The Pandemic Heroes Who Gave us the Gift of Time and Gift of Information
As safe and effective vaccines make news, let's remember the heroism of China's scientists and medical workers
There is excellent news today on the vaccine front. To appreciate how we got here, especially how we got here so fast, we should take a moment to recognize the crucial early role played by Chinese scientists and healthcare workers who gave us a uniquely precious gift—time and information—at great risk to themselves.
Let’s step back. Early on during the pandemic, people were predicting that it would take as long as 18 months to develop vaccines, and some thought that was hopeful. People were hoping for a vaccine that would be 60-70% effective. We’ve blown past all of those expectations.
Today, just ten months after a pandemic was declared, Moderna, a company specializing in mRNA technology, is applying to the US Food and Drug Administration for an emergency authorization of its vaccine, presenting stunning data. The Moderna trial enrolled 30,000 participants in the United States. There were 196 infections across the group, with 185 in the placebo group and just 11 in the vaccine group. The level of efficacy, around 94%, is better than most everything many hoped for in February.
Plus, remarkably, every single one of the 30 severe cases of infection were in the placebo group. Not a single person given the vaccine got a severe infection, which promises 100% efficacy against severe disease. That is remarkable. There appear to be no huge safety concerns, either—patients suffered mostly fever and fatigue for about a day. Plus, we have reason to think that the safety profile will hold since these vaccines are likely to be safe exactly because of the novel technology they use, messenger RNA, which does not pose an infection risk.
The crucial story in this rate of success and speed is that these are new kinds of vaccines. This will be the first time that a technology that uses messenger RNA—messenger ribonucleic acid—has been used at this scale for a vaccine. Pfizer/BioNtech is reporting similar success and efficiency in its trials and that vaccine is also an mRNA one—in effect, a replication—and it is similarly ahead of the pack.
As this explainer from Chemical & Engineering News puts it, and as many of us learned in biology classes, with a vaccine, we are aiming to show the body what the threat looks like, so the immune system can learn how to fight it:
Although vaccines have evolved over the past century, their goal has remained the same: trick the body into thinking it is infected with a virus, give the immune system time to safely study the decoy, and when the real deal strikes, hope that your immune cells took good notes. For many years, scientists used dead or weakened viruses for the job, grown in chicken eggs. Some vaccine makers have shifted to using vats of genetically engineered cells to produce particular viral proteins; this approach helps the immune system study the most important part of the virus.
While they also work well, traditional vaccines can require “the laborious production of actual viruses or viral proteins,” whereas the gene-based vaccines can be designed quickly from the genetic sequence. With such vaccines, all that is encoded is a particular viral protein—in this case, the spike protein of SARS-Cov-2, which acts like a key to our cells. The mRNA vaccine temporarily instructs our cells to make just the spike protein, which cannot infect us (it’s not the whole virus! Hence the safety advantage!) but offers our immune systems “target practice.” And then it all goes away, leaving us with much better protection.
And, amazingly, these vaccines can be designed very quickly—they just need the genetic sequence. Moderna’s vaccine was apparently designed in just a few days, over a weekend, after the genetic sequence became available on January 10th, 2020.
Here’s why that date matters: the sequence was published ten days before China acknowledged the severity of the problem by admitting sustained human-to-human transmission and shutting down the city of Wuhan, on January 20th. The sequence was published while China—and the WHO, which depended on China for information—were still downplaying what was going on, in their official statements. The sequence wasn’t published in an official document. Instead, it was published independently in an open-source depository by Yong-Zhen Zhang, a professor at the Shanghai Public Health Clinical Center and School of Public Health.
Zhang had received the virus from Wuhan on January 3rd, around 1:30 p.m., when a metal box continuing a test tube packed in dry ice arrived at his office. The researchers in his team worked feverishly to sequence it over the next two days. Just about 40 hours later, on January 5th at 2 a.m., his team was done. Zhang immediately realized the danger the pathogen posed. As he put it in a later interview with Time magazine:
“I realized that this virus is closely related to SARS, probably 80%. So certainly, it was very dangerous.”
He shared the genome with members of his consortium, which included Australian scientist Eddie Holmes. On the morning of January 11th (in China), Holmes called Zhang as he was about to take off for a trip to Beijing for another meeting concerning the outbreak at Wuhan. Holmes called and asked Zhang for permission to release the genome to the world.
Here’s what happened next:
“I asked Eddie to give me one minute to think,’” Zhang recalls. “Then I said ok.” For the next two hours, Zhang was cocooned from the world at 35,000 feet, but Holmes’ post on the website Virological.org sent shockwaves through the global scientific community.
Holmes sent out a tweet.
So it began. Scientists around the world got to work immediately, to develop tests, to start the race for the vaccine and to better understand this pathogen that would consume our lives. The very next day, researchers began pointing out that the pathogen was clearly related to SARS, which meant it posed an enormous danger. It could potentially become a pandemic.
By the start of the next week, just two days later, the first vaccines were already designed, including the one by Moderna that millions of health-care workers and other high-risk people will start receiving in a few weeks.
It may have taken him a single minute for Zhang to decide, but his bravery was real. This was just 10 days after whistleblowers in Wuhan who had attempted to warn others had been detained by the police. The punishment of these doctors for “rumor-mongering” was broadcast on national TV. Tragically, one of the most prominent whistleblowers, Dr. Li Wenliang, would die of the virus, just a month later (His son was born this summer to his widow). It was a time of silence, not of speaking out. Between January 5th and January 10th, the Wuhan government would not update the number of infected people. It would be another 10 days before the dam broke and President Xi Jinping made his first public statement, saying “the virus must be taken seriously.”
Sadly, the hammer did come down fast. Zhang’s lab was immediately shut down for “rectification”—an obscure term to imply some “malfeasance,” as the South China Morning Post explains.
To many observers, it seemed that furious officials scrambling to snuff out evidence of the outbreak were punishing Zhang simply for sharing the SARS-CoV-2 genome—and in the meanwhile, slowing down the release of this key information.
At the end of February, the South China Morning Post was reporting that Zhang’s lab was still shut down. Things did improve, though. Dr. Zhang continues to carry out important work—and has been recognized with awards.
Professor Zhang's efforts in sharing the first SARS-Cov-2 genome has already been acknowledged around the world, with Time Magazine recognizing him as a "saving grace" and naming him as one of the 100 most influential people of 2020. Stating that: "The Zhang team's unprecedented speed in sharing data envisions what is possible with a collaborative, connected public-health collective."
Professor Loman further highlighted the need for sequence data as the only means to get started on truly managing a viral outbreak, saying: "Whilst the generation of a new viral sequence is a technical accomplishment in itself, much more important is the speed of sharing: until this happens the global scientific community cannot get started on a response. The process of designing diagnostic PCR assays and sequencing protocols are critically contingent on that first genome sequence."
Professor Coin further pointed to how essential having a viral sequence available is to the medical profession, noting: "Early availability of the genome sequence also enabled researchers to start developing vaccines and antiviral therapies even before the virus could be grown in sufficient quantities in cell culture for it to be studied directly."
The availability of this data within weeks of the first identified COVID-19 patient undoubtedly saved many lives and will be highlighted for many years to come as the perfect example of why we can see further by standing on the shoulders of giants. The GigaScience prize was an acknowledgement for all of Prof Zhang and his groups efforts and will likely be one of many recognitions to come.
And in interviews since, Zhang, who still works in China, downplays his role and his bravery.
Still, as the good news from these vaccines rolls in, we should remember and celebrate the gift Dr. Zhang and his team gave us, perhaps the most important ones for fighting a pandemic: the gift of time and gift of information. Dr. Zhang acted without being incentivized by the huge amounts of money that the companies will receive—Moderna’s stock has increased almost 700 percent already—and he faced down potentially catastrophic consequences for himself and his lab.
For many years, we will be analyzing the failure of many governments and our institutions in their responses to this pandemic. But the successes are real, too. More than anything, we should also remember those who bravely stepped up when it counted: the healthcare workers and the researchers around the world—starting with Professor Yong-Zhen Zhang and Doctor Li Wenliang of China.
It's a very important story to tell, and I didn't know of it. Thank you.
Extraordinary, moving story. This line “I asked Eddie to give me one minute to think,’” Zhang recalls. “Then I said ok.” had me in tears.
One minor technical point: the 0 serious cases in the vaccine arm are consistent at the conventional 95% confidence level with an expectation value up to ~3. And the other mRNA vaccine did have 1 serious case out of 10. Overall 1/40 for the two combined. So very likely this will also have an excellent but not 100% effect on reducing serious cases.