Has "the most beautiful brain in the world"
On the eve of the announcement of the winners, Qian Yongjian was told on the phone that he had won the 2008 Nobel Prize in Chemistry and was invited to participate The awards ceremony will be held in Stockholm in December. This is undoubtedly the most important award that Qian Yongjian has received so far.
Previously, Qian Yongjian has received numerous "golden" professional awards, including the Wolf Prize in Medicine, known as the "Nobel Pointer", in 2004. In addition, he holds no fewer than 60 U.S. patented inventions.
With his talents in chemistry and biology, Qian Yongjian found a way to make green fluorescent proteins glow brighter and longer, and created a wider range of fluorescent protein colors, including yellow, blue, and orange. Wait for color. "I have always been attracted by color," Qian Yongjian said. It is color that makes his work more interesting. "When the work is not going well, because of color, I can continue the work. If I am born with Being colorblind, I probably wouldn’t have achieved what I have achieved today.”
Qian Yongjian’s talent and achievements are recognized by people in the industry. Mark Ellison, a long-term collaborator of Qian Yongjian and director of the National Center for Microscopy Imaging and Research at the University of California, San Diego, said that Qian Yongjian is the smartest person he has ever met.
He commented on Qian Yongjian in an interview with the "San Diego Union-Tribune": "He has the most beautiful brain in the world, not only because he can think deeply about how to fill the gaps in the known scientific fields. , more because he knows how to discover new problems. He digs deeply, understands problems quickly, and is good at uniting all parts of the problem and discovering new research tools to help other scientists discover other new problems. "
In this regard, Qian Yongjian humbly emphasized that he was not the discoverer of fluorescent proteins, "I am just a person who makes tools."
After several "turns", he finally returned Chemistry
Qian Yongjian was awarded the Nobel Prize in Chemistry for his achievements in fluorescent protein research. In fact, despite his wide range of interests, he did not choose this path from the beginning.
While continuing his studies at Cambridge University, he wanted to do something more interesting, so he switched from chemistry to molecular biology and then to oceanography. "I always had some dream about sailing on the blue sea, but it turned out that my work had nothing to do with this dream. My research included measuring oil pollution in the bay. In the end, I finally understood that I didn't care about the Algae Sea at all. "The problem of depth."
So Qian Yongjian switched from oceanography to physiology and obtained a doctorate. At that time, his research mainly focused on the human brain, which was more interesting to him.
In Qian Yongjian’s view, the human brain is an intoxicating loom. “It requires more skillful, sophisticated and creative methods to weave the fragments together.” After that, he "returned" to chemistry and began his research on green fluorescent protein.
Confident in his own cancer research
Jenifer, director of organelle biology at the National Institute of Early Childhood Health and Human Development, said: "Qian Yongjian has a huge impact. He demonstrated a series of possible applications of green fluorescent protein-based reactants and facilitated their use in the biological community. Dr. Qian played a crucial impact on the development of cell biology."
Green fluorescent protein is currently receiving more and more attention from the scientific community. Before 1992, there were very few scientific research articles on green fluorescent protein, but in 2007 alone, according to statistics, there were 12,000 scientific research articles related to green fluorescent protein or fluorescent proteins. Some scientists predict that this number will continue to grow.
Qian Yongjian is particularly interested in whether fluorescent proteins can be used in neurobiology and cancer. His father died of cancer. "He had pancreatic cancer and he passed away six months after he was diagnosed.
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Although Qian Yongjian has made revolutionary contributions in the field of fluorescent protein research, he has planned to leave this kind of work to his colleagues and spend more time and energy on human conditions. In terms of research, it includes conquering diseases such as cancer, atherosclerosis and stroke.
Qian Yongjian admitted that his research on cancer may not have any results. “The history of science is full of scientists. An example of success in one study and failure in another. ”
Selected as a first-level academician of the American Institute of Cancer
According to the US “World Journal” report, the “American Association for Cancer Research Academy (AACR)” in Washington, USA It was recently announced that five professors and experts from the University of California, San Diego (UCSD) and neighboring scientific research institutions, including Roger Tsien, a Chinese scientist and 2008 Nobel Prize winner in Chemistry, have been selected as AACR "First-Class Academicians" ( First Class of the Fellows), in recognition of their outstanding contributions to the prevention, treatment and research of cancer.
The announcement issued by AACR stated that the reason for Qian Yongjian's selection is: because of his research in cell biology and research. A revolutionary innovation in the field of neurobiology, scientists can peer into the inner activities of cells and observe the dynamics of molecules in real time. Scientists can also track the expression of certain genes in cells or the entire body. An important scientist related to Osamu's research. In imaging technology, he has two important works that are related to Osamu Shimomura.
The first one is calcium dye
In 1980. Qian Yongjian invented a dye molecule for detecting calcium ion concentration. In 1981, he improved the method of introducing dyes into cells. Later, he invented more and better dyes, which are widely used. There are three methods for detecting calcium: selective electrode, aequorin, and aequorin. Calcium dye. Before Qian Yongjian's calcium dye appeared, only aequorin had spatial detection capabilities. However, at that time, aequorin needed to be injected into cells, which was inconvenient to use. However, Qian Yongjian's dye can penetrate into cells. Aequorin and calcium dyes have their own advantages and disadvantages, and Qian Yongjian has also invented a variety of dyes for studying other molecules.
The second one is GFP. p>Since 1994, Qian Yongjian began to study GFP, improving the luminescence intensity and luminescence color of GFP (inventing variants, many different colors), inventing more application methods, and clarifying the luminescence principle. He is responsible for most of the FPs used in the world. Variations of the invention. His patents are used by many people and sold by companies.
Qian Yongjian's work has attracted attention since the beginning of the 1980s. He was probably invited to give academic lectures. Most scientists listen to his reports on both chemistry and biology, which include technical applications and some very interesting phenomena. He was born in 1952, so his age allows him to wait for many years (but the 80-year-old Osamu Shimomura does not have this advantage). Qian Yongjian has been considered by many to win the Nobel Prize for many years, either in chemistry or physiology. It must be pointed out that Qian Yongjian is very sure of Shimomura's work, and Qian publicly introduced Shimomura's discoveries earlier. p>
The two brothers won the Rhodes and Marshall Scholar Awards respectively (generally considered the two most competitive scholarships for American college students, and President Clinton won the Rhodes). In 1994, Chinese-American scientist Roger YTsien began to transform GFP, with several discoveries. Most of the ones used in the world are variants modified by Qian Yongjian's laboratory. Some have stronger fluorescence, some are yellow or blue, and some can be activated and change color. It has become a hobby of some people to look for colored proteins in organisms that are not commonly used as research models. This phenomenon is just like the wave after the discovery of polymerases for PCR that were widely used in thermophilic organisms. But I didn’t really find many useful things. A successful example is the discovery of other fluorescent proteins from corals by Sergey A. Lukyanov's laboratory at the Institute of Bioorganic Chemistry of the Russian Academy of Sciences, including red fluorescent protein.
The phenomenon of bioluminescence has been studied by Osamu Shimomura and Johansson before. Fireflies fluoresce because luciferase catalyzes the substrate molecule luciferin, which undergoes chemical reactions such as oxidation to produce fluorescence. The protein itself emits light without the need for a substrate. It originated from the research of Osamu Shimomura and Johansson.
Shimomura Osamu and Johnson have used several experimental animals. The one related to this story is the jellyfish with the scientific name Aequoreavictoria. In 1962, Osamu Shimomura and Johnson reported in the Journal of Cellular and Comparative Physiology that they isolated and purified the photoluminescent protein aequorin in jellyfish. It is said that when Osamu Shimomura was extracting luminescent protein from jellyfish, he was going home from work one day. He poured the product into the pool. After turning off the lights before going out, he reluctantly looked back at the pool and saw the pool sparkling. Because the pond also received water from the fish tank, he suspected that the ingredients in the fish tank affected the jellyfish, and soon he determined that calcium ions enhanced the luminescence of the jellyfish. In 1963, they reported the relationship between calcium and aequorin luminescence in Science magazine. Later, Ridgway and Ashley proposed that jellyfish can be used to detect calcium concentration, creating a new method for detecting calcium. Calcium ions are important signaling molecules in living organisms. Aequorin became the first calcium detection method with spatial resolution and is one of the methods still used today.
In 1955, Davenport and Nicol discovered that jellyfish can emit green light, but they did not know why. In the 1962 article by Osamu Shimomura and Johnson on the purification of aequorin, there was a footnote saying that another protein was discovered, which appeared green under sunlight, yellow under tungsten filament, and emitted strong light under ultraviolet light. green. They then carefully studied its luminescent properties. In 1974, they purified this protein, which was called green protein at the time and later called green fluorescent protein GFP. Morin and Hastings proposed that energy transfer can occur between aequorin and GFP. Aequorin emits light when stimulated by calcium, and its energy can be transferred to GFP, stimulating GFP to emit light. This is the discovery in biology of what is known in physical chemistry as fluorescence vibration energy transfer (FRET).
Shimomura Osamu himself is not interested in the application prospects of GFP, nor is he aware of the importance of its application. After he left Princeton and went to the Woods Hole Oceanographic Institution, his colleague Douglas Prasher was very interested in inventing biological tracer molecules. In 1985, Plattish and Japanese scientist Satoshi Inouye independently obtained the gene for aequorin (cDNA to be precise) based on the protein sequence. In 1992, Plattish obtained the GFP gene. With cDNA, it is easy for general biological researchers to use, and it is much more convenient than using proteins.
After Plattish published the cDNA of GFP in 1992, he stopped doing scientific research. When he applied for the National Science Foundation, the reviewers said that there was no precedent for protein luminescence, and even if he found it, it would be of little value. In a fit of rage, he left academia and went to work for the Department of Agriculture's Animal and Plant Services Division at the Massachusetts Air National Guard Base. At that time, if he spent a few dollars, he could do a very beautiful job that any average graduate student could do: put the jellyfish GFP gene into other organisms, such as bacteria, and see fluorescence, which completely proves that GFP itself can emit light. No other substrates or auxiliary molecules are required.
The work of expressing GFP into other organisms was carried out independently in 1994 by two laboratories: Marty Chalfie's laboratory working on nematodes at Columbia University, and the University of California, San Diego and Scripps Institution of Oceanography Two Japanese scientists, Inouye and Tsuji.
Aequorin and GFP both have important applications. But aequorin is still a type of luciferase, and it requires luciferin. The GFP protein itself emits light, which is a major breakthrough in principle.
Chalfie's article immediately caused a sensation, and many biological researchers introduced GFP into their own systems. If you express GFP in a new system, you can publish articles in Nature and Science. In fact, it is just following the trend and has no originality.
Looking at the entire process, from 1961 to 1974, the research of Osamu Shimomura and Johansson was far ahead, but few people paid attention to it. Other biochemists can also obtain aequorin and GFP if they wish, and the technology is not particularly difficult. After 1974, especially after the 1980s, it was easy for many graduate students to do subsequent work. The exception is that Tsien's lab discovered variants with new colors that were not immediately obvious.