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(Sources: theindependent.sg, wikipedia.org) For the first time in living memory, the announcement of the The Nobel Prize in Physiology or Medicine would be moved forward from its usual date in October, and an unprecedented special award session convened by unanimous acclamation of the Nobel Committee, upon global clamour to recognize what has been described as possibly the "breakthrough of the century", hailed by some to be the greatest scientific discovery since Einstein's formulation of general relativity in 1915. The monumentous feat had been achieved by researchers from the National University of Singapore, who demonstrated for the first time in human history "the possibility of running a randomized controlled trial on inexpensive medications towards mitigation of a coronavirus pandemic, on over three thousand subjects, and actually publishing the results", from the Prize citation. "Nobody was expecting this." eminent retired climatologist and member of the Swedish Academy Sven Ludvig Sjögren said, as he presented the golden medal to Professor Paul Anantharajah Tambyah, president-elect of the International Society for Infectious Diseases, who was representing the Singapore team. "I had been assured by all my colleagues in the field that this was absolutely impossible, with known current technology. They estimate that NUS is ten, no, maybe twenty years ahead of everybody else. It's incredible." Professor Tambyah would humbly credit the rest of the study team, and the volunteer participants, as he accepted the prize. In doing so, he becomes the first Singaporean Nobel laureate ever, and only the third such to be associated with his country, after physicist Sir Konstantin Novoselov, and the late biologist Sydney Brenner. Singapore's flagship university has been steadily building its reputation since its founding as what would become the King Edward VII College of Medicine in 1905, but doubts remained over whether it had achieved the heft to truly consider itself amongst the world's premier colleges. Any such remaining misgivings would be well and truly extinguished today, as the National University of Singapore revealed itself at the forefront - nay, far and away setting the pace - of contemporary scientific endeavour. What made the achievement so singular was that it had required simultaneous major discoveries in multiple disciplines, but amongst these various wonders, the sheer scale of the system that they had assembled would overawe the entire community. Tsun-Tsang Cheung, pioneer of quantum mechanics from [Not-A-Country Redacted] and of late involved with the Google team that had claimed quantum supremacy three years ago, would attempt to place the NUS feat in context. "We did it with 54 qubits in our quantum computer, the group from China's University of Science and Technology got up to 76 qubits, and IBM is claiming more than 100 - though I have something to say about that. But then, just imagine, somebody comes out of the blue with three thousand qubits, with undeniable proof! You don't expect these kinds of paradigm leaps nowadays, with all the collaboration going on between top groups!" "Not just three thousand, three thousand and thirty-seven." Cheung's former MIT classmate - and now leading particle physics experimentalist at CERN - Esteban Alvaro Julián Delgado corrected, while shaking his head in admiration. "I truly did not think it within the realm of material plausibility. It is well-known that there is no analytical solution to the three-body problem, so it staggers me to even dream about the computational power and theoretical genius needed to manage not three, not thirty, but over 3,000 of those bodies at once. It beggars belief." Given this, the accompanying Nobel Lecture would be one of the longest in years, as Professor Tambyah was invited to share the basics of his team's numerous groundbreaking innovations with the wider world. The short introductory keynote delivered by Dr. Justin A. Sokratis, former President of the U.S. National Academy of Sciences, would touch on the dangers of partisan politicization of the subject and the abject irresponsibility of the mass media, before Tambyah took to the podium before the packed Stockholm Concert Hall to reveal what had hitherto been some of the most eagerly-awaited secrets in various fields. There was an electric silence as Professor Tambyah began his presentation by displaying an unfamiliar figure to the rapt audience, which had a green bar at the top, and many regularly-sized cells covering the remainder of the image. "This is a screenshot from a program we call 'Microsoft Excel'" the good professor started. "You see, we assign each of our subjects with a random identifier, and each row then corresponds to one of the anonymized subjects." As the distinguished audience oohed and aahed, Professor Tambyah would demonstrate the capabilities of the spreadsheet live. "Every column, then, represents the data for a single day, the medication that the subject consumed for the day. H for HCQ, I for Ivermectin, Z for Vitamin C and Zinc, X for a missed dose, and so on. The second-last column shows the treatment arm that the subject had been assigned to, and the final column has the result of the antibody response test for the coronavirus, at the end of the study. Look, you can add data for a new subject, simply by clicking an empty cell and typing on the keyboard." Professor Tambyah would go on to demonstrate features like "pivot tables" and "macro functions" for half an hour before a deserved intermission, during which the stunned audience struggled to digest what they had just witnessed. "I have never seen mathematical structure like that." whispered Dr. Dimitri Rabinovich, legendary topologist, Fields Medal nominee, and emeritus chair at Moscow State University. "There appear connections to infinite-dimensional manifolds and symmetric lattice methods, but I confess it beyond my full comprehension. It's so... dynamic. Changing the value of one matrix item affects the values of multiple other cells, in an ordered n-ary fashion. Honestly, I have not felt so excited since my sabbatical in France with Grothendieck, as a postdoctoral fellow in the 1970s. I feel young again!" The sense of wonderment only intensified as Professor Tambyah continued the dissertation after the break, as he imported the data into another unknown software that he called "Stata", ran a "logistic regression" with "random effects", and produced a metric that he named the "derived odds ratio", moreover with esoteric references to "Wald p-values" and "bootstrap confidence intervals". More than a few of the attendees were seen furiously scribbling into notebooks, as they strove to catch up on all the new statistics being revealed. "It's almost unfair." probabilist bon vivant James Kenyon Rugger, often spoken of as favourite to succeed to the Lucasian Chair of Mathematics at Cambridge, griped whilst staring at his copious shorthand. "Generating three thousand random numbers, indeed. How can one man know so much?" [Editor's Note: Professor Tambyah would clarify after the ceremony, that the Stata scripts for the analysis had been coded by his second-year intern Vikul Chakrabarti, who has sadly been unable to make it to Sweden due to having been called up for his annual reservist stint with the Singapore infantry. Chakrabarti would however be able to take time off from latrine duty, to modestly decline the praise received.] The second part of the lecture would turn to pharmacology, as Professor Tambyah briefly covered the long medical history of hydroxychloroquine, with a line diagram of the compound's molecular arrangement prominently projected on the screen behind him. Strangely, not a few members of the American contingent were observed taking cover under the tablecloth or making the sign of the cross with tremulous hands for this segment, but these behaviours would be dismissed as delightful quirks not uncommonly seen with academics. There would be a unified gasp as Professor Tambyah extracted a single white tablet, and swallowed it before the assembled dignitaries. "He didn't need to do that!" world-famous entomologist Susan J. Barthemalow, renowned for her seminal tomes on tropical beetle diversity, wheezed as she patted her chest, trying to recover from the shock. "I thought he was going to die! Yes, I had been consuming HCQ weekly together with the rest of the party and the locals when we were on expeditions in Sumatra back in the Eighties, but The New York Times has their experts writing that it's literally poison, and if you can't trust the Times, who can you trust? Once I read that, there was nothing I could do but call in a professional biohazards squad, to dispose of the leftover bottles I had kept in my attic, before disinfecting the house." Cornell organic chemistry professor Sebastian Kolakowski, who is also the founder of the early-stage biomedical startup Konari, would sense opportunity even as he handed Dr. Barthemalow an extra glass of water. "Just between you and me, I don't think Dr. Tambyah and the Singaporean team are revealing everything here." he nodded, a twinkle in his eye. "We all reserve a few trade secrets, eh? I mean, he's still standing and talking like nothing has happened, obviously he has done something to the molecule, an extra bond or amino or such. Well, the possibilities are endless, Konari is ever ready to discuss business." There would be a minor commotion as liveried attendants removed a guest from the back of the hall, as he raved about "needing to check the speaker for his QT-prolongation", but the talk would swiftly resume as if nothing had happened. Professor Tambyah would defer to head nurse Aisyah Sharifah, who had overseen the day-to-day running of the trial experiment, in explaining how its immaculate safety standards had been maintained. "Before we enroll a subject in the trial, we have them undergo a simple intelligence test, in which they are instructed to write down their name, and not stick the pencil up their nose. All of them passed. Given this, we trusted that they would not do something as stupid as consume all the pills at once, not that even that was likely to be fatal anyway." At this astounding revelation, there would be a buzz of conversation throughout the place. "Can we do this?" one of the doctors seated at a table filled with the heads of various Californian hospital clusters was heard asking. "I don't know, sounds like a... revolutionary, even radical concept." came the reply. "We shouldn't presume too much about the I.Q. level of our residents." And then, in a lowered tone. "They said they gave HCQ to 432 humans, and none of them died, or at least vomited blood? You are never getting me to buy that!" Three hours after its inception, Professor Tambyah would complete his speech by explaining how he managed to get the study published ("It really, really helps when the learned society that you are going to be President of, issues the journal"), and finally an exhibition of "drag-and-fill" in "Microsoft Excel"; the sparkling exposition seems destined for the annals of history, from the extended standing ovation that followed. More worldly concerns would inevitably bubble to the fore, as those from the many different nations represented, ruminated over how they could gain access to these earth-shattering life-saving National University of Singapore advances for themselves. "Singapore may be a little red dot, but as they have shown today, they are in science second to none." Indonesian colonel and health ministry attaché Djoko Handayani said. "We believe that they will be more than willing to show ASEAN how they did it. We had advisors from Abrgan BioRegen, one of the U.S. pharma giants, but when we discussed running trials with potential remedies costing US$1 or less per dose, they could never get completed. Then our vitamin warehouse burnt down in the night. But once we considered options at US$100 or more per dose, everything started working, but clearly we cannot afford that for the general populace. So I think Dr. Tambyah and his team are doing a great service for humanity." Bradley N. Schmidt, special consultant to the U.S. National Institutes of Health, had to accept that their tiny city-state ally had stolen a march on the United States here, but that America were confident of regaining leadership in the area, with sufficient funding. "From what we have learnt today, we should be able to run 1,000-person RCTs with drugs costing about US$80 or more per dose by the end of the year, and 2,000-person RCTs at around US$50 per dose by the end of 2023. But the consensus here remains that we shouldn't go much lower than that, because that would be unsafe for the compan... I mean, the consumers. What we really need is a new Manhattan Project to inspire the latest generation, and if Congress earmarks, say, US$1 trillion over ten years, we should get to RCTs with ten thousand participants by the end of the decade." "Ten thousand." Schmidt repeated. "Five digits. Think big!" Before the consultant could continue, however, he would be swarmed by an impassioned throng of Indian scientists, who demanded that the U.S. do more to help their country out materially. "America says India is good friend in the Quad, sir, that we make one billion doses of vaccine together, but now our people are dying in droves from not having enough vaccines for ourselves! We gave America HCQ last year, sir, but America is now not helping at all, it is all pay, pay, pay! Please do needful, sir, or if not, at least give us our HCQ back!" Mr. Schmidt would attempt to explain his way out of the situation. "We follow the Standard Corporo Model of Clinical Trials here in the States. In the model, trial parti-cle-cipants - customos - create a strong repulsive force between them, so you can only gather so many of them together in a confined space, before the trial falls apart. The difficulty is something like keeping the plasma contained in nuclear fusion. Usually there are signs before trial failure, like the principal investigator turning up ashen-faced after a strange phone call, which tends to lead to early termination. Or he just gets reassigned." "To hold the customos particles together in a trial, you need to dope the substrate with dollarinos." Schmidt waved a greenback demonstratively. "The dollarinos possess a weak interaction force, so you need a lot of them to counter the repulsive force of the customos; the bigger the trial, the more customos, thus the more dollarinos required, capisce? Or that was how they explained it to us, at the Big Pharma-sponsored conferences that I attended. I might have forgotten some of the details, because of all the nice young ladies in miniskirts giving out free samples, but the point is that you can't really blame us if your rupeeno to dollarino conversion rate is bad. This is just fundamental physics, take it up with Nature!" The closing statements for the day would be made by Kenyan stateswoman and ethicist Niara Mwangi, who launched into a heartfelt plea for the world to come to their senses against the pandemic. "I do not need to repeat the human toll that is being imposed. The cost-benefit calculus is moreover straightforward. There have been over 170 million COVID-19 cases worldwide, and over 3.5 million deaths. If an early intervention were only 10% successful, that still makes 350,000 lives. But when I check the knowledge base that the WHO is depending on for such early treatments, as maintained in the BMJ, we basically know next to nothing about whether any of them work! It is over fifteen months into the pandemic - how can this be the case? Can anyone here please explain it to me?" Mwangi's more-easily comprehensible appeal would be a welcome change of pace for the audience, after Tambyah's often-impenetrable abstract novelties, and Jeong Dae-Seong, the venerable South Korean elder of analytic philosophy from Sungkyunkwan University, could only agree with her. "It is not really my domain, and alas much of the brilliance that Dr. Tambyah introduced has been lost on me, but morally the case seems clear. I have studied evil in its many guises as the central focus of my career, and I can think of little that is more quintessentially evil than knowingly withholding or discouraging investigations into accessible mitigations, during a plague." "Really, it's a transparent travesty." Todai University star epidemiologist Yahiro Watanabe smirked. "A less gracious man might note that it is exceedingly unlikely that those stalling RCTs into affordable early treatments do not understand what the probable outcomes are, from the results of the many non-RCT experiments, and that these people - some heading major journals and health organizations - are mostly trying to save their own sorry hides. Such a man might also declare that there is nothing that these fuckers could offer him in this life or the next, that could possibly give him half as much pleasure as watching these very sanctimonious hypocritical cocksuckers get the comeuppance that they so richly deserve." "But I am a reserved and polite man, so I would never say such a thing." Watanabe continued, bowing slightly, with palms pressed together in supplication. "Ah, so." A Connecticut physician, seated at the same table at Jeong and Watanabe, confessed that he was of the same opinion on gathering more information on early treatment and HCQ, but requested to remain unnamed. "Please, you must understand, I have not yet finished paying off my loan for medical school, I need this job. And my parents would be so, so disappointed if I got struck off the register, as they are threatening with dissident doctors in the States. I thought this kind of censorship and forcible circumscription of a doctor's own best judgment would occur only in North Korea or China, like when they shut down the Wuhan whistleblower who was trying to inform the public, but I was wrong. I really cannot do anything, I am sorry." There would remain a few scattered detractors of the NUS team's approach, nonetheless, and an elderly gentleman in top hat and monocle would express his dissatisfaction. "I say, these upstarts are providing therapy before the buggers become bedridden, wot. Never heard of such rubbish in my life; tremendously unsporting and all that, these ching-chong gooks. What has the world come to? Bloody Asians!" Dr. Rugger did not seem to hear that, though, as he cradled his head in his hands. "Wald p-values." he muttered. "Regression... logistic. Wow." Update: The Nobel Prize in Physiology or Medicine has since been discontinued, after The New York Times, Washington Post, CNN, MSNBC, Facebook, Twitter, YouTube, OnlyFans, PornHub, several elite general science and medicine journals, a sneaker retailer, a fast food chain and the top ten pharmaceutical firms by market capitalization released a joint statement accusing it of being racist and a symbol of Swedish neoimperialism. It will be replaced by the Brawndo-Duff Beer Award for Socially-Equitable Health, from 2022 onwards. Next: Communications Of The Social Media Gang |
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