Nobel Prize or not

Today is the last day to submit nominations for the 2022 Nobel Prizes. My father, an expert on the Prize, wrote some reflections on some prizes not received last year.. and more generally about the politics of the Prize and also how smaller countries (Hungary in this case) can think about supporting their scientists. This piece was only published in Hungarian at first, but I thought a broader audience would benefit from it so below is the translation.

From the Hungarian literary weekly, Élet és Irodalom (Life and Literature),
Volume 66, Issue No 4 in 2022, January 28

HUNGARIANS AND NOBEL PRIZES
by István Hargittai

2021 was a special year. Two Hungarians did not receive (deserved) Nobel Prizes. The only other year like this was 1994, when two Hungarians did receive (deserved) Nobel Prizes, George Olah, the Nobel Prize in Chemistry and John Harsányi, the Nobel Memorial Prize in Economics. The two non-winners in 2021, Katalin Karikó and Zoltán Hajós, are two different cases both with valuable lessons.

Throughout my six decades as a researcher, and even since the age of 11, I have been interested in the nature of scientific discovery, which has led me to follow the work of Nobel laureates and scientists of the caliber of Nobel laureates. There was a ten-year period in my life when I recorded conversations with such scientists, which, together with my wife and our son, were published in six hefty volumes by a prestigious London publisher. These interviews went far beyond my own field, chemistry, and the conversations meant a second college education for me. For twenty-five years I have been invited annually to be a nominator for the Nobel Prize in Chemistry. I wrote a successful book on the Nobel Prize. I am saying all this to increase the reader’s confidence in what follows.

Many people were expecting Katalin Karikó to win the Nobel Prize for her achievements in the development of the vaccine against the COVID-19. As the date for the announcement of the Nobel Prizes approached in early October 2021, the various prize-giving bodies were practically in a race to honor her. For any prize, it enhances its prestige if its awardee later becomes a Nobel laureate, while awarding the same prize after the Nobel Prize is no longer so elegant. When it turned out that Karikó was not among the 2021 Nobel laureates, there was great disappointment. There were important reasons though why she was not awarded the Nobel Prize in 2021, and there is every reason to expect that she will receive it in 2022, or very soon after, in the category of physiology or medicine (medicice, in short) or of chemistry.

There is a tendency for the Nobel Prizes in medicine to be awarded not for the discovery of a specific drug or procedure, but for the discovery of a principle that facilitates the discovery of new medicines. For example, in 1988, the three scientists awarded the Nobel Prize in Medicine were known for the development of a whole series of new drugs, but the motivation for the award was not these drugs, but the principle of rational drug design. Karikó’s award is more likely to be for her achievements in the widespread use of mRNA than for her specific contribution to the development of a vaccine against COVID-19. The applications of mRNA are yet far from having reached their full potential, and this may have also been the reason to delay the award.

Nominations for any year’s Nobel Prize close on January 31. Anyone not nominated by then will not be eligible that year. For example, even if Karikó had been nominated by January 31, it may be that the prize should be shared with others, if those others had not been nominated by January 31, that could have also resulted in the prize’s postponement. If Kariko’s Nobel Prize is motivated by the development of a vaccine, then the prize in medicine is justified. However, if the motivation is based on her broader mRNA work, then the chemistry prize may have a better chance.

While Katalin Karikó’s Nobel Prize is a safe bet, the chances of Zoltán Hajós, the other non-laureate Hungarian in 2021 will have no other chance. The 2021 Nobel Prize in Chemistry was awarded to an American and a German researcher “for the development of asymmetric organocatalysis..” The motivation for the Nobel Prize is always carefully formulated to include the laureates’ merit, but avoid anything that may be controversial. In this case, the motivation did not include the word ‘discovery’, only ‘development’. The original discoverer was not among the recipients, that was the Hungarian-born American Zoltán Hajós as the principal investigator and his collaborator David R. Parrish. The discovery was made in the early 1970s in a research laboratory of the Hoffmann-La Roche pharmaceutical company. While everyone is already an expert of Karikó’s work, it is necessary to clarify some basic concepts about Hajós’s discovery.

The adjective “asymmetric” refers to chirality. Put simply, many molecules come in two varieties, just like our hands (or feet): there is a left hand and there is a right hand. The adjective chiral, which is applied to them, comes from the Greek word for hand. The two variations of the molecule, like our two hands, are mirror images of each other. They are alike in many ways, but not in all. For decades now, if a molecule used as a medicine can occur in both variants, it should be marketed only in the medicinal variant, because the other variant is either useless and would be a waste of material, or it could be harmful and toxic. The asymmetric production of molecules consists in forming only the desired version.

Some chemical processes take place only under extreme conditions, such as at very high temperatures, but in the presence of certain substances, these are the catalysts, they can also happen at ordinary temperatures. In our bodies, many biochemical reactions can only take place in the presence of complex protein molecules, enzymes. In this case, enzymes are the catalysts. This has been imitated in the industrial production of many important substances by the use of enzyme catalysts. Hajós used the simple chiral amino acid molecule proline to solve a chemical reaction that previously could only be carried out in the presence of enzymes. The reaction serves as a model for the production of important substances, such as steroids, which are often used in medicine. The discovery was published by Hajós and Parrish in 1974 in a well-documented article. The reaction was first referred to as the Hajos-Parrish reaction, and when three German researchers described a similar process, their names were added to the name of the reaction. This meant some inflation, but Hajós was clearly the original discoverer.

The Nobel Prize for asymmetric organic chemical catalysis was awarded to two researchers, and since a Nobel Prize can be shared between a maximum of three winners, there was one ‘unused’ slot that could have been filled by Zoltán Hajós. The narrative describing and justifying the Nobel Prize suggests that, while the method was not previously widespread, the activities of the two laureates have made it so. However, this does not change the fact that Hajós was the original discoverer.

Zoltán Hajós was born on March 3, 1926. He completed his secondary school education at the Trefort Street Gymnasium in Budapest. He studied at the Technical University of Budapest and graduated in 1947 as a student of Zoltán Csűrös. After graduation, he stayed at the Technical University, became an assistant professor, and received his doctorate in 1950. He left Hungary in 1957. In the United States, he worked mainly as a researcher for pharmaceutical companies and for three short periods in a university setting. His most important publication was the description of proline-catalyzed asymmetric synthesis in 1974. This included the statement that the chemical system he had developed could be regarded as a model of a biological system in which the chiral proline molecule plays the role of an enzyme. This statement was so revolutionary at the time that the referee of the manuscript wanted to omit it from the article. But Hajós insisted, and the article was published with this landmark statement. This paper has been cited nearly a thousand times by other authors, indicating widespread recognition and implying usefulness. We know of only one award he received, the Iron Diploma of the University of Technology (in Budapest) in May 2013, which is awarded to all alumni who graduated 65 years earlier.

I would like to continue with this last piece of information. Between this automatically issued honorary diploma and the (missing) Nobel Prize, there are countless possibilities for recognition, but they all eluded Hajós. This is not the fault of the Hungarian scientific community or the Hungarian bureaucracy, as he was not working at home. But perhaps something could have been done nonetheless? As soon as someone’s fame takes off, because they win, say, a Nobel Prize, the domestic recognition follows. Even if the celebrity was not born in Hungary and did not study in Hungarian schools, it is not a barrier to boasting. It suffices if, for example, the name of the distinguished person sounds Hungarian. But Karikó and Hajós were born, went to university, and started their careers in Hungary. Could something have been done to recognize Zoltán Hajós for his achievements? When Tibor Soós, our excellent organic chemist, raised this question, I myself saw no reason to think that we had anything to do with it. However, especially in the wake of the description of the 2021 Nobel Prize in Chemistry, and knowing that Hajós graduated and started his career at the Technical University of Budapest, I now think good it would have been good if we had discovered and helped to get him recognized earlier. [The author is an emeritus professor of the Technical University of Budapest. – Ed.]

The Nobel Prize Organization is not immune to the expectations that surround the recognition of a discovery. It would have been advantageous if a graduate of the Technical University (now, University of Technology and Economics) had become famous for a milestone discovery. The Hungarian universities do little to keep their alumni in their orbit, even though the exodus of the last century would justify this, if only for the universities’ own sake. Karikó now gives a generous account of what her alma mater had given her. If she could have really received support during the lean years of her career, the praise would surely have made sense. In her case, the national recognition happened before the Nobel Prize, but let’s not kid ourselves, if it hadn’t been for the pandemic, it wouldn’t have happened either. At the end of her stunning lecture at the 194th General Assembly of the Academy of Sciences [of which the author is a member – ed] on May 6, 2021, she subtly alluded to this: “I would certainly not have been here today if this pandemic had not happened. I wish I hadn’t been here – there would have been no pandemic.” Perhaps the lesson to be learned from these two cases is that our universities should pay attention to the careers of their graduates. Universities richer than ours are doing it successfully and are profiting from it, handsomely. Katalin Karikó’s example shows the potentias of mutual benefits, while Zoltán Hajós can only be a lesson at this point.

When I raise the point that we should support the recognition of Hungarian scientists who have emigrated, I would like to emphasize even more the importance of recognizing discoverers who stayed in Hungary. The shortcomings here are more striking. When the Nobel laureate George Olah wrote his memoirs, he dealt only briefly with the experiences of his early career in Hungary. The most important of these was not the inferior research facilities or travel difficulties. These he overcame with varying degrees of success. However, even decades later, he still found it important to note that when he had the slightest success, he was immediately surrounded by envy and opposition. As soon as he failed in something, gloating would appear. This is described by the German word Schadenfreude, which has no equivalent in English. Nor could Olah really explain to his American colleagues what it was all about.

For me, the most striking example is the story of Árpád Furka. Furka made a world-changing discovery with the creation of combinatorial chemistry. Before that, it took a long time for a trained researcher to produce a new peptide molecule. Furka developed a method to simultaneously produce peptides in all possible variations within limited time. His work and recognition were hampered by every conceivable challenge. When he wanted to publish his discovery in an international journal, the journal sat on his manuscript for months, made him revise it and only published it after long delays. During this time, three patent applications described his method, presumably by the official reviewers. Thanks to the strength of Furka’s breakthrough achievement, in time he received informal recognition from the international scientific community. He is considered to be the “father” and “pioneer” of combinatorial chemistry. Domestic recognition was delayed, and academic recognition, the deserved membership of the Science Academy, never materialized. Furka is still active, even beyond the age of 90, and has made his discovery public on his website. The lack of academic recognition has been appalling. One of the now late leading organic chemists repeatedly explained to me that Furka would not win the Nobel Prize when I complained about our inability to elect him to the Hungarian Academy of Sciences. The chief organic chemist’s argument made it sound as if we, the members of the Academy, had all won the Nobel Prize to get elected. If Furka had emigrated in his time and achieved the same result with a strong American university backing him, his name would be in glory in Hungary today.

For let us not deceive ourselves with Katalin Karikó’s current domestic recognition. It only started when her name was already a household word. The Karikó fresco on Krisztina körút in Budapest, several stories high, proclaims loudly that “The future is written by Hungarians.” Not even ‘also written by Hungarians’, and they could have added ‘also written by Hungarians, but not at home’. It has also been said that the Pfizer and Moderna vaccines are “Hungarian vaccines.” Of course, we have every right to be proud, primarily the University of Szeged, that Karikó studied there and that other Hungarian emigrants, apart from her, were involved in the development of the vaccines. But researchers from Canada, France, Germany, Greece, Israel, Lebanon, Spain, and Turkey also participated. Therefore, it is an exaggeration to call it a Hungarian vaccine, just as it is an exaggeration to call the Nobel Prize of George Olah or Eugene Wigner a Hungarian Nobel Prize. Of course, both Olah and Wigner are Hungarian, or more precisely Hungarian-American Nobel laureates, but their Nobel Prize is not a Hungarian Nobel Prize.

It has been a time-honored approach by the authorities to view the relatively large number of Hungarian Nobel laureates to be a manifestation of the high standard of science in Hungary. It is right to refer to the large number of Nobel laureates to encourage young people to choose scientific careers, but it is wrong to use it as a justification for the conspicuously low level of support for science in the country. Nor is it right to use it as an excuse for any kind of ‘cultural superiority’ over neighboring countries. The concept of ‘cultural supremacy’ was official policy in the 1930s. At present (early 2022), the official policy has reverted to the 1930s to such an extent that some of these aspects are no longer even noticeable. It is also wrong to refer to our emigrated scientific greats without taking stock of the reasons that forced them to go abroad.

Zoltan Hajós is approaching his 96th birthday. On his last visit home, the elderly scientist suffered an accident, and this circumstance, combined with the pandemic, has prevented his return to his home in New Jersey. Let’s wish the eminent discoverer a happy birthday!

(The author is a member of the Hungarian Academy of Sciences and of Academia Europaea (London) and foreign member of the Norwegian Academy of Science and Letters.)

Translated with www.DeepL.com/Translator, edited by Balázs Hargittai and Eszter Hargittai