History of Neurology Linda Buck, Ph.D. 1947-Present June 5th, 2017 KUMC Neurology Morning Report Richard J. Barohn, MD June 5th, 2017

Linda Buck, Ph.D. Biography YEAR ACHIEVEMENT 1947 B. Seattle, Washington 1975 B.S. in Psychology from Univ of Wash Father was a engineer, mother was a homemaker, solved puzzles 1980 PhD in Neuro-Immunology from UTSW - Dallas Moved to Columbia, NY Post-doc with Dr. Richard Axel at Columbia, Neuroscience 1st project – Kandel’s Aphysia lab; cloned gene in Aphysia in neuron Then began map of the olfactory process at the molecular level

Linda Buck, Ph.D. Biography Year ACHIEVEMENT 1991 Identified family of gene in rats That code for >1000 odor receptors –GI Paper Assistant Professor of Neurobiology, Harvard Med School 1993 Published: How Inputs from different odor receptors are organized in the nose 2002 Moved to Fred Hutchinson Cancer Research Center, Seattle

Linda Buck & Richard Axel A Novel Multigene Family May Encode Odorant Receptors: A Molecular Basis for Odor Recognition Landmark Paper Genes code for odorant sensors in olfactory neurons in nose Each receptor is a protein that changes when an odor attaches to the receptor, then sends signal to the brain Differences between odorant sensors under certain odors cause a signal to be sent to brain We then interpret varying sensory signals from our receptors as speech & sounds Buck, L. and Axel, R. (1991) Cell, 65, 175-187.

Linda Buck & Richard Axel A Novel Multigene Family May Encode Odorant Receptors: A Molecular Basis for Odor Recognition Showed olfactory receptors belong to family of G protein-coupled receptors Analyzed rat DNA & estimated there are approx. 1,000 different genes for olfactory receptors in mammalian genome Led to further work of genetic & molecular analysis of mechanisms of olfaction Each olfactory receptor neurons only expresses one kind of olfactory receptor protein Input from all neurons expressing the same receptor is collected by a single dedicated glomerulus of the olfactory bulb Buck, L. and Axel, R. (1991) Cell, 65, 175-187.

Linda Buck Ph.D. Awards Takasago Award for Research in Olfaction 1992 Takasago Award for Research in Olfaction 1996 Unilever Science Award 2003 Gairdner Foundation International Award  National Academy of Sciences 2004 Nobel Prize in Physiology in Medicine with Richard Axel 2006 Institute of Medicine

Linda Buck, Ph.D. Secrets of Smell

Linda Buck Ph.D. Retracts Papers In 2008, Buck had to retract 2001 nature paper Inability to produce results “inconsistencies between some of the figures and data published the original data” Paper in question is tied to the “mapping of olfaction to discrete parts of the brain” Initial groundbreaking work with Richard Axel still valid Later retracted PNAS 2005 & Science 2006 papers citing she could not reproduce data of these papers Buck stated most of questionable date came from post-doc Dr. Zhihua Zou

. A team of scientists including Linda B Buck, who shared the 2004 Nobel Prize in Physiology or Medicine, has retracted a scientific paper after the scientist could not reproduce their original findings The Harvard Medical School, where the researchers worked when the findings were published in the journal Nature in 2001, has begun a review of the research to determine if there is any evident of misconduct

. Science; 2006: 311, 5766,; 1477-148

Linda Buck, Ph.D. Retracts Papers PNAS Nature

Richard Axel MD 1946-Present . Richard Axel MD 1946-Present

Year ACHIEVEMENT 1946 B. Brooklyn Parents: Polish immigrants who fled Nazis Father- tailor; unacademic upbringing Interests: basketball; played 7’2 Lew Alcindor, who asked him “What are you going to do, Einstein?” HS- scholarship to  Stuyvesant HS, Manhattan Embraced culture & aesthetics of NYC Esp. Reading Room in NYC library College- Columbia; worked in DNA lab (fired as glassware cleaner) Med School- John Hopkins (military deferment) “My clinical incompetence was immediately recognized” “ I sewed a surgeon's finger to a patient ” “I was allowed to graduate med school if I promised never to practice medicine on live patients. After 1 year Pathology  internship “I was asked never to practice on dead patients”

Richard Axel MD Research in genetics Lab Columbia  Mentor: Sol Spiegelman who “taught me how to think about science, to identify important problems and how to effect their solution” NIH Post-Doc Fellowship (“yellow beret”) on DNA structure 1974 Assit Prof  Institute of Cancer Research, Columbia NY DNA mediated transformation of mammalian cells Recombinant DNA 1980

Richard Axel MD 1980s- Switched to Molecular biology of neuroscience problems Worked with Eric Kandel & Tom Jessell on Aplysia genetic issues Then pursued Interest in problem of perception Linda Buck PhD post-doc “A creative fellow in the lab, we began to consider how the chemosensory world is represented in the brain. The problem of olfaction was a perfect intellectual target for a molecular biologist.”