By JOHN RICHARD SCHROCK
On March 31, early in this COVID-19 pandemic, some researchers proposed a very controversial method to speed up research into the effectiveness of proposed new vaccines that were in the first stages of development: human challenge trials.
The normal process for testing candidate vaccines involves vaccination trials in a large number of citizens in a region where the pandemic was common, giving half the vaccine and half a placebo. Then you waited over time until some became naturally infected. If those infected were mostly or all in the placebo group, then as these numbers increased it indicated that the vaccine was effective. That would take trials involving 30,000 to 40,000 subjects and enough time to pass for natural infection to occur in a population that was also social distancing, wearing masks, and washing hands.
“Human challenge trials” would dramatically speed up testing vaccine effectiveness. It would replace this conventional Phase 3 testing by giving volunteers the new vaccine and a few weeks to develop antibodies, and then directly infect these volunteers with the coronavirus. But since there is the potential of death from this virus if the vaccine was ineffective, human challenge trials became a major bioethics debate. On the one side was the benefit of saving many lives by speeding up the evaluation and getting the vaccine to market faster, reducing the global burden.
However, since the fatality rate is lower—but not zero—for younger persons, this posed a dilemma of informed consent. Do we understand enough to know the risk? Many young volunteers came forth. It was proposed that they would be followed closely after being infected, and would receive the best care available if the vaccine did not work. However, now that we are seeing data from the regular 30,000-40,000-vaccination studies using natural infection makes this debate moot.
That leaves a different ethical dilemma that is easier to solve. Half of the participants in these large scale trials received a placebo, which means that they were not protected. At what point in the data analysis over time can we be sure that the vaccine is effective? And when we know that, what do we do for those who received the placebo?
This is not a new dilemma. In trials where a possible medication for a serious ailment is tested on subjects all suffering from that ailment, when a treatment shows dramatic improvement in early stages, the trial is stopped and those who received the placebo now also receive the new treatment. That now appears to be the offer made to those in these trials showing the effectiveness of the mRNA vaccines.
A third vaccine dilemma is occurring with the longstanding polio eradication effort. Folks over 70 will remember the “Mother’s March of Dimes” that funded vaccine research. Jonas Salk was the first with a vaccine based on a totally inactivated polio virus. Although sometimes called a “dead” virus, viruses are never living. These encapsulated bits of DNA or RNA only float around lifelessly until they come in contact with the right host cell, where they are taken in and reproduced. In the mid to late 1950s, to be protected, each person needed the polio shots and they were safe.
But Albert Sabin soon came up with an attenuated polio virus that was administered first by sugar cube, and then by a few drops on the tongue. This polio virus had been passed through animal cells until it was weakened to where it did not cause polio. But it was taken in by intestinal cells, replicated, and shed by the vaccinated person. Close members of the family would then pick up this virus and grow and shed it, also making antibodies and becoming immune. Sabin’s oral vaccine indirectly vaccinated the family and others close to them. The polio immunization program accelerated worldwide.
But there was a problem with the Sabin oral vaccine mutating back to causing full-blown polio paralysis. It happened rarely. Today, wild polio remains a problem in Pakistan and Afghanistan where the science-ignorant Taliban considers it an attempt to sterilize them. But polio has re-emerged this year with over 600 cases in Africa. All of these cases are oral vaccine-caused cases, where the oral vaccine evolves back into the virulent strain. The Bill and Melinda Gates Foundation has paid for 200 million doses of a more stable oral vaccine to be produced in an attempt to continue the worldwide eradication of polio. Only 1200 persons are in the clinical trials, but it must get emergency approval now to defeat this crippling disease.
. . .
John Richard Schrock has trained biology teachers for more than 30 years in Kansas. He also has lectured at 27 universities in 20 trips to China. He holds the distinction of “Faculty Emeritus” at Emporia State University.