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
Q1: What do you think causes ulcers?

A. Stress.
B. Excessive stomach acids.
C. Bacteria.
D. A bad diet and alcohol use.
E. Being overweight.
History of the understanding
of stomach function and ailments

HIPPOCRATES

WILLIAM BEAUMONT
Q2: 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.
 A Possible Study Design
Doctors divide ulcer patients into two groups:
Group 1 received antacids and Group 2 received sugar pills
were instructed to take them and were instructed to take
3x/day. them 3x/day.

After 3 months, the number of ulcers per

patient is assessed.
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
Q3: Which graph most closely matches the results
you predicted?
A B

# Ulcers/ patient
# Ulcers/ patient

Group 1 Group 2
Group 1 Group 2
Treatment Group
Treatment Group

C D

# Ulcers/ patient
# Ulcers/ patient

Group 1 Group 2
Group 1 Group 2 Treatment Group
Treatment Group
 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

Dr. J. Robin Warren (pathologist)

Examined stomach
biopsies of patients with
various stomach
ailments.
Q4: 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.

LOW
B. Only one cell at a time. POWER

C. Organelles within the cells.

D. Bacteria.
E. Viruses.
Dr. Warren thought he saw:
A new species of bacteria
(Helicobacter pylori)
But no one else believed
him!

The black squiggly spots on the slide

are bacteria that Dr. Warren observed
in his biopsy slides.
Q5: 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 patients
stomach ailments.
So, Dr. Warren:

Used a special stain

that highlights bacteria
on his slides.

This convinced his

colleagues that the
bacteria were there.
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...)
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.
Dr. Barry J. Marshall Joins Dr. Warrens
Research
Hypothesis: Bacteria CAUSE stomach ulcers.

If you were working with Drs. Warren and Marshall to

design a study to determine whether the bacteria
caused ulcers, how would you do it?
Their First Survey Study

Dr. Barry Marshall joins Dr. Warrens research group.

Hypothesis: Bacteria cause stomach ulcers.
100 stomach ulcer patients were surveyed (biopsies
taken).
100% had H. pylori present.
Q6: 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.
Important Aspects of
Experimental Design
Testable hypothesis (ie, a way to measure a response
and a way to divide groups up into:)

Control and Treatment Groups

Control is the group that does not get the
hypothesized treatment.
Treatment is the group that does get the
hypothesized treatment.
If they set up their antibiotic study for ulcer patients
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?
Number of ulcers
after 2 months

Control Experimental
Q7: What results would you expect if the old excess acid
hypothesis were supported?
A B
Number of ulcers

Number of ulcers
after 2 months

after 2 months
Con Exptl Con Exptl

C D

Number of ulcers
Number of ulcers
after 2 months

after 2 months

Con Exptl Con Exptl

What results would you expect for ulcer patients if
Drs. Warren and Marshalls bacteria cause ulcers
hypothesis is supported?

Number of ulcers
after 2 months

Control Experimental
Q8: What results would you expect if the new bacteria
cause ulcers hypothesis were supported?
A B
Number of ulcers

Number of ulcers
after 2 months

after 2 months
Con Exptl Con Exptl

C D

Number of ulcers
Number of ulcers
after 2 months

after 2 months

Con Exptl Con Exptl

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.
Q9: If you were 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.
Q10: If you were shown the results of the Warren and
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.
EPILOGUE
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.
 Drs. Warren & Marshall win the 2005 Nobel
Prize in Medicine & Physiology

The Nobel Prize committee recognized that 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.
For Next Lab (cont.)

Read the material for Thursdays lab (Microscopes and Cells).

Be prepared for a quiz!