Teacher notes - Dr Robin Warren

Dr Robin Warren

Pathologist

Contents

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Introduction

Professor Robin Warren was interviewed in 2008 for the Interviews with Australian scientists series. By viewing the interviews in this series, or reading the transcripts and extracts, your students can begin to appreciate Australia's contribution to the growth of scientific knowledge.

The following summary of Warren's career sets the context for the extract chosen for these teachers notes. The extract discusses how Warren first realised that there were bacteria living in the stomach. Use the focus questions that accompany the extract to promote discussion among your students.

Summary of career

John Robin (Robin) Warren was born in Adelaide in 1937. He was educated at the University of Adelaide where he received an MBBS in 1961. All areas of medicine were interesting to him, but he found pathology very interesting. In Adelaide, he was a resident medical officer at the Queen Elizabeth Hospital (1961–62) and registrar in haematology and clinical pathology at the Institute of Medical and Veterinary Science (1962–63) before working as a lecturer in pathology at the University of Adelaide (1963–64).

Warren moved to Melbourne where he was a pathology registrar from 1964 to 1968, becoming a fellow of the Royal College of Pathologists of Australasia in 1967. He moved to the Royal Perth Hospital as a staff specialist in pathology in 1968, and remained there until becoming an emeritus consultant pathologist at the hospital in 1999. He also was appointed an emeritus professor at the University of Western Australia in 2005.

In the 1970s gastric biopsies became more common at the same time Warren was developing improved stains for use on his tissue samples. Then, in 1979 he noticed spiral-shaped bacteria (now known to be Helicobacter pylori) in biopsies taken from patients who were suffering from gastritis and gastric and duodenal ulcers. This was against the conventional wisdom of the time, which was that the stomach was too acidic for bacteria to survive, grow and cause disease.

In 1981 Warren met Dr Barry Marshall who was a gastroenterologist registrar. The two undertook research into H. pylori and its role ulcers and disease. Warren and Marshall spent many years trying to convince the medical establishment of the validity of their work and developing a diagnostic breath test for H. pylori infection. In 1994 the World Health Organization accepted that H. pylori is a causative factor in stomach cancer. Their work received the Nobel Prize for physiology or medicine in 2005.

In addition to the Nobel Prize, Warren has received numerous national and international awards including the Distinguished Pathologist Medal (International Academy of Pathology (Australia), 2007), the Gold Medal of the Australian Medical Association (2006), the Medal of the University ‘La Sapienza’ of Rome (2005), the Centenary Florey Medal (Adelaide 1998), the Medal of the University of Hiroshima (1996) and the Warren Alpert Foundation Prize (jointly with Dr BJ Marshall, Harvard Medical School 1994). He was made a Companion of the Order of Australia in 2007.

Warren was elected a Fellow of the Australian Academy of Science in 2006.

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Extract from interview

Seeing the bacterium for what it is

Robin, when did you take the photograph you have been showing me?

In June 1979. I first saw the bacteria on my birthday, and that photograph would have been taken the day after my birthday.

So this is one of the first photographs you ever took of the bug?

Yes. The tissue for this is from a wax block, whereas a few days later I took a piece of tissue from a special plastic block which is processed for electron microscopy. The earlier one is at a lower power, being taken just from the top of some cells.

Tell me what you thought, how you reacted, when you first saw that.

I thought they were interesting. I have with me here my first report on the original case I had, and I can show you the ordinary microscope view of the original case. And you can have a close-up view yourself. This shows cells bulging out into the lumen, and stuck on the surface of the epithelium are masses of little bacteria which are staining quite nicely with a silver stain – they stain black.

You can see masses of bacteria in the views from that original case, but I didn’t know what they were. The teaching at the time was that bacteria can’t grow in the stomach. (I eventually worked out my own theories as to why they did grow there.)

All we’d ever hear from the clinicians was something like, ‘Peptic ulcer, query carcinoma.’ But I thought these bacteria were interesting. We’re always finding interesting things in pathology. When you look down the microscope at pieces of tissue, though, it’s not unusual to find something unexpected, because there are so many unusual things. And if there are 10,000 unusual things, you find one of them every now and again.

That is exactly right. But not everybody pursues the one interesting thing in the 10,000 that you might see.

Well, you don’t usually try and see them again. But with this one I actually had my own colleagues challenging me: ‘Really, Robin, if you think they are interesting, why don’t you try and find some more?’ So I thought, ‘Okay, there’s no harm in trying to find some more,’ and I started actively looking for these bacteria. They weren’t hard to find once I’d seen them.

It was like opening your eyes in front of you?

Yes. I’d never seen them before that – I ‘knew’ they weren’t there, because everyone said they weren’t there.

In the particular case here, the mucosa in the section are shown at the usual fairly low power, because most of the diagnostic pathology is done using a fairly low-power magnification.

Usually you’re looking at cells and their reaction?

You’re looking at the tissues more than the cells, and with the low power you can see most things. But all I could see of the bacteria was a funny-looking thin blue line stuck on the surface of the cells in some areas. Wondering what that might be, I had a quick look with high power, and it seemed that there might be little organisms there.

So then I had a look with the oil immersion lens, at the highest power we can use for light-microscopy. And to me it seemed obvious that there were little organisms growing around, stuck on the surface of the epithelial cells, but not as clear with the ordinary H&E-stained section. [Hematoxylin and Eosin stain is a popular method for staining cellular proteins and nucleic acids and is one of the stains most widely used in medical diagnosis].

Did you ever find out anything much about that person whose case changed your life?

No.

An edited transcript of the full interview can be found at
http://www.science.org.au/node/326004.

Focus questions

  • What do medical pathologists do?
  • Warren talks about it being not unusual for pathologists to see unexpected things. What role do unexpected things play in scientific studies?
  • Why do you think Warren ‘knew’ there weren’t bacteria in the stomach?

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Activities

Select activities that are most appropriate for your lesson plan or add your own. You can also encourage students to identify key issues in the preceding extract and devise their own questions or topics for discussion.

  • Have students use library and internet resources to investigate Helicobacter pylori. They should find information on its structure, disease symptoms and treatment. Students present their findings as a brief report.
  • People in the pathology laboratory (Lab Tests Online Australasia)
    This website describes the different jobs and pathology disciplines at work in pathology laboratories in Australia. Have students read the material and select a discipline to investigate further independently. They prepare a poster or brief report on their findings.
  • Exploring microscopes (National High Magnetic Field Laboratory, Florida State University)
    An introduction to the light microscope which provides step-by-step instructions that facilitate discovery of how the microscope affects an image. A Java-based interactive simulation is also included to show how magnification changes what is seen through a microscope.
  • Observing cells: using staining – teacher’s guide (The Chemical Heritage Foundation)
    For this microscope activity students should be familiar with the structure and components of the cell, have some understanding of proteins, and comprehend the interaction of cations and anions that is responsible for the binding of stains to proteins in cells. The student version of the activity contains information on the use of staining by medical microscopists throughout history.
  • Discovery School
    • Introduction to bacteria
      Students research how bacteria move, where they live, and how they reproduce, learn how bacteria can be helpful or harmful and create a display illustrating what they learned about bacteria.
    • The how and why of digestive disorders
      Students research one common problem of the digestive system, such as constipation, gas, lactose intolerance, or ulcers and create a brochure, similar to one found at a doctor’s office, that describes the problem, its causes, symptoms, and possible treatments.
  • Bacteria wanted poster project (Access Excellence, USA)
    Students will research one bacterial pathogen and produce a ‘Wanted Poster’ containing a set list of informational items. The list of moneran (bacterial) pathogens that students choose from should include Helicobacter pylori.
  • Ulcer bug breakthrough (Science upd8, UK)
    Students learn that peptic ulcers are caused by bacteria and can usually be cured by antibiotics. They then create an oral news report. Access to activities is free to registered users.

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Keywords

bacteria
disease
microscope
pathology
peptic ulcer

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