(+++) BUSINESS AND SCIENCE: AN UNEASY MIX

The Medical Revolution of Messenger RNA. By Fabrice Delaye. Cold Spring Harbor Laboratory Press. $29.50.

     Stir the nitty-gritty of everyday science into the nitty-gritty of everyday business decision-making and you have a mixture that will be thoroughly unappealing to most of the people whose lives are deeply affected by both science and business. A small group, though, will find the concoction tasty, and for them, Fabrice Delaye’s The Medical Revolution of Messenger RNA will be rather delectable.

     Its prosaic title aside, the book is filled with some fascinating history and some well-done tracing of the intricacies that drive both science and business, each in its own way. The book’s starting point could have been the 2023 Nobel Prize in physiology or medicine, but it came out a bit too soon to begin by commenting on the award of that prize to Katalin Karikó and Drew Weissman for their work on mRNA vaccines. Still, these “mRNA-obsessed scientists,” as Delaye characterizes them – one from Hungary and one from the United States – make more than one appearance in this book, starting with their publication of an article in 2005, in the journal Immunity, that “laid the groundwork for the first two mRNA COVID-19 vaccines, produced by Moderna and Pfizer-BioNTech and approved in autumn of 2020.”

     That 15-year delay between the publication of the article and the approval of vaccines that have saved millions of lives while also generating huge storms of controversy may seem like quite a time span, but in fact the history of mRNA research – and its real-world applicability – goes back much further than that. This is part of what Delaye wants readers to understand: scientific progress moves to a different timetable from the one that science fiction and everyday news reporting indicate, with incremental progress painstakingly made year after year until success is as likely to come with a sigh of relief as with an expression of “eureka!”

     And what exactly is success? In the context of The Medical Revolution of Messenger RNA, success takes two forms: scientific and commercial. And they are often at odds. For example, a chapter called “RNA or DNA? How Merck Missed the Jackpot” explains the onetime internal debate at this major multinational pharmaceutical company about vaccine development focusing on RNA or DNA. Some of the explanatory material may be a bit difficult for non-science readers to follow, as when one researcher explains, “It seemed about as elusive as cold fusion! …The research…had demonstrated protein expression in muscle but not yet in cells containing expressing antigen proteins that provoke the cellular immune response.” And this is a scientist making every effort to explain things clearly.

     The business side of the arguments within Merck is somewhat more readily comprehensible, including the explanation that “we could only produce tiny volumes of mRNA using the standard method at the time. Technology based on mRNA clearly wasn’t a marketable procedure. It also required incredibly expensive reagents.” And right there is the collision between that which science accomplishes, or believes it can accomplish, and what marketability and financial realities (as well as technological ones) will or will not allow it to try to accomplish.

     Even understanding what mRNA is can be a challenge for non-scientists. Messenger RNA – that is the full name of what is generally referred to as mRNA – contains instructions from genes within DNA that tell the body’s cells to create specific proteins. Since there are millions of proteins, each produced on the instruction of specific mRNA, the use of mRNA for disease-fighting is extraordinarily complex: an mRNA vaccine must tell the body to make a specific viral protein so the body’s immune system can recognize that protein and marshal forces against it if it ever appears.

     And this has to happen within the realities of finance. Another element of The Medical Revolution of Messenger RNA that involves COVID-19 vaccines, in a chapter called “Moderna’s Moonshot,” has an entrepreneur make the interesting comment, “Moderna took the same approach as Amazon or Tesla. Spend a lot of money before making any, to corner the market.” And this had to be done after mRNA research on a flu vaccine failed to lead to a commercial product – a leap of faith and finance at the same time.

     The real-world way in which scientific research is done, the painstaking pace at which apparent breakthroughs eventually emerge after decades of work, is foundational to Delaye’s writing in The Medical Revolution of Messenger RNA. Creating something revolutionary – vaccines to correct genetic defects that are expressed as rare and extremely serious diseases, for example – may be scientifically possible but not economically viable. Or such creation may not be scientifically possible with current technology, just as Merck’s “standard method at the time” was not able to produce mRNA-based technology. And some approaches that are scientifically possible are not economically viable at any given time. The complexities of the science-business relationship abound; indeed, The Medical Revolution of Messenger RNA only scratches the surface of the opportunities and obstacles. This is a book that helps explain not only why Karikó and Weissman won their Nobel Prize but also why COVID-19 vaccines that seemed to be developed quickly were actually many decades in the making. Delaye writes clearly about a topic whose complexity makes clarity difficult to obtain. This book may reach only a small audience, but it will be highly informative and thought-provoking for those who are willing to invest the time to read it and think through the topics it explores.