On February 5 President Trump signed an executive order barring transgender student athletes from playing in girls’ sports. On March 19, the National Institutes of Health told grant seekers across the country to remove any reference to mRNA vaccine technology from their grant applications. What do these two things have to do with each other?
Maybe nothing. However, it is also possible that the Trump administration is trying to kill two birds with one stone and is using the University of Pennsylvania as its target. On the same day that the NIH promulgated its directive to remove mRNA vaccine technology from grant applications, the Trump administration “paused” $175 million in grant funding to the University of Pennsylvania. The grants are being “paused,” the administration says, over Penn’s failure to exclude the transgender student Lia Thomas from the women’s swim team. Is it a coincidence that the most notable research team in mRNA vaccine technology, Katalin Karikó and Drew Weissman, work at the University of Pennsylvania Medical School? Oh, and by the way, in 2023 they won the Nobel Prize after their work led to saving an estimated 3 million lives from the scourges of the Covid-19 epidemic.
Whatever you may think about transgender women participating in women’s sports, it’s a very bad precedent that such an executive order pre-empted cases that were before the courts (Penn swimmers are suing the university), and it’s equally bad that Penn is being punished for a “failure” that is long past (Lia Thomas has graduated). But by targeting Penn, they are also targeting a Nobel Prize-winning team of scientists who are working on one of the most promising technologies currently available for treating dangerous viruses and cancer. One only hopes that those proposed $175 million cuts do not affect their research effort (they are heavily funded by NIH), but that remains to be seen.
Continuing my effort to explain the devastation being wreaked on American science, here is another effort to describe the incremental steps that led up to the Covid-19 vaccine and that Nobel Prize.
As before: some basic science information is worthwhile.
1) Basic molecular biology: DNA, the famous double helix, unwinds and provides a template for RNA. This is called “transcription.” RNA, which comes in both double and single strands, then codes for proteins. This is called “translation.” Proteins make up just about everything in the body…muscles, bones, nerves, everything.
2) Basic immunology: When a virus invades the human body, the immune system recognizes it, and, if we’re lucky, mounts a response to destroy it. How does it “recognize” it? Molecules (called Toll receptors) on or within immune system cells match up with certain age-old molecular patterns on pathogens. When those receptors meet their match, the cells go into action by producing antibodies and/or other components of the immune response.
3) Basic vaccine biology: The protection afforded by vaccines has been known since 1796 when Edward Jenner realized that small doses of smallpox protected people from getting the full-blown symptoms of the disease. It took another hundred years (1890) before the concept of antibodies was promulgated and another 70 years after that (1958) before the structure and function of antibodies were known. And many years after that before the understanding of the immune cascade that produces them in the first place. Understanding how vaccines work to create antibody protection has been the focus of a massive research effort ever since. The National Institute of Allergy and Infectious Diseases provides about $6.5 billion annually to support that research.
4) How are these things related? That’s what took some time to discover.
That DNA had something to do with heredity was discovered in the 19th century, but its structure was not known until 1953. This discovery is famously described in the book by James Watson, The Double Helix. Watson, Francis Crick, and their male collaborator (Maurice Wilkins), but not their female collaborator (Rosalind Franklin), were awarded the Nobel Prize in 1962. Not surprisingly, then, the 1950’s and 60’s saw an explosion of research in DNA technology leading to an understanding of protein biosynthesis as described above.
In the meantime, work on the immune system progressed apace. While it was clear from research going back 100 years that certain molecules were able to stimulate an immune reaction, the mechanism by which this occurred was largely unknown until Toll receptors were discovered in 1985. They were discovered in embryos of Drosophila, i.e., fruit flies (another Nobel Prize for the team), but their role as the triggers of immune system function did not come for another ten years. Research on these basic elements of immune system activation flourished, and by the early 2000’s, nine different Toll-like receptors had been identified, some of which recognize RNA.
The plot thickens.
So. What if you could engineer a specific RNA to enter an immune cell, translate a small portion of an ugly virus…say, the “spike” surface protein of the Covid virus…then have that surface protein expressed by a non-viral cell? Since the surface protein by itself is harmless without its viral host, such production would not constitute a full-blown viral infection. The RNA would, of course, need to be modified so that it translated the protein but didn’t cause an overwhelming inflammatory response via those pesky Toll receptors. This necessary modification was the genius of Karisó and Weissman at Penn. The modified RNA would then stimulate intracellular Toll receptors to produce a more modest immune response. Would the immune system simultaneously recognize the surface protein and the modest Toll receptor response and mount a reaction that included the production of antibodies against the surface protein? Would that be the equivalent to a vaccine against Covid-19? And the answer is…well, yes. But how to get that RNA into the cell in the first place?
Another discovery, beginning in the 1960’s, showed that tiny lipid (fatty) droplets (nanoparticles) could encapsulate molecules like RNA and “squeeze” it into cells. Hence, they provided a delivery system for the RNA. And this observer has not a single idea about how one gears up the production of this entire apparatus to enable the vaccination of millions of humans. Enter the technology of the pharmaceutical giants….way beyond the scope of this humble essay.
In short, several strands of research over many decades had to come together in order to beat the Covid virus. But questions remain. Can we use this technology to fight cancer? Autoimmune diseases? As-yet-unknown pathogens? Well, we won’t know if the Trump administration bans funding for anything smacking of the pernicious “mRNA technology.” Call your Congress person…NOW.
