Stanley Prusiner, winner of the 1997 Nobel prize for medicine, devoted two decades of research to answer this question
when Stanley Prusiner, a neurologist at the University of California, San Francisco , suggested in 1982 that certain misshapen proteins can deform regular protein molecules, he was derided by most colleagues. But his persistent research in this area despite stiff opposition and ridicule from fellow scientists has finally paid off. He has been awarded the 1997 Nobel prize for physiology or medicine for his discovery of prions -- proteinaceous particles that cause brain infections like mad cow's disease, scrapie in sheep and Creutzfeldt-Jakob disease (cjd) in humans.
But the story goes back further than the two decades of Prusiner's work. And the discovery calls into question the very basis of our understanding of life. There are two threads in the story: one goes back some 45 years, when J D Watson and F H C Crick published their findings about the structure of deoxyribonucleic acid (dna), the double helix (spiral) structure which encodes the entire information about an organism. The crucial implication was that first, dna can make copies of itself with a high degree of fidelity, and second, that dna sequences could specify the information needed to synthesise other molecules known as proteins.
This established that dna (and rna -- which is very similar to dna in structure and function) -- is the essential basis of life. Spontaneous and unpredictable errors, or mutations, can occur in the process of dna duplication or replication. These variations and natural selection are the raw material for evolution.
The second thread of the story also dates from about the same time. A medical anthropologist, D C Gaiduschek, investigated a fatal disease called Kuru which occurred among cannibalistic tribals of Papua New Guinea. The onset of Kuru appeared to be sudden and unrelated to any predisposing factors. Affected persons exhibited symptoms of lethargy, muscular weakness and degeneration of neurones -- nerve cells -- and eventually died.
In a classic study that eventually won him the Nobel prize, Gaiduschek established that Kuru was an infection caused by a virus-like substance. It was transmitted when the brain of an infected person was consumed. Since the symptoms of the disease appeared a long time after any such cannibalistic act -- sometimes years -- the link between the act and the disease had been difficult to establish. Work over the past forty years has shown that Kuru is one of a number of similar afflictions -- scrapie, bovine spongiform encephalopathy (bse or 'mad cow disease') and cjd . The recent epidemic of bse in Britain is thought to have been triggered by use of remains of dead, infected cattle, including brains, in preparing synthetic cattle feed.
The suspicion that these diseases were viral in origin encouraged a hunt for the virus. The long period of incubation testified that the virus had unusual properties. Prusiner chose the scrapie virus for his investigations. Almost right away, he stunned the scientific community with the report that try as he might, he could find neither dna nor rna in it. Initial reactions to the claim were almost uniformly sceptical. It was impossible to conceive of a living creature (even an honorary living creature like a virus, which cannot reproduce on its own but needs a host) that did not contain nucleic acids. Because the scrapie virus appeared to consist solely of proteins, Prusiner coined the term prion to describe it.
Painstaking work by Prusiner and many others, which appeared heretical 15 years ago, has now established the existence of prions. Much has been learnt about prions but many puzzles still remain. For one thing, like all proteins, the prion protein is encoded by a gene -- a dna sequence. A prion is synthesised in variety of cells, but especially in nerve cells. The protein can exist in two shapes -- a normal shape, in which the protein is not harmful, and a distorted shape. In rare occurrences, a prion protein changes shape. The misshapen protein molecule induces change in another molecule. And so the process accelerates. The result: high concentration of transformed proteins which get tangled up, eventually impairing functioning of the brain, and appearance of visible disease symptoms.
Moreover, prions exhibit intrinsic variations -- giving rise to different strains of scrapie, for instance. Little is known about this: it may be due to mutations in the dna that encodes prions, or -- a mind-boggling possibility -- the variations may be self-induced. In case the latter turns out to be true, it could mean a form of life that, in principle, is quite independent of nucleic acid chemistry.
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