The Rise of Instruments during World War II | Analytical Chemistry

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Anal. Chem. 2008, 80, 5684–5691

The Rise of Instruments during World War II Rajendrani Mukhopadhyay The pressures of war ushered in new instrumental techniques that changed the nature of chemical analysis forever. Politics and geography are not the only things that were irrevocably changed by World War II (WWII). The war also infiltrated chemistry laboratories. Its demands changed the way measurements were made, by driving instruments that had been hovering on the fringes into mainstream analytical processes. “Instrumentation was arriving in the 1930s, but there was a culture of doing most analytical work by wet chemical methods. There was no particular urgency, financial or temporal, to change habits,” says Davis Baird at the University of South Carolina. “The war provided urgency.” The more widespread adoption of instruments transformed the appearance and feel of the chemistry laboratory. “If you look at a photo of a lab in the pre-1940s, the only things you see are a polarimeter, a refractometer, an analytical balance, a microscope, and lots of glassware,” says Gerald Gallwas, a Beckman Coulter retiree, who is currently on the board of directors at the Arnold and Mabel Beckman Foundation. “If you look at a lab photo in the 1950s, it’s highly instrumented.” MS, IR spectroscopy, and NMR are some examples of analytical techniques that were catapulted into the spotlight by the war’s demands for better analyses of aviation fuel, medicine, rubber, warfare agents, and food supplements. In an article he wrote on the Manhattan Project, Alfred Nier, a pioneer in MS development, reminisced about how the war transformed MS:1 “Prior to World War II there were only a few mass spectrometers in the entire world, and these were built by scientists who used them as tools in their own research, studying the dissociation and ionization of molecules by electron impact or determining the relative abundances of isotopes. The need of the petroleum industry to find better means for analyzing complex hydrocarbon mixtures and the uranium isotope separation and atomic bomb production program (known as the Manhattan Project) stimulated the design and construction of new, improved mass spectrometers. Following the war such instrumentation became widely available commercially and applicable to a wide range of problems.” (To learn more about the history of MS, see Ref. 2.) 5684

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The war’s timing and objectives provided a motive to improve analytical techniques. Once their worth was proven during the war, the instruments’ applications began to expand and evolve. “The use and market for these early analytical instruments were accelerated during the war,” explains David Brock of the Chemical Heritage Foundation. “You then see a tremendous boom in the 1950s and into the 1960s, where all these techniques began to appear commercially;MS, NMR, GC, LC.” Baird explains that a number of companies;such as Beckman Instruments, Baird Associates, and Perkin-Elmer (now PerkinElmer);got their feet wet in the instrument business in the mid-1930s. (Baird’s father, Walter, was the founder of Baird Associates.) Then “the war came along and created a massive demand for process analytical work. All of these companies grew hugely,” he says. “Baird Associates probably prospered the least of the companies, but yet it grew hugely. By the end of the war, there was a substantial industrial 10.1021/ac801205u CCC: $40.75  2008 American Chemical Society Published on Web 07/31/2008

SPECTROSCOPY DURING WWII IR spectroscopy is the poster child for techniques that blossomed during the war (for a comprehensive description of its history, see Ref. 3). “IR [spectroscopy] was one of the first methods that made rather complex chemical manipulations unnecessary,” says Yakov Rabkin at the University of Montreal. “It enabled chemists to make their operations routine and tremendously speed up the process of identification of compounds. It drastically changed the way science was done and conceptualized.” Beckman Instruments, which at the time was called National Technical Laboratories (NTL); Perkin-Elmer; and Baird Associates figured prominently in the development of commercial IR spectrometers in the 1940s. NTL got involved in spectroscopy because its electric circuits, developed for the Beckman pH meter, could measure small electric currents generated in photoelectric cells. The circuits led NTL to develop the Model DU spectrophotometer, the first UV photoelectric spectrophotometer, in 1941. The timing of the instrument’s introduction was a stroke of luck for NTL. Evidence was mounting that vitamin A was an important nutrient. Scandinavian cod-liver oil was an important source, but the war was cutting off transatlantic supplies. The U.S., in its scramble to find domestic sources, turned to shark liver, but researchers needed to measure the quantity of vitamin A in the organ. At the time, measuring vitamin A was an exercise in patience. Approximately 60 rats, aged 21 days, had to be fed liver for 4 weeks. The rats were then weighed and the bone formation in their tails analyzed to determine the vitamin A content of the liver they had been eating. Researchers accepted results if duplicate tests came within 25% of one another. But the Model DU spectrophotometer brought about a radical change. The instrument could measure levels of vitamin A in a few minutes with a precision of 99% without the use of rodents. The spectrophotometer also proved to be useful in measuring toluene and other essential war materials. The synthetic rubber program. One essential war material was rubber, and the U.S. synthetic rubber program spurred the development of IR spectrometers. From 1915 to the 1940s, onehalf to three-quarters of the world’s natural rubber was consumed by the U.S. Most of the natural rubber came from Southeast Asia,

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base, both for the production of instruments and for the use of the instruments. It changed the culture.” The U.S. led the way for instrument innovation and development. “Most of continental Europe was completely destroyed by the war,” says Carsten Reinhardt at the University of Bielefeld (Germany). “There wasn’t much infrastructure left. The exception probably was the U.K.” Reinhardt explains that free-flowing money and close ties between industry and academia bolstered instrument development in the U.S. But the American lead began to falter in the mid- to late 1950s. “You’ll see that around 1960, U.S. scientists and science administrators were very much aware that [instruments] were a key strategy to keep up the advantage of U.S. science and technology. Instrument development was at that time already a major business. It went hand in hand with scientific advances,” says Reinhardt. But in the mid-1960s;with the exception of the computer, which also was regarded as an instrument;all major Western European countries and Japan caught up with the U.S. in their use of IR, UV, NMR, and MS instrumentation.

Bob Brattain of Shell Development designed the IR-1 spectrophotometer manufactured by NTL, the forerunner to Beckman Instruments. but the Pearl Harbor attack of 1941 and the fall of the British military base in Singapore to the Japanese in 1942 halted supplies. Rubber imports into the U.S. became limited to what could be grown in South America, which was much less than prewar quantities. Rubber was indispensable for the U.S. military. Airplanes, tanks, and battleships required hundreds of tons of rubber. Each military staff member needed 32 lb of rubber for footwear, clothing, and equipment. Rubber was quickly placed on the list of materials deemed critical for winning the war. A consortium of companies, under the sponsorship of the U.S. government’s Office of Rubber Reserve, formed to develop and produce a generalpurpose synthetic rubber on a commercial scale. The synthetic rubber effort was based on the polymerization of butadiene that was available from petroleum refinery gases. But the gases contained many different hydrocarbons that required identification. Analyses could be done only by IR spectroscopy. The Office of Rubber Reserve used all the legal and financial incentives at its disposal for the speedy manufacturing of IR equipment. It pitted the instrument designs of three companies;American Cyanamid Co., Dow Chemical Co., and Shell Development Co. (in Emeryville, Calif.);against one another to come up with a standard apparatus for IR analysis that could be used by all corporate participants in the synthetic rubber program. The Shell Development design was finally selected. The company’s resident expert was R. Robert Brattain (sidebar, “R. Robert Brattain”). Brattain’s design for a standardized IR spectrophotometer was handed over to NTL because of its expertise in producing the Model DU spectrophotometer. NTL was told to manufacture the IR instruments on a large scale and distribute them to laboratories working on synthetic rubber. Analytical Chemistry, Vol. 80, No. 15, August 1, 2008

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R. Robert Brattain R. Robert Brattain was recruited to the Shell Development Co. in Emeryville, Calif., in 1938 by Otto Beeck. (Brattain’s brother, Walter, was one of the three recipients of the 1956 Nobel Prize in Physics for the invention of the transistor.) Brattain had cut his teeth on IR spectroscopy while a graduate student at Princeton University in the laboratory of R. Bowling Barnes. Beeck realized IR spectroscopy was a valuable tool for studying molecular structure and instructed Brattain to design and build an IR spectrometer at Shell Development. Brattain completed the project as the war began to loom in Europe and as he was busy studying the isomerization of n-butane to isobutane for production of high-test gasoline. In an account of his wartime experiences, Brattain described what happened next:5 “One day the laboratory director, Dr. E. Clifford Williams, was showing some important visitors around, and in an effort to show the usefulness of the instrument said to me, ‘Could you determine the amount of iso-butane in a butane mixture?’ Feeling that the question somewhat demeaned the real purpose of my instrument, I replied, ‘That’s trivial.’ That afternoon Otto Beeck phoned and asked whether I had said that to Williams. When I said yes, he said, ‘Well, you better start doing it,’ and our plunge into spectroscopy as a chemical analytical tool began.”

By 1945, NTL had produced 75 copies of Brattain’s prototype under direct contract from the Office of Rubber Reserve. The instrument’s manufacture had the top-level AAA priority rating during the war, but Arnold Beckman later said, in a 1975 lecture:4 “We were proud of our selection as sole manufacturer, but we were to learn, sadly, that our sole-source contract had an unsuspected negative feature. The IR-1, as the instrument was called, carried top AAA priority rating. That helped us get scarce materials, but we could deliver the IR instruments only to AAA customers. That did not bother us, for we readily sold all the IR1s we could make. When the war was over, however, and we started to market a greatly improved model, designated IR-2, we encountered difficulty.” (“Other NTL wartime efforts” describes more of Beckman’s activities during WWII.) IR spectrophotometers by Perkin-Elmer and Baird Associates. American Cyanamid was one of the first companies to use IR analysis in the 1930s; its staff built the apparatus. When more instruments were needed for the synthetic rubber program, American Cyanamid contracted out production to Perkin-Elmer. American Cyanamid chose Perkin-Elmer because it specialized in high-quality optics and because both companies were in Stamford, Conn. During the war, Perkin-Elmer was involved in lower-priority government programs. Therefore, it operated under looser controls than NTL did and was free during the war to discuss the industrial uses of IR technology. 5686

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Paul Wilks had joined Perkin-Elmer just as the company was starting production of its first IR spectrometer in the 1940s. “I was given the job of assembling it, testing it, and getting it ready for shipment,” says Wilks, who now runs Wilks Enterprise. “For the next couple of years, that was my job at Perkin-Elmer; assembling their IR instrument.” The biggest problem in assembling the prism instrument, Wilks recollects, was getting sufficiently large rock-salt crystals. “Originally, the large crystals came from Russia because they were able to get large single crystals out of their salt mines. But right about [wartime], Harshaw Chemical Company in Cleveland developed a way of synthetically growing large rock-salt crystals. That was the source for several years of this material.” (Ref. 6 provides Wilks’s detailed account of the development of the early IR spectrometers.) Baird Associates’ contribution to IR spectroscopy was its dualbeam IR spectrometer (NTL’s instrument was single-beam). The dual-beam instrument was thought to have better precision and accuracy. “But it was big,” says Baird. “Baird Associates never gained sufficient market share to make its contribution to IR profitable, and they dropped the line in the early to mid-1950s.” The penicillin program. The wartime penicillin program was an important forum in which IR spectroscopy could prove its worth. Penicillin was the wonder drug of the mid-20th century, and the war only increased demand for it. A crucial step in creating an abundant supply for the armed forces was to determine the compound’s structure. That was key to synthesizing the antibiotic, which would be much faster than the cumbersome process of extraction from cell cultures. Efforts to determine the structure of penicillin were launched concurrently in the U.S. and the U.K. and initially enveloped in secrecy. In his Nobel lecture, Ernst Chain;who, along with Howard Florey and Alexander Fleming, won the Nobel Prize in Physiology or Medicine in 1945 for work on penicillin;said:7 “In 1943 the British and U.S. Governments imposed a ban on the publication of all chemical work on penicillin and simultaneously negotiations were begun between the two governments for the purpose of finding a suitable method for a complete exchange of information between the various groups of workers on both sides of the Atlantic. . . . In February, 1944, agreement for exchange of information between the British and American workers was reached; in Britain the Medical Research Council (M.R.C.) formed the ‘Penicillin Synthesis Committee’ to which were sent papers by British authors; in America the Office of Scientific Research and Development (O.S.R.D.) delegated Dr. Hans T. Clarke of Columbia University to co-ordinate the chemical research work on penicillin in the U.S.A. and to receive monthly reports from its contractors. These two bodies, the M.R.C. and O.S.R.D., agreed to exchange their reports at monthly intervals, and in April 1944 we received the first American reports on penicillin.” The British team of scientists included Robert Woodward, one of the organic chemists who wholeheartedly embraced the new IR, UV, and NMR instruments; and Sir Robert Robinson. Leo Slater at the U.S. Naval Research Laboratory studied the relationship between Woodward and Robinson as an example of two scientists from different viewpoints.8 “They weren’t far apart in age, but Sir Robert seemed nostalgic for a time;which you could call the pre-war period;when you would determine chemical

Other NTL wartime efforts

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Arnold Beckman had come up with the Helipot, a helical potentiometer, to solve a problem in the pH meter. In early 1942, he received a mysterious phone call asking him to go to Boston, where he was introduced to a wartime secret;radar. The radiation laboratory at the Massachusetts Institute of Technology had discovered that the Helipots were more accurate than other potentiometers on the market. Beckman was asked whether his company would be willing to manufacture them according to military specifications for the radar program, and he agreed. The potentiometer design was unsuitable for military use because mechanical blows would cause the circuits to momentarily open up. NTL engineers were asked to redesign the potentiometer. Beckman recalls:4 “That’s where trouble entered;almost an inhouse mutiny. Our research engineers were busy with sophisticated infrared spectrophotometers involving fancy optics and electronics. It was almost insulting to ask them to work on a mere potentiometer. So Helipot development lagged. I began getting calls from top military brass, ‘ Where are the blankety-blank Helipots?’” During one particularly sleepless night, Beckman thought up a new design. The next day, avoiding the engineers, he went directly to the machinist and asked him to build the part, which Beckman had sketched out in pencil. Two days later, after a second pencil redesign, the Model A Helipot was born, and this one met the military needs of radar. Going straight to the machinist was a trademark move of Beckman’s. Gallwas says, “He did a lot of work in support of military projects, and after talking to people, he would come in with a drawing on a back of an envelope. The machinist would make the part, and he would take the part and the envelope. Nobody would be the wiser.” Toward the end of 1940, a meeting of scientists and military personnel was held to discuss ways to measure atmospheric oxygen. Linus Pauling was at the meeting. He recognized that oxygen had paramagnetic properties and was attracted by a magnetic field, whereas all other common gases are diamagnetic. He went home and within 2 weeks came up with a design of an oxygen analyzer. “It was a rather innovative design based on solid physical chemistry,” says Gallwas. But Pauling did not have the means to make it. He turned to Beckman, who was his colleague at the California Institute of Technology at one time, and asked if he could implement this design. By 1943, NTL was supplying the military with oxygen analyzers that were used on submarines and aircraft. Beckman later recounted reading an article in the Saturday Evening Post.4 Doctors at Johns Hopkins Hospital were concerned that one-third of premature babies at the “better” hospitals were becoming permanently blind. The doctors were able to determine, with the help of the Beckman oxygen analyzers, that when the oxygen levels in the neonatal incubators exceeded 40% (oxygen levels are kept high to help premature babies breathe), retrolental fibroplasia struck the babies. Beckman said he was happy to learn that the analyzers were critical in saving eyesight of babies.

The Perkin-Elmer Model 21 double-beam IR spectrophotometer evolved from its predecessor, the Model 12, which was developed in the 1940s. The Model 21’s success shot Perkin-Elmer from relative obscurity into the Fortune 500 category.

structures of natural products by chemical degradation. . . . There was almost a cultural resistance to the instruments.” Woodward’s

enthusiasm for new-fangled instruments rubbed Sir Robert the wrong way. But “the structure that Woodward had selected [for penicillin] was the correct one, and he picked it based on IR spectra. It’s an early example of instrumentation proving to be useful for structure determination by organic chemists,” says Slater. The secrecy surrounding the penicillin project caused twin discoveries to be made on the two sides of the Atlantic. On the American side, Brattain had been initiated into the war penicillin program. He formed a team with three organic chemists;including S. A. Ballard;to work on synthesizing possible penicillin analogs. IR spectroscopic studies of the analogs were carried out by Shell Development’s Robert Rasmussen (who wrote a detailed account of the company’s IR spectroscopic studies on penicillin9), Donald Tunnicliff, and Brattain. The British had given the American scientists three possible structures of penicillin suggested by Sir Robert. Brattain and his colleagues quickly realized that the two structures most favored from a chemical viewpoint were wrong. The third structure, with fused β-lactam and thiazolidine rings, seemed to be the correct one. Brattain remembers:5 “Ballard and I went east on the train to report these findings at a secret meeting in Washington, D.C., in November 1944. Our data were in a black leather briefcase Analytical Chemistry, Vol. 80, No. 15, August 1, 2008

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(Left to right) Walter S. Baird, Davy Low, and John Sterner (cofounder with Walter Baird of Baird Associates) inspect the guts of the Baird Associates IR spectrophotometer. with a handcuff to attach the case to one of our wrists per secrecy rules. At breakfast one morning we suddenly discovered that neither of us had the case and we headed for the compartment so quickly that we got stuck in the dining car doorway.” Everyone involved in the penicillin program on both sides of the Atlantic was present at the secret Washington meeting. Brattain wrote that all the chemists dismissed the β-lactam thiazolidine structure at each presentation given throughout the day. Ballard got up at the end of the day and announced that on the basis of the IR spectra, the two favorite structures were not correct. A stunned silence followed. Once they recovered from the shock, the chemists grilled Ballard and Brattain and were convinced by the data to change their minds. Shortly after Ballard and Brattain returned to Emeryville, the chemists in their team were able to synthesize three fused β-lactam thiazolidine compounds that allowed the spectroscopists to confirm that the strange absorption band in the IR spectrum of penicillin was the result of a fused β-lactam thiazolidine structure. Lore has it that X-ray crystallography work by Dorothy Crowfoot’s team in the U.K. ultimately provided the conclusive structure for penicillin. But Brattain later said:5 “Crowfoot’s results pinned the structure down without any shred of doubt and she arrived at her conclusion unaware of our results. As a matter of fact she had been told that the infrared spectra indicated that it was not the thiazolidine-β-lactam structure. When our secret report, mailed through the necessary channels in early February 1945, arrived at her lab in England about 4 days after she had arrived at her conclusion she was really happy. The fact is that 5688

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we and Crowfoot arrived at the correct structure almost at the same time without being aware of the others’ results. How do I know all of this? Dorothy Crowfoot came to Emeryville after the war specifically to discuss the work on penicillin.” Post-WWII. After the war, the manufacturers and users of IR instruments joined forces to promote the technique. For instance, “Ohio State University had every June what they called the Columbus Symposium, which was a gathering of academic people and industrial people to give papers on new developments in spectroscopy,” says Wilks. “It was an effort to bring industry and academia together, and it was very successful. It did get emphasis from the war, but it continued after the war. In fact, it’s still going on today.” In addition, Wilks says, “every year there was a training course at [the Massachusetts Institute of Technology] that Beckman Instruments, Perkin-Elmer, and Baird Associates all participated in. Even though we were competitors, we also were trying to promote the field.” Reinhardt explains that academic science caught up with industrial science in the uses of IR spectroscopy after the war. Much of the credit for introducing academic scientists to the technique goes to organic chemists such as Roger Adams at the University of Illinois. Adams was involved in the synthetic rubber program and “knew this instrumentation was around through his contacts in war-related industries. He got hold of an instrument and made use of it immediately after the end of the war,” says Reinhardt. Because of such efforts by academic researchers and manufacturers, more of the instruments began to pop up in laboratories. NMR SPRINGS FROM WAR EFFORTS The NMR instrument was the offspring of the wartime development of radar. The story of Varian Associates;the company that made NMR a cornerstone in chemical analysis;and its instruments echoes IR spectroscopy’s tale. The story exemplifies how the synergy of a good idea, perfect timing, and a critical mass of like-minded people can lead to something with lasting impact (for a detailed history of Varian’s development of NMR instruments, see Ref. 10). Radar was initially studied in the late 1930s but was vigorously developed only during the war years. Accompanying the development of radar was a major burst in innovative electronics. “Radar first appeared as a high-frequency radio device and then moved into the microwave world. Major labs were established in the early 1940s to develop the technology. There were lots of new vacuum tubes and electronic circuits that were developed at that time,” says Christophe Le´cuyer of the University of California. “People who developed the first NMR machines used circuits initially developed for radar systems.” One of the NMR developers was Felix Bloch. The rise of Hitler had forced Bloch to leave Germany in the 1930s; he came to the U.S. and joined the faculty at Stanford University. The new venue gave Bloch the opportunity to work with a very simple neutron source, and in doing so, he realized that the magnetic moment of free neutrons could be observed. By 1939, in collaboration with Isidor I. Rabi, who first discussed the NMR phenomenon in 1937, he determined the magnetic moment of the neutron with an accuracy of ∼1%.

During the war, Bloch got involved in various efforts, including work done at Harvard University on radar countermeasures. The radar work introduced him to the developments in electronics. Toward the end of the war, Bloch realized that electronics, in conjunction with his earlier work on the neutrons, provided a new approach to investigating nuclear moments. He immediately began to work on the new approach when he returned to Stanford in 1945. With the help of William Hansen, Bloch tackled nuclear induction studies, an electromagnetic procedure for the study of nuclear moments in solids, liquids, or gases. A few weeks after the first successful experiments, Bloch received the news that the same discovery had been made independently and simultaneously by Edward Purcell and colleagues at Harvard. Until the early 1950s, no one believed that anyone, aside from a handful of nuclear physicists, would give a hoot about measuring magnetic moments of nuclei. In early 1946, when Bloch wrote to Stanford officials to try to patent nuclear induction, the officials could not see profit in it and dismissed Bloch’s suggestion. In the 1930s, near Stanford in the San Francisco Bay area, Russell and Sigurd Varian developed an “electron tube”, known as the klystron tube. The klystron tube was capable of directing a beam of electrons. The brothers’ aim was to detect airplanes by high-frequency radio signals. Sigurd cajoled Stanford into providing laboratory space and $100 worth of materials. The university also put the Varian brothers in touch with Sperry Gyroscope Co., which agreed to support the research in return for exclusive patent rights. By the summer of 1937, the first klystron tube had been constructed, and in 1939, it was described in the Journal of Physics.

The synergy of a good idea, perfect timing, and a critical mass of like-minded people can lead to something with lasting impact. The British military immediately jumped on klystron technology and applied it to radar. The technology helped them defeat the Luftwaffe’s relentless attacks in the summer and fall of 1940. The Varian brothers, along with Stanford graduate student Edward Ginzton and Bloch’s colleague Hansen, moved to Sperry Gyroscope’s laboratories on Long Island, N.Y., to help with the war effort. The group, reveling in the freedom they were given to pursue research, built klystron tubes for military purposes and participated in the postwar microwave technology revolution, which eventually gave birth to devices such as high-energy particle accelerators, communication satellites, and cell phones. In 1945, Sigurd Varian continued to work for Sperry Gyroscope, but Russell Varian, Hansen, and Ginzton returned to their beloved San Francisco Bay area. Since 1943, they had been ruminating about starting a company that focused on microwave measurement and instrumentation. With the Cold War escalating in 1948, the researchers realized that there would be a greater demand for the military technologies that the group had worked on during WWII. So the Varian brothers, Ginzton, Hansen, and Leonard Schiff, the chair of the Stanford physics department, invested $22,000 to form Varian Associates. One of the hopes of Varian Associates was to bypass the restrictions imposed on university research

agendas by the government right after the war and to enjoy the same freedom the founding members had experienced at Sperry Gyroscope. Bloch was not a founding member, but he supported Varian Associates and eventually became a paid consultant to the company. Russell Varian had been able to convince Bloch and Hansen in late 1946 to file a patent on the principle of nuclear induction, a move that bore fruit when chemical shift and spin-spin coupling were later demonstrated. In the early 1950s, NMR as an analytical tool was a mere castle in the air. Varian Associates survived by applying its expertise in klystron tubes to aerial navigation and missile guidance while struggling to develop NMR. The establishment of NMR as a commercial instrument faced two key challenges: producing a high-quality spectrometer for reliable structure determinations and recruiting scientists willing to gamble and work on a technique that had yet to gain acceptance in the chemistry community. But the commercial success of IR spectrometers opened a potential market for instruments that could explore other frequencies in the electromagnetic spectrum. From 1952 to 1965, Varian Associates invested heavily in NMR research. Its expertise with electronics, electromagnets, and microwave-based technologies came into play. In 1957, Varian committed to engineer and manufacture a successful commercial NMR instrument, the Varian A-60. The first A-60s were produced in 1961. But to sell the NMR instruments, Varian Associates had the formidable task of convincing chemists to use them. At the time, chemists did not know much about the technique and found the amount of physics involved daunting. James Shoolery, who had joined Varian Associates in 1953, guessed that NMR instruments would have to compete with IR spectrometers. So Varian Associates came up with ways to associate the two instruments. They renamed the instrument the “nuclear magnetic resonance spectrometer” instead of “nuclear induction device”, the name that Bloch and Hansen had used in their 1946 patent. The display printouts, size, and appearance of the NMR instruments mimicked those of the user-friendly IR spectrometers. And they were priced only slightly higher than high-end IR spectrometers. Just as it had done for IR spectrometry, Varian Associates established NMR workshops in 1957. “They convinced chemists to adopt [NMR] by giving workshops on the technique and its theory for many years,” says Le´cuyer. “The other way they convinced chemists to adopt NMR techniques was to buy the back page of one of the leading chemical journals, where they would publish the results coming from NMR. The first thing chemists would do when they received the latest issue of the journal was to look at the back page and see what new information they could find about NMR.” The publication was the Journal of the American Chemical Society. NMR exemplified how investigators pioneering a new technique were convinced that the instrument would lead to new frontiers. “Makers of the NMR really had to work to get the technique adopted. It wasn’t like people were standing around, saying, ‘Oh, if only we had something that could measure the chemical shift, everything would be great,’” says Brock of the Chemical Heritage Foundation. “They had no idea of the potential. It was more speculative and creative on the part of the people who were developing the basic technique and making the commercial devices.” Analytical Chemistry, Vol. 80, No. 15, August 1, 2008

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Varian Associates worked hard to promote the advantages of NMR to the chemistry community. In the 1960s, it ran one-page ads in the back inside cover of the Journal of the American Chemical Society that described its latest instrumentation developments. Brock also says it further explains why many instrument companies had an active applications research division. “You would have chemical researchers in the instrumentation company collaborating with the very high-profile figures from the academic research community to use the instrumentation.” Richard Ernst, who won the Nobel Prize in Chemistry in 1991 for his work on NMR, is such a researcher. He collaborated with Varian scientists to introduce stand-alone computers dedicated to NMR data analysis. WWII’S LASTING IMPRINT WWII left the U.S. with a substantially increased capacity to make new and interesting instruments. “We also had the cultural belief that science won the war,” says Baird. “Science provided us with radar. It provided us with the instruments that had, in somewhat prosaic roles, given us the atom bomb. The atom bomb drove the cultural perception of science winning WWII.” Franklin D. Roosevelt’s science adviser, Vannevar Bush (no relation to the current U.S. president), was highly influential. His report, Science: The Endless Frontier, resulted in the development of the National Science Foundation in 1951. He supported the view that in order to maintain its competitive stance on the international 5690

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stage, the U.S. had to, as a matter of national security and prestige, promote science. Baird says, “Money started to be poured into academic science departments, and the money was spent on what? On instruments!” But instrumentation had to compete with entrenched mindsets, as seen in the conflict between Woodward and Sir Robert. “You had certain blockades in attitudes and in the practice of research that hindered certain developments after the war,” says Reinhardt. “One famous example is MS. It was intensely used during the end of the war in the chemical industry, but it took >10 years, until around 1960, before it was used in academic chemistry.” It was not as if the instrumentation were inadequately developed. The manufacturers had poured a lot of effort into designing reliable instruments, “but the mind-set of the academic chemists was not ready to use this instrumentation,” says Reinhardt. Reinhardt, who has written extensively on the applications of NMR and MS in organic chemistry,11 says some of the pioneers of MS in organic chemistry told him that others in the community regarded the technology as black magic. “To bridge these mindsets, there was a lot of effort [exerted] by chemists, both in industry and at the universities, who concentrated on developing methods and explaining MS in terms of physical organic chemistry.” Some science historians hold that the technologies that emerged from WWII shaped the frontiers of science. Rabkin explains, “We often perceive technology as depending on science, being engendered by science. In this particular case, we have a reverse relationship;technology affects science. And it’s not technology coming out of nowhere but technology coming from the industrial sector. This is not the influence that we usually think about but is, in fact, another aspect of the gradual merging of science and technology into what the French call ‘technoscience’.”

WWII left the U.S. with a substantially increased capacity to make new and interesting instruments. Baird, whose research focuses on how technology drives science, echoes Rabkin’s sentiment. “New instruments are probably the most important driver for scientific development, rather than plain old resources like money,” he says. “One of the things that happened in the mid-20th century is we started to develop a lot of new interesting instruments, and they absolutely did drive the development of science.” Rabkin suggests that one reason instruments shaped research directions was the marketing strategies of the manufacturers. “Once the war was over, the instrument-making companies had to decide how to find a new market. They were one of the first to adopt the policy of creating a demand for their product. It is not very different from what cell phone companies do today! They organized summer schools for chemists and explained to them what a wonderful instrument they had at their disposal.” Applying this marketing strategy to scientific tools was radical at the time. Besides defining scientific frontiers, instruments also changed other facets of science. “In order to be able to make good use of instruments, you had to develop methods for using them,” says Reinhardt. “In the 1940s, and especially in the 1950s and 1960s,

quite a large group of scientists, mainly in academia but also in industry, did nothing much else except develop methods. They closely collaborated with instrument manufacturers to make methods. You could call them the method makers.” John D. Roberts is an example of a method maker. He started off as a traditional physical organic chemist. After he got involved in NMR, he became well-versed in biochemistry, and by the end of his career, he was very much involved in medicine. And throughout his career, he brought along NMR. “He would solve a crucial riddle, promote it, and write textbooks;the normal procedure, if you will;and would try to sell his method to an audience of chemists, biochemists, and medical scientists. When the method became routine, he changed subjects and went on to developing more difficult methods with more advanced instrumentation,” says Reinhardt. The creation of methods for instruments injected fluidity into scientific boundaries. Baird says, “There was a real boundary question between chemistry;in particular analytical chemistry;physics, and instrumentation. Most of the instruments were being developed by people with a physics or physics-related background, especially in optics. But the primary markets for these instruments were clearly in analytical chemistry, not physics.” Baird notes that in the late 1940s, Analytical Chemistry reflected the confusion over the scope of the discipline. “People were clearly uncertain of boundaries and how to think of the nature of these disciplines. They tried ‘physical chemistry’ or ‘chemical physics’ or ‘analytical physics’. None of these worked brilliantly”.12 As instruments slowly transformed the mind-set of a generation of scientists raised on wet chemical methods, they gradually changed the social structure of science, too. The preWWII single-investigator type of science waned. Team science became the rage and eventually the norm, simply because instruments required experts to get them to work. If an instrument were to be pushed to its limits to reach a new

frontier in science, individuals with expertise in instrument mechanics, chemistry, and biology had to work jointly. Highly specialized instruments brought the age of the individual pioneer to a close and ushered in the age of collaborative, team science. Instruments changed the nature of making measurements. And by changing the nature of measurements, the instruments created the look, feel, and culture of the laboratory of today. ACKNOWLEDGMENT It is beyond the scope of this article to give proper credit to every individual involved in the development of IR spectroscopic and NMR instruments. I encourage readers to explore the reference list’s histories of the scientists and engineers who gave us analytical instruments. Rajendrani Mukhopadhyay is a senior associate editor of Analytical Chemistry.

REFERENCES (1) (2) (3) (4) (5) (6) (7) (8)

(9) (10) (11)

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Nier, A. O. J. Chem. Educ. 1989, 66, 385–388. Griffiths, J. Anal. Chem. 2008, 80, DOI 10.1021/ac8013065. Rabkin, Y. ISIS 1987, 78, 31–54. Beckman, A. O. Presented at the National Meeting of the Newcomen Society in North America, New York, NY, November 10, 1975. Brattain, R. R. Spectrum 1999, 53, 1–7. Wilks, P. A. Anal. Chem. 1992, 64, 833 A-838 A. Ernst B. Chain Nobel Lecture. http://nobelprize.org/nobel_prizes/ medicine/laureates/1945/chain-lecture.html. Slater, L. Organic Chemistry and Instrumentation: R. B. Woodward and the Reification of Chemical Structures. In From Classical to Modern Chemistry: The Instrument Revolution; Morris, P. J. T., Ed.; Royal Society of Chemistry, Science Museum London, and Chemical Heritage Foundation: Cambridge, U.K., 2002; pp 212-228. Rasmussen, R. S. Prog. Chem. Org. Nat. Prod. 1948, 5, 331–386. Lenoir, T.; Lecuyer, C. Perspec. Sci. 1995, 3, 276–345. Reinhardt, C. Shifting and Rearranging: Physical Methods and the Transformation of Modern Chemistry; Science History Publications/USA: Sagamore Beach, MA, 2006. Baird, D. Thing Knowledge: A Philosophy of Scientific Instruments; University of California Press: Berkeley, CA, 2004; Chapter 5.

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