The Yamanaka affair – Bangalore Mirror – Bangalore Mirror

By: Santanu Chakraborty

We can now use our own cells to replenish the ones that are lost, weak or old

Observing the news from around, rather depressing and mostly violent, the world these I cannot but feel that the desire for immortality is part of what might fuel the end of our species. The level of conflict that can be provoked by unverifiable untestable ideas is rather striking. But there is another sphere, another kind of immortality that mankind perhaps covets even more than the lasting fame, power and grip of its belief systems. The literal one. I mean the power to be physically alive, preferably young, forever. Stories from many lands over many eons have eulogized various elixirs of life. Potions with the power to present eternal youth, at least life, to those who consume them.

Now these dreams havent really come true for humans. Now biological science has certainly advanced over the past century. So much so that if the ancients could peer into the future they might have seen the tremendous gain in life expectancy in our generation and wondered if we were onto somekind of elixir of life. After all the average life expectancy has more than doubled since the middle ages. Quite a remarkable achievement for medical science. Yet the methods used could be called death prevention instead of life extension, as the technolgies that have driven humans living longer are really things like antibiotics: things which have prevented that extraordinary number of premature deaths. You could say that better nutrition amounts to some life extension. It does but you wont live forever no matter how well you eat. In fact there is a growing body of evidence that suggests that eating a diet rich in nutrients but low in calories - which means hunger - actually promotes longevity. So its all very confusing with only one certainty. Death.

Now that is unless we can turn our cells new again. A tremendous advance towards this end was made when John Gurdon, an English scientist, did an unthinkable experiment. Gurdon knew that a fertilized egg, one made when a sperm and a naiive egg fuse together, is what gives rise to an entire animal. It was in 1962 that John Gurdon replaced a fertilized frog egg cells nucleus with another nucleus, this one from the intestine of a tadpole. Think of cells as two concentric balloons, the smaller one (nucleus) contained within the larger one. The spaces inside these membranes contain a tremendous amount of molecular machinery that enables these cells to divide and produce near perfect replicas of themselves. And that is just the begining. A fertilized egg divides into two cells first and then they divide again. The cells start out identical but soon start producing different cells to make the varying organs of the body. What would you expect to happen when a nucleus that was made after many many replications inside the tadpoles intestine is reimplanted into a from egg, its raisondetre not to mention its ancestral environment.

A crude analogy would be grafting organs from an old human into a young one. Out gut instinct is to think that this would not work, except in the reverse. Young tissue can replace old but never the other way around. What Gurdon found was that the egg cell implanted with an old nucleus grew into a frog without breaking a sweat. Thus was the worlds first clone was born. Its more famous sister Dolly, the sheep, was cloned by nuclear transfer many years later in 1997 by Ian Wilmut. Many scientists looked beyond the excitement to discern a subtle fact. Gurdons idea was a demonstration that even cells that have divided many times and settled into their final form - fully differentiated cells - contain all the genetic information required to turn into an entire living organisms. Within each of our cells then is contained the elixir of life. An especially remarkable finding in light of the legends that indicate mankind has perhaps looked far and wide searching for fountains of eternal youth.

How could we then turn our own cells to a slightly more primordial state so that they may divide and replenish the ones that are lost, weak or old. These cells we could pluripotent - with the potential to turn into many different cell types. The ability to make them at will would be particularly valuable, in fact they would be a revolution for medicine. Shinya Yamanaka, a Japanese doctor, took up the challenge. His answer came after a long and winding road full of challenges tackled over many years. It was almost unbelievably simple. Of the thousands of genes that make protein in the nucleus of a cell, and their many potential combinations, Yamanaka showed that forced activation of only four genes would turn the clock back all the way to make what he called induced pluripotent stem cells.

Today these cells are taking center stage as scientists develop the next generation of regenerative therapies and even in the fight against cancer.

Life may just get a little longer in the decades to come thanks to the courage of scientists who persisted against considerable social odds to get humanity tantalizingly close to immortality.

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