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Sunday, March 27, 2016

Georgi Marinov reviews two books on junk DNA

The December issue of Evolution: Education and Outreach has a review of two books on junk DNA. The reviewer is Georgi Marinov, a name that's familiar to Sandwalk readers. He is currently working with Michael Lynch at Indiana University in Bloomington, Indiana, USA. You can read the review at: A deeper confusion.

The books are ...
The Deeper Genome: Why there is more to the human genome than meets the eye, by John Parrington, (Oxford, United Kingdom: Oxford University Press), 2015. ISBN:978-0-19-968873-9.

Junk DNA: A Journey Through the Dark Matter of the Genome, by Nessa Carey, (New York, United States: Columbia University Press), 2015. ISBN:978-0-23-117084-0.
You really need to read the review for yourselves but here's a few teasers.
If taken uncritically, these texts can be expected to generate even more confusion in a field that already has a serious problem when it comes to communicating the best understanding of the science to the public.
Parrington claims that noncoding DNA was thought to be junk and Georgi replies,
However, no knowledgeable person has ever defended the position that 98 % of the human genome is useless. The 98 % figure corresponds to the fraction of it that lies outside of protein coding genes, but the existence of distal regulatory elements, as nicely narrated by the author himself, has been at this point in time known for four decades, and there have been numerous comparative genomics studies pointing to a several-fold larger than 2% fraction of the genome that is under selective constraint.
I agree. That's a position that I've been trying to advertise for several decades and it needs to be constantly reiterated since there are so many people who have fallen for the myth.

Georgi goes on to explain where Parringtons goes wrong about the ENCODE results. This critique is devastating, coming, as it does, from an author of the most relevant papers.1 My only complaint about the review is that George doesn't reveal his credentials. When he quotes from those papers—as he does many times—he should probably have mentioned that he is an author of those quotes.

Georgi goes on to explain four main arguments for junk DNA: genetic load, the C-value Paradox, transposons (selfish DNA), and modern evolutionary theory. I like this part since it's similar to the Five Things You Should Know if You Want to Participate in the Junk DNA Debate. The audience of this journal is teachers and this is important information that they need to know, and probably don't.

His critique of Nessa Carey's book is even more devastating. It begins with,
Still, despite a few unfortunate mistakes, The Deeper Genome is well written and gets many of its facts right, even if they are not interpreted properly. This is in stark contrast with Nessa Carey’s Junk DNA: A Journey Through the Dark Matter of the Genome. Nessa Carey has a PhD in virology and has in the past been a Senior Lecturer in Molecular Biology at Imperial College, London. However, Junk DNA is a book not written at an academic level but instead intended for very broad audience, with all the consequences that the danger of dumbing it down for such a purpose entails.
It gets worse. Nessa Carey claims that scientists used to think that all noncoding DNA was junk but recent discoveries have discredited that view. Georgi sets her straight with,
Of course, scientists have had a very good idea why so much of our DNA does not code for proteins, and they have had that understanding for decades, as outlined above. Only by completely ignoring all that knowledge could it have been possible to produce many of the chapters in the book. The following are referred to as junk DNA by Carey, with whole chapters dedicated to each of them (Table 3).

The inclusion of tRNAs and rRNAs in the list of “previously thought to be junk” DNA is particularly baffling given that they have featured prominently as critical components of the protein synthesis machinery in all sorts of basic high school biology textbooks for decades, not to mention the role that rRNAs and some of the other noncoding RNAs on that list play in many “RNA world” scenarios for the origin of life. How could something that has so often been postulated to predate the origin of DNA as the carrier of genetic information (Jeffares et al. 1998; Fox 2010) and that must have been of critical importance both before and after that be referred to as “junk”?
You would think that this is something that doesn't have to be explained to biology teachers but the evidence suggests otherwise. One of those teachers recently reviewed Nessa Carey's book very favorably in the journal The American Biology Teacher and another high school teacher reveals his confusion about the subject in the comments to my post [see Teaching about genomes using Nessa Carey's book: Junk DNA].

It's good that Georgi Marinov makes this point forcibly.

Now I'm going to leave you with an extended quote from Georgi Marinov's review. Coming from a young scientist, this is very potent and it needs to be widely disseminated. I agree 100%.
The reason why scientific results become so distorted on their way from scientists to the public can only be understood in the socioeconomic context in which science is done today. As almost everyone knows at this point, science has existed in a state of insufficient funding and ever increasing competition for limited resources (positions, funding, and the small number of publishing slots in top scientific journals) for a long time now. The best way to win that Darwinian race is to make a big, paradigm shifting finding. But such discoveries are hard to come by, and in many areas might actually never happen again—nothing guarantees that the fundamental discoveries in a given area have not already been made. ... This naturally leads to a publishing environment that pretty much mandates that findings are framed in the most favorable and exciting way, with important caveats and limitations hidden between the lines or missing completely. The author is too young to have directly experienced those times, but has read quite a few papers in top journals from the 1970s and earlier, and has been repeatedly struck by the difference between the open discussion one can find in many of those old articles and the currently dominant practices.

But that same problem is not limited to science itself, it seems to be now prevalent at all steps in the chain of transmission of findings, from the primary literature, through PR departments and press releases, and finally, in the hands of the science journalists and writers who report directly to the lay audience, and who operate under similar pressures to produce eye-catching headlines that can grab the fleeting attention of readers with ever decreasing ability to concentrate on complex and subtle issues. This leads to compound overhyping of results, of which The Deeper Genome is representative, and to truly surreal distortion of the science, such as what one finds in Nessa Carey’s Junk DNA.

The field of functional genomics is especially vulnerable to these trends, as it exists in the hard-to-navigate context of very rapid technological changes, a potential for the generation of truly revolutionary medical technologies, and an often difficult interaction with evolutionary biology, a controversial for a significant portion of society topic. It is not a simple subject to understand and communicate given all these complexities while in the same time the potential and incentives to mislead and misinterpret are great, and the consequences of doing so dire. Failure to properly communicate genomic science can lead to a failure to support and develop the medical breakthroughs it promises to deliver, or what might be even worse, to implement them in such a way that some of the dystopian futures imagined by sci-fi authors become reality. In addition, lending support to anti-evolutionary forces in society by distorting the science in a way that makes it appear to undermine evolutionary theory has profound consequences that given the fundamental importance of evolution for the proper understanding of humanity’s place in nature go far beyond making life even more difficult for teachers and educators of even the general destruction of science education. Writing on these issues should exercise the needed care and make sure that facts and their best interpretations are accurately reported. Instead, books such as The Deeper Genome and Junk DNA are prime examples of the negative trends outlined above, and are guaranteed to only generate even deeper confusion.
It's not easy to explain these things to a general audience, especially an audience that has been inundated with false information and false ideas. I'm going to give it a try but it's taking a lot more effort than I imagined.

1. Georgi Marinov is an author on the original ENCODE paper that claimed 80% of our genome is functional (ENCODE Project Consortium, 2012) and the paper where the ENCODE leaders retreated from that claim (Kellis et al., 2014).

ENCODE Project Consortium (2012) An integrated encyclopedia of DNA elements in the human genome. Nature, 48957-74. [doi: 10.1038/nature11247]

Kellis, M., Wold, B., Snyder, M.P., Bernstein, B.E., Kundaje, A., Marinov, G.K., Ward, L.D., Birney, E., Crawford, G.E., and Dekker, J. (2014) Defining functional DNA elements in the human genome. Proc. Natl. Acad. Sci. (USA) 111:6131-6138. [doi: 10.1073/pnas.1318948111]

When philosophers write about evolution

The latest issue of Evolution: Education and Outreach contains a review of two books about evolution written by philosophers. The author of the review is Egbert Giles Leigh Jr. You can read it for free at: Questions about NeoDarwinism: a review of two books.

The books are,
Mind and Cosmos: Why the Materialist NeoDarwinian Conception of Nature is Almost Certainly False by Thomas Nagel. New York: Oxford University Press, 2012. ISBN 978-0-19-991975-8.

Are You an Illusion? by Mary Midgley. New York, NY: Routledge. 2014. ISBN 978-1-84465-792-6.
Both of these books challenge the idea that random mutation and natural selection can explain the world we see around us today.

The reviewer responds with a defense of natural selection from an adaptationist perspective.

I think Nagel and Midgley are wrong but for different reasons. I think that the history of life is the culmination of many random and accidental events and it could easily have gone in different directions [see Replaying life's tape]. I also think that lots of modern features are epiphenomena and not adaptations. Consciousness, to the extent that it actually exists, is one of them.

Nevertheless, Leigh's review is interesting and informative and I urge you to read it if you are interested in knowing why philosophers attack evolution. It helps us understand, once again, where philosophy is going wrong.

Friday, March 25, 2016

Teaching about genomes using Nessa Carey's book: Junk DNA

Nessa Carey's book about junk DNA is an embarrassment to the scientific community [Nessa Carey doesn't understand junk DNA] [The "Insulation Theory of Junk DNA"].

Today, while searching for articles on junk DNA, I came across a review of Nessa Carey's book published in The American Biology Teacher: DNA. The review was written by teacher in Colorado and she liked the book very much. Here's the opening paragraph,
The term junk DNA has been used to describe DNA that does not code for proteins or polypeptides. Recent research has made this term obsolete, and Nessa Carey elaborates on a wide spectrum of examples of ways in which DNA contributes to cell function in addition to coding for proteins. As in her earlier book, The Epigenetics Revolution (reviewed by ABT in 2013), Carey uses analogies and diagrams to relate complicated information. Although she unavoidably uses some jargon, she provides the necessary background for the nonbiologist.
The author of the review does not question or challenge the opinions of Nessa Carey and, if you think about it, that's understandable. The average biology teacher will assume that a book written by a scientist must be basically correct or it wouldn't have been published.

That's not true, as most Sandwalk readers know. You would think that biology educators should know this and exercise a little skepticism when reviewing books. Ideally, the book reviews should be written by experts who can evaluate the material in the book.

Now we have a problem. The way to correct false information about genomes and junk DNA is to teach it correctly in high school and university courses. But that means we first have to teach the teachers. Here's a case where professional teachers have been bamboozled by a bad book and that's going of make it even more difficult to correct the problem.

The last paragraph of the review shows us what influence a bad book can have,
As a biology teacher who enjoys sharing with students some details that go beyond the textbook or that challenge dogma, I enthusiastically read multiple chapters at each sitting, making note of what I cannot wait to add to class discussions. “Junk DNA” may be a misnomer, but Junk DNA is an excellent way of finding out why.
Oh dear. It's going to be hard to re-educate those students once their misconceptions have been reinforced by a teacher they respect.

Tuesday, March 22, 2016

How do you characterize these scientists?

We've been having a discussion on another thread about ID proponents. Are some of them acting in good faith or are they all lying and deceiving their followers?

I have similar problems about many scientists. I've been reading up on pervasive transcription and the potential number of genes for noncoding, functional, RNAs in the human genome. As far as I can tell, there are only a few hundred examples that have any supporting evidence. There are good scientific reasons to believe that most of the detected transcripts are junk RNA produced as the result of accidental, spurious, transcription.

There are about 20,000 protein-coding genes in the human genome. I think it's unlikely that there are more than a few thousand genes for functional RNAs for a total of less than 25,000 genes.

Here's one of the papers I found.
Guil, S. and Esteller, M. (2015) RNA–RNA interactions in gene regulation: the coding and noncoding players. Trends in Biochemical Sciences 40:248-256. [doi: 10.1016/j.tibs.2015.03.001]
Trends in Biochemical Sciences is a good journal and this is a review of the field by supposed experts. The authors are from the Department of Physiological Sciences II at the University of Barcelona School of Medicine in Barcelona, Catalonia, Spain. The senior author, Manel Esteller, has a Wikipedia entry [Manel Esteller].

Here's the first paragraph of the introduction.
There are more genes encoding regulatory RNAs than encoding proteins. This evidence, obtained in recent years from the sum of numerous post-genomic deep-sequencing studies, give a good clue of the gigantic step we have taken from the years of the central dogma: one gene gives rise to one RNA to produce one protein.
The first sentence is not true by any stretch of the imagination. The best that could be said is that there "may" be more genes for regulatory RNAs (> 20,000) but there's no strong consensus yet. Since the first sentence is an untruth, it follows that it is incorrect to say that the evidence supports such a claim.

It's also untrue to distort the real meaning of the Central Dogma of Molecular Biology, which never said that all genes have to encode proteins. The authors don't understand the history of their field in spite of the fact they are writing a review of that field.

Here's the problem. Are these scientists acting in good faith when they say such nonsense? Does acting in "good faith" require healthy criticism and critical thinking or is "honesty" the only criterion? The authors are clearly deluded about the controversy since they assume that it has been resolved in favor of their personal biases but they aren't lying. Can we distinguish between competent science and bad science based on such statements? Can we say that these scientists are incompetent or is that too harsh?

Furthermore, what ever happened to peer review? Isn't the system supposed to prevent such mistakes?

Sunday, March 20, 2016

Another failure: "The Mysterious World of the Human Genome"

The Mysterious World of the Human Genome
by Frank Ryan
William Collins, an imprint of Harper Collins, London UK (2015)
ISBN 978-0-00-754906-1

This is just another "gosh, gee whiz" book on the amazing and revolutionary (not!) discoveries about the human genome. The title tells you what to expect: The Mysterious World of the Human Genome.

The author is Frank P. Ryan, a physician who was employed as an "Honorary Senior Lecturer" in the Department of Medical Education at the University of Sheffield (UK). He's a member of The Third Way group. You can read more about him at their website: Frank P. Ryan.

You need to understand biology if you are going to debate an Intelligent Design Creationist

Last night's debate between Lawrence Krauss, Stephen Meyer, and Denis Lamoureux was very entertaining. I finally got to meet Stephen Meyer in person. (My photographer wasn't very good at focusing.)

There were some interesting exchanges during the debate. I want to talk about one of them.

Krauss tried to hammer Meyer on the "ID is not science" issue using quotes from a judge based on things said by lawyers in the Dover trial.1 Krauss tried to dismiss ID by saying that it never makes predictions but Meyer countered effectively by pointing out that ID predicts that most of our genome is functional and claiming that the prediction was confirmed by the ENCODE study.

The ID position is that Darwinists predicted that our genome would be full of junk while Intelligent Design Creationists predicted that most of our genome would be functional. ID was correct and Darwinism was wrong, according to this story.

Both Lawrence Krauss and Denis Lamoureux accepted the "fact" that ENCODE was right and most of the DNA in our genome has a function. Krauss was also hampered by his misunderstanding of evolution. It's obvious that he accepts the Richard Dawkins view of evolution so he tried to accommodate the ENCODE results by saying it's what you would expect of natural selection. This is the Richard Dawkins position.

Krauss tried to downplay the issue by saying that ID had not predicted what those functional parts of the genome would be doing but this was a weak rebuttal.

The facts are these ....
  • "Darwinists"—those who claim that natural selection is the only game in town—were opposed to the idea that most of our genome is junk. They still are.
  • Today, the majority of experts believe that most of our genome is junk in spite of the ENCODE publicity campaign from 2012.
  • The ENCODE Consortium has backed off it's original claim and now agrees that they misused the word "function." Some of them blame the media for distorting their position.
  • The ID "prediction" has been falsified.
A competent biologist would have known all this and could have challenged Meyer's statement. A biologist would have then demanded that Meyer explain how a genome that is 90% junk fits with Intelligent Design Creationism.

I talked to Denis Lamoureux after the debate to let him know that he was wrong about ENCODE and he was very gracious. I promised to send him more information. A genome full of junk DNA poses no threat to his version of Theistic Evolution.

Lawrence Krauss is an expert on cosmology but he's very weak on biology. I know it's common for physicists to think they are experts in everything but that's just not true. It was demonstrated in last night's debate.

1. This is a bad strategy. It's better to accept that ID proponents are doing science but just doing it very badly. Meyer ignored the issue of whether ID counted as science. He just presented the scientific case for ID and forced Krauss to respond to his "evidence."

Saturday, March 19, 2016

God, Science, and the Universe

Today's the day we find out "What's Behind It All?" The decision will be announced at the University of Toronto (Toronto, Ontario, Canada) by Lawrence Krauss when he educates the audience at Convocation Hall starting at 7 pm. Stephen Meyer (Intelligent Design Creationist) and Denis Lamoureux (Theistic Evolution Creationist) will also be there to learn the answer. (Spoiler Alert: the answer is "nothing.")
It's not too late to buy tickets. Email me if you want to join some of us for dinner before the event.

The event is being sponsored by Wycliffe College at the University of Toronto. This is an Anglican College that trains people to become Anglican Ministers (among other things). The college is the prime mover behind this series of events and it deserves a great deal of credit for the effort. Co-sponsors include the Centre for Inquiry, Canada and three Christian groups.

The event is being video-hosted at many locations around the world. See the list here. If you don't want to watch with others, you can see the live stream on YouTube at: Krauss, Meyer, Lamoureux: What’s Behind it all? God, Science and the Universe. It starts at 7 pm EST. (It's probably over already in Australia.)

The ID crowd is already anticipating defeat so they're preparing their audience by warning them that Lawrence Krauss will be nasty (i.e. refute their arguments) [see Watch Meyer Take on Krauss and Lamoureux, Streaming Live at Evolution News on March 19]. (Warning: check your irony meters before reading the first paragraph.)
Those on the Darwinist, materialist, atheist side of the debate that we follow here aren't normally very good at listening and responding to scientific perspectives at variance from their own. They are much more interested in condemning and ridiculing -- which has got to be a poor strategy for them if they want to persuade anyone.

With that as the background, as we noted already, it's refreshing that arch-atheist cosmologist Lawrence Krauss has agreed to participate in a public conversation with Discovery Institute's Stephen Meyer, joined by theistic evolutionist Denis Lamoureux. That will be March 19 at the University of Toronto's Convocation Hall. We're looking forward to it -- and here's the even better news. You won't have to be in Toronto to enjoy the discussion. The event will stream live here at Evolution News.

Monday, March 14, 2016

The best TED talk ever

I'm not a fan of TED talks. Comedian Will Stephen has figured them out and he gives a perfect example of everything that's wrong with a TED talk. Watch "How to sound smart in your TEDx Talk."

Sunday, March 13, 2016

Paradigm shifting

I was reading up on non-coding RNAs and came across this recent paper.
Bhartiya, D., and Scaria, V. (2016) Genomic variations in non-coding RNAs: Structure, function and regulation. Genomics 107:59-68. [doi: 10.1016/j.ygeno.2016.01.005]

Abstract: The last decade has seen tremendous improvements in the understanding of human variations and their association with human traits and diseases. The availability of high-resolution map of the human transcriptome and the discovery of a large number of non-protein coding RNA genes has created a paradigm shift in the understanding of functional variations in non-coding RNAs. Several groups in recent years have reported functional variations and trait or disease associated variations mapping to non-coding RNAs including microRNAs, small nucleolar RNAs and long non-coding RNAs. The understanding of the functional consequences of variations in non-coding RNAs has been largely restricted by the limitations in understanding the functionalities of the non-coding RNAs. In this short review, we outline the current state-of-the-art of the field with emphasis on providing a conceptual outline as on how variations could modulate changes in the sequence, structure, and thereby the functionality of non-coding RNAs.
The concept of a scientific paradigm and a "paradigm shift" was promoted by Thomas Kuhn. His most popular work was The Structure of Scientific Revolutions, published in 1962.

Wednesday, March 09, 2016

University of Toronto post-doc shares lab notes

The University of Toronto publicity department is making a big deal of Rachel Harding. She's a post-doc in the Structural Genomics Consortium (SGC). She works on Huntington's disease.

Here's the link to the press release and the first few paragraphs [Researcher is an Open Book: First to Share Lab Notes in Real Time].

Faculty of Medicine researcher Rachel Harding will be the first known biomedical researcher to welcome the world to review her lab notes in real time. The post-doctoral fellow with U of T’s Structural Genomics Consortium (SGC) is also explaining her findings to the general public through her blog. She hopes her open approach will accelerate research into Huntington’s disease.

“This should drive the process faster than working alone,” Harding says. “By sharing my notes, I hope that other scientists will critique my work, collaborate and share data in the early stages of research.” Her research at SGC is funded by CHDI Foundation, a non-profit drug-development organization exclusively dedicated to Huntington’s disease. Both organizations aim to accelerate research by making it open and collaborative.

Her approach is intended to leverage the experience of a community of scientists. Individual researchers often still work in relative isolation and then publish only their positive discoveries, usually years after the experiments were actually done. Thus, scientists often pursue similar ideas in parallel and miss many opportunities to learn from each other’s mistakes.

She has started by publishing raw data and play-by-play details of her first effort on the CERN open digital repository Zenodo. She also posts regular updates on her blog Lab Scribbles, where she includes an experimental summary written in lay terms.

It's been over 35 years since I first starting thinking and talking about electronic (computerized) lab notes1 and it's been over twenty years since I first heard discussions about putting them online. I seriously doubt that Rachel Harding is the first biomedical researcher to put lab notes on the web. I'm also very skeptical about her keeping up the practice for very long.

Not only is it boring and tedious to write your lab notes in a word processing program but it's kinda embarrassing to post everything you do in the lab. At least it would have been for me. I made lots of mistakes and there are lots of R-rated words and phrases in my notes.

Let's keep an eye on this experiments to see how it goes. So far there are four items on the Zenodo website. The first is a Word document containing a few brief notes from Jan. 6, 7, 9, 11 and 25. There are brief notes posted on Feb. 6 and two on Feb. 11. I hope this isn't the extent of her lab notes.

The blog is Lab Scribbles. There are a few posts. It's interesting but I'm not sure anyone is going to read it even if you're interested in Huntington's.

Has anyone else experimented with open lab notes?

1. I still have a few floppy disks with those attempts from about 1981. Unfortunately, I don't have a machine that can read them.

A 2004 kerfuffle over pervasive transcription in the mouse genome

The first drafts of the human genome sequence were published in 2001. There was still work to do on "finishing" the sequence but a lot of the International Human Genome Project (IHGP) team shifted to work on the mouse genome. The FANTOM Consortium and the RIKEN Genome Exploration Groups (I and II) published an analysis of mouse transcripts in December 2002.
Okazaki, Y., Furuno, M., Kasukawa, T., Adachi, J., Bono, H., Kondo, S., Nikaido, I., Osato, N., Saito, R., Suzuki, H. et al. (2002) Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature, 420:563-573. [doi: 10.1038/nature01266]

Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 ‘transcriptional units’, contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense–antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.

Wednesday, March 02, 2016

When philosophers talk about genomes

Postgenomics is a compendium of twelve scholarly articles by philosophers and sociologists who write about the implication of the human genome sequence and subsequent work on interpreting the results. The volume is 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).

The first essay is by Stevens and Richardson and it outlines the goal of the book.