A most wonderful book offers grounds for optimism
Politics; international relations; social media and AI, all provide excellent reasons for thinking that humankind is well along the way to self-destruction [1]. Yet the book Breaking Through by Katalin Karikó [2] provides a highly welcome reason for a measure of optimism, that humanity can occasionally bring forth such a one as this scientist and author — the person whose work was the most crucial in developing the mRNA technique that produced anti-COVID vaccines at unprecedented speed.
Breaking Through maybe as close to full disclosure as is humanly possible, as Karikó describes her life, her emotions, her family, as well as her single-minded pursuit of understanding of how biology works.
Karikó is of the ilk of those who brought the Scientific Revolution and the Enlightenment: individuals driven helplessly by the thirst for knowledge and understanding. At the same time, her story illustrates and repeatedly acknowledges how family, good friends, and good colleagues can offer the emotional support and emotional security that makes possible the continuing unwavering pursuit of tangible truth.
Breaking Through is highly informative about a very wide range of things, and it is thereby highly instructive, about personal matters as well as scientific ones — and also about some political matters through Karikó’s experience of life under Big Brother in Communist Hungary when anyone might have been a secret informer. Without playing down the intolerable everyday lack of freedom and the pervasive feeling of insecurity, Karikó does point out that the communist ideology brought educational opportunities to people — like herself! — who might otherwise not have found them. In overall pros and cons, that weighs no better than the benefit Mussolini brought by famously making the trains run on time; but it does remind that free societies do not always serve everyone as well as they might, in education or health-care, for instance.
“An extremely brief interlude on science” (pp. 65-69) is a delightfully concise and clear explanation of genetics DNA, RNA, mRNA.
Many readers can cheerfully skip or scan those later parts of the book that describe details of the author’s scientific work; but those with a modicum of understanding of biochemistry will also delight in the clarity with which Karikó relates her efforts. I have only a skin-shallow understanding of immunity matters, just enough, when the popular media disseminated typically superficial stuff about “mRNA” and COVID vaccines, to worry about the possibility of auto-immune reactions and “side” effects; this book’s detailed explanation erased that worry with its discussion of inflammatory reactions avoided by the use of appropriately modified mRNA — one of the many specific discoveries Karikó made during her long quest: mRNA does indeed bring immune activation and inflammation, my layman’s worry; but substituting N1-methylpseudouridine for the uridine in mRNA avoids the inflammatory effect (p. 293).
Karikó’s experiences should also be highly informative to most readers as they illustrate that widespread popular views of scientific activity and the scientific community are off the mark, not an accurate reflection of reality. Naive lay people may imagine that the scientific community is composed of individuals like Karikó, continually looking for and recognizing and valuing the most brilliant ideas and the most striking achievements; but that is very far from the actual case [3]. Scientists are irreducibly human beings, and some of them are as unpleasant as Karikó’s first boss at Temple University (p. 138ff.), a personality twin of her unpleasant high-school Russian teacher “Mr. Bitter”.
As to how the scientific community deals with what eventually become the most lauded achievements: At first they are ignored or dismissed or actively resisted and suppressed [4]. So Karikó’s grant applications for support of mRNA studies were uniformly turned down; and an early manuscript was rejected by one of the leading science journals, Nature (p. 263) — which reminds one that “the whole history of science can be told in terms of things rejected by Nature and Science”, as Paul Lauterbur pointed out [5], who had pioneered what became magnetic resonance imaging, MRI — Nature had indeed first rejected his manuscript about it.
The fact of the matter is that whatever happens to be the generally accepted knowledge in a particular field, the “mainstream consensus”, essentially determines what research gets funded and what articles get published. It is not entirely an over-statement to describe any mainstream consensus as being thereby also the lowest common denominator, so that mediocrity rather than excellence becomes the norm [6].
Towards the end of the book, Karikó speculates about what might have happened had she encountered different people at different times: “There was so much luck involved. . . . Who else was out there and didn't have such luck? Who could use a little lock right now? What are we missing?” (p. 312).
I suspect that it can never be possible to estimate in any general way or any specific case the relative importance of personal initiative and persistence on the one hand and serendipitous encounters on the other; but my guess is that the personal is the essential ingredient, and that the greater the persistence, the greater the chances of serendipity; as the South African golfing Champion Gary Player put it, “The more I practice, the luckier I get” [7].
Everyone can also learn from this book something of great potential benefit in everyday life. Karikó mentions that in her high-school days she had been very taken by a book, The Stress of Life [8]; and she relates how she put its insights into practice in an enormously satisfying way that is likely to surprise or even astonish many readers. This account could stimulate for others, as it did for me, much beneficially useful self- reflection.
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[1] A supporting case seems to be made by cultural historian Jacques Barzun in From Dawn to Decadence: 1500 to the Present: 500 years of Western Cultural Life, (Harper Perennial, 2001).
[2] Published by Crown, 2023, in hardback and E-book. I am disappointed that it lacks an index, as is too often the case nowadays in non-fiction books even from well-established publishers. Rudimentary indexes are trivially easy to prepare using prepared any word-processing software, and little effort is needed to make a truly useful index with sub-headings.
[3] Henry H. Bauer, Science is Not What You Think: how it has changed, why we can’t trust it, how it can be Fixed, McFarland, 2017
[4] Bernard Barber, “Resistance by scientists to scientific discovery”, Science, 134 (1961) 596-602; also Thomas S. Kuhn, The Structure of Scientific Revolutions, University of Chicago Press; 2nd ed., enlarged, 1970 (1st ed . 1962)
[5] Cited at p. 110 in [2], sourcing Nicholas Wade, “American and Briton win Nobel for using chemists’ test for M.R.I.’s”, New York Times, 7 October 2003; http://www.nytimes.com/2003/10/07/us/american-and-briton-win-nobel-for-using-chemists- test-for-mri-s.html (accessed 16 April 2016)
[6] J. Klein, “Hegemony of mediocrity in contemporary sciences, particularly in immunology”, Lymphology, 18 (1985) 122-31
[7] Often attributed to Player, but “in a book written by Player himself in 1962 . . . he credits the aphorism to fellow golfer Jerry Barber” (https://quoteinvestigator.com/2010/07/14/luck). Such deep insights about human nature and behavior are likely to have originated very long ago, possibly even before written documentation was available. Sociologist Robert Merton published a whole book about something often attributed to Isaac Newton but traceable to no later than Roman times: On the Shoulders of Giants: A Shandean Postscript (Free Press, 1965)
[8] Hans Selye, The Stress of Life, McGraw-Hill, 1956; rev. ed., 1978