Britton Chance: His Life, Times and Legacy

First discovery of the generation of ENIAC Global outreach: Going to the East (Asia) BC’s invention of a compass-controlled photoelectric navigator starting at Part of the Rad Lab Steering Committee Dual-beam spectrometer reactive oxygen species H2O2 in SCR-584 Radar 13 y.o., patented in 1930 and tested in ships in 1937 Chance, 1951 (Rev Sci Instrum) mitochondria, 1971

o Compass 45 mirror

New Engl. J. Med. 1985 ML

LD Early abstract Chance B, Sies H, Boveris A. Physiol H. K. Rev, 1979 >3900 citations MS, MD Chance & Williamson, 1955, 1956 (J Biol Chem, Adv Enzymol Rel Subj Biochem etc.) Oxidative stress is an unbalance Anti-aircraft autotracking AB radar system developed by BC in Cambridge Univ. Rad Lab. Action at Anzio, Millikan’s Lab (1938-39) citations :~1300 Normandy and Buzzbombs & >3000 ANTIOXIDANTS Photocells MS, Univ. of Prisms First simulation by the mechanical Mitochondrial bioenergetics OXIDANTS Penn., 1936 Intrinsic fluorescence differential analyzer for solutions of Britton Chance Memorial and electron transport in markers (NADH & Fp) for China’s Friendship Award; Premier non-linear differential equations for BS, Univ. of WWII, MIT Radiation Lab Symposium and Workshop 2011 respiratory chain mitochondria redox state Chemiluminescence Wen, Jia-Bao with Chance (Xinhua, 9/2008) & Centennial Symposium on enzyme action (~1938) Penn., 1935 1941~1945 BC-CBMP, Wuhan, China (1999) (Since 1950s & 60s respectively) of free radicals (1970s) Metabolic Imaging/Spect 2013 Science, 1962 Development of in vivo MRS QL 1910 1930 1950 1970 1990 2010

Born on July 24, 1913 Ph.D. in Physical Chemistry, Biological quantum tunneling NADH fluorometer & NIR spectroscopy & photon diffusion imaging Passed away on Nov 16, 2010 Micro stop-flow device for enzyme Olympic Gold Medal 1973 Joining ISOTT Univ. of Penn., 1940 First evidence by DeVault & redox scanner (1970s) kinetics & mechanisms Science Helsinki, 1952 Chance, Biophy J, 1966 1976 President of ISOTT Birth of diffusive biomedical photonics Chance & Maehly, Methods in Enzymology, 1955 2004 Estb of Britton Chance >1300 citations Ph.D in Physiology, BC in Complex II Award >1,000 citations. Cambridge Univ,1942

D.Sc., Cambridge University, 1952 AM Time resolved spectroscopy to First tomography exp using photon measure tissue properties diffusive waves (O’leary, Boas, Mayevsky & Chance, 1973 (Patterson MS, Chance et al, Chance & Yodh, Optics Let 1995) Applied Optics1989) Director of Johnson AY Chen Y, et al. Applied Phased array Optics, 2002 Foundation (1949-1983) Li, & Chance et al. JIOHS, <1 y.o. A family of sailing BC, his mom and brother 2009 Amplitude Phase Complex III Source

BC Chance et al. PNAS, 2000

First breast cancer MR-NIR imaging LI & Chance et al. PNAS, 2009

Triplet energy transfer h 1

First exp demonstration of Michaelis- O2 Redox scanning of cancer aggressiveness

h 1 + O 2 O Menten enzyme-substrate complex 2 Q Olympic Medal Helsinki 1952 O2 PS Q PS Birthday party in 2010 First USSR world championship, 1962 Enzyme Chance, J Biol Chem, 1943 BQ Clyde B & Chance, et. al. 1978 Enzyme Activation President Ford w/ Chance, N HN NH N H H Chen J, et N Gly-Asp-Glu-Val-Asp-Gly-Ser-Gly-Lys- NH H C 1974 BO O C O O al.,JACS, 2004 Molecular beacons and Yodh & Chance, Zheng G, photodynamic therapy PNAS, 2005 Physics Today, 1995 BO Nanobeacon (LDL)

Life Achievement Chart (by Dr. Chance) Major Scientific Contributions Major Honors and Awards 1. Study of enzyme-substrate kinetics by developing the micro stop-flow device; First experimental demonstration of the existence of Michaelis-Menten 1950 Paul Lewis Award in Enzyme Chemistry, USA enzyme-substrate complex. The mechanism of enzyme action. U.S. President's Certificate of Merit, USA 2. Development of dual beam (dual wavelength) spectrometer which is widely used for studying turbid biological samples. 1952 Olympic Gold Medal in Sailing (Men’s 5.5 Meter Class) 3. Discovery of the intrinsic autofluorescent biomarkers NADH and flavoprotein compounds of mitochondria, opening the field of non-invasive studies of 1961 Morlock Award, Inst. of Electrical & Electronics Engineers (IEEE), USA mitochondrial metabolism in vivo. Development of the NADH fluorometry and NADH/flavoprotein fluorescence imager (the Chance redox scanner) for 1965 Genootschapps Medaille, Dutch Biochemical Soc., The Netherlands metabolic studies in animals and humans. 1966 Harrison Howe Award, Rochester Section, American Chemical Soc., USA 4. In-depth study of mitochondrial bioenergetics including redox state and electron transport chain. Metabolic control mechanisms. Franklin Medal, Franklin Inst., Philadelphia, USA 5. First discovery of calcium uptake by mitochondria. 1968 Pennsylvania Award for Excellence (Life Sciences), USA 6. First discovery of the generation of hydrogen peroxide in mitochondria. 1969 Philadelphia Section Award, American Chemical Society, USA 7. First experimental discovery of the electron tunneling phenomena in biological systems. 1970 Nichols Award, New York Section, American Chemical Soc., USA Heineken Medal, Netherlands Academy of Science and Letters, The Netherlands 8. Ground-breaking development of in vivo magnetic resonance spectroscopy and study of phospho-energetics in perfused organs, animals, and human subjects (athletes and patients with neuroblastoma and genetic diseases etc.). 1972 Gairdner Award, Canada 1974 Semmelweis Medal, Hungary 9. Co-founding the field of biomedical photonics by developing near-infrared spectroscopy and imaging methods including time resolved spectroscopy, photon diffusion tomography, phased array and their biomedical applications to study brain function (fNIR) and various diseases including breast cancer etc. National Medal of Science, USA 1976 ISCO Award for Significant Contributions; Field of Biochem. Instrum., USA 10. Development of electronic circuits, precision targeting radar (SCR-584) and bombing radar and computers in the World War II and the assistance to the circuit development of the world first general purpose computer ENIAC at the University of Pennsylvania.

DaCosta Oration, Philadelphia County Medical College, USA 1984 IEEE Philadelphia Section Award, USA Elections to Academies and Honorary Societies Honorary Degrees

Sober Lectureship Award, American Soc. of Biological Chemists, USA 1954 National Academy of Science, USA 1962 M.D. Karolinska Institute 1986 Elizabeth Winston Lanier Award, American Academy of Orthopaedic Surgeons Kappa Delta Awards, USA 1974 D.Sc., Medical College of Ohio at Toledo 1954 Harvey Society, New York Academy of Medicine Senior Investigator Award, American Heart Assn., USA 1976 D.Sc., Semmelweis University 1955 American Academy of Arts and Sciences, Fellow 1987 Gold Medal Distinguished Service to Medicine, Coll. of Physicians, USA 1977 D.Sc., Hahnemann Medical College 1957 Society of General Physiologists, Councillor (1957-1960) Biological Physics Prize, The American Physical Soc., USA 1985 D.Sc., University of Pennsylvania 1958 American Philosophical Society 1990 D.Sc., University of Helsinki 1988 Gold Medal, Soc. of Magnetic Resonance in Medicine, USA 1959 Royal Academy of Arts and Sciences, Member 1991 M.D., University of Dusseldorf 1989 J. Henry Wilkinson Award, International Soc. for Clinical Enzymology, USA 1959 Biophysical Society, Founder and Councillor (1959-1962) 1993 M.D., University of Buenos Aires 1990 The Benjamin Franklin Medal for Distinguished Achievement in the Sciences, American Philosophical Soc. 1995 M.D., University of Copenhagen 1960 Royal Society of Arts, Benjamin Franklin Fellow 1992 Christopher Columbus Discovery Award in Biomed. Research (USA/NIH) 1997 M.D., University Degli Studi Di Roma “Tor Vergata” 1966 Am. Assoc. for the Advanc. of Sci., VP & Chair, Sec. of Med. Sci. John Scott Medal Award, City of Philadelphia 2008 D.Sc., National Cheng Kung University 1968 Royal Swedish Academy of Sciences, Foreign Member 1995 Stellar-Chance Bldg., Univ. of Pennsylvania, Dedicated June 28, 1995 2009 D.Sc., Huazhong University of Science and Technology 1970 Bavarian Academy of Sciences, Munich, Member 2009 D.Sc., University of the Sciences in Philadelphia 1999 American Coll. of Sports Medicine Honor Award, USA 1971 Leopoldina Academy, Halle, Germany 2010 D.Eng., Southern Taiwan University of Science and Technology 2001 Lifetime Achievement Award in Biomed. Optics, Coherent Laser Group, Lauren Publishing and the Center for Fluoresc. Spect, USA 1971 Int. Federation of Institutes for Advanced Study, Board of Trustees (1971-1982) 2005 International Soc. for SPIE Lifetime Achievement Award 1972 International Union of Pure and Applied Biophysics, VP(1972- 75), Pres.(1975-79), Honorary VP(1979-2010) 2006 Gold Medal, American Roentgen Ray Society, USA 1974 Philadelphia College of Physicians, Fellow Distinguished Achievement Award, American Aging Assn., USA 1974 Max-Planck-Gesellschaft zur Forderung der Wissenschaften, Foreign Member 2008 Friendship Award, China (Highest honor by the Chinese Government for foreign experts working in China) 1975 Argentine National Academy of Sciences, Member 2009 The International Science and Technology Cooperation Award, China (Highest Honor by the Chinese Government) 1981 Royal Society (London), Foreign Member 1987 National Academy of Lincei, Italy, Foreign Member Acknowledgement: The poster was first made by Lin Z. Li and Shoko Nioka at the University of Pennsylvania and Kyung Kang at the University of Louisville for the ISOTT Annual 1988-1990 Society for Free Radical Research (International)(SFRR), President Meeting on July 24-27, 2011. Revision in July, 2013 to honor the 100th birthday of Britton Chance. Thanks to the great help/advice from X Yan, X Sun, HN Xu, M Leonard, A Pugh, JD Glickson, the slides/pictures from H Koizumi, L Dutton, H Sies, A Boveris, A Yodh, M Schnall, Q Luo, B Quistorff, A Mayevsky, B Onaral, G Zheng, M Delivoria-Papadopoulos, D Boas, 1989-1990 The Oxygen Society, Honorary President Y Chen, J Severinghaus, etc. and the courtesy of the Chance family & Johnson Research Foundation, Dept. of Biochem. and Biophys., Univ. of Pennsylvania. Contact: [email protected].