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Linda Buck named recipient of Nobel Prize in "Medicine or Physiology" on October 4, 2004.
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On October 4, 2004, Linda Buck (b. 1947), of Seattle's Fred Hutchinson Cancer Research Center, is named as a recipient of the Nobel Prize for Medicine or Physiology. Buck shares the award with Richard Axel, director of the laboratory at Columbia University where the winning research was conducted. The prize is awarded in recognition of Buck's and Axel's unraveling of many of the mysteries of the sense of smell, first set forth in a 1991 paper published in the journal Cell. In 2002, Buck, a Seattle native, returns to the city of her birth to continue her investigations at the Fred Hutchinson Cancer Research Center. She will receive her Nobel at a ceremony in Stockholm, Sweden, on December 10, 2004. Both at Columbia and in Seattle, her research is funded in large part by the Howard Hughes Medical Institute.
Linda Brown Buck was born in Seattle on
January 29, 1947, daughter of a homemaker mother and a father who was an
electrical engineer. Buck credits her parents with instilling in her the
curiosity and work ethic that would propel her career in the sciences:
"My father was an electrical
engineer who, at home, spent much of his time inventing things and building
them in our basement. It may be that my parents' interest in puzzles and
inventions planted the seeds for my future affinity for science, but I never
imagined as a child that I would someday be a scientist ... .
"I learned to appreciate music and
beauty from my mother and my father taught me how to use power tools and build
things ... .
"I was fortunate to have
wonderfully supportive parents who told me that I had the ability to do
anything I wanted with my life. They taught me to think independently and to be
critical of my own ideas, and they urged me to do something worthwhile with my
life ..." ("Autobiography").
Buck attended the University of
Washington, where she earned a joint bachelor's degree in psychology and
microbiology, graduating in 1975. She considered a career as a psychotherapist,
but spent the next several years living on an island near Seattle, traveling,
and taking a variety of college courses while trying to map her future course. One
of these, a class in immunology, grabbed her interest, and Buck decided to pursue
a career in biology. In 1975 she entered the graduate program in microbiology at
the University of Texas Southwest Medical Center in Dallas, which shortly
before had expanded its research program in immunology.
A Life in Science
Buck's research and thesis at UT studied
B lymphocytes, a component of the human body's immune system. She focused her
research on the function of molecules in the immune response at the cellular
level and was awarded her Ph.D. in immunology in 1980. She then moved on to a
position in post-doctoral research at the Howard Hughes Medical Institute at Columbia
University, New York, working with Dr. Benvenuto Pernis (1923-2011). Pernis,
born in Florence, Italy, was one of the first scientists to conduct fundamental
research in the biology of immune-system lymphocytes and was a key player in
the founding of the famed Basel Institute for Immunology in Switzerland. Buck's
research focused on a class of proteins found on the surface of B lymphocytes.
Put in the most basic terms, the significance of her research was the finding
that, contrary to expectations, the class of proteins under study were being taken
into the interior of a cell and then -- probably -- recycled back to
the cell's surface.
Buck worked under Pernis until 1984.
Then, realizing that the path her interests were taking her required a deeper
knowledge than she possessed of the techniques used to study molecular biology, she moved
to another lab at Columbia. Here, she worked as a postdoctoral fellow with Richard
Axel, M.D., a researcher and professor at the Columbia University College of Physicians and Surgeons. It was the
research they did together that would lead, many years later, to the Nobel
The Sense of Smell
her research in Axel's laboratory trying
to develop a technique for cloning genes expressed by specific neurons (nerve
cells) in Aplysia, a genus of
sea slug. This was to be valuable groundwork for her later accomplishments. As
"During this period, I learned a
lot of molecular biology from Richard and other members of his lab ... . I was
grateful that Richard was tolerant of my high-risk endeavors. He was an unusual
mentor in that he gave people in his lab extensive independence in charting
their own course once they had established themselves"
the end of her sea-slug studies, Buck came upon a 1985 research publication
that, in her words, "changed my life" ("Autobiography"). In
it, prominent neuroscientist Sol Snyder (b. 1938) of Johns Hopkins, discussed
possible mechanisms underlying the ability to detect odors. As Buck explains:
"This was the first time I had ever thought about
olfaction and I was fascinated. How could humans and other mammals detect
10,000 or more odorous chemicals, and how could nearly identical chemicals
generate different odor perceptions? In my mind, this was a monumental puzzle
and an unparalleled diversity problem. It was obvious to me that the first step
to solving the puzzle was to determine how odorants are initially detected in
the nose. This meant finding odorant receptors, a class of molecules that had
been proposed to exist, but had not been found. I decided that this is what I
had to do ..."
In 1988 Buck,
working directly with Axel, turned her attention to the sense of smell, trying to
answer a basic question that had defied resolution: "How does the brain know what the nose is
smelling?" ("Richard Axel, M.D."). Studying both fruit flies (the
workhorses of genetic research) and mammals, the two discovered that at least
100, and probably many more, separate genes are responsible for encoding development
of the odor receptors found in the lining of nasal cavities. What was even more
surprising was the similarity of the olfactory mechanism in two such disparate
classes of life -- insects and mammals. This indicated to Buck and Axel
that, genetically speaking, the mechanisms of smell were extremely ancient, and that "the basic principles of odor
discrimination ... have been conserved over 500 million years" ("Richard
The odor receptors in nasal cavities are responsible for detecting odorants (chemical
compounds having an odor). Buck and Axel mapped the biological pathway for the
sense of smell, and established that the large family of genes responsible for
coding the receptors created a sense of smell that could detect and
discriminate among as many as 10,000 different odors. In 1991, Buck and Axel
published their research results in Cell magazine
in an article entitled "A Novel Multigene Family May Encode Odorant
Receptors: A Molecular Basis For Odor Recognition." This was the work for
which the Nobel Prize was awarded 13 years later. The award citation stated
that the two were honored "for
their discoveries of odorant receptors and the organization of the olfactory
The research article
by Buck and Axel created a stir in scientific circles almost immediately. A
1991 article in The Seattle Times sought to explain why the discovery
was deemed important:
"Strong-smelling substances called
pheromones play a role in insect behavior and reproduction. Learning how those
substances are detected could lead to new means of inhibiting insect
"Before this study, researchers had disagreed about whether smell was
governed by a few genes or a large number. The study suggests that 100 to 200
genes may be involved, Buck and Axel said.
"'The number of genes, if it holds up to be true, is phenomenal,'"
said [Charles ] Wysocki, an authority on the biology and psychology of smell.
'''It makes it now one of the largest related families of genes that's been
"He said the research is 'literally going to open up whole new fields. It's
going to draw people who never even thought of doing work with the sense of
"Odors are detected by tiny tubular extensions on nerve cells high in the
nasal cavity, Buck said. The extensions, called cilia, are believed to be the
location of molecules called receptors. Odor molecules are believed to slip
into receptors as a key slips into a lock" ("Nose Knows Smells Thanks
To Gene Group, Research Finds").
Subsequent research determined that each
odor-sensing cell in the nose possesses only one type of odorant receptor,
which can detect a limited range of specific odors. From here, Buck and her fellow
researchers were able to learn how different odors are perceived by the brain,
and they discovered a "sensory map" for the sense of smell that is
virtually identical in all humans, located in an area of the brain called the
Moving On, Moving Back
After completing the research with Axel,
but long before winning the Nobel, Buck stayed in academia. From 1991 to 1996
she was an assistant professor in the Department of Neurobiology at Harvard
Medical School in Boston, becoming an associate professor in 1996 and a full
professor in 2001. Contemporaneous with her professorships, Buck continued her association
with the Howard Hughes Medical Institute, first as an assistant investigator
and, after 2001, as a full investigator. She continued her research on the
sense of smell, while also tackling other subjects, including the sense of
In 2001, Buck moved back to Seattle,
becoming a member of the basic sciences division at Fred Hutchinson Cancer
Research Center and an affiliate professor of physiology and biophysics at her
alma mater, the University of Washington. In 2003, the year before receiving
the Nobel, she was elected to the National Academy of Sciences, and in that
same year was awarded, together with Axel and others, the prestigious Canada
Gairdner International Award. She received the Nobel at a ceremony in Stockholm, Sweden, on December 10, 2004, the anniversary of Alfred Nobel's (1833-1896) death. This was followed in 2006 by her induction into
the Institute of Medicine, considered one of the highest honors in the field.
A Scientist's Worst Nightmare
Buck's professional reputation seemed
under threat in 2008 when she and her coauthors withdrew a paper on the sense
of smell that was published in 2001 in the prestigious scientific journal, Nature, reporting that they had
discovered problems in the data and were unable to duplicate their findings. The
paper in question was written a decade after the work that had won the Nobel
Prize, and Buck and her colleagues were straightforward on the matter:
"In the retraction,
published by Nature on Thursday, the
researchers said, 'Moreover, we have found inconsistencies between some of the
figures and data published in the paper and the original data. We have
therefore lost confidence in the reported conclusions.'
"'It’s disappointing,' Dr.
Buck, who is now at the Fred Hutchinson Cancer Research Center in Seattle, told
the journal Nature in a news article
about the retraction. 'The important thing is to correct the literature'"
("Nobel Winner Retracts Research Paper").
The lead author on the
withdrawn study was a postdoctoral researcher from China, Zhihua Zou, described
as "the source for the paper's data and figures" ("Nobel Winner
Retracts Research Paper"). Zou, while expressing disappointment, did not
object to the withdrawal of the study and signed the notice of retraction. But
the discovery led Buck and her colleagues to review other work involving Zou,
and more problems were found.
Two years later, in
September 2010, Buck and her team announced the withdrawal of two additional
papers, one published in the Proceedings of the National Academy of Sciences in 2005 and the other in Science in 2006. The reasons were the same -- Buck and her team couldn’t reproduce
findings reported by Dr. Zou. This time, although he was the lead author on
both papers, Zou did not sign the notice of retraction. He had been laid off
from his position as an assistant professor at the University of Texas Medical
Branch in Galveston after the facility was extensively damaged by Hurricane Ike
in 2008. In 2010 a spokesman for UT indicated that Zou had returned to China, and
that his "current whereabouts ... are unknown" ("Nobel Laureate
Linda Buck Retracts Two Studies on Sense of Smell in Brain").
Throughout the ordeal,
there were neither allegations made nor evidence produced that Buck, or any
researchers other than Zou, bore responsibility for the withdrawn papers' questionable
data or irreproducible results. By promptly and forthrightly acknowledging the
problems and withdrawing the papers, Buck and her team fulfilled the ideal of
good science being self-correcting. Although unfortunate, the incidents have had
no lasting detrimental impact on Buck's reputation or her work.
Over her career, Buck has
received numerous awards and much recognition in addition to the Nobel Prize, including induction into the European
Academy of Sciences (2009), the State of Washington Medal of Merit (2007), and the University
of Washington's Distinguished Alumnus Award (2005). Today (2012) she continues
her research at the Hutchinson center, heading the eponymous Linda Buck Lab.
Buck continues to receive
funding from the Hughes institute, and she and her fellow researchers are still
studying the intricacies of the sense of smell, while also branching out into other
areas of scientific interest. In their own words:
"Our laboratory, led
by Linda Buck, Ph.D., is investigating the mechanisms that underlie the
sense of smell and pheromone sensing in mammals. One major question is how
humans and other mammals detect as many as 10,000 or more chemicals in the
external environment. Another is how the brain translates those chemicals into
different smells, such as rose or garlic. A third is how pheromones and
other social cues elicit hormonal changes and instinctive behaviors in animals
... . Our recent work has also touched on aging, particularly the
identification of drugs that might delay the onset of age-associated disease"
("Laboratory of Linda Buck, Ph.D").
In an autobiographical sketch
prepared for the Nobel Institute, Buck reflected on her life in science:
"Looking back over my
life, I am struck by the good fortune I have had to be a scientist. Very few in
this world have the opportunity to do everyday what they love to do, as I have.
I have had wonderful mentors, colleagues, and students with whom to explore
what fascinates me and have enjoyed both challenges and discoveries. I am
grateful for all of these things and look forward to learning what Nature will
next reveal to us.
"As a woman in
science, I sincerely hope that my receiving a Nobel Prize will send a message
to young women everywhere that the doors are open to them and that they should
follow their dreams" ("Autobiography").
"Autobiography," Nobel Prize website accessed
November 23, 2012 (http://www.nobelprize.org/nobel_prizes/medicine/laureates/2004/buck.html);
Giselle Weiss, "Closing of Basel
Institute Scatters Immunologists," Science, Vol. 293, No. 5528 (July 13, 2001), pp. 238-239; "Benvenuto
G. Pernis M.D.: Obituary," Boston
Globe website accessed November 25, 2012 (http://www.legacy.com/obituaries/bostonglobe/obituary.aspx?pid=154279752#fbLoggedOut); "Richard
Axel, M.D.," Howard Hughes Medical Institute website accessed November 25,
2012 (http://www.hhmi.org/research/investigators/axel_bio.html); "The Nobel
Prize in Physiology or Medicine 2004: Richard Axel, Linda B. Buck," Nobel
Prize website accessed November 25, 2012 (http://www.nobelprize.org/nobel_prizes/medicine/laureates/2004/); "Linda B. Buck PhD: Recipient of the
Canada Gairdner International Award, 2003," Gairdner Foundation website
accessed November 25, 2012 (http://www.gairdner.org/content/linda-b-buck); "Linda Buck," Howard Hughes
Medical Institute website accessed November 24, 2012 (http://www.hhmi.org/research/nobel/buck.html); "Nose
Knows Smells Thanks To Gene Group, Research Finds," The Seattle Times, April 5, 1991, p. A-4; "On the Move,"
Ibid., May 19, 2003, p. C-4; "Nobel
Winner Retracts Her Study," Science Digest," Ibid., March 7, 2008, p. A-8; Kenneth Chang, "Nobel Winner
Retracts Research Paper," The New
York Times, March 7, 2009 (http://www.nytimes.com/);
Elizabeth Lopatto, " Nobel Laureate Linda Buck Retracts Two Studies on
Sense of Smell in Brain," Bloomberg.com website accessed November 25, 2012
Note: This essay was slightly revised on October 19, 2014.
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Linda B. Buck (b. 1947), New York, June 2005
Photo by Betsy Devine, Courtesy Wikimedia Commons
Richard Axel M.D., New York, 2004
Courtesy Columbia University
Diagram, molecular configuration of various scents
Courtesy Linda Buck Lab, Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center, Seattle, May 19, 2007
HistoryLink.org photo by Paula Becker