the Indian government.

Is this spine? In response to similar evidence-based allegations of wrongdoing, Bharat Biotech met The Wire Science and The Wire with a defamation suit, a demand of Rs 100 crore and that the two sites not publish articles with “defamatory content” vis-à-vis the company, and obtained an ex parte injunction against 14 articles. This was in addition to the seemingly blanket refusal to respond to our questions for reports we were filing. Other senior Bharat Biotech officials also refused to communicate to anyone else asking probing questions about Covaxin’s clinical trials. No: his quote sounds more like Mohan trying to save Bharat Biotech’s face in front of a western audience (the one our government wants us to believe is inferior) while spinning India’s Bharat’s own take on the vaccine approval process.

Mohan told STAT that they didn’t take any shortcuts – at least not those that weren’t first “vetted” by the Central Drug Standards Control Organisation (CDSCO), a.k.a. the drug regulator. That is to say, the shortcuts were CDSCO-approved, so they weren’t shortcuts. I’m inclined to agree: the rules are after all not based on principles of natural justice but on what the government deems acceptable. /s

Of all the allegations, the one that irks me most is the modification to the phase 2 trial. It compromises our ability to learn anything useful about Covaxin, replacing that knowledge with knowledge of how much better one formulation of Covaxin is from another. The drug regulator should have known this is what the trial would have ended up checking, and if it approved this design anyway, it has engaged in wilful neglect – neglect of science, neglect of integrity, neglect of its mandate to look out for the people. But if we’re to believe Mohan, it’s just “product development” for an unprecedented time, not public health:

“In a classic sense of product development, we would do everything the right way — play by the book and all the rules of the game would be followed. But here was a situation the world didn’t foresee. … Please don’t think there was any issue with the veracity of the data. Yes, it was an unusual approach, but it was dictated by the nature of the pandemic.”

Ah, a classic tactic: Why did you burn down the forest? “It’s the climate crisis, which is unprecedented, and we needed land to erect smog towers.”

Later in the article, in the face of a similar allegation – changing the phase 2 trial protocol – Mohan defends the regulator and blames discrepancies in trial numbers on a company struggling to coordinate multiple teams working separately from each other while being guided by the rule of “let’s get the data out”. I’d buy what he was saying if he was talking about his company HQ installing new air-conditioners and conducting tests of indoor air quality. But he’s talking about a clinical trial for a vaccine, placing misleading data in the public domain and – crucially – implicating a national drug regulator that he claims was in the know but didn’t act.

To STAT, he’s saying they were distracted by the “safety of individuals”, the “ethics of handling subjects” and “manufacturing”, but to Indian journalists, he as well as the regulator have been mum on questions raised by the WHO and ANVISA on manufacturing practices and by almost everyone else about the People’s Hospital death and data.

A (somehow) bigger problem arises soon after when Mohan says:

“Whatever we did was with the clear intention of doing it right. There was no question of reducing sample sizes. … There were not off the cuff or random thoughts. … It was extensively debated with keeping the final objective in mind of getting a vaccine in time and not cutting any corners.”

Getting a vaccine in time and not cutting any corners? It’s baffling that the last sentence is intended as clarification rather than as a potentially tacit admission of wrongdoing. I’m sure you remember when ICMR chief Balram Bhargava called on hospitals around India to complete Covaxin’s phase 3 trials in less than two months, in time for Prime Minister Narendra Modi to avail the vaccine for public use on Independence Day 2020. One independent scientist asked me what I thought Bhargava might have been smoking at the time; it was hard to say.

But what’s tempting to speculate now is that the government realised, based on the backlash to Bhargava’s announcement, that a) a phase 3 trial in six weeks was a bigger problem than it believed, b) it wouldn’t work to have its vaccine development plan in public, c) it could accelerate Covaxin’s clinical trials by forcing Bharat Biotech to do so, and d) approve Covaxin without phase 3 trials by assimilating the drug regulator – all to achieve a similar outcome. Or at least I speculate in the absence of evidence. And until there is, we remain needles in veins.

Bharat Biotech gets 1/10 for tweet

If I had been Bharat Biotech’s teacher and “Where is your data?” had been an examination question, Bharat Biotech would have received 1 out of 10 marks.

The correct answer to where is your data can take one of two forms: either an update in the form of where the data is in the data-processing pipeline or to actually produce the data. The latter in fact would have deserved a bonus point, if only because the question wasn’t precise enough. The question should really have been a demand – “Submit your data” – instead of allowing the answerer, in its current form, to get away with simply stating where the data currently rests. Bharat Biotech gets 1/10 because it does neither; the 1 is for correct spelling.

In fact, the company’s chest-thumping based on publishing nine papers in 12 months is symptomatic of a larger problem with the student. He fails to understand that only data is data, and that the demand for data is a demand for data per se. It ought not to be confused with a demand for authority. Data accords authority in an object-oriented and democratic sense. With data, everyone else can see for themselves – whether by themselves or through the mouths and minds of independent experts they trust – if the student’s claims hold up. And if they do, they confer the object of the data, the COVID-19 vaccine named Covaxin, with attributes like reliability.

(Why ‘he’? The patriarchal conditions in and with which science has operated around the world, but especially in Europe and the US, in the last century or so have diffused into scientific practice itself, in terms of how the people at large have constituted – as well as have been expected to constitute, by the scientific community – scientific authority, expertise’s immunity to criticism and ownership of knowledge production and dissemination apparatuses, typically through “discrimination, socialisation and the gender division of labour”. Irrespective of the means – although both from the company’s and the government’s sides, very few women have fielded and responded to questions about drug/vaccine approvals – we already see these features in the manner in which ‘conventional’ scientific journals have sought to retain their place in the international knowledge production economy, and their tendency to resort to arguments that they serve an important role in it even as they push for anti-transparent practices, from the scientific papers’ contents to details about why they charge so much money.)

However, the student has confused authority of this kind with authority of a kind we more commonly associate with the conventional scientific publishing paradigm: in which journals are gatekeepers of scientific knowledge – both in terms of what topics they ‘accept’ manuscripts on and what they consider to be ‘good’ results; and in which a paper, once published, is placed behind a steeply priced paywall that keeps both knowledge of the paper’s contents and the terms of its ‘acceptance’ by the journal beyond public scrutiny – even when public money funded the research described therein. As such, his insistence that we be okay with his having published nine papers in 12 months is really his insistence that we vest our faith in scientific journals, and by extension their vaunted decision to ‘approve of’ his work. This confusion on his part is also reflected in what he offers as his explanation for the absence of data in the public domain, but which are really his excuses.

Our scientific commitment as a company stands firm with data generation, data transparency and peer-reviewed publications.

Sharing your data in a secluded channel with government bodies is not data transparency. That’s what the student needs for regulatory approval. Transparency applies when the data is available for everyone else to independently access, understand and check.

Phase 3 final analysis data will be available soon. Final analysis requires efficacy and 2 months safety follow-up data on all subjects. This is mandated by CDSCO and USFDA. Final analysis will first be submitted to CDSCO, followed by submissions to peer reviewed journals and media dissemination.

What is required by CDSCO does not matter to those allowing Bharat Biotech’s vaccines into the bloodstreams, and in fact every Indian on whom the student has inflicted this pseudo-choice. And at this point to invoke what the USFDA requires can only lead to a joke: studies of the vaccines involved in the formal vaccination drive have already been published in the US; even studies of new vaccines as well as follow-ups of existing formulations are being placed in the public domain through preprint papers that describe the data from soup to nuts. All we got from the student vis-à-vis Covaxin this year was interim phase 3 trial data in early March, announced through a press release, and devoid even of error bars for its most salient claims.

So even for an imprecisely worded question, it has done well to elicit a telling answer from the student: that the data does not exist, and the student believes he is too good for us all.

Thanks to Jahnavi Sen for reading the article before it was published.

Magic bridges

The last two episodes of the second season of House, the TV series starring Hugh Laurie as a misanthropic doctor at a facility in Princeton, have been playing on my mind off and on during the COVID-19 pandemic. One of its principal points (insofar as Dr Gregory House can admit points to the story of his life) is that it’s ridiculous to expect the families of patients to make informed decisions about whether to sign off on a life-threatening surgical procedure, say, within a few hours when in fact medical workers might struggle to make those choices even after many years of specific training.

The line struck me to be a chasm stretching between two points on the healthcare landscape – so wide as to be insurmountable by anything except magic, in the form of decisions that can never be grounded entirely in logic and reason. Families of very sick patients are frequently able to conjure a bridge out of thin with the power of hope alone, or – more often – desperation. As such, we all understand that these ‘free and informed consent’ forms exist to protect care-providers against litigation as well as, by the same token, to allow them to freely exercise their technical judgments – somewhat like how it’s impossible to physically denote an imaginary number (√-1) while still understanding why they must exist. For completeness.

Sometimes, it’s also interesting to ask if anything meaningful could get done without these bridges, especially since they’re fairly common in the real world and people often tend to overlook them.

I’ve had reason to think of these two House episodes because one of the dominant narratives of the COVID-19 pandemic has been one of uncertainty. The novel coronavirus is, as the name suggests, a new creature – something that evolved in the relatively recent past and assailed the human species before the latter had time to understand its features using techniques and theories honed over centuries. This in turn predicated a cascade of uncertainties as far as knowledge of the virus was concerned: scientists knew something, but not everything, about the virus; science journalists and policymakers knew a subset of that; and untrained people at large (“the masses”) knew a subset of that.

But even though more than a year has passed since the virus first infected humans, the forces of human geography, technology, politics, culture and society have together ensured not everyone knows what there is currently to know about the virus, even as the virus’s interactions with these forces in different contexts continues to birth even more information, more knowledge, by the day. As a result, when an arbitrary person in an arbitrary city in India has to decide whether they’d rather be inoculated with Covaxin or Covishield, they – and in fact the journalists tasked with informing them – are confronted by an unlikely, if also conceptual, problem: to make a rational choice where one is simply and technically impossible.

How then do they and we make these choices? We erect magic bridges. We think we know more than we really do, so even as the bridge we walk on is made of nothing, our belief in its existence holds it up and stiff beneath our feet. This isn’t as bad as I’m making it seem; it seems like the human thing to do. In fact, I think we should be clearer about the terms on which we make these decisions so that we can improve on them and make them better.

For example, all frontline workers who received Covaxin in the first phase of India’s vaccination drive had to read and sign off on an ‘informed consent’ form that included potential side effects of receiving a dose of the vaccine, its basic mechanism of action and how it was developed. These documents tread a fine line between being informative and being useful (in the specific sense of the risk of debilitating action by informing too much and of withholding important information in order to skip to seemingly useful ‘advice’): they don’t tell you everything they can about the vaccine, nor can they assert the decision you should make.

In this context, and assuming the potential recipient of the vaccine doesn’t have the education or training to understand how exactly vaccines work, a magic bridge is almost inevitable. So in this context, the recipient could be better served by a bridge erected on the right priorities and principles, instead of willy-nilly and sans thought for medium- or long-term consequences.

There’s perhaps an instructive analogy here with software programming, in the form of the concept of anti-patterns. An anti-pattern is a counterproductive solution to a recurrent problem. Say you’ve written some code that generates a webpage every time a user selects a number from a list of numbers. The algorithm is dynamic: the script takes the user-provided input, performs a series of calculations on it and based on the results produces the final output. However, you notice that your code has a mistake due to which one particular element on the final webpage is always 10 pixels to the left of where it should be. Being unable to identify the problem, you take the easy way out: you add a line right at the end of the script to shift that element 10 pixels to the right, once it has been rendered.

This is a primitive example of an anti-pattern, an action that can’t be determined by the principles governing the overall system and which exists nonetheless because you put it there. Andrew Koenig introduced the concept in 1995 to identify software programs that are unreliable in some way, and which could be made reliable by ensuring the program conforms to some known principles. Magic bridges are currently such objects, whose existence we deny often because we think they’re non-magical. However, they shouldn’t have to be anti-patterns so much as precursors of a hitherto unknown design en route to completeness.

What the DNA Bill needs

The following article has been published in The Wire, but since it began as a blog post and because I haven’t published anything else in a while, I’m using it here as well.

The Parliamentary Standing Committee on S&T, Forests and Climate Change has submitted its review on the DNA Technology (Use and Application) Regulation Bill 2019 to parliament. On page 9, the report considers the lack of “academic work” on the use of “scientific evidence” in Indian courts and writes:

The Committee, therefore, underlines with utmost importance that it is essential the Bill enables the creation of an ecosystem that benefits from scientific evidence like DNA, therefore allowing the legal system to become experienced in the use and appreciation of DNA evidence. This will enable the legal system to understand the technology’s limitations, identify when it is appropriate to use DNA technology to solve crimes appropriate and over time, substantially minimise all possible errors. Widespread and extensive training is of paramount importance.

These are sage words – but the “creation of an ecosystem that benefits from scientific evidence” requires one more thing that the committee’s report doesn’t mention: humility, of sorts.

At the outset, any ecosystem that upholds the dignity of both science and the law must also accommodate conditions in which scientists can develop a deeper understanding, free of any interference, of the instruments and methods underlying evidence. They must be free to speak up as often as they’re required to do so in the public domain, and, finally, be heard instead of silenced. In addition, given the revolutionary nature of DNA profiling vis-à-vis forensic science, and its vaunted feature of being accurate 99.x% of the time, it takes a certain humility to be able to identify the exceptional instances before it is too late.

The COVID-19 pandemic has taught us many things, including the fact that even when the government is confronted with good science, it will not tolerate disagreement, and dissent even less. In the past 10 months, a small clutch of scientists and other experts have repeatedly spoken up against government mistakes and deceptions while the wider community of experts has stayed noticeably quiet. In turn, the government has pushed back against comments from senior, well-regarded scientists by attacking their credentials instead of their arguments, orchestrating signature campaigns against them and, in one case, going so far as to dismiss legitimate questions because the scientist in question had disagreed with the government’s Citizenship (Amendment) Act 2019.

In addition, no court’s judgment is pronounced in a vacuum. Even if scientists are called to consult on a case, to advise a judge or weigh in for a report, the context in which the scientist discusses a problem, the information that has been shared with them as well as the information based on which they supply their own wisdom matters – especially if the defendant faces many years of imprisonment or the death penalty.

For example, it used to be that investigators could check for the presence of seminal fluid in a given sample; if it was present, the court could conclude the fluid came from the suspect. Today, investigators can – and thus need to – extract Y chromosomes from the seminal fluid, ascertain a match with the suspect, and submit it in court with the caveat that the fluid could have come from the suspect, his father or his grandfather, etc.

But one forensic scientist in the US told The Wire that investigators often skip the seminal-fluid check and jump to a DNA analysis to cut time. This could be a problem if the suspect has aspermia: a condition in which a person’s semen doesn’t have sperm. In such cases, an investigator running a DNA test on some semen will get no results – i.e. a false negative.

More broadly, she continued, there are two new problems today, among others: of analysts exaggerating their results in court, and of investigators overestimating what DNA analysis can tell us. For example, she said, microscopic analysis of hair used to be the norm but today DNA analysis has taken its place. However, only hair root contains nuclear DNA, which can help identify specific people. The rest of the hair contains mitochondrial DNA, which can only say if it came from the suspect, their mother or her grandmother, etc. (even if the suspect is male).

In addition, studying the DNA can’t tell us if the hair has been damaged in a particular way. That information can come only from microscopic analysis – which investigators have been neglecting.

“It’s not the science that’s flawed. It’s the people that claim to be scientists who are often the problem,” the scientist said. “Many investigators in the US have no more than a high-school diploma – but unless they go through rigorous training at the UG level in science, they may not even understand hypothesis testing” to eliminate biases.

So deliberation and accountability are paramount. Transparency will help but simply sharing information may not help so much when complex technical information is involved. Independent experts will need data, and independence itself. And observers such as politicians and policymakers will need to pay close attention to debates between scientists – and listen to them.

In turn, the people at large must be sufficiently informed to understand a verdict and question it if necessary. A topical example where public mobilisation matters is that of air pollution in North India. The Supreme Court of India has on more than one occasion asked the Delhi government why it isn’t installing more smog towers in the city. But as multiple experts have written, smog towers are useless, a waste of money and only perpetuate a fetish with technological solutions that are not designed to solve what remains a deeply regulatory problem.

Finally, an honest appreciation of scientific evidence requires one to admit that one may not know something in the first place, instead of bristling at presumed accusations of ignorance or even impudence, as more than a few members of the judicial system have done of late. Science in particular requires its exponents to begin by acknowledging that they may not know something, and to graduate from this position to learning about it while constantly eliminating biases along the way.

A direct consequence of this process is a heightened appreciation for what science can’t tell us. Until the Supreme Court banned the practice in 2013, for example, officials in India had deemed the two-finger test to be a ‘scientific’ check of whether a victim of rape had been “habituated to sex”, based on digitally probing the laxity of the victim’s vaginal muscles. But the test has nothing to do with science, of course, let alone the possibility of rape having been committed. Instead, it’s rooted in the cultural idea that only those women who don’t have sexual intercourse until after marriage are of ‘good character’ and can therefore be violated at all.

Humility offers a way to negotiate all of these issues – if it existed. India, especially the Government of India, currently has a ‘jagatguru’ complex, presuming to know everything worth knowing before anyone else, thanks to the mythological feats of Hindus who lived here thousands of years ago. This attitude is deeply antithetical to the humility required in a given moment to consider the evidence, set aside any other claims, and determine – in a necessarily limited amount of time – if one is addressing the 99.8% or the 0.2%.

Many experts have previously written that DNA data alone shouldn’t be used to open or close cases, and that it is at best complementary in nature. If followed, this precept should offer a valuable safeguard against overstating the importance of genetic evidence over, say, physical evidence. Another safeguard comes from the judicial system as it is: the integrity of the various courts and their staff members, including the judges, and their daily interpretation of the law.

But having said all this, the possibility exists in India’s wider political climate for judgments to be misled by half-baked science, half-baked scientists, government interference and either public indifference or public arrogance. This is more so since the room to disagree with the government has practically vanished, and those who still disagree are threatened with disproportionate consequences.

In addition, as the forensic scientist said, the science is comfortable with its limitations; it is its practitioners that are often the problem. Just last month, nearly 50 “eminent scientists and doctors” signed a letter saying they were okay with the national drug regulator’s decision to approve two COVID-19 vaccine candidates: one had no efficacy data and the other was confused about the interdose gap. In addition to such unabashed sycophancy, bad journalism has often contributed to the impression that scientists themselves don’t know what they are doing, frequently confusing debate for rhetoric.

As the committee’s report on the DNA Bill says, “widespread and extensive training is of paramount importance.” These words are well-taken but a lot needs to change – more than whatever the Bill by itself could ever manage – for the system to appreciate and use ‘scientific evidence’ right.

Pandemic: Science > politics?

By Mukunth and Madhusudhan Raman

Former Union health secretary K. Sujatha Rao had a great piece in The Indian Express on January 14, whose takeaway she summarised in the following line:

Science, evidence and data analytics need to be the bedrock of the roll-out policy, not politics and scoring brownie points for electoral advantages.

However, we can’t help but be reminded of the difference between what should be and what will be. We all (at least those of us who have been on the same side since 2014) know what should be. But as we’ve seen with the National Registry of Citizens (NRC), the Citizenship (Amendment) Act (CAA) 2019 and most recently the farm laws, our present government doesn’t change its mind.

In the last example, the Supreme Court intervened to stay the laws’ implementation but the mediation committee it put together somehow wound up with most members being known to be sympathetic to the government’s position. So what will be, will be – and this is likely to be true vis-à-vis Covaxin as well.

Prime Minister Narendra Modi has already guaranteed as much by determining to foot the cost of 5.5 million doses of Covaxin using the PM CARES fund, which lies beyond public oversight. The Central Drug Standards Control Organisation also played its part by pushing through Covaxin’s approval on terms no one has heard of – and which no one can therefore falsify.

However, this isn’t a pitch for a nihilist position. When Sujatha Rao writes that the government should prize science, evidence and data more than politics and elections, she is right – but we must also ask why. The government has clear incentives to prioritise politics. By thrusting Bharat Biotech – Covaxin’s maker – to the forefront, Modi can claim his ‘Atma Nirbhar’ and ‘Make in India’ schemes have been successful. Also, two important state elections are around the corner: West Bengal and Tamil Nadu.

These are issues that people, but especially ‘Middle Indians’, have an eye on and according to which they vote. The government has also said it is approving Covaxin because it is concerned with the ‘UK variant’. While no reason can be good enough to justify the use of a vaccine candidate in the population sans data from phase 3 clinical trials, the government has effectively set up Covaxin to be failure-proof: if it works, it works; if it doesn’t, it becomes the fault of the variant.

Taken together, Modi’s biggest mistake here is criminal negligence – for pushing Covaxin in the absence of efficacy data (which leads to a cascade of ethical dilemmas) – especially since there are fewer questions over Covaxin’s safety. And negligence is a difficult case to stick to this party or in fact to many people.

Granted, public-spirited science teachers, communicators and journalists can take it upon themselves (ourselves) to persuade readers as to why Covaxin’s approval is really bad – that though everything may turn out okay, it sets a terrible precedent for what this government is allowed to do, how such unchecked power may wreak deadly havoc in future crises, and ultimately that we become a people okay with settling for less, increasingly blind to the banal incrementalism of evil.

In fact, if the mainstream press manages to forget concerns about vaccine apartheid within the country, the dominant narrative as the vaccine roll-out is a few months in is going to be: “India is doing just fine, thank you very much.”

But while the Modi government’s actions may only be negligent – albeit criminally so – in the domains of public healthcare and ‘scientific temper’, they amount to something more egregious if we include the political dimensions of our present moment as well.

None of this means words like those of Sujatha Rao are unnecessary. We need to never forget what should be, and we need to keep protesting for our own sakes. (“Protests sometimes look like failures in the short term, but much of the power of protests is in their long-term effects, on both the protesters themselves and the rest of society.” – Zeynep Tufekci) If we don’t, this government might pretend even less than it currently does that it is following some rules or guidelines from time to time.

However, limiting our exhortations to insist at every turn that “science is more important than politics during a pandemic” risks playing down the importance and influence of political motivations altogether – as well as assuming that the state machinery will automatically give way to scientific ones when lives are at stake.

A politician’s principal responsibility is not to govern but to win elections; good governance is a means to this electoral end. And the way people have voted for many decades attests to the reality of this incentive. While this claim may not be palatable from a theoretical point of view, consider it empirically: the Indian government has seldom responded to national crises to the detriment of potential electoral gains. Examples of such crises include the 1962, 1971 and 1999 conflicts, the nuclear tests and economic liberalisation. During the Emergency, the government itself embodied this crisis.

More recently, numerous ministers and diplomats urged the India and Pakistan governments to find diplomatic solutions after the Pulwama attack and also after the questionable Balakot airstrike, in early 2019. In previous years, they had been preceded by the disagreeable events of Aadhaar implementation, demonetisation and the Goods and Services Tax. But Modi and his fellows won by a bigger margin in 2019 than they had five years earlier.

This happened partly because his success in elections rests on his impression as the Strongman of India, so his resolutions of choice involve flashy displays of strength and machismo.

Against this background: we need to admit political factors into the conversations we – rather, experts like health policymakers, heads of institutions, epidemiologists, healthcare workers, etc. – have from the beginning, instead of ruing the inevitable influence of politics later, so that we may anticipate it and take advantage of it.

For example, consider the conversation surrounding academic publishing. Academics perform most of the work that goes into publishing an academic paper (research, writing and reviewing). Publishing houses add only marginal value to journals – yet publishers charge exorbitant fees to access the results of publicly funded research once it is published. This is unfair, and many academics have said so.

However, the fact that publishing conglomerates are publicly traded companies whose primary responsibility is to generate profits for their shareholders finds little mention in conversations. In this case, the publishers’ profit-seeking motives are fundamental to the problem at hand – but are often disregarded in the first analysis (what should be) and subsequently bemoaned (what will be). For this to happen once is tragic; for it to repeat itself every few months is wasteful.

Similarly, the nationwide lockdown from March to July 2020 served a political purpose: it was a grand gesture, decisive, appealing to ‘Middle Indians’, in addition to supplying the government a pretext to disband protests against the CAA and the NRC. Just before the lockdown, the public conversation had been centred on what the government should be doing. However, most scientists and economists didn’t engage with the political dimension of this decision.

If we had, we may not have been side-tracked into conversations about weekend curfew versus night curfew, or cash transfers versus vouchers, etc. We would perhaps have recognised that our responsibility is not to operate within the parameters set by the government (“How effective was the lockdown?”) but instead recognise that the government’s decisions are politically motivated – so we can ask “Why lock down in the first place?”

India’s missing research papers

If you’re looking for a quantification (although you shouldn’t) of the extent to which science is being conducted by press releases in India at the moment, consider the following list of studies. The papers for none of them have been published – as preprints or ‘post-prints’ – even as the people behind them, including many government officials and corporate honchos, have issued press releases about the respective findings, which some sections of the media have publicised without question and which have quite likely gone on to inform government decisions about suitable control and mitigation strategies. The collective danger of this failure is only amplified by a deafening silence from many quarters, especially from the wider community of doctors and medical researchers – almost as if it’s normal to conduct studies and publish press releases in a hurry and take an inordinate amount of time upload a preprint manuscript or conduct peer review, instead of the other way around. By the way, did you know India has three science academies?

  1. ICMR’s first seroprevalence survey (99% sure it isn’t out yet, but if I’m wrong, please let me know and link me to the paper?)
  2. Mumbai’s TIFR-NITI seroprevalence survey (100% sure. I asked TIFR when they plan to upload the paper, they said: “We are bound by BMC rules with respect to sharing data and hence we cannot give the raw data to anyone at least [until] we publish the paper. We will upload the preprint version soon.”)
  3. Biocon’s phase II Itolizumab trial (100% sure. More about irregularities here.)
  4. Delhi’s first seroprevalence survey (95% sure. Vinod Paul of NITI Aayog discussed the results but no paper has pinged my radar.)
  5. Delhi’s second seroprevalence survey (100% sure. Indian Express reported on August 8 that it has just wrapped up and the results will be available in 10 days. It didn’t mention a paper, however.)
  6. Bharat Biotech’s COVAXIN preclinical trials (90% sure)
  7. Papers of well-designed, well-powered studies establishing that HCQ, remdesivir, favipiravir and tocilizumab are efficacious against COVID-19 🙂

Aside from this, there have been many disease-transmission models whose results have been played up without discussing the specifics as well as numerous claims about transmission dynamics that have been largely inseparable from the steady stream of pseudoscience, obfuscation and carelessness. In one particularly egregious case, the Indian Council of Medical Research announced in a press release in May that Ahmedabad-based Zydus Cadila had manufactured an ELISA test kit for COVID-19 for ICMR’s use that was 100% specific and 98% sensitive. However, the paper describing the kit’s validation, published later, said it was 97.9% specific and 92.37% sensitive. If you know what these numbers mean, you’ll also know what a big difference this is, between the press release and the paper. After an investigation by Priyanka Pulla followed by multiple questions to different government officials, ICMR admitted it had made a booboo in the press release. I think this is a fair representation of how much the methods of science – which bridge first principles with the results – matter in India during the pandemic.