Where I Agree and Disagree with Precision Medicine’s Chief Critic, Michael Joyner


Author: 
Theral Timpson

Precision Medicine is more than a narrative, a story.  Hundreds of thousands of patients take drugs every day that are precision medicine drugs.  Thousands of women have been tested for BRCA genes and thousands of others diagnosed with lung cancer tested for EGFR mutations.  This has been more than a story for them.  It has saved their lives.  From rare disease diagnoses and therapies to the entire field of non-invasive prenatal testing, genomics has revolutionized medicine. 

In addition, millions of consumers are ordering personal genetic tests.  Some of these tests are reuniting families.  Some, it is true, are merely providing holiday entertainment.  And often it is more Halloween fright than Christmas cheer, for many of these tests are scaring the crap out of people.

Still, there are enough disappointments with the genomic revolution that the skeptics may easily earn their keep.     I’ve encountered several of these critics in my time hosting a podcast on the subject, but perhaps none as strong and relentless as Michael Joyner, a physician and researcher from the Mayo Clinic who joined us on the show last week.   

Whereas many of the others have tended to be arm chair critics--mostly journalists--Joyner is actively working on just the kinds of studies he thinks we should be doing rather than pursuing genomics, namely:  physiology and behavioral modeling.   This is no small feat in an age when the NIH is dominated by the genomic approach  And I might add, in an age when the Mayo Clinic is also generally an adherent of precision medicine as well.  (In order to do our interview, Joyner and I had to agree to say that his comments were not representative of Mayo’s institutional views.)

Joyner also stands out in that he is not a libertarian fantasist, one of the so called “free thinkers” who says the government should not be in the business of healthcare and that the NIH shouldn’t be funding any science.  They naively argue the market will take care of it all.  Joyner advocates for a dramatically increased NIH budget.  And though he waffled on the percentage of the budget he thought should go to basic science (it kept going up during our interview), he did agree that we should keep funding basic science.

I have quoted Joyner often on the program to keep the “hype factor” in check.  He has been a reliable go-to voice on Twitter against genetic determinism and the steady stream of papers that seem to find a gene for absolutely everything.  Joyner is right.  The simple genotype to phenotype causal connection that was anticipated before sequencing the human genome by many geneticists has simply not panned out.  I could cite study after study here and put in footnote after footnote, but you know what I’m talking about.  And besides, I don't do footnotes.  I don't have enough titles after my name for that. 

So things got more complicated than we thought for the common diseases.  We have to look at many genes.  Will polygenic risk scores pan out?  Maybe.  There is some genuine excitement there.  Euan Ashley and Josh Knowles out of Stanford say genetic risk predicts future cardio disease better than traditional risk factors.  They are not for population screening, but they do say that it’s time to incorporate genetic risk scores into clinical practice.  If it’s helpful and available, why not use it?

But maybe we have to keep working at it too.

Here’s my two points of contention with Joyner.

Number one.  Who gets to say when we throw our hands up in the air and give up on the reductive genomic approach that we've inherited from generations of biologists?

Number two.  What is the alternative?

It is a very bold position to say, OK, we tried, and now it’s time to give up.   At least Joyner has made a solid philosophical argument.  He reasons that there is no simple causal relationship of genotype to phenotype because the body uses redundancy.  One system or pathway fills in for another broken system or pathway to get the ultimate job done.  And that ultimate job is making sure the phenotype happens.  It was the phenotype that was selected for with evolution, not the genotype.  Therefore, it’s useless studying the genotype because biology will come up with constant new tricks to get to the phenotype.  There is nothing usefully predictable underneath the phenotype.  It is a black box under the phenotype.

But hey, with so much resources going into genomics, somebody oughta question it.   I’d like to see the NIH’s response.

Joyner does have an alternative to offer, but I have issues with it.  He thinks we should be pursuing more policy changes to impact healthcare.  For example, he said “it’s known that if we raised the cigarette tax nationally by a dollar a pack, it would increase lifespan by one year.”  He also points to the historical fact that we improved sanitation long before we knew what germs were.  Joyner wasn’t specific on how new policies would happen.  I challenged him, “you don’t do this at the NIH.”  He said, no, but you can model this kind of thing.  So he advocates doing behavior model studies and policy changes based on these studies.  This sounds to me like a heavy socialist government.    It turns out that far from being a libertarian, Joyner is a socialist.

This is in the direction of Bloomberg’s sugar tax.  I’m against it.  Actually California did impose a $2/pack tax on cigarettes last year.  There is no data in yet, but no matter the data how do you justify a majority imposing a health tax on a minority?  I understand banning smoking in public places because it impacts the health of others.  But how can society penalize someone for living unhealthy themselves?  In Notes from the Underground, Dostoevsky talks about just this thing, man’s need to be irrational at times, to be “unhealthy” if he chooses, to smoke a cigarette.  Will I also have to give up wine and will the police come knocking to make sure I have exercised my one hour a day under Joyner's proposals?

Finally, I’ll bring up another writer from the past, David Hume, the Scottish philosopher who got many of the empiricists going.  He’s known for Hume’s Law, the idea that you cannot get an “ought” from an “is.”  This is the famous problem that it is not obvious how one goes from descriptive statements to prescriptive ones.  Many philosophers since Hume have attempted to solve this problem, also called the fact/value dichotomy, notably Hilary Putnam in a famous economics lecture.

I think it is a blaring distinction that is inherent and not easy to explain away.  Remember back in gradeschool being presented with simple math problems such as 2 + 2.  Math was very straight forward.  You could come up with the right answer.  Then remember those questions in literature, such as what did the main character in the story do wrong?  I hated literature for this reason.  You could answer anything and be right.  Or you could answer what you deduced and be wrong.

So far we have been filling in the “is” of biology.  The facts.  The human genome is there.  One can download it.  One can get one’s own genome sequenced today and print it out.  It will be a fact.  What you do with it is something else.   Even if there is a “finding of clinical significance,” what you “ought” to do with it is something else entirely.  Joyner is for more exercise and a better diet.  I think most people already know they "ought" to do this.  The history of science has been about establishing the facts.  Getting them down on paper.  It’s the first step.  At one point science had to figure out how we weigh ourselves.  Getting weighed was the BRCA testing of diet and exercise.  

Joyner is a physician.  It is true that science is not medicine, medicine is not science.  And medicine has its own history.  But the history of medicine has gone best when it has been based on science.

There is one question that Precision Medicine hasn't answered well.  Modern medicine in general hasn't fared any better.   That is, what is health?  For the last three years lifespan in America has gone down as the biomedical gurus have pipetted and typed furiously away.  The number one reason lifespan has gone down in America is because of suicide.  People don't want to live.  Oops.  Where do you look in the genome for that?  There is a limitation to genomic science, genomic medicine--it's true.  But the answer is not in socialism.  And while we must ask the bigger question of what is health, we must go on asking what is going on in human biology.  

What are the facts?

When Joyner says that Collins, Varmus, and others over promised this and that in the 90's from genomic science, we must not get hung up on exactly the words they used but instead look at their vision.  I think most biologists do.

 

 

Comments

Yes, Theral, Dr. Joyner is indeed a socialist. But what keeps you from realizing that the best way forward is indeed to get the government out of science and let ideas compete on their own merit? Proclaiming that option to be "a "libertarian fantasy" doesn't make it so--except to the extent that your is a common (shall I say banal?) opinion.

You don't want the government to take over science. Good for you! But how much government involvement do you think is reasonable? A reasonable amount? What does that mean? Why should the government even have an inch of involvement in science?

Do you really think people would just give up doing science if the government was not involved? Do you think private companies would not step up ? Do you not know that some of them are *loaded* with money?!...And the money need not necessarily come from an oligarchy of sources: private mechanism would likely emerge for crowdfunding of science--even the existing equity markets would indirectly channel money from diverse sources to scientific research.

Do you think private entities could not invest in science as wisely as the government? Do you think competition between private sources of funding would not lead to a better allocation of funds, both in terms of allocation to scientists with better skills and ideas, but also in terms of allocation to projects that have a greater social value? Do really you think the political/bureaucratic system works better that way? Give me one reason to think government funding works better!

Great show/great podcast. Cheers. Michel

Hi Michel,

Thanks for the comment. Sorry I somehow missed the notification back in March and only landed here reviewing the article just now for another piece of writing.

I could answer with a brief review of some history that would include mention of things like atom bomb, space flight, the integrated circuit, the internet, the Human Genome Project, biosecurity, and so forth. Or I could talk about the misalignment of corporate incentives with the public good and make notice of tobacco companies and fake research or the suppression of the "sugar papers" or the fossil fuel industry and resistance to climate change science. But I guess the quickest response is the fundamental theoretical one: science has turned out to be the best knowledge accumulation system. Knowledge is power. Governments exist to maintain and expand power.

So I think I should be asking you, why wouldn't a government fund science?

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