| PERSPECTIVES Martynas Ycas:ˇ The “Archivist” of the RNA Tie Club Bernard S. Strauss1 Department of Molecular Genetics and Cell Biology, The University of Chicago, Illinois 60637 ORCID ID: 0000-0001-7548-6461 (B.S.S.) ABSTRACT Between about 1951 and the early 1960s, the basic structure of molecular biology was revealed. Central to our understanding was the unraveling of the various roles of RNA, culminating in the identification of messenger RNA (mRNA) and the deciphering of the genetic code. We know a great deal about the role of Brenner, Crick, Jacob, and Nirenberg in these discoveries, but many others played important supporting parts. One of these is a little-known scientist, Martynas Ycas,ˇ who appears in histories, generally without explanation, as the “archivist of the RNA Tie Club.” Ycasˇ was born in Lithuania. His father helped write the Lithuanian Constitution in 1919. He studied Roman Law and served in the Lithuanian army before escaping from the Russians in 1940. The records of correspondence of Ycasˇ with the physicist George Gamow and with Francis Crick throw some light on the genesis of our understanding of the role of mRNA. The story of the “RNA Tie Club” illustrates the difficulty in assigning credit for important discoveries and underscores the importance of a free exchange of information, even (or especially) among competitors. istory may be written by the winners, and it certainly connected in some way.The experiments of Beadle and Tatum Hemphasizes their role. Still, in 1676, or maybe 1675 de- and their followers had provided reasons for believing that a pending on whether one uses the Julian or Gregorian calendar, single gene determined, or controlled, a single enzyme (Beadle Isaac Newton wrote to Robert Hooke “If I have seen further it 1950). But just what that meant in biochemical, or even ge- is by standing on ye sholders of Giants.” Scientific discovery is netic, terms was not clear. The evidence pointed more and not so different 400 years later. My story has as its background more to DNA as the genetic material, but how a substance with the elucidation of the genetic code and the understanding of (apparently) so dull a structure could manage this “control” the roles of the different RNA molecules, particularly mRNA. was unknown. Blackboards were full of balloons labeled There is no dearth of rightful claimants to the discoveries: “gene” with arrows leading to rectangles labeled “protein” Francis Crick, Sydney Brenner, James Watson, François Jacob, but what any of that meant in molecular terms was mysterious. Jacques Monod, and Matt Meselson come to mind. This nar- Not only was the structure of DNA an unknown, the structure rative is an attempt to explain the contribution of two largely of proteins was not clear. It was not even certain that proteins overlooked scientists: George Gamow, a well-known astro- were specific molecules with a definite structure. It was not physicist and, particularly, Martynas Yˇcas, a little known bi- until 1952 that Sanger and Tuppy (Sanger 1952; Stretton ologist. There are others who contributed importantly, but, in 2002) showed that insulin was a protein of specific amino acid my mind, these two are special in representing one of the rare sequence, thereby defining primary structure. The major fea- benefits that accrued to the United States from the tragedy of ture of the secondary structure of proteins—the coplanar ar- the second World War: the migration of foreign scientists, in rangement of the atoms in the peptide bond—had been this case scientists from Russia and the Baltic countries. discovered by Pauling, Corey, and Branson in 1951 (Pauling A graduate student in genetics or in biochemistry in and Corey 1951; Pauling et al. 1951; Eisenberg 2003). 1950 might be expected to know that genes and enzymes were Consider the situation in 1963, just 12 years later. The structure of molecular biology more or less the way we know it today had been ascertained. The nature of protein struc- Copyright © 2019 by the Genetics Society of America doi: https://doi.org/10.1534/genetics.118.301754 tures, whether primary, secondary, and tertiary, were no Manuscript received October 31, 2018; accepted for publication December 26, 2018; longer absolute mysteries. The role of genes in determin- published Early Online December 31, 2018. fi 1Address for correspondence: 5550 S.Shore Dr. #509, Chicago, IL 60637. E-mail: ing the speci city of proteins by serving as the source of in- [email protected] formation for amino acid sequence was understood. The Genetics, Vol. 211, 789–795 March 2019 789 biochemistry of protein synthesis was understood in essence, both of whom, I contend, were serious participants in the if not in detail, and, by 1963, there was real evidence for the effort to understand the genetic code and the mechanism way all this was regulated (Jacob and Monod 1961). Al- by which information traveled from the gene to the pro- though there have been major advances since, the first edi- tein-synthesizing machinery. Others made the final steps tion of Watson’s Molecular Biology of the Gene written in but Gamow and Yˇcas were important contributors to the en- 1965 still feels almost up-to-date as compared to any text vironment that made their discoveries possible. Gamow is written just a decade earlier. How did this spectacular leap perhaps best known for being the father (or at least one of in our knowledge happen in just one decade? the uncles) of the “Big Bang” theory in cosmology (Segre’ In retrospect, a convincing case could be made that these 2011). Yˇcas is often mentioned in histories of this period developments were the result of careful biochemical work but mostly in passing without any identification (Cobb from a number of laboratories. However, that was not the way 2015). Crick (1988) mentions Yˇcas, but without any identi- it seemed to a group of what came to be called “molecular fication or elaboration as to his role. I knew him as a fellow biologists,” practicing, as Chargaff wrote, “biochemistry with- graduate student, and afterward when we were both on fac- out license” (Chargaff 1963). It was the physicist George ulties in Syracuse. His role is interesting since it illustrates Gamow who immediately saw that the Watson-Crick struc- how close some of the minor players may be to a major dis- ture implied a code, which he thought could be deciphered, covery. It also illustrates how a series of discoveries can be and who recruited a group of theoretically minded scientists suddenly put together to clarify a whole series of phenomena. to work out the details from published data. And it was a The background work is essential, but it is simpler to ascribe Lithuanian refugee from the Russian occupation, Martynas the final result to one, or a very few, individual(s). Yˇcas, who provided Gamow with biological background and then provided Brenner and Crick with confirmatory ev- Martynas Ycasˇ idence for their concept of an RNA messenger. This is an account of how Yˇcas came to the United States, how he came Martynas came from a well-educated, upper class, Lithuanian to be a member of Gamow’s informal group, and what he family. His father (Martynas Sr.) was a lawyer who had been accomplished. elected to the Russian Duma, even though committed to the cause of Lithuanian independence. His mother Hypatia was an American citizen from Scranton Pennsylvania whose father The Effects of World War II and its Antecedent Years had been an agitator for Lithuanian independence. Martynas Whatever the cause, the second World War saw the introduc- Sr. met her (according to one of the Yˇcas family) during a tion of transformative technologies into biology. Radioactive round-the world-tour. The result was that Martynas and three isotopes became readily available. Less impressive, but no less younger sisters grew up bilingual (Yˇcas 2005). Martynas’ important, technologies, such as column and paper chroma- father participated in the 1919 Peace Conference as a Lithua- tography, made it possible to achieve quantitative analyses of nian delegate and was Lithuanian Finance Minister during proteins, nucleic acids, and their components. More impor- the 1920s. This was clearly an upper-class family as indicated tantly, and for a variety of reasons, the war directed a new by the following personal experience. During the 1960s I sort of scientist to study biological problems. Some were had invited Martynas to give a seminar at The University of intrigued by Schrödinger’s arguments in his book What is Life Chicago. Mrs. Musteikas, one of our laboratory technicians of (Schrödinger 1946), and, at the same time, were looking for Lithuanian ancestry saw the seminar notice and asked to an intellectual challenging field that did not have military meet him. She curtsied on being introduced! Not a usual re- implications. But there were other sources of new talent. A sponse to visiting speakers! Yˇcas had studied law in Lithuania, major one was one of the greater pieces of social legislation but that was ended by the Russian occupation, and he had in the United States: the GI Bill of Rights. This law provided served as a cadet in the Lithuanian artillery. On confiscation a path to a college education for numerous individuals who of their family estate by the Russians in 1940, the whole family otherwise would not have thought such a pathway possible. managed to escape across the border, through East Prussia In addition, the influx of new students provided a financial to Berlin. They then traveled through Europe to Portugal, stimulus to Colleges and Universities just emerging from the managed to get to Rio de Janeiro and then, after a short stay, Depression years.