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www.japanprize.jp

No. 45Jan. 2011

2011 Japan Prizes Awarded to :Dr. Dennis Ritchie and Dr. Ken Thompson
for the development of UNIX,
Dr. Tadamitsu Kishimoto and Dr. Toshio Hirano
for the discovery of interleukin-6“Information and Communications” field“Bioscience and Medical Science” field

Dr. Dennis M. Ritchie

Dr. Ken L. Thompson

Dr. Tadamitsu Kishimoto

Dr. Toshio Hirano

United States

United States

Japan

Japan

Distinguished Member of Technical Staff Emeritus,
Bell LabsDistinguished Engineer,
Google Inc.

Emeritus Professor,
Osaka University

Professor,
Osaka University

It has been decided that The Japan Prize Foundation will award the 2011 Japan Prizes to Dr. Dennis Ritchie,
Distinguished Member of Technical Staff Emeritus at Bell Labs, Dr. Ken Thompson, Distinguished Engineer at
Google Inc., Dr. Tadamitsu Kishimoto, Emeritus Professor at Osaka University, and Dr. Toshio Hirano, Professor at
Osaka University.
Dr. Ritchie and Dr. Thompson will be awarded in the field of “Information and Communications” for theircontributions to the development of the operating system, UNIX.
Dr. Kishimoto and Dr. Hirano will be awarded in the field of “Bioscience and Medical Science” for their discovery ofinterleukin-6 and its application in treating diseases.
The laureates deserve the utmost honor for contributing to the peace and prosperity of mankind through theirsignificant roles in the advancement of science and technology.
They will be formally honored at the Presentation Ceremony to be held in Tokyo on April 20, 2011.

The Japan Prize is awarded to scientists throughout the world who havebeen credited with original and outstanding achievements and have mademajor contributions to the advancement of science and technology, thereby
manifestly furthering the cause of peace and the prosperity of mankind.

While the prize encompasses all categories of science and technology, twofields of study are designated for the prize each year in consideration ofdevelopments in science and technology.
Each Japan Prize laureate receives a certificate of merit and a commemorative
medal. A cash award of 50 million yen is also made for each prize field.

"Information and Communications" field
Achievement: Development of the operating system, UNIX

Dr. Dennis M. Ritchie
Born : September 9, 1941 (Age 69)
Distinguished Member of Technical Staff Emeritus, Bell Labs

Dr. Ken L. Thompson
Born : February 4, 1943 (Age 67)
Distinguished Engineer, Google Inc.

Summary
With present computer systems, basic software called operating
systems are used in addition to application software to perform word
processor, spreadsheet tasks, and so on. Dr. Dennis Ritchie and
Dr. Ken Thompson developed an advanced operating system called
UNIX in 1969. The operating systems in those days were increasingin scale but becoming complex and disorderly. With UNIX, stability
and high-speed performance could be attained by combining modularized programs. UNIX’s superior design concept has been carriedon by many computer technicians, and has supported the development of an advanced information society including the Internet.

Operating systems which make user-friendly computers possible
With present computers, multiple software usually functions hierarchically (Figure 1). For example, application software works closest to the user in operating a spreadsheet or in processing photographs. The operating system works in between the application software and hardware (machine). The role of the operating system is tomake the hardware which includes the hard disk constituting thecomputer abstract and present it to the application software. Thanks
to it, the application software can simplify such commands as“record data” or “print.” In addition, the operating system can
execute multiple tasks concurrently and also perform basic tasks
such as connecting to the network.

Figure 1 Software hierarchical diagram

The early computers which appeared on the scene in the 1940’s
did not, in fact, have an operating system. In the 1950’s, programs
came to be used as tools to simplify hardware usage, which established the concept of an operating system. Then in the 1960’s, computer developers were competing to upgrade the operating system
functions. In those days, large-scale and high-speed computers wererapidly being developed, and a time sharing system was achieved
where one high performance computer was used concurrently bymultiple persons. In order to improve the user-friendliness of thesecomputers, the development of an operating system became indispensable.
In the U.S. in 1964, Massachusetts Institute of Technology (MIT),in collaboration with Bell Labs and General Electric (GE), began ajoint research project to develop a time sharing operating systemcalled Multics. Multics aimed to use the capacity of highperformance computers to the full, in order to achieve an interactive
user interface that could be used like a telephone or electricity,which was a breakthrough system back then.
Dr. Ritchie and Dr. Thompson, both of whom were then in their20’s, were among those who participated in the project as researchers of Bell Labs. Dr. Ritchie was developing an efficient programming language for Multics, and Dr. Thompson came up with the ideaof a hierarchical filing (document management) system which later
became the core technology for UNIX. However, between 1968 and1969, Bell Labs decided to withdraw from Multics development.
The verdict reached by Bell Labs was that Multics, in pursuingideals, had become too massive and complex, and not much hope
could be held for the overall system performance.

The development of Multics at Bell Labs was discontinued, but
Dr. Thompson and his colleagues who were deeply involved in thedevelopment carried on independent research. They felt they did notwant to lose the convenient user interface which Multics provided at
its development stage, and began to search for an alternative system.
In particular, Dr. Thompson was very fond of an interactive computer game called “Space Travel” that he programmed himself.

Figure 2 UNIX philosophy

Small things have advantages that large things do not have. By separating the
programs into small modules as much as possible, they can be used in combinations.

(2) One program with one function:
Programs separated into small modules should each have one definite and reliable
function.

application(3) More emphasis on portability than efficiency:
Rather than having maximum capabilities on one particular hardware, by maximizing
functions on as many computers as possible, the computer environment is enhanced.

(4) Emphasis on data portability:
operating system

Even if the program is portable, information cannot be shared. All number data
should be stored in ASCII flat files.

(5) Avoid excessive interactivity:
Data flow is disrupted during the time users are interacting. Aim to achieve amoderately interactive interface.

hardware

In time, the spelling of UNICS became UNIX, and its superior
functions became known to researchers as well. In addition tohaving a hierarchical filing system that enables a quick search ofdesired information, because its basic parts were developed by ahandful of people, it was a simple yet relatively trouble-free, solid
operation system. In 1970, it was ported to a higher performancecomputer (PDP-11), and Bell Labs’ patent department became oneof its users.
The next issue which the now highly-evaluated UNIX faced, was
the improvement of the programming language. From his
experience with Multics, Ritchie felt the need for a “high-level
language” programming with a higher abstraction level ofcommands. Dr. Ritchie along with Dr. Thompson were jointly
developing B language, but they completed the improved version,
the C language, and in 1973, UNIX was rewritten in the C language.
Through this development, it became possible for UNIX to be usedin computers around the world. In 1974, both doctors publishedtheir long-awaited UNIX article, and UNIX became known
worldwide.

In want of making their own operating system(1) Small is beautiful:
Users (people)

Thus, he ported the computer game into an old computer (DEC’s
PDP-7) which was lying idle at the laboratory . With Dr. Ritchie’s
help, he gradually added functions in Multics which were thought tobe particularly important. Dr. Thompson’s filing system which wasleft in limbo was also ported, and by 1969, it came to have an
appearance of a new operating system. In the process, this operating
system came to be known among the staff as UNICS. The name was
supposedly given to emphasize its compact and single layer (UNIplex) image in contrast to Multics’ massive and multilayer(Multiplex) image.

An open culture achieved by UNIX
Both UNIX and the C language which were developed by both
doctors greatly influenced the information science in later years. In
those days, Bell Labs provided free-of-charge UNIX and the sourcecode (number sequence indicating basic commands to the hardware)to universities and research institutes; thus they were usedproactively by researchers around the world. UNIX has created an
open culture where researchers share ideas among themselves, which
in turn, leads to new developments. As bamboo shoots after the rain,
design concepts which sprung up one after the other has been handed
down as UNIX philosophy. Many improvements have also been
made to the C language, and many operating systems today havebeen written in the C language from the beginning.
In retrospect, many basic technologies in the information field
have been conceived with UNIX as the basis. Noteworthy of them isthe Internet. University of California, Berkeley developed BSD
UNIX, which is the extended version of the Version 6 UNIX
functions. From this, Internet protocol (TCP/IP)-mounted UNIX
originated, greatly contributing to the realization of the Internet.
At present, there is a license system where certain regulations areapplied to UNIX usage. However, “open source,” which is a method
where the source code is disclosed while protecting the copyright ofthe software producer, is also under parallel development. Operating
systems carrying on the UNIX philosophy are now being usedwidely from mobile phones to supercomputers.

"Bioscience and Medical Science" field
Achievement: Discovery of interleukin - 6 and its
application in treating diseases

Dr. Tadamitsu Kishimoto
Born: May 7, 1939 (Age 71)
Emeritus Professor, Osaka University

Dr. Toshio Hirano
Born: April 17, 1947 (Age 63)
Professor, Osaka University

Summary
Our bodies detect external invasions of bacteria and viruses andeliminate them. This mechanism is called “immunity.” Immunity is
a complex system consisting of various cells such as lymphocytes(T-cells, B-cells) and macrophage, but the substance which plays animportant role in transmitting information between cells is calledinterleukin. Dr. Tadamitsu Kishimoto and Dr. Toshio Hirano havepurified interleukin 6 (IL-6), which plays a vital part in the production of antibodies, and also succeeded in gene cloning in 1986. In
addition, the two doctors have identified a wide range of functions of
IL-6 and their research results have contributed to the progress ofbioscience and the development of therapeutic drugs for inflammatory diseases.

In quest of a substance which transmits immune cell commands
The knowledge that the human body has an immune system
which, once exposed, builds in us resistance to a certain illness, hasbeen long-established. Modern medicine started off with researchers
confronted with the challenge of revealing what the immune system
is. At the end of the 19th Century, Shibasaburo Kitazato andGerman physician Behring conducted research on the serum therapyof tetanus and diphtheria and discovered that a substance whichattacks the pathogen is formed within the body once we are exposed
to such infectious diseases. Thus, the concept of the immune system
where the antibodies recognize and eliminate antigens was established. Around the same period, Russian microbiologist Mechnikov
claimed that leukocytes within the blood attack pathogens such asbacteria in a mechanism called “phagocytosis,” thus establishing thefoundations of immunology.
Coming into the 20th Century, the characteristics of antibodies as
substances were clarified and in a wider sense, the immune systemcame to be identified as a complex system made up of a wide varietyof cells including companions of leukocytes such as lymphocytes,
macrophage and dendritic cells. It was not until the late 1960’s thatthe research regarding the essence of the immune system proceeded
rapidly. It was then discovered that there were two types of lymphocytes, namely T-cells and B-cells, and that it was by mutual transmission of information between these two cell types that enabled thevarious antibodies to be produced efficiently. By defining thesignaling mechanism, knowledge about the complex immune system
can be acquired. The protein used to transmit information among thecells is called cytokine, and among these, interleukin is the substancemost closely connected to the immune system. It was the study ofinterleukin which researchers around the world were competing toundertake.

(6) Design all programs as filters:
The basis of software is not to generate data but to process it. The programs should
be designed as filters.

It was immunology, a field in which cutthroat competition was
already underway, that Dr. Kishimoto who graduated from Osaka
University, Graduate School of Medicine, in 1969, decided to aim for.

The catalyst for his decision was in his 5th year of
medical school when heheard the lecture by thelate Yuichi Yamamura, apioneer in immunologicalresearch in Japan. He wasintrigued by the discourse
about autoimmune disorders where the immune
system, which should protect our bodies from pathogens, revolts and attacks
our bodies.

Figure Functions of lymphocyte-produced interleukin - 6
Conceptual diagram of cytokine eﬀects

Interleukin - 6 involvement in rheumatoid arthritis
Inﬁltration into the bonemarrow tissue

Cytokine
Receptor

Activation of T cells

Cell membrane

Stimulation of
the intercellularsignaling mechanism

Expression andcontrol of intranuclear
genes

Cellular level
Cellular growth induction
Cellular differentiation induction
Cell death induction Control of cellular functions

Thrombocytosis
Megakaryocyte
maturation
IL- 6

liver
Acute inflammatory
protein induction

CRP, ﬁbrinogen increase
Hypoalbuminemia
SAA elevation
Secondary amyloidosis
Rheumatism factor
production,
Hypergammaglobulinemia

Activation of B cells

Dr. Kishimoto studied
Bone resorption
Individual levelfor 4 years from 1970 at
Inflammation/allergy Immunity/biological defense
Activation of osteoclastic cells
Morphogenesis
Hematopoietic system
the Johns Hopkins UniverIt has been made clear that interleukin 6 has various cytokine effects.
Endocrine system
Nervous systemsity in Baltimore, U.S.,
Among them, the above effects are thought to be associated with the
Various diseases
onset of rheumatoid arthritis.
under Professor Kimishige
Ishizaka (the 2000 Japan
Prize Laureate), who discovered immunoglobulin E. After returnApplication of research results to the therapeutic drug foring to Japan, he became an assistant at Osaka University, Facultyrheumatoid arthritis
of Medicine, and in 1975, he was able to do research for 3 months
After the success of gene cloning, by means of the genetic modiunder Robert Good, the Director of Laboratory at the Memorial
fication technique, a highly pure IL-6 was obtained, and progress
Sloan-Kettering Cancer Center, who was closely following
was also seen in the clarification of its mechanism. The research
Dr. Kishimoto’s research. During that short period, he discovered agroup with both doctors as core members also identified the strucnew interleukin candidate substance which generates from T-cells
ture of the IL-6 receptor. In addition, they explained the intraceland creates antibodies within B-cells. The research results thereofluar signals which transmit IL-6 information to the cell nucleus.
were posted and published in a British science magazine “Nature.”
By publishing various articles about the IL-6 mechanisms one after
Success in gene cloning after much hardshipanother, they became the world’s leading researchers in this field.
All seemed smooth sailing, but it was only the beginning ofresearch for Kishimoto. The characteristic of cytokine is that
What proved fortunate for both doctors was that as the research
one type has many combined functions, and there are many comprogressed, it became evident that IL-6 not only enhances antibody
panions with overlapping functions. Even if the biological activiproduction, but also has a wide variety of functions. For example,
ties of the discovered substance were studied, it would be difficult
it has a mechanism for stimulating the production of protein within
to prove whether it was really a new substance. The academic
the liver (CRP) when an acute inflammation occurs in the body. It
society only acknowledged a new substance if the gene which crealso has a mechanism for increasing platelets within the bloodates a substance is extracted singularly (cloning).
components which coagulate blood in the event of an injury. Thereis also a mechanism for thickening heart muscles. The more
What provided a boost to Dr. Kishimoto who was in search ofresearch is done, the more functions are discovered, thus contributthe gene of the discovered substance, was the establishment of theing to the progress of medicine.
Institute for Molecular and Cellular Biology at Osaka University in
1982, which became the center of bioscience. In the following
Particularly noteworthy was the discovery that IL-6 is involved
year, Dr. Kishimoto, who became a professor at the above institute,in the onset of rheumatoid arthritis, which is representative of autowelcomed Dr. Hirano as his research partner. Dr. Hirano graduimmune disorders. The two doctors had already noted from anated the Faculty of Medicine at Osaka University and went on toearly stage of their research that IL-6 is deeply involved in the
study immunology at the National Institute of Health (NIH) at
inflammatory reactions within the body, but it was newly discovBaltimore, U.S., so they had been acquaintances from their days inered that a large quantity of IL-6 exists in the joint fluid of rheumathe U.S. Moreover, Dr. Hirano, after returning to Japan, had been
toid arthritis patients. From this discovery, an important result wascontinuing his research at Habikino Hospital and the School of
obtained about its pathogenic mechanism.
Medicine at Kumamoto University, and had independently discovered interleukin and was working on the cloning.
Both doctors are currently involving themselves diligently inresearch activities. Dr. Kishimoto, based on basic research, has
Both doctors adopted the leading-edge genetic engineering techjointly developed, with a pharmaceutical company, an antibody
niques and continued in their gene hunt. They were unable todrug Tocilizumab which inhibits IL-6 action. After being
obtain the desired results, and continued in their low-profile experiapproved in Japan in 2008, the drug has become approved in 70
ments for days and then for years, often struggling with frustration.
countries worldwide including Europe and U.S. Dr. Hirano
However, in May, 1986, they finally succeeded in capturing a pardefined the mechanism of the onset of autoimmune diseases inticular gene. In 1988, at the international conference, the nameaddition to discovering that IL-6 plays a vital role in the initialinterleukin 6 (IL-6) which meant that this was the 6th interleukinstage of the emergence of fish. Research originating from thethat the two professors cloned, was given.
discovery of IL-6 has broadened its horizons from leading-edge
medicine to bioscience.

"Information and Communications" field
Achievement: Development of the operating system, UNIX

Dr. Dennis M. Ritchie

Born : September 9, 1941 (Age 69)
Distinguished Member of Technical Staff Emeritus, Bell Labs

Dr. Ken L. Thompson

Born : February 4, 1943 (Age 67)
Distinguished Engineer, Google Inc.

Summary

With present computer systems, basic software called operating
systems are used in addition to application software to perform word
processor, spreadsheet tasks, and so on. Dr. Dennis Ritchie and
Dr. Ken Thompson developed an advanced operating system called
UNIX in 1969. The operating systems in those days were increasingin scale but becoming complex and disorderly. With UNIX, stability
and high-speed performance could be attained by combining modularized programs. UNIX’s superior design concept has been carriedon by many computer technicians, and has supported the development of an advanced information society including the Internet.

Operating systems which make user-friendly computers possible

With present computers, multiple software usually functions hierarchically (Figure 1). For example, application software works closest to the user in operating a spreadsheet or in processing photographs. The operating system works in between the application software and hardware (machine). The role of the operating system is tomake the hardware which includes the hard disk constituting thecomputer abstract and present it to the application software. Thanks
to it, the application software can simplify such commands as“record data” or “print.” In addition, the operating system can
execute multiple tasks concurrently and also perform basic tasks
such as connecting to the network.

Figure 1 Software hierarchical diagram
Users (people)

The early computers which appeared on the scene in the 1940’s
did not, in fact, have an operating system. In the 1950’s, programs
came to be used as tools to simplify hardware usage, which established the concept of an operating system. Then in the 1960’s, computer developers were competing to upgrade the operating system
functions. In those days, large-scale and high-speed computers wererapidly being developed, and a time sharing system was achieved
where one high performance computer was used concurrently bymultiple persons. In order to improve the user-friendliness of thesecomputers, the development of an operating system became indispensable.
In the U.S. in 1964, Massachusetts Institute of Technology (MIT),in collaboration with Bell Labs and General Electric (GE), began ajoint research project to develop a time sharing operating systemcalled Multics. Multics aimed to use the capacity of highperformance computers to the full, in order to achieve an interactive
user interface that could be used like a telephone or electricity,which was a breakthrough system back then.
Dr. Ritchie and Dr. Thompson, both of whom were then in their20’s, were among those who participated in the project as researchers of Bell Labs. Dr. Ritchie was developing an efficient programming language for Multics, and Dr. Thompson came up with the ideaof a hierarchical filing (document management) system which later
became the core technology for UNIX. However, between 1968 and1969, Bell Labs decided to withdraw from Multics development.
The verdict reached by Bell Labs was that Multics, in pursuingideals, had become too massive and complex, and not much hope
could be held for the overall system performance.

In want of making their own operating system

The development of Multics at Bell Labs was discontinued, but
Dr. Thompson and his colleagues who were deeply involved in thedevelopment carried on independent research. They felt they did notwant to lose the convenient user interface which Multics provided at
its development stage, and began to search for an alternative system.
In particular, Dr. Thompson was very fond of an interactive computer game called “Space Travel” that he programmed himself.

Figure 2 UNIX philosophy(1) Small is beautiful:

Small things have advantages that large things do not have. By separating the
programs into small modules as much as possible, they can be used in combinations.

(2) One program with one function:
application

Programs separated into small modules should each have one definite and reliable
function.

(3) More emphasis on portability than efficiency:

Rather than having maximum capabilities on one particular hardware, by maximizing
functions on as many computers as possible, the computer environment is enhanced.

(4) Emphasis on data portability:
operating system

Even if the program is portable, information cannot be shared. All number data
should be stored in ASCII flat files.

(5) Avoid excessive interactivity:

Data flow is disrupted during the time users are interacting. Aim to achieve amoderately interactive interface.

hardware(6) Design all programs as filters:

The basis of software is not to generate data but to process it. The programs should
be designed as filters.

Thus, he ported the computer game into an old computer (DEC’s
PDP-7) which was lying idle at the laboratory . With Dr. Ritchie’s
help, he gradually added functions in Multics which were thought tobe particularly important. Dr. Thompson’s filing system which wasleft in limbo was also ported, and by 1969, it came to have an
appearance of a new operating system. In the process, this operating
system came to be known among the staff as UNICS. The name was
supposedly given to emphasize its compact and single layer (UNIplex) image in contrast to Multics’ massive and multilayer(Multiplex) image.
In time, the spelling of UNICS became UNIX, and its superior
functions became known to researchers as well. In addition tohaving a hierarchical filing system that enables a quick search ofdesired information, because its basic parts were developed by ahandful of people, it was a simple yet relatively trouble-free, solid
operation system. In 1970, it was ported to a higher performancecomputer (PDP-11), and Bell Labs’ patent department became oneof its users.
The next issue which the now highly-evaluated UNIX faced, was
the improvement of the programming language. From his
experience with Multics, Ritchie felt the need for a “high-level
language” programming with a higher abstraction level ofcommands. Dr. Ritchie along with Dr. Thompson were jointly
developing B language, but they completed the improved version,
the C language, and in 1973, UNIX was rewritten in the C language.
Through this development, it became possible for UNIX to be usedin computers around the world. In 1974, both doctors publishedtheir long-awaited UNIX article, and UNIX became known
worldwide.

An open culture achieved by UNIX

Both UNIX and the C language which were developed by both
doctors greatly influenced the information science in later years. In
those days, Bell Labs provided free-of-charge UNIX and the sourcecode (number sequence indicating basic commands to the hardware)to universities and research institutes; thus they were usedproactively by researchers around the world. UNIX has created an
open culture where researchers share ideas among themselves, which
in turn, leads to new developments. As bamboo shoots after the rain,
design concepts which sprung up one after the other has been handed
down as UNIX philosophy. Many improvements have also been
made to the C language, and many operating systems today havebeen written in the C language from the beginning.
In retrospect, many basic technologies in the information field
have been conceived with UNIX as the basis. Noteworthy of them isthe Internet. University of California, Berkeley developed BSD
UNIX, which is the extended version of the Version 6 UNIX
functions. From this, Internet protocol (TCP/IP)-mounted UNIX
originated, greatly contributing to the realization of the Internet.
At present, there is a license system where certain regulations areapplied to UNIX usage. However, “open source,” which is a method
where the source code is disclosed while protecting the copyright ofthe software producer, is also under parallel development. Operating
systems carrying on the UNIX philosophy are now being usedwidely from mobile phones to supercomputers.

"Bioscience and Medical Science" field
Achievement: Discovery of interleukin - 6 and its
application in treating diseases

Dr. Tadamitsu Kishimoto

Born: May 7, 1939 (Age 71)
Emeritus Professor, Osaka University

Dr. Toshio Hirano

Born: April 17, 1947 (Age 63)
Professor, Osaka University

Summary

Our bodies detect external invasions of bacteria and viruses andeliminate them. This mechanism is called “immunity.” Immunity is
a complex system consisting of various cells such as lymphocytes(T-cells, B-cells) and macrophage, but the substance which plays animportant role in transmitting information between cells is calledinterleukin. Dr. Tadamitsu Kishimoto and Dr. Toshio Hirano havepurified interleukin 6 (IL-6), which plays a vital part in the production of antibodies, and also succeeded in gene cloning in 1986. In
addition, the two doctors have identified a wide range of functions of
IL-6 and their research results have contributed to the progress ofbioscience and the development of therapeutic drugs for inflammatory diseases.

In quest of a substance which transmits immune cell commands

The knowledge that the human body has an immune system
which, once exposed, builds in us resistance to a certain illness, hasbeen long-established. Modern medicine started off with researchers
confronted with the challenge of revealing what the immune system
is. At the end of the 19th Century, Shibasaburo Kitazato andGerman physician Behring conducted research on the serum therapyof tetanus and diphtheria and discovered that a substance whichattacks the pathogen is formed within the body once we are exposed
to such infectious diseases. Thus, the concept of the immune system
where the antibodies recognize and eliminate antigens was established. Around the same period, Russian microbiologist Mechnikov
claimed that leukocytes within the blood attack pathogens such asbacteria in a mechanism called “phagocytosis,” thus establishing thefoundations of immunology.
Coming into the 20th Century, the characteristics of antibodies as
substances were clarified and in a wider sense, the immune systemcame to be identified as a complex system made up of a wide varietyof cells including companions of leukocytes such as lymphocytes,
macrophage and dendritic cells. It was not until the late 1960’s thatthe research regarding the essence of the immune system proceeded
rapidly. It was then discovered that there were two types of lymphocytes, namely T-cells and B-cells, and that it was by mutual transmission of information between these two cell types that enabled thevarious antibodies to be produced efficiently. By defining thesignaling mechanism, knowledge about the complex immune system
can be acquired. The protein used to transmit information among thecells is called cytokine, and among these, interleukin is the substancemost closely connected to the immune system. It was the study ofinterleukin which researchers around the world were competing toundertake.
It was immunology, a field in which cutthroat competition was
already underway, that Dr. Kishimoto who graduated from Osaka
University, Graduate School of Medicine, in 1969, decided to aim for.

The catalyst for his decision was in his 5th year of
medical school when heheard the lecture by thelate Yuichi Yamamura, apioneer in immunologicalresearch in Japan. He wasintrigued by the discourse
about autoimmune disorders where the immune
system, which should protect our bodies from pathogens, revolts and attacks
our bodies.

Figure Functions of lymphocyte-produced interleukin - 6
Conceptual diagram of cytokine eﬀects

Interleukin - 6 involvement in rheumatoid arthritis
Inﬁltration into the bonemarrow tissue

Cytokine
Receptor

Activation of T cells

Cell membrane
Stimulation of
the intercellularsignaling mechanism

Expression andcontrol of intranuclear
genes

Cellular level
Cellular growth induction
Cellular differentiation induction
Cell death induction Control of cellular functions

Thrombocytosis
Megakaryocyte
maturation
IL- 6

liver
Acute inflammatory
protein induction

Activation of B cells

CRP, ﬁbrinogen increase
Hypoalbuminemia
SAA elevation
Secondary amyloidosis
Rheumatism factor
production,
Hypergammaglobulinemia

Dr. Kishimoto studied
Bone resorption
Individual levelfor 4 years from 1970 at
Inflammation/allergy Immunity/biological defense
Activation of osteoclastic cells
Morphogenesis
Hematopoietic system
the Johns Hopkins UniverIt has been made clear that interleukin 6 has various cytokine effects.
Endocrine system
Nervous systemsity in Baltimore, U.S.,
Among them, the above effects are thought to be associated with the
Various diseases
onset of rheumatoid arthritis.
under Professor Kimishige
Ishizaka (the 2000 Japan
Prize Laureate), who discovered immunoglobulin E. After returnApplication of research results to the therapeutic drug foring to Japan, he became an assistant at Osaka University, Facultyrheumatoid arthritis
of Medicine, and in 1975, he was able to do research for 3 months
After the success of gene cloning, by means of the genetic modiunder Robert Good, the Director of Laboratory at the Memorial
fication technique, a highly pure IL-6 was obtained, and progress
Sloan-Kettering Cancer Center, who was closely following
was also seen in the clarification of its mechanism. The research
Dr. Kishimoto’s research. During that short period, he discovered agroup with both doctors as core members also identified the strucnew interleukin candidate substance which generates from T-cells
ture of the IL-6 receptor. In addition, they explained the intraceland creates antibodies within B-cells. The research results thereofluar signals which transmit IL-6 information to the cell nucleus.
were posted and published in a British science magazine “Nature.”
By publishing various articles about the IL-6 mechanisms one after
Success in gene cloning after much hardshipanother, they became the world’s leading researchers in this field.
All seemed smooth sailing, but it was only the beginning ofresearch for Kishimoto. The characteristic of cytokine is that
What proved fortunate for both doctors was that as the research
one type has many combined functions, and there are many comprogressed, it became evident that IL-6 not only enhances antibody
panions with overlapping functions. Even if the biological activiproduction, but also has a wide variety of functions. For example,
ties of the discovered substance were studied, it would be difficult
it has a mechanism for stimulating the production of protein within
to prove whether it was really a new substance. The academic
the liver (CRP) when an acute inflammation occurs in the body. It
society only acknowledged a new substance if the gene which crealso has a mechanism for increasing platelets within the bloodates a substance is extracted singularly (cloning).
components which coagulate blood in the event of an injury. Thereis also a mechanism for thickening heart muscles. The more
What provided a boost to Dr. Kishimoto who was in search ofresearch is done, the more functions are discovered, thus contributthe gene of the discovered substance, was the establishment of theing to the progress of medicine.
Institute for Molecular and Cellular Biology at Osaka University in
1982, which became the center of bioscience. In the following
Particularly noteworthy was the discovery that IL-6 is involved
year, Dr. Kishimoto, who became a professor at the above institute,in the onset of rheumatoid arthritis, which is representative of autowelcomed Dr. Hirano as his research partner. Dr. Hirano graduimmune disorders. The two doctors had already noted from anated the Faculty of Medicine at Osaka University and went on toearly stage of their research that IL-6 is deeply involved in the
study immunology at the National Institute of Health (NIH) at
inflammatory reactions within the body, but it was newly discovBaltimore, U.S., so they had been acquaintances from their days inered that a large quantity of IL-6 exists in the joint fluid of rheumathe U.S. Moreover, Dr. Hirano, after returning to Japan, had been
toid arthritis patients. From this discovery, an important result wascontinuing his research at Habikino Hospital and the School of
obtained about its pathogenic mechanism.
Medicine at Kumamoto University, and had independently discovered interleukin and was working on the cloning.
Both doctors are currently involving themselves diligently inresearch activities. Dr. Kishimoto, based on basic research, has
Both doctors adopted the leading-edge genetic engineering techjointly developed, with a pharmaceutical company, an antibody
niques and continued in their gene hunt. They were unable todrug Tocilizumab which inhibits IL-6 action. After being
obtain the desired results, and continued in their low-profile experiapproved in Japan in 2008, the drug has become approved in 70
ments for days and then for years, often struggling with frustration.
countries worldwide including Europe and U.S. Dr. Hirano
However, in May, 1986, they finally succeeded in capturing a pardefined the mechanism of the onset of autoimmune diseases inticular gene. In 1988, at the international conference, the nameaddition to discovering that IL-6 plays a vital role in the initialinterleukin 6 (IL-6) which meant that this was the 6th interleukinstage of the emergence of fish. Research originating from thethat the two professors cloned, was given.
discovery of IL-6 has broadened its horizons from leading-edge
medicine to bioscience.

Nominations and Selection Process■

Every November the Fields Selection Committee of the Japan Prize Foundation designates and announces two fields
in which the Japan Prize will be awarded two years hence. At the same time, the Foundation calls for over 13,000
nominators, strictly comprised of prominent scientists and researchers from around the world invited by theFoundation, to nominate the candidates through the web by JPNS (Japan Prize Nomination System). The deadline fornominations is the end of February of following year.

■

For each field, a Selection Subcommittee conducts a rigorous evaluation of the candidates’ academic achievements. The
conclusions are then forwarded to Selection Committee, which conducts evaluations of candidates’ achievements from awider perspective, including contributions to the progress of science and technology, and significant advancement
towards the cause of world peace and prosperity, and finally the selected candidates are recommended for the Prize.

■

The recommendations are then sent to the Foundation’s Board of Directors, which makes the final decision on the winners.

■

The nomination and selection process takes almost one year from the time that the fields are decided. Every January,
the winners of that year’s Japan Prize are announced. The Presentation Ceremony is held in mid-April in Tokyo.

November, 2009

End February, 2010

Determinethe fields eligible
for the 2011
Japan Prize
Information andCommunications

January, 2011

Mid. April, 2011

Announce
the Lauretatesof the 2011
Japan Prize

The 2011
Japan Prize
Presentation
Ceremony

Selection Committee

Invite thenominations

Closing of thenominations

Bioscience andMedical Science

Information andCommunications
Selection Subcommittee

Board ofDirectors

Bioscience andMedical Science
Selection Subcommittee

Members of the 2011 Japan Prize Selection Committee
Member Makoto Asashima

Director and Fellow, Research Center for Stem Cell Engineering,
National Institute of Advanced Industrial Science and Technology

Member Kunio Iwatsuki

Director, The Museum of Nature andHuman Activities, Hyogo

ChairmanVice Chairman

Hiroshi Komiyama

Ryozo Nagai

Chairman of the Institute,
Mitsubishi ResearchInstitute, Inc.

Professor, Graduate
School of Medicine,
The University of Tokyo

Member Yoshio Karita

Director, The Japan Prize Foundation

Member Masafumi Maeda

Managing Director, Executive Vice President,
The University of Tokyo

Member Masayuki Matsushita

Director, The Japan Prize Foundation

Member Makoto Misono

Chairman, PO Academy,
Japan Science and Technology Agency

Member Hideo Miyahara

President, National Institute of Information andCommunications Technology

Member Takehiko Sasazuki

University Professor,
Institute for Advanced Study, Kyushu University

Selection subcommittee for the “Information and Communications” field
Member Tomonori Aoyama

Professor, Graduate School of Media andGovernance, Keio University

Member Toru Ishida

Chairman

Deputy Chairman

Hideo Miyahara

Shojiro Nishio

President, National Instituteof Information andCommunications Technology

Trustee and Vice President,
Osaka University

Professor, Graduate School of Informatics,
Kyoto University

Member Masaru Kitsuregawa

Executive Director, Earth Observation Data Integration &Fusion Research Initiative (EDITORIA), The University of Tokyo

Member Masayuki Murata

Professor, Graduate School of Information Scienceand Technology, Osaka University

Member Hidehiko Tanaka

Dean, Professor, Graduate School of Information
Security, Institute of Information Security

Member Yoh'ichi Tohkura

Professor, Deputy Director General, National Instituteof Informatics

Member Hiroto Yasuura

Professor, Executive Vice President,
Kyushu University

Member Akinori Yonezawa

Professor, Graduate School of Information Scienceand Technology, The University of Tokyo

Selection subcommittee for the “Bioscience and Medical Science” field
Member Masato Kasuga

Director-General, Research Institute,
National Center for Global Health and Medicine

Member Kunio Matsumoto

Deputy Director, Cancer Research Institute,
Kanazawa University

Chairman

Deputy Chairman

Makoto Asashima

Kohei Miyazono

Director and Fellow,
Research Center for
Stem Cell Engineering,
National Institute ofAdvanced Industrial
Science and Technology

Professor,
Graduate School of Medicine,
The University of Tokyo

Member Hiroaki Mitsuya

Professor, Faculty of Life Sciences,
Kumamoto University

Member Shimon Sakaguchi

Director, Institute for Frontier Medical Sciences,
Kyoto University

Member Toshio Suda

Professor, School of Medicine, Keio University

Member Naoyuki Taniguchi

Endowed Chair Professor, The Institute of Scientificand Industrial Research (ISIR), Osaka University

Member Shigeo Ohno

Professor, Graduate School of Medicine,
Yokohama City University

Member Hitoshi Okamoto

Deputy Director,
Brain Science Institute, RIKEN

Member Noriko Osumi

Professor,
Tohoku University School of Medicine

Advisor Yukihide Tomari

Associate Professor, Institute of Molecular andCellular Biosciences, The University of Tokyo

Advisor Chikashi Toyoshima

Professor, Institute of Molecular and Cellular
Biosciences, The University of Tokyo( alphabetical order, titles as of December, 2010)

Fields for the 2012 Japan Prize Selected
Area of StudiesⅠ
mathematics, physics,
chemistry and engineering

Fields eligible for the award: Environment, Energy and Infrastructure

Background and rationale:

In recent years, the increase in resource and energy consumption and the destruction of the natural environment caused by various humanactivities have reached a level that is no longer ignorable, prompting negotiations for environmental protection measures on a global scale.
A strong need has thus been reaffirmed for innovation in fundamental technologies that profoundly influences the global environment. They
include technologies for energy production and utilization, material production, water resource management, urban development, physicaldistribution and transportation. Particular importance lies in the promotion of energy saving across civil life and industry, exploitation ofalternative energy resources and new production technology under resource and environmental constrains. Moreover, scientific advancement
and innovation in disaster mitigation and safety measures is another important target for the development of the social infrastructure.

Achievement eligible:

The 2012 Japan Prize in the fields of “Environment, Energy, and Infrastructure” is awarded to individuals who have made significant
contributions to society by achieving momentous scientific and technological breakthroughs in creation, innovation and propagation oftechnologies that are related to environmental protection, energy, environmentally benign production and social infrastructure, thereby
improving and protecting the global environment.

Area of Studies Ⅱ
biology, agriculture andmedical science

Fields eligible for the award: Healthcare and Medical Technology

Background and rationale:

Over the past few decades, dramatic progress has been made in diagnostic accuracy of diseases and physical functions. This has been due tothe advancements of science and technology in the field of diagnostic imaging instrument, information based medical technology, and moreover,the medical diagnostic technology and biochemical-based diagnosis methods based upon the study of genetics.
In addition to the advancements in diagnosis technology, innovations in medical treatment technique including minimally invasive surgery andradiation therapy have improved the curability rate of many diseases, thereby significantly contributing to the well-being of people. Furthermore,even greater developments are being anticipated in the field of medicine, such as diagnostic technology for early detection of diseases,
epoch-making drug discovery and regenerative medicine.
With a rapidly aging population, maintaining and improving health and disease prevention has become increasingly important for the preservationof social vitality. As a result, there are high expectations for further development and advancement of the science and technology in this field.

Achievement eligible:

The 2012 Japan Prize in the fields of “Healthcare and Medical Technology” is awarded to individuals who have made significant
contributions to society by achieving momentous scientific and technological breakthroughs in creating and promoting new technologies
for medical diagnosis and treatment, and those contributing to maintenance and furtherance of our health and disease prevention.

Fields Selection Committee for the 2012 Japan Prize
Member Kazuhito Hashimoto

Professor, Graduate School of Engineering,
The University of Tokyo

Member Noriko Osumi

Member Yoshihiro Hayashi

ChairmanVice Chairman

Yoshio Yazaki

Katsuhiko Shirai

President,
National Hospital
Organization

Former President,
Waseda University

Member Kenichi Mori

Professor, Graduate School of Management of Science andTechnology, Tokyo University of Science

Professor, Human and Animal-Plant Relationships,
Tokyo University of Agriculture

Member Nobuhide Kasagi

Professor, Graduate School of Engineering,
The University of Tokyo

Member Tsutomu Kimura

Professor,
Tohoku University School of Medicine

Member Masakatsu Shibasaki

Executive Director of Board of Directors,
Microbial Chemistry Research Foundation

Member Atsuko Tsuji

Advisor to the Minister of Education,
Culture, Sports, Science and Technology

Editorial writer, The Asahi Shimbun

Member Hiroshi Kuwahara

Senior Advisor Emeritus, Hitachi Maxell, Ltd.

( alphabetical order, titles as of December, 2010)

Schedule (2013-2015)
The fields eligible for the Japan Prize (2013 to 2015) have been decided for the two research areas, respectively.
These fields rotate every three years, basically.
Every year the Fields Selection Committee announces the eligible fields for the next three years.
Areas of Physics, Chemistry and Engineering

Areas of Life Science, Agriculture and Medicine

Year

Eligible Fields

Year

Eligible Fields

2013
2014
2015

Materials, Production
Electronics, Information, Communication
Resources, Energy, Social Infrastructure

2013
2014
2015

Biological Production, Biological Environment
Life Science
Medical Science, Medicinal Science※ As of October 1, 2010, The Science and Technology Foundation of Japan changed its name to “THE JAPAN PRIZE FOUNDATION” .