Nobel winner Barry Marshall and the unfriendly bacteria

This lecture took place in September 2010 and is now available online. I started typing up my notes soon after but have only got about half way through. Normally that would mean it would be ages before I finished and posted them as a blog post, but with my new 'let's serialise everything' plan I'm posting unfinished things and coming back to them later. Not sure when I'll finish it though, as I may have carelessly lost the remaining notes pages, oops.

Barry Marshall
'Past lessons and future opportunities for Helicobacter pylori'
UCL Prize Lecture, 20 September 2010

As soon as we started it was clear we were in for good-humoured fun - the audience was in a cheerful mood and I think it's safe to say we were a 'good crowd'. In number too, there was barely a spare seat in the lecture theatre. As I work at UCL I'm automatically on a list to receive information about our events - if they're public then I'll usually share them on my Posterous blog, but there's a listing of public events here. The event took place in one of the lecture theatres in the gorgeous Cruciform building, designed by the same chap (Alfred Waterhouse) who designed the Natural History Museum.

To start we had a brief introduction from someone who ran through Barry's biography, wryly admitting he'd got it from Google and Wikipedia, which got an appreciative chortle. We also saw a list of previous UCL medal winners, including a number I'd heard of.

As the introducer was about to hand over to Barry he tried to set up the presentation for him, struggling gamely with an animation of the 3D structure of the protein urease that was part of the powerpoint, and expressing amused irritation that the software wasn't yielding to his commands. Barry's 'I can do that', from his audience seat, got a welcoming giggle and he took to the stage.

Barry jokingly suggested that if you're going to make a Nobel-worthy discovery do it while you're young as it'll probably be a couple of decades before you'll get the prize. He and the team he was working with published their findings on the link between H. pylori and gastric ulcer in 1984, he won the Lasker Award in 1995 and the Nobel Prize in 2005. He showed us a rather nice cartoon slide of a couple of the bacteria - this was developed with a graphic designer and submitted to a competition at The Scientist (it's a finalist).

Around the time of the discovery there were a number of possible options for 'things that cause gastric ulcers', stress being thought to play a major role. No-one was terribly excited by the prospect of another possible cause, so the discovery seems to have arrived against a backdrop of 'meh'. Barry then put up a quote from Daniel Boorstin who said that 'the obstacle to discovery is the illusion of knowledge' - there was no particular imperative to search for other causes.

The impact on individual and public health has been notable, not to mention on lost productivity. He suggested the scenario of busy stressed executives with an ulcer being ordered by their doctors to retire early and take to a life of beach-ly leisure. More seriously, ulcers had a major cost impact and wrecked lives with several thousand deaths every year in the 1980s.

While there wasn't much impetus to find alternative causes for gastric / peptic ulcers bacteria were already low on the list of possibilities. The medical textbooks of the time held that the stomach, being highly acidic, was sterile and any bacteria introduced would be killed off. One of the reasons for acidity is to extinguish some newly met bacteria to 'sterilise' food and prevent gastroenteritis, but as we all know now the stomach contains many different bacteria which are considered essential for health. Extremophiles have also been discovered which include bacteria that can survive and thrive in conditions previously considered as unable to support life. Most bacteria are killed at pH4 and the stomach's acidity is at pH1.5 so it's not too surprising that bacterial infection wasn't considered as a likely candidate.

Barry showed us a slide of biopsies taken from 100 patients (quipping that they used 100 patients as they didn't have a computer at the time and so it made the maths easier) where 13 out of 13 patients with peptic ulcer had these twirly bacteria in their biopsies. I couldn't help but be reminded just a tiny bit of a certain struck-off someone who looked at the guts of children and drew some wrong conclusions.

He and a colleague tried to get this data into a meeting but were rejected - he showed us the rejection letter, and recommended that people kept theirs to amuse crowds in future. Apparently of 67 abstracts submitted the organisers could accept only 56 ;)

I missed an interesting aside into statistics, so forgive if this is a little bit wrong, but in the list of 100 patients they spotted that almost everyone with 'oesophagus abnormal' which is also known as acid reflux didn't have H pylori - the level of significance suggested thateliminating H pylori might increase the risk of acid reflux (but I might be wrong).

The next article he showed was 'An attempt to fulfil Koch's postulates for Campylobacter pyloridis' from Medical Journal of Australia, 1985. Koch came up with a series of tests, in the 1800s, in order to demonstrate that a condition had a bacterial cause. First catch your bacteria (from someone who has the disease you're studying), culture it, infect someone or something, wait for your disease to appear then collect evidence of bacterial infection.

This was the next step for H. pylori and Barry drank some (it turned out to be two Petri dishes' worth, someone asked at the end!) to show that they could survive and colonise in his stomach. He showed a biopsy photo which clearly illustrated an infection, and some pretty annoyed stomach lining cells. The infection was accompanied by nausea, vomiting and other gastric disturbances - I think he was fairly prompt with a course of antibiotics after though, so probably didn't have a full blown ulcer. He said he was surprised by how ill he felt - many people have asymptomatic H. pylori for (probably many) years before ulceration shows up.

His suggested explanation is that people acquire their infection in childhood, have a few days of being sick but then recover though the bacteria remain, ready to create ulcers at some future date.

It took quite a while for anyone to be particularly impressed by this and I expect that somewhere there's a seller of nonsense alternative therapies who mentions Barry Marshall in the same breath as Galileo as someone who was ultimately proved right.

In 1997 Abbott, who marketed a treatment for H. p took matters into their own hands and commissioned a cartoonist to visit Marshall's lab and create a storyboard. There was a fantastically lurid drawing of Barry holding a beaker of bubbling green liquid about to drink it saying "there's no other way" with a colleague looking on saying "you're crazy" (17m10s). The resulting cartoonified story was sent to a 150,000 doctors and was apparently very successful in convincing them that peptic ulcers should be treated with a course of antibiotics. Obviously I wondered about other uses of cartoons in communicating science, either in medical education or public engagement!

Apparently the bacterial solution was actually brown but the cartoon people had some involvement in "The Incredible Hulk" and went instead with green...



My l'esprit d'escalier question was "Why did people who had to take antibiotics for other things not notice their ulcer getting better?"