From Street Urchin to Nobel Laureate
By Dr. Syed Amir
Bethesda, MD

In October 2007, the Nobel Committee at Karolinska Institute in Sweden announced the winners of the 2007 Nobel Prize in Medicine or Physiology, as it has been doing every year for the past one hundred years. The highly coveted award this year was shared by three scientists, Martin Evans of Britain, and two Americans, Mario Capecchi and Oliver Smithies.
The 1.54 million dollar prize will be distributed among the three winners. The prize, however, carries a lot more prestige than the money would imply. The Nobel Committee extolled the research contributions of the scientists, describing them as major advances in medical sciences.
Martin Evans, discovered that embryonic stem cells, obtained from mice, could be made to evolve into cells of any type — such as liver, kidney, heart -- and could potentially be used to replace tissues and organs worn out by disease or the normal aging process. Drs. Capecchi and Smithies, on the other hand, developed and refined techniques that gave scientists the ability to modify or delete specific genes in mice and then study the effect of such manipulations on their health and physiology. The technique is referred to as gene targeting and is extensively employed by molecular biologists to determine the role and function of unknown genes.
Dr. Capecchi’s studies were carried out some twenty years ago in mice whose genetic sequence is 95 percent identical to that of humans. This genetic homogeneity is fortuitous, since mice can serve as models to study a variety of human diseases that are rooted in genetic defects. Scientists uncovered the genetic sequence of both humans and mice in 2001. Yet, the function of many genes has remained a mystery. Dr. Capecchi’s research has provided a strategy to obtain this information. Scientists now can delete or modify one or more of the genes, out of some 22,000, and create a mouse model with the missing or altered gene and then evaluate what functions have been modified or lost as a result.
While the contributions of the three Nobel Laureates towards improving the quality of human health and combating the disease process have been astounding, the life story of Dr. Mario Capecchi has received worldwide attention because of its fascinating nature and the human interest it evokes. Currently, a much admired professor at the University of Utah, Salt Lake City, in the Western United States, Dr. Capecchi’s early life was a study in adversity. In the nineteenth century, European countries, especially Italy and France, were considered places with rich cultural milieus that attracted painters, musicians, poets, the practitioners of fine arts, from around the world. Capecchi’s American grandmother, a passionate impressionist painter, moved to Florence, Italy, married and settled there in the waning years of the nineteenth century. She had inherited much wealth and her daughter, Capecchi’s mother, spent her childhood in a state of luxury, living in an Italian villa, staffed with nannies, house servants, cooks and other extravagances.
However, as often is the case in life, the vast wealth and opulence proved only ephemeral. Capecchi’s mother, an accomplished poet and linguistic, moved to Paris and took a job at the Sorbonne, the celebrated University in Paris, teaching French literature. She later moved back to Italy, fell in love with an Italian air force officer, Luciano Capecchi, but the union that produced a son did not last for long. The clouds of Second World War were already gathering on the horizon, as child Capecchi was growing up in a secluded chalet in Italian Alps. Much like some European idealists at the time, his mother was active in antifascist and anti-Nazi causes and her clandestine involvement in these activities was a source of constant worry for the family. The worry, it turned out, was not unfounded. Shortly after the war broke out in 1939, the German Gestapo knocked at the door of the residence, arrested the mother and sent her to prison.
Capecchi’s apparently idyllic life started to unravel, giving way to a nightmare. With remarkable prescience, his mother before her arrest had sold all her valuable possessions and turned the money over to some friends to take care of her young son in case she was unable to do so. After she was taken away, young Capecchi lived on the farm with the family and enjoyed farming practices, growing food, wheat, fruits and vegetables. But it seems that the money his mother had left with the friends soon ran out, and the boy was cut loose by the family he was living with. At the time, he was only four-and-half years old.
Then started an incredible period of hardships for young Capecchi, who became homeless, wandering and living on the street, with nowhere to go and often nothing to eat. As sometime happens to homeless children, he was co-opted by street gangs and became a street urchin, stealing food from venders and peddlers. During those harrowing days, his father took him in for brief periods, but soon put him back on the street. Lack of enough food and adequate nourishment took their toll. He became sick, and somehow got admitted to a hospital near Bologna in Italy, where the conditions were only slightly better than those he encountered out on the street. His daily ration consisted of one cup of coffee and a crust of bread. As he suffered from high fever, there were no sheets or blankets to cover him. Children lay naked on the beds in a congested hospital ward. He was desperate and would have liked to run away. However, with no clothes to wear and a fever that returned regularly everyday, he did not have much choice. The situation, overall, was pretty grim.
However, unbeknown to the youngster, the dark night was soon to come to an end. His mother had been released from the prison, following the allied victory, and started to look for her son at various hospitals and orphanages. After spending a year in the search, she located him in the hospital in Bologna. Young Capecchi, now nine years old, was rescued, had new clothes and enough to eat. The two moved to Philadelphia, where his uncle and aunts had already settled.
For Capecchi, life took a completely new turn and for the better. He was admitted to a Quaker school, a community that places much emphasis on strict moral codes and discipline. Initially, he did not show any perceptible interest in sciences and pursued studies of political science at an undergraduate level. But, after a year, he switched to mathematics and physics and graduated in these subjects. As a graduate student in molecular biology, he joined the laboratory at Harvard University of Dr. James Watson, a celebrity who had won the Nobel Prize along with Sir Francis Crick for unraveling the structure of DNA a few years earlier.
The Boston area has a large number of universities clustered in a small area. While most scientists prefer to have many collaborators and colleagues working nearby, Capecchi’s preference was to move to a quieter university in the American west, where he could conduct his work free from other distractions. It was the start of an amazingly successful career, during which he received numerous prestigious awards, culminating in the Nobel Prize this year.
Dr. Capecchi’s life history is an inspiring tale of the resilience of the human spirit and survival in the face of adversity. Nevertheless, the scars, both physical and emotional, he suffered as a child have never completely gone away. Regardless, Dr. Capecchi has no plans to retire and is quoted as remarking “my wife envisions me dying in the laboratory.”


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Editor: Akhtar M. Faruqui
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