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The scientific method F. Guesdon MED610 DDP March 2013

The scientific method F. Guesdon MED610 DDP March 2013

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Page 1: The scientific method F. Guesdon MED610 DDP March 2013

The scientific methodF. Guesdon

MED610 DDPMarch 2013

Page 2: The scientific method F. Guesdon MED610 DDP March 2013

Is square A darker than B?

“Checker shadow illusion”, first described by Adelson, 1995

Page 3: The scientific method F. Guesdon MED610 DDP March 2013

The “scientific method” modelo Describes “best practice” method for scientific

discovery

o Developed from observation of succesful scientists

Page 4: The scientific method F. Guesdon MED610 DDP March 2013

History10th Centuryo Ibn al-Haytham (Alhacen): Pioneer in experimental

optics and psychology, use of scientific method.

13th and 14th Centurieso Bacon (Collection of facts, induction)o Occam (Parsimony)

17th centuryo Descartes: Deductive method, predictionso Galileo: Experimental approach

Page 5: The scientific method F. Guesdon MED610 DDP March 2013

History - Modern20th centuryo Statistical criteriao Popper: Falsification o Kuhn: non-rational aspects

Page 6: The scientific method F. Guesdon MED610 DDP March 2013

Our learning aimso Reflect on what makes research scientifically

sound

o Understand what the “Scientific Method” is

o Ask if “Scientific Method” really accounts for all scientists need to do

Page 7: The scientific method F. Guesdon MED610 DDP March 2013

Session plan

Problem-solving strategies

Case study 1: The law of falling bodies

Case study 2: The bacterial origin of peptic ulcer

How useful is the “scientific method” model?

Page 8: The scientific method F. Guesdon MED610 DDP March 2013

Thinking about probabilitieso 1% of women have breast cancer (p = 0.01)

o If a woman has breast cancer, the probability of a mammogram detecting it is p = 0.8

o If a woman has no breast cancer, the probability of the test being positive is p = 0.1

Estimate the probability that a woman whose mammogram came up positive actually has cancer

From Gigerenzer, in The evolution of the mind, Dellarosa Cummins and Allen, Eds, 1988, chapter 1

Page 9: The scientific method F. Guesdon MED610 DDP March 2013

Probabilistically correct answero For every 1,000 women tested, 10 will have breast

cancer and 990 won’t

o Of the 10 women with breast cancer, 8 will be diagnosed correctly by the mammogram

o Of the 990 other women, 99 will have falsely positive mammograms

o For every 1,000 women tested, 99 + 8 = 107 mammograms will be positive

o The probability that a positive mammogram indicates a true breast cancer is 8 / 107 = 7.47 %

Page 10: The scientific method F. Guesdon MED610 DDP March 2013

There are two different ways of thinking

Page 11: The scientific method F. Guesdon MED610 DDP March 2013

One way thoughts come to mind:

Is happy

This way of thinking uses perception and intution

Page 12: The scientific method F. Guesdon MED610 DDP March 2013

Is angry

This way of thinking uses perception and intution

Page 13: The scientific method F. Guesdon MED610 DDP March 2013

Another way thoughts come to mind

o Probability of having breast cancer is pc = 0.01 so of 1,000 women, we can expect 1,000 x 0.01 = 10 cases

o And therefore 1,000-10 = 990 healthy women

o The test has a rate of detection of pd = 0.8, so it should pick up 0.8 x 10 = 8 cases from the sample of 1,000

o The test has a false positive rate of p+ = 0.1, so 990 x 0.1 = 99 healthy women will also have a positive result

o So, there will be in total 99 + 8 = 107 positive results.

o If I am one of those, the probablility I have cancer is p= 8/107 ≈ 0.075

Page 14: The scientific method F. Guesdon MED610 DDP March 2013

Type 1 thinking = “natural”o Automatic / intutive / effortless

o Uses perception, common sense, training (skills)

o Jumps to conclusion

o “Heuristic”

Page 15: The scientific method F. Guesdon MED610 DDP March 2013

Limitations of type 1 thinking

o Perception (sensory) biases

o We tend to misjudge numerical information

o We tend to confuse the most typical with the most probable

o We seek solutions that conform with how we perceive a problem rather than how it is objectively (framing, economy of thought)

Page 16: The scientific method F. Guesdon MED610 DDP March 2013

Type 2 thinking: organisedo Based on conscious processing

o Rational, analytical

o “Unatural”, difficult

o Technically accurate

o Slow or unconclusive when dealing with complex problems (social / economy etc.)

Page 17: The scientific method F. Guesdon MED610 DDP March 2013

Common sense relies mostly on type 1 thinking

o Provides fast, practical answers

o Good for practical problems (hunting, farming, buying and selling, stay safe etc.)

o Easy to commmunicate or convince – “Feels right”

o Influenced by and produces common knowledge

Page 18: The scientific method F. Guesdon MED610 DDP March 2013

Contemporary common knowledge

o In a given situation, people from different cultures are likley to react differently

o In a given situation, people will react differently depending on their personality traits

o Women have better verbal skills and more empathy than men

Page 19: The scientific method F. Guesdon MED610 DDP March 2013

Selecting candidates: Common sense approach

o Candidates for PhD position selected by interview

o Staff believe they select the best candidates

o But they can only judge the performance of students they took in

o So how do staff know that they select correctly?

o We think common sense works because it “seems” to work

Page 20: The scientific method F. Guesdon MED610 DDP March 2013

Science developped by mistrusting common sense and organising

knowledge

Page 21: The scientific method F. Guesdon MED610 DDP March 2013

Hypothesiso Focused

o Generates specific predictions

o Designed to be tested rigorously

o Will be rejected as soon as it fails a single test

Theory• Broad scope

• Accommodates alternative hypotheses

• Designed to be inclusive: incorporates as many facts and explanations as possible in a unified framework

• Will be abandonned if cannot generate good hypotheses, or when a better theory is built

Page 22: The scientific method F. Guesdon MED610 DDP March 2013

Problem-solving strategies:Common sense v. rational thinking

Case study 1: The law of falling bodies

Case study 2: The bacterial origin of peptic ulcer

How useful is the “scientific method” model?

Page 23: The scientific method F. Guesdon MED610 DDP March 2013

Aristotle’s description of the motion of falling bodies

The speed of falling objects is proportional to their weights.

H

H

L

L

Page 24: The scientific method F. Guesdon MED610 DDP March 2013

What happens if a light object (L) is tied to a heavy object (H)?

1. The falling speed of the tied objects should be intermediate between those that they would have individually.

2. When tied, the two objects (H+L) form a single object heavier than H, so should fall faster than H alone.

Page 25: The scientific method F. Guesdon MED610 DDP March 2013

Aristotle’s description can lead to contradictory predictions

• Limited predictive value

• Can lead to alternative contradictory predictions

• Does not explain what it tries to describe

Page 26: The scientific method F. Guesdon MED610 DDP March 2013

Identifying the problem1 – Galileo noted the logical inconsistency in Aristotle’s

description

2 - Observed that falling objects appear to start slowly and then accelerate

3 – Looked for supporting evidence: dents in a cushion

4 – Seeked to measure how speed increased with time and describe the relation in a manner fully consistent with measurements

Page 27: The scientific method F. Guesdon MED610 DDP March 2013

How Galileo may have generated his hypothesis

He uses the most simple mathematical description of accelerated motion:

The speed (V) increases in direct proportion to time (T) since the object was dropped:

V = T

Page 28: The scientific method F. Guesdon MED610 DDP March 2013

How to test this? The equation

V = T

leads to a prediction about distance fallen with time:

The distance (D) increases in

proportion to time squared (T2):

D = T2

T = 1D = α

T = 2D = 4 x α

T = 3D = 9 x α

Page 29: The scientific method F. Guesdon MED610 DDP March 2013

The rolling ball experiments (1603)o Problem: Free fall is too fast

o Solution: Study balls rolling down an inclined beam

Gallileo assumed that this motion followed the same law as free fall

D1

D2 D3

Page 30: The scientific method F. Guesdon MED610 DDP March 2013

Simulated Galileo data

The data does not fit perfectly the prediction

Does that means the hypothesis is wrong?

DPrediction Data

T T2 T T2

1 1 1 0.93 0.87

4 2 4 2.15 4.62

9 3 9 3.03 9.18

16 4 16 3.93 15.4

Page 31: The scientific method F. Guesdon MED610 DDP March 2013

Replicating the experiment

The data is never perfectly reproducible either

Does that mean the experiment is not reliable?

DPredicted

T2

Experimental T2

♯1 ♯2 … ♯99

1 1 0.87 1.15 … 1.21

4 4 4.62 4.46 … 3.76

9 9 9.18 8.75 … 8.84

16 16 15.4 15.2 … 14.9

Page 32: The scientific method F. Guesdon MED610 DDP March 2013

o The most important step when interpreting data is ask if the data is good enough to mean anything.

oMany experiments do not give “yes” or “no” answers, just “maybe” answers

Page 33: The scientific method F. Guesdon MED610 DDP March 2013

Simulated Galileo data The differences are not significant, so the

data supports the prediction that

D = T2 DPredicted

T2

Experimental T2

♯1 ♯2 … ♯99

1 1 0.87 1.15 … 1.21

4 4 4.62 4.46 … 3.76

9 9 9.18 8.75 … 8.84

16 16 15.4 15.2 … 14.9

Page 34: The scientific method F. Guesdon MED610 DDP March 2013

Value judgments: Interpreting data

o A researcher must interpret their data - decide what it means.

o Interpretation is informed by controls (standardisation), replication and statistical analysis

o But not fully objective, depends on assumptions

o The interpretation can be contested by other scientists (peers)

Page 35: The scientific method F. Guesdon MED610 DDP March 2013

o The most important step when interpreting data is ask if the data is good enough to mean anything.

oMany experiments do not give “yes” or “no” answers, just “maybe” answers

Page 36: The scientific method F. Guesdon MED610 DDP March 2013

The Scientific Method1. Observe phenomena2. Develop a hypothesis (inductive thinking)3. Derive predictions from the hypothesis

(deductive thinking).4. Test one prediction (experiment)5. Interpret the results: are they consistent with

the prediction?• If yes, the model passes the test; test another

prediction• If no, the hypothesis is proven wrong (falsified);

alter or discard hypothesis

Page 37: The scientific method F. Guesdon MED610 DDP March 2013

Inductive reasoningo Imagines possible causes or mechanisms to

explain the data

o Based on recognition of patterns or trends

o Can be intuitive, subjective

o Error-prone: risks confusing correlation with causality

o Essential to make good hypotheses

Page 38: The scientific method F. Guesdon MED610 DDP March 2013

Standard model of Scientific Method

Hypothesis

Data

PredictionTest

Induction

Deduc

tion

Page 39: The scientific method F. Guesdon MED610 DDP March 2013

Hypotheses are at the core of the scientific method

o A hypothesis is an attempt at explaining

o Testing a hypothesis is testing our understanding

o understanding means being able to make predictions!

o This distinguishes investigative science from descriptive science (mapping, cataloguing, sequencing)

Page 40: The scientific method F. Guesdon MED610 DDP March 2013

Testing hypotheses: Falsification

o Experiments must be designed so as to reveal if the hypothesis is wrong

o Experiments set up to confirm hypothesis are not informative

Karl Popper (1902-1994)

Page 41: The scientific method F. Guesdon MED610 DDP March 2013

Testing to faslsify…

How would you test the following hypothesis?

Page 42: The scientific method F. Guesdon MED610 DDP March 2013

“All cards that have a vowel on one side have an even number

on the other side”

4U

Page 43: The scientific method F. Guesdon MED610 DDP March 2013

Testing the hypothesis

o You have a sample of 4 cards:

Which card(s) do you need to turn over to test the

hypothesis?

Write your choice(s) on a piece of paper

A J 2 7

Page 44: The scientific method F. Guesdon MED610 DDP March 2013

“All cards that have a vowel on one side have an even number on the other side”

A J 2 7

Prediction:

Available cards:

Page 45: The scientific method F. Guesdon MED610 DDP March 2013

Would turning card A test the hypothesis?

o What might we find if we turn over card A?1. An even number2. An odd number

o If it is and odd number, we will have learned that the hypothesis is false

Page 46: The scientific method F. Guesdon MED610 DDP March 2013

Apply this reasoning to all available cards

A J 2 7

“All cards that have a vowel on one side have an even number

on the other side”

Page 47: The scientific method F. Guesdon MED610 DDP March 2013

Correct choices: Cards A and 7

o If you find an odd number on the other side of A, you will know that the hypothesis is wrong

o If you find a vowel on the other side of 7, you will know that the hypothesis is wrong

Page 48: The scientific method F. Guesdon MED610 DDP March 2013

Were our initial choices wrong?Why?

o Card 2 is not informative: whether there is a vowel or consonant on the other side will tell you nothing about the hypothesis - but many people choose it

o Most people choose card A but very few people choose card 7 - this shows a natural bias towards seeking confirmation, but ignores half the evidence available

Page 49: The scientific method F. Guesdon MED610 DDP March 2013

Problem-solving strategies:Common sense v. rational thinking

Case study 1: The law of falling bodies

2: The bacterial origin of peptic ulcer

How useful is the “scientific method” model?

Page 50: The scientific method F. Guesdon MED610 DDP March 2013

Pre-1984 view of peptic ulcero Erosions of the lining of the stomach or duodenumo Believed to be caused by overproduction of

stomach acidso Thought to result from lifestyle factors (stress or

excess absorption of spicy food)o Treatments were: avoiding lifestyle factors,

neutralising stomach acidity or preventing acid secretion by severing nerves

o Alleviated symptoms, did not cure the disease

Page 51: The scientific method F. Guesdon MED610 DDP March 2013

Observations of bacteriao In the 1970s, fiber optic endoscopes made

possible stomach biopsies from live patientso Until then, most samples of peptic ulcer tissues

had been obtained post mortemo In the 1970s, researchers began to report

association of gram-bacillus in 80% of patients with gastric ulcers.

Page 52: The scientific method F. Guesdon MED610 DDP March 2013

Problems with the new observations

o Medical texbooksk asserted that bacteria cannot live in the stomach

o The bacteria could be grown in vitro after isolation from the biopsies, preventing detailed characterisation

o They were assumed to be Pseudomonas, common contaminants of endoscopes

o All this suggested the bacteria seen in ulcer samples were not genuine hosts of the stomach

Page 53: The scientific method F. Guesdon MED610 DDP March 2013

Flaws in accepted knowledgeo Warren noticed that the presence of bacteria in

his biopsies strongly correlated gastritis – suggesting an immune reaction against the bacteria

o Also, the large numbers of bacteria, their homogeneous distribution and their localisation at the top of the cell layer were inconsistent with accidental contamination

Page 54: The scientific method F. Guesdon MED610 DDP March 2013

How could Warren’s hypothesis be tested?

How would you test / prove the role of bacteria in causing peptic ulcers?

Page 55: The scientific method F. Guesdon MED610 DDP March 2013
Page 56: The scientific method F. Guesdon MED610 DDP March 2013

Koch’s postulates1. The microbe must be found in the bodies of the

patients or diseased animals2. The microbe must be isolated from the

patients/ animals and grown outside the body3. The innoculation of the microbe grown in pure

culture should produce the disease in an experimental host

4. The same microbe shoud be re-isolated from the experimental subject after the disease develops

Page 57: The scientific method F. Guesdon MED610 DDP March 2013
Page 58: The scientific method F. Guesdon MED610 DDP March 2013

Read following sections of hand-out:

o The pilot study (p.2)o Isolating the bacteria (p. 3)o The data (pp. 3-4 – Ignore Fig. 3)oPresenting their results (p.5)

Think about questions 4, 1 and 5 (pp.6-7)

Page 59: The scientific method F. Guesdon MED610 DDP March 2013
Page 60: The scientific method F. Guesdon MED610 DDP March 2013

Pilot study (pp. 3-4): Design Marshall and Warren recruited 100 patients or

healthy volunteers undergoing endoscopy. Each participant had to complete a detailed survey on:

o Their symptomso Their lifestyle histories:

Exposure to animals Travels Dental hygiene Diet (Kentucky Fried Chicken?)

Page 61: The scientific method F. Guesdon MED610 DDP March 2013

Why these questions?

Page 62: The scientific method F. Guesdon MED610 DDP March 2013

Aim of the pilot study (1982)o Are there bacteria in normal stomachs?o Does the presence of bacteria correlate with

type and severity of pathology?o Can the bacteria be cultured?

Page 63: The scientific method F. Guesdon MED610 DDP March 2013

Koch’s postulates1. The microbe must be found in the bodies of the

patients or diseased animals2. The microbe must be isolated from the

patients/ animals and grown outside the body3. The innoculation of the microbe grown in pure

culture should produce the disease in an experimental host

4. The same microbe shoud be re-isolated from the experimental subject after the disease develops

Page 64: The scientific method F. Guesdon MED610 DDP March 2013

Testing postulate 2 (Isolation)o Attempts to grow the bacteria in vitro from 30

different biopsies failed repeatedly

o Until an accident happened: Due to an emergency, technical staff once left the petri dishes unattended for 5 days, and were then able to see bacteria. The growth in vitro was too slow for normal 2-days cultures.

Page 65: The scientific method F. Guesdon MED610 DDP March 2013

Testing postulate 3 (Innoculation)

o In spite of repeated attempts, the bacteria grown in vitro did not induce the disease in model animals

o In desperation, Marshall subjected himself to a self-experimentation and injested 30 ml of aliquid culture of H. pylori

o Seven days later, he became ill

Page 66: The scientific method F. Guesdon MED610 DDP March 2013

Postulate 4 – re-isolation

A silver stain of H. pylori on gastric mucus-secreting epithelial cells of Dr Marshall’s stomach biopsy taken 8 days after he drank a culture of H. pylori.

Page 67: The scientific method F. Guesdon MED610 DDP March 2013

Problem-solving strategies:Common sense v. rational thinking

Case study 1: The law of falling bodies

Case study 2: The bacterial origin of peptic ulcer

How useful is the “scientific method” model?

Page 68: The scientific method F. Guesdon MED610 DDP March 2013

Comparing the two case studies

o IF Galileo’s study is taken as perfect example of the scientific method, does the study of the causes of pptic ulcer devaites from it?

Page 69: The scientific method F. Guesdon MED610 DDP March 2013

Is the “Scientific Method” a good model?

o Describes the rational element of scientific research

o Differentiates science from other disciplines

o Does not account for subjective or cultural aspects: How do scientists decide what to study? Who decides what to study? Qualitative (exploratory) research Role of chance discoveries

Page 70: The scientific method F. Guesdon MED610 DDP March 2013

Pitfalls of the scientific methodComplex phenomena cannot always be understood – predicted - through simple hypotheses

Examples: o Complex interactions between multiple factorso Phenomena involving non-linear responses to

small changeso Common chronic diseases, weather, climate

Page 71: The scientific method F. Guesdon MED610 DDP March 2013

“Science is what scientists do, and there are as many scientific methods as there are individual scientists.“

P.W. Bridgman

(Nobel Prize in Physics 1923)

Page 72: The scientific method F. Guesdon MED610 DDP March 2013

Alternatives to the scientific method

1 - Exploratory research (mapping, systematic fact finding) coupled with pattern-finding approaches

• El niño

• Genome-wide associations with diseases, identification of disease markers)

2 – Modelling

Page 73: The scientific method F. Guesdon MED610 DDP March 2013

Any questions?