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Friday, September 29, 2023

Evelyn Fox Keller (1936 - 2023) and junk DNA

Evelyn Fox Keller died a few days ago (Sept. 22, 2023). She was a professor of History and Philosopher of Science at the Massachusetts Institute of Technology (Boston, MA, USA). Most of the obituaries praise her for her promotion of women scientists and her critiques of science as a male-dominated discipline. More recently, she turned her attention to molecular biology and genomics and many philosophers (and others) seem to think that she made notable contributions in that area as well.

I don't agree. I think her publications in that domain are seriously flawed and she is partly responsible for the widespread misconceptions about junk DNA. Here's what she wrote in an essay titled "The Postgenomic Genome" published in "Postgenomics" (2015) edited by Sarah Richardson, a professor in Social Sciences (History of Science) at Harvard University (Boston, Massachusetts, USA), and by Hallam Stevens, a professor of History at Nanyang Technology University in Singapore (Singapore).

Throughout the history of classical genetics and early molecular biology, the science of genetics focused on genes, widely assumed to be the active agents that lead to the production of phenotypic traits. Similarly, the genome (a term originally introduced in 1920) was regarded as the full complement of an organism's genes. Indeed, I claim that this assumption is largely responsible for the widespread interpretation of the large amounts of noncoding DNA identified in the 1970s and 1980s as "junk DNA." Genomic research has not only made this interpretation untenable but also, I argue, supports a major transformation in our understanding of the genome—a shift from an earlier conception of the genome (the pregenomic genome) as an effectively static collection of active genes (separated by "junk DNA") to that of a dynamic and reactive system (the postgenomic genome) dedicated to the regulation of protein-coding sequences of DNA. In short, it supports a new framework of genetic causality.

Of particular importance to this new perception of the genome were the early results of ENCODE, a project aimed at an exhaustive examination of the functional properties of genomic sequences. These results definitely put to rest the assumption that non-protein-coding DNA is nonfunctional. By the latest count, only 1.2 percent of the DNA appears to be devoted to protein coding, while the rest of the genome is nonetheless pervasively transcribed, generating transcripts employed in complex levels of regulation heretofore unsuspected.

This is a seriously flawed analysis as I explained in a 2016 blog post, "When philosophers talk about genomes." Her opinion on junk DNA fits with a worldview that sees the scientists of past generations as old fuddy-duddies who were blinded by their own ignorance. Evelyn Fox Keller thought that modern scientists—a much more diverse and inclusive group—are overthrowing some of the old concepts in molecular biology.

This shift in metaphor—from junk DNA to dark matter—well captures the transformation in conceptual framework that is at the heart of my subject. It was neatly described in a 2003 article on "The Unseen Genome" in Scientific American, where the author, W. Wayt Gibbs, wrote, "Journals and conferences have been buzzing with the new evidence that contradicts conventional notions that genes, those sections of DNA that encode proteins, are the sole mainstay of heredity and the complete blueprint for all life. Much as dark matter influences the fate of galaxies, dark parts of the genome exert control over the development and the distinctive traits of all organisms, from bacteria to humans. The genome is home to many more actors than just the protein-coding genes." Of course, changes in conceptual framework do not occur overnight, nor do they proceed without controversy, and this case is no exception. The question of just how important non-protein-coding DNA is to development, evolution, or medical genetics remains under dispute. For biologists as for physicists, the term "dark matter" remains a placeholder for ignorance. Yet reports echoing, updating, and augmenting Gibbs's brief summary seem to be appearing in the literature with ever-increasing frequency.

She is, or course, entitled to her opinion but she is not entitled to her own version of history. There was never a time since the 1960s when knowledgeable scientists thought that protein-coding genes were the only information in the genome. Back then, we all knew about regulatory sequences in non-coding DNA and we knew that they were important.

There's more—see my 2016 post—but this is enough to illustrate my point. An MIT professor who is widely admired as an expert in the history and philosophy of science is no such thing. In fact, when it comes to genomics she's a bit of a kook.


Anonymous said...

I remember when you wrote about her back in 2016. I wonder if she was ever made aware of that.

Athel Cornish-Bowden said...

I agree with your comment. I feel that Evelyn Fox Keller was the sort of non-scientist who somehow acquired a reputation as a major figure in the philosophy of science without needing to know much about it.

My criticism of her is rather different from yours and concerns her book Making Sense of Life, in which she started by saying sensible things about Stéphane Ledux and D'Arcy Thompson, but went on to set out a very superficial account of more recent ideas of the essence of life. She devoted several pages to the career of Nicolas Rashevsky without a serious examination of his ideas and concentrating on his funding problems. (To be clear, I don't much care for Rashevky's ideas myself, but that's not the point: if you devote several pages to a discussion of someone's administrative problems you should at least look at his ideas.)

Robert Byers said...

A kook? I suspect she just was not worthy of the positions given her and not noticable until real nuts and bolts of science is dealt with. what is a philosoer of science? Somebody swaying others get it wrong from a abstract vstance? Hmm. Being diverse and inclusive is only right if it doesn't get in the way of others and does not promte those not worthy. As a creationist i agree many ideas were wrong and more creationists should be inclusivly and diversely involved but by merir only. Our complain is of direct interference on evidence and not on stats results.