The world’s preeminent scientists say a theory from the Broad Institute’s Alina Chan is too wild to be believed. But when the theory is about the possibility of COVID being man-made, is this science or censorship?
In January, as she watched the news about a novel virus spreading out of control in China, Alina Chan braced for a shutdown. The molecular biologist at the Broad Institute of Harvard and MIT started stockpiling medicine and supplies. By the time March rolled around and a quarantine seemed imminent, she’d bought hundreds of dollars’ worth of fillets from her favorite fishmonger in Cambridge and packed them into her freezer. Then she began to ramp down her projects in the lab, isolating her experimental cells from their cultures and freezing them in small tubes.
As prepared as she was for the shutdown, though, she found herself unprepared for the frustration of being frozen out of work. She paced the walls of her tiny apartment feeling bored and useless. Chan has been a puzzle demon since childhood, which was precisely what she loved about her work—the chance to solve fiendishly difficult problems about how viruses operate and how, through gene therapy, they could be repurposed to help cure devastating genetic diseases. Staring out her window at the eerily quiet streets of her Inman Square neighborhood, she groaned at the thought that it could be months before she was at it again. Her mind wandered back to 2003, when she was a teenager growing up in Singapore and the first SARS virus, a close relative of this coronavirus, appeared in Asia. It hadn’t been anything like this. That one had been relatively easy to corral.
How had this virus come out of nowhere and shut down the planet? Why was it so different? she asked herself.
Then it hit her: The world’s greatest puzzle was staring her in the face. Stuck at home, all she had to work with was her brain and her laptop. Maybe they were enough. Chan fired up the kettle for the first of what would become hundreds of cups of tea, stacked four boxes on her kitchen counter to raise her laptop to the proper height, pulled back her long dark hair, and began reading all of the scientific literature she could find on the coronavirus.
It wasn’t long before she came across an article about the remarkable stability of the virus, whose genome had barely changed from the earliest human cases, despite trillions of replications. This perplexed Chan. Like many emerging infectious diseases, COVID-19 was thought to be zoonotic—it originated in animals, then somehow found its way into people. At the time, the Chinese government and most scientists insisted the jump had happened at Wuhan’s seafood market, but that didn’t make sense to Chan. If the virus had leapt from animals to humans in the market, it should have immediately started evolving to life inside its new human hosts. But it hadn’t.
On a hunch, she decided to look at the literature on the 2003 SARS virus, which had jumped from civets to people. Bingo. A few papers mentioned its rapid evolution in its first months of existence. Chan felt the familiar surge of puzzle endorphins. The new virus really wasn’t behaving like it should. Chan knew that delving further into this puzzle would require some deep genetic analysis, and she knew just the person for the task. She opened Google Chat and fired off a message to Shing Hei Zhan. He was an old friend from her days at the University of British Columbia and, more important, he was a computational god.“Do you want to partner on a very unusual paper?” she wrote.
Sure, he replied.
One thing Chan noticed about the original SARS was that the virus in the first human cases was subtly different—a few dozen letters of genetic code—from the one in the civets. That meant it had immediately morphed. She asked Zhan to pull up the genomes for the coronaviruses that had been found on surfaces in the Wuhan seafood market. Were they at all different from the earliest documented cases in humans? Zhan ran the analysis. Nope, they were 100 percent the same. Definitely from humans, not animals. The seafood-market theory, which Chinese health officials and the World Health Organization espoused in the early days of the pandemic, was wrong. Chan’s puzzle detectors pulsed again. “Shing,” she messaged Zhan, “this paper is going to be insane.”
In the coming weeks, as the spring sun chased shadows across her kitchen floor, Chan stood at her counter and pounded out her paper, barely pausing to eat or sleep. It was clear that the first SARS evolved rapidly during its first three months of existence, constantly fine-tuning its ability to infect humans, and settling down only during the later stages of the epidemic. In contrast, the new virus looked a lot more like late-stage SARS. “It’s almost as if we’re missing the early phase,” Chan marveled to Zhan. Or, as she put it in their paper, as if “it was already well adapted for human transmission.”
That was a profoundly provocative line. Chan was implying that the virus was already familiar with human physiology when it had its coming-out party in Wuhan in late 2019. If so, there were three possible explanations.
Perhaps it was just staggeringly bad luck: The mutations had all occurred in an earlier host species, and just happened to be the perfect genetic arrangement for an invasion of humanity. But that made no sense. Those mutations would have been disadvantageous in the old host.
Maybe the virus had been circulating undetected in humans for months, working out the kinks, and nobody had noticed. Also unlikely. China’s health officials would not have missed it, and even if they had, they’d be able to go back now through stored samples to find the trail of earlier versions. And they weren’t coming up with anything.
That left a third possibility: The missing phase had happened in a lab, where the virus had been trained on human cells. Chan knew this was the third rail of potential explanations. At the time, conspiracy theorists were spinning bioweapon fantasies, and Chan was loath to give them any ammunition. But she also didn’t want to play politics by withholding her findings. Chan is in her early thirties, still at the start of her career, and an absolute idealist about the purity of the scientific process. Facts were facts.
Or at least they used to be. Since the start of the pandemic, the Trump administration has been criticized for playing fast and loose with facts—denying, exaggerating, or spinning them to suit the president’s political needs. As a result, many scientists have learned to censor themselves for fear that their words will be misrepresented. Still, Chan thought, if she were to sit on scientific research just to avoid providing ammunition to conspiracy theorists or Trump, would she be any better than them?
Chan knew she had to move forward and make her findings public. In the final draft of her paper, she torpedoed the seafood-market theory, then laid out a case that the virus seemed curiously well adapted to humans. She mentioned all three possible explanations, carefully wording the third to emphasize that if the novel coronavirus did come from a lab, it would have been the result of an accident in the course of legitimate research.
And that, Chan says, is when “shit exploded everywhere.”
https://cdn10.bostonmagazine.com/wp-...science-13.jpg Photo by Mona Miri
**Alina Chan, a molecular biologist at the Broad Institute, says we can’t rule out the possibility that the**
novel coronavirus originated in a lab—even though she knows it’s a politically radioactive thing to say.
Part of the reason the coronavirus has been so successful - apart from the fact that more than half of cases may be asymptomatic - is that it’s also very good at infecting us, so it spreads very efficiently. And that’s been true since the very first recorded cases in Wuhan. Alina Chan from the Broad Institute and Shing Zhan from the University of British Columbia have analysed the genetic sequences from some of the first samples collected, and compared them. They then compared that variation to the first SARS, and spotted something odd. Phil Sansom asked them what...
Alina - SARS-2 is much more similar to SARS-1 in the late phase of its epidemic. In the case of SARS-1, when it first crossed from animals into humans we could see that the virus underwent adaptation to the new host, which was humans. And this was in the early phase of the epidemic; the virus was mutating, finding adaptive mutations that could help it transmit amongst humans. But by the time it hit the late phase of the epidemic, this genetic diversity was greatly reduced. So this finding suggested that by the time we detected SARS-2 in December of 2019, it was already really optimised, or highly adept at human transmission. So we are missing this whole period where SARS-2 should have been rapidly adapting to its new host, and this raises really important questions about where did SARS-2 come from.
Phil - Shing, could you please explain genetically what it means here for the SARS-2 to be similar to the late version of SARS-1, rather than the early one? What does genetic similarity mean here? Shing - Within roughly the first three months of each outbreak, the genome of SARS-CoV-2 had about one fourth the amount of genetic diversity that was found in SARS-CoV-1. And we did have genetic sequence data for four samples in the Wuhan night seafood market, and we compared the genome sequences recovered from those samples to the genome sequence of the Wuhan reference of SARS-CoV-2; and what we found was that they're very similar. And what that led us to think was, maybe the outbreak that was happening at the market didn't start from some nonhuman intermediate host, but instead it could have come from some people who were already infected at the time and they were doing some grocery shopping at the market.
Phil - Where were these samples actually from? Were they from bits of meat or something?
Shing - The samples were, for example, doorknobs; they had even some samples from the sewers; and they have samples from the surfaces of garbage trucks. What it looked like to us was that the sequences were just very similar to that from humans. So there was no real evidence that data that the virus came from some animal sold at the market.
Phil - Alina, was this surprising to you?
Alina - Yeah, so in the case of SARS-1, they went straight to the local market and there they found numerous species of animals that carry SARS-1-like viruses. But importantly the SARS-1-like viruses were not a hundred percent match, and that's why we're surprised here. Here in SARS-2, when you look at the samples from the market, they're all nearly virtually 100% identical to the human version. And so what that suggests is that these viruses were not from animals that were the source of the virus, but rather that they had been dropped by humans who were infected and had visited the market.
Phil - In that case, where did this actually come from then?
Alina - There are three different scenarios that are plausible. One of them is: SARS-2 would have crossed from an animal into humans a long time ago - this could be months to years - and it just circulated undetected in the human population for that amount of time, picking up adaptive mutations along the way, and then it finally broke out in Wuhan once it had reached the state of high adaptation to human transmission. The second scenario: that SARS-2 was already pre-adapted for humans while in bats on intermediate host. And the last scenario, which is the most controversial, is that SARS-2 could have resulted from lab-based scenarios. And we're not saying this to accuse anyone of malicious intent; lab accidents happen
frequently. Even the first SARS has escaped from many world-class labs, multiple times. Sometimes lab accidents happen.
