Tuesday, January 4, 2011

Mendel's thinking, current thinking, superficial objections and metaphors

Our friend and ex-student, Jen Wagner who is both a knowledgeable geneticist and a practicing lawyer interested in human rights law as it applies to genetics, sent us a link to a blog post that is worth thinking about....carefully. The topic is the often confused nature of the 'gene' or inheritance.  Many people, including many professionals, hold and express strongly causally determining views of what a gene is: they refer to genes 'for' some trait, or implicitly imply that is what they have in mind.  The blog post argues that we've been influenced too much by Mendel's single-gene work (though he didn't have a specific gene concept), whereas the truth is that traits are affected by many different genes whose variation tinkers with the trait's details in each individual.  The blog argues against the widespread metaphoric treatment of genomes as the computer-like information 'program for' the organism, fitting in well with our electronic information age.

We are indeed prisoners of the kind of thinking Mendel was doing in the mid-1800s.  He was looking for integral (that is, whole-number) effects.  That's what is meant by 'gene for' rhetoric: a given gene causes something, or not, depending on the variant in that gene in an individual.  Mendel designed his experiments with peas very explicitly to deal with such simple situations, and he was looking for integral relationships (for example 3 dominant to 1 recessive offspring from certain matings).  He was trained in part by scientists developing the atomic theory of matter, and ideas such as that every element was a multiple of the carbon atom.  Naturally, he sought (and found) such numbers.  His work was so elegant that others later on, in the early 20th century, used it to build what became the theory of the gene, as a single, discrete causal unit of life.

This didn't seem to gibe with complex or quantitative traits (like stature, mentioned as an example in the blog post), but several investigators, including most notably including our friend RA Fisher in 1918, pointed out that if many 'Mendelian' factors contributed to a trait it could appear quantitative, like how tall you are or your blood pressure, even though each factor was a discrete thing (as Mendel's Elements causing green or yellow, smooth or wrinkled peas were).

We now recognize that genomes are concatenations of many different sorts of causal effects, sometimes overlapping along a chromosome, and with complex combinations and interactions.  In that sense, no one gene is 'for' a given trait.  It's an important point, but there's a caution: it's somewhat wrong to diss this view as if it's naive, and as if today we have a theoretically different view, because we really haven't.

Genetic elements are not just protein codes, but do many things.  But they are discrete, and discretely varying, sequence elements in DNA, and they vary in discrete ways.  That they act in combinations is true, and that can bring about complex traits.  But there is nothing conceptually different about this.  And in evolutionary terms, each genetic element evolves as standard theory would have it: by changing frequency of its varied states in populations.

The authors who point out the faults in our 'gene for' models are making valid points, but if they are arguing that there is something fundamentally wrong, they themselves are being misleading.  To speak of the genome as the program for the organism, in computer metaphors is misleading because there are many differences between computer code and genetic code.  But it is clear that the genome is a source of information on which much of the development and life of organisms rest.

What is new, and needs better professional and scientific understanding, are the implications of causation due to hundreds of contributing elements.  It is not a new theory that is needed, though there are many newly known kinds of interactions and causal relationships.  What is needed is a titering of the idea that single genes are dominant in the production of traits, and that evolution usually works by affecting single key genes.  Instead, genetic action in aggregate is more important than is generally recognized and when that is the case, the individual element's contribution is generally very small.  It's a complicated subject, but this takes the focus of biological causation away from individual genome elements on to the action of aggregate variation.

So, while we do seem to be trapped by a history of Mendelian single-gene thinking, because single-gene thinking was incredibly powerful as a research tool, what we need is not new theory or an abandonment of Mendel's ideas, but a recognition of the implications of basic ideas we have had for nearly a century.


Arjun said...

I'm reminded of a fortune cookie I recently opened whose fortune told me "understanding the nature of change changes the nature." Similarly, "recognizing the implications of basic ideas" will expose deficiencies in our current thinking such as those which you have described above, no?

Given the goal of scientific enterprise to increase our insight into the universe, wouldn't we eventually hit a point where a new conceptual framework or theory is necessary to make sense of the information at hand?

Ken Weiss said...

The science play we read with our students last semester, An Experiment with an Air Pump, had the line in it that there are two kinds of scientists, those who want to change the world, and those who want to understand the world.

It seems to be true and, we think unfortunately, in Mall America it is the former who hugely predominate. Basic science is slighted, but even that is over-hyped by claims of relevance (cure all known ills, help find men on Mars, etc.).

It is probably true that science would take different directions if it weren't for the pressure to have immediate practical--usually meaning commercial--yield. But the idea that science is about manipulating Nature goes back to Francis Bacon 300 years ago, so isn't new.

Also it must be acknowledged that even brothel science that reveals things about Nature also changes Nature. How different it would be if we were less venal, how can one say?