The first essay is by Stevens and Richardson and it outlines the goal of the book.
In the wake of the completion of the major genome sequencing project, a more quiescent decade followed, as scientists, science studies scholars, and activists waited to see what the next big breakthroughs would be. The essays in this book step into this open space to put the myriad changes instantiated within the life sciences in the post-HGP period in historical, social, and political context and thereby begin to make sense of them. Exploring the uncertain, transitional, and contested terrain of postgenomics, the contributors adopt a posture of critical reflection mixed with surprise and appreciation for the insights brought by the postgenomic era. They examine the continuities and ruptures, as well as the micro and macro transformations, instituted by the spread of genomic data and technologies throughout the life sciences over the past decade. They balance critiques of the practices and prospects of genome science with grounded analysis of the conceptual shifts and changes in everyday practices initiated by genomic data and technologies in knowledge production. Collectively, these essays document how postgenomics is reshaping debates over genetic determinism, reductionism, the role of the social and the environmental in human health and disease, and even the notion of the genome itself.Most of the essays are boring. I'll not bother to summarize them. The main theme of all of the essays is that wonderful things have come out of the human genome project and our view of genes and genomics has been transformed.
You can get a good idea of the tone from a paragraph in the introductory essay. Stevens and Richardson acknowledge that the ENCODE results were controversial and that many scientists disputed the ENCODE definition of "function." They go on to say,
But the ENCODE controversy is not just about hype, methodology, and organization—it also shows how far biologists are from agreement on an account of genomic action. It is not merely that the definitions of fundamental terms—such as "functionality"—are still open to contestation. The debate points to significant uncertainty about the overlapping roles (and relative importance) of evolution, DNA structure, transcription, and regulation in the human genome. Genes, the New York Times reported in 2008, are having an "identity crisis": acknowledgement of the importance of epigenetic marks, alternative splicing, post-transcriptional modification, and noncoding RNA have rendered the concept almost meaningless.This idea, that scientists are confused and bewildered by the human genome, occurs in many of the essays. It reflects the view from the outside, where even historians and philosophers are having trouble sorting out truth and fact from myth and hyperbole. Frankly, my concept of what a "gene" is hasn't changed from what it was in the 1970s [What Is a Gene?]. I don't know what they're talking about. Maybe they're talking about some people who had some bizarre, nonscientific, definition of a gene? Maybe they're talking about philosophers?
But sorting out the truth is their job, isn't it?
Evelyn Fox Keller an emeritus professor of the History and Philosphy of Science at MIT (Boston, Massachusetts, USA). She has a P.D. in physics and her thesis topic was on gene expression in bacteriophage lambda. She has won a MacArthur Fellowship and a Guggenheim Fellowship. Those are good credentials. She should know what she is talking about.
The title of her essay is "The Postgenomic Genome." The gist of her claim is that the study of the human genome has "turned our understanding of the basic role of the genome on its head." She claims that instead of being a sloppy bunch of chromosomes full of junk, the genome is actually "an exquisitely sensitive and reactive system."
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.This is not a view of history that I support and it is not a view of the truth, either. As I have said repeatedly, there was never a time when knowledgeable scientists thought that all noncoding DNA was useless junk. I can sympathize, barely, with scientists who don't understand the history of their field but here we are dealing with a supposed expert in the history and philosophy of science. I hold her to a higher standard.
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.
She has not met that standard. Her explanation of the meaning of "junk DNA" is misleading.
She has also failed to meet the standard in her interpretation of published experimental results. Scientists can disagree over how much of the genome specifies functional RNAs and Evelyn Fox Keller is perfectly entitled to side with those who support the idea that much of our genome is devoted to producing regulatory RNAs. She is not entitled to lie by implication as she does here. This book is intended for sociologists and philosophers and any of those people who read this paragraph would conclude that the science is settled—ENCODE was right about function. That's disingenuous. The best she could say in support of her claim is that there is a controversy and she sides with ENCODE. If she wanted to be even more correct in 2015, she could have said that hers is the minority view among experts. She could have mentioned that the ENCODE Consortium has partially retracted their claim. That's what an expert historian and philosopher of science should do.
You won't be surprised to learn that Evelyn Fox Keller perpetuates the myth that experts were surprised at the "low" number of genes when the draft sequence of the human genome was published in 2001. She seems to get much of her information from press releases and the popular press. She points out, correctly, that at the beginning of the Human Genome Project (HGP) the experts though that much of our genome was junk. But she errs in claiming that in the postgenomic era that idea gave way to a new metaphor: "dark matter of the genome."
It's not that some people didn't start writing about "dark matter" ... of course they did. That was the group suffering from the Deflated Ego Problem. They never liked the idea of junk DNA so they focused on the idea that most of the genome was a mystery. According to them, we don't know what's in our genome. It could be full of functional stuff.
That idea became popular with science writers who always like a mystery but an academic historian of science should know better. She doesn't ...
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 Gobbs's brief summary seem to be appearing in the literature with ever-increasing frequency.The truth is quite different. No knowledgeable scientists ever thought that protein-coding genes were the only functional thing in our genome. For one thing, no knowledgeable scientist ever thought that all genes were protein-coding. For another, they were all aware of the importance of regulatory sequences based on solid evidence spanning fifty years of work. Knowledgeable scientists do not think that junk DNA is a reflection of our ignorance as the term "dark matter" implies. Instead, they are well aware of the Five Things You Should Know if You Want to Participate in the Junk DNA Debate.
I don't think Evelyn Fox Keller knows any of the positive evidence for junk DNA. She could not write such rubbish about a transformation in conceptual framework if she did. Does this matter? Yes it does. She is writing the history of a field as a professor of the history and philosophy of science. I expect better.
Can it get any worse? You bet.
She even includes a figure from one of his 2011 papers (Mattick, 2011). I've scanned the figure from her essay (left) but I've also included the actual figure from Mattick's paper (below) (Mattick, 2011). I hope most of you remember the Dog's Ass Plot so I don't have to explain what's wrong with these figures. (It's interesting that all you have to do is Goggle "John Mattick" to find out why these kind of plots are so stupid. Critical posts are on the second page of the google search.)
Here's what Keller thinks of Mattick.
Of particular shock value were the dicoveries, first, of how few genes the human genome contained (discussed above) and, second, of how small a portion of the genome's structure is devoted to protein-coding sequences. In a review article published in 2004, [Mattick, 2004] John Mattick published a graph displaying the ratio of noncoding DNA to total genomic DNA as a function of developmental complexity. Prokaryotes have less than 25 percent noncoding DNA; simple eukaryotes have between 25 and 50 percent noncoding DNA; and more complex fungi, plants, and animals have more than 50 percent, rising to approximately 98.5 percent in humans ...
Mattick estimated the proportion of human DNA coding for proteins at 1.5 percent; since then, estimates have decreased to 1 percent. The obvious question is, what is the remaining 98.5-99 percent for?
In 2003, the research consortium ENCODE (Encyclopedia of DNA Elements) was formed with the explicit mandate of addressing this question. More specifically, ENCODE was charged with the task of identifying all the functional elements in the human genome. Early results of that effort (based on analysis of 1% of the genome) were reported in Nature in 2007, and they effectively put the kibosh on the hypothesis that noncoding DNA lacked function (i.e., that it was junk, "for" nothing but its own survival. They confirmed that the human genome was "pervasively transcribed" even where noncoding; and, finally, that noncoding sequences are often strongly conserved under evolution. Furthermore, they showed not only that noncoding DNA is extensively transcribed but also that the transcripts (now referred to as "noncoding RNA" or "ncRNA") are involved in many forms and levels of genetic reglation that had heretofore been unsuspected.
What's implied in her essay is the idea that a significant proportion of our genome is transcribed to produce functional regulatory RNAs. The facts are quite different. It's unlikely that such genes represent more than one percent of our genome even if there are 20,000 of them. That still leaves 98% unaccounted for by her criteria but Evelyn Fox Keller doesn't mention that.
Instead, she says,
Genetics is not just about genes and what they code for. It is also about how the DNA sequences that give rise to proteins are transcribed, spliced, and translated into amino acid sequences, in the appropriate amounts at the appropriate time and place; about how these, once assembled into proteins navigate or are transported to the sites where and when they are needed and so on. All of this requires coordination of an order of complexity only now beginning to be appreciated. And it is now believed that the ncRNA transcripts of the remaining 98-99 percent of the genome are central to this process.Back in the late 1980s—before the human genome project began—I taught a course on how genes—both protein-coding and those that specify functional RNAs—are expressed and regulated. We also covered RNA processing and translational control. We discussed protein sorting and secretion. None of the basics have changed following the sequencing of the human genome and the several hundred million dollars spent on ENCODE. The only thing I can say is that papers published in the 1990s led to the understanding that regulatory RNAs played a more significant role that we may have thought earlier. That was a quantitative change in our under standing, not a revolution.
We did not then, nor do we now, think that there are more genes for regulatory RNAs that there are for protein-coding genes of genes for known funcational RNAs (e.g., tRNA ribosomal RNA, snRna etc.). If you believe the hype promoted by John Mattick and echoed by Evelyn Fox Keller, then there must be almost 100 different regulatory RNA genes for every protein-coding gene! Does that make any sense at all?
If Evelyn Fox Keller is wrong (she is) how does this happen? How can a distinguished professor of the history and philosophy of science at a leading university (MIT) make such a mess of it?
There must be something seriously wrong with the discipline (History and Philosophy of Science) if such shoddy work can be published in 2015.
I suppose it's inevitable, since the science itself—biochemistry, molecular biology, genomics—is in even worse shape. For example, Evelyn Fox Keller tells us at the end of her essay that she has published the same argument elsewhere. The reference is Keller (2014) and the journal is the Journal of Physiology. Keller's affiliation is: MIT, Program in Science, Technology, and Society. Even scientific reviewers can be fooled.
Keller, E.F. (2014) From gene action to reactive genomes. The Journal of physiology, 592(11), 2423-2429. [doi: 10.1113/jphysiol.2014.270991]
Mattick, J.S. (2004) RNA regulation: a new genetics? Nature Reviews Genetics, 5:316-323. [doi: 10.1038/nrg1321]
Mattick, J.S. (2011) The central role of RNA in human development and cognition. FEBS letters, 585:1600-1616. [doi: 10.1016/j.febslet.2011.05.001]