Historical Nobel Price Winners in Medicine

Alfred Nobel (1833 – 1896) Swedish chemist, engineer, industrialist,inventor of dynamite, donator and founder of The Nobel Prize. Global Nobel Prize Under this headline GHN Pharma presented Nobel Medicine Laureates from di erent vintages since 1901, why the researchers were awarded and what their discoveries have led to. First out, in our series is of course Alfred Nobel himself. The concise presentations will remind us of some of the many important life improving medical advances achieved during the last 120 year.We are very grateful for the support and advice from The Nobel Assembly at Karolinska Institutet and The Nobel Foundation in this matter. For more information: www.nobelprize.org “The Nobel Prize in Physiology or Medicine is without a doubt the world’ s most prestigious award for pioneering discoveries in the medical eld.” Thomas Perlmann Professor and Secretary of Nobel Assembly gives that rating in the foreword to the recently published book “Visual and culinary delights for Nobel Medicine Laureates” . The Nobel Prize in Physiology or Medicine is awarded “to the person or persons having made the most important discovery in the eld of physiology or medicine”. The great fortune made by Alfred Nobel during his successful career as industrialist once gave him the attribute “Europe’ s richest man”. In November 1895, Alfred Nobel signed his last will and testament, giving the largest share of his fortune to a series of prizes in Physics, Chemistry, Physiology or Medicine and Literature (Nobel Foundation Stockholm, Sweden) and Peace (Norwegian Nobel Committee, Oslo, Global Nobel Prize Under this headline GHN Pharma will present Nobel Medicine Laureates from di erent Norway) – the Nobel Prizes. In 1968, Sweden’s central bank established The Sveriges Riksbank Prize in Global Nobel PrizeEconomic Sciences in Memory of Alfred Nobel. vintages since 1901, why the researchers were awarded and what their discoveries have led to. First out, in our series is of course Alfred Nobel himself. For 2021 the amount is set at Swedish kronor (SEK) 10.0 million, equivalent to US Dollar 1 158 000 per full Nobel Prize. Under this headline GHN Pharma will why the researchers were awarded an if if ffff

1911 Allvar Gullstrand for his work on dioptrics of the eye Alvar Gullstrand The Swedish ophthalmologist Allvar Gullstrand was entirely self-taught in the elds covering his most important work geometric and physiological optics. The basis of the science he developed was laid in 1890 in his thesis Contribution to the theory of astigmatism. The complete proof of this theory is found in the following three works: General theory of monochromatic aberrations and their immediate signi cance for ophthalmology, 1900, which received awards from the Swedish Royal Academy of Sciences and the Swedish Medical Association; The true optical image, 1906 and The optical image in heterogeneous media and the dioptrics of the human crystalline lens), in 1908. Gullstrand was an honorary Doctor of Philosophy of the Universities of Uppsala, Jena and Dublin, and a member of a number of Swedish and foreign scienti c societies. In 1911 he received the Nobel Prize for his work on the dioptrics of the eye. He was member of the Nobel Physics Committee of the Swedish Academy of Sciences (1911-1929), and its Chairman (1922-1929). In 1927 he was awarded the Graefe Medal of the Deutsche Ophthalmologische Gesellschaft. Fo The Swedish ophthalmologist Allvar Gullstrand was entirely self-taught in the elds covering his most important work geometric and physiological optics. Bildtext: The Swedish ophthalm most important work geometric if if ifif

1936 Sir Henry Hallet Dale and Otto Loewi for their discoveries relating to chemical transmission of nerve impulses Henry and Otto Loewi Henry Dale In 1914 Henry Dale found that acetylcholine generated stimuli in part of the nervous system, the parasympathetic nervous system, which has a dampening e ect on heart activity and other functions. After Otto Loewi demonstrated acetylcholine’s function as a messenger between nerves and organs, Dale and other researchers re ned the understanding of acetylcholine’s role in the nervous system. Otto Loewi In 1921 Loewi discovered the chemical transmission of nerve impulses the research of which was greatly developed by him and his co-workers in the years following, culminating ultimately in his demonstration that the parasympathetic substance («Vagussto ») is acetylcholine and that a substance closely related to adrenaline played a corresponding role at the sympathetic nerve endings. It was for these researches that he received the Nobel Prize in 1936, jointly with Sir Henry Dale. Source and more info: nobelprize.org The Nobel Prize in Physiology or Medicine 1936. Nobel Prize Outreach AB Otto Loewi (1873 – 1961). German-born American physician and pharmacologist. A liation at the time of the award: Graz University, Graz, Henry DaleSir Henry Hallett Dale (1875 – 1968). English pharmacologist and physiologist. A liation at the time of the award: National Institute for Medical Research, London, UK. In 1914 Henry Dale found that ace parasympathetic nervous system, w Otto Loewi demonstrated acetylch ff ifff iff iff

great advance 1945 Alexander Fleming, Howard Walter Florey and Boris Chain for the discoveries of penicillin and its curative effect in various infectious Alexander Fleming, HowardWalter Florey “O and Ernst Boris Chain In St. Mary’s Hospital, birthplace of penicillin jo Alexander Fleming (1881 – 1955) at St. Mary’s Hospital, London Bo University), Howard Walter Florey (1889 – 1968) and Ernst Boris in Chain (1906 -1979) both at Oxford University were awarded the unquestioned 1945 Nobel Prize in Physiology or Medicine for their S discovery of the antibiotic penicillin and identi ed how it cures bacterial diseases. Serendipity Finding penicillin was a lucky accident. While studying bacteria, Fleming already in 1928 noticed that some had been killed and had dissolved away around a spot of blue-green moSultd.wMhicahrbyy’schHanocespital,Sbt.irMthapryla’sceHosfppietanli,cbililritnhplace of penicillin had contaminated one of his dishes. He transferred the mould to broth, wwhhiecnhdhieluftoeudAnhdluehnaxddraesdunschodfateimresF, leminAgle(x1a8n8d1e–r F1l9e5m5i)nagt(S1t8.8M1a–ry1’s9H5o5s)pait aSlt, .L strong e ect on bacteria that even the penicillin completely prevented bacterial growth. This mould Ernst1B9o6r8is) CahnadinE(r1n9s0t 6Bo-1ri9s7C9h)abinot(h19a0t 6Ox-1fo9r7d 1968) andbelonged to the Penicillium group of moulds, and he therefore named the broth, later the substance itself, penicillin. in PhNyosiboelol gPyrizoer MinePdhicyisnieolfoogrythoer iMr deidsiccoinverfyo Nobel PrizeErnst Boris Chain and Howard Walter Florey went on to purify and extract penicillin, enabling it to be produced in large amounts to cures bacterial dicsueraessebs.acterial diseases. treat many di erent bacterial diseases. ff ff if ff SerendipitySt. Mary’s Hospital, birthplace of penicillin“One of the great advances in civilisation” Serendipity In 1945 The Nobel Prize in Physiology or Medicine was awarded jointly to Alexander FhcoiannddtbainmegeiA1Nnnp9loaeek6btnxie8elaildc)leniaPdldolnreniiandhcFzrenoeiawFndFaoEnldneliddmafretnihitnnbasismhgcna,uPmseHriadagotishetwinviaelBnyndprdgudesoWaiieecksiasc(trltnotk1sihieeinlrsyilovF8ledcaoloerlir8Csaioegvdulyo.c1shlaeyinnnicdaafdne–oiEecnirdtninroaswdut1eosBwMod(n9afri1hsiseast5ehCa9as.hye5daiasWd0i.sn)ia“6cflodhdraruiotnhiit-iceslsu1edeSkshisn9cyotofesdv7.oletsarMv9yur.acoe)fdatcpdsehbyirnpdiyceoiailnlo’eiistnwrgnhtHdatoba.oyif

1936 Sir Henry Hallet Dale and Otto Loewi for their discoveries relating to chemical Pro transmission of nerve impulses the Daniel Bovet Pho Daniel Bovet discovered antihistamine The Nobel Prize in Physiology or Medicine 1957 was awarded to Daniel Bovet “for his discoveries relating to synthetic compounds that inhibit the action of certain body substances, and especially their action on the vascular system and the skeletal muscles.” Prize share 1/1. Daniel Bovet (1907 – 1992) is best known for his discovery in 1937 of antihistamines, which block the neurotransmitter histamine and are used in allergy medication. Daniel Bovet was head of the Psychobiology and Psychopharmacology Laboratory of the National Research Council, in Rome, before stepping down to become a professor at the University of Rome La Sapienza. Source and more info: www.nobelprize.org. Professor Daniel Bovet receiving the 1957 The Medicine Prize medal from the Swedish King Gustav VI Adolf. Daniel Bovet discovered antihistami

2008 Harald zur Hausenfor his discoveries that oncogenic human papilloma virus caused cervical cancer and Francoise Barré-Sinoussi and Luc Montagnier fort their discovery of human immunodeficiebncy (HIV) Harald zur Hausen, Françoise Barré-Sinoussi and Luc Montagnier Harald zur Hausen went against current dogma and postulated that H oncogenic human papilloma virus (HPV) caused cervical cancer, the D second most common cancer among women. He realized that HPV-DNA a could exist in a non-productive state in the tumors and should be detectable by speci c searches for viral DNA. He found HPV to be a Harald zur Hausen, Germany. MD at University of Düsseldorf, Germany. Professor heterogeneous family of viruses. Only some HPV types cause cancer. His emeritus and former Chairman and Scienti c Director, German Cancer Research Centre, H discovery has led to characterization of the natural history of HPV infection, an understanding of mechanisms of HPV-induced carcinogenesis and the development of prophylactic vaccines against HPV acquisition. Françoise Barré-Sinoussi and Luc Montagnier discovered human immunode ciency virus (HIV). Virus production was identi ed in lymphocytes from patients with enlarged lymph nodes in early stages of acquired immunode ciency, and in blood from patients with late-stage disease. They characterized this retrovirus as the rst known human lentivirus based on its morphological, biochemical and immunological properties. HIV impaired the immune system because of massive virus replication and cell damage to lymphocytes. The discovery was one prerequisite for the current understanding of the biology of the disease and its antiretroviral treatment. Françoise Barré-Sinoussi, born 1947 in France, French citizen, PhD in virology, Institut Pasteur, Garches, France. Professor and Director, Regulation of Retroviral Infections Unit, Virology Department, Institut Pasteur, Paris, France. Luc Montagnier, born 1932 in France, French citizen, PhD in virology, University of Paris, Paris, France. Professor emeritus and Director, World Foundation for AIDS Research and Harald zur Hausen went agaiPrevention,Paris,France. ifififif if if

2014 John O´Keefe, May-Britt Moser and Edvard Moser for their discoveries of cells that constitute a positioning system in the brain John O’Keefe, May-Britt Moser and Edvard I. Moser The Nobel Prize in Physiology or Medicine 2014 was divided, one half “Our inner GPS” awarded to John O’Keefe, the other half jointly to May-Britt Moser and The Nobel Prize in Physiology or Medicine 2014 was divided, one half awarded to John Edvard I. Moser “for their discoveries of cells that constitute a positioning O’Keefe, the other half jointly to May-Britt Moser and Edvard I. Moser “for their discoveries system in the brain”,popularly called our inner GPS. The discovery is a of cells that constitute a positioning system in the brain”,popularly called our inner GPS. positioning system that makes it possible for us to orient ourselves in The discovery is a positioning system that makes it possible for us to orient ourselves in space, demonstrating a cellular basis for higher cognitive function. space, demonstrating a cellular basis for higher cognitive function. In 1971, John O Ḱ eefe discovered the rst component of this system. More than three decades later, in 2005, May.Britt and Edvard Moser discovered another key component of the brains positioning system. Together they have solved a problem that has occupied philosophers and scientists for centuries – how the brain creates a map of the space surrounding us and how can we navigate our way through a complex environment. London taxicab drivers In his Nobel Lecture “Spatial Cells in the Hippocampal Formations” John O’Keefe refers to a study by Maguire and colleagues showing that London taxicab drivers had a larger posterior hippocampus than controls and that this increase in size was directly related to the amount of time as a cab driver. This showing that the important factor was the experience of London’s complicated street patterns and that London cab drivers are probably not born with bigger hippocampi but develop them. “Our inner GPS” if

2015 Tu Youyou for her discoveries concerning a novel therapy against malaria and to P​ h Willia C Cambell and Sathosi Omura for their discoveries concerning a novel therapy An against infections caused by roundworm parasites m TuYouyou,William C. Campbell and Satoshi © mura 2 2015 Nobel Medicine Prize to Malaria and roundworm parasite p researchers The Nobel Prize in Physiology or Medicine 2015 was divided, one half to Tu Youyou “for her discoveries concerning a novel therapy against Malaria, and the other half jointly to William C. Campbell and Satoshi Ômura “for their discoveries concerning a novel therapy against infections caused by roundworm parasites”. William C. Campbell and Satoshi mura discovered a new drug, Avermectin, the derivatives of which have radically lowered the incidence of River Blindness and Lymphatic Filariasis, as well as showing e cacy against an expanding number of other parasitic diseases. Tu Youyou discovered Artemisinin, a drug that has signi cantly reduced the mortality rates for patients su ering from Malaria. After studies of traditional herbal medicines in the 1970’s, Youyou Tu managed to extract artemisinin, a substance which inhibits the malaria parasite. Drugs based on artemisinin have led to the survival and improved health of millions of people. Source and more info: www.nobelprize.org Ancient Chinese texts inspired Tu Youyou to search for her Nobel-prize winning medicine ffif iff̄O ̄O

2018 James P. Allison and Tasuku Honjo for their discovery of cancer therapy by inhibition of negative immune regulation James P. Allison andTasuku Honjo The 2018 Nobel Prize in Physiology or Medicine was awarded to James P. Allison and Tasuku Honjo “for their discovery of cancer therapy by inhibition of negative immune regulation.” Cancer kills millions of people every year and is one of humanity’s greatest health challenges. By stimulating the inherent ability of our immune system to attack tumor cells the 2018 Nobel Laureates have established an entirely new principle for cancer therapy. James P. Allison studied a known protein that functions as a brake on the immune system. He realized the potential of releasing the brake and thereby unleashing our immune cells to attack tumors. He then developed this concept into a brand-new approach for treating patients. In parallel, Tasuku Honjo discovered a protein on immune cells and, after careful exploration of its function, eventually revealed that it also operates as a brake, but with a di erent mechanism of action. Therapies based on his discovery proved to be strikingly e ective in the ght against cancer. Allison and Honjo showed how di erent strategies for inhibiting the brakes on the immune system can be used in the treatment of cancer. James P. Allison: A liation at the time of the award: University of Texas MD Anderson The seminal discoveries by the two Laureates constitute a landmark in Cancer Center, Houston, TX, USA , Parker Institute for Cancer Immunotherapy, San our ght against cancer. Source and more info: nobelprize.org MahmoudFrancisco, CA, USA. Prize share: 1⁄2. © Nobel Media AB. Photo: A. Mahmoud Tasuku Honjo: A liation at the time of the award: Kyoto University, Kyoto, Japan. Prize share: 1⁄2. © Nobel Media AB. Photo: A. Ancient Chinese texts inspired Tu Youyou to search for her Nobel-prize winning The 2018 Nobel Prize in Physiology their discovery of cancer therapy by i iff iff ifff ifffff

The Nobel Assembly at the Karolinska Institute has decided to award the 2021 Nobel Prize in Physiology or Medicine to David Julius and Ardem Patapoutian “for their discoveries of receptors for temperature and touch”. David Julius and Ardem Patapoutian The Nobel Assembly at the Karolinska Institute has decided to award the 2021 Nobel Prize in Physiology or Medicine to David Julius and Ardem Patapoutian “for their discoveries of receptors for temperature and touch”. ”… a novel ion channel protein and this newly discovered capsaicin receptor was later named TRPV1.” ”The groundbreaking discoveries of the TRPV1, TRPM8 and Piezo channels by this year’s Nobel Prize laureates have allowed us to understand how heat, cold and mechanical force can initiate the nerve impulses that allow us to perceive and adapt to the world around us.” Source: NobelPrize.org. Nobel Prize Outreach AB 2021. Further info: www.nobelprize.org David Julius. Born 1955, New York, NY, USA. A liation at the time of the award: University of California, San Francisco, CA, USA. Prize share: 1/2. Ardem Patapoutian. Born 1967, Beirut, Lebanon A liation at the time of the award: Howard Hughes Medical Institute, Scripps Research, La Jolla, CA, USA Prize share: 1/2 iff iff