Tag: biochemistry

The constructionist hypothesis and expertise during the pandemic

Now that COVID-19 cases are rising again in the country, the trash talk against journalists has been rising in tandem. The Indian government was unprepared and hapless last year, and it is this year as well, if only in different ways. In this environment, journalists have come under criticism along two equally unreasonable lines. First, many people, typically supporters of the establishment, either don’t or can’t see the difference between good journalism and contrarianism, and don’t or can’t acknowledge the need for expertise in the practise of journalism.

Second, the recognition of expertise itself has been sorely lacking across the board. Just like last year, when lots of scientists dropped what they were doing and started churning out disease transmission models each one more ridiculous than the last, this time — in response to a more complex ‘playing field’ involving new and more variants, intricate immunity-related mechanisms and labyrinthine clinical trial protocols — too many people have been shouting their mouths off, and getting most of it wrong. All of these misfires have reminded us of two things: again and again that expertise matters, and that unless you’re an expert on something, you’re unlikely to know how deep it runs. The latter isn’t trivial.

There’s what you know you don’t know, and what you don’t know you don’t know. The former is the birthplace of learning. It’s the perfect place from which to ask questions and fill gaps in your knowledge. The latter is the verge of presumptuousness — a very good place from which to make a fool of yourself. Of course, this depends on your attitude: you can always be mindful of the Great Unknown, such as it is, and keep quiet.

As these tropes have played out in the last few months, I have been reminded of an article written by the physicist Philip Warren Anderson, called ‘More is Different’, and published in 1972. His idea here is simple: that the statement “if everything obeys the same fundamental laws, then the only scientists who are studying anything really fundamental are those who are working on those laws” is false. He goes on to explain:

“The main fallacy in this kind of thinking is that the reductionist hypothesis does not by any means imply a ‘constructionist’ one: The ability to reduce everything to simple fundamental laws does not imply the ability to start from those laws and reconstruct the universe. … The constructionist hypothesis breaks down when confronted with the twin difficulties of scale and complexity. The behaviour of large and complex aggregates of elementary particles, it turns out, is not to be understood in terms of a simple extrapolation of the properties of a few particles. Instead, at each level of complexity entirely new properties appear, and the understanding of the new behaviours requires research which I think is as fundamental in its nature as any other.”

The seemingly endless intricacies that beset the interaction of a virus, a human body and a vaccine are proof enough that the “twin difficulties of scale and complexity” are present in epidemiology, immunology and biochemistry as well – and testament to the foolishness of any claims that the laws of conservation, thermodynamics or motion can help us say, for example, whether a particular variant infects people ‘better’ because it escapes the immune system better or because the immune system’s protection is fading.

But closer to my point: not even all epidemiologists, immunologists and/or biochemists can meaningfully comment on every form or type of these interactions at all times. I’m not 100% certain, but at least from what I’ve learnt reporting topics in physics (and conceding happily that covering biology seems more complex), scale and complexity work not just across but within fields as well. A cardiologist may be able to comment meaningfully on COVID-19’s effects on the heart in some patients, or a neurologist on the brain, but they may not know how the infection got there even if all these organs are part of the same body. A structural biologist may have deciphered why different mutations change the virus’s spike protein the way they do, but she can’t be expected to comment meaningfully on how epidemiological models will have to be modified for each variant.

To people who don’t know better, a doctor is a doctor and a scientist is a scientist, but as journalists plumb the deeper, more involved depths of a new yet specific disease, we bear from time to time a secret responsibility to be constructive and not reductive, and this is difficult. It becomes crucial for us to draw on the wisdom of the right experts, who wield the right expertise, so that we’re moving as much and as often as possible away from the position of what we don’t know we don’t know even as we ensure we’re not caught in the traps of what experts don’t know they don’t know. The march away from complete uncertainty and towards the names of uncertainty is precarious.

Equally importantly, at this time, to make our own jobs that much easier, or at least less acerbic, it’s important for everyone else to know this as well – that more is vastly different.

Corrected: ‘Life’s Greatest Secret’ by Matthew Cobb

An earlier version of this post was published by mistake. This is the corrected version. Featured image credit: amazon.in

When you write a book like Siddhartha Mukherjee’s The Gene: An Intimate History, the chance of a half-success is high. You will likely only partly please your readers instead of succeeding or even failing completely. Why? Because the scope of your work will be your biggest enemy, and in besting this enemy, you will at various points be forced to find a fine balance between breadth and depth. I think the author was not just aware of this problem but embraced it: The Gene is a success for having been written. Over 490 pages, Mukherjee weaves together a social, political and technical history of the genome, and unravels how developments from each strain have fed into the others. The effect is for it to have become a popular choice among biology beginners but a persistent point of contention among geneticists and other researchers. However, that it has been impactful has been incontestable.

At the same time, the flipside of such a book on anything is its shadow, where anything less ambitious or even less charming can find itself languishing. This I think is what has become of Life’s Greatest Secret by Matthew Cobb. Cobb, a zoologist at the University of Manchester, traces the efforts of scientists through the twentieth century to uncover the secrets of DNA. To be sure, this is a journey many authors have retraced, but what Cobb does differently are broadly two things. First: he sticks to the participants and the progress of science, and doesn’t deviate from this narrative, which can be hard to keep interesting. Second: he combines his profession as a scientist and his education as an historian to stay aware, and keep the reader aware, of the anthropology of science.

On both counts – of making the science interesting while tasked with exploring an history that can become confusing – Cobb is assisted by the same force that acted in The Gene‘s favour. Mukherjee banked on the intrigues inherent in a field of study that has evolved to become extremely influential as well as controversial to get the reader in on the book’s premise; he didn’t have to spend too much effort convincing a reader why books like his are important. Similarly, Life’s Greatest Secret focuses on those efforts to explore the DNA that played second fiddle to the medicinal applications of genetics in The Gene but possess intrigues of their own. And because Cobb is a well-qualified scientist, he is familiar with the various disguises of hype and easily cuts through them – as well as teases out and highlights less well-known .

For example, my favourite story is of the Matthaei-Nirenberg experiment in 1961 (chapter 10, Enter The Outsiders). Marshall Nirenberg was the prime mover in this story, which was pegged on the race to map the nucleotide triplets to the amino acids they coded for. The experiment was significant because it ignored one of Francis Crick’s theories, popular at the time, that a particular kind of triplet couldn’t code for an amino acid. The experiment roundly drubbed this theory, and in the process delivered a much-needed dent to the circle of self-assured biologists who took Crick’s words as gospel. Another way the experiment triumphed was by showing that ‘outsiders’ (i.e. non-geneticists like the biochemists that Nirenberg and Heinrich) could also contribute to DNA research, and how an acceptance of this fact was commonly preceded by resentment from the wider community. Cobb writes:

Matthew Meselson later explained the widespread surprise that was felt about Nirenberg’s success, in terms of the social dynamics of science: “… there is a terrible snobbery that either a person who’s speaking is someone who’s in the club and you know him, or else his results are unlikely to be correct. And here was some guy named Marshall Nirenberg; his results were unlikely to be correct, because he wasn’t in the club. And nobody bothered to be there to hear him.”

This explanation is reinforced by a private letter to Crick, written in November 1961 by the Nobel laureate Fritz Lipmann, which celebrated the impact of Nirenberg’s discovery but nevertheless referred to him as ‘this fellow Nirenberg’. In October 1961, Alex Rich wrote to Crick praising Nirenberg’s contribution but wondering, quite legitimately, ‘why it took the last year or two for anyone to try the experiment, since it was reasonably obvious’. Jacob later claimed that the Paris group had thought about it but only as a joke – ‘we were absolutely convinced that nothing would have come from that’, he said – presumably because Crick’s theory of a commaless code showed that a monotonous polynucleotide signal was meaningless. Brenner was frank: ‘It didn’t occur to us to use synthetic polymers.’ Nirenberg and Matthaei had seen something that the main participants in the race to crack the genetic code had been unable to imagine. Some later responses were less generous: Gunther Stent of the phage group implied to generations of students who read his textbook that the whole thing had happened more or less by accident, while others confounded the various phases of Matthaei and Nirenberg’s work and suggested that the poly(U) had been added as a negative control, which was not expected to work.

A number of such episodes studded throughout the book make it an invaluable addition to a science-enthusiast’s bookshelf. In fact, if something has to be wrong at all, it’s the book’s finishing. In a move that is becoming custom, the last hundred or so pages are devoted to discussing genetic modification and CRISPR/Cas9, a technique and a tool that will surely shape the future of modern genetics but in a way nobody is quite sure of yet. This uncertainty is pretty well-established in the sense that it’s okay to be confused about where the use of these entities is taking us. However, this also means that every detailed discussion about these entities has become repetitive. Neither Cobb nor Mukherjee are able to add anything new on this front that, in some sense, hasn’t already been touched upon. (Silver lining: the books do teach us to better articulate our confusion.)

Verdict: 4/5