Dr. Steven Griffiths Monthly Column, published in the Times & Transcript

Bazza's Bugs

Tuesday July 22, 2008

First, a Science of Life Anatomy and Medicine pop quiz!

1. Name a celebrity that gets out of Limos flashing some anatomy nicknamed after a small Canadian wood nibbler

2. What is the major cause of ulcers and persistent tummy troubles?

Most of us get the first one on the fly. Heck, I think there are four possible answers. But the second one? Who said “stress” or “spicy food”? I’m one.
Click Picture to Zoom

Neerrrrk (that will be the “wrong” buzzer then).The number one cause of ulcers and a host of other gastric maladies is a corkscrew of a microbe called Helicobacter. A driven young intern named Barry Marshall and his unassuming yet heroic boss, Robin Warren, identified this cause and effect relationship in Australia, 25 years ago. Today, it seems important that we need to be informed of the exposure of celebrity nether-regions, antipodean anatomy if you will. But most of us would not be able to name two Aussies named Barry and Robin except perhaps as two of the Bee Gees (although that would be pretty swift).

There are some sad truths here. As far as science “news” reporting goes, we generally get to hear that someone had an adverse reaction to something that otherwise benefited millions-and we’re all expected to panic and drive up advertising; perhaps we might be informed that someone grew a human ear on the back of a mouse. Science should enrich, illuminate and enhance our appreciation of life, not give us the willies. Quite aside from allowing us to make better decisions, provide perspective and context in quotidian life, knowledge of science prevents us from getting ripped off, intellectually and financially. And yes, Virginia, we can still have our Brindsay cake and eat it.

Unfortunately, as the beatific Carl Sagan frequently pointed out, we are served by a popular media interested in selling titillation, fear, angst and conspiracy. Sagan is still spot-on: When science is allowed out to play, it is presented as quirky, creepy or malevolent. Ineluctably, this lack of exposure also explains why we still sponsor weird psychopathic divine beings that drive international and domestic policy, or permit us to dwell on space-aliens that peep through bedroom windows.

Well OK, you might say, let’s get back to the original story. Barry and his mates discovered that microscopic drill bits are currently wiggling around in 80% of us with a spectrum of irritation between zero and morbidity. Why might these Aussies be considered brave and heroic?

Unlike myths that are simply recognized because, well, they just are (and grandfathered directly into our lives), scientists poke, prod and ridicule each other to the point of career assassination. They don’t hold grudges to the point of harming each other. But, quite often, even the most eminent of our respected elders are blinkered like Shire horses-what they were taught in medical school or by their supervisor is the bill of goods. Plus, like any rat race, there are a lot of failed professionally jealous mammals slithering about out there.

So: when upstarts, like Barry and Robin come along to present data that, despite being so glaringly self-evident, so intuitively elegant, it goes against the grain, is considered heresy. The apostates receive a frosty reception, if not derision. It can be a painful process that may drive one half mad. However, in science, the truth will always out.

Here’s Barry reminiscing about sharing his early observations of Helicobacter and the treatment of his patients with gastric distress (parentheses mine):

“One day, after I presented my histology (microscopic) data showing the healing of Gastritis with bismuth (pepto-bismol), the senior hospital pathologist stated “Dr Marshall these changes seem very subtle.” Actually the changes were quite dramatic, and this was the first time anyone in the world had been able to heal gastritis! I bit my tongue to stop myself from saying “are you crazy?” Others suggested again that these commensal (harmless) bacteria merely infected people who already had ulcers. But quite clearly I had presented data from patients with gastritis who did not have ulcers. By combining bismuth with metronidazole (an antibiotic), I was able to eradicate Helicobacter in most patients, in just two weeks. When that failed I could use bismuth with amoxicillin (another antibiotic) to cure half the remainder. For people facing stomach surgery for ulcers, all these antibiotics seemed rather trivial.”

He saw many patients with symptoms, but with no ulcers. Many doctors believed that such patients had it all in their heads. However, Barry treated many “crazy people” whose symptoms improved during antibiotic treatment. He continues:

“I realized then that the medical understanding of ulcer disease was akin to a religion. No amount of logical reasoning could budge what people knew in their hearts to be true. Ulcers were caused by stress, bad diet, smoking, alcohol and susceptible genes. A bacterial cause was preposterous.”

Lesser mortals might be cowed by rejection and subtle if not outright derision. Not Barry. What did he do?

He drank some.

He got very ill: cramps, fevers, vomiting, halitosis- the whole Kahuna. Finally they were able to prove that a human subject- to whit, Barry- could be infected by, suffer from, and be treated for, the squiggly demon. He further reasoned that it might be possible that ulcer patients would not recall an initial infection at an early age, perhaps between 2–3 years. The spectacular projectile vomiting that many of us witness as parents may settle into a prolonged symptom free phase leading to ulcers and a host of other tummy troubles: because the bacteria are not affected by any of the usual therapies, the disease may thus become a lifelong see-saw. Sound familiar? It is possible to be infected by family members, so it seemed to be hereditary- another old chestnut. In truth Helicobacter is spread by the faecal-oral route or exposure to vomit from sick brothers and sisters: this melted in with the observation that individuals in lower socio-economic groups were more at risk. Finally, in contrast to his patients, Barry’s self inflicted infection ran its course: he did not remain infected. His altruism yielded the first indication that such things might happen regularly, or that there are some of that are able to deal with an acute infection without further worry………for now.

After Barry Marshall’s heroism, the pennies started to drop in the greater scientific community- the cries turning from hooey to huzzah. Some reluctance to funding remained because, in terms of economics, a cure is not a moneymaker for the government or the pharmaceutical industry. Most of us that were teenagers or older remember the miracle drug Tagamet that enjoyed huge profits when ulcers were believed to be due to excessive acid, but then turned out to be tangential to what we now know as the major cause (note that the active ingredient of Pepto-bismol is a bacteria killer). You will not see any reference to Helicobacter on the wikipedia page for Tagamet to this day. We’ll return to this issue when we talk about sparse funding for vaccines (i.e. successful product= lack of return business).

As indicated above, 80% of us are, or have been infected with Helicobacter and it may never cause any problems. These fellows have been with us for a very long time- in fact they may be used as molecular clocks. By comparing Helicobacter DNA sequences, we can determine where their hosts-our ancestors-took a left or right turn from their cousins during the trek out of Africa. Further back in our ancestry, dolphins have their own species of Helicobacter too which means that they were around when their ancestors were out on solid ground with the shared progenitors of deer and hippos- some 50 million years ago- and then took them back to the beach.

You know me as a cancer researcher, so why should I be so interested in gut rot beyond infection among the below stairs staff at Griffiths Manor? Well, beside the inspiring story that some times the good guys win (Barry and Robin did win the Nobel Prize for Medicine in 2005), it now turns out that the connection between Helicobacter and stomach cancer is as strong as that for cigarettes and lung cancer. If you were drinking coffee, I’ll excuse the spit take.

Yes. The attention given to Helicobacter further accentuated an established observation that cancers, particularly of the mucosal surfaces such as the gut lining, frequently correlate with inflammation- that reddening that indicates that the riot police of the immune cells have moved into the area. These guys are armed to the membranes with biochemical tools and weapons that serve two major purposes: first stomp on the baddies (i.e. micobes) and, secondly, get bystander cells to multiply and repair the damage- kinda like microscopic road crews only with not as many standing around watching the individual filling the hole. Our cellular riot police would not get high marks at the Geneva convention- they go in swinging and essentially go postal on anything that hints of naughty behaviour- expand surrounding blood vessels and make them leaky so that fluid and more reinforcements can get whistled in (a modified version of this happens when we get allergies). The riot control gear includes biochemicals that kill infected cells and their contents- it’s a real scorched earth policy- and these include things that damage the DNA with substantial collateral damage and friendly fire. It’s all pretty harsh-whenever inflammation occurs we generally feel like crap due to swelling, itching and general malaise. We have here two predicates for cancer- DNA damage that loads the genetic dice to come up with something that subverts the orderly replication of cells, combined with the impetus for multiplication that allows extra free throws- millions of free throws. Under optimal circumstances we feel crappy and the situation is dealt with: the riot police put up the yellow tape and the road crews fix the hole. Unfortunately some infections don’t go quietly and the riot police and road crews pull round the clock shifts for a very long time. This is what we would call persistent or chronic inflammation, a hallmark of debilitating gastritis. With all that front line activity and multiplication going on, there is a greater possibility that the genetic chips will stack up and create a misbehaving cell- thumbing its nose at the instructions for white picket fences and good grooming that are generally observed outside the melee of inflammation. It is for good reason that cancers have been said to emerge from “wounds that never heal”.

The labyrinthine forks that determine whether you, I or our children will ever experience symptoms or nurture something far more troubling, are highly complex-dependent upon the landscape of environmental and internal factors that influence the “emergent phenotype” (see last column).

Medical policy makers are now vigorously researching and discussing the pros ands cons of prevention. Should we consider blanket vaccination? It’s a toughie even to the point that the recruitment of control, or placebo, groups are ethically challenging because Helicobacter is a registered carcinogen. Also, perhaps as might be expected after a decade of acceptance (quiz your family doctor just to be on the safe side), we’re now seeing antibiotic resistant Helicobacter that require increasingly shrewd combinations of anti-bacterials. Here is another problem arising from patients that do not complete antibiotic treatment- substantial wriggle room for the emergence of bacteria decked out in molecular kevlar. There is a parallel here of course to the scourge of antibiotic resistant bacteria that are affecting our hospitals - it’s evolution going on right under our noses- and similarly given a boost by poor education and hence hygiene. And here we are again-if there was a greater appreciation for the Science of Life we may improve the quality of our existence, save billions in health care and inspire new generations to help us and our offspring stay healthy wealthy and wise. Well at least healthy and wise.

Meanwhile, has Angie had those twins yet?
(foot note: it turns out she was having them during the completion of this article)

Links

* Read about Robin Warren and Barry Marshall (click on the little arrows to see a cool slide show on the connection between ulcers, gastritis and Helicobacter)
* Please read Barry Marshall’s Nobel Prize lecture (as quoted above)- it’s a great read
* Here’s a free Helicobacter comic!
* Space aliens that peep through bedroom windows
* “The Demon Haunted World: Science as a Candle In the Dark” by Carl Sagan.

Article as published:
http://timestranscript.canadaeast.com/news/article/361518

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(Published in Times & Transcript)