Free Radicals - Michael Brooks [53]
More recent studies have placed the correlation between duodenal ulcers and spiral bacteria at 92 per cent – so twelve out of thirteen is perfectly acceptable. Marshall, though, was determined to make his case – even if it involved a little ‘normal misbehaviour’. As the clinician reporting the presence or absence of ulcers, it was not Marshall’s place to make a unilateral addition to the infected group. Warren was the one who should have declared whether bacteria were present or not. That is, no doubt, why Marshall writes in his Nobel autobiography, after mentioning his addition, ‘Later, Robin must have rechecked the samples and agreed that bacteria were present.’ We can regard this as another example of the way things have to be done to get at the truth – and that line of Marshall’s is akin to something that Stanley Prusiner might have said. Warren actually has no memory of the incident.
Unearthing this kind of link allows a scientist to form a hypothesis, but it takes courage to stand up for it. Marshall had evidence to show that duodenal ulcers are tightly associated with the presence of a new, as yet uncharacterised, bacterium. While Agatha Christie’s Hercule Poirot might leap from such evidence straight to an accusation, a scientist has to be much more circumspect, and Marshall was forced to spend a couple of years carefully making his case.
He had already made a connection between antibiotics – bacteria killers – and cures for stomach problems. He had even tried it out on a patient: an elderly Russian man with ‘intractable abdominal pain’. An endoscopy revealed spiral organisms in the man’s stomach, and Marshall put him on tetracycline, an antibiotic. Even with the consent of the patient and his physician, this was ethical quicksand – and Marshall knew it. ‘This was the first time I realised that our clinical research project was probably overstepping the bounds of what would normally occur,’ he later wrote. ‘Taking an unnecessary biopsy was one thing, but using obscure findings from that specimen to justify antibiotic therapy was another. Nevertheless, we pressed on …’
It was time to do a study that would stand up to scrutiny. The focus of Marshall’s attention was now bismuth, a metal that had been used in Germany for more than two centuries as a cure for stomach problems. Bismuth was also used to treat bacterial infections such as syphilis. And syphilis was already known to be caused by a spiral bacterium. The circumstantial evidence was piling up.
Marshall conducted his study with some colleagues at Fremantle Hospital. They dipped some small discs of filter paper in a bismuth-containing medicine called De-Nol, then put the papers in the centre of a culture of the spiral bacteria. Four days later, the bacteria had died, showing up in a clear ring around the papers. The bismuth had killed them. Marshall describes that as probably the most exciting moment of his life. ‘It all fitted too perfectly to be a coincidence,’ he later wrote. ‘I think that was the first time it crossed my mind that we might win the Nobel Prize.’
Next, Marshall treated a handful of stomach ulcer patients with a mix of bismuth and metronidazole, another antibiotic. Four were cured. It sounds as though by now there should have been enough evidence to convince anyone. But there wasn’t.
Marshall needed to provide satisfactory answers to a set of questions known to medical researchers as Koch’s postulates. Outlined by bacteriologist Robert Koch in 1890, they provide four hurdles to be jumped before an infection can be said to be inextricably linked with a disease. Marshall