OPINION Guest column

Developing a treatment

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

Reality doesn’t mirror the big screen. As the public has learned it might take 18 months or longer to develop a vaccine for the virus that causes covid-19, many wonder why the process takes so long.

Although the speed of vaccine development has increased significantly, it still takes 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 tetanus deaths of 12 children.

As a result, the government saw the need to become more involved, 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.

Other incidents followed. In the 1930s, two teams worked to develop polio 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 set back polio vaccine research by two decades.

Later, when Jonas Salk and Albert Sabin developed their 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. Each contained a small amount of live virus, which caused polio infections and resulted in 250 cases of paralysis and 11 deaths. This led to greater oversight of vaccine production and testing.

Vaccines must be tested thoroughly to ensure their safety. The process has become much safer but also much longer as researchers are required to adhere to much-needed regulations.

It starts with developing a protocol for producing a vaccine. This might be through inactivation of a virus: weakening a live virus so it causes an immune response but doesn’t infect a host, or other methods.

These experimental vaccines are often tested in living cells grown in dishes to make sure they don’t produce infections. Next, they are tested in living animals because no culture mechanism replicates the immune system of a living mammal. This can take years or decades of continual iteration or refinement, although several strong covid-19 vaccine candidates are already past this stage.

Vaccines that have proven safe and produced immunity in animal trials will first be tested for safety in humans. Increasing doses are given to human volunteers to determine a safe dose that does not produce significant side effects. This is a phase I clinical trial.

In a phase II trial, a vaccine that has passed phase I will be tested. 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. 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.

Each stage can take months or years. Occasionally, the FDA will fast-track approval of a drug for an urgent medical need if the results are extremely promising. Currently, hundreds of trials are ongoing for vaccines against the virus that causes covid-19 or for treatments that might lessen the severity of its burden.

We’ve already experienced the risks of rushing treatments in this pandemic as studies have found that hydroxychloroquine, initially touted by some as a treatment of covid-19, seems to have no benefit and increases the risk of death.

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

Jonathan Berman is an assistant professor of basic sciences at New York Institute of Technology College of Osteopathic Medicine at Arkansas State University.

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