Free Radicals - Michael Brooks [36]
Proteins are long strings of acid molecules that play specific roles within the body after folding themselves into particular shapes. Haemoglobin is a protein that carries oxygen through the body, for example, and insulin is a protein that signals the presence of excess sugar that needs storing. But for all the impressive cleverness of proteins, Griffith’s suggestion seemed, at first glance, ridiculous. To cause an infection, you need an agent that can reproduce itself – and proteins can’t do that.
In orthodox molecular biology, the instructions for replication are encoded in nucleic acids. Viruses contain nucleic acids. So do bacteria. That’s why they can reproduce, and that’s why the mainstream view was that scrapie must be caused by a slow-acting virus. A protein, however, is the product of the instructions encoded in nucleic acids. There is, on the face of it, no way that a protein can be a creative entity.
Griffith knew that, but as a mathematician he wasn’t constrained by the norms of molecular biology. He put forward three ways in which a protein might conceivably replicate itself. ‘There is no reason to fear that the existence of a protein agent would cause the whole theoretical structure of molecular biology to come tumbling down,’ he said. And he suggested that scrapie infections could quite conceivably be caused by a protein that the animal is ‘genetically equipped to make’. Perhaps, he said, the animal wouldn’t normally make this protein, at least not in a form that folds into this shape. But, passed from another animal, the protein might stimulate the animal’s natural proteins to take on another, dangerous shape.
Prusiner was intrigued, and decided to look more closely at what the infectious agent might be. By 1974, he had secured the funds to set up a laboratory that processed scrapie-infected brains to extract the infectious material in as pure a form as possible. Equipped with what he terms ‘the optimism of youth’ and a ‘cocky’ nature, he succeeded where others had failed. By 1982, he was able to report that the concentrated infection agent for scrapie consisted almost entirely of protein. It appeared to contain no nucleic acids – and thus no genetic material. It was not, as most people thought, a virus. It was, Prusiner said, a protein, just as Griffith had suggested it might be.
Prusiner made the claim in a paper published in the journal Science in 1982. It was meant to be a review of scientists’ current understanding of scrapie. Instead, Prusiner used the commission from the journal as a platform from which he could announce an entirely new discovery. Biology says that there are only two types of infectious agent: the bacterium and the virus. Stanley Prusiner now introduced a third: the ‘prion’, a clever contraction of ‘proteinaceous infectious agent’.
He pronounces it pree-on – though I was interested to note during a telephone conversation that Laura Manuelidis, the head of neuropathology at Yale University, pronounces it pry-on. I’m sure it doesn’t matter to her; she still doesn’t believe that prions are real, and no one else can be sure whether to believe that prions exist. As a February 2010 article in Science pointed out, ‘three decades of investigation have yielded no direct experimental proof’ that the cause of these infections is exclusively down to a protein. Not that this held back Prusiner’s Nobel Prize.
‘At every crossroads on the road that leads to the future, tradition has placed against us ten thousand men to guard the past.’ That was how, in 1992, Prusiner chose to preface a collection of conference papers about his work. The bitter tone was intentional: his colleagues and peers had been standing against him for a decade, ever since that Science paper. Prusiner claims that the acceptance of his research represents ‘a triumph of scientific process over prejudice’. So where did this prejudice-driven rejection come from? From those who believe that evidence is the most important thing in science.
Byron Caughey, laboratory