Dr. Osamu Shimomura
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1928 |
Born in the city of Fukuchiyama, Kyoto Prefecture Spent his childhood in places like the cities of Sasebo, Osaka, and Isahaya (Nagasaki area). Graduated from the College of Pharmaceutical Sciences, Nagasaki Medical College (now the School of Pharmaceutical Sciences, Nagasaki University) |
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1951 |
Research Method Instructor, School of Pharmaceutical Sciences, Nagasaki University |
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1955 |
Research Student in Organic Chemistry Research Lab, School of Science, Nagoya University |
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1958 |
Research Associate, School of Pharmaceutical Sciences, Nagasaki University |
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1960 |
Doctor of Science, Nagoya University Researcher, Princeton University (Fulbright exchange student) |
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1963 |
Assistant Professor, Water Quality Science Research Facility, School of Science, Nagoya University |
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1965- 1982 |
Senior Researcher, Princeton University |
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1982 |
Visiting Associate Professor, Boston University |
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1984 |
Visiting Professor, Boston University |
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2000 |
Emeritus Professor, Boston University |
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2008 |
Special Senior Fellow, Marine Biological Laboratory (Woods Hole, Massachusetts) |
A Coincidence leading to a move to Hirata Laboratory
One day in March 1955, Dr. Shimomura, who was a Research Method Instructor at Nagasaki University at the time, went with former professor Shungo Yasunaga to request an in-country exchange in molecular biology under Nagoya University's famous Professor Fujio Egami. However, Professor Egami was away on a business trip. As he was leaving, Professor Yasunaga stopped to greet Professor Hirata, and Dr. Shimomura went with him. They told Professor Hirata how they were unable to see Professor Egami, and after a few minutes of conversation, as they were leaving Professor Hirata's office, Professor Hirata said to Dr. Shimomura,
"Come to my lab. You can start whenever."
At that time I thought Professor Hirata's words might be an order from heaven above.
From Osamu Shimomura's book Learning From Jellyfish, published by Nagasaki Bunkensha
Three Former Professors
Looking back on the path he took, Dr. Shimomura said, "The path I chose is not one I found by myself. I just took the path that was shown to me by a mentor." Professor Yasunaga let him do an in-house exchange at Hirata Laboratory at Nagoya University, and he took the data he got from Professor Hirata on crystallizing Cypridina luciferin (from sea fireflies, Cypridina hilgendorfii), and embarked on the path of bioluminescence research. After Dr. Shimomura succeeded in crystallizing luciferin, Professor F. H. Johnson from Princeton University invited him there, where he researched the bioluminescence of the Aequorea Victoria jellyfish. However, this was never an easy road and, needless to say, Dr. Shimomura's success was down to the hard work he put in.
Encounter with Sea Firefly Research
The topic given to Dr. Shimomura as a researcher at Hirata Laboratory was to "determine the structure of Cypridina luciferin". This was a topic that had been studied for 20 years at Professor Harvey's laboratory at Princeton University, without success. The research topic for a Bachelor's thesis or a Master's thesis would be a topic that could probably be solved within 1 to 2 years, but it seems that the policy was to give researchers research topics that were more difficult. Professor Hirata said, "Refine and crystallize the luciferin to determine its structure." At the time, crystallization was the only way to prove purity. Dr. Shimomura immersed himself in this research.
Unstable Luciferin
Luciferin is extremely unstable, and quickly breaks down in the presence of oxygen. The question was how to obtain a large amount of this unstable substance. Dr. Shimomura proposed a special extraction device. This device would be able to extract approximately 500g of dried sea firefly, which was 10 times the amount Princeton University had been using in previous research. Then he conducted extraction tests using hydrogen gas, so that the luciferin would not be exposed to oxygen. At that time, gases like nitrogen and argon had low purity, and it was difficult to remove oxygen from them. However, it was easy to remove oxygen from hydrogen, although it was dangerous, so hydrogen was used.
Crystallizing Luciferin
These improvisations made the refining work on luciferin go smoothly. However, it was difficult to crystallize, which resulted in failure after failure. Then, 10 months later, on a cold day in February of 1956, Dr. Shimomura obtained luciferin crystals through a coincidence. He added hydrochloric acid for the objective of analyzing the components, and went home. When he looked at it the next morning, a very small amount of red needle crystals had formed on the bottom of the test tube. Through this good luck, Dr. Shimomura was able to determine the structure and luminescence of luciferin. These results were a milestone in bioluminescence research and were talked about both in Japan and overseas. Then, in 1960, Dr. Shimomura received his Doctoral degree at Nagoya University with the topic "Structure of Cypridina Luciferin".
Friday Harbor Laboratories
Dr. Shimomura was invited by Dr. Johnson at Princeton University, and went to the US as a doctoral researcher. Dr. Shimomura's daily work on Aequorea Victoria jellyfish began in the summer of 1961, at Friday Harbor Laboratories in the state of Washington on the west coast of the US.
Initially, they thought that the structure of the luminescence of the Aequorea Victoria jellyfish was the same as many other luminescent organisms and that luciferase and luciferin contributed, and they were trying to extract those substances separately. However, it did not go well. Dr. Shimomura changed his way of thinking and proposed that they take the direction of extracting any luminescent substance. However, Dr. Johnson did not agree with this plan, and for a while Dr. Johnson and others were testing on one lab table, and Dr. Shimomura was running tests by himself nearby.
New Idea
Dr. Shimomura continued to think non-stop about how he could extract a luminescent substance. One afternoon, when he was on a boat thinking dreamily, an idea suddenly occurred to him.
"Luminescent reactions are probably closely related to proteins. If this is true, acidity (pH) should have a strong effect on them."
Dr. Shimomura quickly went back to the laboratory, made solutions with various pHs, and tried to extract fluid from a jellyfish ring. When extracted fluid with a pH of 4 was filtered and had cells removed, the liquid did not luminesce. However, when it was neutralized to pH 7, he found that the luminescence returned. This means that fermented substances from a jellyfish can be extracted at a pH of 4.
Dr. Shimomura took this opportunity to obtain a luminescent substance from an Aequorea Victoria jellyfish. Approximately 10,000 jellyfish were collected, the rough luminescent product from those was refined over a period of approximately 6 months, and Dr. Shimomura managed to obtain approximately 5 mg of an almost pure luminescent substance. At the same time, Dr. Shimomura was also able to refine the proteins that produce the green phosphors eluted before aequorin. This is the green fluorescent protein (GFP) that revolutionized the field of molecular biology research.
Aequorea Victoria jellyfish
Dr. Shimomura collected approximately 850,000 Aequorea Victoria jellyfish. This many were needed because only a tiny amount of luminescent substance could be obtained from each jellyfish. This major effort has led to current scientific developments. In recent times, the numbers of Aequorea Victoria jellyfish have decreased. If the research had started 20 years later, this result could not have happened. Dr. Shimomura says that this research could not have been accomplished without a "blessing from heaven".
"I have felt overjoyed twice in the past. This was when I succeeded in crystallizing Cypridina luciferin in 1956, and when I discovered how to extract aequorin from Aequorea Victoria jellyfish in 1961. The joy of these two times was far greater than any other. I was part of a group of scientists, and I gained confidence that I could make it as a scientist. I was happy from the bottom of my heart.
From Osamu Shimomura's book Learning From Jellyfish, published by Nagasaki Bunkensha
Message from Dr. Shimomura
Researching the unknown structure of bioluminescence was not just rote repetition. It was a process of running into various difficulties and problems, and I had to solve each one as I went along in order to go forward. Something easy can be solved in weeks or months. But no matter how difficult the problem, if you don't give up, you can overcome it one day. Then if you can solve it without giving up, that will lead to confidence, which will help you solve the next problem. So the important thing is to solve the first difficult problem you encounter. If you give up once, you will probably give up the next time as well.
From Osamu Shimomura's book Bioluminescence : Chemical Principles and Methods