Vaccines for votes

A week or so ago, the Bharatiya Janata Party in Bihar released its poll manifesto, the first point on which was that should the party win, it would make a COVID-19 vaccine cleared by the ICMR available for free to every resident of the state. It was an unethical move, and Siddharth Varadarajan and I explained why.

Soon after, trolls on Twitter pointed out that Joe Biden had made the same promise ahead of the US presidential elections. And this morning, Indian Express quoted the Election Commission saying the BJP’s promise didn’t violate the poll code; the report also included a curious paragraph: that “the EC had taken the same stand on a complaint received during the Lok Sabha elections last year against the Congress’s NYAY scheme that guaranteed a minimum income of Rs 6,000 per month, or Rs 72,000 a year, for 25 crore people.”

The BJP’s promise still feels unethical to me. This isn’t for reasons that have anything to do with the poll code if only because the poll code’s scope doesn’t extend beyond the election itself, to the bigger picture.

At the outset, I don’t think vaccines should feature at all in election rhetoric (even if this may be wishful thinking with a majoritarian-populist government). But here we are.

The BJP is in power at the Centre – it runs the national government – and is hoping to come to power in the state. It isn’t necessarily including Nitish Kumar, the state’s incumbent chief minister and whose party the BJP is allied with, because the vaccine promise appeared only in the BJP’s manifesto, not in the alliance’s, and was announced with much fanfare by the Union finance minister. So Kumar was nowhere in the picture but the Centre was. This is a slight but significant difference vis-à-vis Biden’s promise.

State is a health subject in India but a COVID-19 vaccine, should one become available, will have significant participation by the Centre, from purchasing to distribution. Note that India’s states didn’t fight polio – they simply couldn’t. The country has a whole did and today COVID-19 presents an even bigger challenge.

A new study, echoing some older ones, has found that antibodies to COVID-19 fade over a few months. Assuming for a moment that vaccine-induced antibodies work like natural antibodies, and setting aside the fact that the question of antibody persistence is yet to be settled, access to vaccines (including the question of affordability) matters as much as its uniformity. That is, the level of access should be uniform across the epidemic’s ‘jurisdiction’.

For example, if a state with poor pubic health care and infrastructure to begin with is forced to administer the vaccine by itself, failures on its part could allow the virus to become endemic to that region, and allow it spread once again through the rest of the population once their antibody responses have weakened. So an additional pitfall here is if the BJP fragments the responsibility of distributing and administering a COVID-19 vaccine to the states, in an effort to legitimise piecemeal agreements based on political expediency, the vaccination drive will fail, especially in states like Bihar.

So while state governments will be able to decide whether to sell the vaccines for free, the decision depends considerably on the Centre’s cooperation. In effect, the BJP at the Centre abdicates the option to ensure everyone gets the vaccine at no cost when it offers to do so only in a specific area, and in exchange for votes.

Biden is not entirely in the clear either: ‘vaccines for votes’ is a prompt for voters to think of their choice of president as a question of life or death, which is nothing but a dire threat. But neither his case nor that of the Congress’s NYAY scheme are ones of abdicated responsibilities. Neither is yet in power in their respective countries, so neither is pulling back on their existing responsibilities, making their exercise contingent on electoral outcomes or vouchsafing the rewards to – from the epidemic’s PoV – an arbitrary section of the population.

Powerful microscopy technique brings proteins into focus

Cryo-electron microscopy (cryo-EM) as a technology has become more important because the field that it revolutionised – structural biology – has become more important. The international scientific community had this rise in fortunes, so to speak, acknowledged when the Nobel Prize for chemistry was awarded to three people in 2017 for perfecting its use to study important biomolecules and molecular processes.

(Who received the prize is immaterial, considering more than just three people are likely to have contributed to the development of cryo-EM; however, the prize-giving committee’s choice of field to spotlight is a direction worth following.)

In 2015, two separate groups of scientists used cryo-EM to image objects 2.8 Å and 2.2 Å (1 nm is one-billionth of a metre; 1 Å is one-tenth of this) wide. These distances are considered to be atomic because they represent the ability to image features about as big as a smallish atom, comparable to that of, say, sodium. Before cryo-EM, scientists could image such distances only with X-ray crystallography, which requires the samples to be studied to be crystallised first. This isn’t always possible.

But though cryo-EM didn’t require specimens to be crystallised, they had to be placed in a vacuum first. In vacuum, water evaporates, and when water evaporates from biological objects like tissue, the specimen could lose its structural integrity and collapse or deform. The trio that won the chemistry prize in 2017 developed multiple workarounds for this and other problems. Taken together, their innovations allowed scientists to find cryo-EM to be more and more valuable for research.

One of the laureates, Joachim Frank, developed computational techniques in the 1970s and 1980s to enhance, correct and in other ways modify images obtained with cryo-EM. And one of these techniques in turn was particularly important.

An object will reflect a wave if the object’s size is comparable to the wave’s wavelength. Humans see a chair or table because the chair or table reflects visible light, and our eyes detect the reflected electromagnetic waves. A cryo-EM ‘sees’ its samples using electrons, which have a smaller wavelength than photons and can thus reveal even smaller objects.

However, there’s a catch. The more energetic an electron is, the lower its wavelength is, and the smaller the feature it can resolve – but a high-energy electron can also damage the specimen altogether. Frank’s contributions allowed scientists to reduce the number of electrons or their energy to obtain equally good images of their specimens, leading to resolutions of 2.2 Å.

Today, structural biology continues to be important, but its demands have become more exacting. To elucidate the structures of smaller and smaller molecules, scientists need cryo-EM and other tools to be able to resolve smaller and smaller features, but come up against significant physical barriers.

For example, while Frank’s techniques allowed scientists to reduce the number of electrons required to obtain the image of a sample, using fewer probe particles also meant a lower signal-to-noise ratio (SNR). So the need for new techniques, new solutions, to these old problems has become apparent.

In a paper published online on October 21, a group of scientists from Belgium, the Netherlands and the UK describe “three technological developments that further increase the SNR of cryo-EM images”. These are a new kind of electron source, a new energy filter and a new electron camera.

The electron source is something the authors call a cold field emission electron gun (CFEG). Some electron microscopes use field emission guns (FEGs) to shoot sharply focused, coherent beams of electrons optimised to have energies that will produce a bright image. A CFEG is a FEG that reduces the brightness in favour of reducing the average difference in energies between electrons. The higher this difference – or the energy spread – is, the more blur there will be in the image.

The authors’ pitch is that FEGs help produce brighter but more blurred images than CFEGs, and that CFEGs help produce significantly better images when the goal is to image features smaller than 2 Å. Specifically, they write, the SNR increases 2.5x at a resolution of 1.5 Å and 9.5x at 1.2 Å.

The second improvement has to do with the choice of electrons used to compose the final image. The electrons fired by the gun (CFEG or otherwise) go on to have one of two types of collisions with the specimen. In an elastic collision, the electron’s kinetic energy doesn’t change – i.e. it doesn’t impart its kinetic energy to the specimen. In an inelastic collision, the electron’s kinetic energy changes because the electron has passed on some of it to the specimen itself. This energy transfer can produce noise, lower the SNR and distort the final image.

The authors propose using a filter that removes electrons that have undergone inelastic collisions from the final assessment. In simple terms, the filter comprises a slit through which only electrons of a certain energy can pass and a prism that bends their path towards a detector. This said, they do acknowledge that it will be interesting to explore in future whether inelastically scattered electrons can be be better accounted for instead of being eliminated altogether – akin to silencing a classroom by expelling unruly children versus retaining them and teaching them to keep quiet.

The final improvement is to use the “next-generation” Falcon 4 direct-electron detector. This is the latest iteration in a line of products developed by Thermo Fisher Scientific, to count the number of electrons impinging on a surface as accurately as possible, their relative location and at a desirable exposure. The Falcon 4 has a square detection area 14 µm to a side, a sampling frequency of 248 Hz and a “sub-pixel accuracy” (according to the authors) that allows the device to not lose track of electrons even if they impinge close to each other on the detector.

A schematic overview of the experimental setup. Credit: https://doi.org/10.1038/s41586-020-2829-0

Combining all three improvements, the authors write that they were able to image a human membrane protein called ß3 GABA_A R with a resolution of 1.7 Å and mouse apoferritin at 1.22 Å. (The protein called ferritin binds to iron and stores/releases it; apoferritin is ferritin sans iron.)

A reconstructed image of GABA_A R. The red blobs are water molecules. NAG is N-acetyl glucosamine. Credit: https://doi.org/10.1038/s41586-020-2829-0

“The increased SNR of cryo-EM images enabled by the technology described here,” the authors conclude, “will expand [the technique] to more difficult samples, including membrane proteins in lipid bilayers, small proteins and structurally heterogeneous macromolecular complexes.”

At these resolutions, scientists are closing in on images not just of macromolecules of biological importance but of parts of these molecules – and can in effect elucidate the structures that correspond to specific functions or processes. This is somewhat like going from knowing that viruses infect cells to determining the specific parts of a virus and a cell implicated in the infiltration process.

A very germane example is that of the novel coronavirus. In April this year, a group of researchers from France and the US reported the cryo-EM structure of the virus’s spike glycoprotein, which binds to the ACE2 protein on the surface of some cells to gain entry. By knowing this structure, other researchers can design the more perfect inhibitors to disrupt the glycoprotein’s function, as well as vaccines that mimic its presence to provoke the desired immune response.

In this regard, a resolution of 1-2 Å corresponds to the dimensions of individual covalent bonds. So by extending the cryo-EM’s ability to decipher smaller and smaller features, researchers can strike at smaller, more precise molecular mechanisms to produce more efficient, perhaps more closely controlled and finely targeted, effects.

Featured image: Scientists using a 300-kV cryo-EM at the Max Planck Institute of Molecular Physiology, Dortmund. Credit: MPI Dortmund.

A future obscured by exponential growth

A couple months into the COVID-19 pandemic, I think most of us realised how hard it is to comprehend the phenomenon of exponential growth. Mathematically, it’s trivial – a geometric progression – but more physically, the difference between linear and exponential growth is very non-trivial, as a cause-effect chain where each effect leads to multiple new cases according to a fixed growth ratio. The effect is an inability to fully anticipate future outcomes – to prepare mentally for the ‘speed’ with which an exponential series can scale up – rendered remarkable by us not having planned for it.

For example, the rice and chessboard problem is a wonderful story to tell because it’s hard for most people to see the punchline coming. To quote from Wikipedia: “If a chessboard were to have wheat placed upon each square such that one grain were placed on the first square, two on the second, four on the third, and so on (doubling the number of grains on each subsequent square), how many grains of wheat would be on the chessboard at the finish?” The answer is 18,446,744,073,709,551,615 – a 100-million-times greater than the number of stars in the Milky Way. Many people I know have become benumbed by the scale of India’s COVID-19 epidemic, which zipped from 86k active cases on May 30 to 545k on July 31, and from 1M total cases on July 17 to 7.3M on October 15. On August 1, 1965, Vikram Sarabhai delivered the convocation address at IIT Madras, which included the following quip:

Everyone here is undoubtedly familiar with the expression ‘three raised to the power of eighteen’. It is a large number: 38,74,20,489, thirty-eight crore, seventy-four lakh, twenty thousand, four hundred and eighty-nine. What it means in dynamic terms is quite dramatic. If a person spreads gossip to just three others and the same is passed on by each of them to three others, and so on in succession, in just eighteen steps almost the entire population of India would share the spicy story.

Because of its mathematical triviality and physical non-triviality, I think we have a tendency to abstract away our impression of exponential growth – to banish it out of our imagination and lock it away into mathematical equations, such that we plug in some numbers and extract the answers without being able to immediately, intuitively, visualise or comprehend the magnitude of change, the delta as it were, in any other sense-based or emotional way. And by doing so, we are constantly surprised by the delta every time we’re confronted with it. Say the COVID-19 epidemic in India had a basic reproductive number of 1.4, and that everyone was familiar with this figure. But simply knowing this value, and the fundamental structure of a geometric progression, doesn’t prepare people for the answer. They know it’s not supposed to be N after N steps, but they’re typically not prepared for the magnitude of 1.4^N either.

I recently came across a physical manifestation of this phenomenon in a different arena – technology – through a Twitter account. The oldest Homo sapiens technologies include fire, tool-making, wheels and cropping. But while the recursive application of these technologies alone may have given rise, in a millennium (i.e. 1,000 steps), to, say, a subsistence agriculture economy with some trade, that’s not what happened. Instead, two other things did (extremely broadly speaking): the technologies cut down the time required for different processes, and which subsequently came to be occupied by the application of these technologies to solve other problems. The geometric-like progression that followed exponentiated not the technologies themselves but these two principles, of sorts, rapidly opening up new methods and opportunities to extract value from our surroundings, and eventually from ourselves, to add to the globalising value chain.

To get a quick sense of the rapidity of this progress, check out @MachinePix on Twitter. Their latest tweet (as of 11 am on October 17) describes a machine that provides a “motion-compensated” gangway for workers moving between a ship and an offshore wind turbine; many others depict ingenious contraptions ranging from joyously simple to elegantly complicated – from tape-dispensers and trains windows that auto-tint to automated food-packaging and super-scoopers. There’s even a face-mask gun that seems to deliver an amount of pain suitable for anti-maskers.

But closer to the point of this discussion: taken together, @MachinePix’s tweets demonstrate the extent to which we have simplified and/or automated different processes, and the amount of time humans have collectively saved as a result. This, again, can’t be a straightforward calculation: we don’t just apply the same technologies over and over to perform the same tasks. We also apply technologies to each other to compound or even modify their effects, effectively leading to new technologies and, thus, new applications – from the level of toothbrush plus toothpaste to liquefaction plus rocket engines. The tools we develop also alter the structure of society, which in turn changes aspirations and leads to the birth of yet more technologies, but ordered along different priorities.

In the last few months, I learnt many of these features in an intimate way through Factorio, a video-game that released earlier this year. The premise is that your spaceship has crashed on an alien planet, with many of the same natural resources as Earth. You now need to work your way through a variety of technologies and industrial systems and ultimately build a rocket, and launch yourself off to Earth. The ‘engine’ at the game’s centre, the thing that drives your progress, is a recipe-based manufacturing system. You mine resources, process them into different products, combine them to make components, and combine the components to make machines. The machines automate some or all of these processes to make more sophisticated machines and robots, and so forth. To move objects, you use different kinds of inserters and conveyor belts; for fluids – from water to lubricant – there are pipes, tanks, even fluid wagons attached to trains.

A zoomed-out scene from Factorio. This is ‘Main Station’, one of five bases I operate in this scenario.

I’m still finding my way around the extent of the game; the technology tree is very high and has scores of branches. The scenario I’m currently playing goes beyond a rocket to using satellites, but doesn’t include the planet’s alien creatures, who attack your base if you antagonise them or pollute too much. I often think it would’ve been much better to allow final-year students of mechanical engineering (which I studied) to play this game instead of making them sit through hours of boring lectures on logistics, quality control, operations research, supply-chain management, etc. Factorio doesn’t set out to teach you these things but that’s what you learn – and on the way, you also discover how easy it is for things to get out of control, become too complicated, too chaotic – sometimes just too big to fail.

Sometimes, you’ve invested so much in developing one technology that you’re unable to back out, and you start to disprivilege other ambitions in favour of this one. This happened to me recently: being hell-bent on building nuclear reactors to keep up with the demand for power, I had to give up on building a satellite.

Instead of a linear or even a tree-like model of technology development, imagine a circular one: at the centre is the origin, and the circumference is where you are, the present (it’s not a single point in space-time; it’s multiple points in space at one time). Technologies emerge from the origin and branch out towards the perimeter in increasingly intricate branches. By the time they’ve reached the outer limits, to where you are, you have nuclear power, rocketry, robotic construction networks and high-grade weapons. But in this exponentially interconnected world, what do you change and where to effect a difference somewhere else? And how can you hope to be sure there won’t be any other effects?

My new favourite example of this, from the few-score @MachinePix tweets I’ve scrolled through thus far, is the rotary screen printer. It shows, among many other things, that there’s a second way in which exponential growth disrupts our ability to predict its outcomes. Could a fantasy writer working all those millennia ago have predicted this device’s existence? They may have, they may have not, just as we contemplate what the future might look like from today, but sometimes presume to anticipate – even though we really can’t – the full breadth of what lies in store for humankind. Can we even say if the rotary screen printer will still be around?

Featured image: An artist’s rendering of spaceships hovering above a city. More importantly, this image belongs to a genre quite popular in the 2000s, perhaps the late 1990s too, when image-editing software wasn’t as versatile as it is today and when the internet was only just beginning to democratise access to literature and videos, among other things, so the most common idea of first contact looked a lot like this. Credit: Javier Rodriguez/pixabay.

The climate change of bad news

This post flows a bit like the 1987 film Full Metal Jacket. As one friend put it, “It starts somewhere and then goes in a different direction.”

This year hasn’t been beset by the same old steady drizzle of bad news we have every year – but has borne the brunt of cyclonic storms, each one distinctively episodic and devastating. The latest of these storms is l’affair Rukmini Callimachi. To the uninitiated: Callimachi is a reporter with the NYT who shot to fame from 2015 or so onwards for her inside reports of the Islamic Caliphate; she later dramatised her efforts to produce these stories in a podcast called Caliphate. And in this time, she raked up four Pulitzer Prize nominations (although I don’t set much store by prizes in general).

I haven’t read or listened to her work, so when a friend shared a link to the NYT’s own report, by its media columnist Ben Smith, discussing the charges against Callimachi and their newfound, but evidently delayed, efforts to reevaluate her work, I wasn’t guilty of not having criticised her myself. (If you think this is a tall order: the headline of Jacob Silverman’s review of this storm for The New Republic describes, in a few words, how quickly her house of cards seems to fall down.)

However, these days, a successful journalist is two things: she is the producer of stories that have changed the world, and which continue to live lives of their own, and she is a role-model of sorts. Her output and her resolve represent what is possible if only one tried. An even greater example of such work is that of the journalists at the Miami Herald – especially Julie Brown – who exposed Jeffrey Epstein and brought on, among other changes, a reckoning at various universities around the US that had knowingly accepted his money and overtures.

But now, with Callimachi’s articles seemingly teetering on the brink of legitimacy, both the things she stood for are on the edge as well. First, the good thing: her stories, which – if Smith’s account is to be believed – Callimachi seems to have composed in her head before moving in to report them, often, if not always, with the spiritual and material support of many of NYT’s senior editors. Second, the bad: her legacy, such as it is – erected as a façade at which we could all marvel, at least those of us who unquestioningly placed our faith and hope in the greatness of another. This is the guilt I feel, a fractured reflection of what Callimachi’s coverage of the Islamic Caliphate at the NYT is itself going through right now.

However, I will also be quick to shed this guilt because I insist that as much as I’m tasked – by my employer, but the zeitgeist, so to speak – to be wary, cautious, skeptical, to fact-check, fact-check, fact-check, to maintain cupfuls of salt at hand so I’m never taken for a ride, just as much as I’m behooved to stand on guard, I’m also fortifying an increasingly small, and increasingly precious, garden in a corner of my mind, a place away from the bad news that I can visit in my daydreams, where I can recoup some hope and optimism. Today, the winds of l’affair Callimachi blew away her articles and podcasts from this place.

Make no mistake, I will still call out everything that deserves to be called out: from the multiple red-flags Silverman spotlighted to the anti-oriental undertones of Callimachi’s methods, of her claims and even of the self-recrimination bubbling up around her, to a lot of which Rafia Zakaria has (repeatedly) called attention. I’m only saddened, for now, by the unstoppable eradication of all that is good, such as it is, and by the guilt for my part in it. As a political being, in this moment I deem this march upon ignorance to be necessary, but as a human one, it is deeply, and to my mind unforeseeably, exacting. A cognitive dissonance for the times, I suppose, although I’m sure I will cope soon enough.

Fortunately, perhaps in a counterintuitive sense, the Callimachi episode is personally not very hard to recover from. While it is true that what Callimachi and her collaborators have (still largely allegedly) done is quite different from, say, what Jonah Lehrer did, they were both motivated by a common sin: to print what could be instead of what is (and even these words might be too strong). More specifically, reporting on war brings with it its own seductions, many of them quite powerful, to the extent that some – as Zakaria implied in her piece for The Baffler – may choose to believe Callimachi et al’s failings are still the failings of an institution vis-à-vis conflict journalism. But no, the problem is pervasive.

However, looking on this shitshow from not-so-distant India, two bells have been quick to go off. First, this is very old wine in a new bottle, in which, to borrow Zakaria’s words, “the greed for catching terrorists” is pressed into the service of making “white journalists’ careers”; you could replace ‘terrorists’ with anything else that has been touched, at any point in its history, by a colonist or invader. Also read Priyanka Borpujari’s 2019 essay in the Columbia Journalism Review, in which she writes:

The title ‘foreign correspondent’ has long been synonymous with whiteness, maleness, and imperialism—journalists fly in from North America, Europe, and Australia to cover the poverty and wars of the non-Western world. In recent years, a push for diversity has meant that more women are pursuing stories in what was once the domain of men—conflict zones and fractured democracies—or in traditionally private female spaces. But the opportunities for journalists in non-Western nations to tell their own stories in international outlets have not been as great. Overwhelmingly, foreign reportage still relies on a model of Western, and largely white, reporters hiring local journalists in subservient roles.”

And thanks to biases in the way technology is constructed, used as well as located around the world, the problem extends to the consumption of journalism as well. To quote from an older post:

Where an app [that amplifies content] was made matters because nobody is going to build an app in location A and hope that it becomes popular in faraway location B. Pocket itself is San Franciscan and the bias shows: most recommendations I’ve received, or even the non-personalised trending topics I’ve spotted, are American. In fact, among all the tools I use and curation services I follow, I’ve come across only two exceptions: the heartwarming human-curated 3QuarksDaily and Quora. I’m not familiar with Quora’s story but I’m sure it’s interesting – about how a Q&A platform out of Mountain View came to be dominated by Indian users.

I notice a not insignificant number of articles and essays, in English, to this day emerging from blogs and publications in Central, South and Southeast Asia, South America and of course Africa that will never go viral on Twitter, make it to the list of ‘most read’ articles on Pocket or be cited by even the most quirky columnist – even as the same ideas and arguments will virtually ‘break the internet’ the moment they emerge from The Atlantic or New Yorker a few months later.

None of the writers of The Atlantic or New Yorker can be blamed, at least not most of the time, for something quite hard to discover in the first place, but that doesn’t mean Big Tech isn’t distorting our view of who is doing good work and who isn’t. And many Indian journalists and writers are often at the wrong end of this discovery problem.

In this light, what Callimachi and the NYT did is not new at all but in fact further widens, or accentuates, the divide between being non-white, non-Western and being white and Western. This is a divide that I and many others, perhaps especially the others, have been habituated to ignore – especially when the crime at hand appears to be victimless but in fact quietly sidelines those who have already been historically, and today structurally, displaced from the ‘mainstream’.

On the other hand, what the NYT has perpetrated here is akin to what many in India (myself included) have done and, to different degrees, continue to have a part in. Specifically, the second bell that goes off has to do with my privileges, one product of which is that I will always be a parachute-journalist in my own country – a member of the top 1% who claims to understand the problems of the 99%.

Journalism professor Justin Martin gently defended parachute journalism in a 2011 essay, deeming fluency in “one of the main local languages” to be a prerequisite of parachuting well. I am not likely to speak any other languages than the four I already know, and less literally, I can never know, in any meaningful sense, what it means to be poor, transgender, tribal, of a lower caste; that lived experience will stay out of reach, and my assessment of what is right will always be inferior to those of, say, a desperate job-seeker, a transgender activist, a member of a tribe, a Dalit scholar when, for example, the topic at hand is poverty, gender, Indigenous people’s rights and caste.

As Martin also admits, “Hiring correspondents who live in the countries and regions they cover … is ideal”, and my higher social status in India does place me in a country other than the one I’m writing about. Although I may not be guilty of allowing information sources I haven’t vetted enough to feed exaggerated stories that I can’t prove in any other way to be true – that is, although we may not all be Rukmini Callimachis ourselves – the composition of our newsrooms means we are only one illegitimate source away, only one moment of weakness for what could be in place of what is away, from creating the next storm.