Transcript An End to Ulcers? By Kristi Hannam and Rod Hagley

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
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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.
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History of the understanding
of stomach function & ailments
HIPPOCRATES
WILLIAM BEAUMONT
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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!
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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.
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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.
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A Possible Study Design
• Doctors divide patients into two groups:
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
• 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.
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# Ulcers/ patient
Draw this graph: Predict what the results would
look like if the “excess acid theory” was supported
by the results of this study:
Group 1
Group 2
Treatment Group
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B
# Ulcers/ patient
A
# Ulcers/ patient
CQ4: Which graph most closely matches
the results you predicted?
Group 1
Group 2
Treatment Group
# Ulcers/ patient
C
D
Group 1
Group 2
Treatment Group
# Ulcers/ patient
Group 1
Group 2
Treatment Group
Group 1
Group 2
Treatment Group
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• 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
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Dr. J. Robin Warren: (pathologist)
Examines stomach
biopsies of patients
with various stomach
ailments.
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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. Warren’s 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.
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So, Dr. Warren:
• Used a special stain
that highlights
bacteria on his
slides.
• This convinced his
colleagues that the
bacteria were there.
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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 stomach’s defenses.
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Dr. Barry J. Marshall Joins Dr.
Warren’s 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 …
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Number of ulcers
after 2 months
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?
Control
Experimental
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B
C
Con
Exptl
Number of ulcers
after 2 months
Con
D
Con
Exptl
Exptl
Number of ulcers
after 2 months
A
Number of ulcers
after 2 months
Number of ulcers
after 2 months
CQ8: What results would you expect if the old
“excess acid hypothesis” were supported?
Con
Exptl
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Number of ulcers
after 2 months
What results would you expect if Drs.
Warren and Marshall’s “bacteria cause
ulcers” hypothesis is supported?
Control
Experimental
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C
Number of ulcers
after 2 months
Con
Con
Exptl
A
Con
Number of ulcers
after 2 months
B
Exptl
D
Exptl
Number of ulcers
after 2 months
A
Number of ulcers
after 2 months
CQ9: What results would you expect if the “bacteria
cause ulcers hypothesis” were supported?
Con
Exptl
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Actual Results of Warren &
Marshall’s 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.
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Drs. Warren & Marshall win the 2005
Nobel Prize in Medicine & Physiology
The Nobel Prize committee recognized
Warren & Marshall’s work changed peptic
ulcers from one of the world’s 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.
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