Commentary: Why the Wait?

May 7, 2020

Credit NYITCOM at A-State

Jonathan Berman, PhD, is an assistant professor of basic sciences at New York Institute of Technology College of Osteopathic Medicine at Arkansas State University. His book, “Antivaxxers: How to Address a Misinformed Movement,” will be available on September 8.

Over the years, Hollywood has given us numerous pandemic-themed television shows and films that typically conclude with the hero developing a treatment at the last moment that is rapidly adopted.  As a result, humanity is saved in an instant.  

Unfortunately, we’re living in a reality that doesn’t mirror the big screen. As the public has learned that it might take 18 months or longer to develop a vaccine for the virus that causes COVID-19, many have wondered why the process takes so long. 

Vaccines must be safe and effective before they’re ready to be delivered.  Although the speed of development for many vaccines has increased significantly, it still takes many months for them to reach approval. Why be so cautious? It’s a lesson learned through trial and error.

In 1901, a horse named Jim was used to produce serum containing diphtheria antitoxin. However, Jim contracted tetanus and died. Nonetheless, Jim’s serum was distributed and was traced to the deaths of 12 children, all of whom died from tetanus.

As a result, the government saw the need to become more involved in the process, and the Biologics Control Act of 1902 was implemented to regulate biological products such as vaccines. Later, the Pure Food and Drug act of 1906 added regulations. Since then, quality assurance has been folded into the Food and Drug Administration (FDA). 

Other incidents followed in the effort to eradicate polio. In the 1930s, two teams worked to develop vaccines. One was led by John Kolmer of Temple University and another by Jeremiah Milbank and Morice Brodie. Their vaccines were each tested in thousands of children. Between the two vaccines, a number of allergic reactions occurred, resulting in the deaths of six children and the paralysis of 10 others. The public outrage that followed these deaths arguably set back polio vaccine research by two decades.

Later when Jonas Salk and Albert Sabin developed their polio vaccines, another incident occurred. Salk’s vaccine used inactivated polio virus, which means the virus was “killed” by treatment with formalin so that it could not infect cells. Cutter and Wyeth Laboratories improperly inactivated more than 100,000 doses of polio vaccine. In this case, the vaccine contained a small amount of live virus, which caused polio infections and resulted in 250 cases of paralysis and 11 deaths. The Cutter incident led to greater oversight of vaccine production and testing.  

Although these incidents occurred almost 100 years ago, we still take stock in the lessons they teach.

Like any other drug or biologic that will be administered to many people, vaccines must be tested thoroughly to ensure their safety. As the previous examples show, a lack of precaution can have unintended effects, and that preparation takes time. It can’t be rushed. The process has become much safer but also much longer as researchers are required to adhere to more and more much-needed regulations. 

Vaccine development begins with exploratory research, which develops a protocol for producing a vaccine. This might be through inactivation of a virus, the attenuation of a live virus - weakening it so it causes an immune response but doesn’t infect a host - or other methods.

These experimental vaccines are often tested in cultured cells - living cells grown in dishes - to make sure they don’t produce infections. Next, these drugs are typically tested in living animals because no culture mechanism adequately replicates the immune system of a living mammal with all its complexity. These tests look for safety, and in animals vulnerable to infection, may look for the generation of immunity. This initial development and testing can take years or decades of continual iteration or refinement, although several strong COVID-19 vaccine candidates are already past this stage.

In clinical trials, vaccines that have proven safe and produced immunity in animal trials will first be tested for safety in humans. Here, increasing doses of vaccine are given to a small number of human volunteers to determine a safe dose that does not produce significant side effects. This is called a phase I trial. 

In a phase II trial, a vaccine that has passed phase I without causing significant side effects will be tested for effectiveness. For example, a group of people vaccinated against SARS-COV-2 might be followed for several weeks to determine if they are less likely to test positive for SARS-COV-2 than those who have been vaccinated with a placebo. These trials provide additional information about safety. Phase III trials scale up testing to hundreds or thousands of patients. Following rollout of a vaccine, further studies are conducted to ensure that it does not cause additional problems that weren’t previously noticed.

Each of these stages often takes months or years. Occasionally, the FDA will fast-track approval of a drug for an urgent unmet medical need if the results are extremely promising, such as with the development of Gleevec, a common cancer medication.  Currently, hundreds of trials are ongoing for either vaccines against the virus that causes COVID-19 or for treatments that might lessen the severity of its disease burden, such as antivirals or convalescent plasma.

We’ve already experienced the risks of rushing treatments in this pandemic as studies have found that hydroxychloroquine, which was initially touted by some for a treatment of COVID-19 but seems to have no benefit and increases the risk of death. We must be cautious that when a vaccine does become available, it’s been proven to be both safe and effective.

Patience is a virtue that does not come easily in our world that is accustomed to immediate gratification, but it’s one that must be practiced as we let the scientific process play out.

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About NYITCOM at Arkansas State University:

New York Institute of Technology College of Osteopathic Medicine at Arkansas State University, located on A-State’s Jonesboro campus, is dedicated to improving access to health care for the underserved and rural populations in Arkansas and the Mississippi Delta Region. Arkansas ranks 48th in overall population health status due to low health indicators including obesity and number of adults who smoke. The state also ranks 46th in the number of active physicians per capita and 39th in the number of primary care physicians. NYITCOM at A-State was established in 2016 with the mission of meeting the need for more physicians in this medically underserved area.