Pervasive Transcription

"Pervasive transcription" refers to the idea that a large percentage of the DNA in mammalian genomes is transcribed. The idea became popular with the publication of the ENCODE results back in 2007 (Birney et al. 2007). Their results indicated that at least 93% of the human genome was transcribed at one time or another or in one tissue or another.

The result suggests that most of the genome consists of functional DNA. This pleases those who are opposed to the concept of junk DNA and it delights those who think that non-coding RNAs are going to radically change our concept of biochemistry and molecular biology. The result also pleased the creationists who were quick to point out that junk DNA is a myth [Junk & Jonathan: Part 6—Chapter 3, Most DNA Is Transcribed into RNA].

THEME:
Transcription
The original ENCODE paper used several different technologies to arrive at their conclusion. Different experimental protocols gave different results and there wasn't always complete overlap when it came to identifying transcribed regions of the genome. Nevertheless, the combination of results from three technologies gave the maximum value for the amount of DNA that was transcribed (93%). That's pervasive transcription.

The implication was that most of our genome is functional because it is transcribed.¹ The conclusion was immediately challenged on theoretical grounds. According to our understanding of transcription, it is expected that RNA polymerase will bind accidentally at thousands of sites in the gnome and the probability of initiating the occasional transcript is significant [How RNA Polymerase Binds to DNA]. Genes make up about 30% of our genome and we expect that this fraction will be frequently transcribed. The remainder is transcribed at a very low rate that's easily detectable using modern technology. That could easily be junk RNA [How to Frame a Null Hypothesis] [How to Evaluate Genome Level Transcription Papers].

There were also challenges on technical grounds; notably a widely-discussed paper by van Bakel et al, 2010) from the labs of Ben Blencowe and Tim Hughes here in Toronto. That paper claimed that some of the experiments performed by the ENCODE group were prone to false positives [see Junk RNA or Imaginary RNA?]. They concluded,

We conclude that, while there are bona fide new intergenic transcripts, their number and abundance is generally low in comparison to known genes, and the genome is not as pervasively transcribed as previously reported.

The technical details of this dispute are beyond the level of this blog and, quite frankly, beyond me as well since I don't have any direct experience with these technologies. But let's not forget that aside from the dispute over the validity of the results, there is also a dispute over the interpretation.

As you might imagine, the pro-RNA, anti-junk, proponents fought back hard led by their chief, John Mattick, and Mark Gerstein (Clark et al., 2011). The focus of the counter-attack is on the validity of the results published by the Toronto group. Here's what Clark et al. (2011) conclude after their re-evaluation of the ENCODE results.

A close examination of the issues and conclusions raised by van Bakel et al. reveals the need for several corrections. First, their results are atypical and generate PR curves that are not observed with other reported tiling array data sets. Second, characterization of the transcriptomes of specific cell/tissue types using limited sampling approaches results in a limited and skewed view of the complexity of the transcriptome. Third, any estimate of the pervasiveness of transcription requires inclusion of all data sources, and less than exhaustive analyses can only provide lower bounds for transcriptional complexity. Although van Bakel et al. did not venture an estimate of the proportion of the genome expressed as primary transcripts, we agree with them that “given sufficient sequencing depth the whole genome may appear as transcripts” [2].

There is already a wide and rapidly expanding body of literature demonstrating intricate and dynamic transcript expression patterns, evolutionary conservation of promoters, transcript sequences and splice sites, and functional roles of “dark matter” transcripts [39]. In any case, the fact that their expression can be detected by independent techniques demonstrates their existence and the reality of the pervasive transcription of the genome.

The same issue of PLoS Biology contained a response from the Toronto group (van Bakel et al. 2011). They do not dispute the fact that much of the genome is transcribed since genes (exons + introns) make up a substantial portion and since cryptic (accidental) transcription is well-known. Instead, the Toronto group focuses on the abundance of transcripts from extra-genic regions and its significance.

We acknowledge that the phrase quoted by Clark et al. in our Author Summary should have read “stably transcribed”, or some equivalent, rather than simply “transcribed”. But this does not change the fact that we strongly disagree with the fundamental argument put forward by Clark et al., which is that the genomic area corresponding to transcripts is more important than their relative abundance. This viewpoint makes little sense to us. Given the various sources of extraneous sequence reads, both biological and laboratory-derived (see below), it is expected that with sufficient sequencing depth the entire genome would eventually be encompassed by reads. Our statement that “the genome is not as not as pervasively transcribed as previously reported” stems from the fact that our observations relate to the relative quantity of material detected.

Of course, some rare transcripts (and/or rare transcription) are functional, and low-level transcription may also provide a pool of material for evolutionary tinkering. But given that known mechanisms—in particular, imperfections in termination (see below)—can explain the presence of low-level random (and many non-random) transcripts, we believe the burden of proof is to show that such transcripts are indeed functional, rather than to disprove their putative functionality.

I'm with my colleagues on this one. It's not important that some part of the genome may be transcribed once every day or so. That's pretty much what you might expect from a sloppy mechanism—and let's be very clear about this, gene expression is sloppy.

You can't make grandiose claims about functionality based on such low levels of transcription. (Assuming the data turns out to be correct and there really is pervasive low-level transcription of the entire genome.)

This is a genuine scientific dispute waged on two levels: (1) are the experimental results correct? and (2) is the interpretation correct? I'm delighted to see these challenges to "dark matter" hyperbole and the ridiculous notion that most of our genome is functional. For the better part of a decade, Mattick and his ilk had free rein in the scientific literature [How Much Junk in the Human Genome?] [Greg Laden Gets Suckered by John Mattick].

We need to focus on re-educating the current generation of scientists so they will understand basic principles and concepts of biochemistry. The mere presence of an occasional transcript is not evidence of functionality and the papers that made that claim should never have gotten past reviewers.

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1. Not just an "implication" since in many papers that conclusion is explicitly stated.

Clark, M.B., Amaral, P.P., Schlesinger, F.J., Dinger, M.E., Taft, R.J., Rinn, J.L., Ponting, C.P., Stadler, P.F., Morris, K.V., Morillon, A., Rozowsky, J.S., Gerstein, M.B., Wahlestedt, C., Hayashizaki, Y., Carninci, P., Gingeras, T.R., and Mattick, J.S. (2011) The Reality of Pervasive Transcription. PLoS Biol 9(7): e1000625. [doi: 10.1371/journal.pbio.1000625].

Birney, E., Stamatoyannopoulos, J.A. et al. (2007) Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447:799-816. [doi:10.1038/nature05874]

van Bakel, H., Nislow, C., Blencowe, B. and Hughes, T. (2010) Most "Dark Matter" Transcripts Are Associated With Known Genes. PLoS Biology 8: e1000371 [doi:10.1371/journal.pbio.1000371]

van Bakel, H., Nislow, C., Blencowe, B.J., and Hughes, T.R.. (2011) Response to "the reality of pervasive transcription". PLoS Biol 9(7): e1001102. [doi:10.1371/journal.pbio.1001102]

Don Johnson

Don Johnson has written a book that I'm probably going to have to buy (and read) if I ever hope to understand Intelligent Design Creationism.

Who is Don Johnson? Here's what it said on Uncommon Descent a few months ago [Why one scientist checked out of Darwinism].

The author worked for ten years as a Senior Research Scientist in the medical and scientific instrument field. The complexity of life came to the forefront during continued research, especially when his research group was involved with recombinant DNA during the late 1970′s. … After several years as an independent consultant in laboratory automation an other computer fields, he began a 20-year career in university teaching, interrupted briefly to earn a second Ph.D. in Computer and information Sciences from the University of Minnesota.Over time, the author began to doubt the natural explanations that had been so ingrained. It was science, and not his religion, that caused his disbelief in the explanatory powers of nature in a number of key areas including the origin and fine-tuning of mass and energy, the origin of life with its complex information content, and the increase in complexity in living organisms. This realization was not achieved easily, as he had to admit that he had been duped into believing concepts that were scientifically unfounded. The fantastic leaps of faith required to accept the natural causes in these areas demand a scientific response to the scientific-sounding concepts that in fact have no known scientific basis.”

Sounds like a typical run-of-the-mill creationist. He has several of the common characteristics of Intelligent Design Creationist proponents: (1) religion, (2) a background in engineering and/or computer science, (3) no obvious expertise in evolutionary biology, (4) multiple Ph.D.s. I'm really intrigued by the fact that so many IDiots have more than one Ph.D. because I hang out with real scientists all the time and none of them have ever felt the need to be a graduate student more than once in their lives.

Why is this book interesting? Well, for one thing, there's this excerpt from Don Johnson's website [Science Integrity (sic)].

"In the absolute sense, one cannot rule out design of anything since a designer could design something to appear as if it weren’t designed. For example, one may not be able to prove an ordinary-looking rock hadn’t been designed to look as if it were the result of natural processes. The 'necessity of design,' however, is falsifiable. To do so, merely prove that known natural processes can be demonstrated (as opposed to merely speculated from unknown science) to produce: the fine-tuning empirically detectable in the Universe, life from non-life (including the information and its processing systems), the vast diversity of morphology suddenly appearing in the Cambrian era, and the increasing complexity moving up the tree of life (with the accompanying information increase and irreducibly complex systems). If those can be demonstrated with known science, the 'necessity of design' will have been falsified in line with using Occam’s Razor principles for determining the most reasonable scenarios. If the 'necessity of design' is falsified, some may continue to BELIEVE in design, but ID would no longer be appropriate as science." (p. 92)

Isn't that cool? It absolves Intelligent Design Creationism from any burden of proof since things are said to be designed unless you can prove the negative. If real scientists can't prove beyond a shadow of doubt that life came from non-life then design can't be falsified and must be true.

It doesn't matter how many times we can demonstrate that some things evolved, that still doesn't demonstrate that evolution is true. We can only do that if we fill in the most famous gaps existing in the early 21st century. That's the only way to falsify Intelligent Design Creationism. One of the ironies is that there's really no explanation to falsify other than "it has to be designed." This is quite clever. By refusing to offer an explanation of how life began, or how animal diversity arose 500 million years ago, the IDiots insulate themselves from the same criticism they level at evolutionary explanations.

I was prompted to write about Don Johnson after reading another except form his book. An excerpt that particularly impressed Denyse O'Leary. She posted this on uncommon Descent: What will be the next time and money-wasting error Darwinism leads scientists into?¹].

Researchers are discovering that what had been dismissed as evolution’s relics are actually vital to life. What used to be considered evidence for neo-Darwinism gene-formation mechanism can no longer be use as such evidence. In this case, neo-Darwinism has been a proven science inhibitor as it postponed serious investigation of the non-coding DNA within the genome, which was “one of the biggest mistakes in the history of molecular biology” [John Mattick, BioEssays, 2003 930-939].” This is reminiscent of the classification of 86 (later expanded to 180) human organs as “vestigial” that Robert Wiedersheim (1893) believed “lost their original physiological significance.” in that they were vestiges of evolution. Functions have since been discovered for all 180 organs that were thought to be vestigial, including the wings of flightless birds, the appendix, and the ear muscles of humans.”

This is more than a little confusing since the statement is wrong about the scientific facts. But even more interesting is the implication that the presence of junk DNA and/or vestigial organs is a threat to Intelligent Design Creationism. What kind of threat? Here's how Denyse O'Leary describes it.

The explicit reason for both the junk DNA error and the vestigial organs error was the need to find evidence for Darwinism in the form of stuff in life forms that doesn’t work. Without that need, these errors would not have been made.

Setting aside the lie about these being errors, let's try and see why this is such a big deal for the IDiots.

As we saw from the first quotation, everything is assumed to be designed unless we can prove that the "big four" have a purely natural explanation. So why would the IDiots be concerned about some little fish like junk DNA and vestigial organs? If a large part of our genome turns out to be junk and at least one organ turns out the be truly vestigial does this mean Intelligent Design Creationism is falsified?

Not bloody likely. The real issue here is not whether Intelligent Design Creationism has a better explanation for the organization of the human genome. It doesn't. The real issue is that these topics can be used to discredit science and evolutionary biologists. (Hence, the title of the articles.)

As I point out in class, this is the 21st century and everyone needs to have science on their side. This includes the IDiots and the climate change deniers. They can't just take the position that they are opposed to science—even though they are. That strategy hasn't worked since Darwin.

So, what do you do when the science seems to refute your claims? You resort to the only option available, attack the science and discredit the messengers. That's why we see so many stories about evil "Darwinists" and that's why people like Denyse O'Leary pounce on any opportunity to point out errors and mistakes in the scientific literature. And if you can't find any real mistakes you can always just make them up.

Intelligent Design Creationism is not about proposing alternative explanations. It's about attacking evolution and evolutionary biologists. Don't believe me? Just look at the books and the blogs. Something like 99.9% of what's written by the IDiots is attacking evolution and science. When's the last time you ever saw anything explained by Intelligent Design Creationism?

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1. Aren't you glad that Denyse O'Leary is a professional journalist? Can you imagine what her titles migh look like if she didn't have professional training?

Shame on Canadian Blood Services

Canadian Blood Services is a non-profit organization charged with the responsibility of collecting and managing the blood supply for Canadians (except Québécois). They have a website called What's Your Type: Find out what your blood type says about you ...

Here are the answers.

• Type A: So, you’re an A. You already know that having type A blood suggests that you are reliable, a team player and may benefit from a vegetarian diet*. Did you also know that anthropologists believe that type A blood originated in Asia or the middle east between 25,000 and 15,000 BC?


• Type B: So, you’re a B. You already know that having type B blood suggests that you are independent, a self-starter and may benefit from a wholesome well-balanced diet*. Did you also know that anthropologists believe that type B blood appeared between 15,000 and 10,000 BC in the Himalayas?


• Type AB: So, you’re an AB. You already know that having type AB blood suggests that you are organized, friendly and may enjoy a vegetarian or wholesome well-balanced diet*. Did you also know that anthropologists believe that type AB blood did not originate until 900-1000 years ago and came into existence when eastern Mongolian invaders overran the last of European civilization?


• Type O: So, you’re an O. You already know that having type O blood suggests that you might be competitive, goal oriented and a real meat eater*. Did you also know that anthropologists believe that type O is the oldest and most common blood type, originating in Southern Africa?

I bet there's lots of stuff there that you didn't know. I was particularly intrigued by the genetic data. Did you know that humans were originally Type O—the null allele? Only later did mutations arise that created the active N-acetylaminogalactosyltransferase enzyme (Type A).¹


Theme

ABO Blood TypesI was shocked to learn that Mongolians overran the last of European civilization in 1000 AD. I'm a bit of a history buff, especially European history, and this nasty little fact completely escaped my notice. How come the citizens of Western Europe didn't notice that they were overrrun by Mongolians? And how come the history books say the main Mongolian invasions were in about 1220 AD?

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1. All knowledgeable scientists agree that this is the primitive allle, present in all primates. Subsequent mutations created the null allele (O) and the B allele, which is a modified version of the wild-type allele. I assume that Canadian Blood Services must be in possession of very recent information that overthrows all those previous scientific papers.

Dennis Markuze Gets on TV

Problem is, Dennis Markuze is never identified by name. There are other inaccuracies in the news report but at least something is being done (at last) [see Montreal Police: Take "Mabus" death threats seriously]. It's beginning to look like Dennis Markuze may be shut down. I hope his mother wakes up and realizes that her son is deeply disturbed.

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Hat Tip: Greg Laden

Why Reasonable People Should Not Debate William Lane Craig

William Lane Craig is promoting his Reasonable Faith Tour of the UK this October. He would like to debate atheists during his visit to the United Kingdom because it's good publicity and a good revenue generator [see william lane craig resources if you want to contribute].

So far, he hasn't been able to sucker induce any prominent atheist to engage him except for Polly Toynbee, President of the British Humanist Association. However, she recently withdrew from her debate after realizing what kind of things go on during a debate with William Lane Craig British Humanists take to the Bunkers]. Good for her.

The President of the British Humanist Association has pulled out of debating renowned Christian philosopher William Lane Craig. Polly Toynbee, Guardian columnist and prominent critic of religion, readily agreed in April to debate Craig on the Existence of God but withdrew her involvement last week saying "I hadn't realised the nature of Mr Lane Craig's debating style, and having now looked at his previous performances, this is not my kind of forum".

What could possibly have convinced her that this was a set-up—one where Craig has no intention of actually addressing the issue? Well, the data are readily available, even on YouTube.

I'm going to show you a YouTube video made by Craig's supporters. It's a clip from his debate with Christopher Hitchens at Biola University in 2009. Ignore the text comments—they're simply an extreme version of the debating technique that Craig employs.

Note that Christopher Hitchens does a perfectly fine job of defining his version of atheism—it happens to be the same as mine. Hitchens has not found any convincing evidence that gods exist so he doesn't believe in them. He also doesn't believe in Santa Claus for the same reason, he's an a-santaclausian. Watch how Craig then present Hitchens with a false trichotomy. He demands that Hitchens choose between three beliefs, none of which correspond to what Hitchens has just described. Finally, Craig gets Hitchens to say that there are no gods. Then he pounces, demanding to know how Hitchens can prove a negative.

This quickly morphs into a discussion of whether absence of evidence is evidence of absence. Hitchens, to his credit, does not view that as an open and shut proposition since, as we all know, absence of evidence is, indeed, part of the reason for not believing in gods. But to a slick apologist like Craig, that can be a devestating admission.

The point is that William Lane Craig is a typical Christian apologist who would prefer to focus on rhetoric than on truth. Most atheists will find this method of debate frustrating and aggravating. They have to be constantly on their guard against a "gotcha" moment, knowing that Craig will pounce whenever he gets a chance.



Here's another example of the style of argument used by Craig. You can see the trick. He simply refuses to accept the analogy being made and prefers to twist it around to make his point. Listen to what he says about "evidence" that there is no Santa and that there's no teapot. Don't we have the same kind of "evidence" for the non-existence of gods? Of course we do, but it's not "evidence" of nonexistence of Santa and teapots—it's simply evidence that particular claims about Santa and teapots have not been proven. Lots of claims about gods fall into that category as well.



Who wants to spend half an hour debating the meaning of atheism or whether we can prove the non-existence of teapots in space? The real issue is whether gods—or in Craig's case the Christian gods—actually exist?

Here's another example of Craig's style of argument. Who in their right mind wants to engage in this sort of debate?

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What Drives Darwinian Scientists to their Fury

In spite of what they promised earlier, the Evolution News & Views (sic) blog does not allow comments. That's why I'm posting a quotation from today's piece by David Klinghoffer: What Drives Darwinian Scientists to their Fury

You may have wondered why Darwinists in academia get so worked up about intelligent design. Reading what they write about our scientists and their work, you picture these guys turning red and sweating a lot. Alternatively, they try to mask their rage by getting all sarcastic and pseudo-witty -- a man of mature age like Larry Moran, for example, calling other adults "IDiots."

I get "worked up" about Intelligent Design Creationism because it's anti-science and one of my issues is the promotion of scientific literacy (and rationalism). It's wrong to describe my feelings as "rage." My feelings about Intelligent Design Creationists are more akin to my feelings about people who believe they were abducted by aliens, or people who believe in bigfoot. "Bemused," "flabbergasted," and "sad" are more appropriate terms to describe how I react when I read the name "David Klinghoffer."

I'm very picky about who I call an IDiot. It's restricted to that subset of adults (and those who wish they were adults) who believe in Intelligent Design Creationism. It's a useful term, just as the terms "Darwinist" and "pompous professor" seem to be useful to David Klinghoffer [see hypocrisy].

A guy like Professor Pompous or any of the better known Darwinian-scientist writers you can think of aren't driven to their fury directly by the scholarly work of Michael Behe, Doug Axe or Stephen Meyer, but rather indirectly every time a student brings it up in class. Every year a new cohort of young people comes through the lecture hall and some number of them -- probably a growing number -- have been exposed somewhere to ID's critique and alternative to neo-Darwinism. Every time a student puts her hand up and politely asks something along the lines of, "But what about irreducible complexity?" it throws the class discussion down a totally different corridor of the mind than the professor meant it to go.

I hate to be the bearer of bad news, David, but the vast majority of students in my classes have never heard of Intelligent Design Creationism. In my Fall course we discuss Jonathan Wells' book Icons of Evolution as an example of anti-science writing but I have to explain to the class what Intelligent Design Creationism is all about. It never comes up in other classes.

In my own writings on the subject, I concentrate mostly on what the minor IDiots are writing on their blogs and on what the bigger names are saying in their books. That's why I've been spending so much time lately discussing Jonathan Wells' new book The Myth of Junk DNA. I've also written about Michael Behe, Stephan Meyer, and Doug Axe.

So, David, you are dead wrong about almost everything you write if it refers to me. I suspect it doesn't apply to most other professors who oppose the IDiots. We're not troubled—and certainly not "enraged"—by what students are saying. We prefer to make fun of the "big guns" but even those targets aren't much of an intellectual challenge.

Instead of constantly acting like a crybaby over perceived insults to your intelligence, why don't you try responding to the rational, scientific arguments we're making? You might learn something.

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You can buy the T-shirt at Endangered Outlaw.

Non-Allopathic (Non-Conventional) Therapies in Medical Practice

The College of Physicians and Surgeons of Ontario has produced a draft policy on Non-Allopathic (Non-Conventional) Therapies in Medical Practice. The document is flawed from the beginning because it gives credence and respectability to "alternative medicine," otherwise known as non-evidence based medicine or quackery.

The policy is designed to provide guidelines for physicians who are: (1) tempted to employ non-evidence based medicine, (2) tempted to condone non-evidence based medicine in situations where it might harm patients. We all recognize that front-line physicians face these issues all the time and they often find themselves in a position where they disagree with the choices their patients are making.

However, most physicians don't hesitate to tell you that you should stop smoking. They seem to enjoy lecturing you on the benefits of diet and exercise even when it's clear that a patient prefers a different lifestyle. Why should it be any different when a patient reveals that they are taking homeopathic concoctions or when they refuse to vaccinate their children. Don't physicians have a professional responsibility to inform their patients that they are making unwise decisions?

The draft policy address these issues but it does so in a way that's far too lenient toward quack medicine. To begin with, it defines allopathic medicine as,

Different operative terms have been adopted that were deemed to be value-neutral: ‘Allopathic medicine’ refers to traditional or conventional medicine (as taught in medical schools) and ‘non-allopathic therapies’ refer to complementary or alternative medicine.

This is idiotic. "Allopathic" medicine is NOT a value-neutral term. It's the term used by homoepathic quacks to describe medicine that uses drugs to treat patients. By adopting this terminology, the College of Physicians and Surgeons is playing right into the hands of the quacks.

Allopathic Medicine: refers to the type of treatment, diagnostic analysis and conceptualization of disease or ailment that is the primary focus of medical school curricula and which is generally provided in hospitals and specialty or primary care practice.

Non-Allopathic Therapies (Non-Conventional Therapies): refers to a broad range of procedures or treatments that are not commonly used in allopathic medicine; this includes those referred to as complementary or alternative. Non-allopathic therapies tend to differ from allopathic medicine in terms of diagnostic techniques, theories of illness and disease, and treatment paradigms. The categorization of specific therapies as non-allopathic is fluid: as clinical evidence regarding efficacy is accumulated, certain non-allopathic therapies may gain broad acceptance and thus be accepted in allopathic medicine.

I work in a medical school. The operative phase is "evidence-based medicine" and I suspect that's a term used in most medical schools in Ontario. That's what is taught in medical schools and hospitals and that's how you describe proper medicine.

The opposite of evidence-based medicine is "non-evidence-based treatment." Those are not "value-neutral" terms. They are something different—it's called "truth," and truth is not neutral. The College of Physicians and Surgeons needs to acquire some gumption and stand up for what's being taught in the medical schools and stand up for science. This draft policy is ridiculous, it announces that the College is abandoning science and evidence in favor of condoning quackery.

Here's how the draft policy would read if we substitute the true definitions.

Respect Patient Autonomy

Patients are entitled to make treatment decisions and to set health care goals that accord with their own wishes, values and beliefs. This includes decisions to pursue or to refuse evidence-based or non-evidence based therapies.

The College expects physicians to respect patients’ treatment goals and decisions, even those which physicians deem to be unfounded or unwise. In doing so, physicians should state their best professional opinion about the goal or decision, but must refrain from expressing non-clinical judgements.

Nothing has been lost by using "evidence-based" instead of "allopathic." Now, let's look at the meaning of this policy statement.

It's classic gobbledygook because it confuses "respect" with "responsibility." Physicians are not obliged to "respect" parents who refuse to give their child a life-saving blood transfusion. They aren't obliged to "respect" parents who deny their children vaccinations. They certainly don't "respect" parents who abuse their children. And I've never encountered a physician who "respects" smokers and drug users, have you?

Lots of patients don't earn respect and don't deserve it.

Read the guideline carefully as I amended it. If they were adhered to, then no physician could possibly recommend non-evidence based therapies since that would conflict with their professional opinion (or, at least it should). But later on we read,

Providing Non-Allopathic Therapies

When providing non-allopathic therapies, physicians are expected to demonstrate the same commitment to clinical excellence and ethical practice, as they would when providing allopathic care.

What the heck is that all about? The policy should read ...

Any physician who provides non-evidence based therapies (especially for a fee) will be subject to charges of professional misconduct and may lose his/her license to practice medicine in Ontario.

That's the only sensible policy that's consistent with what's written elsewhere in the document. You simply can't provide non-evidence-based therapies while maintaining "a commitment to clinical excellence and ethical practice." That's oxymoronic.

The Committee for the Advancement of Scientific Skepticism (CASS) is very interested in this issue. Read what Michael Kruse has to say on his blog Skeptic North: Ontario Doctors Given Green Light to Promote Quackery.

I would not be writing this if I thought we could do nothing to oppose and change the viewpoint of the CPSO. That is why CASS is calling on members of both the public and the medical field to read the policy and comment on it. There is strong representation in the current comments of supporters of alternative medicine and we do not want all of the feedback to be pro-pseudoscience. Please visit the CPSO policy site above and fill out the comment form available at the bottom of the page. The deadline for this consultation is September 1st 2011, so we must move quickly and let the CPSO know the safety of Ontarians depends upon sound medical opinion based on modern scientific evidence.

Please voice your opinion at Feedback: Non-Allopathic Therapies draft policy. Your response has to sent by email to ThirdPartyProcesses@cpso.on.ca. I have no idea how much censorship is applied to the responses they post—I suspect it's considerable so don't expect criticisms to appear on the website.

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Blown Out of the Water

Barry Arrington tries to convince us that Intelligent Design Creationism is scientific [The ID Hypothesis].

He writes about "complex specified information" (CSI) and "irreducible complexity" (IC). According to Barry Arrington ...

The answer is that the hypothesis is, in principle, falsifiable.

All it would take is even one instance of CSI or IC being observed to arise through chance or mechanical necessity or a combination of the two. Such an observation would blow the ID project out of the water.

We need a good definition of irreducible complexity. I like the one proposed by Michael Behe in Darwin's Black Box.

By irreducibly complex I mean a single system composed of several well-matched, interacting parts that contribute to the basic function, wherein the removal of any one of the parts causes the system to effectively cease functioning. An irreducibly complex system cannot be produced directly (that is, by continuously improving the initial function, which continues to work by the same mechanism) by slight, successive modifications of a precursor system, because any precursor to an irreducibly complex system that is missing a part is by definition nonfunctional.

If you read this carefully you'll see the catch. What Behe is saying is that a true irreducibly complex system can only arise by a single mechanism, namely one where the precursor has the same function. But the precursor can't, by definition, have the same function if it's missing some of the parts required in the final version. Thus, the only way for an irreducibly complex system to arise—by definition—is if it is created instantaneously as a complex system.

Behe is correct in his claim that such systems cannot evolve by any known mechanisms of evolution. Therefore, if a true irreducibly complex system exists, it cannot be as a result of evolution.

Let's look at an example. The citric acid cycle is a cycle of eight interacting enzymes that catalyze the oxidation of a 2-carbon molecule (an acetyl group) to CO₂. The pathway won't work if you remove any one of the enzymes. Thus, it seems on the surface to be an example of an irreducibly complex system.


However, we have a very good understanding of how the citric acid cycle evolved from simpler pathways. Most species of bacteria don't have a citric acid cycle. Instead they have two separate pathways, reductive and oxidative, that are similar to the left and right halves of the citric acid cycle respectively. We can easily construct a plausible scenario that joins the two branches to create a cycle. Does this mean that we have a good example of the evolution of an irreducibly complex system, thus blowing ID out of the water?


Of course it does. But the IDiots will never admit it. Instead, they note that such a pathway involves precursors that don't have the same function as the complete citric acid cycle; therefore, the citric acid cycle wasn't really irreducibly complex. In order to be irreducibly complex, sensu Behe, it has to be impossible for it to arise by evolution.

The bacterial flagellum is another example of a postulated irreducibly complex system. But we now have a pretty good idea of how it evolved. It evolved from a primitive type III secretion mechanism. Even if the IDiots were to accept this explanation—they don't—it would not refute irreducible complexity since the type III secretion mechanism has a different function. All this means is that the bacterial flagellum wasn't really irreducibly complex to begin with because irreducibly complex systems can't arise by natural means. You can't win.

Where does that leave us? It leaves us with a tautology: "... a series of self-reinforcing statements that cannot be disproved because the statements depend on the assumption that they are already correct." Irreducibly complex systems are, by definition, things that cannot evolve. If you postulate that something is irreducibly complex, then show later on how it evolved, it wasn't irreducibly complex to begin with. The definition is not falsifiable. The best that can happen is that the number of postulated irreducibly complex systems gets smaller and smaller until there are none left. The number is not likely to ever reach zero since the IDiots are really good at combing the scientific literature in order to discover something that almost nobody is working on.

This is not science. It is simply a rhetorical attack on the concept of evolution. That's what Intelligent Design Creationism is all about.¹

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1. Attacking evolution is scientific. After all, lots of us question certain aspects of evolution and still call ourselves scientists. It's the concept of Intelligent Design Creationism as an explanation for observed events that's not scientific. Intelligent Design Creationism never explains anything. You're never going to see an IDiot explain how the bacterial flagellum arose—not even in a creationist textbook.

Hubris

According to Wikipedia,

Hubris ... means extreme haughtiness, pride or arrogance. Hubris often indicates a loss of contact with reality and an overestimation of one's own competence or capabilities, especially when the person exhibiting it is in a position of power.

There are two possible examples in this video: (1) most knowledgeable molecular biologists and biochemists; or, (2) Jonathan Wells and his sycophants (e.g. Denyse O'Leary). You be the judge.



UPDATE: t_p_hamilton points out in the comments that the IDiots don't even get the structure of DNA correct in the video. Why are we not surprised?

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Scientific Errors and Fraud

I teach a course called "Scientific Controversies and Misconceptions." (You won't be surprised to learn that one of the main topics is evolution vs. creationism.) The most difficult part of the course is teaching students to be skeptical about the scientific literature. The reason why this is difficult is because the main focus is evidence based reasoning and science is an important way to gather reliable evidence. It's uncomfortable to have to mention that errors and fraud are not uncommon in the scientific literature.

I haven't figured out a way to teach students to read the scientific literature with the same skeptical perspective as those of us who have been doing it for decades. It seems as though this is a skill that must be learned through experience and can't be taught.

Almost every issue of Science has a retraction or a caution about a recently published paper. It's easy to get the impression that retractions are on the rise. Is this true? Yes, it is. Here's the data from PubMed Retractions. It shows a 15-fold increase in the number of retractions per publication.


This is quite alarming. Does it mean an increase in the number of papers containing significant errors? Does it mean an increase in scientific fraud and misconduct? Or, does it mean that the scientific community is becoming more active in removing suspect papers from the literature?

Here are articles from two bloggers who discuss these issues:

Orac at Respectful Insolence: Scientific fraud and journal article retractions.

Ed Silverman at Pharmalot: Retractions Of Scientific Studies Are Surging.

In both cases the focus is on the medical literature but the problem is not confined to medical journals. Personally, I think this is just the tip of the iceberg. For every article that's retracted there are a hundred articles that contains serious errors and misconceptions.

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Advice for Wine Lovers

Ralph de Amicis claims to be an expert on wine. He lives in the Napa Valley in California and runs tours of the vineyards with his wife, Lahni.

Apparently there's a belief among wine connoisseurs that the way you swirl your wine makes a difference in how you perceive the flavors. Here's how Ralph describes it [Wine Swirling, Left or Right? It Matters!],¹

When you swirl your wine to the left (counter clockwise) the scent you pick up is from the barrels over the grapes, what we call the spice shelf. When you swirl the wines to the right (clockwise) you pick up more flavors from the fruit.

I’ve shown this to clients in the tasting room and experimented with it myself and found it to be true, and especially noticeable with wines that have spent significant time in newer oak barrels.

Isn't that amazing? You may be asking yourself how the direction of swirling can make such a difference. Well, Ralph wondered the same thing but he has the background to answer such a question.

Now, as a master herbalist and aroma-therapist, and as someone who has lectured extensively on natural health, anatomy and physiology I know a thing or two about plants, and how people perceive them. So, based upon what I know about how living cells function, these are my insights.

With credentials like that I just had to read on ...

Like all living things wine cells have a magnetic polarity, just like humans and the Earth. The positive pole is more highly charged, just like the North Pole of the Earth, which is why there are Northern Lights in the Arctic Circle, but not Southern Lights in the Antarctic. This polarity tends to keep wine cells generally upright, spinning on their axis when they are being swirled. This magnetic action within a liquid is commonly demonstrated in laboratories. Because plant molecules are mostly liquid, when they form they are also subject to the electromagnetic forces that are a component of the rotation of the Earth. As a result, the pores on the surface of the molecules develop based on that rotation, like the shingles on a roof.

When you swirl the wine counter-clockwise you are pushing against the molecules nap, just like stroking the fur of a cat the wrong way, this dislodges anything on the surface. Since the flavor from the barrel is introduced fairly late in the wine's development it tends to concentrate in the outer layers. When you swirl the wine counter-clockwise it dislodges that flavor, while at the same, pushing liquid into the pores, inhibiting the fruit flavors that are inside the cell from coming out.

In comparison, when you swirl the wine clockwise the pressure of the surrounding fluid forces the fruit flavors out through the pores. It also pushes any flavors concentrated on the surface down onto the skin of the molecule. The fact that the wine is alive, electrically charged, and still changing is why this happens. So, when you swirl the wine to the right or left think of it as if you are stroking your favorite pet. Sometimes they like it rough, but mostly they like it smooth.

I assume that most readers of Sandwalk will find this as amusing as I did. But just in case you don't get the joke, here's what Derek Lowe has to say: In Which We Learn Lots About Wine Swirling.

Ralph de Amicis is a kook. Does mocking his ignorance serve a useful purpose? Some would argue that it's impolite to make fun of the opinions of others. I'm not one of those people. I think that scientific ignorance needs to be exposed and I'm happy to provide another website that will pop up in Google searches for "Ralph de Amicis." Maybe he will pay more attention to what he writes in the future so we don't have to point out his complete lack of understanding of science.

For no particular reason, here's a picture of aurora australis (Southern lights) from space [Aurora australis (southern lights)]. It's just simple physics.

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1. For extra amusement, you might want to read Followup Swirling Article in which Ralph de Amicis responds to those who criticized his first article.

Hat Tip: Chad Orzel: The Stupidest Thing You'll Read Today

Photo Credits: (top) Amicis Tours Blog, (bottom) Wine Tour in the Napa Valley

Junk & Jonathan: Part 9—Chapter 6

This is part 9 of my review of The Myth of Junk DNA. For a list of other postings on this topic see the links below. For other postings on junk DNA check out the links in Genomes & Junk DNA in the "theme box" below or in the sidebar under "Themes."

• Junk & Jonathan: Part 1—Getting the History Correct
• Junk & Jonathan: Part 2— What Did Biologists Really Say About Junk DNA?
• Junk & Jonathan: Part 3—The Preface: Preface
• Junk & Jonathan: Part 4—Chapter 1: The Controversy over Darwinian Evolution
• Junk & Jonathan: Part 5—Chapter 2: Junk DNA: The Last Icon of Evolution?
• Junk & Jonathan: Part 6—Chapter 3: Most DNA Is Transcribed into RNA
• Junk & Jonathan: Part 7—Chapter 4: Introns and the Splicing Code
• Junk & Jonathan: Part 8—Chapter 5: Pseudogenes—Not so Pseudo After All

Jumping Genes and Repetitive DNA
The title of Chapter 6 is "Jumping Genes and Repetitive DNA." Wells describes transposons as jumping genes and includes them in the category of "Repetitive Non-Protein-Coding DNA." This category makes up 50% of the genome, according to Wells. The breakdown is as follows. LINES 21%; SINES 13%; retroviral-like elements 8%; simple sequence repeats 5%; and DNA-only transposons 3%. These percentages are similar to those published in a wide variety of textbooks and scientific papers. [What's in Your Genome?] [Junk in your Genome: LINEs] [Junk in Your Genome: SINES]


Many LINES and SINES are Functional

Most of the transposons in the human genome are fragments or otherwise mutated versions of the original mobile elements. This is a good reason for assigning them to the junk DNA category. They are a form of pseudogene. What this means is that half of our genome is composed of defective transposons that can't "jump." This is non-functional DNA, otherwise known as "junk."

This conclusion is unacceptable to Jonathan Wells. In order to prove that junk DNA is a myth he must show that most of this DNA has a function. He begins with a section called "Many LINES and SINEs are functional.

Theme

Genomes
& Junk DNAThe first evidence for functionality comes from the data showing that most of the genome is transcribed—the main theme of Chapter 3. If most of these defective transposons are transcribed then it seems likely that they have a function. But the evidence for widespread transcription is not widely accepted and one of the main criticisms is that it's extremely difficult to tell which repeated sequences are actually transcribed and which ones just happen to be very similar to a family member that is transcribed. We know that active LINES and SINES have to be transcribed at some time and we know that many defective transposons will still be transcribed even if they are non-functional. The question is not whether any transposons are transcribed, it's whether all (or most) of them are. The answer is almost certainly that very few are transcribed on a regular basis. The pervasive transcription reported in some papers is most likely accidental transcription at a very low level or artifact.¹

Nishihara, H., Smit, A.F., and Okada, N. (2006) Functional noncoding sequences derived from SINEs in the mammalian genome. Genome Res. 16:864-874.

The first "function" paper Wells mentions is Nishihara et al. (2006). These workers characterized a new class of SINES in the human genome. They consist of a hybrid of 5S RNA and a tRNA (~300 bp). These SINES are found in most vertebrates (fish, amphibians, birds, mammals). There are about 1000 of these SINEs in the human genome and in 105 of them there seems to be more sequence conservation in the central portion of the sequence than expected from junk DNA. For example, the overall sequence similarity between human and zebrafish is about 59% in a stretch of 338 nucleotides. (The authors refer to these as regions that are "under strong selective constraint." That's a bit exaggerated.)

This section contains three other examples of sequence similarities in a small class of transposons. These are the only examples where he makes the case for widespread functionality of defective transposons.

Wells is happy to accept the arguments that sequence similarity is evidence of homology and also of function.² Several possible functions were ruled out in these studies but it's possible that they have some undiscovered function that results in moderate sequence conservation. If this turns out to be true it would mean that 0.01% of the genome should be moved from the "junk" category to the "functional" category.

Some Specific Functions of LINES and SINES

Wells then proceeds to a discussion of papers that demonstrate a function for individual transposon fragments. Before we look at those studies, it's worth keeping the big picture in mind. A typical eukaryotic genome has a million defective transposons and a dozen or so functional transposons that are still capable of jumping to new locations. If you examine the genomes of a dozen or so eukaryotes you can expect to find some examples where these bits of DNA have been co-opted to perform some new function. If you collect together all these examples from many different species then it looks like an impressive array of functional transposon sequences but impressions can be deceptive. It's still true that 99.9% of defective transposons are junk.

This section of the book consists of four pages of specific examples of presumed functional transposon-like sequences from mouse, rat, human, hamster, silkworm, fruit fly, and Arabidopsis (plant). There are 54 references to the scientific literature. Wells makes no attempt to asses the reliability of these studies, nor does he indicate whether the claims have been independently confirmed by other labs.

It's a typical ploy of creationists to focus on specific examples of unusual adaptations and ignore the context. In this case, all those specific individual examples don't amount to a hill of beans when compared to the vast majority of junk in eukaryotic genomes.

However, in fairness it's not just Jonathan Wells and the creationists who fail to see the forest for the trees. There are many scientists who also think that the evidence quoted by Wells is conclusive proof that junk DNA is a myth. Wells has no trouble finding such scientists whose views are expressed in the scientific literature.

Walters, R.D., Kugel, J.A., and Goodrich, J.A. (2009) Critical Review (sic): InvAluable Junk: The Cellular Impact and Function of Alu and B2 RNAs. Life 61:831-837.

Finding that Alu and B2 SINEs are transcribed, both as distinct RNA polymerase III transcripts and as part of RNA polymerase II transcripts, and that these SINE encoded RNAs indeed have biological functions has refuted the historical notion that SINEs are merely "junk DNA."

Endogenous Retroviruses

About 8% of your genome consists of endogenous retroviruses. Most of them are defective, usually because large parts of them have been deleted. Some are still capable of producing viable retrovirus, like HIV or hepatitis B. There are about 30,000 loci in your genome where endogenous retroviruses are located.

Endogenous retroviruses contain strong transcriptional promoters since they have to produce a lot of transcripts when they are induced. Some of these small promoter regions (called "LTRs") have become incorporated into the promoter regions of regular genes. What happened is that millions of years ago a retrovirus accidentally integrated into the genome near the 5′ end of a gene and when parts of the endogenous retrovirus were lost by deletion the remaining retroviral promoter region became active leading to enhanced transcription of the adjacent gene. Over time this piece of the retrovirus evolved to become an integral part of the regulation of the gene.

Wells describes several examples of such events in different mammals. He also describes a famous example where expression of a modified envelope protein from a defective endogenous retrovirus has taken on a role in the development of the mammalian placenta. Together, these examples of co-opted retroviral sequences account for about a dozen of the 30,000 copies in your genome. Naturally, this is assumed to be proof that none of the defective endogenous retroviruses are junk. That's the logic of creationists.

Francis Collins and Repetitive Elements

The last section of this chapter is pure rhetoric. Wells is upset because Francis Collins, a Christian, wrote the following in The Language of God (pages 135-136):

Even more compelling evidence for a common ancestor comes from the study of what are known as ancient repetitive elements (AREs). These arise from "jumping genes," which are capable of copying and inserting themselves in various other locations in the genome, usually without any functional consequences. Mammalian genomes are littered with such AREs, with roughly 45 percent of the human genome made up of such flotsam and jetsam. When one aligns sections of the human and mouse genomes, anchored by the appearance of gene counterparts that occur in the same order, one can usually also identify AREs in approximately the same location in these two genomes.

Some of these may have been lost in one species or the other, but many of them remain in a position that is most consistent with their having arrived in the genome of a common mammalian ancestor, and having been carried along ever since. Of course, some might argue that these are actually functional elements placed there by the Creator for a good reason, and our discounting them as "junk DNA" just betrays our current level of ignorance. And indeed, some small fraction of them may play important regulatory roles. But certain examples severely strain the credulity of that explanation. The process of transposition often damages the jumping gene. There are AREs throughout the human and mouse genomes that were truncated when they landed, removing any possibility of their functioning. In many cases, one can identify a decapitated and utterly defunct ARE in parallel positions in the human and mouse genome.

Wells is upset because this is a double-barreled attack on intelligent design. Not only does Collins describe these sequences as junk but he also uses them as evidence of common ancestry. This is one of the reason why creationists like Wells maintain that junk DNA is used to support evolution.

Wells says,

Collins's argument rests on the assumption that those repetitive elements ... are nonfunctional. Yet their similar position in the human and mouse genomes could mean that they are performing some function in both. Given the rate at which functions are being discovered, Collins's assumption seems foolhardy, and his argument could easily collapse in the face of new scientific discoveries.

As long as most of these repetitive elements remain non-functional they pose a serious problem for Intelligent Design Creationists. The IDiots have been wishing for evidence of function for 20 years but "wishing" isn't a very scientific argument. Given the rate at which functions are being discovered, it's going to be a long, long time before all those hundreds of thousands of repetitive elements are assigned a function (i.e. never!). The vast majority of them are junk and discovery of a few co-opted sequences isn't going to change that fact.

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1. As a general rule, Wells "forgets" to mention when one of his "facts" is disputed in the scientific literature. Like most creationists, he is delighted to quote any scientific studies that confirm his bias but he is somewhat more reluctant to quote papers that don't. In this case—pervasive transcription—the criticisms in the scientific literature are so well-known that he is forced to discuss them in Chapter 9.

2. This is a bit strange coming from someone who doesn't believe in evolution but logic has never been a strong point is Wells' writing. Note that Wells does not accept the corollary argument that lack of conservation implies lack of function.

Retrotransposons/Endogenous Retroviruses

 
RNA viruses are viruses that contain RNA instead of DNA. When the RNA molecule is injected into the cell it serves immediately as a template for translation. All RNA viruses have genes for making new viral particles and new copies of the RNA genome.

In eukaryotes, there is a large class of RNA viruses known as retroviruses. They have an obligatory stage where the RNA is reverse transcribed into DNA and the DNA is inserted into the genome where it resides as a provirus.

The structure of the integrated retrovirus genome is shown above. The ends of the viral genome contain long terminal repeat (LTR) sequences of several hundred base pairs. Both LTRs are arranged in the same orientation and the outside ends of each are flanked by short inverted repeats. The host DNA at the site of the insertion contains a short (5- bp) repeated sequence that is produced on integration as in transposons [Transposons: Part I].

There are three open reading frames (ORFs) in the retrovirus genome. One of these encodes a protein called gag that's involved in packaging the retroviral RNA in the virus particle. The gag protein is cleaved after translation to produce a number of individual proteins.

The pol ORF (gene?) encodes another polyprotein that is cleaved to produce reverse transcriptase, integrase, and a protease. The key enzymes are the reverse transcriptase, which copies RNA into double-stranded DNA, and integrase, which catalyzes the insertion of retroviral DNA into the host genome.

The third ORF encodes the coat proteins of the mature viral particle.

All eukaryotic genomes contain integrated retroviruses. Some are still capable of producing new viral particles under the right conditions while others have become defective over the course of millions of years of evolution. The defective retrorvirus genomes are a kind of pseudogene. Collectively they are known as endogenous retroviruses. [See ERV.] About 8% of mammalian genomes consists of defective retroviruses [What's in Your Genome?].

A common class of eukaryotic transposons is derived from retroviruses. These retrotranspsons contain the pol gene for reverse transcriptase and integrase and usually part of the gag gene that encodes a protein that interacts with DNA. When the transposon is transcribed the reverse transcriptase converts the RNA into double-stranded DNA and the integrase allows it to be inserted into the genome. Like many other transposons, these retrotransposons are examples of selfish DNA whose only "function" is to propagate itself within the genome [Transposons: Part II]. The yeast Ty element and the copia transposon of Drosophila melanogaster are the classic examples of retrotransposons.


The key features of these transposons are the pol gene and repeat sequences at the terminii. These repeats are usually called LTRs as in retroviruses but sometimes the have a different name. The yeast Ty repeats are called δ elements. Those features are all that are necessary for these genes to propagate in the genome.

Unlike the transposons described earlier, the retrotransposons do not excise from the genome in order to jump to a new spot. Instead, the existing transposon sequence is transcribed and then a DNA copy of the transcript is re-inserted. Thus, the number of retrotransposons increases whenever a new integration occurs.

There are about 35 copies of the Ty transposon in the genomes of most strains of yeast. In addition, there are many copies of defective transposons containing pieces of the original intact Ty element. The typical fruit fly genome has about 100 copies of copia and about 5000 copies of all types of retrotransposons. Many of these are defective and they contribute to a substantial percentage of the junk DNA in the Drosophila genome.

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Dinner with Bjørn

Bjørn Østman of Pleiotropy and Carnival of Evolution was in town for a visit on Monday, Aug. 8, 2011. We talked about evolution, accommodationism, atheism, PZ, education, visas, politics, carnivals, the USA, adaptationism, blogging, and careers in science.

I think he was happy to learn that I agreed with him on almost everything.

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Sophisticated Theology

Atheists are often accused of being ignorant about modern sophisticated religion. We're supposed to be stuck in the middle ages attacking a strawman version of religion that has no relevance to the beliefs of 21st century theists.

This argument has always puzzled me since I seem to have completely missed all the modern sophisticated proofs of the existence of God that these people talk about. Richard Dawkins also apparently missed them all in The God Delusion.

Last September I embarked on a voyage of discovery where I asked for a brief description of modern sophisticated theology: A Challenge to Theists and their Accommodationist Supporters. You probably won't be surprised to discover that after 552 comments nobody came up with anything that was less than 500 years old.

But, in fairness, the big names of philosophy, theology, and science didn't contribute to that discussion on Sandwalk. So here's your chance to see what modern sophisticated theology looks like in the 21st century. Only this time it's the top thinkers in philosophy and theology who are giving us the answers.

Jerry Coyne has posted brief summaries of their answers at: 20 voices of belief. I urge you to watch the video yourself—that way nobody can ever accuse you of being ignorant of the very best arguments for the existence of God.

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The image from The Emperor's New Clothes is a reference to The Courtier's Reply, which remains the best description of what modern sophisticated theology is all about.