“Despite the complete absence of an early nurturing environment, the intrinsic drive to make a difference in our world is not easily quenched and that given an opportunity, early handicaps can be overcome and dreams achieved. …”

~ Mario Capecchi, recipient of the 2017 Nobel Prize in Physiology or Medicine.

Mario Capecchi’s name will forever be inextricably linked to mice. Along with Martin Evans and Oliver Smithies, he was awarded science’s greatest honor in 2017 for his pathbreaking contributions to the development of gene targeting in mouse embryo-derived stem cells, a technology that allows scientists to create mice with mutations in any desired gene and which has become a major tool in revealing the extent of genetic influences on human disease.

But Dr. Capecchi’s route to the pinnacle of success was circuitous and tortuous, and for the very same reasons, is a tale of enormous inspiration for budding scientists and ordinary folks alike. Below is the riveting story of the man who almost didn’t make it.

The Makings of a Scientist
Edited excerpts of Mario Capecchi’s Nobel Prize Speech

“I was born in Verona, Italy on October 6, 1937. Fascism, Nazism, and Communism were raging through the country. My mother, Lucy Ramberg, was a poet; my father, Luciano Capecchi, an officer in the Italian Air Force. This was a time of extremes, turmoil and juxtapositions of opposites.

My mother’s love and passion was poetry. She published in German. She received her university training at the Sorbonne in Paris and was a lecturer at that university in literature and languages. At that time, she joined with a group of poets, known as the Bohemians, who were prominent for their open opposition to Fascism and Nazism. In 1937, my mother moved to the Tyrol, the Italian Alps. We lived in a chalet there until I was 3½ years old.

In the spring of 1941, German officers came to our chalet and arrested my mother. This is one of my earliest memories. My mother had taught me to speak both Italian and German, and I was quite aware of what was happening. I sensed that I would not see my mother again for many years, if ever as she was incarcerated as a political prisoner in Germany. Though she was released years later, and lived until she was 82 years old, she never psychologically recovered from her wartime experiences.

For reasons that have never been clear to me, my mother’s money ran out after one year and at age 4½, 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. My recollections of those four years are vivid but not continuous, rather like a series of snapshots. Some of them are brutal beyond description, others more palatable.

In the spring of 1945, Munich was liberated by the American troops. After my mother was released from captivity, she set out to find me. In October 1946, she succeeded. She found me on my ninth birthday, but I did not recognize her. In five years she had aged a lifetime. I was in a hospital when she found me. All of the children in this hospital were there for the same reasons: malnutrition, typhoid, or both. The prospects for most of those children ever leaving that hospital were slim because they had no nourishing food. Our daily diet consisted of a bowl of chicory coffee and a small crust of old bread.

My mother’s younger brother, Edward, had sent her money to buy two boat tickets to America. I was expecting to see roads paved with gold in America. As it turned out, I found much more: opportunities.

On arriving in America, my mother and I lived with my uncle and aunt, Edward and Sarah Ramberg. Edward, my mother’s younger brother was a brilliant physicist. He was a Ph.D. student in quantum mechanics with Arnold Sommerfeld and translated one of Sommerfeld’s major texts into English. Among Edward’s many contributions was his discovery of how to focus electrons, knowledge which he used in helping to build the first electron microscope at RCA Laboratory.

My aunt and uncle were Quakers and they did not support violence as solutions to political problems anywhere in the world. During World War II, my uncle did alternative service rather than bear arms. He worked in a mental institution in New Hampshire, cleared swamps in the south, and was a guinea pig for the development of vaccines against tropical diseases. After the war he settled in a commune in Pennsylvania, called Bryn Gweled, which he helped found. People of all races and religious affiliations were welcomed in this community. It was a marvelous place for children: it contained thick woods for exploration and had communal activities of all kinds – painting, dance, theater, sports, electronics, and many sessions devoted to the discussion of the major religious philosophies of the world.

The contrast between living primarily alone in the streets of Italy and living in an intensely cooperative and supportive community in Pennsylvania was enormous. Time was needed for healing and for erasing the images of war from my mind. I remember that for many years after coming to the United States I would go to sleep tossing and turning with such force that by morning the sheets were torn and the bed frame broken.

My aunt and uncle took on the challenge of converting me into a productive human being. This, I am sure, was a very formidable task. I had received little or no formal education or training for living in a social environment. Quakers do not believe in frills, but rather in a life of service. They taught me by example. I was given few material goods, but every opportunity to develop my mind and soul. What I made of myself would be entirely up to me.

The day after I arrived in America, I went to school. I started in the third grade in the Southampton public school system. Sarah also took on the task of teaching me to read, starting from the very beginning.

I attended an outstanding high school, George School, a Quaker school north of Philadelphia. The teachers were superb, challenging, enthusiastic, competent, and caring. They enjoyed teaching. The campus was also magnificent, particularly in the spring when the cherry and dogwood trees were bursting with blossoms.  I then went to Antioch, a small liberal arts college in Ohio. At Antioch College I became a serious student. Coming from George School, I carried the charge of making this a better, more equitable world for all people. Most of the problems appeared to be political, so I started out at Antioch majoring in political science. However, I soon became disillusioned with political science since there appeared to be little science to this discipline, so I switched to the physical sciences – physics and chemistry. I found great pleasure in the simplicity and elegance of mathematics and classical physics. I took almost every mathematics, physics, and chemistry course offered at Antioch, including Boolean algebra and topology, electrodynamics, and physical chemistry.

Although I found physics and mathematics intellectually satisfying, it was becoming apparent that what I was learning came from the past. The newest physics that was taught at Antioch was quantum mechanics, a revolution that had occurred in the 1920’s and earlier. Also, many frontiers of experimental physics, particularly experimental particle physics, were requiring the use of larger and larger accelerators, which involved bigger and bigger teams of scientists and support groups to execute the experiments. I was looking for a science in which the individual investigator had a more intimate, hands-on involvement with the experiments. new work experience. So one quarter off I went to Boston and the Massachusetts Institute of Technology (MIT). There I encountered molecular biology as the field was being born (late 1950’s). This was a new breed of science and scientist. Everything was new. There were no limitations. Enthusiasm permeated this field. Devotees from physics, chemistry, genetics, and biology joined its ranks. The common premises were that the most complex biological phenomena could, with persistence, be understood in molecular terms and that biological phenomena observed in simple organisms, such as viruses and bacteria, were mirrored in more complex ones.

I set off for what I perceived as the “Mecca” of molecular biology, Harvard University. I had interviewed with Professor James D. Watson (of “Watson and Crick” fame), and asked him where should I do my graduate studies. His reply was curt and to the point: “Here. You would be fucking crazy to go anywhere else.” The simplicity of the message was very persuasive.

Doing science in Jim’s laboratory was exhilarating. As a graduate student, I was provided with what appeared to be limitless resources. I could not be kept out of the laboratory. Ninety-hour weeks were common. The lab was filled with talented students, each working on his or her own set of projects. Represented was a mixture of genetics, molecular biology, and biochemistry. We were cracking the genetic code, determining how proteins were synthesized, and isolating and characterizing the enzymatic machinery required for transcription. It was a productive time, but it wasn’t work. It was sheer joy.”