About half of all cancers are just bad luck. It's not your fault.

There's been a lot of talk recently about a paper claiming that two thirds of all cancers are due to bad luck [Bad Luck of Random Mutations Plays Predominant Role in Cancer, Study Shows]. The take-home message was that you could get cancer even if you ate "healthy," took lots of vitamins, didn't smoke, and went to the gym every day. That's not what people wanted to hear.

But scientists have known for decades that many cancers are due to random mutations that just happen. These cancers are not hereditary and are not caused by the environment. There's nothing new here.

That didn't stop a number of people from criticizing the article and some of the criticisms were justified. Nevertheless, what the article showed was that cancers tended to occur more often in tissues with lots of cell divisions (and DNA replications). That's exactly what you expect if random mutations due to replication errors are the cause of the cancer mutations.

David Gorski of Science-Based Medicine sorts it all out for us [Is cancer due mostly to “bad luck”?]. Please read his lengthy article if you want to understand the issues. David Gorski concludes ...

It’s understandable that humans crave explanation, particularly when it comes to causes of a group of diseases as frightening, deadly, and devastating as cancer. In fact, both PZ Myers and David Colquhoun have expressed puzzlement over why there is so much resistance is to the concept that random chance plays a major role in cancer development, with Colquhoun going so far as to liken it to ” the attitude of creationists to evolution.” Their puzzlement most likely derives from the fact that they are not clinicians and don’t have to deal with patients, particularly given that, presumably, they do have a pretty good idea why creationists object to attributing evolution to random chance acted on by natural selection and other forces.

Clinicians could easily have predicted that a finding consistent with the conclusion that, as a whole, probably significantly less than half of human cancers are due to environmental causes that can be altered in order to prevent them would not be a popular message. Human beings don’t want to hear that cancer is an unfortunately unavoidable consequence of being made of cells that replicate their DNA imperfectly over the course of our entire lives. There’s an inherent hostility to any results that conclude anything other than that we can prevent most, if not all, cancers if only we understood enough about cancer and tried hard enough. Worse, in the alternative medicine world there’s a concept that we can basically prevent or cure anything through various means (particularly cancer), most recently through the manipulation of epigenetics. Unfortunately, although risk can be reduced for many cancers in which environmental influences can increase the error rate in DNA replication significantly, the risk of cancer can never be completely eliminated. Fortunately, we have actually been making progress against cancer, with cancer death rates having fallen 22% since 1991, due to combined efforts involving smoking cessation (prevention), better detection, and better treatment. Better understanding the contribution of stochastic processes and stem cell biology to carcinogenesis could potentially help us do even better.

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The Quacks Fight Back

 
Last week David Colquhuon gave a talk sponsored by the Centre for Inquiry and the University of Toronto Secular Alliance [Quackery in Academia] [Science in an Age of Endarkenment].

During his visit to Toronto he was interviewed by Michael Enright of the CBC Radio show The Sunday Edition. The interview was broadcast on Sunday, January 27th. As you might imagine, there were lots of comments and emails and a second show was required in order to restore some "balance." The second show was broadcast on Sunday, February 3rd [The Sunday Edition].

A stirred-up hornet's nest is a mild disturbance compared to the firestorm we unleashed last week over my conversation with Dr. David Colquhoun. Dr. Colquhuon is a gangly, pipe-puffing British pharmacologist who thinks all alternative medicine, all of it, is a fraud perpetrated by quacks. But he went further, somehow suggesting that those who believe in it probably supported Margaret Thatcher, Ronald Reagan and the Ayatollah Khomeini. He pooh-poohed acupuncture, chiropractic, homeopathy, even vitamins.

Well, his remarks opened the floodgates of listener mail, screaming for Dr. Colquhoun's head on a pike. In a few moments, alternative or complimentary medicine strikes back. With the help of two experts, we will try to give the other side of contentious Colquhounism.

Two quacks were required to restore the rift in the space-time continuum caused by too much rationality: Dugald Seely of the Canadian College of Natrupathic Medicine and Dr. Kien Trinh of the DeGroote School of medicine at McMaster University in Hamilton. It's shocking that one of them is from a genuine medical school: he's in a Ph.D. program.

You can listen to the podcast on the CBC website but I can assure you that you won't learn anything new. There's some important issues here. Here's one of the letters that was read on the show ...

Most proponents of alternative medicine do not deny the place of Western medicine. It is too bad that for some the respect is not reciprocal.
                                 Dale Jack

The logic here is that just because some quacks are able to recognize the value of evidence-based medicine then it follows that scientists should extend the same respect to quacks who promote non-evidence-based medicine.

It's a mark of how silly our society has become that such an argument even merits a response. It would be like saying that the most outlandish ideas deserve equal time as long as their proponents are respectful to the proponents of reality.

Here's a similar comment ...

He [Colquhoun] is the very representative of the darkness of the scientific method. He is one of the very ilk that would have driven the new hand-washing surgeons to suicide. As a past-President of the Complementary and Integrative Physicians of B.C., I do hope you will spend the next few weeks in contrition—to re-establish your usually balanced and worthwhile reputation.
                                 Steven Faulkner

Coming from a quack, I guess we shouldn't be surprised at the "logic" exhibited here. The first example is the old saw about truly brilliant innovators who were originally scoffed at. The idea is that because one person took on the scientific establishment and won, it follows logically that all renegades must be right. Conversely, scientists who scoff at quacks must be wrong.

No, this does not compute. As they say, people laughed at Galileo but they also laughed at Bozo the clown.

The second example of silly logic is the concept of "fairness" and "balance" that is used time and time again by quacks and IDiots. Apparently it doesn't matter how stupid your ideas are, society demands that you be given a hearing if you are attacked. Well I've got news for all you quacks out there. You don't get to promote your crazy ideas just because you have them. There's no rule that says you have to be given a platform on public radio just because you've been criticized.

If you want to be heard go the Hyde Park on a Sunday morning. Take a soapbox.

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Quackery in Academia

 
Last night was lots of fun. A bunch of us went to the Centre for Inquiry for a pre-talk reception with David Colquhoun (pronounced "Ca-hoon"). There were light refreshments and lots of talk about atheism, blogs, science, and of course pseudoscience. About 30 friends of the centre showed up.

David Colquhoun is cool. He even agreed to pose with me for a picture. We look like two old curmudgeons but of course we're really not.

After the reception we all walked up to the campus were we heard Prof. Colquhoun talk about alternative medicine. In case, anyone is confused about alternative medicine, the definition is very simple. We all know about evidence-based medicine. That's the kind that's been shown to work. Everything else is "alternative" medicine—medicine that has not been shown to work.

In some cases we know that the "medicine" is not effective. This is the case with homeopathy, a scam that charges patients $2000/litre for water. In other cases, we don't know whether the treatment is helpful or harmful (e.g., some herbal remedies). What we do know is that the claims are wrong. (Because the claimants don't know whether they work either.)

You can find reviews of the talk at Mike's Weekly Skeptic Rant, The Frame Problem, and The Unexamined Life. The only thing I want to add is that Prof. Colquhoun made a strong case for academic quackery. He showed us a long list of universities that now have Departments of Alternative Medicine. The list included some Canadian schools like McMaster University in nearby Hamilton. Colquhoun pointed out that there are many legitimate academics who have fallen for the anti-science crap that is alternative medicine and he calls upon us to take notice and do something about it.

Fellow blogger Ron Brown (right)(The Frame Problem) and old friend Rob Day (left) were at the reception. Rob is a veteran of talk.origins and the creation/evolution controversy from way back—even before my time. It was fun to meet them and Mike (Mike's Weekly Skeptic Rant) again. I'm sorry I didn't get to meet the student behind The Unexamined Life. I guess he/she wanted to remain anonymous.

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Science in an Age of Endarkenment

 
The University of Toronto Secular Alliance is one of the hosts of tomorrow's talk by David Colquhoun [University of Toronto Secular Alliance].

If you live anywhere near Toronto you should come and hear him speak and support the various groups that are sponsoring the event (University of Toronto Secular Alliance, Centre for Inquiry, Skeptics Canada)

U of T Secular Alliance Presents Professor David Colquhoun, FRS - Friday, January 25th, 2008

SCIENCE IN AN AGE OF ENDARKENMENT - SOME EXAMPLES FROM SCIENTIFIC FRAUD, QUACKERY, RELIGION AND UNIVERSITY POLITICS

Should complementary and alternative medicine be considered alongside evidence-based medicine? What role does it play in today's society? Should unscientific medicine be taught in universities? David Colquhoun tackles these issues and more.

Eminent UK scientist and noted skeptic David Colquhoun, FRS is a professor of Pharmacology at University College London, fellow of the Royal Society, and blogger (Improbable Science). He was recently the centre of controversy surrounding his popular blog, dedicated to exposing alternative medicine and pseudoscientific claims, after criticizing a herbal medicine practitioner about her questionable practices. This herbalist threatened legal action and Prof. Colquhoun was forced to remove his site from the UCL server. After much backlash from the scientific community, his website was revived. A leader in the skeptical community, Prof. Colquhoun will be speaking on issues surrounding alternative medicine, academia, and the intersection between the two.

Dr. Colquhoun's website: http://www.dcscience.net

Friday, January 25th 2008, 7pm-9pm
McLeod Auditorium, Medical Sciences Building, University of Toronto (1 King's College Circle, Toronto)
$7, $4 for students
Tickets available at the door.

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Science in an Age of Endarkment

 
Be sure to come to this special event sponsored by the Centre for Inquiry, Toronto. The talk will be given in the auditorium just beside my building. I'll be going to the reception beforehand at CFI—join CFI and you can come too!!!

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SCIENCE IN AN AGE OF ENDARKENMENT: scientific fraud, quackery, religion and university politics

Friday, January 25th, 2008: 7:00 pm - 9:00 pm, MacLeod Auditorium, Medical Sciences Building, University of Toronto (1 King's College Circle, Toronto)

When alternative medicine and academia collide... Featuring a major public symposium with David Colquhoun

Eminent UK scientist and noted skeptic David Colquhoun was recently at the centre of controversy after critiquing the pseudoscientific claims of a homeopathic practitioner. Prof. Colquhoun was asked to remove his site from the UCL server, but after a backlash from the scientific community, his website was revived. He will be speaking about alternative medicine, academia, and the conflicts that arise when the two intersect.

David Colquhoun is professor of pharmacology at University College London and fellow of the Royal Society. He runs a blog called "Improbable Science" (http://www.dcscience.net) dedicated to exposing and debunking pseudoscientific claims.

Dr. Colquhoun will appear at a special reception with food and drinks exclusively for Friends of the Centre from 5:00-6:30pm at CFI Ontario preceding his talk. Contact us at toronto@centerforinquiry.net to find out how you can join.

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[Image Credit: Homeopathy wars in the UK]


[For a short summary of the blogging ban see University College London Restores Professor Colquhoun's Website]

University College London Restores Professor Colquhoun's Website

 
David Colquhoun has a website at University College London where he regularly debunks the claims of "medical" quacks. Recently a herbal medicine practitioner took offense at this debunking and threatened legal action against the university. The university responded by removing the website.

Today the website has been restored [DC's Improbable Science] and University College London has published a press release explaining why [Joint statement by Professor Colquhoun and UCL].

While it's encouraging that the university decided to restore the website, the fact that it buckled to pressure in the first place is disturbing. What's the point of academic freedom if you abandon it whenever you're threatened with a lawsuit?

UCL has a long and outstanding liberal tradition and is committed to encouraging free and frank academic debate. The evidence (or lack thereof) for the claims made for health supplements is a matter of great public interest, and UCL supports all contributions to that debate. The only restriction it places on the use of its facilities is that its staff should use their academic freedom responsibly within the law.

To this end, the Provost and Professor Colquhoun have taken advice from a senior defamation Queen’s Counsel, and we are pleased to announce that Professor Colquhoun’s website – with some modifications effected by him on counsel’s advice - will shortly be restored to UCL’s servers. UCL will not allow staff to use its website for the making of personal attacks on individuals, but continues strongly to support and uphold Professor Colquhoun’s expression of uncompromising opinions as to the claims made for the effectiveness of treatments by the health supplements industry or other similar bodies.

I'm curious about the "minor modifications" and I'm troubled by the prohibition against "the making of personal attacks on individuals." It seems to me that such a prohibition could be used in a way that inhibits academic freedom. For example, would it prohibit a university Professor from criticizing Tony Blair for the war in Iraq? Would it block any negative comments about Prince Charles (pictured at left)? Does it mean that the UCL website is completely devoid of any negative comments about Richard Dawkins?

Perhaps more importantly, does this mean that university Professors cannot point out on their websites the stupidity of administration officials such as UCL President and Provost Malcolm Grant?

Glyphosate-resistant Weeds

Roundup® (glyphosate) has been used to control weeds since 1974 [How Roundup® Works]. In all those years, the number of reported cases of resistant plants has been far below predictions. Only in the past ten years have Roundup®-resistant plants been identified and there are only 11 species of resistant weeds known at last count (Perez-Jones et al. (2007).

We now know from studies of the mechanism of resistance of the C4 EPSP synthase that resistance to glyphosate requires very special circumstances; namely, an enzyme active site that can exclude glyphosate while still allowing phosphoenolpyruvate to bind efficiently [The Molecular Basis of Roundup® Resistance]. Thus, with hindsight, it is perhaps not surprising that so few resistant plants have turned up.

One of the first resistance mechanisms to be discovered was one that evolved in a population of goosegrass from Malaysia (Baerson et al. 2002). The glyphosate-resistant biotype (strain) was from a region that had been continuously sprayed for 10 years.

Baerson et al. (2007), working out of the Monsanto Labs in St. Louis MO (USA), discovered that the resistant strain of goosegrass was resistant to about five times the normal level of glyphosate. All of this resistance was apparently due to a single amino acid change in the active site of EPSP synthase. The substitution of a proline for a serine residue at position 106 decreased glyphosate binding without affecting phophoenolpyruvate binding.

Taken together, these studies suggest that an altered EPSPS provides a significant component of the glyphosate resistance mechanism in goosegrass, and represents the first example for target-based resistance to glyphosate occurring in any plant species.

The authors cannot explain why this P106S substitution confers resistance in the goosegrass enzyme, since similar substitutions in other plant enzymes affect substrate binding and render the enzyme ineffective. They conclude with,

It is possible that goosegrass may be predisposed to this type of mechanism due to species-specific genetic or physiological characteristics that remain obscure at present.

This has important implications for our understanding of evolution. Taken at face value, it suggests that in some species an evolutionary path is simply not available—there may not be a route to the so-called "top of the fitness peak." On the other hand, in other species a path can open up with a single mutation because that species, by chance, has the right kind of background. Evolution by accident.

Glyphosate-resistance has independently evolved in two strains of Italian ryegrass (Lolium multiflorum) from Oregon and Chile. The mechanism of resistance was studied by Perez-Jones et al. (2007). In this case there are two different mechanisms of resistance.

The strain from Chile had the same EPSP synthase mutation as that found in goosegrass (proline for serine at position 106). The Orgeon strain was defective in absorbing glyphosate in the roots suggesting a defect of some sort in absorption and/or transport. This is a new kind of resistance and it's not well understood at this time.

There have been rumors of Roundup® resistant coca plants in Bolivia—the ones whose leaves are used to produce cocaine. The rumors were so persistent that the magic crop was tested to see if it had been genetically engineered in a secret lab sponsored by the drug lords [The Mystery of the Coca Plant That Wouldn't Die]. The article reports that tests for C4 EPSP synthase were negative suggesting that the plants have acquired a natural resistance.

The implication is that the farmers' decentralized system of disseminating coca cuttings has been amazingly effective - more so than genetic engineering could hope to be. When one plant somewhere in the country demonstrated tolerance to glyphosate, cuttings were made and passed on to dealers and farmers, who could sell them quickly to farmers hoping to withstand the spraying. The best of the next generation was once again used for cuttings and distributed.

This technique - applied over four years - is now the most likely explanation for the arrival of Boliviana negra. By spraying so much territory, the US significantly increased the odds of generating beneficial mutations. There are numerous species of coca, further increasing the diversity of possible mutations. And in the Amazonian region, nature is particularly adaptive and resilient.

"I thought [genetic engineering] was unlikely," says Gressel, the plant scientist at the Weizmann Institute. "But farmers aren't dumb. They obviously spotted a lucky mutation and propagated the hell out of it."

The effects of this are far-reaching for American policymakers: A new herbicide would work only for a limited time against such a simple but effective ad hoc network. The coca-growing community is clearly primed to take advantage of any mutations.

From what we know of glyphosate resistance it seem unlikely that these Bolivian plants are actually resistant to Roundup®. It's probably just over-active imagination.

Baerson, S.R., Rodriguez, D.J., Tran, M., Feng, Y., Biest, N.A., Dill, G.M. (2002) Glyphosate-resistant goosegrass. Identification of a mutation in the target enzyme 5-enolpyruvylshikimate-3-phosphate synthase. Plant Physiol. 129:1265-1275. [PubMed]

Perez-Jones, A., Park K.W., Polge, N., Colquhoun, J., and Mallory-Smith, C.A. (2007) Investigating the mechanisms of glyphosate resistance in Lolium multiflorum. Planta. 2007 Feb 24 (electronic publication, ahead of print).