Homage to Victor A. McKusick

on the occasion of the 20th edition of the Course in Medical Genetics May 5-11, 2007
Bertinoro, Italy

organized by the

EUROPEAN SCHOOL OF GENETIC MEDICINE

and proceedings of the awarding of the Laurea ad honorem in Medical Biotechnologies

by the

ALMA MATER STUDIORUM UNIVERSITY OF BOLOGNA on May 12, 2007 in Bologna, Italy

to Victor A. McKusick and Mario Capecchi

2 ESGM - EUROPEAN SCHOOL OF GENETIC MEDICINE

The European School of Genetic Medicine (ESGM) is the only initiative in Europe that offers advanced training in the different fields of genetics and genomics in medicine (see www.eurogene.org).

More than 5,000 students attended ESGM courses over the last 20 years, enabling the School to expand its course offerings to a total of 10 courses per year. Still, each year the number of participants in ESGM courses increases as does the variety of nations represented by our participants. This has facilitated and amplified the exchange of ideas between scientists of different research institutions, has created new opportunities for collaboration and has expanded pre-existing scientific networks.

The primary purpose of the ESGM courses is to provide advanced training in genetics and genomics to junior scientists from across Europe. The secondary purpose of these courses is to provide opportunities for junior scientists to establish professional contacts with colleagues from across Europe, including the ESGM faculty. It is in fact of paramount importance to involve young scientists in competitive European research projects at a critical moment in their careers.

Legend to picture (page 2). The picture was kindly provided by Prof. A. Ballabio (TIGEM, Naples). This is the detail of a group picture taken during the 1st Course in Medical Genetics held in Sestri Levante (Genova) in the Spring of 1988: in the front row Victor A. McKusick (right) and Giovanni Romeo (left); behind McKusick stands Andrea Ballabio; behind him stands Wilson Lo; behind him stands Marcus Pembrey.

3 The ESGM is also attracting students from an increasing number of EU Associate States (like Turkey and Israel) as well as from other countries of the southern rim of the Mediterranean. Training scientists and medical specialists from these nations is essential for the purposes of disseminating modern genetic knowledge in the Mediterranean region and the Middle East. Furthermore, the increased participation of female scientists from these countries will help to ensure that current knowledge of genetics be applied within the field of reproductive healthcare. This will increase reproductive choices, thus promoting remarkable social change.

While ESGM courses are offered in different venues across Europe and the Mediterranean region, the primary training site is the Bologna Residential Center in the medieval town of Bertinoro di Romagna. This venue provides a quiet learning environment equipped with the technology and resources of a major University. Thanks to these resources the ESGM makes its courses available online to those researchers who are unable to travel to Bertinoro, thus priming the development of a very interesting educational format named Hybrid courses. These training events are broadcasted through live streaming on our website from the Main Training Centre (MTC), usually located in Bertinoro (Italy), to the authorized Remote Training Centres (RTC). They are called hybrid because they combine e-learning and face-to-face learning. On-line courses are available both live and on-demand streaming on the EGF website.

Because of this history, in 2005 the President of the European Genetics Foundation, Prof. Giovanni Romeo, received the European Society of Human Genetics Educational Award in Prague.

4 EGF - EUROPEAN GENETICS FOUNDATION

Eight years after the founding of the European School of Genetic Medicine (ESGM) in 1988, it became necessary to establish an organizing and governing body to oversee not only the School’s activities but also the School’s expansion. Thus, the European Genetics Foundation was established in 1996 by a group of geneticists already involved in the activities of the School.

In March 1997, during the 29th Congress of the European Society for Human Genetics in Genoa, Italy, the European Genetics Foundation organized a series of concerts to accompany the scientific programme of the Congress. This “Meeting of Music and Genetics” promoted a further expansion of the European School of Genetic Medicine. The initiative proved extremely successful, allowing the ESGM to upgrade its facilities, to increase the number of its courses and to attract more and more students from across Europe. Furthermore, the funds raised at the time allowed EGF to organize various projects in the field of the public awareness of genetics. Since then EGF and ESGM have grown, providing specialized education to thousands of young scientists, coordinating international research projects and establishing collaborations among research institutions, private companies, and the European Union.

In 2004 EGF received a donation from the Monastic Order of the Servants of Mary (Province of Piedmont and Romagna) consisting in a piece of land of 16,500 sqm located in the hills surrounding Bologna, i.e. in Ronzano, 3.5 km from downtown Bologna. In this site EGF will build a new venue for the ESGM, which will complement the bigger one of Bertinoro. This new venue will host several projects of EGF, among which the Euro-

5 Mediterranean center for Genetic Medicine dedicated to Giuseppe Levi and Victor McKusick (www.eurogene.org). In order to raise funds for the construction of this new venue, EGF launched in 2006 a big event for the public understanding of genetics, named “Festa della Musica e della Genetica” (www.musicagenetica.it), which will be repeated every year.

The present Trustees of the European Genetics Foundation are: Giovanni Romeo (President), Professor of Medical Genetics, University of Bologna Medical School (Italy); Roberto Ravazzolo (Vice-President), Professor of Human Genetics, University of Genoa Medical School and Istituto Giannina Gaslini, Genoa (Italy); Michele Bianco, Managing Director of the European Genetics Foundation, Bologna (Italy); Martin Bobrow, Emeritus Professor of Medical Genetics, University of Cambridge (UK); Stefano Di Donato, Director of the Neurogenetics Laboratory, Istituto Besta, Milan (Italy); Jennifer Howse, President of the March of Dimes (USA); Victor A. McKusick, University Professor of Medical Genetics, Johns Hopkins Medical School, Baltimore, MD (USA); Stephen Desiderio, Director of Institute for Basic Biomedical Sciences, Johns Hopkins School of Medicine, Baltimore, MD (USA).

6 20th Course in Medical Genetics Bertinoro, May 5-11, 2007

COURSE DESCRIPTION This is a week-long postgraduate course addressed to both researchers and clinicians seeking an up-to-date overview of the field of medical genetics. The 20th edition of the course was divided in the following sessions: Introduction to Genetic Analysis, Clinical Genetics and Cytogenetics, From clinical observations to the lab, Translational research in genetics, Cancer Genetics, Neurogenetics, Complex Genetic Disorders. The course consisted of review lectures given during the plenary morning sessions and of concurrent afternoon practical workshops.

Legends for pictures of pages 9-11 Page 9: group picture with numbers corresponding to names listed on page 8 Page 10: group picture in front of the main entrance of the “Rocca di Bertinoro” Page 11: group pictures taken on the occasion of the visit of Dr. Katami, former President of the Islamic Republic of Iran, to the Museum of the three monotheistic religions and to the European School of Genetic Medicine in Bertinoro Page 12: Nationalities of the 104 partecipants to the 20th course in Medical Genetics. About 200 additional students attended the same course diffused by webcasting through Internet to the following Remote Trainig Center (RTCs): Hopital Charles Nicolle, Tunis (Tunisia); The Cyprus Institute of Neurology and Genetics, Nicosia (Cyprus); Genetics Research Center University, Tehran (Iran); University of Medical Sciences, Tehran (Iran); National Research Centre (Egypt); Facultad de Medicina de Valladolid (Spain); Athens University (Greece); Ministry of Health (Israel); Université Mohammed V Souissi (Morocco).

7 ( M. Kriek ( Lundin ( Lundin H. ( Sondess Mohammadi-Asl ( Mohammadi-Asl 29 Rudd ( ( Netherlands ( 54 ( ( Chaabouni-Bouhamed ( M. A. Adank ( Adank A. M. STUDENTS Scotland N. Katsanis ( S. Zuckerman ( 106 Italy M. Capecchi (USA), F. Cucca ( FACULTY Van Engelen ( Van Engelen ( L.M.J. Boon ( Boon L.M.J. ( McKusick V.A. DIRECTORS ( A.P. Norambuena ( Denmark Lebanon Leuven, Belgium Leuven, The Netherlands The Netherlands Turkey Belgium ), E.J. Jaakkola ( Jaakkola E.J. ), ), M. Petrillo M. ), ( ), J. ( ), Wincent - 25 Sweden - ) - -

48 2 ), F. El Kerch ( 80 Sweden - ), M. Speicher ( Speicher M. ), 75 ), C.L. Harteveld ( ), C.L. - The Netherlands ), der N.S. ( van Crabben 47 ), J. Torsvik ( - Tunisia ), A. Corveleyn ( Corveleyn A. ), Baltimore, USA 32 The Netherlands The Netherlands Netherlands - - Israel - - 28 33 14 87 ), R. Sanchez ( Italy Baltimore, USA Baltimore, Sweden ), F. Maio ( ), T. Meitinger ( Meitinger T. ), Finland Iran ), A. Finotti), ( A. ), M. Bahuau ( Chile - - - 45 86 93 - 21 ). ), Stavrou E. ( - Morocco ), S. Picelli ( Picelli S. ), - Tunisia 4 Gratz, Austria Gratz, 5 - - ), A. Molyneux ( - ), A. Yunis ( ), A. Norway 110 66 16 ), Numitone G. ( ), Y. Aflalo ( Aflalo Y. ), ), F. Kersten ( ), P. Lichter), P. ( The Netherlands ), A. Bremer ( Bremer A. ), ), M. Lamp ( - Italy 104 Belgium ), I. Chelly ( - Sassari, Italy Spain 90 - Italy 43 - - ), H.H. Vetti ( 6 France ), O.M. Elruby ( ), O.M. 71 Munich, Germany Munich, ), A. Trimarco ( ), H. Brunner ( H. Brunner ), - Italy ), C. Meloni ( The Netherlands - 56 10 - Israel - Greece 72 1 ), A. Sbiti ( Sbiti A. ), ), E. Gean ( ), A. Spinazzola ( Spinazzola A. ), - - 34 ), E. Dominguez ( 27 Israel Estonia The Netherlands UK - ), T.A. Dragani ( Heidelberg, Germany Heidelberg, ), J. Bergman ( ), Bergman J. - Italy 46 Sweden ), A. Puchmajerová ( Tunisia 63 ), S. Suleiman ( ), S. Zaimidou ( Zaimidou S. ), - - ), S.A. Hassan ( Hassan S.A. ), 78 94 - 99 Norway - ), K. Muscat ( ), A. Al-Ashtar ( - Italy 83 ), M.T. Nyberg ( Nyberg M.T. ), ), Mendell ( J. 3 - Egypt Nijmegen, The Netherlands The Nijmegen, Morocco - Italy 84 ), Z.N. Brownstein ( Brownstein Z.N. ), 92 ), E.N. Larsson), ( E.N. Spain - ), S.D. Cherkaoui ( ), L. van derKolk ( 69 - - - 13 98 39 Milan, Italy - ), T. Mina ( - 55 - ), M. Vignoli ( Vignoli M. ), 89 ), F. Tüzün ( ), F. Tüzün 85 The Netherlands ), P. Fanis ( P. Fanis ), Milan, Italy Milan, Spain ), M.Kousi ), M.Kousi ( Malta ), S. Gebre-Medhin ( ), S.P. Seitsonen), ( ), E. Maestrini ( Maestrini E. ), Greece Egypt Malta Baltimore, USA Czech Republic Czech - 58 - Lybia 73 - Denmark - - 62 18 42 ), A. Efthymiadou), ( Italy ), R. Talmaci ( Talmaci R. ), - Finland ), B. Emanuel ( 52 ), P. Zavattari ( ) ), Hauke ( J. Cyprus

- Turkey 77 Greece ), E. Nannenberg ( Nannenberg E. ), - Israel Italy 109 - Morocco Netherlands ), N. Alonso ( 102 - - 40 114 - ), A. Mishori-Dery ( A. Mishori-Dery ), - - 37 ), M. Buono ( M. Buono ), 70 24 - - ), S. Berland ( Bologna, Italy Bologna, - ), S. Antonarakis ( Antonarakis ), S. 67 49 Finland 18 - ), M. Oti ( Oti ), M. ), A. Leontiadou ( ), A. Leontiadou 91 ), G. Farina ( ), F. Vorraro ( Vorraro F. ), - ), L.Kraoua ( ), B.W.M. van Bon ( van ), B.W.M. ), A. Raitila ( Raitila A. ), 81 ), A. ( Metspalu Sweden Germany ), I. Christiaans ( Christiaans I. ), Romania - Philadelphia, USA Philadelphia, Italy 26 - 19 ), L.T.J.N. van der Veken ( Veken der van L.T.J.N. ), Greece Spain - ), J.P. Silva ( - 36 The Netherlands The 61 ), J.L. Mandel ( J.L. Mandel ), - 74 Italy ), Georgitsi M.A. ( The Netherlands ), B. Zirn ( - Norway 76 Italy - ), M.J.Heeley ( - Finland Tunisia 53 Brasil 88 ), S. Temtamy ( ), S. Temtamy - 95 Israel Geneva, Switzerland Geneva, ), A. Andersson ( A. Andersson ), - ), M.M. Eid ( Eid ), M.M. Greece 103 Tartu, Estonia ), J. Camajova ( - - 9 107 - - Portugal - ), E. Fateen, ( ), E.W. Blom ( The Netherlands The Netherlands The 82 15 35 ), C.P. ( Howson Germany - ), M.R. Wevers ( 59 ), Riessland M. ( - ), I. Krapels ( ), M.H. Modarressi ( Modarressi M.H. ), 64 Strasbourg, France Strasbourg, ), F. Lundberg ( ), F. Lundberg - ), L. Pérez Cabornero ( Cabornero L. Pérez ), 101 - UK 23 - ), L. Nazaryan ( Egypt Greece ), ( Monckton D. 17 ), C. Sofokleous ( Egypt ), M. Hempel ( Hempel M. ), ), Zuccato C. ( Sweden ), G. Romeo ( Romeo G. ), Czech Republic Czech Egypt The Netherlands - - ), N.F. Van Der Aa Aa Van Der N.F. ), - 7 The Netherlands 97 - The Netherlands 60 30 ), H.T. El Achkar New York, USA York, New ), R. Collin ( Collin R. ), ), A. Gundogdu - ), M.P. Torring Germany - The Netherlands 50 31 ), G. Matthijs ), G. Matthijs Sweden ), I. Feenstra Feenstra I. ), ), K. Ansink Iran Armenia Germany Italy - Glasgow, Glasgow, - - - Bologna, Bologna, 68 100 Greece 65 44 - Spain 8 ), H. - ), K. - ), E. ), C. - 20 22 ), J. J. ), The 11 ), ), ), ), ), ), ), ), ), - - -

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12 European School of Genetic Medicine Alumni Personal Tributes to Victor A. McKusick on the occasion of the 20th Course in Medical Genetics Bertinoro, May 5-11, 2007

Armenia

Dear dr. McKusick, on behalf of the medical geneticists of Armenian Center of Medical Genetics and Society of Human Genetics I would like to express our greatest gratitude to you for the foundation of annual courses in Medical Genetics organized by the European School of Genetic Medicine. You are known as “father of genetic medicine”, and your valuable contribution to medical genetics remains inestimable. Our congratulations for receiving a honorary degree at the University of Bologna. This is indeed a recognition of your great contribution. We attended the courses in Italy many times. We have our personal experience of the courses and state the greatest importance for us and for all medical geneticists of different countries. We greatly appreciate you and professor Giovanni Romeo for the wonderful annual courses of genetic medicine. I hope a long and productive cooperation will be established and I look forward to new courses. Best regards. Sincerely Prof. Tamara Sarkisian, MD, PhD, DSc. Director of Center of Medical Genetics and Primary Health Care of Armenia 13 Head of Department of Molecular Medicine of State Medical University Chief Geneticist of Ministry of Health of Armenia [email protected]

Australia

Dear Giovanni, I should say Happy Anniversary European School of Genetic Medicine! Well done Giovanni & Victor! I have participated to the School in 1990 and the School certainly provided the springboard to my career in human molecular genetics, which continued through Marseille, France (1991-1993) and Adelaide, Australia (1994 - present). I treasure my experience and memories from Sestri Levante 1990. Coming from Czechoslovakia the experience for me was extraordinary, meeting people like yourself, Ed Southern, Victor McKusick, Tony Monaco and many others did change my life and further fueled my enthusiasm and passion for science I am doing till today. Thank you again for the opportunity to participate to the School and for the generous support I received. I do not have only memories left, but collaborations and friendships which lasted till today. Well Done and Congratulations!!! Cheers, Jozef Gecz Women's and Children's Hospital Adelaide, South Australia [email protected]

14 Cuba

We attended the Edition of Medical Genetics organised by the European School of Genetic Medicine on 2000, which took place in Sestri Levante, Italy. That experience was extremely important for us and for our careers of Medical Geneticists, because we got acquainted with new and unexpected Knowledge. As we come from a tropical country, cold weather was shocking sometimes, but the warmth and affection of classmates and professors were compensating. Professor Victor McKusick participated in all teaching sessions imprinting a special character to the course. Once, when we thought that we would be the first one to arrive to the top of the hill where classes were delivered, we were surprised because Professor McKusick surpassed us, arriving first. We will remember this experience forever and will always be grateful to Giovanni Romeo for his invaluable help. Without him, it would have been impossible for us to attend. Attached we are sending photographs of that unforgettable moment. Sincerely yours, Dra. Rita Sanchez Lombana and Dra. Estela Morales Peralta Hospital G. O “Ramón González Coro” Ciudad de la Habana, Cuba [email protected]

Czeck Republic

Although I was already teaching genetics at the time when I attended the ‘school’ in Genoa and also later in Sestri Levante, it was a fascinating experience that suggested me not only what to speak about in my lectures but also how to teach genetics. It is true that we (Czechs) were a little selfmade geneticist as in our country

15 for a few decades dominated Lysenko and Lepeschinska imported from Russia, and any contact with the situation of freely developing science was of a great value. Participation in the courses left an unforgettable impression upon me and I really feel obliged to you for offering me and my students the possibility to attend. Radim Brdicka IHBT - Institute of Hematology and Blood Transfusion Prague, Czeck Republic [email protected]

Czech geneticists of old generation remember thankfully Prof. Dr. Victor A. McKusick, who visited Prague in spring 1970. In this period after Soviet occupation the frontier of our republic was closed and research literature, especially dealing with genetics, was unavailable. Prof. McKusick presented us with his Catalog Mendelian Inheritance in Man, which had been the only copy in Czechoslovakia for 10 years and therefore very valuable. Nowadays his "RED BOOK" (colour of this edition) sits on a prominent place in our library: first of all as a memory of international solidarity during the severe period of our history and secondly as a source of valuable knowledge for a generation of Czech geneticists. Best regards from Prague Eva Seemanová Department of Biology and Medical Genetics Charles University Prague, Czeck Republic

Egypt

When I started my career in Egypt as human geneticist in 1991, Prof. Samia Temtamy taught us how to use Medelian Inheritance In Man (McKusick’s book). It was of great benefit for us in the

16 diagnosis and differential diagnosis. I followed this book since it was yellow until online. The knowledge and accuracy is quite contagious! In many occasions, Prof. Temtamy was telling us about her great Prof. McKusick and she called him the God father of human genetics and she is always talking about how she learnt a lot from him while writing her thesis which later was published as a well known reference book on the Genetics of Hand Malformations. I have never met him but I've learned a lot from all his prestigious books and publications. Thank you for opening my mind to the wonders of human genetics. I really enjoyed these hybrid courses especially the one on Medical Genetics that I attended in 2005; and I wish that this course will be available freely for us every year. I appreciate your thoughts and support and look forward to many successful years. I would like to extend my appreciation for all your coworkers on the great OMIM. Thank you for being a limitless source of knowledge. Ghada Abdelsalam National Research Center Cairo, Egypt

Dear Professor Victor McKusick, In such a wonderful occasion it is a great chance and a honor to share with you some of my personal feelings towards you and my experiences with the EGF courses and the Medical Genetics course co-founded by you 20 years ago. Being myself a student of one of your students and colleagues (Professor Temtamy) from Egypt, I was always inspired by you, your photos are all over Professor Temtamy's desk, we learnt from her how great, devoted, disciplined, simple and loving to genetics you are. We learnt from her how to admire her professor and how to be a good model for your students as you were to her. 17 It has been a privilege for Genetics to be headed by you. You succeeded in introducing this science to the world and increasing the awareness of its importance and significance as the science of the future. Giving the chance to scientists from different countries to be supervised by you helped to disseminate genetics all over the world. Each of your students had built a nucleus for this science in his (her) own country with the enthusiasm, love and understanding of genetics as you taught them. The European Genetics Foundation (EGF) headed by Professor Romeo, is a clear example and a superior model of such efforts. Training courses arranged by EGF gave the chance both to faculty and students from all over the globe to meet, share experiences and gain up to date knowledge in genetics in a sincere and friendly atmosphere. EGF courses have tackled different disciplines in genetics; the Medical Genetics course is an extremely important course to medical geneticists, bringing the latest developments in the field to their knowledge. The extension of EGF courses including Medical Genetics course to remote training centers, specially to Mediterranean countries, allowed physicians and health professionals to attend highly specialized courses on genetics without requiring them to invest time and most importantly resources for travel. Being a student at many EGF courses including Medical Genetics, I had a great opportunity to attend different courses in Alexandria, Tunisia and Bertinoro as well as all courses that were broadcasted to Cairo. Each course added to my knowledge and appreciation of genetics and gave me the chance to meet and exchange experiences with famous faculty and make new friends in the field from different scientific and cultural backgrounds. It widened my sense of genetics from music and genetics, genetics and the community to the very sophisticated molecular basis of genetics. My honoured professor, as the godfather of genetics you must be very proud of your efforts crowned by this celebration of the 20th anniversary of the Medical Genetics course. Even though many of us (middle aged scientists) were not able to meet you in person, you are always an inspiration and a model to us. 18 Please accept my congratulations and my sincere wishes for a life full of health, happiness, more success and achievements. Yours Sincerely, Dr. Mona Aglan Assistant Professor of Clinical Genetics Human Genetics & Genome Research Division National Research Centre, Cairo, Egypt [email protected]

Dear Prof. Romeo, Thank you for your kind email. I wasn't available and I've just read your email and unfortunately I couldn't prepare the pictures of the courses attended. I would like to thank Dr. McKusick for his great effort in the development of the field of dysmorphology and his valuable publications that added a lot to our knowledge and scientific research. Regarding my experience with the European School of Medical Genetics, I would like to say that I had the great pleasure to attend two different courses in the field of medical genetics which were very interesting, updated and well experienced and I really appreciated the organizers very much. Hoping to have the opportunity to attend and share more events through the European School of Medical Genetics. Thanks in advance Dr. Ahmed A. Dardir, Ass. Prof. of Paediatrics and Clinical Genetics National Research Center Cairo, Egypt [email protected] [email protected]

Dear Sir, It is a great pleasure for me to meet you during this course in Italy. Unfortunately I did not meet you in person before. However I knew you through my eminent professor Dr. 19 Temtamy. I joined the Genetics Department at the National Research Center (NCR) at 1977 as a medical student under her supervision. The first thing that attracted my attention was your picture with Professor Dr. Temtamy at Johns Hopkins University. Then I knew you even more through your impressive book with Dr. Temtamy “The Genetics of Hand Malformations” and through “The Catalogue of Inheritance in Man”. OMIM and the hybrid courses of the “Gen Med Gen” of the European Genetics Foundation were my most recent encounters with deep issues in genetics. These courses are of high standard, highly informative and very competitive, lectured by highly professional and well accomplished doctors. These courses give us the opportunity to meet and discuss many genetic dilemmas that concern geneticist. It is an honour to meet you and celebrate with you this memorable day. Best regards, Mona El Ruby Professor and Head of Clinical Genetics Department National Research Center Cairo, Egypt [email protected]

Dear Professor Romeo, It is a splendid idea to have students of your courses express their feelings towards professor Victor A. McKusick the God Father of Medical Genetics all over the World. My student and now my colleague, Dr. Mona Aglan, who is enjoying these courses showed me her email to you in response to yours. I think she conveyed her feelings and expressed them very well, and I am proud to have transmitted my feelings of great admiration to professor McKusick to different generations of medical geneticists in Egypt even though they may not have personally seen him. I think Dr. Mona was not yet on the Human Genetics

20 research staff in my department of Human Genetics when I invited Victor and his beloved wife Anne to an International Conference of Human Geneticsand physical anthropology which I organised in Cairo in December 1989. I am sure Dr McKusick and Anne still remember their visit to us when they also had the chance to have a Nile cruise to Luxor and Aswan. I wish I could repeat the invitation since all my 100 available staff now in the Division of Human Genetics and Genome Research have heard a lot about him from me and visit his OMIM daily. I wish all the happiness and health for my Great professor Victor McKusick who is in all our hearts and brains. As you know one of the main reasons for me to participate in the Medical Genetics Course in May 2007, is to see my dear professor McKusick and congratulate him personally on this very special occasion that you gracefully organised. Looking forward to meet you all. Sincerely, Samia Temtamy, M.D., Ph.D Professor of Human Genetics National Research Centre El-Tahrir Street El-Dokki, Cairo, Egypt [email protected]

Finland

Dear Dr Victor McKusick, I attended the 19th course of Medical in Genetics held in Bertinoro last May. It was a wonderful course, which gave valuable knowledge for my future work in the field of medical genetics and with families with genetic problems. I enjoyed also the nice company of the other students, the excellent food, and

21 the lovely and historical surroundings. In Finland we had almost ice age when you build your castles. Thank You very much for initiating the course 20 years ago, and congratulations to the 20th anniversary of the course. Best regards, Carola Saloranta Helsinki University Hospital, Finland [email protected]

France

Dear Victor, I want to express all the admiration I have not only for your invaluable contribution to genetics but also for having transmitted both your knowledge and enthusiasm to our community. I had so much pleasure to meet you each year at Sestri Levante and Bertinoro. I also keep wonderful memories of Urbino visit with you and your wife. Françoise Clerget-Darpoux INSERM Paris, France [email protected]

Dear Giovanni, sorry to do not be with all of you for this important event specially for Victor Honorary nomination! Tell to Victor I will participate through my "souvenir " on Saturday morning May 12. Victor may remember that one of the first time we met was in Oxford with Walter Boodmer in 1975. Since he was always taking picture with his "antique" camera he may show, with pictures, to all of you all the past friendly history of Human Genetics.

22 Could you send me the program of such event Marc and as usual also a "souvenir" to my best friend who is not with us to day: Tomy Meo Pr. Marc Fellous Human Genetics Cochin Institute, ICGM Paris, France [email protected]

Germany

Dear Victor A. McKusick, thank you very much for organizing the courses in Medical Genetics in Italy. I was happy to attend the 19th Courses in Medical Genetics in Bertinoro and fortunate to receive the best poster award in the field of clinical genetics from you. It was a great experience to get to know you. Best regards, Dr. med. Diana Mitter Institut für Humangenetik Universität Essen Hufelandstr. 55 45122 Essen, Germany [email protected]

Dear Colleagues and Friends, Dear Giovanni, Dear Victor, at the suggestion of Giovanni Romeo, the convener and director of the courses in Medical Genetics of the European School of Genetic Medicine I am writing as a former member in of the faculty of this course, 1990 in Sestri Levante and 1991 in Trieste.

23 In both courses Victor McKusick played the leading role as we all have become accustomed to. For me, it was by no means the first time to witness Victor in a conference. This experience dates back to the influential Baltimore Conferences on The Delineation of Birth Defects 1968-1972, which really was the delineation of medical genetics. Later I was an attendant of the Bar Harbor Course in Mammalian Genetics in 1986 and as a member of the faculty in 1987. Perhaps three characteristics stand out in my memory: (1) Victor always is open to new and young attendees, encouraging us, being supportive. (2) On conference discipline: Victor always wears his name badge throughout a conference, although he really is the one who needs it the least. However, he says (and have heard him say this more than once when he runs a conference): “Please always wear your name badge. You may think that everybody knows you. But believe me, there will always be some who don´t.” (3) Victor raises constructive questions that advance the field. He never embarrasses a speaker after a perhaps confusing or not so successful presentation by difficult questions. Through Victor McKusick the quality and atmosphere of the Bar Harbor Course were transferred to Europe and afforded an opportunity for a generation of European human geneticists to enter the field in an international spirit. With my very best personal wishes, Eberhard Passarge, M.D. Emeritus Director Department of Human Genetics, University of Duisburg-Essen, Germany [email protected]

24 Dear Giovanni, taking part in the EGF courses both as a student, lecturer and coordinator of the e-Learning webpages has meant quite a lot to me. The interaction with some of the best faculty in the world and with highly motivated students gave me a perspective on genetics that could not be obtained from any other source and helped to get my career in this field to a great start. I congratulate both you and professor McKusick on this incredibly valuable achievement for genetics in Europe and wish you continued success! Best wishes, Dr. med. Peter N. Robinson, MSc. Institut für Medizinische Genetik Universitätsklinikum Charite Humboldt-Universität Berlin, Germany [email protected]

Greece

Dear Prof. Romeo, On behalf of a 12-member Greek genetic team working in Athens, Greece, who scientifically “grew up” with the book Mendelian Inheritance in Man written by the father of Medical Genetics, one of the earliest scientists to suggest that “just as the gross anatomy in the Middle Ages was important to medicine, every medical specialty now uses mapping genes for diseases”, I would like to express our deep respect to Professor Victor McKusick and thank him for being a tutor, an adviser and a mentor to all of us working in Medical Genetics across Europe. Being with you in spirit, please offer him, on behalf of my team, a present that all of us hope that he will appreciate. It is a Calendar of 2006 with 12 images of the human genome, produced at our

25 lab, using various methodological approaches. The pictures were selected by artistic, not scientific criteria, to illustrate the human genome, in addition of being an object of study, is an endless artistic gallery. The calendar is written in Greek, a language that has contributed a lot to the international genetic terminology. Best regards Georgia Bardi, PhD Associate Professor of Experimental Clinical Genetics Founder and Scientifc Directyor BioAnalytica – Geno Type SA Athens, Greece [email protected]

Germany

Prof. McKusic in one of the first courses in Sestri Levante (see letter below)

26 Dear Giovanni, I would have loved to participate in the celebration of the 20th anniversary of the course in Medical Genetics of the European School of Genetics and to honor Victor McKusick and Mario Capecchi. Both of them have "imprinted" me tremendously. Both of them are role models for me since the time I met them. I participated about 3-4 times as a faculty member of the Medical Genetics course. As a "mouse" person it was a key experience to meet and discuss with those people that see real patients. I think the course anticipated by two decades what everybody now calls "translation". Enclosed you find a picture from Victor McKusick. I don’t remember why he left on his coat and hat. Either he was so excited about "OMIM" or the heating system in the castle broke down. Please give my regards to Victor and to Mario and my thanks for teaching me more than they are aware of. Yours Rudi Balling Helmholtz-Zentrum für Infektionsforschung Braunschweig, Germany [email protected]

Iran

Dear Prof. Romeo, thanks for giving us an opportunity to present something to Victor. Here are some pictures of our previous EGF course on medical genetics (18th) held in 2005, Tehran. You can choose any of them if you like. the number of attendee was great looking to Victor's talk. He did great efforts on medical genetics and we wish him health and success in future. All the best Seyed Mohammad Akrami, M.D, Ph.D Assistant Professor

27 Medical Genetics Department, Tehran University of Medical Sciences, Poursina St., Tehran, Iran [email protected]

Dear Dr. McKusick, Nowadays, the world is obliged to your great efforts of the last 20 years whether he is directly involved in the Genetic Medicine field or benefiting of the valuable results and impacts. The Genetic Medicine is known simply by your esteemed name. You no longer belong to your home country but you belong to a scientific community worldwide which everybody is proud of. The Iranian Genetic Medicine Society welcomes the 20th anniversary of European School of Genetic Medicine and wishes to extend his heart-felt appreciation to your sincere efforts. We wish you and your family wonderful days to come from almighty God. With best regards, Vahid R Yassaee (MD, PhD) Genomic Research Center Shaheed Beheshti University of Medical Sciences Tehran, Iran [email protected]

Italy

The Course in Medical Genetics of the European School of Genetic Medicine co-funded by Victor McKusick and Giovanni Romeo 20 years ago has been one the most outstanding initiative in teaching Medical Genetics in the developed as well in developing word. The courses were organized in a magnificent way, and the teachers were the most outstanding people on the different fields of medical genetics. The topics selected were very stimulating and the atmosphere realized was very nice and

28 constructive, thereby determining a fruitful participation of the pupils. The presence of Victor McKusick at the courses was critical for its success because of his elevated stature in Medical Genetics, his contribution to the development of this important field of Medicine and his charming personality. I was invited to participate as teacher to three of the courses, the first one held in Sestri Levante and the latter two in Bertinoro giving lectures on different aspects of thalassemias and on the utility of the founder Sardinian population for students of Medical Genetics and especially for those interested in complex diseases. I enjoyed participating in these courses and I felt honoured to be included in the list of the teachers. These courses of Medical Genetics in my opinion are on the top of teaching initiatives for all the aspects mentioned and especially for the charming and constructive atmosphere created between the teachers and pupils. Cari saluti Prof. Antonio Cao Istituto di Neurogenetica e Neurofarmacologia Cittadella Universitaria di Monserrato [email protected]

Dear Gianni, sorry for the delay in replaying you. Unfortunately, I can't come on May 12 to Bologna and attend to the celebration of the 20th anniversary of the Course of Medical Genetics. Nevertheless, I am present "in spirit", and considering our busy agendas I have decided to take some time to Easter to write few sentence on my personal experience as a Faculty of a couple of courses some years ago when it was still held in Sestri Levante. When, for the first time, you invited me and I came to Sestri, I was quite afraid being involved as a Faculty in such highly scientific course, together with extremely professional colleagues coming from all over Europe and World. But, after few hours I felt like at home

29 in an extremely pleasant stay with a lot of friends, in the wonderful scenario of the Castle and the Sestri Bay. Now, sitting on a sofa and listening the "Four seasons" of Vivaldi, my thoughts go back to those days and I can clearly remember Faculties spread in different tables at lunch with students willing to learn and always ready to ask, the McKusick Box for after lunch questions (like a TV quiz!), extremely pleasant discussions with Faculties and students some of which are now good friends and collaborators, rainy days and fireplaces not working! But one of the most pleasant memories I have is a fascinating trip to the "Sentiero dell'Amore" at Cinque Terre. I remember Massimo Zeviani, Brunella Franco and myself walking on the path and talking with Victor and his wife. We were all impressed by their ability in going up and down through the hills, as very professional trekking people! After the trekking we recovered in front of a glass of good white wine and some slices of focaccia in the sunset, in a small pub on the seashore! I really wish the best to Victor and to the Medical Genetics course which is now one of the best worldwide recognized courses in this field Best regards Paolo Gasparini IRCCS Burlo Trieste, Italy [email protected]

The course in Medical Genetics of the European School of Genetic Medicine helped so much to build an European genetic awareness common not only to the first members of CEE but also to all Est-Europe scientists! Prof. Orsetta Zuffardi Genetica Medica Università di Pavia, Italy [email protected]

30 Jordan

Dear Professor Romeo, I am Dr Amin Aqel PhD in Molecular Microbiology. I attended the 18th Course in Medical Genetics, Bertinoro, Italy. I was very excited from the large and concentrated information in medical Genetics which is helped me in my field and so my students who I converted my experience to them which I gain from the course. Actually I would thank Professor McKusick for his big support for the Medical Genetics courses and I congraduate him for his honory degree from Bologna University. Professor McKusick is a well known person in Medical Genetics field and I talked to him and to his wife during the course, I noticed what personable and simple people they are. I attach some pictures from my last attendance to the 18th Course in Medical Genetics With my greetings Yours Amin A Aqel, DVM, PhD Assistant Professor Faculty of Allied Medical Sciences Department of Medical Technology Zarqa Private University, Jordan [email protected]

Morocco

I was very honored and proud to be part of the faculty in the 1st Course in Neurogenetics organised in Rabat, Marocco on June 8th -11th, 2005, by the European Genetics Foundation. It was a great time for me to meet Members of this Foundation and I wish all the best to all the founders. Please find attached a photo souvenir of a nice evening during this course.

31 Best wishes, Meriem Tazir Service de neurologie CHU Mustapha [email protected]

Romania

Dear European School of Genetic Medicine staff, the courses you have organized permit us to understand and to improve the new perspectives of medical genetics. Laudy Cherry University of Bucharest Bucharest, Romania [email protected]

I attended the XIV Medical Genetics Course in 2001 thanks to a fellowship offered by European School of Genetic Medicine and with the incredible help of Professor Giovanni Romeo, at that time being difficult for a Romanian to obtain a visa. This first experience at an international course opened to me the gate for the Genetics World and made me understand the real level of the knowledge and the spirit of the geneticists. I had the great honour to meet and to discuss with Professor Victor McKusick, and I appreciated very much his friendly attitude. Only the photo that he was so kind to pose in with me was the proof for my colleagues that I really had a talk with one of the most famous geneticists from the world. Six years later, I still have the same nice feeling thinking about that week of amazing scientifically talks that were very new for me, and I still keep in mind Professor McKusick’s handshake with a young unknown geneticist from Romania.

32 All my best for Professor Victor McKusick Best wishes for European School of Genetic Medicine staff and my deeply thanks for all this tremendous work done in Genetics to train so many people; You really contributed to my career in Genetics. Sincerely yours, Cristina Skrypnyk, MD, PhD University of Oradea, Faculty of Medicine, Genetics Department Oradea, Romania [email protected]

Spain

It was a very special experience to share science and good moments within the context of the most updated global knowledge in Human Genetics. Thank you so much to Dr. McKusick for making it possible and for his great contribution to science. I feel privileged for having had the chance of meeting him and attending this course in its 19th edition. Happy 20th “course-birthday”!!. Eva Ruiz-Casares Madrid, Spain [email protected]

Sweden

Clearly, as its co-founder Prof. V.A. McKusick him self, the European course in Medical Genetics has become legendary. I am really enthusiastic to attend the course in 2007 within short and my expectations are mounting each day! Sincerely, Samuel Gebre-Medhin, MD PhD

33 Associate Professor Department of Clinical Genetics University Hospital Lund, Sweden [email protected]

Switzerland

Dear Victor, As I was told, the University of Bologna decided to follow the University of Zurich in honouring you and your work. For Bologna in particular, but for all European geneticists, your contribution to the foundation and continuation of the European School of Genetic Medicine is one of the most important activities you did for us. You therefore truly deserve the honour from one of the oldest and most prestigious universities of Europe. This school is a hallmark in the education of European medical geneticists. Personally, my congratulations especially to your wife Ann: We all know that without the care of our spouses we would live far shorter and less good. It’s to the choice for her that we all have to congratulate you as she enabled and greatly contributed to your great and successful work. Hope to see you soon, With all my wishes for the future, Yours Prof. Albert Schinzel Institute of Medical Genetics Schwerzenbach, Switzerland [email protected]

34 Tunisia

Dear Romeo, As a partner of Ithanet project, I appreciate very much the excellent initiative of organizing the EGF courses. Two of my collaborators attend the bio-informatics course in Bertinoro. This course was very interesting and helpful for them and for all the team of our laboratory in Tunis. This initiative of the European School of Genetic Medicine was a great opportunity for all of us to improve our daily work. Thanks to you and to Victor With sincere congratulations. Best regards Prof. Slaheddine Fattoum Hôpital d'Enfants de Tunis [email protected]

I am Ines Ouertani from Tunisia, I am medical doctor and I am following my genetic training. I have been to Bertinoro twice on September 2006 and November 2006. it was an interesting experience. I met people from different countries and cultures. I think that such courses are important and indispensable to the young geneticists to meet each other, exchange their experiences and ideas and to be up to date. With best regards Ines Ouertani EPS Charles Nicolle [email protected]

35 Turkey

Although I have never had the opportunity to meet Dr. McKusick personally, his name had always been familiar to me. Now available in electronic format, his monumental work "McKusick's Mendelian Inheritance in Man" is and will be one of the main references. I could attend only one course organized by the European School of Genetic Medicine; that was in 1999 in Sestri Levante. Although he was not there personally, I could feel his great contribution to the event: I can remember the famous "McKusick box", invented by Dr. McKusick apparently for "shy" attendees who were unwilling to express their ideas and questions orally. I wish him good health and continue his activities in Genetics. Dr. Kivanc Cefle Istanbul University Istanbul Medical Faculty Dept. of Internal Medicine Division of Medical Genetics [email protected]

I participated in the 16th course of medical genetics in 2003, from Turkey. As long as the course, Mr and Mrs McKusick listened to all presentations and both took notes. I feel so lucky that I can continue to work on this subject I like so much. After I met them I have the expectation that I will like my job as long as I live. Herein I want to say that I suggest to my students, “not to lose their ‘desire-love to learn’, as Mr and Mrs McKusick” while I’m telling them about my journey to Bertinoro. I’m also sending the pictures I could find. With my best wishes Ozlem Giray, MD

36 Dokuz Eylul University, Faculty of Medicine, Department of Pediatrics, Division of Genetics, 35340 Inciralti, Izmir Turkiye [email protected]

Dear Romeo, It is very kind of you to organize the presentation of gifts to Professor McKusick on the occasion of the 20th Anniversary of the course. I wish I could be there with you in May; however, I am afraid I have a prior engagement to give a talk at a Congress. I will prepare a gift package and send it to you by DHL in the coming days. Enclosed please find a picture of Professor McKusick, Professor Sevim Balci and myself. If I am not mistaken, this picture was taken during the opening ceremony of the American Society of Human Genetics meeting in San Francisco in 1999, when Uta Francke was the President of the Society. Our gift to Professor McKusick will be embroidered genome art motifs. With kind regards and sincerely yours, Tayfun Ozcelik, MD Professor of Human Genetics Bilkent University Department of Molecular Biology and Genetics Bilkent – Ankara, Turkey Tel: +90-312-290 2139 Fax: +90-312-266 5097 [email protected]

Very Dear Giovanni Romeo, I am thanks to Dr. McKusick that he gave wonderful contribution to the Medical Genetics. This service contributes to all over the world for learning about genetic strategies how to

37 work and also I admire his research about population like Amish and so on. His experience and contribution are marvellous. What I will say many thanks to God created Dr. McKusick for genetic societies. Please convey my heart. Many congratulations for the celebration of the 20th anniversary of the European Genetics School as well as for the Honorary Degree conferred by the Alma Mater Studiorum-University of Bologna. Congratulations to Prof. Mario Capecchi too. Many thanks for your performance With Warmest Greetings and Respects Prof. Dr. Ilhan Sezgin Cumhuriyet University, Faculty of Medicine, The Head of Medical Genetics Department Sivas,Turkey [email protected]

United Kingdom

Dear Prof McKusick, Many congratulations on the 20th birthday of your prestigious course which has trained geneticists from all over the world. Education is essential to encourage research questions in the next generation. Your course has been at the centre of this endeavour- thank you for you wonderful leadership. With our best wishes Ros Eeles, Audrey Ardern-Jones and colleagues in The Translational Cancer Genetics Team & Cancer Genetics Unit The Institute of Cancer Research & The Royal Marsden NHS Foundation Trust London UK [email protected] [email protected]

38 Dear Victor, We all owe you (and Anne) more than it is possible to express, and I hope that this is a very happy 20th anniversary for you! With respect and love, Peter S. Harper University Research Professor in Human Genetics Cardiff University Wales, United Kingdom [email protected]

Greetings Victor, and thank you for your invaluable advice on many aspects of human genetics; not only via OMIM but through enjoyable personal interactions over nearly 40 years. And also of course for your great support of standard gene nomenclature! Sue Povey Haldane Professor of Genetics Department of Biology University College London London, UK [email protected]

USA

The initiation of the Sestri Levante course was one of those brilliant things that do not happen often. For the faculty it was to some extent just another meeting , but I was able to witness what an extraordinarily fine thing it was for the students. I truly believe that few things have a stronger impact on peace and mutual understanding in Europe than events like this one. The students were absolutely thrilled to go to Sestri Levante. Of course Giovanni Romeo is to be lauded for this – I believe it totally carried his signature. But it was a stroke of genius to ask

39 Victor McKusick to co-direct the course – and an act of wisdom and friendship of Victor to accept. So here hundreds of young European geneticists were able to interact directly, repeatedly, face-to-face with this great man in genetics. I do not think I need to say more. The two or three courses I attended were delightful; and scientifically stimulating. I have tried to find pictures or other materials, but totally without success. I thought that in lieu of pictures from Sestri Levante that I do not have, I would at least send a picture e.g. of Victor receiving his hat on the occasion of his becoming an honorary MD at the University of Helsinki May 29, 1981. I have a clear memory of a picture where the promoter (NB not suppressor) Niilo Hallman places the hat on VMcK:s head. Mysteriously, the university cannot find the picture. Finally, in 1981 Victor and Anne extended their visit to Finland by going to Oulu to see Henrik and Harriet Forsius who are sending their very best regards and are so sorry that they cannot find a picture they know exists showing the McK:s having lunch by an open fire somewhere in Lapland. Henrik suspects the picture may have been taken with Victor’s camera. A final note: I asked the people here at the Ohio State University to find a picture taken when Victor and Anne visited here on Jan 30, 2003, but again, unbelievably, no picture was found. So on behalf of many, many admirers in Finland and Ohio, Clara and I send our congratulations on this important anniversary. Albert de la Chapelle, M.D., Ph.D. Distinguished University Professor Human Cancer Genetics Program Comprehensive Cancer Center The Ohio State University 646 Tzagournis Medical Research Facility Columbus, Ohio, USA [email protected]

40

Dear Giovanni and Victor, I have only recently become involved in the courses in Medical Genetics organized by the European School of Medical Genetics, but they are certainly legendary. The numbers of students trained and the quality of the course is a testament to the extraordinary efforts put forth by many individuals, most notably you and Victor. You are to be congratulated for providing many individuals around the globe with a knowledge of genetics and the desire to work in the field of human genetics. It is a result your extraordinary efforts and teaching skills that the course has been so very successful!! The attached photos are a reminder of the blending of the Bertinoro Course with the annual event of public understanding of genetics, the Festival of Music and Genetics. May our understanding of the evolution of the human genome blend with our awareness of music and its role in the history of mankind. With many congratulations and warmest wishes...... Sincerely, Beverly S. Emanuel The Children’s Hospital of Philadelphia Philadelphia, USA [email protected]

Dear Victor, you have led the way in medical genetics in the US, Europe and the world. We all are in your debt and treasure your contributions. Barbara B. Knowles, Ph.D The Jackson Laboratory Bar Harbor, Maine, USA [email protected]

41 Dear Victor, Congratulations on 20 years of Spring courses in Europe! While I only had the pleasure of participating in the course once, I know that the course has had a profound influence on a great many students over its history, including many who have gone on to make substantial contributions to our favorite field. You and Giovanni should be very proud of your efforts. I only wish I could be there to congratulate you in person. Best wishes, David Nelson, Ph.D. MRDDRC Associate Director Houston, Texas, USA [email protected]

42

LAUREA AD HONOREM

Saturday, 12TH May, 2007 Aula Absidale Santa Lucia Bologna

43 The Rector of Alma Mater Studiorum – University of Bologna Pier Ugo Calzolari

The Dean of the School of Medicine Maria Paola Landini

are glad to invite you to the Ceremony of conferring the Laurea ad honorem

to

Mario R. Capecchi

Victor A. McKusick

in

Medical Biotechnologies

44 Laudatio for Mario Renato Capecchi by Giovanni Romeo

Mario Renato Capecchi (Investigator of the Howard Hughes Medical Institute since 1989, and Professor of Human Genetics, University of Utah School of Medicine) is the inventor of the system of transgenic mice, first put into practice in 1986 by means of the homologous recombination in murine stem cells. Since then such system allowed a number of laboratories to “build” mice with tumor, heart diseases, Alzheimer disease, cystic fibrosis, hypertension, etc., therefore revolutionizing the approach to the study to genetic diseases.

This very concise description of Mario Capecchi’s work is very meaningful for those who work in biomedical research but is practically incomprehensible for outsiders. I will try therefore in the next ten minutes to make a connection between the personal history of this great colleague of ours and his scientific success. For this purpose he gave me his permission to recall the first years of his life, when he was an abandoned child living in the streets of Italy afflicted by the war. The history of little Mario is a history of hunger. As we say in Italy, la fame aguzza l’ingegno (necessity is the mother of invention), Mario himself stated that his scientific success might be considered as the result of his experience of fighting for survival in his childhood. Moreover Mario’s personal history is a great teaching of humility and determination, both extremely important qualities for a researcher. Mario was born in Verona in 1937, from a short relationship between Lucy Ramberg, an American poet, and Luciano Capecchi, a pilot of the Italian Air Force.

45 His mother’s family, from Oregon, nurtured many artists and had a long-lasting exchange with Italy. Actually Mario’s grandmother, a painter, is buried in Assisi cemetery next to St. Francis Basilica.

When Mario was four his mother, living in Bolzano and part of a group of artists called Bohemiens in open clash with the Nazis’ regime, was arrested by the Gestapo and imprisoned in Dachau. Short before being arrested, Mario’s mother sold all her assets and gave the proceeds to a peasants’ family who promised to take care of the child. But for reasons that always remained unclear the money finished within six months, and Mario was abandoned. He survived for five years, wandering around the cities of Northern Italy together with other abandoned children. In an interview entitled “From rags to research” published in Nature on July 1, 2004, Mario stated that in those years he survived by begging and stealing. He lived with other kids organized in small gangs. In 1945 his mother, who survived Dachau, returned to Italy and starter to look for him, and eventually in 1947 she managed to find him in a hospital in Reggio Emilia, naked, hungry and undernourished. Mario was nine then and he would not even recognize her. Three days later, the pair boarded a ship bound for the United States to live with Capecchi’s uncle, who with his wife had founded a Quaker community north of Philadelphia. Capecchi’s mother never recovered from her wartime experiences. So it was left to his uncle and aunt to bring up the young boy.

Capecchi’s experiences have left him fiercely self-sufficient, and keenly aware of the importance of supportive and inspiring mentors. When choosing new members of his team, Capecchi applies his philosophy of looking beyond people who have the obvious scientific backgrounds. He puts much more emphasis on

46 applicants’ drive and passion, rather than their curriculum vitae. Given his own experiences, he is much more interested in where his protégés end up, rather than where they started. His nomadic beginnings are reflected in his science. Capecchi likes to change fields roughly every seven years. He worked on bacterial viruses before moving into the mammalian genetics for which he is renowned. Today, he is interested in the developmental genetics of the nervous system and behaviour. Capecchi credits his love of pursuing big questions to James Watson, the Nobel Prize winner who, together with Francis Crick, co-discovered the DNA double helix structure. Watson was his PhD supervisor at Harvard University.

Through Jim Watson the cultural heritage or the genealogical tree of his cultural affiliation can be tracked back in Italy. Actually Jim Watson had studied with a great Italian researcher, Salvador Luria, Nobel Prize winner for Physiology or Medicine in 1969 for his research on the genetics of bacterial viruses (bacteriophages). Luria in his turn, before fleeing Italy in 1938 because of race laws, completed his education under the guidance of Giuseppe Levi, the greatest Italian biomedical researcher between the two world wars, who founded in Turin a school where three Italian scientists graduated before winning later on a Nobel Prize: the first one was Salvador Luria (1969), the second one is Renato Dulbecco (1975) and the third one is Rita Levi Montalcini (1986). Levi is better renown in Italy as the father on Natalia Ginsgurg, author of the novel “Lessico familiare” (Family Sayings) in which Levi is the main character. In this cultural genealogical reconstruction Mario is the great-grandchild of Giuseppe Levi and the nephew of Renato Dulbecco and Rita Levi Montalcini.

But Mario’s relationship with his famously outspoken mentor wasn’t without friction. He recalls the time they disagreed over the results of an experiment on the rates at which the subunits of

47 ribosomes, the cellular bodies that make proteins, come together and separate. Mario was not convinced by the data and suspected that an unknown protein might be involved. He wanted to repeat the work; Watson thought the case was closed. When the argument escalated, Mario threw glass plates bearing key data into the bin, ensuring that he would not have to publish the results. But he was right: a few years later a ribosomal dissociation factor was discovered. Meeting the quietly spoken Mario today, it is difficult to imagine him being confrontational. He shuns large conferences, and prefers to keep his research group to a manageable size of about ten postdocs and five graduate students.

Faithful to his style, i.e. using his fantasy and his proverbial determination in directing his small research group, in the last years Mario Capecchi developed new models of transgenic mice to systematically modify genes of the HOX family, regarded as the general switches that control embryonic development. He therefore produces very useful models to study severe defects of human development. Moreover Capecchi and his co-workers have recently developed the first model of mouse with alveolar rabdomyosarcoma, an aggressive form of child muscle tumor. Finally it has to be mentioned that Mario has generously participated for the last two years in the European School of Genetic Medicine, that holds its courses in the Bologna University Residential Center of Bertinoro. In particular Mario, with Victor McKusick and other 25 European and American colleagues, has just finished to teach in the 20th Course of Medical Genetics in Bertinoro, that saw the participation of 110 students from all over Europe and additional 200 students who followed the course live via the internet (webcasting) from five Mediterranean countries.

48 To pay a tribute to Mario Capecchi’s latest interests of research, as well as Victor McKusick’s fields of investigation, this afternoon in this very hall a scientific symposium will be held in honour of our two newly-graduated doctors, entitled Mitochondria and Cancer. You are all invited.

49 Doctoral Lecture Alma Mater Studiorum University of Bologna Bologna, Italy May 12, 2007

Mario R. Capecchi

It is a great honor for me to receive a laurea honoris causa in Biotechnology Medicine from the University of Bologna. Not only does the University of Bologna share a historical tradition that is unequalled among all Universities in the world, but through the ages it has been a center for learning, particularly in medicine and the biological sciences, and this tradition continues.

For me it’s a very special honor because I was born in Italy, close to Bologna, in Verona. My family resided in Florence just south of Bologna. I lived in Italy from birth until I was nine years old and then immigrated to the United States with my mother. My daughter, Misha Capecchi, spent a year, 2006, at the University of Bologna as a student, studying art and working at the Genetics Clinic under the supervision of Dr. Laura Mazzanti. My daughter became fluent in Italian and had a marvelous experience at your great university. Her supervisor, Dr. Laura Mazzanti was an outstanding mentor and also took excellent care of her which I greatly appreciated. Particularly my wife, was worried about our daughter since she was such a long distance from our home. She need not have worried. We did have the opportunity to visit her during her stay here and fell in love with your beautiful city; its marvelous colors, its people, and your superb cuisine. The food is so good that its enjoyment almost becomes a mystical experience.

50 My experience as a child in Italy certainly forged my future. From birth until the age of three and one-half years old I lived in the Dolomites north of Bolzano. It is not possible to imagine more beautiful mountains. My mother was a poet and belonged to a group of poets known as the Bohemians. She received her training at the Sorbonne in Paris and was a lecturer at that university in literature and languages. They wrote pamphlets against Nazism and Fascism. She knew that sooner or later she would be picked up by the Gestapo. In the spring of 1941 she was picked up and taken to Dachau, near Munich, as a political prisoner. Anticipating her arrest she had sold most of her possessions and gave the proceeds to an Italian peasant family in the Tyrol so that they could take care of me. I lived on their farm for one year. It was a very simple life. They grew their own wheat, harvested it and took it to the miller to be ground. From the flour they made their own bread which they took to the baker to be baked. In the late fall, the grapes were harvested by hand and put into enormous vats. The children, including me, stripped, jumped into the vats and became squealing masses of purple energy. I still remember the pungent odor and taste of fresh grapes.

World War II was now in full swing. For reasons that have never been clear to me, my mother’s money ran out after one year, and at age 4  I set off on my own. I headed south, sometimes living in the streets, sometimes joining gangs of other homeless children, sometimes living in orphanages, and most of the time being hungry.

In the spring of 1945 Dachau was liberated by the American troops. My mother survived the concentration camp and set out to find me. In October of 1946 she succeeded and brought me to America where her brother was living. My aunt and uncle were Quakers. They took on the task of converting me into a

51 productive human being. This was a formidable task. I had received no formal education or training for living as a social being. Quakers do not believe in frills, but rather in a life of service. I was given few material goods but every opportunity to develop my mind and soul. The day after I arrived in America I went to school.

I went to college at Antioch where I majored in physics and chemistry. From there I went to graduate school at Harvard and worked in the laboratory of Dr. James D. Watson. At the time the molecular biology revolution was in the process of being born and Dr. Watson personified molecular biology. He was our guru and we were the eager practitioners. His bravado encouraged self-confidence in those around him. His stark honesty made our quest for truth uncompromising. He taught us not to bother with small questions, for such pursuits were likely to produce small answers.

From Watson’s laboratory I became a member of the faculty at Harvard School of Medicine. I stayed there for four years and then moved to Utah. The experiments that led to the development of gene targeting started at the University of Utah. I will describe the beginning of gene targeting and how it has revolutionized the study of human medicine.

52

Mario Renato Capecchi (left) and Rettore Pier Ugo Calzolari (right)

53

Victor A. McKusick (left) and Rettore Pier Ugo Calzolari (right)

54 Laudatio for Victor A. McKusick by Giovanni Romeo

Victor A. McKusick (University Professor and not Professor Emeritus of the Johns Hopkins School of Medicine of Baltimore, as he wishes to define himself to stress the fact that his academic activity is still under way) is the most outstanding figure in the field of Medical Genetics in the U.S. and in the world. As I already did in the case of Mario Capecchi, before talking about Victor’s scientific success I would like to dwell upon the history of his youth, in particular a very interesting genetic characteristic that the underlined in an interview to the Baltimore Sun about ten years ago. This interview started with the statement: “I am a clone too”. Actually Victor has an identical twin, Vincent, who pursued a completely different career. Vincent, after a degree in Law, became first judge of the Supreme Court of Maine. In the interview, Victor said that he and his twin brother grew up on a dairy farm in Maine in a family that valued academic achievement. They split up when they went to college, Vincent to Bates and Victor to Tufts, partly to avoid competing with each other for scholarship support but also because their career goals had diverged. Vincent had been long set for the law; Victor’s goals were altered by an experience that Vincent did not share. At the age of 15 he developed an abscess of his left axilla and ulcer of the right elbow that would not heal. After many efforts to culture the causative organism(s) he ended up in the Massachusetts General Hospital in Boston where he spent 10 weeks in 1937. There a microaerophic streptococcus was cultured that had escaped detection previously in Maine because of its fastidious cultural requirements. The lesions healed and stayed healed. In the process he saw much of medicine and decided that it was the field for him. In his last semester at Tufts he took an elective course in genetics with Professor Paul A. Warren, an

55 inspiring teacher, who made the topic of classic Mendelism exciting.

He was accepted to matriculate in March 1943 at Johns Hopkins, and after completing four academic years of medical school in three calendar years, his class graduated from Johns Hopkins Medical School in March 1946. He then embarked on an internship in internal medicine at the Johns Hopkins Hospital, April 1, 1946 to July 1, 1947. He had fully expected that after medical school and a certain amount of postdoctoral training he would go back to Maine to enter the general practice of medicine. “That was not to be” he said “because of my ambitions for the internship on the prestigious Osler Medical Service with its tradition of training for academic medicine, and because of career-changing developments during my years of hospital training.”

Hence the description of his most important scientific results can begin, as Victor will illustrate in a few minutes. I just wish to highlight that his contribution to the development of medical genetics are very numerous as shown in his resume. His most valuable achievement in the medical-biotechnological field is the development, starting from 1960, of the first and most important database on genetic diseases, today available on-line with the name of OMIM (On-line Mendelian Inheritance in Man). This has become the reference source most used by physicians, biologists, biotechnologists and geneticists from all over the world. For the present computer standards it is “low-tech stuff” but it did have the pioneering feature that it went on the computer in 1964, was a pioneer in computer-based scientific book publication (1st edition in 1966), and a pioneer in use of the internet for distribution (beginning in 1987).

56 In 1968 McKusick with his co-workers carried out the first mapping of a human gene on one of the 22 autosomes (Duffy blood group located on chromosome 1). After this very first mapping of a human gene (located out of chromosome X), McKusick and Frank Ruddle of the Yale Medical School coordinated the activity of genetic mapping of man that was developing in many American and European laboratories. This coordination represented the “prehistory” of what was later called “Human Genome Project” of which McKusick was one of the founding fathers. Thanks to his commitment in the work of human genetic mapping that was at that time mainly based on the genetics of somatic cells, McKusick was the first president elected of HUGO (Human Genome Organization), that has had a crucial role in the development of the Human Genome Project . Among other acknowledgements, Victor McKusick was awarded the William A. Allan Award of the American Society of Human Genetics, the James Murray Luck Award of the National Academy of Sciences, the Gairdner Award, the Passano Award, the Lasker Award, the Mendel’s Medal of the Villanova University and the Benjamin Franklin’s Medal of the American Philosophical Society. In 2002, Victor McKusick receive the National Medal for Sciences from the President of the United States.

The McKusick-Nathans Institute of Genetic Medicine in Baltimore was dedicated to Victor by his Alma Mater. Daniel Nathans was Professore of Molecular Biology at Hopkins and was awarded the Nobel Prize in 1978 for discovering restriction enzymes, which are at the basis of genetic engineering. In the world there are two more centers or Genetic Medicine Institutes that bear the name of Victor McKusick. The first one was founded in 2000 by Wilson Lo, a medical geneticist who trained with Victor, at the Peking Union Medical College. The second

57 one is in Bologna’s hills, in Ronzano, and it was dedicated to Victor almost exactly two years ago, on May 13, 2005, in the presence of Victor himself, our Rettore PierUgo Calzolari, the president of Hopkins William Brody, the Major of Bologna Sergio Cofferati and many other city Authorities. The center is named “Giuseppe Levi and Victor McKusick EuroMediterranean Center for Genetics and Medicine” and it will begin to host courses of the European School of Genetic Medicine in the next June. In order to celebrate the 20th edition of the Course in Medical Genetics, where Victor and other geneticists like Mario Capecchi have been teaching, the European Genetics Foundation assembled a collection of photographs, personal memories and comments from a number of alumni and faculty who participated in the courses over the last 20 years. This booklet will be available on the web site: www.eurogene.org. I leave to you to judge these memorabilia that in my opinion represent the most significant documents of Victor’s invaluable contribution to the education of so many generations of medical geneticists in Italy, in Europe and in the world.

58 Doctoral Lecture Alma Mater Studiorum University of Bologna Bologna, Italy May 12, 2007

Victor A. McKusick, M.D.

Magnifico Rettore PierUgo Calzolari, Dear Colleagues, Ladies and Gentlemen,

I am immensely pleased to receive this honorary degree from the historic first university of the Western World. None of my previous honorary degrees will I cherish more than this one from Bologna. My other honorary degrees carry various monikers, most often Sc.D. and M.D., but this is my first doctorate honoris causa in Medical Biotechnology. I presume this is in recognition of my work in the bioinformatics of human genetics.

Beginning in the early 1960s I compiled a comprehensive listing, with annotation and bibliographic references, of inherited human traits, under the title Mendelian Inheritance in Man (MIM for short), with the subtitle Catalogs of Autosomal Dominant, Autosomal Recessive, and X-linked Phenotypes. That was before the days of the word-processor. I had the wit to take the advice of my computer assistant and “put it on the computer” (the main- frame at Johns Hopkins University) in early 1964. Computerization of the compilation facilitated updating and book publication. With its first print edition in 1966, MIM was a pioneer

59 in computer-based publication. The indices and pagination were created by computer. Eleven other editions of the book followed, all published by photo offset of the computer output, with the most recent edition, the 12th in 3 volumes, in 1998. In the 1980s the computer file for MIM was used at the National Library of Medicine for development of a system for presentation and search of full-text information. In 1985 my colleagues at Johns Hopkins put the file online under the name OMIM (online MIM; pronounced “oh-mim”). General distribution of OMIM on the Internet began in 1987 from the Welch Medical Library at Johns Hopkins. Beginning in 1995, OMIM has been distributed on the Internet from the National Center for Biotechnology Information (NCBI) of the National Library of Medicine in Bethesda, Maryland, USA. It serves as a hub for a considerable number of genetics databases that are managed and distributed from NCBI. The URL for OMIM is: http://www.ncbi.nlm.nih.gov/omim. Throughout, MIM and its online version have been authored and edited in my department at Johns Hopkins with assistance of many colleagues at Hopkins and elsewhere.

Old age, despite its attendant infirmities, has some compensations, some rewards. For one, survival to this age allows me to witness developments in science and medicine I never could have dreamed of. For a second, it has given me a chance to see fulfillment of one of the wildest of my dreams. These days, because of the advances in genetics, there are many developments that I could never have foreseen. For reasons I will tell you, my favorite, selected from many, is the successful pharmaceutical treatment of the Marfan syndrome. Persons with Marfan syndrome tend to have abnormalities of the skeleton (being unusually tall with “spider fingers” and spinal curvature), the eyes (most specifically dislocated lenses), and, as the main life- threatening feature, the aorta (dilation and rupture). It is a rare disorder - perhaps 1 in 5,000 births in the US - but for families

60 who carry the gene the frequency of this autosomal dominant disorder is not 1 in 5,000 but can be 1 in 2, or 50%! Studies of the Marfan syndrome were my transition from cardiology to medical genetics in the early 1950s. The first edition of my monograph Heritable Disorders of Connective Tissue was published in 1956 and comprised a comprehensive discussion of Marfan syndrome and 4 other related disorders. The work was dedicated to Archibald Garrod, and “to all who believe, as he did, that the clinical investigation of hereditary disorders can shed light on normal development and biochemical mechanisms”. Garrod was the English physician who developed the concept and name Inborn Errors of Metabolism. We conceived that the Marfan syndrome results from a mutation-determined defect in one element of connective tissue wherever it exists in the body: skeleton, eye, and aorta. And it seemed most likely in 1956 that the defect was in a structural element, a fibrous element, of connective tissue. In 1991 when mutations causing Marfan syndrome were localized to fibrillin, it seemed that structural weakness of that specific fibrous element was responsible for the features of Marfan syndrome. On further analysis, however, it turned out that the pathogenesis of Marfan syndrome is related to another function of fibrillin: fibrillin sequesters, and in general regulates, the activity of transforming growth factor beta (TGF-beta), which it binds in an inactive form. The work of Hal Dietz and coworkers in the Institute of Genetic Medicine at Hopkins indicates that the pathologic changes in Marfan syndrome are caused by dysregulation of TGF-beta and excessive activity in the TGF-beta pathway. Furthermore, losartan, a drug used for treatment of hypertension, suppresses TGF-beta function. In both an authentic mouse “knock-in” model of Marfan syndrome and in an initial series of severely affected children with Marfan syndrome, Dietz and his colleagues have shown that losartan reverses the histopathologic changes in the aorta and stays or reverses the dilation of the aortic root. I never expected to see

61 such a thing in this disorder I had considered to be a primary defect in a structural element of connective tissue.

My fondest dream, which has now been fulfilled, was that all the genes would be mapped to their specific chromosomal locations. In 1968, my colleagues and I mapped the first gene to a specific one of the non-sex (autosomal) chromosomes, the gene for Duffy blood group to chromosome 1. The next year, in August 1969, in a closing address at the International Conference on Birth Defects in The Hague, I suggested that a good way, perhaps the best way, to arrive at basic understanding of birth defects would be to map all the genes on the chromosomes. A month earlier, in July 1969, Neil Armstrong and Buzz Aldrin had landed on the moon. An exciting moon-landing mind-set infected biology in the early 1970s when we and others claimed that exploration of the inner space of the cell nucleus, specifically the chromosomes, had as much or more usefulness than exploration of the planets and moons of outer space. The time-line of the Human Genome Project (HGP) is usually given as follows: complete sequencing proposed in 1985; discussed, debated, and planned 1985-1990; initiated (NIH project) in 1990; and “completed” in 2003. I have always defined the HGP as one to map all the genes to their chromosomal sites and to sequence the entire DNA. By this definition the HGP started in the early 1970s. Frank Ruddle and I initiated international Human Gene Mapping Workshops in 1973. For the next 20 years, aficionados of gene mapping met each year or two as a consortium, if you will, of investigators to collate information on the gene map. By 1985 when complete sequencing was proposed, the consortium could count about 600 gene loci that had been assigned to specific chromosomes. Many of these were the genes for hereditary diseases; others were the genes for various blood groups, serum proteins, and enzymes. By 1980, Ruddle and

62 I were predicting that all the genes would be localized on the chromosomes by the end of the 20th century.

I am certain that in 1970 we did not have a clear idea of what methods would permit mapping all the genes nor were we fully clear how mapping would aid in elucidating birth defects. The arrival of molecular genetics to human genetics in the 1980s supplied both. It provided methods for mapping by use of radio- labeled gene probes in somatic cell hybrids and for in situ hybridization to chromosomes, and especially it provided a myriad of DNA markers (RFLPs, VNTRs, SNPs, and others) that could be used in family linkage studies. How did the map of genes help with the basic understanding of birth defects and indeed their diagnosis and management? In the 1980s, positional cloning of the genes mutant in “mystery diseases” such as Huntington disease, muscular dystrophy, and cystic fibrosis came along. Positional cloning involved first mapping the locus of the gene by linkage and then “walking in on it”, from flanking markers for example. Once the precise gene defect (mutation) was known it was then possible to devise specific DNA diagnosis as well as figure out the steps between gene and phene (connecting the mutant gene with the disorder) and the derangements therein that was responsible for the birth defect or clinical disorder. Knowing those steps might permit design of effective therapy. The related positional candidate approach led to finding the defect of fibrillin in Marfan syndrome and then to working out the pathogenesis of that disorder and the therapeutic usefulness of losartan.

When the Human Genome Project was under discussion (1986- 89), Walter Gilbert pointed out to me that complete sequencing would be necessary just to find all the genes. Indeed, such is the case. Now that we have the complete DNA sequences, all the genes have been mapped by their identification in that sequence.

63 In the application of gene mapping to birth defects, many mendelian disorders (those with simple patterns of inheritance) have been elucidated and also complex traits, which many birth defects are. All of these are chronicled in OMIM which now has the subtitle, A catalog of human genes and genetic disorders. The gene discovery process, the repertoire of disease-related mutations in the more than 2,000 genes in which one or more disease-related mutations are now identified, the pathogenesis of the mutant phenotype, as well as descriptions of the clinical phenotype and practical matters of diagnosis and management are all recorded diachronically in OMIM. It is very heavily consulted worldwide daily. My profound thanks for the recognition this ancient university has given me and OMIM through this doctorate honoris causa in the new field of medical biotechnology.

64 Mitochondria and Cancer 3rd Bologna Genetic Medicine Day and Scientific symposium in honour of Prof. V.A. McKusick and M.R. Capecchi Bologna – May 12, 2007 Aula Absidale di Santa Lucia via de’ Chiari, 25

Programme

Chair: G. Romeo, G. Lenaz, M. Rugolo, Università di Bologna

14.00 E. Bonora (U.O. Genetica Medica, Policlinico S.Orsola-Malpighi, Bologna) The model of familial Non-Medullary Thyroid Cancer (fNMTC)

14.15 G. Tallini (Dip. Anatomia Patologica, Ospedale Bellaria, Bologna) Mitochondria-rich (oncocytic) tumors

14.30 A. Ghelli (Dip. Biologia Evoluzionistica, Università di Bologna) Oxidative phosphorylation dysfunctions: role of the Bcl2 Protein

65 15.00 G. Gasparre (U.O. Genetica Medica, Policlinico S.Orsola-Malpighi, Bologna) MtDNA mutations as molecular hallmarks of oncocytomas

15.30 M. DiRenzo (ICRT, Università di Torino) The fumarase mitochondrial tumor suppressor gene

16.00 G. N. Ranzani (Dip. Genetica e Microbiologia, Università di Pavia) Characterization of mutations in MYH, a base excision repair gene, associated to familial colon adenomatous polyposis

16.30 M. Genuardi (Dip. Patofisiologia clinica, Università di Firenze) The Birt-Hogg-Dubé syndrome: a tumor-predisposing condition associated with mitochondrial alterations

17.00 A. Rasola (Dip. Scienze Biomediche, Università di Padova) Hexokinase: between energy metabolism and cell death

17.30 S. Salvioli (Dip. Patologia Sperimentale and Centro Interdipartimentale L.Galvani, Università di Bologna) P53 and mtDNA: an interaction affecting aging, longevity and Cancer

18.00 V.A. McKusick (Johns Hopkins Hospital, Baltimore) and M.R. Capecchi (Howard Hughes Medical Institute, Salt Lake City) Conclusions of the symposium

66 Mitochondria and Cancer

ABSTRACTS

The model of familial Non-Medullary Thyroid Cancer (fNMTC) Elena Bonora Unità di Genetica Medica, Policlinico Universitario S. Orsola-Malpighi; Università di Bologna, Bologna, Italy

Thyroid cancer is the most common malignancy of the endocrine system. It consists of four different forms of neoplasia: papillary (PTC), follicular (FTC), undifferentiated (anaplastic) (UTC) and medullary thyroid carcinoma (MTC). PTC, FTC and UTC, collectively labeled as Non-Medullary Thyroid Carcinoma (NMTC) derive from thyroid follicular epithelial cells, whereas MTC derives from parafollicular C-cells. NMTC includes accounts for 80-90% of all thyroid neoplasias. Familial NMTC (fNMTC) represents 3-7% of all thyroid tumors and is associated with some of the highest familial recurrence among all cancers, with a risk for first-degree relatives of 5/10-fold. Tumors are multifocal, recur more frequently, and show an earlier age of onset than sporadic cases. Inheritance patterns indicate that fNMTC is transmitted as an autosomal dominant trait with reduced penetrance, but a multigenic inheritance could not be excluded. Considering the high recurrence risk and the mode of inheritance of fNMTC, this type of tumor represents an excellent model to study the predisposing genes to familial cancer. In collaboration with the International Consortium for the Genetics of fNMTC, we previously mapped two predisposing loci. The first one, TCO (Thyroid tumor with Cell Oxyphilia), was mapped to the 19p13.2 region (Canzian et al., 1998). The second locus, NMTC1 (Non-Medullary Thyroid Carcinoma 1), was

67 mapped to chr2q21 and was associated with the follicular variant of PTC (fvPTC) (McKay et al., 2001). Evidence for an interaction between the two loci has been provided in a subset of fNMTC families, with a two-locus mode of inheritance when both the histological variants of oncocytoma and fvPTC were present (McKay et al., 2004). The TCO locus is associated with recurrence of oncocytic tumors, characterized by the presence of Hürthle cells, rich in mitochondria. In order to identify the TCO nuclear gene, genes mapping to the chromosome 19p13.2 have been analyzed in the patients derived from the families contributing to the linkage region. We identified new variants in the coding region of TIMM44 and MUC16, a member of the complex for mitochondrial import of nuclear-encoded proteins and of the mucin family and highly expressed in thyroid tumors, respectively. Functional studies of these variants are undergoing. References: Canzian F, et al. (1998). A gene predisposing to familial thyroid tumors with cell oxyphilia maps to chromosome 19p13.2. Am J Hum Genet. 63(6):1743-8. McKay JD, et al. (2001) Localization of a susceptibility gene for familial non-medullary thyroid carcinoma to chromosome 2q21. Am J Hum Genet 69, 440-446. McKay JD, et al. (2004).Evidence for interaction between the TCO and NMTC1 loci in familial non-medullary thyroid cancer. J Med Genet. 41(6):407-12

The fumarase mitochondrial tumor suppressor gene Maria Flavia Di Renzo Università di Torino at IRCC, Candiolo, Torino

Germline mutations in the fumarate hydratase (FH) gene predispose to leiomyomatosis, renal cysts, and renal cell cancer

68 (HLRCC). FH functions as a tumor suppressor gene, as heterozygous mutations have been found in the germline of HLRCC patients and loss of the wild type allele occurs in somatic cells and results in the near complete loss of enzyme function. HLRCC tumors overexpress HIF1alpha and hypoxia responsive genes, which might contribute to tumor onset and progression. It was demonstrated that, in FH deficient cells, the accumulated fumarate competitively inhibits the 2-oxoglutarate-dependent dioxygenases that regulate hypoxia-inducible factor (HIF). The targeted inactivation of the fh gene in the mouse kidney caused the development of renal cysts that overexpress HIF1alpha and beta. Here we show that the reduction of FH enzymatic activity by means of interfering RNA leads to anchorage independent growth of already transformed cells and protection of both normal and transformed cells from apoptosis induced by various stimuli, such as serum withdrawal and DNA damaging agents. We found that apoptosis protection does not depend on HIF1alpha increase, as it occurs after HIF1alpha down modulation by RNA interference and in cells showing a defect of HIF2alpha, which is the obligatory HIF partner in transcription activation. These data show that a primary event in epithelial carcinogenesis, such as protection from the apoptotic death triggered by DNA damage, occurs in FH defective cells independently from HIF pathway activation.

MtDNA mutations as molecular hallmarks of oncocytomas Giuseppe Gasparre Unità di Genetica Medica, Policlinico Universitario S. Orsola-Malpighi; Università di Bologna, Bologna, Italy.

Oncocytic tumors are lesions composed of cells characterized by mitochondrial hyperplasia particularly common in the thyroid gland. Because of their distinctive features they represent a good

69 model to study the role of mitochondria in tumorigenesis. We recently demonstrated the association between two pathogenic mitochondrial mutations and a defective biochemical phenotype in a cell line model of oncocytoma. To understand whether specific mitochondrial DNA (mtDNA) mutations are associated with the oncocytic phenotype we sequenced the entire mtDNA in 45 oncocytic thyroid tumors (HCTs), 5 oncocytic breast tumors and 52 control cases (21 non-oncocytic thyroid tumors, 15 breast carcinomas and 16 gliomas) utilizing a recently developed technology (Applera). Thirteen oncocytic lesions (26%) presented disruptive mutations (nonsense or frameshift), whereas only 2 samples presented such mutations in the non- oncocytic control group (3.8%). In one case with multiple thyroid nodules analyzed separately a disruptive mutation was found in the only nodule with oncocytic features. In one of the 5 oncocytic breast tumors a disruptive mutation was identified. All disruptive mutations were found in complex I subunit genes and the association between these mutations and the oncocytic phenotype was statistically significant (p=0.001). To study the pathogenicity of these mitochondrial mutations, primary cultures from oncocytic tumors and corresponding normal tissues were established. Molecular and biochemical analysis and electron microscopy showed that primary cultures derived from tumors bearing disruptive mutations failed to maintain the mutations and the oncocytic phenotype. We conclude that disruptive mutations in complex I subunits are markers of thyroid oncocytic tumors.

70 The Birt-Hogg-Dubé syndrome: a tumor-predisposing condition associated with mitochondrial alterations Maurizio Genuardi Dipartimento di Fisiopatologia Clinica, Università degli Studi di Firenze

Birt-Hogg-Dubé syndrome (BHDS) is an autosomal dominant condition characterized by the phenotypic triad of benign skin tumors, renal tumors and spontaneous pneumothorax. Mutations of the FLCN gene, located on chromosome 17p11.2, are found in the majority of BHDS cases. FLCN encodes for a protein named folliculin, whose function has not yet been fully elucidated, although there is evidence that FLCN is involved in energy and nutrient-sensing signalling pathways. About 50% of FLCN germline mutations are represented by small frameshift insertions/deletions occurring in a stretch of 8 cytosines within exon 11. FLCN is thought to act as a tumor suppressor gene, as FLCN loss of heterozygosity has been documented in renal tumors from BHDS patients. The phenotype of BHDS is highly variable. Different types of renal and skin tumors are associated with this condition; BHDS kidney tumors include oncocytomas, chromophobe carcinomas, mixed oncocytic/chromophobe tumors, and clear cell carcinomas; trichodiscomas and fibrofolliculomas, which derive from the hair follicle, are the typical BHDS skin tumors. Oncocytic and chromophobe renal tumors are characterized by the presence of quantitative and/or qualitative mitochondrial alterations. Based on the molecular and pathological characteristics of its main component tumors, BHDS shares pathogenetic similarities with other hamartomatous syndromes, such as Peutz-Jeghers and Cowden syndrome and tuberous sclerosis, whose gene products are involved in mTOR signalling pathways. The clinical and molecular findings in a series of BDHS will be presented, with focus on the significance of further clinical manifestations, including parotideal oncocytomas and colorectal tumors.

71 Oxidative phosphorylation dysfunctions: role of the Bcl-2 protein Anna Ghelli Dip.di Biologia Ev. Sp. Via Irnerio 42, Università degli Studi, Bologna, Italy

The proto-oncogene Bcl-2 prevents apoptosis and some forms of necrosis, although its exact mechanism of action is not well defined. Bcl-2 has been shown to localise to multiple cell compartments, including the outer mitochondrial membrane, the endoplasmic reticulum and the nucleus. Accumulating evidence indicates that rather than antagonizing specific steps of the apoptotic pathway, Bcl-2 could regulate mitochondrial metabolism, including adenine nucleotide exchange (1) and permeability to metabolic anions (2). Recently, Bcl-2 overexpression has been shown to significantly improve oxidative phosphorylation in cells bearing pathogenic mutations in mitochondrial DNA (mtDNA) affecting tRNA genes, which cause a severe energetic failure (3). The aim of this study is to verify whether Bcl-2 overexpression can improve the energetic function and survival of cells with severe complex I dysfunctions. To this purpose, we have chosen two cellular models bearing mtDNA mutations affecting the ND subunits of complex I. In particular a thyroid oncocytic cell line (XTC.UC1) with a frameshift mutation in the ND1 gene, which generates a truncated protein, and a cybrid cell line bearing a pathogenic missense mutation causing Leber’s Hereditary Optic Neuropathy (HL180) have been utilized. Both these cell lines were unable to survive in galactose medium, a condition which forces cells to rely solely on mitochondria for ATP production. Furthermore, the rate of mitochondrial ATP synthesis driven by complex I substrates was greatly reduced. However, Blue Native electrophoresis showed that complex I was disassembled in XTC.UC1 cells, but not in HL180.

72 Upon microscopic inspection, Bcl-2-overexpressing cells incubated in galactose medium appeared healthy. However, the ATP levels of the XTC.UC1 Bcl-2 cells remarkably decreased in a similar manner to the XTC.UC1 cell line, whereas the HL180 Bcl-2 cell line maintained an ATP content significantly higher than non-transfected cells. Accordingly, the rate of ATP synthesis driven by complex I was reduced in the XTC.UC1 Bcl-2 line and slightly enhanced in HL180 Bcl-2 cells. Immunoprecipitation analysis showed that Bcl-2 and complex I physically interacted in HL180 but not in XTC.UC1 cells. These results suggest that Bcl- 2 is unable to restore the mitochondrial energetic competence in cells with mutations causing the disassembly of complex I. Conversely, overexpression of Bcl-2 can ameliorate the oxidative phosphorylation performance in cells bearing a mild mutation of complex I, thus increasing cell viability and promoting survival. This appears to be a direct effect of Bcl-2 on the respiratory complex. Despite the fact that Bcl-2 did not effect the mitochondrial function of XTC.UC1 cells, its overexpression was able to safeguard cellular morphology and adhesion. This was achieved through inhibition of actin proteolysis, which was observed in XTC.UC1 cells incubated in galactose medium by western blot analysis. In conclusion, in this cell line, the main target of Bcl-2 is the cytoskeleton/adhesion machinery. References: 1. Vander Heiden MG et al., (1999) Mol Cell. 3:159-167 2. Vander Heiden MG et al., (2000) Proc Natl Acad Sci U S A. 97: 4666-4671 3. Manfredi G et al., (2003) J Biol Chem. 278: 5639-5645

73 Familial adenomatous polyposis associated with MYH base excision repair gene Guglielmina Nadia Ranzani Dept. of Genetics and Microbiology, University of Pavia

Familial adenomatous polyposis is an inherited syndrome conferring a very high risk of colorectal cancer through the formation of multiple colorectal adenomas. The number of adenomas, the age of onset of adenomatosis and carcinoma, as well as the possible presence of extracolonic manifestations, vary both between and within the affected families. In the “classic” disease, the number of adenomas ranges from a hundred to thousands and polyps usually emerge during the second-third decade of life. On the other hand, the so-called “attenuated” polyposis (<100 adenomas) is characterized by a milder course of the disease. Both classic and attenuated polyposis can be associated with germline mutations of either APC tumor suppressor gene or MYH (MUTYH) DNA base excision repair gene. Classic (FAP) and attenuated (AFAP) polyposis linked to APC gene follow a dominant mode of inheritance, whereas the MYH-associated disease (MAP) is recessively transmitted. Interestingly, no inherited deficiencies of base excision repair (BER) had been associated with disease, until the recent recognition of MAP. Patients with MAP are carriers of MYH biallelic mutations that predispose to the development of multiple colorectal adenomas and carcinomas. Tumor cells of these patients contain an excess of somatic mutations consisting of G:C>T:A transversions: in addition to the G to T mutations of APC gene, MAP adenomas show a specific G12C KRAS mutation, that also results from G to T transversion. This pattern is typically associated with defective repair of mutations caused by reactive oxygen species (ROS). ROS generated during aerobic metabolism represent a

74 source of DNA damage: the oxidation product 8-oxoG is stable and mispairs with adenine. Unless repaired, this leads to G:C>T:A transversion at the next round of DNA replication. MYH is a DNA glycosylase that plays a crucial role in repair of 8- oxoG mismatches by removing the mismatched adenine. Numerous MYH variants that are likely to be pathogenetic have been reported, including missense mutations; however, very few MYH variants have so far been subjected to functional analysis. To investigate the frequency of MYH- versus APC-associated polyposis and to characterize MYH mutations in patients from southern Europe, we searched for MYH germline changes in polyposis patients from Italian families. Moreover, by transfecting wt or mutant MYH-cDNA in myh-/- mouse cells, we investigated the biological effects of MYH mutated proteins in a mammalian cell background.

Hexokinase: between energy metabolism and cell death Andrea Rasola Dip. Scienze Biomediche, Università di Padova

Mitochondria are multifunctional organelles whose activities are at the heart of crucial biological processes such as cell proliferation, survival and senescence. Deregulation of mitochondrial function is associated with more than 40 known acute and chronic human disease states, including neurodegenerative and neuromuscular diseases, diabetes, cancer, and aging. In all these cases, subtle alterations in mitochondrial physiology cause changes in the survival/death equilibrium leading to the pathologic condition. The key player of this fine and complex tuning is the Permeability Transition Pore (PTP), a high conductance mitochondrial channel, whose opening induces a sudden increase of the inner mitochondrial membrane permeability to ions and solutes, prompting cell death. We found

75 that PTP displays a central role in death regulation both in physiologic conditions and in models of disease, making it a putative target of pharmacological apoptosis modulators. At present, the only known pore regulator is Cyclophilin D, whose inhibition by Cyclosporin A (CsA) renders the pore more refractory to openings. The use of CsA allowed to identify the role of the PTP in some carcinogenesis models. Indeed, most tumor types are endowed with a reduced apoptosis and can exploit an enhanced glycolysis to meet up with their energy demand. We had previously observed that a profound ATP depletion affects apoptosis progression, suggesting that the comprehension of the interactions between energy metabolism and regulation of cell demise is a promising strategy to find out selective devices for wiping off neoplastic cells. In this framework, it was found that the glycolytic enzyme hexokinase is partially associated to the outer mitochondrial membrane, where it might be involved in apoptosis regulation, acting at the crossroad between energy metabolism and cell survival. Understanding the mechanistic features that link hexokinase to pore opening and apoptosis sensitization in diverse tumor cell models is therefore a promising advance for the identification of selective anti-tumor tools.

p53 and mtDNA: an interaction affecting aging, longevity and cancer Stefano Salvioli Department of Experimental Pathology and CIG - Interdepartmental Centre for Studies on Biophysics, Bioinformatics, and Biocomplexity - University of Bologna

Most cancers are age-related diseases, and aging is considered a strong risk factor for neoplastic diseases. In fact, aging and cancer share a number of modifications occurring at cellular level, and in

76 particular mitochondria have been recognized since long time as possible major determinants in both aging and cancer because of their role in the production of Reactive Oxygen Species and in apoptosis. Recent evidence indicate that also mitochondrial genome (mtDNA) is involved in both aging and cancer1,2. It has been reported that, during aging, tissues steadily accumulate mtDNA mutations3 and that such mutations can affect carcinogenesis. Indeed, large scale mtDNA deletions have been detected in breast cancers (BC)4 and it has been observed that the in vitro depletion of mtDNA does induce chromosomal instability and rho0 cells have a transformed phenotype5. Moreover, it has been reported that, beside mtDNA somatic mutations, mtDNA inherited variants (haplogroups) are associated with longevity or diseases such as Alzheimer's Disease6,7 and can modulate the expression of nuclear genes8. These data suggest that in humans, as in animal models, a sort of cross-talk between the mitochondrial and nuclear genomes does exist, and that this cross-talk may have a deep influence in complex traits (such as aging, longevity and cancer). Conversely, many nuclear factors can impinge upon mtDNA stability. As an example, it has been reported that p53, best known as a pivotal sensor of DNA damage, oxidative stress and nutrient levels, is able to bind to and modulate the activity of polymerase gamma, a key factor for mtDNA replication and repair9,10. On the basis of these data, we presented a project aimed to answer the following questions: i. are inherited mtDNA haplogroups correlated with some parameters of BC, such as disease-free and total survival, or susceptibility to therapy? To test this hypothesis, we will determine the haplogroup of 1,000 BC patients thoroughly studied and collected at the Istituto Tumori in Milan. ii. is this correlation, if present, influenced by TP53 common polymorphism such as the one at codon 72, already known to influence gene transcription activity and subcellular localization of p5311,12? In this case, the same BC sample will be

77 genotyped for TP53 codon 72 polymorphism and the genetic data will be stratified accordingly. iii. is TP53 codon 72 polymorphism able to influence the accumulation of mtDNA somatic mutations, due to a possible interaction with polymerase gamma? We will test this possibility by resequencing the D-Loop region (or the entire mtDNA molecule) of subjects with different TP53 genotype in BC samples and in normal, non transformed tissues of subject of different age. In the meantime, we are resequencing the entire mtDNA of centenarians who, despite their long life, escaped the most common cancers and we are studying the interactome of the above mentioned p53 variants. References 1. Santoro A et al., Biochim Biophys Acta. 2006; 1757:1388; 2. Verma, Cancer Res 2007; 67:437-9; 3. Chomyn A and Attardi G. Biochem Biophys Res Commun. 2003; 304:519; 4. Zhu et al., Cancer Detect Prevent 2004; 28:119; 5. Singh et al., Gene 2005; 354:140; 6. De Benedictis et al., FASEB J. 1999; 13: 1532; 7. Carrieri et al., Hum Genet 2001; 108: 194; 8. Bellizzi D et al., Genes Cells. 2006;11:883; 9. de Souza-Pinto et al., Oncogene 2004; 23:6559; 10. Achanta et al. EMBO J 2005; 24:3482; 11. Bonafe M et al., Cell Death Differ. 2004; 11:962; 12. Salvioli S et al., Cell Cycle. 2005; 4:1264

78 Mitochondria-rich (oncocytic) tumors Giovanni Tallini, M.D Professor of Pathology, University of Bologna School of Medicine

Pathologists have long been aware of the existence of a distinctive type of tumor composed of cells with abundant granular cytoplasm and with strong affinity for eosin, the pink stain used for histology sections. These peculiar cells were first described in 1898 in the thyroid gland by Askanazy (a german pathologist) and in the parathyroid gland by Welsh (an english scientist). In the 1930s Hamperl (another german pathologist) coined for them the term "oncocyte" (from the Greek word onkoustai, to swell) and pointed out that they may give rise to tumors with corresponding morphologic features - i.e. "oncocytic tumors" - both benign (oncocytic adenomas) and malignant (oncocytic carcinomas). Electron microscopy in the 1950s and 1960s demonstrated that the granular eosinophilia of the cells is due to an abnormal increase of the mitochondrial mass, and showed a variety of mitochondrial alterations none of which are, however, either specific or of diagnostic value. Oncocytic tumors, although generally uncommon, are by no means rare and have been described in virtually every organ, including thyroid, kidney, pituitary, parathyroid, salivary glands, liver, breast, lung and pancreas. They more frequently originate from epithelial cells with endocrine function (thyroid follicular cells, pituitary and parathyroid cells) and/or high metabolic activity (renal tubular cells, intercalated duct cells of the salivary gland), they are often very sensitive to ipoxia and may undergo infarction spontaneously or after fine needle aspiration, and - in the thyroid gland - are often aneuployid. The clinical behaviour of oncocytic tumors varies according to their pathologic features and to the site of origin: while the vast majority of renal tumors are clinically benign and do not metastasize regardless of their dimensions, oncocytic carcinomas of the thyroid gland have a worse

79 prognosis when compared with other follicular cell-derived tumors, probably due to their decreased competence in 131I uptake, required for effective thyroid cancer treatment. The biogenesis of mitochondria in oncocytic neoplasms is obviously abnormal and its relationship to tumor development still obscure. However, the importance of the biological processes involved justifies any effort to unravel the pathogenesis of this peculiar tumor phenotype. References 1. Askanazy M (1898) Pathologish-anatomische Beitrage zur Kenntnis des morbus Basedowii, insbesondere uber die dabei auftretende Muskelerkrankung. Deutsches Arch Klin Med 61:118-186. 2. Tandler B, Hutter RVP, Erlandson RA (1970) Ultrastructure of oncocytoma of the parotid gland. Lab Invest 23:567-580. 3. Tallini G (1998) Oncocytic tumors, a review. Virchows Arch 433:5-12. 4. Welsh DA (1898) Concerning the parathyroid glands: A critical anatomical and experimental study. J Anat Physiol 32:292-307, 380-401. 5. World Health Organization Classification of Tumors, Pathology and Genetics of Tumors of Endocrine Organs, IARC press, 2004

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Giovanni Romeo (left) and Victor McKusick wearing T-shirt of the “Festa della Musica e della Genetica”, the public awareness of genetics event which followed the awarding of the honorary degree to V.A. McKusick and Mario Capecchi (see the programme in the next pages)

81 FESTA DELLA MUSICA E DELLA GENETICA Bologna, 12-22 maggio 2007

82 FESTA della MUSICA e della GENETICA Bologna 12-22 maggio 2007

Sabato 12 maggio: 10.30 Aula Absidale di Santa Lucia Laurea Honoris Causa Prof. Victor A. McKusick e Prof. Mario R. Capecchi

Lunedì 14 maggio:
18.00 Sala del Baraccano Le ricadute sociali del Progetto Genoma Estone C. Faralli (Univ. di Bologna) A. Metspalu (Univ. di Tartu, Estonia)
21.00 Sala del Baraccano Armonia Celeste e Dodecafonia (2006), ed. BUR Autore: A. Frova (Univ. La Sapienza, Roma) Intervistatori: G. Zanarini (Univ. di Bologna)

Martedì 15 maggio:
18.00 Sala del Baraccano Legge 40 (procreazione medicalmente assistita) e corporeità femminile Relatori: S. Canestrari (Univ. di Bologna), E. Porcu (Univ. di Bologna) Intervistatore: E. Tola (Radio3 Scienza)

Mercoledì 16 maggio:
18.00 Sala del Baraccano Particolarità dei dati genetici C. Faralli (Univ. di Bologna) S. Rodotà (Univ. La Sapienza, Roma) H. Chneiweiss (INSERM; Collège de France, Parigi)
21.00 Sala del Baraccano ENERGIA oggi e domani. Prospettive, sfide, speranze (2006), ed. Bononia University Press Autori: N. Armaroli (CNR) e V. Balzani (Univ. di Bologna)

Venerdì 18 maggio:
18.00 Sala del Baraccano OGM sì, no, forse A. Segrè (Univ. di Bologna)

83 Da Domenica 20 a Martedì 22 maggio:
Palazzo Re Enzo (Sala del Quadrante) Mostra etnografica sulla Mongolia
Palazzo Re Enzo (Sala del Capitano) Filmato: Misteri per caso in Mongolia - Syusy Blady
Palazzo Re Enzo (Salone del Podestà) Mostra “X, cioè sconosciuto”

Domenica 20 maggio:
10.30 Palazzo Re Enzo (Salone del Podestà) Gobi (2006), ed. Bonanno Presentazione libro e diapositive Autore: R. Ive
12.30-14.30 Palazzo Re Enzo (Sala Re Enzo) Viaggio attraverso il cibo: cultura nomade mongola ed enogastronomia locale - Pranzo etnico presentato da Syusy Blady e Patrizio Roversi. Accompagnato dall’esibizione del Quintetto Hosoo Transmongolia (musica dalla Mongolia)
15.00 Palazzo Re Enzo (Salone del Podestà) VI Raid in Mountain bike: il deserto del Gobi (Mongolia) Riding in Gengis Khan’s footsteps to help Mongolian children Riprese Video e commento in diretta di Gabriele Rossi
18.00 Palazzo Re Enzo (Salone del Podestà) Tsaatan - Gli uomini renna Documentario Autore: D. De Toffol
21.00 Palazzo Re Enzo (Salone del Podestà) La genetica svela i misteri- con Syusy Blady, Patrizio Roversi, Francesco Cavalli Sforza, Guido Barbujani, Adriano Forgiane. A seguire Concerto del Quintetto Hosoo Transmongolia (Musica dalla Mongolia)

Lunedì 21 maggio:
10.00 Percorso didattico sulla Mongolia per Scuole Elementari e Scuole Medie
12.00 e 14.30 Palazzo Re Enzo (Sala Re Enzo) Esecuzione di brani cameristici a cura dei musicisti dell'Accademia dell'Orchestra Mozart
15.00 Palazzo Re Enzo (Sala Re Enzo: Spazio Libri) L’invenzione delle razze. Capire la biodiversità umana (2006), ed. Bompiani Autore: G. Barbujani (Univ. di Ferrara) Intervistatore: Patrizio Roversi
16.30 Palazzo Re Enzo (Sala Re Enzo: Spazio Libri) Perché ci piace la musica (2007), Sironi Editore Autore: Silvia Bencivelli

84 Intervistatore: Francesco Guccini
18.00 Palazzo Re Enzo (Salone del Podestà) Non oltrepassare-Cortometraggio e presentazione sulla Polizia Scientifica… quella vera V.Q.A. dott. G. Ceccaroli Interviengono Patrizio Roversi, Marcello Fois.

Martedì 22 maggio:
10.00 Palazzo Re Enzo (Salone del Podestà) Non oltrepassare-Cortometraggio e presentazione sulla Polizia Scientifica… quella vera V.Q.A. dott. G. Ceccaroli
11.30 Palazzo Re Enzo (Sala Re Enzo) Esecuzione di brani cameristici a cura dei musicisti dell'Accademia dell'Orchestra Mozart
14.00 Palazzo Re Enzo (Salone del Podestà) Research on music and emotion at InfoMus Lab A. Camurri (Casa Paganini - InfoMus Lab Univ. di Genova)
14.30 Palazzo Re Enzo (Salone del Podestà) Effetto note: Vedere e ascoltare la musica con Musicolor, una nuova forma naturale di arte tecnologica G. Caglioti (Politecnico di Milano) T. V. Tchouvileva (Politecnico di Milano)
18.00 Palazzo Re Enzo (Salone del Podestà) Genetica e musica nella violenza sessuale Le tracce svelate dal DNA M. Virgilio (Assessore, Comune di Bologna) S. Pelotti (Univ. di Bologna) G. Di Giorgio (Procura della Repubblica di Bologna) D. Tassinari (Univ. di Bologna) L. Roewer (Charité - Universitätsmedizin Berlin) M. Collina (Attrice)
18.00 Palazzo Re Enzo (Sala Re Enzo: Spazio Libri): Permette un ballo, signorina? (2007), Mondadori Autore: Andrea Mingardi
21.00 Sala Bossi Concerto Finale: Accademia dell’Orchestra Mozart

LEGENDA:
Tavole Rotonde
Incontri con l’autore
Mostre ed esposizioni
Musica e/o Teatro
Meeting

85 INTERNATIONAL WORKSHOP ON THE BIOLOGY AND GENETICS OF MUSIC Bologna , 20-22 May 2007

86 INTERNATIONAL WORKSHOP ON THE BIOLOGY AND GENETICS OF MUSIC 20-22 May 2007 Palazzo Re Enzo - Sala degli Atti Bologna

PROGRAM

Sunday, 20 May
8.30: Registration
9.00 - 12.00: Morning Session Hunting for music genes Genetics and phenotypes in tune-deafness - D. Drayna (N.I.D.C.D., Rockville, MD, USA) Absolute pitch: genetics and perception - J. Gitschier (U.C.S.F., San Francisco, USA) The genetics of congenital amusia (or tone-deafness): family aggregation- I. Peretz (Univ. de Montréal, Canada)
12.00 - 15.00: Posters
15.00 - 18.00: Afternoon Session Evolution of Music Evolution and natural meaning in music - I. Cross (Univ. of Cambridge, UK) Probing the evolutionary origins of music perception - J. McDermott (MIT, Cambridge, USA) Genetic boundaries and linguistic boundaries - G. Barbujani (Univ. of Ferrara, Italy)

Monday, 21 May
9.00 - 12.00: Morning Session Genes, neurodevelopment and cognition Music and child neurology: a developmental perspective - L. Lopez (Univ. Tor Vergata of Rome, Italy) Could a congenital disorder of musical perception ever be explained by a single gene? Relating neuronal organisation to a complex behavioural phenotype - T. Griffiths (Univ. of Newcastle upon Tyne, UK) Explaining exceptionally high and exceptionally low achievement in music: elite performers, savants, and the self-defined "tone deaf" - J. Sloboda (Keele Univ., UK)
12.00 - 15.00: Posters 87
15.00 - 18.00: Afternoon Session Music, language and neurosciences The function of prosody in the acquisition of language - M. Nespor (Univ. of Ferrara, Italy) The naturalness of music: a mathematical perspective - D. Tymoczko (Princeton University, USA) Structural and functional features of human auditory-related cortex: possible clues in the search for genetic links – R.J. Zatorre (McGill Univ. & Montreal Neurological Institute, Canada)

Tuesday, 22 May
9.00 - 12.00: Morning Session Evolution of the sense of beauty The beauty of symmetry? G. Caglioti (Politecnico of Milan, Italy) What is the meaning of "beauty" in the musical field? - M. Baroni (Univ. of Bologna, Italy) Modeling tonal tension: hierarchical representations in music and language.- C. L. Krumhansl (Cornell Univ., USA)
12.00 - 15.00: Posters
15.00 - 18.00: Afternoon Session (this session will take place in Salone del Podestà) Biological identities and cultural identities Genetic methodology applied to the study of human cultural evolution – La metodologia genetica applicata allo studio dell’evoluzione culturale umana - F. Cavalli Sforza (Milan, Italy) Genetic and musical heritage of European populations – Eredità genetica e musicale delle popolazioni europee - P. Francalacci (Univ. of Sassari, Italy) Recent cultural changes in Mongolia - Recenti cambiamenti culturali in Mongolia - R. Ive (Milan, Italy)
21.00: Sala Bossi Concert: Academy of Orchestra Mozart

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89

90 Legends for pictures of pages 82, 86, 89 and 90 Pag 82: The main venue of the Festa della Musica e della Genetica (Palazzo Re Enzo). Pag 86: The Hall of the Workshop of the Biology and Genetics of Music inside Palazzo Re Enzo. Pag 89 Top: The Exhibition “X, as unknown” showing the X chromosome DNA sequence in the Hall of Podestà (Palazzo Re Enzo), was kindly provided by Prof. T. Metinger, GSF National Research Center, Technical University Munich (TUM) and the Sanger Institute (Cambridge U.K.). Pag 89 Bottom: the Concert of the Transmongolia group on May 20. Pag 90 Top: The hall of Baraccano hosting round tables and conferences for the public understanding of genetics. Pag 90 Bottom: The Concert of the Academy of the Mozart Orchestra closing the Festa della Musica e della Genetica on May 22 in Sala Bossi (Conservatory of Bologna).

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www.eurogene.org

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