O/T Barry Marshall: I don't do authority

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January 17, 2009

http://www.timesonline.co.uk/tol/life_and_style/health/article5524990

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Times Online - UK

Barry Marshall: I don't do authority

The Australian doctor who found a cure for stomach ulcers believes

that being a rebel is good for medicineSimon Crompton

As legendary medical stories go, Barry Marshall swigging a test tube

full of potentially lethal bacteria to prove his controversial

theory stands somewhere between Fleming, the discoverer of

penicillin, spotting mould on his Petri dishes and Dr Henry Jekyll

transforming himself into Mr Hyde.

As a 32-year-old upstart gastroenterologist at Royal Perth Hospital,

West Australia, Marshall defied the conventional wisdom that ulcers

in the stomach and the gut (peptic ulcers) were caused by excess

stomach acid, stress and spicy food, and insisted that they were

caused by a new bacterium that he had discovered. Rubbish, said

peers and colleagues, who said that every study he had produced had

failed to prove anything, even though their existing treatments were

ineffective. So, in 1984, Marshall decided to infect himself with

the bug Helicobacter pylori to demonstrate how quickly he developed

signs of an ulcer.

It worked; and he survived. Within a decade, Marshall had gained

heroic status among the public and much of the medical community -

not so much because his devotion to proving a theory had endangered

his life, but because it was a delicious example of someone

rejecting orthodox thinking and being proved right. His astute act

of rebellion was eventually rewarded with a Nobel prize in 2005.

His discovery has been hailed as the most significant in the history

of gastroent-erology and has been compared to the development of the

polio vaccine and the eradication of smallpox. It has resulted in

stomach ulcers, once potentially fatal, being easily treated with

patented antibiotic drugs, many developed by Marshall with pharma

companies.

From rebel to establishment figure

Today, a youthful 57, Marshall is somehow reconciling his rebellious

restlessness with the fact that he has become a lauded establishment

figure. He is Professor of Infectious Disease at the University of

Western Australia and he has his own research department and biotech

company, studying potential uses of the unusual bacteria he has

discovered, including carrying vaccines into the body.

But he is also true to his anti-establishment bent, lecturing

students around the world about the benefits of working hard at what

interests them rather than what they're told to. His mantra is that

the greatest obstacle to knowledge is not ignorance but the illusion

of knowledge.

When I meet him in London he insists that winning the Nobel prize

hasn't changed him, it has just given him more opportunities and

academic freedom. " Most of all it was a great party after the

presentation, " he deadpans. The story goes that he was in the Perth

pub he frequented every Nobel night when he got the news. It was the

pub where he and his co-researcher Warren light-heartedly

drowned their sorrows because they hadn't won anything. He was told

that he had become a laureate on his mobile phone minutes before the

official announcement. " I think I was just frozen, " he says. " You

think, this is great, but then, what do I do now? "

He is visiting England to support a new global foundation that will

provide funding so that doctors and academics who come across

promising research leads in their day-to-day work (as he did) can

take time out to pursue them. He is also visiting his daughter, a

legal secretary working in London for a year. Hunched against the

cold as we take pictures on an unusually clement winter day, he

doesn't have the swagger you might expect.

Approachable and down to earth, his mind regularly wanders into the

areas that interest him rather than those you direct him to. It

hasbeen a problem since he was a schoolboy, he admits, when he found

it impossible to stick with the syllabus, even in subjects such as

chemistry, which he loved. Electronics is a passion; when we meet he

is preoccupied that his hotel doesn't seem to have heard of USB

connections for computers.

So what did Helicobacter pylori taste like? " It was like clear beef

soup, " he says. " Drinking it was a difficult thing to do, and I

suppose it was like bungee jumping; taking that leap is exactly the

same kind of adrenalin rush as drinking a test tube full of

bacteria. " He took the draft in the hospital lab shortly after a

presentation of his work to gastroenterologists at a national

meeting in Australia was poorly received: some people were rude.

That pushed him over the edge after many years of professional

scepticism. " I had to decide whether I wanted to spend the rest of

my life working on this thing and getting nowhere, or do the

definitive experiment. " It began in 1981, when he arrived at the

gastroenterology department of Royal Perth Hospital, still training

as a specialist doctor. He had been intrigued by patients who had

stomach pain but no diagnosis, and teamed up with Warren, the

hospital's pathologist, who had found a strange spiral bacterium in

their stomachs.

In their spare time, the two worked out that this bacterium was

causing infections and unpleasant symptoms that would lead to damage

of the gut wall, and full-blown ulcers. But even their bosses didn't

believe them; after all, in theory, bacteria shouldn't be able to

survive in the acidic stomach. And Marshall wasn't even a fully-

fledged gastroenterologist (something, he now believes, was

invaluable in giving him an objective view of problems unalloyed by

conventional wisdom). " There was a real urgency because we were

talking about a disease that affects millions of people and was

sometimes fatal. Every night on call in gastroenterology wards there

would be people coming in with huge gastrointestinal bleeding, and

having half their stomachs removed, and when you knew you could

possibly prevent this with a dose of penicillin ...

" We were labelled maniacs and zealots from an early stage. We could

think about and speak about nothing else, but no one else could have

a proper opinion on it because it wasn't part of existing science.

We were pretty incorrigible and annoying to our professors and

seniors because we always reckoned we knew more than they did, which

was true enough in that area. Now that I am older I can see that I

must have been a difficult person to work with. I never had any

respect for authority. "

That started as a kid, when he moved from a provincial mining town,

Kaloorlie, to be schooled in Perth, and immediately felt like the

outsider - a country bumpkin among townies, poor at sport, smart in

science, but unable to impress with top marks because he preferred

to do his own experiments in his dad's shed at home, making radios,

explosives and a hydrogen generator for balloons. " If my science

teacher told me one thing, I'd be there trying to prove him wrong,

continually looking for an alternative. Maybe it's laziness on my

part; if there's anything difficult and tedious, I think there must

be an easier way to do this. "

He admits that there was something of the show-off about this. When

he chose medicine as a career (fearing his maths was not good enough

for electrical engineering) he quickly noticed that everyone

remembered the spectacular diagnosis, even if you made only one a

year. " They'd forget about the ten incorrect ones you'd made using

standard techniques, so it was better to stick your neck out and

have a go at these things. "

As with many tales of dedicated discoverers, you marvel at the

tolerance of the family. When Marshall conducted his experiment on

himself, he and his wife Ariadne, a psychologist, had four children

aged between 10 and 3. He didn't inform Ariadne, or any of his

colleagues, about what he was doing, mainly because he knew they'd

object.

" I'm a selfish so-and-so "

" A few days after taking the bacteria I began to feel this heavy

fullness after eating, and then on day five the vomiting started.

One of the reasons I didn't tell my wife about it was that she had

whiplash from a car accident. There was a lot of chaos in the family

and in the middle of this each morning I would wake before dawn and

run to the toilet to vomit. I had bad breath and I looked terrible.

You have to admit I'm a selfish so-and-so to even go ahead with the

experiment. "

Ten days after drinking the bacteria, Marshall had an endoscopy and

other tests to show that his previously bug-free stomach was

thoroughly infected and that he was showing the same signs as his

patients.

" At that point I couldn't restrain myself; I had to tell the wife.

She was speechless. " He laughs. " But it's easier to ask for

forgiveness than permission. " She insisted that he took antibiotics

to clear up the infection straight away, though Marshall wanted to

continue until he had a full-blown ulcer.

A paper in the Medical Journal of Australia followed and, gradually,

Marshall gained more and more high-powered supporters across the

globe. By 1997, with the marketing of new patented antibiotic

treatments, the global battle against stomach ulcers really began.

What became apparent with time was not only that more than half the

people in the world were infected with Helicobacter pylori, but that

the better their hygiene and living conditions, the less likely they

were to have it. Now there is a Helicobacter Foundation, founded by

Marshall in 1994, dedicated to finding ways of diagnosing, treating

and eradicating the bacteria, which is " out of control " in some

countries and in others still isn't tested for in cases of stomach

problems. " There's still a long way to go, " he says.

Marshall is still pushing at the boundaries with his work looking at

Helicobacter pylori as a vaccine carrier. The theory is that, since

the bacteria are immune to stomach acid, they will be able to carry

flu and other vaccines into the body by this route, making gaining

immunity as easy as taking a probiotic drink.

" I'd say that 50 years from now all those vaccinations we worry

about won't even exist, it will be just built into the food supply, "

Marshall asserts confidently.

What drives him on with this may still be that strange restlessness

he felt all those years ago in a Perth pub when he heard that he had

become a Nobel laureate. Now what? Maybe, he admits, he has got half

an eye on another Nobel prize.

Top five self-experimenting doctors

Cardiac catheterisation

In 1929, the German surgeon Werner Forssman took a 65cm-long

catheter and threaded it from an incision in his arm up to the right

atrium of his heart, and then took an X-ray to prove that catheters

can be inserted into the heart for investigational purposes.

Polio

In the 1950s, the American Jonas Salk, by killing a sample of the

polio virus and then administering it to animal test subjects and

eventually to himself, discovered that patients became immune to the

live virus. This led to the modern polio vaccine.

DNA

The British scientist lind lin, who had an instrumental

role in discovering the structure of our DNA, died of cancer,

possibly because of exposure to X-rays she used in her experiments

in the early 1950s. Her X-ray photographs established unequivocally

the structure of DNA.

Gonorrhoea

Hunter, an 18th-century surgeon and anatomist, gave himself

gonorrhoea by applying the pus of an infected patient to his own

penis to test his theory that it would develop into syphilis. The

experiment was flawed, but was later repeated my medical students to

produce the correct results.

Anaesthetic

The ish obstetrician Sir Young Simpson tested chloroform

on himself and two assistants in 1847. All three were discovered

unconscious under a table. After dramatic successes on patients, the

anaesthetic won royal approval when Queen enjoyed a pain-

free childbirth with the aid of chloroform in 1853.

Stomach ulcers - the facts

Peptic ulcers - those found in the stomach and the part of the

intestine just below it - are caused by the bacterium Helicobacter

pylori. The bacteria cause gastritis (inflammation of the stomach

lining), which can lead to ulcers when stomach acid exploits the

weakened areas.

Famous people troubled by H. pylori infection include Joyce,

Bush (Sr), Pope II, Imelda Marcos and Alfred Nobel.

The Iranian leader Ayatollah Khomeini and the actor Lorne Green died

of bleeding ulcers.

The bacterium is passed on orally, possibly via water or food

tainted by faecal matter. In Britain, about 30 per cent of the

population are infected. The rate is 20 per cent among affluent

groups, and the likelihood of having it increases with age. Most

adults in developing countries are infected.

Symptoms Many of those carrying the bacteria have no symptoms, but

all have inflammation of the stomach lining, which can lead to

heartburn, belching and many other abdominal problems.

Have you got it? Gastroenterologists can find out whether you are

infected with breath tests, blood tests and internal examination via

endoscopy.

Treatment is usually simple, with anti-acid and antibiotic drugs,

although there can be unpleasant side-effects.