'Mario', have you finally rescued Princess 'Gene'?

Mario Capecchi

You might think Snake and Ladder is a game of chance where you might go from the very top to rock bottom or vice versa but I would say it is nothing compared to human life. True, some of us start in middle and end somewhere slightly above or below, also some others start at top or bottom and remain there forever without any worries of sudden change. Also, there are some among us who start at one extreme and reach the other extreme. But then there are even smaller sub-group of people who start at one extreme go the other extreme and then come back to the same place in a better condition.

Mario Capecchi is one such man. He started near the top(his grandmother a painter, mother a poet, father an aviator, grandfather an archeologist and his uncle a physicist who developed first electron microscope and contributed to development of TV) went all the way to bottom and some more underneath and then came back to the top to set a new limit or as 2 famous WWE superstars say 'We don't set the bar, WE ARE THE BAR'.

The drive for passion comes in blood or more appropriately "genes". Mario's grandmother, Lucy Dodd, breaking all conventions of time had sailed from the US to Italy to pursue her career as a painter. It is there she met German archaeologist Walter Ramberg and they had 3 children of which Mario's mother Lucy Ramberg was one. Mario Capecchi would be born as the only child of Lucy&Luciano in Verona, Italy on 6th October 1937.

For the moment he was a normal child with a normal life but as fate would have it that wouldn't last long. By the time he was aged four his family, like millions of others, was shredded by the second World War. Father, Luciano, went missing in the course of the war and mother Lucy had joined a group opposing fascism, which ultimately brought Gestapo(official secret police under Nazi rule) to her doorsteps. So by the time he was aged four, poor Mario had lost his parents, their care, love and everything else they gave.

For around a year he lived with a peasant family near Bolzano, living by the money which his mother had provided by selling everything she had. But soon the money exhausted and family couldn't take care of him and hence was transferred to God's hands. No, not the church but to the streets of war-torn Italy, where it was not living but survival was the question.

It was the period where even those who had a shelter where dying like lab rats and the boy was in streets. For the next four years he would be a street child- living & sleeping in the streets, bombed buildings, sometimes joining other gangs of homeless children, some orphanages/hospitals but, as he would later say, always hungry. Life in these four years was brutal- no clothes, no food, no shelter- and as a result the boy was malnourished to the edge of death and his body a house of diseases. (I would love to say that the fact that the boy lived at all is a miracle but that would be like wasting the phrase when we see how his life would turn and what he would achieve next)

Around 1945 Germany was liberated and mother Lucy, who had miraculously survived the concentration camps, was freed and finding the boy was her only goal. She searched for almost a year and as a movie plot would have it, she found him on October 6, 1946 - his 9th birthday. As he himself says, Mario could not recognize his own mother - she had aged beyond belief in 5 years and psychological scars were so deep that she would never go to discuss the war until her death(she died in her eighties) and she was always in her own imaginative world. Even Mario was in such a state that only after he met his mother did he have his first bath in 6 years and wore decent clothes.

After their reunion, Mario and his mother traveled back to the US as planned by his uncle. Mario says that he had expected to find roads paved with gold but when he finally did reach there he found much more than what he expected!!!...OPPORTUNITIES.

A laboratory mouse in which a gene affecting hair growth has been knocked out (left), is shown next to a normal lab mouse(Wikipedia)

His uncle was Edward Ramberg, he had built the first Electron Microscope and was took part in the development of both Black&White and Color Television. But ironically Mario would not get to watch TV as the TV was not allowed in his uncle's house! His uncle and aunt would act as his Parent's for the rest of his life. They took on the task of converting trash into treasure and boy did they succeed!

Mario had no formal education to start with and very rough childhood he faced was always a problem either in his personality or personal life. But because of the efforts of his uncle and aunt, by high school Mario had already become fluent in English and academics was coming naturally for him. It might be because of his past or his upbringing when the time came for him to decide his future goals Mario chose Political science as the path so that he could solve the world's problems.

But in time he was dissatisfied with it and changed his stream to Physics and Chemistry. He loved it. Such was his intellect and passion that he would go on to complete almost all Math, Physics and Chemistry courses offered in his university. Even then he was not satisfied and luckily for him(or more aptly 'luckily for us') he got a chance to visit Molecular Biology department at MIT where he would find his new passion.

But until then he had not taken any biology courses. What would you do now? Simple, just go and talk to a Nobel Laureate asking to work under him! That is exactly what Mario did. They say 'Fortune favors the brave' and it sure did in this case. Mario says that when he asked Professor James D. Watson- Yes, the same Watson in 'Watson crick double helix model of DNA' - where should he join to do his graduate studies in Molecular biology Watson(he was working in Harvard) replied "Here. You would be fucking crazy to go anywhere else". So he did and after his graduation, he went to the 'Mecca' of Molecular Biology- Harvard and became a mentee under Watson (Mother&Father both are WW2 fighters, Uncle who developed Electron Microscope-TV, the Nobel Laureate as the Mentor .... Not a bad list of 'People I know'!).

After his Ph.D.(1968) he worked there for some more time and in all almost 8 years later he left Harvard as he found it to have too much of a competitive atmosphere and joined Utah university in 1973. This turned out to be exactly what he wanted.

Mario Capecchi receiving Nobel Prize

Mario's area of interest was targeted gene manipulation i.e manipulating an existing gene by replacing it or disrupting it with an artificial piece of DNA. This was the dream of all biologists- manipulating/removing genes and being able to study their features, effects individually. In 1980 Mario applied for National Institutes of Health(NIH), the main US Government research health agency, grant for this research of his. But they replied that his ambitions are not worthy of pursuit.

Being the man of passion he was, he redirected the funds of his other research to this. This was a great risk because failure would result in loss of reputation and thus no funding for future projects. But for a man who survived 5 years in streets, this would have looked like a much smaller bet and success meant betterment for humankind and a personal glory. He went ahead with his research and four years later he was successful and had developed a gene mutation technique called Homologous recombination.

He again applied for the grant with a working technique and unlike last time he got a positive reply. The technique was so revolutionary and held so much promise that approval letter from NIH scientists read 'We are glad that you didn't follow our advice --- '!

By 1987 he had refined the method so much that he was ready to test it on a mice and by 1989 he had live mice with targeted mutations. This he had achieved along with two other biologists- Martin Evans and Oliver Smithies. This kind of mouse is called Knockout Mouse. A knockout mouse is a genetically modified mouse in which researchers have inactivated, or "knocked out", an existing gene by replacing it or disrupting it with an artificial piece of DNA.

This work got him a lot of attention and in 2007 he got his ultimate prize- The Nobel Prize in Medicine which he shared along with Martin Evans and Oliver Smithies. The technique has far reaching consequence and is hope to curing various diseases like diabetes, obesity, Parkinson's disease, even cancer.

Oliver Smithies (left), Mario R. Capecchi (middle) and Sir Martin J. Evans (right) at their interview with Nobelprize.org in Stockholm, 6 December 2007 (Nobel Prize website)

No, this is not the plot for Good Will Hunting 2 nor a Cinderella story. This is the life of a child who lost everything becoming a street-child in a war-torn country by 4. By 9 the world had already shown him the worst of worst and a peek into the world of the dead but he became the boy who lived. He showed the world what hard work was and himself became the BAR to reach. Yes, now we can say that his life indeed is a miracle.

There are around 50 million street children around the world(some estimates go up to 100 million). From a small subgroup of them, the world got a solution to gene manipulation. That thought almost blew me out. What about you? What more can we get from the rest of 50 million? Is it them that the world is missing?

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