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Bill C-51: A Rant

There's a whole lot of fear-mongering going on about Canadian Bill C-51, an amendment to the Food and Drugs Act. Facebook groups are popping up against the bill, protests are being organized and a website has been set up to organize the troops.

What C-51 is, quoting from the bill, is an attempt

to modernize the regulatory system for foods and therapeutic products, to strengthen the oversight of the benefits and risks of therapeutic products throughout their life cycle, to support effective compliance and enforcement actions and to enable a greater transparency and openness of the regulatory system.

In other words, it's an attempt to regulate therapeutic health products to ensure their safety and efficacy. Obviously, this has raised the ire of the natural products industry who has responded with 'news' pieces like this with alarming 'facts' such as "C-51 is outlawing herbs, supplements and vitamins", or "a mother giving an herb to her child, under the proposed new language, could be arrested for engaging in the sale of unregulated, unapproved 'therapeutic substances.'" (more on that one in a moment). This alarmism is stirred in with a nice painting of draconian enforcement and a dollop of Big Pharma conspiracy theory to make it an amusing, if typical, propaganda piece.

I'm obligated to point out that I am not a lawyer, but I've read the bill. It is NOT outlawing products, but rather bringing the natural health product industry up to a certain standard of testing. It's an attack on deceptive labeling, improper health claims and pseudoscience. No thug is going to kick down your door for serving dandelion greens at dinner. What is being outlawed is selling dandelion greens in a misleading way (eg. with untested health claims).

This brings us to the definition of 'sell', which is a major point for the alarmists. The amended act, if passed, will define sell as

offer for sale, expose for sale or have in possession for sale — or distribute to one or more persons, whether or not the distribution is made for consideration — and, in relation to a device, includes lease, offer for lease, expose for lease or have in possession for lease.

The phrase that the bill-opposers have latched onto is 'distribute to one or more persons'. They take that to mean that, to use the above example, serving dandelion greens for supper counts as 'selling'. While this interpretation of the new wording is technically true, one has to look at the contexts in which the word "sell" is used in the bill. Reading through it, it becomes clear that it's very specific things that run contrary to the proposed law. For example, 'selling' dandelion greens is only prohibited if they have a poisonous or harmful substance in or on it; if they are unfit for human consumption; are adulterated; are injurious to human health; or are processed, manufactured, stored, etc. in unsanitary conditions. That does NOT sound like draconian restrictions on what you can put on your table or give your family. It sounds like common sense. The bill goes further than that, prohibiting 'selling' "a food in a manner that is false, misleading or deceptive or is likely to create an erroneous impression regarding its character, value, quantity, composition, merit, safety or origin." For a therapeutic product, this is expanded to include "creat[ing] an erroneous impression regarding its benefits, risks, conditions of use." In other words, no false claims. So, to the people who oppose this language change, is it because you want to be free to distribute harmful goods, or because you're interested in making false or untested claims about your product?

Shawn Buckley, natural product lawyer, has weighed in with a 20 page review of C-51. (You may remember his name being thrown around by the pro-algae folks on the StemEnhance thread) He goes on to list a number of concerns. First on his list is that roughly 60% of of natural health product licenses are failing, meaning that with this amendment over 60% of the products on the market will become illegal and can be removed from the market by Health Canada. What is implied in this statement, is that 60% of the natural health products already on the market are not licensed. Nor does he state why these licenses are being denied. Is he seriously pushing for unlicensed health products - products that have failed to get government approval - to remain on shelves?

Buckley tries to portray the government as being bullies towards the natural health product industry. He points to language changes proposed by the act, such as replacing 'drug' with 'therapeutic product' and then asks "is the change of terminology directed at the Natural Health Product industry or are there other reasons?" My guess is that the answer is 'yes' and I would respond with the question 'So?' The changes in the act seem to have in mind the goal of bringing the natural product industry to a particular standard. The pharmaceutical industry is already regulated in terms of safety requirements, evidence-based results, etc. Obviously bringing drugs and natural products under the same 'therapeutic product' umbrella is designed to ensure that ALL of these products are safe, effective and work as advertised. As Buckley himself points out, the pharmaceutical industry already has a high compliance rate with Health Canada rulings, while 60% of natural products go to market having their licenses denied.

What is more concerning is the National Health Products Protection Association (NHPPA, of which Buckley is president) position. In the legal review of C-51, their goals are listed as a regulatory environment where, among other things, "NHPs [natural health products] are presumed to be safe. A NHP cannot be taken off of the market unless the Government can prove that it is unsafe." This is just a ridiculous attitude. If the default position for a natural product is 'safe', that means people have to start getting ill or dying before somebody steps in. The reality is that health products should be deemed safe before they go to market. Just because it's labeled natural doesn't make it safe. As I've pointed out before, several potent cancer drugs are natural products. Would the NHPPA have these, or any future similar discoveries given a blanket 'safe' label and start selling to people?

Therein is the lunacy of the natural product position: The want their products to be at once efficacious and totally harmless. For any product to be useful in some therapeutic way, it has to have a biological effect. If it has a biological effect, then you have to start thinking about how it works, safe doses, potential side-effects, etc. Now don't get me wrong, I don't think the bottle of vitamin C in the medicine cabinet is particularly dangerous (of course, anything is at a high enough dose), but natural health products include more than standard vitamin supplements with known tolerances. They include products that claim to mobilize stem cells, alter gut flora composition, and stimulate the immune system as well as non-standard megadoses of of common vitamins. All of these effects have the potential to cause adverse events. The default position is not 'totally harmless'.

Mr. Buckley does raise some interesting points about the use of the word 'government' in the bill, and how it may affect adoption of future regulations. In C-51, the definition of government includes international bodies and foreign governments and states that "A regulation may incorporate by reference documents produced by a person or body other than the Minister of the Canadian Food Inspection Agency including ... (c) a government." This sounds like the amended bill makes it easier to incorporate foreign policies into Canadian law. However, given Buckely's position with the NHPPA, I doubt the sovereignty of Canadian law is his primary concern.

Of course there will be people arguing that the government has no right to tell us what to put in our bodies. That's not what these changes are doing. It doesn't say you can't eat your dandelion greens, take your garlic supplement or multivitamin. It says that the products must be safe and that their sales and marketing can't be false, misleading or deceptive. You can eat your greens, but they can't be sold as age-reversing. You can take your garlic pills, but they can't be sold as cancer-curing. Unless, of course, there's evidence.

Canada Wide Science Fair

For the past two days, I've been a judge at the Canada Wide Science Fair here in Ottawa. The students and their projects have been extremely impressive. For those in the Ottawa area who want to see some of the future stars of Canadian research and innovation, there is a public viewing this Saturday, May 17th between 9am and noon in Montpetit gym at the University of Ottawa.

Octane Rating

Just a little FYI. I was stumped today on what exactly an octane rating on gasoline meant.
The octane rating is based on results using a test engine. It is the resistance to autoignition that is being measured. Autoingition is undesirable in a gasoline engine as this produces knocking. It is called an octane rating as iso-octane is defined as 100 and n-heptane is defined as 0. So a mixture of 87% iso-octane and 13% n-heptane would have an octane rating of 87%. However that doesn't mean that a fuel with a 97 octane rating has 97% octane, it just has characteristics as if it was 97% octane and 3% n-heptane.

Research is a money pit

Do you ever get the sense that research money often goes wasted? Even if you ignore all the research dead-ends and the discoveries which have limited implications, and just concentrate on what you can get for your tax money. How often does an expensive machine get used for only one experiment, how often do we throw out stuff that still works. And not to mention the price gouging that suppliers are guilty of. I don't understand how a ice pack for a western apparatus can be 10 times more expensive than a regular one, or why a research fridge is four times the price of a regular fridge. It's certainly not for the reliability, from what I've seen of our fridges. Some of the kits you can get now are ridiculous, especially considering the hourly wage of the person using it. It begs the question: should we hold the researchers accountable for the money they use? Between two researchers who produce the same work, should we choose the one who will do it for cheaper, or do we risk stifling innovation? Just take this example of a researcher who used his grant money for chrome wheels and big screen TVs. It sounds like he got off easy:

"Another $123,703.20 in expenditures appeared to be "inconsistent" with his research grant proposals, the documents say. But university investigators gave him the benefit of the doubt saying the nine computer monitors and other items "might have been related" to his research from a "general scientific perspective."

The university then made an arrangement with the researcher that in the "event of timely repayment" of $24,767.33, it would not ask for the rest of the money back.

The university returned $21,485.67 to NSERC. The documents indicate the other $3,000 refunded by the scientist was sent back to other agencies that had also financed his research."

Everything You Wanted to Know About the Human Genome But Were Too Lazy to Figure Out

This new book sounds cool. "A Short (173pp) Guide to the Human Genome", by Stewart Scherer. Probably a great one for your bathroom or outhouse collection. Such a reference is drastically needed - everyone in biology should know the human genome inside out, but who has the time to fish out all the info? Now we don't have to. Sweet.

Go to Europe if You're Into Gene Therapy

It can be pretty frustrating to be a scientist in gene/virotherapy vector development these days. Not because vector development is particularly difficult. The ideas, expertise and lab resources are there. As far as the science goes, we are totally capable of kicking the shit out of genetic diseases and a lot of cancers with the myriad innovative therapies we are dishing out of the lab every day. The bottleneck lies in getting the money, infrastructure and approval set up to test the new therapies in the clinic. Getting this done in North America, especially the US, is next to impossible, unless you happen to have a few billion dollars to burn.

Anyway it's interesting to note that over in Europe they seem to be having a lot more success getting cool new gene therapies into the clinic. Hence, as this Molecular Therapy editorial points out, the "vector drain" phenomenon, where vectors being developed in North America find the clinic in Europe. Will this also lead to a brain drain? It would be pretty attractive for vector researchers to just move the whole operation to an environment where their creations are likely to see implementation. Not to mention, you get to live in Europe. If some of these countries get their acts together and set up more research facilities, they'd be in position to score a real research coup.

Do Not Fear; Solar Power Plants are Almost Here

I thought this NPR Podcast from back in March was pretty good. Ira talks to a bunch of people from the solar power industry and the message is surprisingly optimistic. Large-scale solar power plants are apparently on the verge of becoming profitable, and utility companies are getting seriously interested. The clincher is that if the ball gets rolling, they claim that a hundred 10,000 square-mile plant would be enough to provide a sustainable source of energy to the entire US (does this include the aircraft carriers and nuclear submarines?).

Maybe the imminent end of oil doesn't spell Armageddon for civilization after all. Although it's not clear how efficient fertilizer production would be without fossil fuels as a hydrogen source, and we'd still need to come up with a replacement material for the plastic in those Falcon tubes. But, unlike biofuels, solar power may provide a feasible option for a sustainable, but still modern economy.

ERRATUM: I believe I erroneously cited that a 100 mile squared piece of land would collect enough solar power for the US. I think what they actually say is 100 miles by 100 miles, or 10,000 square miles. Thus proving that you're better of just listening to the podcast yourself...

Who Wants to Solve a Protein Structure?

The Folding@Home project allows PS3 and computer owners to use spare processor cycles to help solve 3-dimensional protein structures. A new game allows players to use spare brain power to do the same. Foldit taps into human 3-D problem solving skills getting players to fold proteins in a video game interface, giving points based on energy required for a given configuration. The game has been in testing phase using proteins with known structures, but is about to challenge players with unknown structures.

Try it out or read more about the game here.

A Challenge for Science Bloggers

Skull in the stars has issued a challenge to science bloggers: "Read and research an old, classic scientific paper and write a blog post about it." The suggestion is pre-WWII papers, but I've decided to pick something slightly more recent (pre-Woodstock, instead).

So that's the challenge: Pick a classic, write a post and submit the link in the comments over there so they can all be compiled in one list. Get it all done by the end of May. Have fun!

On Codon Usage

Each amino acid in a protein sequence is represented by a 3-letter 'word' (codon) in the genetic code. Since there are 4 'letters' (A,C,G,T) there are 64 potential words to represent 20 amino acids, plus stop codons. The code is unambiguous - each codon represents only a single amino acid. It also has redundancies - most amino acids are represented by multiple codons (glycine, for example, can be represented 4 different ways). One might think that the diversity of life on the planet would come with a diverse difference in codon usage. This is not the case. There are differences in codon preference, both within and across species but usage is almost universal. For example, in humans the triplet ATC (20.8 codons/1000 codons) is preferred over the triplet ATA (7.5 codons/1000 codons) and in the yeast S. cerevisiae ATT is preffered to both of those (30.1 codons/1000 codons). However, in each of those cases - and virtually every other species - all three of those triplets code for isoleucine. Codon preference is related to abundance of the respective transfer RNA. (Larry Moran touches upon codon bias and why mutations that change the codon but not the amino acid may not be neutral in an article here)

There is experimental evidence for a universal genetic code:

mRNAs can be correctly translated by the protein synthesizing machinery of very different species. For example, human hemoglobin mRNA is correctly translated by a wheat-germ extract [...] bacteria efficiently express recombinant DNA molecules encoding human proteins such as insulin.
(Stryer, L. Biochemistry 3rd Ed. p 108)

A universal code is the basis of many techniques (and headaches) in the lab. For example, in vitro protein synthesis can involve rabbit reticulocyte lysates (or wheat germ, as above) translating non-rabbit proteins. Non-mouse sequences can be used to introduce genes into mice. E. coli is often used for recombinant protein production. In this latter case, the difference in codon preference between E. coli and other species is a common problem for high level recombinant expression (eg. if a codon is preferred in humans - CCC for proline - but not in E. coli, this limiting tRNA could hinder protein production).

That the genetic code is universal is not entirely true; some inter-species differences are being discovered. There are some species, such as ciliated protozoa have slight variations (in ciliates, TAA and TAG are glutamine rather than stop codons). Mitochondria are another important exception.

Mitochondria carry their own circular DNA which encodes for, among other things, a set of 22 tRNAs. Because it doesn't use the set of nuclear-encoded tRNAs, it isn't restricted to the standard code. In fact, human mitochondrial codon use differs from nuclear codon use in 4 places. For example, in the isoleucine example above, the codon AUA codes for methionine in mitochondria (see table, reproduced from Stryer). This isn't news, but something I failed to appreciate before. A difference in codon usage between species might not be surprising (in fact the consistancy in usage among species is surprising - until you consider the far reaching effects a change in codon use would have: Every protein would be affected). A difference in usage within a single cell is more striking, unless you're familiar with endosymbiotic theory.

Endosymbiotic theory, popularized by Lynn Margulis, describes the origins of eukaryotic organelles: mitochondria and chloroplasts. These organelles were once autonomous organisms that were taken up by other cells in a symbiotic relationship. Both organelles have strong resemblences to the proposed parent prokaryotes, as detailed in the above link. Codon use separate from nuclear DNA can be added to that list.

Read more about the different codon usage sets here.
Codon preference numbers from here.

Platypus Genome Complete

We've talked before about the platypus and all it's strangeness. The platypus genome has has just been sequenced, revealing some things we already suspected: the platypus shares features with birds, reptiles and mammals. Follow the link for the Nature News story, podcast and video interview with the authors behind the project.

Lethal Injection

I have had to euthanize mice for experiments before. The animal care people here are very adamant that the animals experience the least amount of discomfort as possible, as they should, it's their job. One acceptable way to euthanize a mouse is an intraperitoneal injection of euthasol, which is a barbituate, a class of CNS inhibitors commonly used as anesthetic.
If this is the most humane way to euthanize that should mean that lethal injections, as practiced by countries that euthanize convicted criminals as part of capital punishment, should be the same. I guess, that is, assuming that the point of lethal injection is to be more humane than previous methods of euthanization. I was surprised to learn that lethal injection is not very simple.
Lethal injection in the United States consists of three sequentially administered drugs. These drugs are sodium thiopental, pancuronium bromide, and potassium chloride given intravenously in that order. This is a similar procedure to what is on wikipedia for physician assisted suicide.
Sodium thiopental, also used as 'truth serum', induces relaxation and release from social inhibitions. It is a short-acting barbituate that at the doses for lethal injection rapidly induces a coma. It inhibits CNS activity by activating GABAa receptors. Alcohol acts on these same receptors, however, barbituates are not used much recreationally anymore, I think, as they have been largely replaced by benzodiazepines. 'benzos' (apparently safer and more fun). Relevant to lethal injection is that sodium thiopental has no analgesic effects ie. not a painkiller.
Then comes the pancuronium bromide. This blocks acetylcholine at neuromuscular junctions, rendering the convicted paralyzed, including breathing muscles. Hopefully that thiopental coma is going well or it would be like drowning.
Then just to ensure death, potassium chloride. Such a simple salt of two ions that are very common in your body is deadly? Really it is because the large bolus IV injection at a high dose messes with the electrochemical gradient needed for proper cardiac muscle function. The heart is stopped.
I wonder how much this combo has to do with ensuring death, and making it less traumatic for the witnesses than it does with being humane. A good way to go might be an overdose of an opiate or something but seeing a convict get all high and say weird things might be too much.

Greatest application of physics and the internet EVAR!

In the quest for perfect BT (bra technology), the folks at 'shock absorber' have managed to create a mesmerizing website. To check out the bounceometer be sure to have your cup size and an estimation of your level of activity ready, and watch the efficiency of the 'shock absorber'.

Viagra nation

I watched the newest vidcast of diggnation over the weekend, as I usually do. It is a reasonably good show about the most popular stories covered on digg.com. Alex Albrecht is too cool, mostly because he drinks beer, plays pencil and paper D&D, is on the totallyradshow, and kicks Kevin Roses arse at Call of Duty 4. That is some serious geek street cred.
This past eppisode though, they revealed some ignorance about the mechanism of Viagra. Kevin Rose (seriously check out how badly he is pwned by Albrecht on CoD4) thought that you could take Viagra and have a voluntary errection where you would have to 'be in the mood'. Someone from the audience who identified themselves as a 'life scientist' said that it was not voluntary. Well, Kevin Rose was right and the 'life scientist' was wrong. Strange since I find Kevin Rose usually talks out his ass.
As I understand it viagra mearly inhibits the degradation of cGMP, which directly initiates and maintains an errection. However it is produced in response to nitric oxide. The nitric oxide is produced upon sexual stimulation, therefore even with viagra it should still be a voluntary thing. That's got to be a relief for those who take the drug since you are supposed to take it 4 hours before you think you will need it. That would be a long 4 hours if it was involuntary.

Photo Caption Contest

I stole this idea from Rob, but he's a bit busy to post it himself.

This photo of the Governator in 'research mode' is just begging for a witty caption, so have at it! After an inderminate amount of time, the funniest one will be chosen arbitrarily and the author showered with praise (sorry, our prize budget doesn't allow for much more than that).(Photo source: Nature News)

Just to get things going, here's my entry: "It's not a too-mah."

1000th post!

For the occasion I wish to share with you interesting tidbits about penguin sexuality:

Penguins are famous for engaging in animal homosexual behaviour. They even sometimes steal eggs from heterosexual couples and rear the youngs. A famous case at the NY zoo, and reports in zoos from all over the world have confirmed that not only are homosexual couples frequent, but the bonding between the gay partnersis strong . Case in point: a zoo in Germany tried importing Swedish chicks and even they couldn't lure the males away!

Penguins are also known to prostitute themselves for a rock. They will let other penguins exchange sexual favors for nest building material.

Penguins sometimes engage in inter-species sex. Perhaps unwillingly. sometimes sexually frustrated seals molest penguins on the beach. I am not even making that stuff up!

Cancer Carnival #9 is Here!

The 9th Edition of the Cancer Research Blog Carnival has gone live at Hematopoiesis. Your host, Alexey, has a nice collection of posts, including news from the recent AACR meeting. The next edition is set for June 6 so start penning your submissions. Contact the Bayblab if you're interested in hosting a future edition.

Thanks to Alexey for a great job and, as always, hats off to Ben for designing the logo.

Insurance and the Age of Personal Genetics

In the age of the personal genome, companies like 23andMe are springing up, offering personal genetic profiling and ancestry tracing. While there are questions about the accuracy of their claims, the interpretation of the results (are we about to see a boom in genetic counsellors?) and other ethical and privacy considerations, the US Senate has made a pro-active move in passing a bill banning genetic discrimination. In short, the bill prohibits employers or insurers to use personal genetic information in decision making. Ars technica takes a closer look at the insurance angle, explaining why the bill is a good idea. From the article:

Worse yet, the very concept [of insurance based on genetics] threatens to undermine another of the greatest potential benefits of the genome: personalized medicine. The goal of personalized medicine is to tailor treatments to a the unique genetic defects that have helped foster a disease, be it diabetes or cancer. But, if insurers can deny coverage based on those same genetic traits, the patient may never see the treatment.

GSK acquires Sirtris Pharmaceuticals

Pharm giant GlaxoSmithKline acquired Sirtris Pharmaceuticals for the tidy sum of $720 million US last week.

This story is interesting not because of the excitement of corporate deals and stock market fluctuations, but because Sirtris Pharmaceuticals specializes in developing small molecule activators of SirT1. And anything involving SirT1 - my protein of interest - is inherently fascinating.

It's actually more interesting for other reasons. Previously on this blog, I've echoed a sentiment common in the skeptical blogosphere: There's no such thing as alternative medicine. Once a treatment has been shown to work, it becomes part of mainstream medicine. Resveratrol, a polyphenol, is a SirT1 activator. SirT1 (I told you it was interesting) has been shown to be involved in insulin signaling, energy metabolism and lifespan extension in model organisms. Other work has shown resveratrol to have cardioprotective and anti-cancer effects. Resveratrol has long been thought to be a molecule behind the 'drink red wine' wisdom.

This all sounds great. And 'alties' probably feel vindicated: Resveratrol has been on sale in health food and dietary supplement stores for ages. Before many of the studies mentioned above had been done, in fact. But don't go reaching for your wineskin just yet. Studies have also shown that oral resveratrol has poor bioavailability.

That's where Sirtris comes in. They develop compounds that are analogs of resveratrol to improve potency and bioavailability (and patentability), and test those compounds. And Big Pharma (GSK) has taken notice, decided this is viable science, and acquired Sirtris in the hopes of turning these compounds into diabetes, anti-obesity or anti-aging drugs. Like other examples we've discussed this is a case of a natural or alternative medicine becoming mainstream (or, rather, the beginning steps of that process).

The moral of the story isn't that natural products work. In this case it doesn't - all resveratrol supplements will give you is expensive urine. The point is that if the science is there, the medicine will come.

There's still a possibility that these compounds will fail for one reason or another. Perhaps they won't be effective in humans as in rodents. Maybe there will be toxicity issues. If this happens, no doubt that Big Pharma conspiracy theorists will jump up and down saying that GSK made the purchase to squash a promising natural medicine. An almost 1 billion dollar investment seems to be a bit much for such a petty goal. If I was the big, evil corporation, I'd sink that money into the supplement makers and keep it on the shelves. But shrewd companies know that a tested drug has more value than an untested one. The only reason not to get science onside is if you don't think it will support you.