Gregorio Weber: From Sheffield to Urbana

by Woody Hastings

Department of Molecular and Cellular Biology
Harvard University,

Cambridge,

MA 02138

Those who knew and worked with Gregorio Weber were fortunate indeed. He was a man of truly extraordinary qualities in many different realms. With a keen intellect and lively mind, he combined wisdom and wit, perception and persuasiveness with personal warmth and generosity of spirit. Now, more than a decade after his death, his friendship remains with me as an indelible trace, buoying me in many ways.

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I first met Gregorio in 1959, when he came from Sheffield University as a visiting Professor in the Biochemistry Division at the University of Illinois. Recruited by chairman Irwin Gunsalus (Gunny), he taught a summer course on the properties of light, especially fluorescence and fluorescence polarization. The lectures, which many faculty members attended, revealed a whole new aspect of physical biochemistry; for me it was exciting, especially because I was then working on the role of flavin in the bacterial luciferase reaction, which I had discovered some years earlier to be involved the bioluminescence (McElroy et al., 1953).

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The impact of the lectures was not due only to Gregorio’s knowledge and keen intellect; his warm and engaging personality played an important role. As we came to know him, we found that his remarkable insight and perceptive understanding of matters relating to all aspects of human behaviour put him in a class by himself. No matter what the topic or the question, Gregorio always showed himself to be well informed, and always in a modest way; his observations were invariably astute and persuasive. His wry sense of humor added greatly to his persona.

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The biochemists at Brandeis, always on the cutting edge, invited Gregorio as a visiting professor the next year, where he not only had a similar intellectual impact; he directed the construction of new instrumentation. Having become good friends with overlapping interests in science, I visited him there on more than one occasion.

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In subsequent years Gunny proceeded to invite several other biochemists from Sheffield. In 1960 Vincent Massey joined us for a full semester, bringing a wealth of knowledge and boundless enthusiasm for flavins and flavoenzymes. From Vince I gained further new insights concerning how a flavin might serve as a substrate (a luciferin) in a bioluminescent reaction.

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But it was the next visitor, Quentin Gibson, then the chairman of Biochemistry at Sheffield, with whom I became deeply involved at the bench. He arrived at Chicago O’Hare on January 28, 1961. I had volunteered to meet his plane and bring him with family (wife Jane and four small children), not knowing that my own fourth child Karen would be born that afternoon. I learned that news after we arrived home, having been accompanied on the drive down by a brilliant red sunset seen on the horizon across the frigid plains. A striking introduction for the Gibsons.

Jane worked in the Gunsalus lab on photosynthetic bacteria, while Quentin was given a lab next to mine, with an inside connecting door. With his luggage he had carried one of his newly designed and developed Stopped Flow devices, which was able to mix two reagents in a millisecond and to make spectral observations thereafter at specified wavelengths. “What might I want to study, Quentin queried?” “The reaction of reduced flavin mononucleotide with oxygen”, I replied. And so we did, (Gibson and Hastings, 1962), this being a prelude to the study of the reaction of reduced flavin with oxygen in the presence of luciferase, measuring emission of light instead of absorption.

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In the course of the spring we realized that we would not have time to work with the luciferase catalyzed reaction before the end of the semester, when the Gibsons would return to Sheffield and I would be going to the MBL at Woods Hole for the entire summer. One day, while watching a reaction take its (somewhat slow) course in Bill Rutter’s Cary recording spectrophotometer, we discussed how to proceed. “Why don’t you come to Sheffield next year?” Quentin asked. At first I had doubts. I had an active lab and had purified large quantities of the luciferase for a study of the reaction mechanism. “How can I leave all these students in the lab for a year?” I asked Gunny. “Well”, he said, “if they are no longer here when you return you will know it wasn’t worth it.”

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And so in early September I went directly from Woods Hole ( Boston airport) to Sheffield with wife Hanna and the four children, the youngest only nine months old, the oldest not yet six. At that time luggage was subject to surcharges for overweight, so each of the three older children was strapped with a mini rucksac. After a harrowing night, with a diversion to New York and then Prestwick, we arrived at the Manchester airport, where Theo Hoffman, a faculty member in the department, met us. In retrospect it’s difficult to know how he got us all with luggage into his mini wagon. Our five bedroom house had no heating other than open fireplaces in each room, and the city had not yet converted from soft coal, so black soot and the smell of sulfur was pervasive. Years later in East Berlin I was haunted by the familiar smell only to finally realize that it was the same as Sheffield.

The department was housed in three buildings, one of which was an abandoned cinema theater, the “Scala”, used mostly for large scale biochemical preparations and storage. While I had a bench and desk in the main building on the hall with Gregorio and Vince, I needed a completely dark room for my experiments, as well as the ability to run reactions below room temperature. The Scala fit the bill perfectly; there was an available room with no windows and the building was not heated, so in the winter months it was perfect. In the first draft of the publication reporting on the work done there (Hastings and Gibson, 1963), the inclusion of a statement in Experimental Procedure that “all reactions were carried out at room temperature, 10 degrees C.” was vetoed by coauthor Gibson.

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I also carried out a project with Gregorio in the Scala, in which we established a liquid light standard suitable for determining the total photon flux from chemi- and bioluminescent reactions (Hastings and Weber, 1963). The standard contained radioactive hexadecane-1-C    in a scintillation solution; under an atmosphere of argon the emission of such standards has remained constant now for over forty years. Although later determinations indicated that the specified photon flux was too high by a factor of about 2, it was and is very useful; it also served to stimulate workers in the field to report results in absolute instead of relative units.

While Gregorio was much involved in the design and interpretation of the Scala experiments, he was not able to be there very much. During that winter he spent several months in the hospital, as a retinal detachment had caused a severe loss of vision. He attributed this, as I recall it, to his repeated visual inspection of a UV light source used in his experiments, and I do recall him doing just that. I visited him frequently in the hospital where he was typically upbeat and anxious to discuss science and politics.

After discharge from hospital, he went for an extended time to a village outside Cambridge to recuperate, where I also visited him. Although his vision was compromised for the remainder of his life, he did not complain, nor did he let it reduce his productivity or pleasure in life.

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During that year Gunny came up with an offer of a Professorship at the University of Illinois. I think that the decision was a very difficult one for Gregorio, and it must have caused much unhappiness among his colleagues at Sheffield and the three mentioned above soon followed him to North American. Gregorio was indeed an important intellectual centerpiece in the department, and assumed a similar position in Urbana.

Gregorio arrived in the fall of 1962 and moved into newly renovated space down the hall from me in the building then called East Chemistry (now the Roger Adams lab), so we had frequent and strong interactions. In short order his ideas and impact spread throughout the department and the University, leading to significant long-term collaborations with many others in Chemistry, including Nelson Leonard, in the Organic Division and Harry Drickamer downstairs in Chemical Engineering. But we had only three years together; I took a sabbatical at Rockefeller in 1965 and then accepted a position at Harvard in 1966.

But our interactions and communication did not diminish; Gregorio came to visit both at Rockefeller and Harvard, and later in Paris and on many other occasions. In the late 1960s I was able to arrange for him to spend a semester as a visiting professor in my Department at Harvard, where he again taught his course on properties of light and fluorescence. Ernst Mayr was away on sabbatical that semester so he was able to live in Ernst’s house on Chauncy Street, two blocks from the lab.

George Mitchell, a graduate student who started in Urbana and moved with me to Harvard had also become captured by the theory and application of fluorescence in biochemistry. In my lab at Harvard he wrote his thesis on fluorescent species in bacterial bioluminescence. Having skills in both electronics and machining, George designed and constructed the first solid state photomultiplier photometer, and modified our commercial Amino-Bowman fluorimeter to provide corrected spectra. Returning to Urbana in 1961 as a post doc with Gregorio, they developed a polarization fluorimeter (Jamieson et al., 1978), which George and two colleagues, Dick Spencer and David Laker, constructed and marketed. The company name, SLM, was derived from their surnames. A great success, SLM later acquired Amino-Bowman prior to being sold.

Over the next nearly 30 years Gregorio’s frequent visits to Cambridge included social as well as scientific interactions. Early on he introduced us to his lifelong friend Carola Eisenberg, a Medical School classmate from Argentina. With her husband Leon, they have become our own treasured friends in Cambridge.

It was a disappointment that Gregorio could not get to my 70th birthday celebration held in May 1997 at the Marine Biological Laboratory in Woods Hole. He had hoped and planned to come en route to Argentina, but his physician, Tamara Mitchell, judged it inadvisable, and he agreed. Knowing that he would not live long, Gregorio wrote a poignant good bye letter.

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• McElroy, W.D., Hastings, J.W., Sonnenfeld, V., and Coulombre, J. (1953) The requirement of riboflavin-phosphate for bacterial luminescence. Science 118: 385-386.

• Gibson, Q.H. and Hastings, J.W. (1962) The oxidation of reduced flavin mononucleotide by molecular oxygen. Biochem. J. 83: 368-377.

• Hastings, J.W. and Gibson, Q.H. (1963) Intermediates in the bioluminescent oxidation of reduced flavin mononucleotide. J. Biol. Chem. 238: 2537-2554.

• Hastings, J.W. and Weber, G. (1963) Total quantum flux of isotropic sources. J. Opt. Soc. Am. 53: 1410-1415.

• David M Jameson, Gregorio Weber, Richard D Spencer, and George Mitchell. Fluorescence polarization: measurements with a photon-counting photometer. Rev Sci Instruments 49: 510-514, 1978.