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Coronavirus Disease 2019

Trial and Error in Developing Vaccines

The uncertain process of trial-and-error should be celebrated, not lamented.

Key points

  • Finding solutions to challenging problems is vital to our survival. Yet, those solutions can often be difficult and slow to discover.
  • Nevertheless, we must engage the proven process of trial-and-error. It can be slow and halting. But, with experience, we can speed the process.
  • The rapid process of developing a safe and effective coronavirus vaccine proves that practical wisdom can come from trial-and-error learning.

“Can we really afford trial and error when it comes to vaccine development?”

Noted journalist and historian Walter Isaacson posed this vexing question to bestselling author Matt Ridley in a May 2020 PBS interview. Four months earlier, the CDC had confirmed the first case of COVID-19 in the U.S., and by that May, the coronavirus pandemic had already become unnervingly urgent. Adding to the mounting sense of alarm was the fact that developing a new vaccine from scratch normally takes from 10 to 15 years—far too long for millions of potential victims to wait.

Yet, on December 11, 2020, the FDA issued the first emergency use authorization for the Pfizer vaccine, followed a week later by authorization of the Moderna vaccine. How could this record-setting pace have been achieved? Had safety been sacrificed in favor of speed?

The Accelerated Path to a COVID Vaccine

There are several reasons for the swift development of extremely safe and effective COVID-19 vaccines, including: decades of prior research on viruses from the same family; the creation of faster manufacturing techniques; streamlined regulations and authorizations prompted by the dire threat posed by the virus; and massive bankrolling that encouraged numerous competing companies to conduct concurrent clinical trials.

Focusing on the first reason, scientists were not caught flat-footed when the SARS-CoV-2 coronavirus was detected; they had already been investigating closely related coronaviruses causing SARS and MERS. So, much had been learned about the organic structure of such viruses, how they exert their harmful bodily effects, and how they are transmitted. Several possible ways to thwart those effects were also being investigated that harnessed innovative immunological and molecular genetic technologies.

Notably, that prior work had itself resulted from an inevitable trial-and-error process, in which hunches were played—some providing promising answers to scientific questions, but many others failing to do so. Success in vaccine development is far from certain. It took almost 50 years of trial and error to develop the first polio vaccine. Even now, 40 years after discovery of the AIDS virus, researchers have yet to find an effective vaccine against it. Nevertheless, the cumulative nature of scientific knowledge makes it increasingly likely that future challenges can be met more effectively and promptly.

Turning to the final reason, the slowest facet of vaccine development is testing candidate treatments for efficacy and safety—first in cells and animals (preclinical trials) and later in humans (clinical trials). Mandated human clinical testing generally requires three phases, with each succeeding phase involving increasing numbers of study participants and proportionately rising costs.

Largely unappreciated is that the conduct of clinical trials has itself evolved—this too resulting from a decidedly trial-and-error process. The history of clinical trials goes back hundreds of years, with improvements made in response to recognized deficiencies in design, analysis, and interpretation. Indeed, today’s standard design features—control groups, randomized participant assignment, and double blinding—are actually of recent origin.

Lessons from the Push for a Polio Vaccine

Once called the “Greatest Public Health Experiment in History” took place in 1954. In the midst of the Cold War, another tense battle was being waged—the war against polio. This viral disease attacks the nervous system, causing muscle wasting, paralysis, and even death. Although polio was then (and still is) incurable, Dr. Jonas Salk developed a promising vaccine to prevent infection—so promising that he successfully tested it on himself, his wife, and his three sons.

However, to properly assess its efficacy and safety, Salk initiated a trailblazing study. Some 623,972 schoolchildren were injected with either the vaccine or a placebo while more than a million others served as noninjected controls. Neither the children receiving injections nor those giving the injections knew whether the vaccine or the placebo had been administered until the trial ended.

So, the indisputable answer to Walter Isaacson’s question—“Can we really afford trial and error when it comes to vaccine development?”—is “we simply have no choice!” We must accept the necessity of trial and error in developing vaccines just as we must accept that virtually all human progress hinges on the same hit-or-miss process. Of course, that does not mean that vaccine development cannot be made more reliable and efficient. The precedent-setting pace of today’s COVID-19 vaccines underscores that point.

Still, important warnings must be heeded. There will inevitably be roadblocks and setbacks along the way. Some previously approved COVID-19 vaccines may have hazardous side effects. Even the Salk vaccine prompted a frightful scare when faulty manufacturing led to several children being infected with the polio virus and some of those children dying.

Furthermore, viruses are not invariant adversaries—they mutate. What are now effective vaccines may prove ineffective in combating future variants, necessitating the development of boosters. The cycle of trial and error will thus begin again.

We can, of course, lament the meandering nature of trial-and-error learning. Or we can embrace it, as has American author Phyllis Theroux, observing that “Mistakes are the usual bridge between inexperience and wisdom” as well as Irish novelist James Joyce remarking that “Mistakes are the portals of discovery.” There is also the inimitable Yoda in Star Wars: The Last Jedi perceptively, but ungrammatically claiming that “The greatest teacher, failure is.”

Perhaps the best lesson to be learned was offered by American automaker Henry Ford: “Failure is the opportunity to begin again more intelligently.” As long as we are prepared to do so, we will prevail against future viruses and other threats to our wellbeing.


Edward A. Wasserman. As if by design: How creative behaviors really evolve. Cambridge University Press, 2021.

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