1. Using Critical Reasoning to Make Sense of Hopes and Hypes The Promise of Precision Medicine
A. Cecile J.W. Janssens, PhD
Professor of Translational Epidemiology
Department of Epidemiology

5. Two questions to make sense of promises
What exactly is the promise?
How likely is it to be true?
What exactly is the promise?
… closer …
… like …
… personalized …
… need …
… healthier …

6. The Problem of ‘Fact’-Checking Promises
Promises are about the future
We cannot check in the present whether they are true
We can only reason whether they likely might be true … and then check the validity and strength of the premises
Promises
Unlikely
Impossible
Adapted from: Elizabeth Goodman (via sharenet)

7. What is reasoning?
Reasoning: the process of thinking about ‘something’ in a logical way in order to form a conclusion or judgment (Merriam-Webster)
‘something’ = observations, facts, rule, laws of nature, etc.
Inference: Reaching the conclusion based on observations through reasoning
Argument: the set of sentences that state the observations (premises) and the conclusion
such that the conclusion is asserted on the basis of the premises
and the premises are reasons to believe that the conclusion is true
Adapted from Talbot, 2014

8. Example of argument Premise 1: All swans are white
Premise 2: The bird is a swan
Conclusion:
If the premises are true,
you know that the bird is white because the reasoning is logically valid.
You do not need to see the bird to know this.
The bird is white

9. Example of argument in prenatal testing
Premise 1: All fetuses with 3 copies of chromosome 21 have Down syndrome
Premise 2: The fetus has three copies of chromosome 21
Conclusion:
If the premises are true,
you know that the baby has Down syndrome because the reasoning is logically valid.
Because this is logically valid, you do not have to wait until the baby is born, you can draw that conclusion prenatally, in very early stage of fetal development
The fetus has Down syndrome

10. Premise 1: All fetuses with 3 copies of chromosome 21 have Down syndrome Premise 2: The fetus has three copies of chromosome 21 Conclusion: The fetus has Down syndrome Is this really valid? What is missing? (What is assumed?)

11. Hidden premises
Premise 1: All fetuses with 3 copies of chromosome 21 have Down syndrome Premise 2: The fetus has three copies of chromosome 21 Premise 3: The chromosome test is 100% valid Conclusion: The fetus has Down syndrome Hidden, or surpressed, premises are implicit, not specified, but essential for the validity of the reasoning. They may be neutral and too obvious to even consider as premise, but they may also be controversial

12. Example of surpressed premise
In human gene editing research the embryo is always killed, so human gene editing research is wrong because it is wrong to kill innocent persons.
Premise 1: In human gene editing research the embryo is always killed
Premise 2: It is wrong to kill innocent persons
(Surpressed) Embryos are persons
Conclusion: Human gene editing research is wrong
Adapted from Talbot, 2014

13. Another example
Premise 1: All women with a known BRCA 1/2 mutation develop breast cancer
Premise 2: The woman has a known BRCA 1/2 mutation
Conclusion: The woman will develop breast cancer
A valid argument?
Yes, it’s logically valid, but it is not sound
Arguments are sound when the premises are correct
How can we change the premises/conclusion to make the argument correct?

14. Another example
Premise 1: The majority of women with a known BRCA 1/2 mutation develop breast cancer
Premise 2: The woman has a known BRCA 1/2 mutation
Conclusion: The woman may develop breast cancer
A valid argument?
Can the opposite be true?
Conclusion: The woman may not develop breast cancer
Which conclusion is most likely?

15. Can we make the latter argument stronger by adding premises?
Premise 1: The majority of women with a known BRCA 1/2 mutation develop breast cancer
Premise 2: The woman has a known BRCA 1/2 mutation
Premise 3: ???
Conclusion: The woman may not develop breast cancer
The woman had mastectomy

16. Down Syndrome
BRCA 1/2
By Farcaster - PowerPoint slide based on argument terminology

17. Errors in reasoning: fallacies
Argument 1:
Premise 1: All fetuses with 3 copies of chromosome 21 have Down syndrome
Premise 2: The fetus has three copies of chromosome 21
Conclusion: The fetus has Down syndrome
Argument 2:
Premise 1: All fetuses with Down syndrome have 3 copies of chromosome 21
Why is the second argument invalid?

18. Using logic to validate conclusions
Conclusion: The bird is white
Premise 1: The bird is a swan
Premise 2: ???
What need to be the other premise(s) to make the conclusion logically valid?

19. Using logic to validate conclusions
Conclusion: The man will develop Huntington’s disease
Premise 1: …
Premise 2: …
Conclusion: The man will develop type 2 diabetes
Premise 2: …
Premise … …

21. Using logic to validate conclusions
Conclusion: Genetically-personalized diet recommendations work better than standard diet Premise 1: Premise 2: Premise 3: Premise 4: Can you make an argument that lead to this conclusion? Hint: try to make a strong argument, premises do not need to be true

22. Possible argument
Conclusion: Genetically-personalized diet recommendations work better than standard diet Premise 1: General one-size-fits-all diets don’t work for many people Premise 2: Genes have statistically significant association to nutrition, usually in studies published before 2008 Premise 3: A (wishy-washy small) RCT showed one or more (borderline) statistically significant benefits between the genetically-personalized and control diet Premise 4: A statistically significant result in the RCT means that the genetically-personalized diet works better

24. Conclusion: The Precision Medicine Initiative will find how to match a cancer cure to our genetic code Premise 1: Premise 2: Premise 3: Premise 4:

25. Conclusion: The Precision Medicine Initiative will find how to match a cancer cure to our genetic code Premise 1: A blood transfusion can be matched to a blood type: targeting treatment solves ‘problem’ Premise 2: PMI will sequence a large number of cancer tumors Premise 3: Mutations in cancer tumors will match with treatment response Premise 4: Response to treatment means cure of cancer Which premises are most uncertain to be true?

26. Take home message
We can’t check promises (because they are about the future), but we can check the premises on which they are possibly based
Promises mostly result from inductive reasoning, they are true with some degree of probability
Logic reasoning gives guidance for identifying weak/strong promises
Judging whether a promise is likely true
Think about possible valid arguments that lead to promise
Evaluate their premises: are they true and convincing?
Use your expertise, and lots of common sense

27. Further reading
Talbot, 2014