Author: Vernon Gambetta

 I had no idea who Koichi Tanaka was until I read the following in Garrison Keillor’s Writers Almanac  http://writersalmanac.publicradio.org/ on August 3. It certainly supports my life view that those with persistence and curiosity prevail. The italics and highlights in the least paragraph are mine. Three cheers for the generalists in this world who can see the big pig picture, because they have not limited their knowledge. You can bet I am going to learn more about this guy. Today is the 50th birthday of the only man without a post-bachelor degree to win a Nobel Prize in the sciences, Koichi Tanaka, born in Toyama, Japan (1959). When he received the Nobel Prize in chemistry, he was one of the youngest science laureates ever, and the 2002 Nobel Prize that he received was actually for a discovery that he made when he was only 25 years old. In 1985, he found a new and better way to analyze biological macromolecules such as proteins. His contribution has been integral to drug research and development; to early detection of ovarian, breast, and prostate cancers; to diagnosing and studying the spread of malaria; and to finding out which substances made during mass food production may be harmful. Though a good student in high school, he slacked off some in college, and after failing German class, he had to repeat an entire year. He majored in electrical engineering because he thought it would be easy to get a job with the degree, but he failed the entrance examination for the electronics company he wanted to work for. His college mentor suggested he consider working for Shimadzu Corporation, a manufacturer of scientific instruments and medical equipment such as X-ray devices. He hoped to work in the medical equipment area and easily passed the employment examination. But rather than putting him in the medical manufacturing section, the company sent him to work in research and development in the analytical instruments division. His specific task there, he said, was "to search for a matrix that would enable nondestructive ionization of macromolecules by efficiently absorbing the laser energy." In other words, they were looking for a way to analyze macromolecules (such as proteins) with a scientific instrument called a mass spectrometer — but the twist was to do it such a way as to leave the protein intact. The problem with a macromolecule such as protein was that the process of ionizing (giving them an electrical charge) caused the macromolecule to fragment into tiny pieces, destroying its structure. So Tanaka's task was to come up with the right combination of chemicals that would allow the protein's structure to remain intact. The laboratory where he worked stocked hundreds of substances that were possible solutions for the matrix, and the options were multiplied many times over by the possible combinations. Since he'd majored in electrical engineering and had a limited background in chemistry, there was a big gap in his knowledge level compared to other researchers in this area. He worked his way by trial and error through the seemingly endless list of possible solutions, repeating the process so often that he said he'd "become one with these substances and the instrument." Then, on a February day in 1985, he mistakenly used a glycerin-Ultra Fine Metal Powder mixed matrix instead of the cobalt one he'd intended. He realized right away what he'd done, but his grandmother's words "what a waste" floated through his mind, and he set aside the mistaken mixture instead of throwing it away. He put it in the vacuum chamber of the mass spectrometer to dry it out and evaporate the unwanted glycerin, hoping that he could salvage the part of the mixture that he had intended to use in the first place. Wanting to hurry the process, he turned on the laser beam and irradiated the mixture. He kept his instrument, the mass spectrometer, running and he kept glancing at the results because he wanted to make sure that all of the glycerin had disappeared, at which point he'd be able to use the mixture as first intended. As he monitored the results he noticed a signal peak he'd never seen before. It was mixed in with noise peaks on the machine, which always annoyed him, and so it caught his attention. He repeated his experiment, confirmed his findings, and refined his experiments. After the patent application had been completed, the process, called soft laser desorption-mass spectrometry (SLD-MS) was reported to the scientific community in 1987. Tanaka later said that because he was not a specialist, he might have been at a disadvantage in looking for the correct matrix, but that it turned out that common knowledge was an obstacle. At the time, most chemists thought that it was impossible to ionize big molecules like proteins. But because he wasn't aware of many of the commonly held rules of chemistry, he tried things that everyone else knew would not work. Tanaka has noted that it was a "monumental blunder" that led to the discovery of Soft Laser Desorption. The improved method of analysis has led to huge advances in chemistry, medical and veterinary science, pharmaceuticals, and food science in the past two decades.