Accademici defunti

Andrzej Szczeklik


Cracovia, Polonia, 29/7/1938 - 3/2/2012
Nomina 16/10/1994
Disciplina Medicina
Titolo Professore

Commemorazione – I am honored and grateful to speak in memory of our beloved colleague Andrezej Szczeklik. I met him for the first time at our Academy in 1994 and I will always remember his self-presentation, modest and to the point. He gave a moving testimony of his admiration and love for Pope John Paul II. A few years later he gave me as a gift his inspiring book Catharsis: On the Art of Medicine with a foreword by the great Polish humanist and poet Czesław Miłosz. A continuation of this book is called Koré: On Sickness, the Sick, and the Search for the Soul of Medicine, a suggestive title that reveals the spirit and mission of a man totally dedicated to his patients and to science.
Andrezej Szczeklik was born in 1938 in Cracow, where he studied medicine. He did post-doctoral training and research at the Karolinska Institut, Uppsala University and North Carolina-Chapel Hill. He became professor and chairman of the Jagiellonian University School of Medicine, Cracow, and president of the Copernicus Academy of Medicine. He was a member of the Polish Academy of Arts and Sciences, the Royal College of Physicians, the American College of Physicians and the Pontifical Academy of Sciences. He became an active participant in all our Plenary Sessions. He received honorary doctorates from the Schools of Medicine of Wrocław, Warsaw, Katowice and Łódz. He was awarded the Gloria Medicinae Medal by the Polish Society of Medicine. He received the first prize of The Lancet for his paper on genetic polymorphism of leukotriene C4 synthase. In 2001 he was awarded the Gold Medal and The Robert A. Cook Memorial Lectureship by the American Academy of Allergy, Asthma and Immunology.
His whole life was dedicated to the study and treatment of cardio-pulmonary diseases. He was one of the first to discover the mechanisms of non-steroidal anti-inflammatory drugs that precipitate asthma attacks in sensitive patients by inhibiting cyclooxygenase (COX-1), a key enzyme in the metabolism of eicosanoids (substances produced by arachidonic acid). He was a leader of the European Network on Aspirin-Induced Asthma centered in Cracow. He discovered the genetic polymorphism and over-expression of leukotriene C4 synthase in patients with aspirin-induced asthma and the alteration of the metabolism of arachidonic acid common to asthma and urticaria.
He studied the history of salicylates, the forbears of aspirin, the drug that was produced by the pharmaceutical firm Bayer in 1899 and became the most popular drug in the world. His paper The history of aspirin: the discoveries that changed contemporary medicine presented at our Plenary Session 2004 and published in Paths of Discovery was a remarkable contribution to our understanding of clinical investigations.
He also worked in the mechanisms related to blood clotting after the discovery by his colleague Ryszard Gryglewski in 1976 of prostacyclin in humans, a local substance produced by the lining of blood vessels that produces vasodilation and inhibits blood clotting. In his book Catharsis he vividly described the first test of the drug in themselves at the Hospital of Cracow using a sample of the molecule synthesized by Joseph Fried, and how he was affected with high fever after the intravenous infusion (the prostacyclin was contaminated by bacteria) and how Gryglewski lost consciousness (because of the massive vasodilation and the lowering of blood pressure). After further experiments on himself without any complications they started to treat patients with serious diseases of peripheral vessels. I quote “How many days and nights we spent at their bedsides, listening out for the piercing pain in their feet to quieten down, and not believing our own eyes where the deep ulcers on their skin shrank and dwindled as the blood was mixed with a daily dose of prostacyclin”. Today stable analogues of prostacyclin are used in the treatment of pulmonary hypertension and also in the treatment of arteriosclerosis. It was further discovered that aspirin inhibits blood clotting and that those statins that reduce blood cholesterol also inhibit blood clotting.
Szczeklik, the remarkable internist and scientist, the mentor of generations of Polish physicians who published more than six hundred papers, was also a humanist, writer, musician, lover of the arts and a man of deep faith that practiced medicine as a sublime humanitarian art. He said “An internist is like a symphony orchestra conductor; specialists are like individual instrumentalists. They do the playing, but only the conductor knows all the instruments and what to expect from them”. In his book Catharsis he wrote that “Medicine concerns perhaps the strongest of human desires – our longing for love, which is usually unfulfilled”. We will miss him.

Antonio Battro


Principali premi, riconoscimenti e accademie
Premi: Premio Sniadecki dell’Accademia delle Scienze polacca (1974); Premio G. Sadoul, European Respiratory Society (1990); Premio Gloria Medicinae, Società di Medicina polacca (1995); Primo Premio del The Lancet per una relazione sul polimorfismo genetico del leucotriene C4 sintasi (1997); Primo Premio della Fondazione per le Scienze polacca (1998); medaglia del Robert Cook Memorial Lectureship, American Academy of Allergy and Immunology (1980). Accademie: Accademia polacca delle Arti e delle Scienze (1990); Pontificia Academia Scientiarum (1994); Academia delle Scienze polacca (1995); Royal College of Physicians, Londra (1998); American College of Physicians (2007). Lauree honoris causa: Facoltà di Medicina, Università di Wrocław (1999); Varsavia (2001); Katowice (2002) e Łódz (2003).

Riassunto dell’attività scientifica
Il contributo principale di Szczeklik è stato nel campo delle malattie cardiopolmonari. Inizialmente le sue ricerche hanno portato alla formazione dell’ipotesi che spiega il meccanismo dell’asma indotta dall’aspirina, una sindrome clinica comune che colpisce il 10% degli adulti asmatici. L’ipotesi, che è stata dimostrata negli anni successivi, afferma che l’aspirina e vari altri farmaci antiinfiammatori non steroidei causano attacchi d’asma in pazienti sensibili inibendo la cicloossigenasi (COX-1), l’enzima chiave nel metabolismo degli eicosanoidi, sostanze prodotte dall’acido arachidonico dalla maggior parte delle cellule del nostro corpo. Ha inoltre dimostrato l’esistenza di una forte sovraespressione del leucotriene C4 sintasi nei bronchi dei pazienti con asma indotta dall’aspirina e ha scoperto un polimorfismo genetico di questo enzima, associato alla malattia in forma grave. Questi studi, premiati con il primo premio dalla rivista The Lancet, hanno stimolato le ricerche sul coinvolgimento degli eicosanoidi nelle malattie polmonary e hanno portato alla fondazione del European Network on Aspirin-Induced Asthma (AIANE), che riunisce 25 dipartimenti universitari di 14 paesi, coordinati dall’Università di Cracovia. Le sue ricerche più recenti hanno svelato alterazioni interessanti nel metabolismo dell’acido arachidonico che sono comuni nell’asma e nell’orticaria. Nel 1977 A. Szczeklik ha praticato su se stesso e sui suoi colleghi iniezioni di prostaciclina, un ormone locale prodotto dal tessuto endoteliale e recentemente scoperto. Ha descritto le azioni potenti della prostaciclina nell’uomo (vasodilatazione, inibizione della coagulazione del sangue) e l’ha introdotta nella terapia dei disordini vascolari. Oggi, gli analoghi della prostaciclina e i suoi congeneri sono sistematicamente usati per il trattamento delle malattie vascolari periferiche, per le malattie infiammatorie delle arterie e per l’ipertensione polmonaria primaria. Le sue ricerche più recenti hanno portato alla scoperta di una nuova azione dell’aspirina: inibisce la generazione di trombina nel sangue in coagulazione. Lo stemperamento del potente meccanismo di coagulazione del sangue da parte dell’aspirina potrebbe spiegare, almeno in parte, i suoi effetti benefici preventivi e terapeutici nella cardiopatia ischemica e nell’ictus. È interessante notare che questa azione dell’aspirina è più debole nell’ipercolesterolemia e anche nel polimorfismo genetico comune delle glicoproteine delle piastrine, perciò i soggetti con un tasso elevato di colesterolo nel sangue o con una variante genetica delle piastrine potrebbero beneficiare meno di altri dell’effetto antitrombotico di questo farmaco. Questi studi hanno portato allo sviluppo di un nuovo modello sensibile per lo studio della generazione della trombina in vivo, a dimostrazione che le statine, potenti farmaci che abbassano il tasso di colesterolo nel sangue, deprimono le reazioni specifiche dei meccanismi di coagulazione del sangue.

Pubblicazioni principali 
Szczeklik, A., Gryglewski, R.J., Czerniawska-Mysik, G., Relationship of inhibition of prostaglandin biosynthesis by analgesics to asthma attacks in aspirin-sensitive patients, Br. Med. J., 11, 1, pp. 67-9 (1975); Szczeklik, A., Gryglewski, R.J., Czerniawska-Mysik, G., Clinical patterns of hypersensitivity to nonsteroidal anti-inflammatory drugs and their pathogenesis, J. Allergy Clin. Immunol., 60, pp. 276-84 (1977); Szczeklik, A., Niźankowski, R., Skawinski, S., Szczeklik, J., Głuszko, P., Gryglewski, R.J., Successful therapy of advanced arteriosclerosis obliterans with prostacyclin, Lancet, 26, pp. 1111-4 (1979); Szczeklik, A., Sładek, K., Szczerba, A., Dropinski, J., Serum immunoglobulin E response to myocardial infarction, Circulation, 77, pp. 1245-9 (1988); Szczeklik, A., Krzanowski, M., Góra, P., Radwan, J., Antiplatelet drugs and generation of thrombin in clotting blood, Blood, 80, pp. 2006-11 (1992); Szczeklik, A., Musiał, J., Undas, A., Swadzba, J., Góra, P., Piwowarska, W., Duplaga, M., Inhibition of thrombin generation by aspirin is blunted in hypercholesterolemia, Arterioscl. Thromb. Vasc. Biol., 16, pp. 948-54 (1996); Sanak, M., Simon, H.U., Szczeklik, A., Leukotriene C4 synthase promoter polymorphism and risk of aspirin-induced asthma, Lancet, 350, pp. 1599-1600 (1997); Szczeklik, A., Gryglewski, R.J., Vane, J.R., (eds), Eicosanoids, aspirin and asthma, Marcel Dekker, Inc., New York-Basel-Hong Kong (1988); Cowburn, A.S., Sładek, K., Soja J., Adamek, Ł., Niźankowska, E., Szczeklik, A., Lam, B.K., Penrose, J.F., Austen, F., Holgate, S.T., Sampson, A.P., Over-expression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma, J. Clin. Invest., 101, pp. 834-46 (1998); Undas, A., Brummel, K., Musiał, J., Mann, K.G., Szczeklik, A., Pl(A2) polymorphism of beta(3) integrins is associated with enhanced thrombin generation and impaired antithrombotic action of aspirin at the site of microvascular injury, Circulation, 27, 104, pp. 2666-72 (2001); Szczeklik, A., Musiał, J., Undas, A., Reasons for resistance to aspirin in cardiovascular disease, Circulation, 106, e181-182 (2002); Undas, A., Sydor, W.J., Brummel, K., Musiał, J., Mann, K.G., Szczeklik, A., Aspirin alters the cardioprotective effects of the factor XIII Val34Leu polymorphism, Circulation, 107, pp. 17-20 (2003); Bochenek, G., Nagraba, K., Niźankowska, E., Szczeklik, A., A controlled study of 9alpha,11beta-PGF2 (a prostaglandin D2 metabolite) in plasma and urine of patients with bronchial asthma and healthy controls after aspirin challenge, J. Allergy Clin. Immunol., 111, pp. 743-9 (2003); Szczeklik, A., Stevenson, D.D., Aspirin-induced asthma: advances in pathogenesis, diagnosis, and management, J. Allergy Clin. Immunol., 111, pp. 913-21 (2003); Szczeklik, A., Sanak, M., Niźankowska-Mogilnicka, E., Kiełbasa, B., Aspirin intolerance and the cyclooxygenase-leukotriene pathways, Curr. Opin. Pulm. Med., 10, pp. 51-6 (2004); Catharsis, On the Art of Medicine, by A. Szczeklik, A. Lloyd-Jones (translator), University of Chicago Press, December 2005, pp. 172.


Discovery of the Defensive System of the Endothelium, the Lining of the Arterial Wall (PDF) 2010

The History of Aspirin: The Discoveries that Changed Contemporary Medicine (PDF) 2004

The Art and Science of Medicine (PDF) 2002