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Koichi Tanaka, on Turning an Experimental Mistake Into a Nobel Prize

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At A Glance

Name: Koichi Tanaka

Age: 43

Position: Fellow, General Manager, Mass Spectrometry Research Laboratory, Shimadzu, Kyoto, Japan

Won the Nobel Prize in Chemistry, 2002

Prior Experience: since 2002 Analytical & Measuring Instruments Division, Life Science Business Unit, Shimadzu, Japan

1999-2002 Kratos (subsidiary of Shimadzu), Manchester, UK

1997-1999 Shimadzu Research Laboratory, Manchester, UK

1992-1997 R&D Department of Analytical Instruments Division, Shimadzu, Japan

1992 Kratos, Manchester, UK

1983-1991 Central Research Laboratory, Shimadzu, Japan

Undergraduate degree in Electrical Engineering, 1983, Tohoku University

 

Koichi Tanaka is a humble man. Having won the Nobel Prize in Chemistry last year for his development of soft laser desorption of intact proteins, he was no doubt a celebrity at the recent annual meeting of the American Society for Mass Spectrometry in Montreal. But when a scientist at the conference approached him between sessions with “Congratulations, Dr. Tanaka!” his reply revealed that he only takes credit for what he believes he deserves: “It’s Mr. Tanaka, not Dr. Tanaka,” he said. “I am an engineer.”

This theme of modesty and understatement continued throughout his plenary lecture, attended by hundreds of participants who were curious to hear what this 43-year-old engineer who has spent his entire career with Shimadzu and rarely gives talks at international meetings had to say.

“I will not forget the evening on October 9 when I was receiving the phone call from the Swedish Nobel something or other,” Tanaka started out. “My first reaction was, ‘What in the world? What happened? Why on earth did they select me?’”

The main reason, he tried to convince his audience, was a fortunate experimental mistake he made back in 1985. At the time, Tanaka had been working in Shimadzu’s Central Research Laboratory, which he joined straight out of Tohuko University, for almost two years. As part of a group focusing on laser ionization mass spectrometry, he had the task of preparing samples for analysis. Back then, Tanaka recalled, the molecular weight of compounds that could be ionized by a laser and transferred into the gas phase without breaking them apart was about 100 daltons, and doing the same with compounds that exceeded 10,000 daltons in molecular mass was considered to be impossible by chemists. “However, not being a specialist in chemistry, I was unaware of the difficulty,” he said.

By mixing analyte molecules with a highly absorbing matrix that was made up of cobalt ultra fine metal powder (UFMP) — also known as “Japanese powder” — his group improved the spectra they obtained from high molecular-weight substances such as polyethylene glycol. However, proteins were still beyond their reach.

An experimental error provided the solution: While playing around with the concentration of metal powder and organic solvent one day in early 1985, “by mistake I used glycerol instead of the acetone,” Tanaka remembered. “Since UFMP is expensive, throwing it away would be wasteful,” he said, “so I used that ruined preparation of the matrix,” thinking that glycerol would rapidly evaporate in the vacuum. To speed the process up, he continued to irradiate the sample with the laser and monitored the time-of-flight spectra. Though the signal-to-noise ratio was poor, he saw a small signal emerge that he had not observed before. “No matter how many times I performed the measurement, these peaks were always there,” he remembered. As it turned out, glycerol was necessary for this to happen: “Had I thrown away the mixture because it was ruined, most likely I would not be here in front of you all,” Tanaka concluded.

After optimizing the concentrations of sample and glycerol and the laser strength, his group was able to measure intact proteins of up to 35 kilodaltons molecular weight, a major breakthrough at the time (Tanaka emphasized that it was a team effort). That summer, Tanaka and his colleague filed a patent application in Japan (which later issued as JP01769145), long before they would tell the rest of the world about his discovery. [That happened in 1987 at the 2nd Japan-China Joint Symposium on Mass Spectrometry in Japan where Tanaka presented a poster.]

Tanaka admitted that he was never really interested in the theoretical underpinnings of his discovery: Being an engineer, he was most concerned about his invention being “useful and practical.” This did not mean instant commercial success, though. The first product resulting partially from his discovery, the LAMS-50K mass spectrometer launched in 1988, was only sold once.

But his discovery paved the way for matrix assisted laser desorption ionization, and there is hardly a proteomics lab in the world today that does not feature a MALDI mass spectrometer. Tanaka, nevertheless, does not claim to have invented the technology, and pointed out emphatically in his lecture that Michael Karas and Franz Hillenkamp are the true fathers of MALDI, and that his discovery merely inspired their efforts. “Which is more important? Both are important. Without either contribution, there [would have been] no real achievement,” he said.

Soft laser desorption was not the only technology discovered at the Shimadzu labs that had the potential to greatly impact mass spectrometry. In 1985, Tamio Yoshida, a colleague of Tanaka, developed a technique called time-delayed ion extraction, which increases the resolution of a time-of-flight mass spectrometer. Further development, though, was stalled because the effect was not considered strong enough. “This technology subsequently underwent great development and became, as we all know, one of the indispensable technologies for TOF,” Tanaka said. “This is an example of a technology that we mistakenly thought would be of little usefulness, so we unfortunately abandoned [it].” On another occasion, Tanaka recalled, he missed the fact that he was measuring ions generated by post source decay, another important MALDI-MS technology.

But despite numerous developments MALDI mass spectrometry has undergone over the years, Tanaka does not think it has yet reached its maximum potential. The structural analysis of complex molecules like oligosaccharides will open up new applications for MALDI in combination with MSn, he said. One commercial incarnation of this is the MALDI-QIT-TOF instrument that Tanaka helped develop until last year. “However, a great deal of more development must [still] take place,” he said. “It will be necessary to develop innovative technology, hopefully in cooperation with all of you together in this hall.”

During the final minutes of his talk, Tanaka mused on what it takes to make a Nobel-worthy discovery. He cited the director of the Nobel Museum, who once put up a list of traits and prerequisites, ranging from courage, work, and persistence to playfulness, chance, and a moment of insight. Tanaka’s encouraging conclusion: Everybody has the potential for a Nobel Prize in them, and it does not take a special gift to be creative. “All of you who are here are naturally endowed with great talent. I detected soft laser desorption when I was in my 20s. Professor John Fenn invented ESI at the age of 70. Anyone can demonstrate creativity at any time.”

 

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