An End to Ulcers

1
An End to Ulcers?

• A Case Study in the Scientific Method
• by
• Kristi Hannam, State University of New York -
  Geneseo
• and
• Rod Hagley, University of North Carolina -
  Wilmington

2
CQ1 What do you think causes ulcers?

• A Stress.
• B Excessive stomach acids.
• C Bacteria.
• D A bad diet and alcohol use.
• E Being overweight.

3
History of the understanding of stomach function
ailments
HIPPOCRATES
WILLIAM BEAUMONT
4
What Causes Ulcers?

• Design an experiment to test if the excess acid
  hypothesis is true.
• In your small groups, design the experiment.
  Remember, be specific about how you would treat
  your groups and what you would measure!

5
CQ2 Which is a good way to test the excess acid
hypothesis?

• A Examine ulcer patients of a range of ages and
  measure their stomach acid levels.
• B Have volunteers drink alcohol and measure
  their stomach acid levels.
• C Lower stomach acid levels of some volunteers
  (using drugs/antacids), and measure numbers of
  ulcers in all volunteers.
• D Examine patients of a range of ages and
  measure the number of ulcers in each person.
• E Put volunteers through a stress test and then
  measure their stomach acid levels.

6
CQ3 What step in the scientific method does this
test represent?

• A Making observations.
• B Developing a hypothesis.
• C Determining predictions.
• D Testing a hypothesis.
• E Assessing support for a hypothesis.

7
A Possible Study Design

• Doctors divide patients into two groups
• After 3 months, the number of ulcers per patient
  is assessed.
• Predict what the results would look like if the
  excess acid theory was supported.

Group 1 received antacids and were instructed to
take them 3x/day
Group 2 received sugar pills and were instructed
to take them 3x/day
8
Draw this graph Predict what the results would
look like if the excess acid theory was
supported by the results of this study
Ulcers/ patient
Group 1 Group 2 Treatment Group
9
CQ4 Which graph most closely matches the results
you predicted?
B
A
Ulcers/ patient
Ulcers/ patient
Group 1 Group 2 Treatment Group
Group 1 Group 2 Treatment Group
D
C
Ulcers/ patient
Ulcers/ patient
Group 1 Group 2 Treatment Group
Group 1 Group 2 Treatment Group
10

• Unfortunately, this type of controlled experiment
  was NOT conducted.
• BUT, patients who took antacids had decreased
  ulcer symptoms.
• If the patients stopped taking the antacids their
  ulcers returned.

Image by Midnightcomm
11
Dr. J. Robin Warren (pathologist)

• Examines stomach biopsies of patients with
  various stomach ailments.

12
CQ5 The slides that Dr. Warren examined had
smudges that were not clearly visible under low
power, so he attached a high-power lens to his
microscope. What do you think he was able to see
then?

• A Many cells at once.
• B Only one cell at a time.
• C Organelles within the cells.
• D Bacteria.
• E Viruses .

LOW POWER
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Dr. Warren thought he saw

• Helicobacter pylori (a new species of bacteria)
• But no one else believed him!

The black squiggly spots on the slide are
bacteria that Dr. Warren observed In his biopsy
slides.
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CQ6 Dr. Warrens colleagues did not believe
there were bacteria in the stomach. Why do you
think other pathologists did not believe bacteria
were in the stomach biopsies?

• A Bacteria are never found inside the human
  body.
• B The pH of the stomach is too acidic for any
  bacteria to survive.
• C No one else had reported seeing bacteria in
  their biopsy samples.
• D Ulcers and stomach cancer are caused by age,
  stress and diet bacteria have nothing to do
  with the problems the patients came to the
  hospital for.

15
So, Dr. Warren

• Used a special stain that highlights bacteria on
  his slides.
• This convinced his colleagues that the bacteria
  were there.

16
Talk to your neighbor

• Dr. Warren thinks H. pylori causes ulcers.
• What is another hypothesis to explain why Dr.
  Warren was finding bacteria on his slides? (there
  are at least three alternative hypotheses...)

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Alternative explanations (hypotheses)

• 1. The biopsy specimens were contaminated AFTER
  samples were taken from the patients.
• 2. The bacteria live in the stomach, but do no
  damage.
• 3. The bacteria are an opportunistic species that
  arrives AFTER ulcers have already weakened the
  stomachs defenses.

18
Dr. Barry J. Marshall Joins Dr. Warrens Research

• Hypothesis Bacteria CAUSE stomach ulcers.
• If you were working with Drs. Warren Marshall
  to design a study to determine whether the
  bacteria caused ulcers, how would you do it?

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Their First Survey Study

• 100 stomach ulcer patients surveyed (biopsy
  taken).
• 100 had H. pylori present.

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CQ7 The doctors treated ulcer patients with
antibiotics to see if the disease stopped. What
is missing from their study?

• A An experimental treatment.
• B A control group.
• C An independent variable.
• D A dependent variable.
• E A hypothesis.

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Important Aspects of Experimental Design

• Testable hypothesis, i.e., a way to measure a
  response and a way to divide groups up into
• Control and Treatment Groups
• Control is group that does not get the
  hypothesized treatment.
• Treatment is group that does get the hypothesized
  treatment.

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The Importance of Controls

• Why do we need controls? Explain to your
  neighbor

23
If they set up their antibiotic study with a
treatment group receiving antibiotics and a
control group receiving a placebo (no
antibiotics), what results would you expect if
the original excess acid hypothesis was
supported?
24
CQ8 What results would you expect if the old
excess acid hypothesis were supported?
B
A
Number of ulcers after 2 months
Number of ulcers after 2 months
Con Exptl
Con Exptl
D
C
Number of ulcers after 2 months
Number of ulcers after 2 months
Con Exptl
Con Exptl
25
What results would you expect if Drs. Warren and
Marshalls bacteria cause ulcers hypothesis is
supported?
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CQ9 What results would you expect if the old
bacteria cause ulcers hypothesis were supported?
B
A
Number of ulcers after 2 months
Number of ulcers after 2 months
Con Exptl
Con Exptl
C
D
A
Number of ulcers after 2 months
Number of ulcers after 2 months
Con Exptl
Con Exptl
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Actual Results of Warren Marshalls Study

• When treated with antibiotics, 80 of patients
  were permanently cured of their ulcers.
• To further demonstrate the cause and effect
  relationship, Dr. Marshall (who did NOT suffer
  from ulcers), swallowed a flask of H. pylori from
  the lab.
• Within a week he was suffering from symptoms of
  gastritis and had H. pylori populations in his
  stomach!
• He cured himself with an antibiotic treatment.

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CQ10 If your father was diagnosed with stomach
ulcers, what do you think the recommended
treatment would be?

• A Lower stress levels.
• B Change diet to eliminate spicy food.
• C Take a course of antibiotics.
• D Drink milk to lower stomach acid levels.
• E Lose weight and exercise.

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CQ11 If you were shown the results of the Warren
Marshall antibiotic study, you would conclude

• A The excess acid hypothesis is supported and is
  the best explanation for the causation of ulcers.
• B The bacteria cause ulcers hypothesis is
  supported and is the best explanation for the
  causation of ulcers.
• C The excess acid hypothesis has not been
  overturned, but bacteria might have something to
  do with ulcers.
• D This study supports the bacteria cause ulcers
  hypothesis, but I need more evidence.

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EPILOGUE
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Medical doctors worldwide were NOT easily
convinced

• Drs. Warren and Marshall had trouble getting
  their results published in scientific journals
  and presenting results at scientific meetings.
• It took over 15 years and many more studies from
  researchers all over the world, before the
  bacteria cause ulcers hypothesis was accepted
  by the medical community.

32
Drs. Warren Marshall win the 2005 Nobel Prize
in Medicine Physiology
The Nobel Prize committee recognized Warren
Marshalls work changed peptic ulcers from one of
the worlds most common chronic, debilitating
diseases to one easily cured with a simple drug
regimen. Opened new avenues of research
-microbial causes of other chronic inflammatory
diseases. Also increased understanding of links
between chronic infection, inflammation, and
cancer.
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CQ12 If your father was diagnosed with stomach
ulcers, what do you think the recommended
treatment would be?

• A Lower stress levels.
• B Change diet to eliminate spicy food.
• C Take a course of antibiotics.
• D Drink milk to lower stomach acid levels.
• E Lose weight and exercise.