"The Soul of the Matter"

Meet Bruce Buff. He's a big fan of the Discovery Institute as he explains in this video.

Bruce Buff has written a novel (fiction) called The Soul of the Matter. The Intelligent Design Creationists are all over it. So far they've put up two posts advertising the novel: Excerpt: The Soul of the Matter, Chapter 3; Excerpt: The Soul of the Matter, Chapter 4.

Here's the description from the publisher's website ...

A scientist’s claim that he’s found the secrets of the universe's origin encoded in DNA sparks a race against time to uncover the truth in this fast-paced thriller of science and faith, power and murder, loss and redemption.

Dan Lawson, a former government cyber-intelligence analyst, is surprised to be contacted by his estranged friend Stephen Bishop, a renowned geneticist. Stephen says that he’s discovered amazing information within DNA, including evidence of a creator, and needs Dan’s help to protect his findings. Dan is skeptical and wonders whether he is being manipulated, or if the recent illness of Stephen’s only child, Ava, has caused his childhood friend to fall back on religion for answers to questions best left to science. Spurred by his desire for proof that life has meaning, however, Dan puts aside his doubts and agrees to help.

I haven't read the book but there may be a clue on the cover. I think the amazing information might be that the DNA helix is left-handed instead of right-handed [On the handedness of DNA ]. It's a little hard to tell from the image on the cover.

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How many lncRNAs are functional: can sequence comparisons tell us the answer?

A large percentage of the human genome is transcribed at some time or another during development. The vast majority of those transcripts are very rare transcripts that look very much like spurious products of accidental transcription initiation at sequences resembling true promoters. They have been rejected by genome annotators. They do not define genes. They are junk RNA. Pervasive transcription does not mean that most of the genome is functional.

Among the transcripts is a class called long non-coding RNAs or lncRNAs. These are usually defined as capped and polyadenylated transcripts longer than 200 nucleotides. Many of them are processed by splicing. They look a lot like mRNA except they don't encode any polypeptides.¹

We don't know how many of these RNAs exist because different labs use different criteria to describe them. Some databases exclude low abundance lncRNAs and some include non-polyadenylated RNAs. There is general agreement that they number in the tens of thousands. A common number in the scientific literature is 60,000 lncRNAs.

Splice variants of the human triose phosphate isomerase gene: is alternative splicing real?

Triose phosphate isomerase (TIM) is one of the enzymes in the gluconeogenesis pathway leading to the synthesis of glucose from simple precursors. It also plays a role in the degradation of glucose (glycolysis). The enzyme catalyzes the following reaction ....

Triose phosphate isomerase is found in almost all species. The structure and sequence of the enzyme is well-conserved. It is a classic β-barrel enzyme that usually forms a dimer. The overall structure of a single subunit is classic example of an αβ-barrel known as a TIM-barrel in reference to this enzyme.

To the best of my knowledge, no significant variants of this enzyme due to alternative promoters, alternative splicing, or proteolytic cleavage are known.¹ The enzyme has been actively studied in biochemistry laboratories for at least eighty years.

Understanding Michael Behe's edge of evolution

It's been about twenty years since Intelligent Design Creationism rose to prominence. Just last week the Center for Science and Culture celebrated it's 20th birthday [Twenty Years Ago Today, Did This Change the Evolution Debate Forever?]. In all that time, the best that ID proponents can come up with is some work by Michael Behe that attempts to discredit evolution.

The first book by Behe was Darwin's Black Box where he developed the notion of irreducible complexity. The definition of irreducible complexity has changed over the years but the basic idea is that some biological structures are very complex and the removal of any one part will render the complex nonfunctional. This presents an enormous problem for evolution, according to Behe, because all the presumptive intermediates will be nonfunctional.

The conclusion is that it's impossible to evolve an irreducibly complex structure. Evolutionary biologists have no problem accepting the existence of irreducibly complex structures. They see them all the time. What they object to is the idea that irreducibly complex structures cannot have arisen by evolution. Behe's conclusion has been shown to be false and he has admitted on multiple occasions that irreducibly complex structures can arise by purely natural means (evolution).

Do you believe what's written in the introduction to this paper?

I came across this paper while doing research on alternative splicing. The introduction annoyed me. It illustrates what to my mind are some serious problems with modern scholarship.

Scotti, M.M. and Swanson, M.S. (2016) RNA mis-splicing in disease. Nature Reviews Genetics 17:19–3 [doi: 10.1038/nrg.2015.3]

Here's part of the first paragraph in the paper.

Recent analysis from the Encyclopedia of DNA Elements (ENCODE) project (GRCh38, Ensembl79) indicates that most of the human genome is transcribed and consists of ~60,000 genes (~20,000 protein-coding genes, ~16,000 long non-coding RNAs (lncRNAs), ~10,000 small non-coding RNA and 14,000 pseudogenes). Although this gene inventory will change with further analysis, the number of protein-coding genes is surprisingly low given the proteomic complexity that is evident in many tissues, particularly the central nervous system (CNS). High resolution mass spectrometry studies have identified peptides encoded by most of these annotated genes, but the number of isoforms expressed from this gene set has been estimated to be at least 5–10-fold higher. For example, long-read sequence analysis of adult mouse prefrontal cortex neurexin (Nrxn) mRNAs indicates that only three Nrxn genes produce thousands of isoform variants. This diversity is primarily generated by alternative splicing, with >90% of human protein-coding genes producing multiple mRNA isoforms.

Here are some of the problems I have with this introduction. My opinions on these issues differ from those of the authors.

1. I think that pseudogenes are not genes.
2. I think there are NOT ~16,000 lncRNAs and ~10,000 small-noncoding RNA genes. Instead, there are approximately this many putative or predicted genes, many of which will undoubtedly turn out not to be genes. Some of them will be pseudogenes.
3. I don't think there's a discrepancy between the known number of protein-coding genes and proteomic complexity; therefore, it is misleading to say that the number of protein-coding genes is "surprisingly low."
4. I'm pretty sure that nobody has ever proposed a truly scientific "estimate" of isoforms showing that the number should be 5-10-fold higher than the number of genes. This is all speculation and guesswork based mostly on deflated egos.
5. It is not true that >90% of human genes produce multiple mRNA isoforms by alternative splicing. What IS true is that for every human gene researchers have detected low levels of non-canonical splice events upon careful analysis of the transcriptome. We do not know whether these represent true biologically relevant alternative splicing or simply splicing errors. All available evidence suggests that the vast majority are splicing errors.

The authors are certainly entitled to their opinion ... even if it differs from mine!

But surely there has to be a better way of expressing this opinion to make it clear that they aren't stating facts but just their own personal views based on their own interpretation of the literature? This becomes very important if there's widespread scientific controversy over some of these opinions. (It's not so important if there's widespread agreement, or consensus, in the scientific community. In those cases, you aren't obliged to mentions alternative views held by kooks.)

I believe that scientists have an ethical obligation to distinguish between fact and opinion and to make it very clear in their writings which is which. I don't know whether Scotti and Swanson know about the controversial aspect of their statements and are deliberately avoiding any mention of them, or whether they actually believe that their statements are factual. Either way, we have a problem.

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Twenty "sciencey" questions for Trump and Clinton

ScienceDebate.org is a group that wants a "science" debate between Presidential candidates in the upcoming American election. That's not going to happen so the next best thing is to demand that the candidates answer their 20 questions about Science, Engineering, Technology, Health, and the Environment. I would not answer these questions if I were a candidate. Many of them require extraordinarily complex answers. Some of them are based on false premises. Several are loaded. Some of the problems can't be dealt with in any realistic way by a President of the United States. Quite a few cannot be answered in any meaningful way without writing a book.

I'm not sure what this group expects. This seems to be a colossal waste of time. It also seems to be very low on the priority list given all the other problems with Trump and Clinton. The questions don't inspire confidence in ScienceDebate, in my opinion. Here are the questions from: 20 Questions.

1. Science and engineering have been responsible for over half of the growth of the U.S. economy since WWII. But some reports question America’s continued leadership in these areas. What policies will best ensure that America remains at the forefront of innovation?
2. Many scientific advances require long-term investment to fund research over a period of longer than the two, four, or six year terms that govern political cycles. In the current climate of budgetary constraints, what are your science and engineering research priorities and how will you balance short-term versus long-term funding?
3. The Earth’s climate is changing and political discussion has become divided over both the science and the best response. What are your views on climate change, and how would your administration act on those views?
4. Biological diversity provides food, fiber, medicines, clean water and many other products and services on which we depend every day. Scientists are finding that the variety and variability of life is diminishing at an alarming rate as a result of human activity. What steps will you take to protect biological diversity?
5. The Internet has become a foundation of economic, social, law enforcement, and military activity. What steps will you take to protect vulnerable infrastructure and institutions from cyber attack, and to provide for national security while protecting personal privacy on electronic devices and the internet?
6. Mental illness is among the most painful and stigmatized diseases, and the National Institute of Mental Health estimates it costs America more than $300 billion per year. What will you do to reduce the human and economic costs of mental illness?
7. Strategic management of the US energy portfolio can have powerful economic, environmental, and foreign policy impacts. How do you see the energy landscape evolving over the next 4 to 8 years, and, as President, what will your energy strategy be?
8. American students have fallen in many international rankings of science and math performance, and the public in general is being faced with an expanding array of major policy challenges that are heavily influenced by complex science. How would your administration work to ensure all students including women and minorities are prepared to address 21st century challenges and, further, that the public has an adequate level of STEM literacy in an age dominated by complex science and technology?
9. Public health efforts like smoking cessation, drunk driving laws, vaccination, and water fluoridation have improved health and productivity and save millions of lives. How would you improve federal research and our public health system to better protect Americans from emerging diseases and other public health threats, such as antibiotic resistant superbugs?
10. The long-term security of fresh water supplies is threatened by a dizzying array of aging infrastructure, aquifer depletion, pollution, and climate variability. Some American communities have lost access to water, affecting their viability and destroying home values. If you are elected, what steps will you take to ensure access to clean water for all Americans?
11. Nuclear power can meet electricity demand without producing greenhouse gases, but it raises national security and environmental concerns. What is your plan for the use, expansion, or phasing out of nuclear power, and what steps will you take to monitor, manage and secure nuclear materials over their life cycle?
12. Agriculture involves a complex balance of land and energy use, worker health and safety, water use and quality, and access to healthy and affordable food, all of which have inputs of objective knowledge from science. How would you manage the US agricultural enterprise to our highest benefit in the most sustainable way?
13. We now live in a global economy with a large and growing human population. These factors create economic, public health, and environmental challenges that do not respect national borders. How would your administration balance national interests with global cooperation when tackling threats made clear by science, such as pandemic diseases and climate change, that cross national borders?
14. Science is essential to many of the laws and policies that keep Americans safe and secure. How would science inform your administration's decisions to add, modify, or remove federal regulations, and how would you encourage a thriving business sector while protecting Americans vulnerable to public health and environmental threats?
15. Public health officials warn that we need to take more steps to prevent international epidemics from viruses such as Ebola and Zika. Meanwhile, measles is resurgent due to decreasing vaccination rates. How will your administration support vaccine science?
16. There is a political debate over America’s national approach to space exploration and use. What should America's national goals be for space exploration and earth observation from space, and what steps would your administration take to achieve them?
17. There is a growing opioid problem in the United States, with tragic costs to lives, families and society. How would your administration enlist researchers, medical doctors and pharmaceutical companies in addressing this issue?
18. There is growing concern over the decline of fisheries and the overall health of the ocean: scientists estimate that 90% of stocks are fished at or beyond sustainable limits, habitats like coral reefs are threatened by ocean acidification, and large areas of ocean and coastlines are polluted. What efforts would your administration make to improve the health of our ocean and coastlines and increase the long-term sustainability of ocean fisheries?
19. There is much current political discussion about immigration policy and border controls. Would you support any changes in immigration policy regarding scientists and engineers who receive their graduate degree at an American university? Conversely, what is your opinion of recent controversy over employment and the H1-B Visa program?
20. Evidence from science is the surest basis for fair and just public policy, but that is predicated on the integrity of that evidence and of the scientific process used to produce it, which must be both transparent and free from political bias and pressure. How will you foster a culture of scientific transparency and accountability in government, while protecting scientists and federal agencies from political interference in their work?

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A refreshing admission on Uncommon Descent

Some of us have been debating Intelligent Design Creationists for many years. Some of us have even visited the creationist blogs like Uncommon Descent where we discover that no facts and no logic will ever shake their obsession with proving evolution wrong and promoting their gods. That's why it was refreshing to read the following comment by William J. Murray in his post on "The Benefit of Arguments at UD." I only had time to read the first few lines but you get the gist ...

Probably one of the most daunting aspects of carrying on debates either about proper critical thinking, theism vs atheism, or intelligent design and its implications is the seeming implacable nature of those we debate here and elsewhere. It most often seems that no amount of logic, evidence or even reasonable discourse makes one iota of difference ...

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This anti-science creationist could be Vice-President of the United States of America

Thanks to PZ Myers for digging up this speech by Mike Pence in the House of Representatives [Mike Pence, creationist]. I think Pence is trying to make America great again by returning the country to the stone age.

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Why are academics such bad writers?

Not all academics are bad writers but the exceptions are few and far between. Several recent articles in The Chronicle of Higher Education have attempted to explain why we can't write. There are two types of academic writing. The style you use in your academic papers differs from the style you use in writing for a general audience. There's absolutely no debate about the style of writing in the academic literature: it is horrible and it needs to change.

I want to talk about the other kind of writing; the kind where academics try to explain things to non-academics. I'll concentrate on science writing although I'm sure the same issues apply to history, philosophy, and all the other academic disciplines. I'm particularly sensitive to this problem since I'm working on a book about genomes and junk DNA and it's very different than writing a biochemistry textbook.

The latest (Aug. 1, 2016) article is an interview with Steven Pinker, the well-known Harvard psychologist. He's published seven trade books and is widely perceived to be a good example of how academics should write for a general audience [Scholars Talk Writing: Steven Pinker].

More junk science in Science

The latest issue of the journal Science (Aug. 1, 2016) has an article on a recent paper by Aires et al. (2016) published in Developmental Cell. Here's the abstract of the paper ...

Vertebrates exhibit a remarkably broad variation in trunk and tail lengths. However, the evolutionary and developmental origins of this diversity remain largely unknown. Posterior Hox genes were proposed to be major players in trunk length diversification in vertebrates, but functional studies have so far failed to support this view. Here we identify the pluripotency factor Oct4 as a key regulator of trunk length in vertebrate embryos. Maintaining high Oct4 levels in axial progenitors throughout development was sufficient to extend trunk length in mouse embryos. Oct4 also shifted posterior Hox gene-expression boundaries in the extended trunks, thus providing a link between activation of these genes and the transition to tail development. Furthermore, we show that the exceptionally long trunks of snakes are likely to result from heterochronic changes in Oct4 activity during body axis extension, which may have derived from differential genomic rearrangements at the Oct4 locus during vertebrate evolution.

... those ignorant of history are not condemned to repeat it; they are merely destined to be confused.

Stephen Jay Gould
Ontogeny and Phylogeny (1977)The results were written up by a freelance journalist named Diana Crow [‘Junk DNA’ tells mice—and snakes—how to grow a backbone]. She writes ...

‘Junk DNA’ tells mice—and snakes—how to grow a backbone

Why does a snake have 25 or more rows of ribs, whereas a mouse has only 13? The answer, according to a new study, may lie in "junk DNA," large chunks of an animal’s genome that were once thought to be useless. The findings could help explain how dramatic changes in body shape have occurred over evolutionary history.

Scientists began discovering junk DNA sequences in the 1960s. These stretches of the genome—also known as noncoding DNA—contain the same genetic alphabet found in genes, but they don’t code for the proteins that make us who we are. As a result, many researchers long believed this mysterious genetic material was simply DNA debris accumulated over the course of evolution. But over the past couple decades, geneticists have discovered that this so-called junk is anything but. It has important functions, such as switching genes on and off and setting the timing for changes in gene activity.

Sandwalk readers will see all the mistakes and misconceptions in these paragraphs. She's talking about regulatory sequences that were never, ever, thought to be junk. The paper being discussed has nothing to do with junk DNA and the results do not in any way alter our understanding of developmental gene regulation.

If you look carefully at the abstract, you'll see the word "heterochronic." This is one of Stephen Jay Gould's favorite words. He wrote about it in Ontogeny and Phylogeny.

I wish to emphasize one other distinction. Evolution occurs when ontogeny is altered in one of two ways: when new characters are introduced at any stage of development with varying effects upon subsequent stages, or when characters already present undergo changes in developmental timing. Together, these two processes exhaust the formal concept of phyletic change.; the second process is heterochrony. [my emphasis ... LAM] If change in developmental timing is important in evolution, then this second process must be very common.

This was written in 1977—that's almost 40 years ago! These ideas were around for decades before Gould wrote his book¹ and they have been shown to be correct by numerous studies in the 1980s.

What's going on here? Science is supposed to be one of the leading science journals. How could it publish an article that misrepresents the field so badly? Do the editors send these "Latest News" articles out for review?

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1. Ed Lewis shared the Nobel Prize in 1995 for his contribution to "the genetic control of early embryonic development" [The Nobel Prize in Physiology or Medicine 1995].

Siddhartha Mukherjee tries to correct his book

There are lots of things wrong with Mukherjee's best-selling book The Gene. I've listed a few things that I know about [What is a "gene" and how do genes work according to Siddhartha Mukherjee?]. Others have come up with different problems.

The biggest problem is that Mukherjee misrepresents the current state of knowledge in genetics, biochemistry, and molecular biology. His misleads his readers by promoting silly viewpoints that conflict with the consensus view. He doesn't mention that there are other views that are well supported by tons of scientific evidence.

The best example is regulation of gene expression. He fails to explain the standard textbook understanding of transcriptional regulation by transcription factors—a view that's solidly backed by decades of work in biochemistry, developmental genetics, molecular biology, and genomics. Instead, he promotes a flaky epigenetic theory that, according to him, threatens to overthrow Darwinian evolution.

The most important thing about nature according to Bill Martin

My friend and colleague, Alex Palazzo, alerted me to an interview of Bill Martin published in the July 11, 2016 issue of Current Biology [Bill Martin]. I loved all his answers—Bill Martin is one of my scientific heroes—but his answer to the last question was particularly insightful. The question was, "What’s the single most important thing that you have come to realize about nature?"

His answer was ....

Life is an exergonic chemical reaction. It’s the energy releasing redox reaction at the core of metabolism that makes life run, and throughout all of life’s history it is one and the same reaction that has been running in uninterrupted continuity from life’s onset. Everything else is secondary, manifestations of what is possible when the energy is harnessed to make genes that pass the torch.

I'm a biochemist so you might think I'm a little bit biased but let me tell you why this answer is so important.

You are junk

There's an article about junk DNA in the latest issue of New Scientist (July 27, 2016) [You are junk: Why it’s not your genes that make you human]. I've already discussed the false meme at the beginning of the article [False history and the number of genes: 2016]. Now it's time to look at the main argument.

The subtitle is ...

Genes make proteins make us – that was the received wisdom. But from big brains to opposable thumbs, some of our signature traits could come from elsewhere.

You can see where this is going. You start with a false paradigm, "Genes make proteins make us," then proceed to refute it. This is called "paradigm shafting."¹

False history and the number of genes: 2016

There's an article about junk DNA in the latest issue of New Scientist. The title is: You are junk: Why it’s not your genes that make you human. The author is Colin Barras, a science writer from Michigan with a Ph.D. in paleontology.

He begins with .....

IT WAS a discovery that threatened to overturn everything we thought about what makes us human. At the dawn of the new millennium, two rival teams were vying to be the first to sequence the human genome. Their findings, published in February 2001, made headlines around the world. Back-of-the-envelope calculations had suggested that to account for the sheer complexity of human biology, our genome should contain roughly 100,000 genes. The estimate was wildly off. Both groups put the actual figure at around 30,000. We now think it is even fewer – just 20,000 or so.

"It was a massive shock," says geneticist John Mattick. "That number is tiny. It’s effectively the same as a microscopic worm that has just 1000 cells."

What is "THE" theory of evolution?

I wish people would stop referring to "THE" Theory of Evolution. What they really mean, of course, is "The Theory of Natural Selection"—part of modern evolutionary theory. There's no question about the importance of natural selection and the major contribution of Charles Darwin in discovering it and promoting it to the general public. However, in 2016 there's a lot more to evolutionary theory than just natural selection and the public needs to know this. Many scientists need to know this.

There's also no debate about Darwin's contribution to promoting the evidence of evolution and descent with modification. He made a brilliant case for evolution in his books. Subsequent discoveries have demonstrated beyond a reasonable doubt that modern life is the product of billions of years of evolution. Descent with modification is a scientific fact. The fact that evolution has occurred is not a theory. It is not a "theory" that humans and the other apes have descended form a common ancestor ... it is a fact [Evolution Is a Fact and a Theory].

We perpetuate confusion in the minds of the general public if we don't make it abundantly clear that modern evolution theory is not about whether evolution occurred and it's not just about natural selection.

I was prompted to write this blog post by a recent article in New Scientist: Darwin’s discovery: The remarkable history of evolution.¹ The author is John van Wyhe of the National University of Singapore. He is a historian of science with a special interest in Charles Darwin and Alfred Russel Wallace.

The article contains a box that says ...

Evolution in a nutshell

Darwin’s and Wallace’s theory of evolution maintains that new species are descended from earlier ones. This long-term process happens because all organisms vary. The tiny variations are naturally “selected” by virtue of whether or not they help an organism to survive the brutal struggle for existence in nature. Many are born, but few survive; fortuitous variations are preferentially passed on. This process of endless filtering works to adapt organisms to their environment.

This is misleading in two ways. First, it states that common descent is part of the the theory of evolution. Second, it only talks about natural selection as a mechanism of evolution.

We wish to question a deeply engrained habit of thinking among students of evolution. We call it the adaptationist programme, or the Panglossian paradigm.

S.J. Gould & R.C. Lewontin (1979) p. 584Fortunately, the main body of the article is quite a bit better. Here's what John van Wyhe actually says about evolution.

Despite its baptism of fire, On the Origin of Species almost single-handedly convinced the international scientific community that evolution was a fact. In his 1889 book Darwinism, Wallace wrote of the revolution Darwin effected: "this totally unprecedented change in public opinion has been the result of the work of one man, and was brought about in the short space of twenty years!"

The theory of evolution has come a long way since. Today we think of it in terms of genes and DNA, but Darwin and Wallace had no idea of their existence. It was only in the 1930s and 1940s that genetics was incorporated into evolutionary theory. Even now, new discoveries are shaking up our understanding, but at the core of the modern theory remains Darwin’s idea of descent with modification.

Today evolution has many critics outside the scientific community, especially in the US, where a significant percentage of the population are creationists. What is forgotten is that the scientific debate over evolution was over by the 1870s and has never again been a matter of serious dispute.

Darwin showed that evolution is a fact and it's good that van Wyhe made this point in a article aimed at the general public. It's not good when he says "the core of the modern theory remains Darwin’s idea of descent with modification."

It's not good that he still refers to "THE" theory of evolution instead of "evolutionary theory," which encompasses all kinds of things other than natural selection.

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1. The title in the print edition is: "The Evolution Revolution."

The seven biggest problems in science

Here's an interesting article about the biggest problems in (American) science: The 7 biggest problems facing science, according to 270 scientists. Most of them apply to science in other countries.

I've added brief comments under six of the headings. Those are MY opinions, not necessarily those of the authors. The comment under #6 is a direct quote from the article.

1. Academia has a huge money problem.
   There's not enough money to do high quality science, especially basic science.
2. Too many studies are poorly designed. Blame bad incentives.
   Some experiments are poorly designed. All scientists are under pressure to make their results seem important.
3. Replicating results is crucial. But scientists rarely do it.
   Replication is important—especially in medical studies—but I think this problem is exaggerated.
4. Peer review is broken.
   The system (peer review) isn't working well. That doesn't mean there's a better system.
5. Too much science is locked behind paywalls.
   This was never a problem in the past when you had to go to the library to read science journals. You could photocopy whatever you wanted. Now it's a problem because we want instant access from our laptops.
6. Science is poorly communicated to the public.
   "But not everyone blamed the media and publicists alone. Other respondents pointed out that scientists themselves often oversell their work, even if it's preliminary, because funding is competitive and everyone wants to portray their work as big and important and game-changing.
   
   'You have this toxic dynamic where journalists and scientists enable each other in a way that massively inflates the certainty and generality of how scientific findings are communicated and the promises that are made to the public,' writes Daniel Molden, an associate professor of psychology at Northwestern University. 'When these findings prove to be less certain and the promises are not realized, this just further erodes the respect that scientists get and further fuels scientists desire for appreciation.'"
7. Life as a young academic is incredibly stressful.
   This is not just a problem for my younger colleagues. It affects all of us. It affects morale in an academic department and it affects the way science is done.

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Bastille Day

Today is the Fête Nationale in France known also as "le quatorze juillet" or Bastille Day.

This is the day in 1789 when French citizens stormed and captured the Bastille—a Royalist fortress in Paris. It marks the symbolic beginning of the French revolution although the real beginning is when the Third Estate transformed itself into the National Assembly on June 17, 1789 [Tennis Court Oath].

Ms. Sandwalk and I visited the site of the Bastille (Place de la Bastille) when we were in Paris in 2008. There's nothing left of the former castle but the site still resonates with meaning and history.

One of Ms Sandwalk's ancestors, William Playfair witnessed the storming of the Bastille.

In honor of the French national day I invite you to sing the French national anthem, La Marseillaise. An English translation is provided so you can see that La Marseillaise is truly a revolutionary call to arms. (A much better translation can be found here.)

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Check out Uncertain Principles for another version of La Marseillaise—this is the famous scene in Casablanca.

Reposted from 2009.

A genetics professor who rejects junk DNA

Praveen Sethupathy is a genetics professor at the University of North Carolina in Chapel Hill, North Carolina, USA.

He explains why he is a Christian and why he is "more than his genes" in Am I more than my genes? Faith, identity, and DNA.

Here's the opening paragraph ...

The word “genome” suggests to many that our DNA is simply a collection of genes from end-to-end, like books on a bookshelf. But it turns out that large regions of our DNA do not encode genes. Some once called these regions “junk DNA.” But this was a mistake. More recently, they have been referred to as the “dark matter” of our genome. But what was once dark is slowly coming to light, and what was once junk is being revealed as treasure. The genome is filled with what we call “control elements” that act like switches or rheostats, dialing the activation of nearby genes up and down based on whatever is needed in a particular cell. An increasing number of devastating complex diseases, such as cancer, diabetes, and heart disease, can often be traced back, in part, to these rheostats not working properly.

Science journal tries to fix problems with transparency and trustworthiness

The editors of Science recognize that they have a problem. They aren't very transparent or trustworthy. This is true. These same editors have been guilty of publishing and promoting lots of poor quality science over the past few years. Three examples come to mind ...

• Arseniclife: Science published a ridiculous claim that arsenic could replace phosphorus in DNA. That paper has been refuted but never retracted.
• Ardipithicus ramidus: Science fell for the authors' hype.
• ENCODE: Science falls for the hype promoted by ENCODE leaders. Editorial and feature writers announce the death of junk DNA

Don't worry. The editors have been working hard to fix the problem. After a year of study they announce their solution in the June 3, 2016 issue in the lead editorial: Taking up TOP. The author is the current Editor-in-Chief, Marcia McNutt.

She begins with ...

Nearly 1 year ago, a group of researchers boldly suggested that the standards for research quality, transparency, and trustworthiness could be improved if journals banded together to adopt eight standards called TOP (Transparency and Openness Promotion).* Since that time, more than 500 journals have been working toward their implementation of TOP. The editors at Science have held additional retreats and workshops to determine how best to adapt TOP to a general science journal and are now ready to announce our new standards, effective 1 January 2017.

So, what is TOP and how is it going to make Science more trustworthy? Does it involve firing some well-known writers and editors? Does it involve better reviewers?

Nope. TOP is just a way of making sure that raw data is available to other researchers.

... we believe the benefits of requiring the availability of data, code, and samples on which the authors' interpretations rest are worth the effort in compliance (and in some cases in adjusting data ownership expectations), while acknowledging that some special circumstances will require exemptions. This practice increases transparency, enables reproducibility, promotes data reuse, and is increasingly in line with funder mandates. We are also requiring the citation of all data, program code, and other methods not contained in the paper, using DOIs (digital object identifiers), journal citations, or other persistent identifiers, for the same reason. Citations reward those who originated the data, samples, or code and deposited them for reuse. Such a policy also allows accurate accounting for exactly which specific data, samples, or code were used in a given study.

That's not going to fix the main problem.

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Nature journal tries to fix the problem of a scientific literature that's too complex to understand

I recently posted some thoughts on the complexity of the scientific literature noting that many papers are simply too difficult to understand. This includes papers that are well within my areas of interest [How to read the scientific literature? and The scientific literature is becoming more complex].

Nature journal recognizes that there's a problem. A few weeks ago (June 16, 2016) they published a brief comment on Nature distilled.

They begin by describing the problem ...

Any journal that tries to publish the most important results that it is sent, in all fields of science, will run into the same problem. Every bit of our output, we hope, is useful and interesting to somebody somewhere. But even the most optimistic of our editors would concede that the pool of readership for each of these specific advances is only a small subsection of our audience, professional researchers included. To the outside world, science is science. To those who read Nature, science is a multiplicity of specialisms — and specialists.

We know that most of you are specialists, and that you don’t read most of what we present to you. You’re busy people. It is hard enough to follow the literature that you need to read. Even the titles of research papers in an unfamiliar field can look incomprehensible. But if you’re anything like us, one reason you got into science in the first place was curiosity about the world — and not just the tiny piece of it that you now focus on. Wouldn’t it be useful and interesting to keep better track of the rest? Or at least, the rest that is published in Nature, and therefore already judged to be important?

Let's make one thing clear. It's not just the complexity of a paper that's the problem and it's not just that the science isn't explained in easy to understand sentences. There's also the more serious problem of content. Sometimes the papers are hard to understand because the significance of the results is exaggerated and its importance is not placed in proper context.

The ENCODE papers are good examples of this problem. It wasn't easy to understand that they did but, more importantly, it wasn't easy to understand the significance of their results because the authors didn't explain their results very well. They made unsubstantiated claims.

Here's how Nature hopes to fix the problems they identified.

We think so, and this week we begin an experiment to see how many of you agree. We have revisited 15 recently published Nature papers and asked the authors to produce two-page summaries of each. The summaries remain technical — these are not articles suitable for the popular press — but they try to communicate both the research advance and why it matters. The authors of these papers have been enthusiastic — they want the broadest possible readership — and we thank them for their cooperation. Now we want to know what you think. The first three summaries are published online this week (see go.nature.com/1uhcy3x). The rest will be released in the coming weeks. Please take a look. Be brave — pick a topic that you expect to struggle with — and then fill in the online survey to let us know what you think. The rest will be released in the coming weeks. Please take a look. Be brave — pick a topic that you expect to struggle with — and then fill in the online survey to let us know what you think.

I looked at two papers that were about biology and I didn't think the summaries added anything to my understanding. That's partly because the papers weren't that hard to understand in the first place if you were just satisfied with knowing what they did.

Both papers raised lots of questions in my mind about the biological significance of the studies and whether they were accurate and reproducible. The author summaries didn't help much. [Non-coding recurrent mutations in chronic lymphocytic leukaemia and DNA-dependent formation of transcription factor pairs alters their binding specificity].

If the scientific literature is difficult to understand, and it is, then there's a problem with the authors. They aren't able to explain what they did in a reasonable manner and they aren't able to place their work in a proper context so we can evaluate the significance of the result. Asking them to try again (and doubling their citations) is probably not going to help.

The ENCODE authors couldn't do it.

It's a lot like asking the fox to guard the henhouse.

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What is a "gene" and how do genes work according to Siddhartha Mukherjee?

It's difficult to explain fundamental concepts of biology to the average person. That's why I'm so interested in Siddhartha Mukherjee's book "The Gene: an intimate history." It's a #1 bestseller so he must be doing something right.

My working definition of a gene is based on a blog post from several years ago [What Is a Gene?].

A gene is a DNA sequence that is transcribed to produce a functional product.

This covers two types of genes: those that eventually produce proteins (polypeptides); and those that produce functional noncoding RNAs. This distinction is important when discussing what's in our genome.

Paradigm shifting at the Royal Society meeting in November

Suzan Mazur has been making a name for herself by promoting the overthrow of modern evolutionary theory. She began with a lot of hype about the Alternberg 16 back in 2008 and continued with a series of interviews of prominent evolutionary biologists.

Now she's focused on the upcoming meeting in November as another attempt to shift paradigms [see New Trends in Evolutionary Biology: The Program]. She's not entirely wrong. Many of the people involved in those meeting see themselves as paradigm shifters.

TED-Ed misrepresents epigenetics

TED-Ed is the educational arm of TED. Here's what TED says about itself and about TED-Ed ...

TED believes passionately that ideas have the power to change attitudes, lives, and ultimately, the world. This underlying philosophy is the driving force behind all of TED’s endeavors, including the TED Conferences, TEDx, TED Books, the TED Fellows Program, and the TED Open Translation Project. With this philosophy in mind, and with the intention of supporting teachers and sparking the curiosity of learners around the world, TED-Ed was launched in 2012.

TED-Ed is TED’s youth and education initiative. TED-Ed’s mission is to spark and celebrate the ideas of teachers and students around the world. Everything we do supports learning — from producing a growing library of original animated videos , to providing an international platform for teachers to create their own interactive lessons, to helping curious students around the globe bring TED to their schools and gain presentation literacy skills, to celebrating innovative leadership within TED-Ed’s global network of over 250,000 teachers. TED-Ed has grown from an idea worth spreading into an award-winning education platform that serves millions of teachers and students around the world every week.

The scientific literature is becoming more complex

A recent paper by Cordero et al. (2016) looked at the biological scientific literature in 1993, 2003, and 2013. They found that the average publishable unit (APU) almost doubled in twenty years. There were substantial increases in the number of tables & figures and the number of panels per figure. The number of pages increased as did the number of references and the number of authors.

I agree that papers are becoming more complex and more difficult to understand for the average scientist; especially those outside of the specific field of study. The authors of this study point out a number of problems with this increase. I'd like to highlight one of them.

With respect to the number of authors, they say,

Concomitantly, with the increase in information density we note a significant increase in the number of authors per article that also correlated with the average IF of the journal. Since the famous de Solla Price predictions [38], trends toward an increasing number of authors per publication have been widely documented [23,39–44]. Such a trend of increasing collaboration could be explained by the causes suggested above for the growth of information density. The costs associated with the generation of cutting-edge scientific information, the funding restrictions, and the associated risks in scientific publishing in a “winner-take-all” reward system [45] may motivate scientists to team-up, pool resources and fractionate the risks through co-authoring. Also, the increasing complexity of scientific research has resulted in greater specialization of scientists [46], which in turn suggests that the inclusion of additional techniques requires the recruitment of additional investigators to provide that data and thus serve as co-authors. This trend could have both positive and negative consequences. Increased interaction between scientists in diverse fields could translate into greater communication and the possibility for advances at the interfaces of different disciplines. On the other hand, an increase in the number of authors, some of whom bring highly specialized knowledge, could result in reduced supervision of larger groups, and less responsibility per author for the final product and reduced integration of data.

I think the major consequence is the lack of responsibility of individual authors in a multi-author study. With increased specialization, there are fewer and fewer authors who see the big picture and who are capable of integrating the results from several subspecialties. The fact that the studies include work from several highly specialized techniques that only a few people understand also makes it harder for the average reader to evaluate the paper.

It's likely, in my opinion, that many of the authors on the paper don't fully understand the techniques being used by their colleagues. This is a big change from the science I grew up with.

Cordero et al. are worried about the possibility of fraud.

The growth in authors brings with it the concerns about the possibility that as more authors are added, there is an increased likelihood of some individuals with reduced integrity and capable of misconduct joining the group. In this regard, we note that the inclusion of one individual who has been accused of misconduct in numerous studies has led to dozens of retractions of scientific publications.

This is a very real danger but I think that outright fraud is not a significant worry. What concerns me more is the tendency to gloss over the limitations and possible misinterpretations of complex data analyses. The specialist who performs these analyses probably doesn't intend to misrepresent or exaggerate the significance of the result; it's just that they have become so used to using a particular technique (i.e. a software package) that they have forgotten those limitations. They don't communicate them to their colleagues who, because they don't understand the technique, don't realize there's a problem.

Cordero et al. summarize their results ....

In summary, our study documents a change in the literature of the biological sciences toward publications with more data over time. The causes for these trends are complex and probably include increasing experimental options and changes to the culture of science. At first glance, this data could be interpreted as a cultural change opposite to data fragmentation practices. However, it is also possible that an increase in publication density can still occur over a ‘salami slicing’ culture if the publication unit to be segregated is larger to begin with, as the result of technological improvements and increasing numbers of scientific authors. The benefits and debits of this trend for the scientific process are uncertain at this time but it is clear that there have been major changes to the nature of scientific publications in the past two decades that are likely to have major repercussions in all aspects of the scientific enterprise.

I think they're on to something.

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Cordero, R. J., de León-Rodriguez, C. M., Alvarado-Torres, J. K., Rodriguez, A. R., and Casadevall, A. (2016). Life Science’s Average Publishable Unit (APU) Has Increased over the Past Two Decades. PloS one, 11(6), e0156983. [doi: 10.1371/journal.pone.0156983]

How to read the scientific literature?

Science addressed the problem of How to (seriously) read a scientific paper by asking a group of Ph.D. students, post-docs, and scientists how they read the scientific literature. None of the answers will surprise you. The general theme is that you read the abstract to see if the work is relevant then skim the figures and the conclusions before buckling down to slog through the entire paper.

None of the respondents address the most serious problems such as trying to figure out what the researchers actually did while not having a clue how they did it. Nor do they address the serious issue of misleading conclusions and faulty logic.

I asked on Facebook whether we could teach undergraduates to read the primary scientific literature. I'm skeptical since I believe it takes a great deal of experience to be able to profitably read recent scientific papers and it takes a great deal of knowledge of fundamental concepts and principles. We know from experience that many professional scientists can be taken in by papers that are published in the scientific literature. Arseniclife is one example and the ENCODE papers published in September 2012 are another. If professional scientists can be fooled, how are we going to teach undergraduates to be skeptical?

Do Intelligent Design Creationists still think junk DNA refutes ID?

I'm curious about whether Intelligent Design Creationists still think their prediction about junk DNA has been confirmed.

Here's what Stephen Meyer wrote in Darwin's Doubt (p. 400).

The noncoding regions of the genome were assumed to be nonfunctional detritus of the trial-and-error mutational process—the same process that produced the functional code in the genome. As a result, these noncoding regions were deemed "junk DNA," including by no less a scientific luminary than Francis Crick.

Because intelligent design asserts that an intelligent cause produced the genome, design advocates have long predicted that most of the nonprotein-coding sequences in the genome should perform some biological function, even if they do not direct protein synthesis. Design theorists do not deny that mutational processes might have degraded some previously functional DNA, but we have predicted that the functional DNA (the signal) should dwarf the nonfunctional DNA (the noise), and not the reverse. As William Dembski, a leading design proponent, predicted in 1998, "On an evolutionary view we expect a lot of useless DNA. If, on the other hand, organisms are designed, we DNA, as much as possible, to exhibit function."

I'm trying to write about this in my book and I want to be as fair as possible.

Do most ID proponents still believe this is an important prediction from ID theory?

Do most ID proponents still think that most of the human genome is functional?

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New Trends in Evolutionary Biology: The Program

I'm going to London next November to attend The Royal Society conference on New trends in evolutionary biology: biological, philosophical and social science perspectives. This is where all the scientists who want to change evolution will be gathering to spout their claims.

Developments in evolutionary biology and adjacent fields have produced calls for revision of the standard theory of evolution, although the issues involved remain hotly contested. This meeting will present these developments and arguments in a form that will encourage cross-disciplinary discussion and, in particular, involve the humanities and social sciences in order to provide further analytical perspectives and explore the social and philosophical implications.

The program has been published. Here's the list of speakers ...

Gerd B. Müller
The extended evolutionary synthesis

Douglas Futuyma
The evolutionary synthesis today: extend or amend?

Sonia Sultan
Re-conceiving the genotype: developmental plasticity

Russell Lande
Evolution of phenotypic plasticity

Tobias Uller
Heredity and evolutionary theory

John Dupré
The ontology of evolutionary process

Paul Brakefield
Can the way development works bias the path taken by evolution?

Kevin Laland
Niche construction

James Shapiro
Biological action in read-write genome evolution

Paul Griffiths
Genetics/epigenetics in development/evolution

Eva Jablonka
Epigenetic inheritance

Greg Hurst
Symbionts in evolution

Denis Noble
Evolution viewed from medicine and physiology

Andy Gardner
Anthropomorphism in evolutionary biology

Sir Patrick Bateson
The active role of the organism in evolution

Karola Stotz
Developmental niche construction

Tim Lewens
A science of human nature

Agustín Fuentes
Human niche, human behaviour, human nature

Andrew Whiten
The second inheritance system: the extension of biology through culture

Susan Antón
Human evolution, niche construction and plasticity

Melinda Zeder
Domestication as a model system for evolutionary biology

I didn't know that Paul Griffiths and Karola Stotz were going. It's a bit surprising that they would associate with some of these views. I'm glad that Douglas Futuyma will be there to represent the voice of reason. He seems to be one of the few speakers who understands modern evolutionary theory.

There are still a few spots available, according to the organizers. Sign up quickly.

The meeting is at Carlton House Terrace, which is just a few blocks from Trafalger Square and a short walk down The Mall to Buckingham Palace where the Corgis live.

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What does a person's genome reveal about their ethnicity and their appearance?

If you knew the complete genome sequence of someone could you tell where they came from and their ethnic background (race)? The answer is confusing according to Siddhartha Mukherjee writing in his latest book "The Gene: an intimate history." The answer appears to be "yes" but then Mukherjee denies that knowing where someone came from tells us anything about their genome or their phenotype. He writes the following on page 342.

... the genetic diversity within any racial group dominates the diversity between racial groups. This degree of intraracial variability makes "race" a poor surrogate for nearly any feature: in a genetic sense, an African man from Nigeria is so "different" from another man from Namibia that it makes little sense the lump them into the same category.

For race and genetics, then, the genome is strictly a one-way street. You can use the genome to predict where X or Y came from. But knowing where A or B came from, you can predict little about the person's genome. Or: every genome carries a signature of an individual's ancestry—but an individual's racial ancestry predicts little about the person's genome. You can sequence DNA from an African-American man and conclude that his ancestors came from Sierra Leone or Nigeria. But if you encounter a man whose great-grandparents came from Nigeria or Sierra Leone, you can say little about the features of this particular man. The geneticist goes home happy; the racist returns empty-handed.

I find this view very strange. Imagine that you were an anthropologist who was an expert on humans and human evolution. Imagine you were told that there's a woman in the next room whose eight great-grandparents all came from Japan. According to Mukherjee, such a scientist could not predict anything about the features of that woman. Does that make any sense?

I suspect this is just a convoluted way of reconciling science with political correctness.

Steven Monroe Lipkin has a different view. He's a medical geneticist who recently published a book with Jon R. Luoma titled "The Age of Genomes: tales from the front lines of genetic medicine." Here's how they explain it on page 6.

Many ethnic groups carry distinct signatures. For example, from a genome sequence you can usually tell if an individual is African-American, Caucasian, Asian, Satnami, or Ashkenazi Jew, even if you've never laid eyes on the patient. A well-regarded research scientist whom I had never met made his genome sequence publically available as part of a research study. I remember scrolling through his genetic variant files and trying, more successfully than I had expected, to guess what he would look like before I peeked at his webpage photo. The personal genome is more than skin deep.

This makes more sense to me. If you know what you look for—and Simon Monroe certainly does—then many of the features of a particular person can be deduced from their genome sequence. And if you know which variants are more common in certain ethnic groups then you can certainly predict what a person might look like just by knowing where their ancestors came from.

What's wrong with that?

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Can scientists describe what they're doing to a fifth grader?

I'm working on a review of "The Gene" by Siddhartha Mukherjee. It raises a huge number of issues about science writing and the conflict between producing a bestseller and educating the public about science.

As part of the research for that blog post I've been reading all the reviews of his book and I came across an interview with Mukherjee on the Smithsonian website [Siddhartha Mukherjee Follows Up Biography of Cancer With “An Intimate History” of Genetics].

Here's an interesting answer to an important question ...