"There is a triple sight in blindness keen"

Well, it's the quiet season, one for peace and reflection on the nature of life and friendship. So while everyone is (over)indulging in good times, we felt we would not just slow down our post-speed but also change pace a bit. Here is something to think about:

I had not a dispute but a disquisition, with Dilke on various subjects; several things dove-tailed in my mind, and at once it struck me what quality went to form a Man of Achievement, especially in Literature, and which Shakespeare possessed so enormously - I mean Negative Capability, that is, when a man is capable of being in uncertainties, mysteries, doubts, without any irritable reaching after fact and reason-

So wrote the poet, John Keats, in a letter to his brothers in 1817. And, in a related vein, he wrote in his sonnet, To Homer, in 1818:

...Aye on the shores of darkness there is light,
And precipices show untrodden green,
There is a budding morrow in midnight,
There is a triple sight in blindness keen...

Negative Capability has been read by some to mean, as in the example Keats uses in his letter, the Shakespearean ability to suspend judgment and have complete empathy for a character, or by others to mean suspension of disbelief, so that a mystery needn't be considered a mystery. Still others have applied the term to people like Barack Obama and his ability to find no contradiction in making peace through war. Indeed, Keats himself in his sonnet seems to be making non-contradiction of contradiction, reinventing Yin and Yang.

Negative capability can also be related to the understanding of what we don't understand in what our old friend, Stanford historian Robert Proctor, coined as the field of 'agnotology', the study of culturally induced ignorance. It occurs when things are intentionally misrepresented by scientists or those who have something to gain by doing so.

Negative capability seems to be a Rohrschach test, interpreted in many ways, and applied as people see fit. So, we here apply it as we see fit, to genetics.

We've written often before on this blog (e.g., here and here) about genomewide association studies, and why they don't, and can't be expected to explain more than a fraction of complex disease risk. And we've published papers on why we shouldn't expect complex diseases to be reducible to single genes (e.g., here). So let's here define negative capability as the ability to accept complexity on its own terms. The beauty of Keats' idea, to us, is that rather than knocking our heads against the wall of reductionism, we should accept that complex diseases are complex, accept that our methods aren't capable of explaining each case of disease genetically when everyone has his or her own unique genome, because science relies on replication for explanation and prediction.  But more importantly, we should accept that we really do understand complexity. The mystery is that people continue to see it otherwise.

It is ironic because in this, the season of trying to understand life and its meaning, we think that science shows us what we don't know as much as what we know. Really knowing what we don't know, or even that which with current methods and concepts we can't know, is a valuable kind of knowledge. Most scientists seem to fear this and indulge in agnotology by promulgating ideas that what we don't know we soon will know (if we have enough more grant money).

Instead, much of life's mysteries are not as mysterious as they seem. When things are really complex, it may be that our methods in science cannot untangle them into usefully understood individual components or interactions, if only for statistical reasons of the sample sizes needed to do it meaningfully.  No need for irritable reaching after meaning that can't be found.

Meanwhile, we do know that many things could be done with respect to preventing complex disease, if that were really the goal. For example, nutritional reduction would remove vastly more diseases related to obesity than genetic measures, and at a fraction of the cost. How much climate change is due to humans may be unknown, but we do know that climate is changing and we know what that's doing. We do know that cutting back on our level of consumption will have many material benefits, and history shows that people can be just as 'happy' as they are today when consuming less.  And so on.

So, in this time of reflection we might reflect on how to use what we do know to further societal objectives, and understand what we don't know, rather than just hoping Santa will come down the chimney with all the answers. 

Enjoy being in mysteries, uncertainties and doubts...

Happy Holidays
  Anne and Ken