What Makes Some People Immune To Diseases While Others Struggle?

A medical worker fills a syringe with a dose of the Pfizer-BioNTech coronavirus disease (COVID-19) vaccine as Japan launches its inoculation campaign, at Tokyo Medical Center in Tokyo, Japan February 17, 2021. Behrouz Mehri/Pool via

We are always intrigued by the tolerance of some people who never catch a disease or, if infected, exhibit mild symptoms. On the flip side, other people need hospitalization to recover from diseases. Why do some people never get sick? A study on tadpoles may hold the answer.

According to the study published in Advanced Science, Harvard scientists have discovered biological mechanisms that enhance disease tolerance in frog embryos and based on these findings identified drugs that reduce disease progression in the embryos, SciTech Daily reported Sunday.

Interestingly, many of the same mechanisms exist in mammals as well. This makes it possible that these techniques could be targeted one day to treat infections in humans and other animals, the report said.

“The standard approach to treating infections for the last 75 years has been to focus on killing the pathogen, but the overuse of antibiotics in livestock and in humans has led to the emergence of antibiotic-resistant bacteria that we are having a harder and harder time killing,” said first author Megan Sperry, a Postdoctoral Fellow at the Wyss Institute.

“Our research has shown that focusing on modifying a host’s response to a pathogen rather than killing the pathogen itself could be an effective way to prevent death and disease without exacerbating the problem of antibiotic resistance,” Sperry added.

The genetic expression of frog genes was studied when the embryos were placed in the presence of different pathogens. Gene pathways involved in metal ion binding and hypoxia (low oxygen levels) were found to be the ones closely linked with increased tolerance in the tadpoles, and administration of compounds like deferoxamine and 1,4-DPCA in embryos infected with lethal A. hydrophila showed increased survival despite high pathogen load.

“This is (a) wonderful example of turning scientific or medical paradigms on their heads: rather than searching for yet another highly targeted antibiotic that pathogens will develop resistance to in the future, we chose to discover ways to stimulate the host to be tolerant to a broad range of infections. While this work is far from the clinic, it demonstrates the value of thinking outside the box, and opens up new approaches to therapeutics development,” senior author and Wyss Founding Director Donald Ingber said.