Donald J. Cram: Science Begins with Faith, Results Guide Research

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On 17 June 2001, Donald J. Cram (1919–2001) passed away in Palm Desert, CA. He was an American chemist who was educated at Rollins College, University of Nebraska and Harvard University. As biographies note, his father passed away when he was three years old, leaving Cram and his siblings to his mother, who supported the family with the financial assistance of “Aid to Dependent Children,” and who sent young Donald off to a variety of jobs including: working on fruit farms, delivering newspapers, and painting houses, while he still found time to barter for piano lessons.

His career research was focused on “container molecules” (also called “host-guest” molecular pairs), which are able to store a guest-ligand until sufficient activation energy disrupts the host/container conformation to release the encapsulated guest-ligand. This advance in organic chemistry has demonstrated numerous potential applications, including biomedical pharmacological-delivery (e.g. anti-tumor drugs), environmental removal of toxic or radioactive materials (e.g. Cesium-137), the encapsulating of nanowire filaments in nanowire growth (e.g. bi-copper complex in polymer nanowires), and sequestering chemical groups in food processing, etc.

For his work, Professor Cram shared the 1987 Nobel Prize in Chemistry with Jean-Marie Lehn (b.1939) and Charles J. Pedersen (1904–1989) “for their development and use of molecules with structure-specific interactions of high selectivity.”

His Nobel autobiography noted the motivating principle behind his work ethic. Quote: “Chemical research became my god, and the conducting of it, my act of prayer…” Another statement from Cram characterizing his view of research (Cambridge, 1997):

“An investigator starts research in a new field with faith, a foggy idea, and a few wild experiments. Eventually the interplay of negative and positive results guides the work. By the time the research is completed, he or she knows how it should have been started and conducted.”

Referenced:
— “Donald J. Cram – Biographical.” Nobel Prize Online.
Cram, Donald J., and Jane M. Cram. Container Molecules and their Guests. (Cambridge, UK: Royal Society of Chemistry, 1997), 1. Image online: ©QuotationOf.com.
For a good review article discussing some of the container molecule structure-designs, see: Liu, Fang, Roger C. Helgeson, and K. N. Houk. “Building on Cram’s Legacy: Stimulated Gating in Hemicarcerands.” Accounts of Chemical Research 47.7 (2014): 2168-2176.

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Barbara McClintock: Getting to the Root of Scientific Research

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On 16 June 1902, Barbara McClintock (1902–1992) was born in Hartford, CT. A biologist and geneticist, she was awarded the 1983 Nobel Prize in Physiology or Medicine “for her discovery of mobile genetic elements.” By studing Zea mays (maize) with variably colored kernels, she was able to analyze the independent genetic formation & development of hundreds of offspring and thereby determine the allelic patterns within plant seeds. One article notes: “McClintock’s observation of the behavior of kernel color alleles was revolutionary in its proposition that genomic replication does not always follow a consistent pattern. Indeed, as a result of both autonomous and activator-controlled transposition at different stages of seed development, the genes of maize kernels are capable of producing a variety of coloration patterns.”

A reflection on Professor McClintock’s research from an edited volume:

“It is perhaps fitting to end with the reflections of a scientist―another Nobel Laureate― and with a return to what might unite the poet and the scientist and point to a way forward for the rest of us. ‘Good research,’ Barbara McClintock has said, ‘requires a disposition to hear what the material has to say to you.’ This is not simply a device to fathom the reasons governing the world. ‘It is,’ as her biographer notes, ‘a longing to embrace the world in its very being, through reason and beyond, a capacity for union with that which is known.’ It is not too much to describe this, in the life of a research scientist, as a a religious longing. It is a desire to move beyond mere certainty to a reverence for the given, ‘a disposition to hear what the material has to say to you’.

Referenced:
― Pray, Leslie, and Kira Zhaurova. “Barbara McClintock and the Discovery of Jumping Genes (Transposons).” Nature Education 1.1 (2008): 169.
― Soskice, Janet Martin. “The Ends of Man the Future of God.” in The End of the World and the Ends of God: Science and Theology on Eschatology. Eds. John Polkinghorne and Michael Welker (Harrisburg, PA: Trinity Press Int., 2000), 87. Image: WordPress.

Wendell Meredith Stanley: Ancient Science Advances by New Faith

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On 15 June 1971, Wendell Meredith Stanley (1904–1971) passed away in Salamanca, Spain. An American biochemist, he was co-awarded the 1946 Nobel Prize in Chemistry with John Howard Northrop (1891–1987) “for their preparation of enzymes and virus proteins in a pure form” along with James Batcheller Sumner (1887–1955) “for his discovery that enzymes can be crystallized.” Later in life, he authored Chemistry: A Beautiful Thing, for which he was nominated for the Pulitzer Prize.

His Nobel Lecture had described the historical roots of virology:

“Although the idea that certain infectious diseases might be caused by invisible living agents was expressed by Varro and Columella about 100 B. C., there was no experimental proof and the idea was not accepted. The cause of infectious disease remained a mystery for hundreds of years. Even the wonderful work of Leeuwenhoek and his description of small animals and bacteria during the years from 1676 to 1683 failed to result in proof of the relationship between bacteria and infectious disease. There was, of course, much speculation and during the latter half of the 19th century great controversies arose over the germ theory of disease…

“Attempts to learn something about the nature of viruses through studies on their general properties began with Beijerinck’s work in 1898 and were continued in different laboratories for over thirty years without too much success. Although Beijerinck and Allard made important contributions, perhaps the most significant work was that of Vinson and Petre during the years from 1927 to 1931 when they showed that tobacco mosaic virus could be subjected to several kinds of chemical manipulations without loss of virus activity. Nevertheless, when the work on viruses, which is recognized by the 1946 Nobel Prize for Chemistry, was started in 1932, the true nature of viruses was a complete mystery…”

Similarly, an edited volume by Prof. Stanley notes the ancient roots of this research area, and further noted the need for faith to make progress.

“In his classic paper, which appeared in 1915, Twort discussed the possible nature of the infectious agent: it could be an ultravirus, or a small parasite reproducing at the expense of the bacterium, or a phase of the life cycle of the micrococcus, or an autocatalytic enzyme, or a primitive form of life. The existence of acute infectious diseases of bacteria was confirmed two years later by d’Hérelle, who named the agent bacteriophage… Until the end of the nineteenth century, the history of viral diseases is just a part of the history of infectious diseases. In about 2500 B.C., the Chinese had identified smallpox and knew that it was transmissible. Aristotle was aware of the fact that rabies was transmitted by the bite of dogs; the Hebrews used to compare this bite to that of a venomous snake. In Latin, virus means ‘venom’ or similar poisonous fluid. Virus was something which could produce a disease. And in A.D. 50, Cornelius Aulus Celsus produced this remarkable sentence: ‘Rabies is caused by virus.’ Ideas concerning infectious diseases remained metaphysical until the notion of a specific agent emerged, and until, mainly as a consequence of Pasteur’s work, the agents of infectious diseases were identified as microbes.” (Lwoff)

“The nucleic acid of the tobacco mosaic virus was itself shown to be capable of initiating infection by Gierer and Schramm (1956a,b) and a similar, but less-detailed study was made simultaneously by Fraenkel-Conrat (1956). The idea that the nucleic acid might be the infectious agent was not a new one, but the general opinion was that it might be too unstable to exist in an infectious form for any time… When one considers the relative lack of infectivity of untreated virus, and that some 10⁸ particles of nucleic acid were therefore needed to cause a single infection, a certain amount of faith is required in the interpretation of the results, particularly if one considers that the absence of active virus can only be controlled by indirect methods. In particular, the infectivity possessed by the nucleic acid preparations is very labile to the action of pancreatic ribonuclease at concentrations of the latter which have little effect on whole virus (Gierer, 1957). Conversely, the activity is much less affected by antiserum to the whole virus, though it is indeed surprising that the serum used did not contain enough ribonuclease to inactivate the nucleic acid… As has been mentioned, the present evidence is that the infectivity of the tobacco mosaic virus resides in its nucleic acid component. If this is so, then chemical or physical agents which inactivate the virus must act in one of two ways…” (Markham)

wm stanleyA biography at the Bancroft library notes: “In addition to his research activities, Stanley was interested in educating new generations of scientists. He lectured widely throughout his career, both as part of honorary lectureships such as U.C. Berkeley’s Hitchcock Professorship, Cornell’s Messenger Lectureship and Princeton’s Vanuxem Lectures, and on television and radio…He was a member of many national committees and panels and for many years served on the World Health Organization’s Expert Advisory Panel on Virus Diseases. He was active on the editorial boards of several journals and for five years held the chairmanship of the Editorial Board for the Proceedings of the National Academy of Sciences.”

Referenced:
Stanley, Wendell M. “Nobel Lecture: The Isolation and Properties of Crystalline: Tobacco Mosaic Virus.” Stockholm, SWE. 12 Dec 1946.
Bacterial Viruses. Eds. F.M. Burnet, W.M. Stanley (New York, NY: Academic, 1959), 188, 84.
“Guide to the Wendell M. Stanley papers, 1926-1972.” Online Archive of California. Univ. CA Bancroft Library. Images: ©Biografías y Vidas, 2004-2018, http://amzn.to/2EO0imA.

Georg von Békésy: Bringing the Imagination to Nature’s Limits

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On 13 June 1972, Georg von Békésy (1899–1972) passed away in Honolulu, HI. He was a Hungarian-American biophysicist who won the 1961 Nobel Prize in Physiology or Medicine “for his discoveries of the physical mechanism of stimulation within the cochlea.”

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Through anatomical studies of the inner ear and basilar membrane, Békésy was able to determine the maximum sound wave amplitudes along the base forming the logarithmic spiral of the cochlea. As he discovered, high frequencies cause more vibration at the base of the cochlea while low frequencies create more vibration at the apex.

His Nobel Lecture recounted the inspiration he derived from studying the works of Leonardo da Vinci (1452–1519).

“In my student years I was very much concerned with the question, why it is so difficult to imagine something new? Where are the limits of fantasy, was my daily question. It is very difficult to recognize these borderlines in a chemistry or physics book. But it is easy to see them in the history of art. Between the 12th and 15th centuries it was the custom in Europe to use fantastic animals as decoration. If you compare the Figs. 5 through 9, it will surprise you to see how limited the fantasy really is, for most of the figures are nothing more than the combination of parts of other figures. They were much more original in the Near East in the first half of the first millennium B.C. But even so, my question remains, how is it possible to produce new discoveries in science when our imagination is so limited? It was the study of the drawings of Leonardo da Vinci that gave me the answer. If you compare the drawing of the flower in Fig. 10 with the drawing of the storm in Fig. 11, you will have the impression that da Vinci was able to cover a velocity range that to my knowledge no other artist has been able to equal. Why? I believe it is because da Vinci did not try to outdo Nature with his fantasy, but, quite the opposite, he tried to learn from Nature. It was this very simple finding that gave me, in my student years, the hope that perhaps in time I would be able to produce something of enduring interest… Nothing has been more rewarding than to concentrate on the little discrepancies that I love to investigate and see them slowly disappear. This always gives me the feeling of being on the right track, a new track.”

Referenced:
“Georg von Békésy: Research.” Wikipedia. Wikimedia Foundation.
Békésy, Georg von. “Nobel Lecture: Concerning the Pleasures of Observing, and the Mechanics of the Inner Ear.” Stockholm, Sweden. 11 Dec 1961. Image: stoccolmaaroma.it

Roger Bacon: Putting Faith in the Experimental Method

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On 11 June (?) 1292, Roger Bacon (1214–1292) died at Oxford, England.

He was a Franciscan monk who was one of the first to propose mathematics & experimentation as methods of science. Drawing on Latin translations of Aristotle and the writings Arab scientists, he described a repeating cycle of observation, hypothesis, experimentation, and verification. 

His interest in foreign languages and other philosophical traditions began as a student. Reading biblical manuscripts at Paris, he encountered discrepancies in the texts; thereafter, he endeavored to uncover their true meaning and assess their claims against the discoveries of the natural sciences. One biographer notes:

“He is never tired of pointing out the amount of injury done to the spread of knowledge, and to the Church in consequence of the utter neglect of these languages. He frequently reminds his readers that all science was originally revealed to the ancient Hebrews, from whom it descended to the Egyptians and the Greeks… ‘prima tradita est principaliter et complete in lingua Hebraea’ (Opus Tertium, x)… ‘Latini nullum textum composuerunt, scilicet, neque theologiae neque philosophiae… manifestum est necessarium fore Latinis, ut si volunt puro, et sano, et efficaci sapientiae liquore potari, quod in fonte Hebraici sermonis, et Graeci, et Arabici, tanquam in primitivis vasis, discant sapientiam exhaurire’ (Compendium Studii Philosophiae, vii.). He urges, therefore, the study of Hebrew and Greek, as being indispensable to the spread of true knowledge, to the preparation of accurate translations of the works of the ancients…”

Through the writings of Roger Bacon, the Church gave Europe the mindset needed to believe it could study and learn about the natural world through experimentation, rather than reason alone, utilized by the Ancient Greeks.

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Source: Nolan, Edmond & S.A. Hirsch. The Greek Grammar of Roger Bacon and a Fragment of his Hebrew Grammar. (Cambridge, GB: The University Press, 1902), xv-xvi.
Image: https://crev.info/scientists/roger-bacon/

Patrick Matthew: Origins of a Theory

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On 08 June 1874, Patrick Matthew (1790–1874) passed away at Edinburgh, Scotland. A farmer,  biologist and merchant, he is considered by some historians to have anticipated Darwin’s theory of evolution by natural selection.

Beginning with the 3rd edition of Origin of Species and following in subsequent editions, acknowledgments of Patrick Matthew’s theory, as expressed in the appendices and addendum of his 1831 book, ‘On Naval Timber and Arboriculture’, were included in Darwin’s publications.

“In answer to a letter of mine (published in Gard. Chron., April 13th), fully acknowledging that Mr. Matthew had anticipated me, he with generous candour wrote a letter (Gard. Chron. May 12th) containing the following passage: —‘To me the conception of this law of Nature came intuitively as a self-evident fact, almost without an effort of concentrated thought. Mr. Darwin here seems to have more merit in the discovery than I have had; to me it did not appear a discovery. He seems to have worked it out by inductive reason, slowly and with due caution to have made his way synthetically from fact to fact onwards; while with me it was by a general glance at the scheme of Nature that I estimated this select production of species as an à priori recognisable fact—an axiom requiring only to be pointed out to be admitted by unprejudiced minds of sufficient grasp.’”

A recent article in Zygon discusses both this influence of Patrick Matthew’s theory as well as Darwin’s use of the metaphor of an ‘architect’ in biological development to explain chance and free will.

Reference: Noguera‐Solano, Ricardo. “The Metaphor of the Architect in Darwin: Chance and Free Will.” Zygon 48.4 (2013): 859-874.

Image: Amazon.

Karl Darrow: Excavating for Hidden Clues

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On 7 June 1982, Karl Kelchner Darrow (1891–1982) passed away. A student of Robert A. Millkan (1868–1953), he was an American physicist working at Western Electric from 1917-1925 and then Bell Laboratories from 1925-1956. The author of over 200 technical articles, histories, and critical reviews in the Bell System Technical Journal, his books included Introduction to Contemporary Physics (1926), Electrical Phenomena in Gases (1932), The Renaissance in Physics (1936), and Atomic Energy (1948). Darrow also served as the secretary of the American Physical Society from 1941-1967.

In his book Introduction to Contemporary Physics (1926), Darrow made several references to the need for faith in theoretical and experimental discoveries: (“Fermat had faith in ‘economy of time’ as a fundamental principle of Nature” p. 158; “…such curves appear in the literature of physics, showing more or less conspicuous breaks; some are as striking as the best instances in the figure, some require a good deal of care and experience to locate them properly, and some, one is driven to conclude, are visible only to the eye of faithp. 286).

The text quoted above is taken from The Renaissance in Physics (1936):

I like to compare that classical era of discovery with the gradual excavation of some great ancient city long interred. All through the middle ages, and even to this day, there have been localities where scattered columns project here and there from a vast expanse of ground. For hundreds or thousands of years all who see them are content merely to look and pass ; but finally the archaeologists come with their spades, and after years of work they uncover the city, and anyone can see its scope and its plan and its organization… Electricity lay thus buried in dense matter for all but the three latest centuries of history, and only a couple of eminences jutted up into sight. One of these was the curious power of amber. The Greeks and many others looked at it and passed by. [William] Gilbert [(1544–1603)] began to investigate it, and the successors of Gilbert came—one by one at first, and then in legions—not with spades but with the tools of the physicist. By now they have revealed such great and unexpected wonders that hardly anyone ever thinks of the little phenomenon which was the guide of the pioneers: so trivial a thing it seems, so little and inconsequential, and yet it was the key to all the rest.

His Physics Today obituary recorded: “In 1951, he was made a Chevalier of the French Legion of Honor for ‘services rendered to the international relations of science and to the cultural relations between France and the United States.’ Van Vleck chose the word ‘style’ to characterize Darrow’s unique role in US physics. His colloquium talks were models of clarity, timing and subtle humor. His scientific articles were lucid… Darrow was at the same time an internationally renowned author and lecturer and a patron of the arts. As Van Vleck so cogently stated, ‘if all savants were like him, C. P. Snow would never have been able to coin the phrase “the two cultures”.’”

Referenced:
“Karl Kelchner Darrow.” Wikipedia. Wikimedia Foundation.
Darrow, Karl K. Introduction to Contemporary Physics. (New York, NY: Van Nostrand Company, 1939), 158; 286.
Darrow, Karl K. The Renaissance in Physics. (New York, NY: Macmillan. 1936), 29-20. (full text at hathitrust.org). Amazon: https://amzn.to/2xQ5E1W.
Havens, W.W. “Obituaries: Karl K. Darrow.” Physics Today 35.11 (1982): 83-84.