First, Do No Harm
ex·per·i·ment noun /ikˈsperəmənt/: a scientific procedure undertaken to make a discovery, test a hypothesis, or demonstrate a known fact.
In recent weeks, two Coronavirus vaccine trials and a Covid-19 treatment trial, combining a new monoclonal antibody with the medication Remdesivir, have been temporarily paused while scientists evaluate harmful effects that have been observed in test subjects enrolled in the trials. Each of these announcements has been treated as breaking news by media outlets. They have also led to swirling conspiracy theories, endorsed by our president, that the scientists behind the delays are politically motivated. But the reality is, that these events are neither newsworthy nor unusual. The slow and careful process behind the development of new vaccines and drug protocols is always filled with such episodes. By the time a new treatment makes it to market, it has been through years, sometimes decades, of research marked by false starts, wrong turns and adjustments. Sometimes, ideas have to be scrapped altogether because of adverse events that occur in the development process.
When these things happen, it is, of course, bad news for the many people who are suffering from a disease and awaiting treatment or a preventative vaccine. The unfolding tragedy of Covid-19 is made all the more painful by the uncertainty surrounding the timing of an available vaccine and the relative dearth of treatment options available to combat the illness. But there is a flip-side to the news that the scientists and drug companies are moving carefully and looking closely at potential harms. If the drug companies were to rush through this process and begin widespread dissemination and use of an intervention that later proved dangerous, it could cause severe and, possibly, irreparable harm to hundreds of thousands, if not millions, of people.
Such a scenario is not hypothetical and has happened a number of times in modern history. In 1976, a new vaccine for the swine flu, which appeared safe after undergoing the full 3-phase vaccine development process, was rolled out for widespread dissemination to the general population. Before long, it became clear that a rare but extremely serious complication, known as Guillain-Barre Syndrome, was occurring in 1 out of every 100,000 people who were given the vaccine. This adverse reaction had not been identified during the trial period simply because of the fact that nowhere near 100K people had participated in the vaccine trial. And while 1 in 100K may seem like a small number, when adjusted for population, it could mean that thousands of people might suffer paralysis, or even death, as a result of something that was designed to protect them from illness. The severity of the condition was such that use of the vaccine was halted entirely.
The fastest that any vaccine has ever come to market was the mumps vaccine, which became available in 1967. Only four years earlier, the pathogen had been replicated in a lab by an enterprising young scientist at Merck, who used his own daughter’s throat culture to grow a line of cells that remain in use today for the mumps portion of the MMR vaccine, which is now a standard part of pediatric care. That four-year figure, however, is somewhat deceptive and does not tell the whole story. There are descriptions of a mumps-like illness as early as the 5th century BC, but the etiology of the disease was not truly known until the virus was isolated in 1945. At that time, in the close quarters of soldiers’ barracks, mumps outbreaks became a serious issue in the military. A relatively mild childhood disease, mumps can be quite severe in adults, often leading to long term negative effects, including sterility. The military rushed to create an inoculation that used the inactivated virus and became available in 1948. Unfortunately, it offered only partial short-term immunity. Later, after the rapid creation of the 1967 version of the vaccine was developed, it underwent numerous changes before it was rolled out and widely available in a combined form in the early 70s. Moreover, it was not until 1977, when the US government made it a priority to achieve a 90% vaccination rate in American children, that the funding and infrastructure made it possible for the poorest children in underserved communities to receive the preventative injection.
There is no question that with “Operation Warp Speed,” as the administration has dubbed the effort to speed a vaccine to stop the spread of Coronavirus, we can be hopeful that our population will benefit sooner rather than later from a vaccine to keep us safe. But given the fact that we have only known this pathogen for less than a year and that the development process will not involve certain types of test subjects, such as children and other vulnerable groups, we need to be prepared for the reality that it may take several tries for us to get it right.
Likewise, medical interventions such as monoclonal antibodies and anti-viral medications being studied are not new to medicine, but they remain on the cutting edge of our scientific knowledge. They are currently in use for treatment of cancers and other deadly diseases such as Ebola and the SARS and MERS viruses. Each are being used for Covid-19 only in the context of Emergency Use Authorizations (EUAs) because they have not been widely enough studied for scientists to be confident that they are safe and effective. Many clinicians were appalled that they were used in this fashion on someone as important as the President of the United States, given that an adverse event could have had huge consequences. My assumption, and I think, the assumption of many other clinicians, is that in choosing to use them, the doctors, who were trying to hide the severity of the president’s illness, tipped their hand by doing so. It would only make sense to take such an uncharted path, if the risk of doing nothing was far worse. Regardless, it would be foolish of us to think that, because one individual came through the experiment unscathed, we can now rush forward toward widespread use of the same regimen in the population as a whole.
I am heartened to hear that scientists are not being pulled into the political push to skip steps. They would put American lives at risk by rushing out vaccines and treatments. The death toll from this disease is truly horrifying, but the prime directive of all medicine is to “do no harm.” We would not be helped if the public health crisis of the century were to be made worse by the medical community perpetrating harm on our population through accidental negligence.
Instead, we must remain vigilant about protecting ourselves from the disease, so that we can allow our scientists time to find safe ways to prevent and treat the illness. It may seem frustrating to some, that the best methods we have of doing so are so low tech and old-fashioned. How is it possible that in the context of modern medicine, a mask and a measuring tape are our best interventions? But that is the truth of the slow and careful progress of science, and we must embrace that reality in order to stay alive.
Originally published at http://rebeccafullerdotblog.wordpress.com on October 16, 2020.