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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