History and Science

The beginning of Molecular Biology

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            This Analysis is based on a document containing historical Sources; some of these Sources are based on original interviews or on published text not translated in English until now.

            Scientific collaboration and discussion norms depend in part on the types of problems encountered. As an example, we illustrate in another section the idea-sharing norms developed by scientists working in particle physics, which are very different from those currently used in biology.

            A 2009 Interview with Renato Dulbecco (Nobel Medicine, 1975), however, describes a time when biologists were also communicating more openly (Sources, 1). He commented about a paragraph from his autobiography, where, in 1989, he said: “What a difference between the time of Luria and Delbrück and now! I had learned that science is open, that there are no secrets. [...] Now the world of science is made of sealed compartments, even within the same laboratory sometimes you would not know what the others are doing”. 

            After training with Giuseppe Levi in Turin, Italy, Dulbecco joined the lab of Salvador Luria (Nobel Medicine, 1969) at Indiana University in 1947 and moved to Caltech to work with Max Delbrück (Nobel Medicine, 1969) in 1949. He stayed at Caltech until 1962. See Sources, 2, for a longer translation of this part of the Dulbecco autobiography. In the longer quotation he attributes the decrease in discussions of plans and ideas in biology to the rise of commercial interests.

            Alice Huang, a former President of AAAS, worked with Dulbecco at the Salk Institute in the late 60s. She kindly shared her memories and commented on the issues raised by Dulbecco in his Interview and in the autobiography (Sources, 3). In her interview she confirmed the view of Dulbecco, mentioning how when she worked at the Salk postdocs and senior scientists "were all able to talk to each other very freely". She provided examples showing that not only commercial interests but also increased academic competition played a role in changes in the discussion habits of the biomedical community that were more evident from the early 70s. She also mentioned that Paul Berg (Nobel Chemistry, 1980), another collaborator of Dulbecco, made similar statements, and indeed in a published interview Berg lamented the loss of "the spirit of openness and collaboration that dominated the early years of molecular biology" (Sources, 4). Sidney Brenner (Nobel Medicine, 2002) also wrote in 2001 that "There is a lot of concealment nowadays. A lot of work is kept secret and there’s no free exchange in the sense that people don’t tell you what they’re doing if they think you’ll get there first. So competition does make for a kind of struggle that has its bad effects.” (Sources, 5). Susumu Tonegawa (Nobel Medicine, 1987) worked in the lab of Dulbecco in the late 60s and has also provided a comment about the importance of communication among scientists.

            Dulbecco mentioned Giuseppe Levi, Salvador Luria and Max Delbrück as mentors that influenced him and many other scientists (Sources, 8,9). Luria and Delbrück were well-known leaders of a group of scientists that were at the origin of molecular biology. Giuseppe Levi was the teacher and mentor of three Medicine Nobel Prize winners that trained with him in Turin, Italy: Renato Dulbecco, Salvador Luria and Rita Levi-Montalcini (Sources, 10-11). They obtained the Prize in different years and for different research topics, not related to their work with Levi. It is remarkable to note that there has been only one other scientist trained at Italian University that has obtained the Nobel Prize in Medicine, in 1906. Dulbecco was also recognized as scientific leader. We found several descriptions of Giuseppe Levi (Sources, 10-13) and Max Delbrück (Sources, 14-22) which show that they had common traits, also shared by Dulbecco (Source, 3). Delbrück modeled his leadership style on that of his mentor, Niels Bohr, part of the group that developed quantum mechanics, one of the major achievements of physics and of science on general (Sources, 16).

            These senior figures were described as moral leaders, in the sense that they provided an example by putting science before personal advantage; they were very critical, in a constructive way; they were ready to change their mind when shown new evidence and happy to recognize the achievements of those that did not follow their suggestions; they provided recognition in an impartial way. They promoted openness and encouraged social interactions. Many contemporaries state that these leaders could often be wrong, but the discussions were always helpful, and they allowed their trainees to follow their own ideas and supported them. The progressive gain of independence that this facilitated is described by both Dulbecco and Levi-Montalcini (Sources, 15 and 12). It has been noted that their presence created trust and promoted the open exchange of ideas, by providing fair recognition for intellectual contributions (Sources, 17). It is possible that broader social factors, including the well-known opposition to fascism and nazism of Levi, Delbrück, Luria, Dulbecco and other scientific figures, contributed to the development of a leadership style that was the opposite of that of the political dictators. We spoke with Carlo Ginzburg, one of the most famous living historians and also the grandson of Giuseppe Levi. He pointed out that examples of his grandfather's readiness to change his mind when presented with new evidence were seen by younger scientists as demonstrating the sincerity of his commitment to science.

             In addition to ideal motivations, scientific mentors had a role as mediators of support to younger scientists from foundations and academic institutions.  Examples of support mediation were the funds from a wealthy donor provided by Delbrück to Dulbecco to start his work on animal viruses (34) and the reported persuasion by Delbrück and Luria of the March of Dimes foundation to support Jim Watson's stay in Cambridge, where Jim did his work on DNA structure (35). For both Dulbecco and Watson this research led to their Nobel prizes. The mentors also benefited from the intellectual interaction. 

            The temporary counterbalance provided by moral leaders could not withstand the centrifugal forces originating from the growing size of biomedical research community and by increased competition between academic groups and companies for limited resources. Alice Huang describes vividly this period of inevitable transition (Sources, 3). Having more biomedical scientists is a positive and necessary development. There are certainly fundamental problems that are addressed more efficiently by competing academic scientists and applied problems that are more suitable for biotech and pharma companies. There are, however, also recent challenges that require a concerted effort of the biomedical community.

            Paul Nurse (Nobel Medicine, 2001) wrote recently (Sources, 6) that many biologists feel that they must present just data in talks and publications. He states that "Researchers seem reluctant to come to biological conclusions or present new ideas. [...] It is as if speculation about what the data might mean and the discussion of ideas are not quite ‘proper’." Understanding the historical origins, from competitive concerns, of these norms might help to encourage the open discussion of ideas for broader problems where secrecy does not provide an individual advantage (an example is the survey on AI).

            The response of the biomedical community to the Covid pandemic also shows that biologists can adopt more collaborative styles when faced with a major challenge, as described by Alessandro Sette. Magdalena Skipper, Editor-in-Chief of Nature, stated in an interview (31) with Eric Topol that the wide adoption of preprints by the medical and clinical community was spearheaded by the response to the Covid pandemic. She said that during the Covid pandemic they mandated the deposition of Covid-related papers in a preprint server. As a general policy Nature encourages authors to use preprint servers but they do not mandate it.

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The origin of modern science

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            Modern science started in the 16th and 17th centuries (this has been called the Scientific Revolution) and was accompanied by a substantial increase in open communication about the fundamental knowledge of Nature. This increase was gradual and did not evolve equally in every field, responding to different incentives. It was more limited when applications of economic relevance were considered possible.

            Carlo Ginzburg (Source, 23) and Joel Mokyr (Sources, 24) describe changes from the norms of secrecy that had prevailed during the Middle Ages and the Renaissance. An example of the enforcement of these norms is the story of Menocchio, a miller in Northern Italy who was sentenced to death in 1599 by the Inquisition for suggesting original ideas about religion and about the Universe (1). However, from the beginning of the seventeenth century, scientific knowledge was communicated more freely (Sources, 24). The Scientific Revolution, with its effects on technology, was one of the key factors that made the Industrial Revolution possible (Sources, 25) (2) and therefore it has been one of the engines of economic growth in the last centuries.

            As pointed out by Margaret Jacob (see Interview) we should not think of changes in communication at the time simply as results of conscious efforts to make it more open, and we should be aware of limitation originating from individual and national rivalries and from profit motives.

            Paul David has described how the emergence of open science in the seventeenth century was in part due to the support of rulers for scholars that could bring prestige with their published discoveries. Galileo and Kepler are among those that benefited from this patronage system. The multiplicity of Western Europe’s contending noble courts created conditions that were more favorable for scientific progress compared to a monolithic political system (3). The rulers would compete for the best scientific minds and scientists could circumvent censorship by printing their work in a different country or by moving abroad.

            The first scientific use of the telescope, and the astronomical discoveries made possible by it, were described by Galileo in March of 1610 (4) in the Sidereus Nuncius, a book dedicated to the Grand Duke of Tuscany, Cosimo II de' Medici. Galileo also named the moons of Jupiter he had discovered as the Medicean Stars, to honor his patron. Soon after the publication of this book Galileo obtained a position at the Medici Court in Florence. Rapid publication allowed Galileo to obtain priority and credit for the discoveries.

            Galileo had previously been involved in a bitter and public priority dispute with a student In Padua about the invention of a type of compass (5). After publishing the Sidereus Nuncius Galileo told a friend that the book was “written for the most part as the earlier sections were being printed,” fearing that “someone else might find the same things and precede me [to print].”(5) He also sent copies of the book and telescopes he built to Princes and Cardinals, to help them verify his discovery, which now affected not only his reputation but that of his patron (5). He did not provide in the book a description of the improvements he had made to the telescope, which had made his discoveries possible, but equally good instruments were soon available. By December of the same year the Jesuits in Rome were able to confirm his observation using a telescope they had obtained independently (5,6).

             There are many similarities between the scientific and career strategies of Galileo and those of Vesalius, also a Professor at the University of Padua when he wrote the book that transformed the study of human anatomy. It has been said that "The publication of the De Humani Corporis Fabrica of Andreas Vesalius in 1543 marks the beginning of modern science. It is without doubt the greatest single contribution to the medical sciences" (32). Vesalius also dedicated the book to his patron, Emperor Charles V, and obtained a job at the court soon after the publication. In the preface he thanks the Emperor for protecting him from the attacks of colleagues following the teachings of Galen, who had published his works more than 1,300 years before (Sources, 30). Other scientific colleagues were however supporting Vesalius and his experimental approach (32, 33). Galen had erroneously described as existing in humans anatomical findings from other animals and Vesalius was able to show this with careful human dissections.

            Wealthy patrons not only supported individual scientists but also the first scientific societies. One early example is the Accademia dei Lincei, of which Galileo was a member, founded in Rome in 1603 and supported by Prince Federico Cesi (7). The Accademia supported the publication of a book by Galileo and of some of his letters. Several members of the Academy had important roles in the Catholic hierarchy, and one was a Cardinal and nephew of the Pope. As observed by Lawrence Principe, Galileo had supporters and opponents both inside and outside the hierarchy of the roman Church. His trial was not a simple matter of science versus religion. It did however make many Catholics reluctant to express Copernican convictions during the 17th century (8).

            Another notable scientific society, the Royal Society, was established in London in 1660. The King initially provided only very limited financial support but granted licenses related to printing and to the undisturbed exchange of letters with all sorts of foreigners regarding "philosophical, mathematical or mechanical" matters (9). The main source of funding came for the combined contributions of the members, some of which were very wealthy (10). Other members, among these Robert Hooke and Henry Oldenburg, received a salary for their services. Some members were not active scientists, but they simply had an interest in science and contributed to the Society by paying their membership fees (10). 

            Scholars and scientists in the 16th, 17th, and 18th century frequently used the term Republic of Letters to denote their international community. This consisted of networks of scholar who communicated by means of letters, without distinctions originating from national or religious differences, at a time when these differences were frequent causes of wars between and within states (11,12,13). Some scholars had hundreds of correspondents with which they exchanged thousands of letters. The letters were generally not considered private, they were shared with other contacts and in some cases even printed to facilitate distribution.

            The ideal values of this community were stated, for example, by Pierre Bayle in 1684 (14):

"This is not about religion. This is about science. We must therefore put aside all terms that divide men into different factions, and consider only the point at which they meet, which is the quality of being an illustrious man in the Republic of Letters. In this sense, all scholars must see themselves as brothers, or as all coming from an equally good family. They must say, 'We are all equal, we are all related as children of Apollo.'"

            Descartes explained in 1637 that he felt a moral obligation to communicate his scientific finding because this promoted the "general good of mankind". He added that he was confident that major advances in knowledge could take place but that the complexity and magnitude of the task required communication because "connecting the lives and labours of many, we might collectively proceed much farther than each by himself could do" (Sources, 26).

            These ideal motivations were widely expressed but were not the only factors promoting the sharing of knowledge. When Oldenburg (Secretary of the Royal Society) wrote to Newton in 1672 asking if he could share information about his newly discovered reflecting telescope in a letter to Huygens, he pointed out that this would contribute to make it public and help him gain priority for his invention, "that it being too frequent that new inventions and contrivances are snatched away from their Authors by pretending bystanders" (Sources, 27).  

            Joel Mokyr has pointed out (12) that patrons did not have the technical expertise to evaluate scientists and therefore peer review by the scientific community was needed. Reputations could only be improved by openly communicating findings; evaluation was also based on reproducibility of experimental results. However, some well-known scientists, like Boyle, one the founders of the Royal Society, were wealthy and were not in need of patronage. Mokyr recognizes that then, as now, scientific research and intellectual innovation were motivated by a combination of factors, including individual financial incentives, search for recognition, curiosity and moral obligations to benefit the common good (12).

            It was a time of experimentation in scientific communication, including innovations that are still in use and others that seem bizarre to us now. As the number of scientists and the volume of correspondence became larger, it was natural to progress from the publication of individual letters to the first scientific and scholarly journals that aggregated news and information from multiple sources. The first journal solely dedicated to science was the Philosophical Transactions, published by Henry Oldenburg in 1665. It was licensed from and dedicated to the Royal Society, but it was also a for-profit initiative of Oldenburg that hoped to supplement his salary as Secretary of the Society (15). In the Introduction of the first issue Oldenburg explained the ideal aims of the initiative, writing that nothing is more necessary than communication for promoting the improvement of natural knowledge and that this will contribute to the "Universal Good of Mankind" (Sources, 28).

            A habit we might find surprising was that of using anagrams in letters and publications and only later revealing their meaning. The purpose was that of gaining priority for discoveries and at the same time being temporarily the only user of the information. Examples can be found in letters from Galileo to Kepler, for example in 1610 (6). Hooke used an anagram in the last pages of a 1676 publication to describe what is now called Hooke's law (16). He included this anagram within a list of topics that he planned to address in the future when he would get "opportunity and leisure" to do so. The key to the anagram was published by him in 1678 (17), and he specified that he had found this law eighteen years before, stating that "designing to apply it to some particular use,  I omitted the publishing thereof". Another notable example was that of anagrams describing calculus used by Newton in a letter to Leibniz, sent using Oldenburg as intermediary in 1676 (18). Decades later Newton and Leibniz were involved in a public and bitter fight about priority for the discovery of calculus (19), showing that the use of anagrams was ineffective in establishing priority in this case.

            Another approach that did not survive in the long term was that of publishing scientific contribution without naming the individual authors. Two notable examples can be mentioned which differed in many respects. One is the publication by Théophraste Renaudot of discussions that were held regularly from 22 August 1633 through 1 September 1642, each Monday afternoon in Paris (20). The meetings were open to anyone, and Renaudot did not attempt to summarize a common position but reported the different opinions. The participants in the meetings themselves choose the weekly topics and many were on scientific or medical subjects. Reports of the conferences were published each week, they were also published as collections and translated in English in 1664 (21). Renaudot stated that anonymity was requested by the participants, and he pointed out that because names were not attached to opinions it was easier to consider the different ideas as common property and focus on the collective search for truth (21). The other example is the publication strategy of the Accademia del Cimento, which was active in Florence from 1657 to 1667 (22). The members were chosen by the patron, Prince Leopoldo De' Medici and the activities were focused on the careful performance and repetition of experiments. Some of the experiments performed were described in 1666 in a collective publication, with no mention of the names of the individual scientists or of any difference in opinions (23). There is evidence that the investigators were not entirely happy with the lack of individual recognition and the Accademia ceased to function when the Prince was named a Cardinal and started spending most of his time in Rome (22).

            Some profit motives contributed to make scientific information public. Examples are those of Oldenburg and his income from Philosophical Transactions and the increased activities of book publishers, especially successful in the Netherlands, taking advantage of more lenient censorship rules (see interview with Margaret Jacob). Publishing books could be remunerative for their authors and there are several examples of financial contracts across religious divides, like that in 1661 of the Jesuit Athanasius Kircher, based in Rome, with the Protestant Dutch publisher Janssonius (24).   Telescope makers also published reports of the observations made with their instruments, comparing them with those made by rival firms, and were motivated to publicize their scientific findings by competitive motives (25,26). Applied science of commercial value was however treated differently from fundamental knowledge of nature, and some of it was kept secret, even if the introduction of the patent system encouraged disclosure in exchange for temporary exclusivity (27).

            An example of a discipline where secrecy persisted even in the 17th and early 18th centuries is that of Alchemy (28). Only when it renamed itself as Chemistry did it fully join the communication methods of other sciences. The first books of Alchemy go back almost two thousand years and one of its aims had always been the making of gold by transforming other metals (28).  Many claimed to have reached this objective over the centuries and described their methods using obscure language; the secrecy was justified on the grounds that unrestricted knowledge of gold making would destroy economies. Well-known natural philosophers like Boyle and Newton were involved in alchemic experiments and did publish only very incomplete and sporadic accounts (in the case of Boyle) or nothing at all (in the case of Newton). A private letter from Newton to Oldenburg, sent in 1676, encourages Boyle not to disclose details of his alchemic work because they might cause immense damage to the world if the claims of the alchemist were true (Sources, 29). The case of another member of the Royal Society, James Price, shows how general scientific opinion had shifted by the late 18th century. James Price claimed to have discovered a method to make gold and even sent a sample of the gold he was supposed to have made to King George III. Joseph Banks, the President of the Royal Society (a naturalist who had been with Captain Cook in his first voyage around the world) asked him to repeat the experiment in front of delegates of the Society. Price found excuses to postpone the demonstration but finally agreed and, on the appointed day in August 1783, when three representatives of the Royal Society arrived at his laboratory, he committed suicide by drinking poison in front of them (29,30).

            Technical advances also played a role in facilitating scientific communication in the early modern period.  Among these were the invention of the printing press, and improvements in travel infrastructure and in the postal system, that were driven by the needs of commerce and finance (12,13). Travel took also place for cultural reasons, this was the time of the "Grand Tours", and allowed the establishment of contacts that were later followed by exchanges of letters (13). 

            Several lines of evidence support the view that no single factor is sufficient to explain the improvements in scientific communication that took place in and around the 17th century, and that a combination of factors was needed (12). Technical advances assisted communication but cannot explain all its manifestations, given that, for example, more than 200 years passed from the invention of printing to the printing of the first scientific journal. The limited lifespan of initiatives based on anonymous contributions, where individual credit could not be assigned, shows that ideal motivations were not sufficient. Incentives provided by wealthy patrons certainly played a role, but the patrons were motivated by an increase in prestige that would only have existed if large parts of society believed that scientific knowledge could benefit the common good.

REFERENCES

1- Ginzburg, Carlo. The cheese and the worms: the cosmos of a sixteenth-century miller. JHU Press, 2013.

2- Jacob, Margaret C. The first knowledge economy: Human capital and the European economy, 1750–1850. Cambridge University Press, 2014.

3- David, Paul A. "The Historical Origins of 'Open Science': an essay on patronage, reputation and common agency contracting in the scientific revolution." Capitalism and society 3.2 (2008).

4- Galilei, Galileo. Sidereus Nuncius, or the sidereal messenger. University of Chicago Press, 2016.

5- Biagioli, Mario. Galileo's instruments of credit: Telescopes, images, secrecy. University of Chicago Press, 2019.

6- Wootton, David. Galileo: Watcher of the skies. Yale University Press, 2010.

7- Drake, Stillman. "The Accademia dei Lincei: Modern scientific societies owe many of their important traditions to the Lincean Academy, founded in 1603." Science 151.3715 (1966): 1194-1200.

8- Principe, Lawrence. The scientific revolution: A very short introduction. Oxford University Press, USA, 2011.

9- https://royalsociety.org/about-us/governance/charters/

10- Hunter, Michael. The Royal Society and its fellows 1660-1700: the morphology of an early scientific institution. British Society for the History of Science, 1994.

11- Van Miert, Dirk. "What was the Republic of Letters? A brief introduction to a long history." Groniek 204/5 (2014).

12- Joel, Mokyr. A culture of growth: The origins of the modern economy. Princeton University Press, 2016. (especially Chapter 12)

13- Harris, Steven J. "Networks of travel, correspondence, and exchange." The Cambridge history of science 3. Cambridge University Press (2006): 341-362.

14- Pierre Bayle. Preface of Nouvelles de la République des Lettres, 1684

https://books.google.com/books?id=I3E3AAAAMAAJ

original text: " "Il ne s'agit point ici de Religion: il s'agit de Science on dois donc mettre bas tous les termes qui divisent les hommes en differentes factions, & considerer seulement le point dans lequel ils se reünissent, qui est la qualité d'Homme illustre dans la Republique des Lettres. En ce sens-là tous les Sçavans se doivent regarder comme freres, ou comme d'aussi bonne maison les uns que les autres. Ils doivent dire “Nous sommes tous égaux, nous sommes tous parents comme enfants d’Apollon”"

15- Hall, Marie Boas. Henry Oldenburg: Shaping the Royal Society. OUP Oxford, 2002.

16- Hooke R. "A Description of Helioscopes and Some Other Instruments", 1676

https://books.google.com/books?id=KQtPAAAAcAAJ

17- Hooke R. " Lectures de Potentia Restitutiva", 1678

https://www.google.com/books/edition/Lectures_de_Potentia_Restitutiva_Or_of_S/LAtPAAAAcAAJ

18- Letter from Isaac Newton to Henry Oldenburg. (dated 24 October 1676.)

https://www.newtonproject.ox.ac.uk/view/texts/normalized/NATP00196

19- Gleick, James. Isaac Newton. Vintage, 2007.

20 - Solomon, Howard M. Public Welfare, Science and Propaganda in 17th-Century France: The Innovations of Theophraste Renaudot. Princeton University Press, 2015.

21 - “A General Collection of Discourses of the Virtuosi of France, Upon Questions of All Sorts of Philosophy, and Other Natural Knowledg" 1664

https://www.google.com/books/edition/A_General_Collection_of_Discourses_of_th/UVz4Hw62EpIC

22 - Beretta, Marco. "At the source of western science: the organization of experimentalism at the Accademia del Cimento (1657–1667)." Notes and records of the Royal Society of London 54.2 (2000): 131-151.

23 - "Saggi di naturali esperienze fatte nell'Accademia del cimento sotto la protezione del serenissimo principe Leopoldo di Toscana e descritte dal segretario di essa accademia" 1666.

https://library.si.edu/digital-library/book/saggidinaturali00acca

24- Stolzenberg, Daniel. "The Holy Office in the Republic of Letters: Roman Censorship, Dutch Atlases, and the European Information Order, circa 1660." Isis 110.1 (2019): 1-23.

25- Campani, G "Ragguaglio di due nuove osservazioni" 1664

https://preserver.beic.it/delivery/DeliveryManagerServlet?dps_pid=IE8044668

26- Divini, E "Lettera di Eustachio Divini. Intorno alle macchie nuovamente scoperte nel mese di luglio 1665. nel pianeta di Giove con suoi cannocchiali." 1666

https://books.google.com/books?id=1noSyWI5ccsC

27- Eamon, William. "From the secrets of nature to public knowledge: The origins of the concept of openness in science." Minerva (1985): 321-347.

28- Principe, Lawrence M. The secrets of alchemy. University of Chicago Press, 2012.

29- Duveen, Denis. "James Price (1752-1783) Chemist and Alchemist." Isis, (1950): 281-283.

30- Cameron, H. Charles. "The last of the alchemists." Notes and Records of the Royal Society of London 9.1 (1951): 109-114.

31- Interview of EricTopol with Magdalena Skipper, Editor-in-Chief of Nature. Aug 19, 2023
https://erictopol.substack.com/p/straight-talk-with-magdalena-skipper

32- Saunders, J. B. and O’Malley, Charles D.  "The Illustrations from the Works of Andreas Vesalius of Brussels", Dover Publications, (1950, 1973 reprint)

33- O'Malley, Charles D. "Andreas Vesalius 1514–1564*: In Memoriam." Medical History 8.4 (1964): 299-308.

34 - https://www.nobelprize.org/prizes/medicine/1975/dulbecco/biographical/

35 - Stent, Gunther S. “Quiz kids” p. 9-14 in "Inspiring science: Jim Watson and the age of DNA" CSHL Press, 2003.

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