Microsoft founder Bill Gates cautioned in 2015. The next catastrophically deadly global event, he predicted, was “most likely to be a highly infectious virus rather than a war.”
In 2019, Johns Hopkins researchers issued an even more specific warning. In the article “Characteristics of Microbes Most Likely to Cause Pandemics and Global Catastrophes,” a team led by physician Amesh Adalja identified respiratory transmission as the “mechanism most likely to lead to pandemic spread.” They noted that “diseases that are contagious prior to symptom development” pose the greatest risk, especially if a significant proportion of the human population were “immunologically naïve to the agent,” and that the ability to latch onto common cellular receptors located throughout the human body would make such a pathogen highly infectious. Finally, they singled out RNA viruses emerging from an animal species as the “most probable” cause of such a pandemic.
In a September 2019 report, the Global Preparedness Monitoring Board convened by the World Health Organization (WHO) and the World Bank warned that “there is a very real threat of a rapidly moving, highly lethal pandemic of a respiratory pathogen killing 50 to 80 million people and wiping out nearly 5 percent of the world’s economy.” The authors added, “A global pandemic on that scale would be catastrophic, creating widespread havoc, instability and insecurity. The world is not prepared.”
These predictions proved horrifically correct: Gates identified the type of threat. The COVID-19 virus ticks every one of the boxes specified by the Johns Hopkins researchers for a microbe capable of causing a global catastrophic biological risk. And although COVID-19 deaths, fortunately, amount so far to only about 5 percent of the dire scenario sketched in the Global Preparedness Monitoring Board report, the World Bank estimates that the global economy did contract by 4.3 percent in 2020 as a result of the pandemic.
“This will not be the last pandemic, nor the last global health emergency,” declared WHO Director-General Tedros Adhanom Ghebreyesus in a September 2020 report. A World in Disorder estimated that the world’s governments had already spent $11 trillion (of often borrowed money) in response to the COVID-19 pandemic, which has so far resulted in 115 million diagnosed cases and 2.6 million deaths.
But take heart: There are good reasons to believe that the WHO director-general is wrong. The greatly speeded-up biomedical innovation provoked by the current global scourge has provided future generations with tools to keep subsequent viral invasions at bay. These include fast new vaccine production platforms, the development of better diagnostic and disease surveillance monitoring, and progress in the rapid design of therapeutics.
Calibrating the role of governments in staving off future threats remains a challenge. But the horrors of the last year have spurred humanity to quickly develop an unprecedentedly flexible and powerful toolkit that may well make COVID-19 the last true pandemic.
“HOPEFULLY IN THE not too distant future, in a year, year and a half, two years, we’ll have a vaccine,” said Centers for Disease Control and Prevention (CDC) Director Robert Redfield during congressional testimony on February 27, 2020. At a televised cabinet meeting on March 3, 2020, National Institute of Allergy and Infectious Diseases (NIAID) Director Anthony Fauci suggested that a “deployable” vaccine against the COVID-19 virus would be available in, “at the earliest, a year to a year and a half, no matter how fast you go.” At that point, just 100 Americans had been diagnosed with the illness and only nine had died of it.
Many considered this timeline bullish to the point of insanity. “When Dr. Fauci said 12 to 18 months, I thought that was ridiculously optimistic,” Paul A. Offit, co-inventor of the rotavirus vaccine, said a month later on CNN. “And I’m sure he did, too.” After all, the fastest vaccine developed at that point had been for mumps, and that took four years in the 1960s. An influential 2013 study in the journal PLOS One analyzing a database that included all vaccine projects in development from 1998 to 2009 found that “the average vaccine, taken from the preclinical phase, requires a development timeline of 10.71 years and has a market entry probability of 6 percent.”
As it happened, even the wild-eyed optimists were too pessimistic. The Food and Drug Administration (FDA) issued emergency use authorizations (EUAs) for the Pfizer/BioNTech and Moderna messenger ribonucleic acid (mRNA) COVID-19 vaccines on December 11 and 18, 2020, respectively.
In fact, researchers at Moderna had developed their vaccine by January 13, 2020—only two days after Chinese researchers had shared the genetic sequence of the COVID-19 virus. BioNTech launched its COVID-19 vaccine program by mid-January and signed up with Pfizer to manufacture it in mid-March. The first volunteer was injected with Moderna’s vaccine on March 16, 2020.
In other words, at the moment Fauci was being derided for being too optimistic about having one working vaccine in 12–18 months, researchers had already developed and were on the verge of launching clinical trials for two.
This previously unthinkably rapid timeline was possible because researchers weren’t just making new vaccines; they were making vaccines in a new way.
The vast majority of vaccines heretofore have been based on inactivated, weakened, or genetically modified viruses and bacteria. But mRNA vaccines are different, constituting what is essentially a plug-and-play platform technology.
The process involves creating a synthetic version of the mRNA that the coronavirus uses for the construction of the spike proteins that enable it to infect human cells. The injected mRNA tricks muscle cells in our arms into making some of the viral proteins that then induce the immune system to produce antibodies in response. Antibodies bind themselves onto attacking viruses, disabling them or marking them for death by other parts of the immune system, like the cell-devouring macrophages.
Since the cells in our bodies quickly degrade mRNA, the key to getting the vaccines to work was to encapsulate the fragile mRNA within tiny protective fat particles. The muscle cells absorb the fat particles, enabling the mRNA to deliver its instructions to the cellular machinery to make the viral proteins that prime the body’s immune system to fend off the real virus.
In fact, mRNA technology wasn’t quite new. Research had been plodding along for a couple of decades prior to 2020. Moderna was working on vaccines for the Zika and H7N9 bird flu viruses. BioNTech was primarily focused on using mRNA vaccines to treat various cancers. But the urgent need for a response to COVID-19 sent researchers scrambling for the right technology to apply, and reaching for this tool turned out to be a master stroke.
Now that the safety and efficacy of mRNA vaccines have been established, companies can within days assemble and install appropriate mRNA sequences from other pathogens into protective fat droplets to create new vaccines. More good news is that capabilities for producing mRNA vaccines have risen greatly as a result of pandemic manufacturing. In addition, the CDC suggests that future mRNA vaccine technology may allow for one vaccine to provide protection against multiple diseases, thus decreasing the number of shots needed for protection against common vaccine-preventable illnesses.
Viral vector vaccines are another plug-and-play development platform in which genes that would provoke an immune response, such as those for the COVID-19 spike proteins, are spliced into weakened, harmless versions of other viruses. The COVID-19 vaccines from Johnson & Johnson and AstraZeneca and Russia’s Sputnik V vaccine are based on inactivated cold viruses that had already been used to develop vaccines against HIV, Ebola, and Zika. The inactivated viruses enter human cells and deliver the genes for the COVID-19 spike protein, which the invaded cells then produce and which subsequently stimulate the body’s immune system.
In the future, these new vaccine manufacturing platforms could be used to rein in outbreaks by developing and deploying new vaccines in only three to four months. Florian Krammer, a medical researcher at the Icahn School of Medicine at Mount Sinai, outlines an overall strategy in which researchers would survey and select representative strains from the virus families most likely to cause new pandemics. These families include influenza viruses, pneumoviruses (respiratory syncytial virus), henipaviruses (Nipah and Hendra diseases), picornaviruses (polio and the common cold), and, of course, coronaviruses. Krammer suggests that 50–100 different viruses could be selected, broadly covering the virus families that are most likely to pose a major pandemic threat in the future.
Once the viruses have been selected, vaccines could be produced using the new platforms and then tested in small phase 1 and phase 2 safety and efficacy trials, which would involve around 1,000 volunteers total.
Krammer estimates that developing and testing the anticipatory vaccines for each of the selected candidate viruses would cost about $30 million. The overall cost would be somewhere between $1 billion and $3 billion. This is cheap compared to the vast economic havoc wreaked by the current pandemic, as well as compared to the cost of more traditional vaccine development.
If a new virus emerges to threaten humanity, the vaccine closest to the new strain would be selected and updated to match. Production could start immediately, and phase 3 trials to see if the vaccine prevents or ameliorates the infection could be initiated within a month.
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