Mario Capecchi has led a remarkable life. At four-and-a-half years old, during World War II, his mother was sent to Dachau concentration camp leading-eventually- to Mario living as a street child for nearly four years, coming in and out of orphanages and almost dying of malnutrition.
From this hugely challenging start in life, Mario went on to study chemistry, physics and eventually molecular biology at MIT. He transferred to the lab of James D. Watson (the co-discoverer of the structure of DNA) and flourished, eventually becoming joint recipient of the 2007 Nobel Prize in Physiology or Medicine for the discovery “of principles for introducing specific gene modifications in mice by the use of embryonic stem cells.” He is now Professor in the Department of Human Genetics and adjunct professor in the Department of Oncological Sciences at the University of Utah, and is the recipient of many more of the most prestigious prizes in science and medicine.
In this exclusive interview, I spoke to Dr. Capecchi about his life, his struggles through the war, and what he’s learned about life from his incredible journey.
Q: What are your memories from some of your earliest years?
[Mario Capecchi]: When I was very young, my Mom had given almost all of her money to a family she knew- as she was aware that sooner or later, she was going to be picked-up by the Gestapo. She sold many of her possessions, gave her money to this family, and in Spring ’41, she was picked-up and I went to that family. Essentially, I shadowed the women of the farm; whatever they were doing, I’d follow along- and I’d help with harvesting, that kind of thing- it was a small farm. I’ve visited there again; and the same family that was there at the time still owns it. They took me around the farm, and I remembered where the chicken coops were, and how the farm used to be. At the time, I’m not sure what happened, but the family’s money ran-out and they had a stark choice of either feeding an extra person, or for me to be on the streets; and that’s what occurred. Aged four and a half, I started to live on the streets of Bolzano, and just kept migrating south; nobody was able to give me any food, so you had to steal- the people got to know you, made things very unpleasant, and you had to move-on. I went in a straight line south through Verona, down to Reggio Emilia where my mother eventually found me.
I didn’t have a childhood- I didn’t play- every day was about survival. I was always moving to a different-place on a weekly/monthly basis. Since the only food I had was stolen, your presence was soon known by the local shopkeeper and they would make things miserable for you often calling the local police and they would place you in a local orphanage. That was worse than being on the streets. They had little or no food. A stale piece of bread so hard you could not break it with your teeth, a bowl of hot water containing chicory weeds. Often the people that ran the orphanage were masochistic beating the kids to maintain discipline. There was no way to survive in the orphanage. The only recourse was to escape. And I would.
Even as a child, I was very aware of the war. I remember they would drop these insidious bombs, designed to look like toys so that kids would pick them up- they would blow your hands off immediately. You were aware that you were living in dangerous times, and at a time where people didn’t have much for themselves, never mind for kids in the streets. There were quite large groups of us- we would sometimes function alone, sometimes with another group.
Q: How did you reconnect with your mother?
[Mario Capecchi]: My mother found me in Reggio Emilia after being freed from Dachau by the Americans in the spring of ’45 she moved to Rome. From Rome she started calling hospitals to see if anyone by the name of Mario Capecchi had been registered there. A year and a ½ later she made contact. She found a child of the right age registered in Reggio Emilia. She made a really dramatic entrance. – she arrived on my birthday. I don’t know how I knew it was my birthday, but it was. Initially, I couldn’t recognise her- it had been 5 years- and we had both changed. I was in a small hospital at the time and I was very sick with typhoid and malnutrition.
Q: How did you come to the USA?
[Mario Capecchi]: My mother eventually got hold of her brother, my uncle. His name was Edward Ramberg. He sent money for our boat trip to the United States. When my mother found me, I was obviously sick, and the hospital kept us from running away by keeping your clothes; Rows and rows of beds, just a mattress, all kids with typhoid naked on beds. My mother bought some clothes and took me to Rome to get custody- my father refused to cede unless she also paid for his transit to the USA- and eventually this all went to court. Amazingly, she won custody. So from a week after her arriving in Reggio, we went to Rome, went to court, and then went to Naples to board an old army freighter which took two weeks to get to get to New York City. On arrival that night we all stared at the Statue of Liberty all night.
Q: How did you find your feet in the United States, and settle-in?
[Mario Capecchi]: it was dramatic going from a very difficult situation in Italy to a very social situation in the United States. My uncle had helped to organise a commune- It was open to all races and religions- there were 65 families all living communally so I went from having no parents, to having 65! For kids, it was fantastic, there were lots of activities, a very strong community, and everyone cared for each other.
I had gone from being on my own, to this wonderful situation- primarily put together by Quakers– with a philosophy that we are not here to accumulate, but rather to provide a service to the world- to live a life of service- a service which included education. I had never been to school- I arrived at the commune on Sunday, and Monday I was off to school- not knowing the language. They arbitrarily put me into 3rd grade… I learned the language… and things progressed from there.
My Mom never recovered psychologically from being in the concentration camp; so, my aunt and uncle inherited me. They received this ‘animal’ with no social upbringing and turned me into a human being.
Q: How did you find your love for science
[Mario Capecchi]: Initially I was in the public education system, it was OK… there were a few good teachers and they took care of me, nurtured me as well as they could, but then I went to a private Quaker school- which had a prep-school for college. That was the complete change, they had a deep academic focus, excellent teaching, and all sorts of activities like sports. The Quaker ethos was always there; they were working on world problems… and whether I was studying social sciences, politics, they were looking at things through the lens of solving problems. I found a love for science at the time and switched to physics (influenced by my uncle)- I loved physics, it was beautiful, but the program I was on was quite unique whereby you studied for a quarter, worked for a quarter and so forth- half the students were working, and half were taking classes – there were jobs all over the United States relating to our interests- and you actually got paid! I went to MIT and worked in a lab there- my mentor was Alexander Rich– a prominent scientist who inspired me to switch from physics to molecular biology. MIT was one of the places where molecular biology was born, and I could participate in this enterprise with my own hands.
Q: How did you survive on the streets?
[Mario Capecchi]: It was many years before I was able to talk about my childhood and early-years. I didn’t speak with my aunt, uncle, anyone… My Mom was the same way- she never talked about her experiences of Dachau– I never got a full explanation of what she went through.
I never had an ethical dilemma with what was going on as a child, it was about pure survival. The kids that survived were the ones who were clever enough to continually get a meal- mostly, I would eat fruit, vegetables and eggs. I had to learn to be patient- to study people… look at them…. Watch their patterns of movements… and then understand how to procure my next meal.
I remember one-time being very indignant. I just got a brand-new set of pears; beautiful, gorgeous pears. I was walking down the street with them, the shop-keeper came running after me and said, ‘you stole my pears!’ I looked at her and said, ‘that’s impossible! If I had stolen these pears from you… you would never have seen me!’
Q: How did your early experiences shape your approach to work?
[Mario Capecchi]: I learned to problem-solve and be self-sufficient at an early age, and that has influenced how I operate my lab. I try to make sure we generate as much of our research, data and activity in house as possible, so that we own what we produce an are not reliant on the involvement on too many other parties. Self-sufficiency is important. It provides ownership and pride of the data you produce.
Today; I look at my own daughter, and think to myself, ‘how could she possibly have survived in the world at 4 and a half…’ it doesn’t seem conceivable- but on the other hand, a child doesn’t even question their situation- I was thrown into a situation and had to respond to it; if I needed food, I had to get food… If I needed shelter, I had to find shelter… and it wasn’t hard to get shelter by the way, there were lots of bombed out houses everywhere. What was hard was food; I didn’t have a cooked meal in 9 years until a street-woman, who turned out to be a prostitute, took pity on me and made me a meal. That was my one hot meal in the time I was living on the streets.
Q: What was the role of diversity in science; and what is it today?
[Mario Capecchi]: The secret of molecular biology at the time of its birth was diversity; we had the infusion of people from physics, mathematics, genetics, medicine, biology… all these people from different backgrounds, getting together and developing new ways of looking at how life functions. That juxtaposition of people with different experiences gave rise to a new way of thinking.
Even today, I send my students to meetings that have nothing to do with their work- just so they can see what’s going on in other fields that might be useful to them.
You also need to be patient, persevere and build resilience. It’s OK that today didn’t work, but tomorrow you must try harder. If you persevere, you get there. And if you give up, you never get there.
Q: What would be your advice to the next generation?
[Mario Capecchi]: Even now, I’m working full time in the lab- in science, you solve one problem, and then all of a sudden you generate 10 new questions… it’s an endless process. I also change fields, on purpose, every 10 years- just to juxtapose and reshuffle my mind. When you go into a new field, it’s transformational- imagine you are working on cancer, then you start going to cancer meetings, and start to see the same people over and over again – then you switch to neurobiology, and suddenly it’s a new field, new people, and new ideas. It also forces you to start at the bottom and work yourself back up again, and that’s good for you.
I also value being naïve; I don’t know the questions I shouldn’t be asking- whereas people in the field know which questions to ask, and which ones to not ask. I’m often asking very different questions, applying all the backgrounds I have acquired in the previous fields, asking the right questions are often the most important part of doing good science.
You have to keep feeling excited, rejuvenating your mind, facing new challenges. You can get stuck only using 5% of your mind- just imagine what that other 95% could do…
MARIO R. CAPECCHI was born in Verona, Italy in 1937. He received his B.S. degree in chemistry and physics from Antioch College in 1961 and his Ph.D. degree in biophysics from Harvard University in 1967. His thesis work, under the guidance of Dr. James D. Watson, included the analysis of the mechanisms of nonsense suppression; the initiation of protein synthesis, including the demonstration of Formylmethionine tRNA as the initiator of protein synthesis; and the mechanisms of protein termination. From 1967-69 Dr. Capecchi was a Junior Fellow of the Society of Fellows at Harvard University. In 1969 he became an Assistant Professor in the Department of Biochemistry, Harvard School of Medicine. He was promoted to Associate Professor in 1971. In 1973 he joined the faculty at the University of Utah as a Professor of Biology. Since 1988 Dr. Capecchi has been an investigator of the Howard Hughes Medical Institute; since 1989, a Professor of Human Genetics at the University of Utah School of Medicine; and since 1993, Distinguished Professor of Human Genetics and Biology. He is also co-chairman of the Department of Human Genetics.MarioMousePic
Dr. Capecchi is best known for his pioneering work on the development of gene targeting in mouse embryo-derived stem (ES) cells. This technology allows scientists to create mice with mutations in any desired gene. The power of this technology is that the investigator chooses both which gene to mutate and how to mutate it. The investigator has virtually complete freedom on how to manipulate the DNA sequences in the genome of living mice. This allows scientists to evaluate in detail the function of any gene during the development or post-developmental phase of the mouse. His research interests include the molecular genetic analysis of early mouse development, neural development in mammals, production of murine models of human genetic diseases, gene therapy, homologous recombination and programmed genomic rearrangements in the mouse.
MCBerlinDr. Capecchi is a member of the National Academy of Sciences (1991), the European Academy of Sciences (2002), the American Academy of Arts and Sciences (2009), and the National Academy of Medicine (2015). He has won numerous awards, including the Bristol-Myers Squibb Award for Distinguished Achievement in Neuroscience Research (1992), the Gairdner Foundation International Award for Achievements in Medical Sciences (1993), the General Motors Corporation’s Alfred P. Sloan Jr. Prize for Outstanding Basic Science Contributions to Cancer Research (1994), the German Molecular Bioanalytics Prize, (1996), the Kyoto Prize in Basic Sciences (1996), the Franklin Medal for Advancing Our Knowledge of the Physical Sciences (1997), the Feodor Lynen Lectureship (1998), the Rosenblatt Prize for Excellence (1998), the Baxter Award for Distinguished Research in the Biomedical Sciences (1998), the Helen Lowe Bamberger Colby and John E. Bamberger Presidential Endowed Chair in the University of Utah Health Sciences Center (1999), lectureship in the Life Sciences for the Collège de France (2000), the Horace Mann Distinguished Alumni Award, Antioch College (2000), the Italian Premio Phoenix-Anni Verdi for Genetics Research Award (2000), the Spanish Jiménez-Diáz Prize (2001), the Pioneers of Progress Award (2001), the Albert Lasker Award for Basic Medical Research (2001), the National Medal of Science (2001), the John Scott Medal Award (2002), the Massry Prize (2002), the Pezcoller Foundation-AACR International Award for Cancer Research (2003), the Wolf Prize in Medicine (2002/03), the March of Dimes Prize in Developmental Biology (2005), the Nobel Prize in Physiology and Medicine (2007) with Oliver Smithies and Martin Evans, the American Heart Association Distinguished Scientist Award (2008), and the American Association of Cancer Research Lifetime Achievement Award (2015).
Research interests include: the molecular genetic analysis of early mouse development, neural development in mammals, production of murine models of human genetic diseases, gene therapy, homologous recombination and programmed genomic rearrangements in the mouse.