Thursday, August 11, 2011

Mendelian inheritance: conclusion

Where does having the right theory make a difference?  Why can't we just assume that a major 'dominant' effect evolves because of its effect?  Why can't we continue to just give genetic counseling risk estimates in Mendelian theoretical terms?

The reason is that these usages are inaccurate at best, and in today's world  not needed.  We have better computational tools than we did when these things began in the mid 1900s.  Instead, for example, of the expected 1/2 for segregation proportions (for traits, not alleles) we can develop estimates of the actual probability of the trait in an offspring of an affected parent.  It would be something like the probability of inheritance of the major parental allele, times the probability of a given effect size (trait measure, for example) plus or times something about environmental effects where known plus  a similar term for the other parent.

Mendel was accused of cheating because his results were too close to his expectations to be due just to chance (there's more to the story since in his case the expectations he was too close to were wrong! see my article in 2002 Evolutionary Anthropology "Goings on in Mendel's garden").  But that is just what genetic risk estimators are doing!  They are using 1/2 for the expected risk of the trait, rather than whatever the empirical evidence, properly studied, shows the risk is.

And similarly, by digesting the message, no longer confounding inheritance of traits with inheritance of genetic elements, we can go beyond rigid statistical 'significance' in GWAS, which is of the same kind as false expectations, and consider all the bits of information that we have.

These are seriously erroneous concepts that misdirect science on a large scale.  They waste funds and lead to false expectations.  It is one thing to pursue ideas that seem, at the time, to be correct even if they eventually prove to be inaccurate--indeed, all ideas are probably of that sort.  But it is quite another to pursue ideas that one knows to be wrong, because that's a way to build a career or you are in a hurry and can't think of better ideas.

Many scientists accept, absorb, and repeat oversimplified dogma.  They teach 'the scientific method', 'survival of the fittest',  classical Mendelism, and the 'modern synthesis'.  They repeat that "nothing in biology makes sense except in light of evolution" (even though most have only a caricature idea of evolution, or what most life scientists actually do on a daily basis).

Maybe they are aware of the inaccuracies, or maybe when teaching they scorn their students' abilities to know the difference.  We think this is  not good for science.  But there is something else, that you might think is even worse.  That is that many if not the vast majority of scientists basically don't bother to think about these things and, like Rhett Butler, simply don't give a damn.

They (we) do our work regardless.  We push ahead to prove our favorite point of view, claiming to follow some principles when it suits us, ignoring them when it doesn't.  It is strictly pragmatic.  There is a lot of dissembling done on a daily basis. Careers have to be made, grants to be garnered, magazines to publish.

All of this is poor practice, but understandable.  Nature is complicated, scientists fallible, experiments and technology often imprecise, and so on.  We stumble, bumble, and bluff our way through.  Things don't go as smoothly as perhaps they might if we were more rigorous relative to theory.  Grants pay for work that they shouldn't.  But, being fallible and having to make a living, we plow ahead and in the end, here and there, there is progress.

In retrospect,  the heroes are remembered and recognized by historians and the media.  Laws of Nature are named after them.  Statues erected, biographies written.  The chaff and blind alleys, and most of us scientists, are  forgotten except by historians.  Philosophers revise their philosophy of science, and science revises its theories.  Life goes on.

That may be the blunt reality, and like other Utopian ideals, our theories of how we act fall short.  In the daily, perhaps rather smug and dismissive, hurly-burly of science, the theoretical fineries are ignored if not actually sneered at.

But shouldn't we do better?  Shouldn't we strive to train students better and to have a better idea of the nature of Nature, so we can be more efficient or effective?  If we are so willing to denigrate alchemy, phrenology,  humoral medicine and phlebotomy, as wrong and wasteful....and to criticize the illusions of religious dogma, should we accept dogmatic ignorance in today's science?  We think not.

Mendelism is we think a good example of something held too rigidly too long past its sell date.  It's taken by rote as a basic core fact of biology, in ways that impede progress and wastes large amounts of funds that service the professions but not the population paying the bill.  We can do better.


Holly Dunsworth said...

Thank you so much for writing this fantastic series on Mendelian inheritance!

James Goetz said...

Hi Ken, I appreciate your two series on Mendelism. I see similar problems and word things a little different. I suppose that Mendelism is commonly oversimplified and misapplied, while it is the oversimplified and misapplied Mendelism that is misleading.

John R. Vokey said...

Brilliant series. You should write a book. Wait, you did! Seriously, this is some of the best writing on this issue I have read. Thank you.

Ken Weiss said...

Thanks for the compliments! We write these thins partly to organize our own thinking. We're on the road in evolution country (Utah, Dinosaur National Park) right now, where one cannot but be impressed with how long, and wonderful time on earth has been. Mathematics lets people try to come to grips with such enormity, but perhaps at the expense of over-smoothing. But very impressive and thought provoking.

Mendelism is an example of such oversimplification that has its uses, and its dangers.