Mon Feb 1, 02021, 11:00PM UTC
Florian Krammer and Preston Estep
Reforming Medicine: Applying the Lessons of SARS-CoV-2
The COVID-19 pandemic has been the single most disruptive event to strike the Globe in almost a century. Those disruptions have disproportionately affected those with the least resources.
The COVID-19 pandemic has been the single most disruptive event to strike the Globe in almost a century. Those disruptions have disproportionately affected those with the least resources. Yet the pandemic has also been a catalyst for innovations which will have long term benefits including virus identification, vaccine development, advance preparation, as well as critical lessons for health policy.
Florian is the Professor of Vaccinology at the Icahn School of Medicine at Mount Sinai and a leading researcher on the biochemistry of viral infection, vaccines and therapeutics. He is the Principal Investigator of the Collaborative Influenza Vaccine Innovation Center (CIVIC), and directs the Krammer laboratory, part of the NIH-funded Centers for Excellence in Influenza Research and Surveillance (CEIRS). Dr. Krammer is an active peer reviewer and editorial board member of a number of leading journals and has published more than 250 scientific papers, including a proposal for preparing for the next outbreak.
Preston is the founder and Chief Scientist of the Rapid Deployment Vaccine Collaborative (RaDVaC), the first-ever open-source vaccine project. Early in the SARS-CoV-2 pandemic, RaDVaC created rapid-deployment vaccines and published all formulas and protocols on the internet to enable production and self-administration of RaDVaC vaccines. Prior to RaDVaC, Preston was the Chief Scientific Officer and co-founder of Veritas Genetics. He is an inventor of several technologies, and is an adviser to many biotech startup companies. Preston was a previous Long Now Boston speaker on DNA technology breakthroughs: Our Past is our Future.
In 2015, Bill Gates was asked what kept him up at night. His answer (on YouTube): A pandemic as bad or worse that the one we experienced a century ago. In 1917 the Spanish Flu emerged, featuring both high fatality and high transmissibility. It swept across the world, resulting in 65 Million deaths, rivalling the loss of life from World War II. The modelling Bill’s team was doing said that if the same thing were to happen today, it could be so much worse, as global travel was now 50 times greater. Four years after Bill’s talk, SARS-COV2, a highly fatal, highly transmissible respiratory virus, emerged from the zoonotic pool and race around the world in record time. No nation or population has been spared.
In commenting on the video clip, Preston said, “Yes, Bill was right – and the SARS-COV2 pandemic could have been a lot worse.” But we had the benefit of twenty years of research on the coronavirus SARS-COV1 and MERS. That gave us a huge head start on COVID-19 and brought powerful new tools – like mRNA vaccines. In fact, Preston noted that the first vaccine candidates were developed in three months. The biomedical community across the Globe, including research scientist and scientist in the biopharmaceutical industry, demonstrated unprecedented transparency and cooperation, facilitating a network of research discovery and demonstration that resulted in numerous successful vaccine candidates in record time.
But things could also have been a lot better. It took 10 months to get those vaccines tested and approved. Meanwhile, millions were dying, and the pandemic was running rampant across the globe. Community and family life as well as local, national and global commerce, were severely disrupted and medical facilities overwhelmed. Had accelerated testing and approval of the early vaccines been facilitated by public health agencies, and had we done more planning and preparation in advance, many lives would have been saved and the economic disruptions would have been far less damaging.
Florian helped unpack the difficulties in researching and preparing for zoonotic virus emergence. There are pools of potentially dangerous viruses constantly circulating and mutating in animal populations. Some research has been done, but not nearly enough to prepare inventories and studies of those that might pose the greatest risk. The intimacy and scale of animal / human interactions are at unprecedented levels. This substantially increases the risk of infections crossing the boundary to humans. We need to know more, but we also need to develop experimental vaccines targeted to classes of virus likely to be the most dangerous. If researchers had a portfolio of previously tested and approved vaccine candidates, they could pull them off the shelf in response to an outbreak. Vaccine deployments would be measured in months not years. Such a program would vastly accelerate future vaccine deployment and save a significant number of lives. The investment is relatively small. By comparison, global pandemics can kill as many people as global wars. Yet the cost of defending against a pandemic is vastly lower than what we are spending on military defense. One pre-approved vaccine might cost $20M, significantly less than the cost of a single fighter jet.
Asymmetries in Risk Assessment
Preston also identified weaknesses in the current regulatory environment. He used the analogy of the Trolley Problem, which poses a hypothetical choice between letting five people be killed by a runaway trolley, or taking action to switch the trolley to another line, killing one. COVID-19 is the Trolley, and the choice is being made by the regulators. Do they approve a vaccine that will save millions of lives, but which may kill or injure a small but unknown number, or do they require more testing? The default mode is to require large-scale, placebo-controlled, randomized clinical trials, which are lengthy, difficult and expensive. SARS-COV2 vaccines were developed in 3 months. It took another 10 months to get them fully approved.
Moreover, if possible side effects do appear, trials can be halted, as they were for the Astra-Zeneca vaccine. In a trial pool of 18,000 individuals, 2 adverse reactions were noted, and the trail was halted. The trial itself saved many more lives in the trial pool than the number of adverse reactions. The asymmetry gets worse when you look at the problem of public attitudes about vaccines. A handful of reported negative side effects can go viral and significantly impact public confidence. Most of those anecdotes are either false, or mistakenly attributed to the virus, but the damage has been done. As Florian noted, the problem of trust is highly significant, but one that he has no solutions for, other than better and more consistent messaging and transparency.
Preston and Florian were not suggesting that we throw out the old system – just reform it. Fast tracking vaccines in a pandemic makes eminently good sense. Modernizing the regulatory process to enable alternatives like Challenge testing when warranted would save significant time and money. Investing in zoonotic research and candidate vaccines is highly cost-effective. These changes alone could reduce the next global pandemic vaccine deployment to 3 months.
These reforms will just take a little long term thinking.