Canadian Health Concerns

There have been a couple of items in the news recently regarding Canadian health issues. Both of them have been touched on before (which should come as no surprise - we're visionaries here at the Bayblab).

The first is Listeria which began with an outbreak which left one dead and several others ill and the subsequent product recall and shutdown of the Toronto Maple Leaf production facility. We've tackled Listeria before, and discussed some of the strategies companies use to minimize contamination - mainly sanitary design and proper cleaning. In the US, bacteriophage are also used for Listeria management. In Canada, we have yet to adopt these measures:

[Retired Health Canada microbiologist and food inspector Bill] Riedel said Canada needs a system like one approved in the United States two years ago, in which bacteriophage therapy is used to combat Listeria monocytogenes found in foods. Bacteriophages are viruses that infect and destroy bacteria.

As of Wednesday, the number of deaths caused by the outbreak was 6, with 10 others under investigation. Major fast-food chains McDonalds and Mr. Sub were affected by the recall. I wonder if bacteriophage technology would have prevented this outbreak, and if the death toll and economic impact will accelerate a move towards it.

Second up is the mumps outbreak in western Canada. I've written about disease resurgance before, usually measles. This time it's mumps. Close to 200 cases have been reported in the Chilliwack region of British Columbia - a province that typically sees no more than 5 cases per year (according to CBC.ca).

Of the 191 cases reported so far since the outbreak began in Chilliwack in February, 10 to 20 are still active. Half of the people who have been infected have not been immunized, a quarter have had at least one shot and a quarter do not have vaccination records, Dr. Brodkin said. One person developed meningitis, nine suffered hearing loss and 26 had swollen testicles or ovaries. It is not clear how many of those cases will result in permanent deafness or sterility.

Officials fear that up to two-thirds of cases are going undetected and continue to spread the virus. The outbreak has been linked to religious groups in the area who are opposed to vaccination due to their beliefs.

Hypothesizing about Hypotheses

I guess that it is important to properly pose your question/model ect when designing experiments and doing science in general. This article is right up Bayman's alley of interest. Published in Cell, the authors discuss the brief history of the hypothesis and some interesting thoughts about the way which science is actually done, without hypothesizing. Access to Cell is required to actually read the full text.
“Hypotheses are not to be regarded in experimental Philosophy” (Newton, 1721).

Dawkins' emails...

Cancer Research Blog Carnival: A New Site

In honour of its first birthday, the Cancer Research Blog Carnival is moving out. For those of you who are readers of the monthly carnival, I've set up a new site that's CRBC specific. The goal was to create a centralized place to go for archives of previous editions as well as news and announcements for upcoming ones. Hopefully it will continue to grow and improve over the next year and beyond.

And don't forget to get your submissions in for the 13th edition to be hosted September 5 at Highlight HEALTH.

Science Olympics

Are you an expert at the 10m Namedrop? The Data Stretch? The Long Jump-ing to conclusions?

Whether you're doing the summer student sprint or running a marathon on the tenure track, check out these events for the Science Olympics, or come up with some of your own.

[via A Blog Around the Clock]

Street Corner Science

I love this idea, We've been talking about doing something similar at the student pub for some time now for the bayblab podcast... But obviously this guy is in another league...

Bayblab podcast: Episode18/19

After a summer off the bayblab podcast is back. In this delayed episode we drunkenly ramble about non-coding RNA's, phages, science in the news and the optimal amount of beer for various activities... Don't miss out on episode 19 (and episode 7 part 4) which will be out any day now :). We'll be back with a bigger better podcast in September so refresh the bayblab podcast on your itunes or other rss clients in anticipation...

On hybrid fruits...

So I had the chance over the weekend to try a new fruit advertised as "dinosaur egg". The vendor claimed that it was a nectarine/plum hybrid. Yeah right I thought, nectarines and plums seem like very different fruits to me, and it's not like people are still inventing fruits right, it's just probably a plum variety with a taste similar to a nectarine. wrong.

Turns out it's a pluot, an interspecific hybrid fruit with 3/4 plum and 1/4 apricot, and there are several varieties of pluots to boot (13 according to wikipedia). How is that possible. Well they are derived from a 1:1 hybrid of plum and apricot, the plumcot, which was generated simply by cross-pollination. The plumcot can then be crossed back to either an apricot or a plum tree to get different percentage contribution (which you could probably track by QTL analysis).

In fact you can do this with apricot, plum, cherry, peach and almond trees. For example the peacotum is a peach/apricot/plum hybrid which tastes just like fruit punch. Zaiger's Genetic from California holds the patent and trademarks to pretty much all these hybrids.

People sometimes mistake nectarines as a cross between plum and peach, but in fact nectarines are just a cultivar of peaches with a recessive mutation. The fuzziness of peaches is a dominant trait.

So there you go, we are still inventing new fruits, and there is still room for innovation by using simple crosses. Who knew those fruit trees were related enough to be crossed, and that the hybrids would be fertile. Now if one of them mutha uckas fruit vendors could make me a grapple, we would be in business...

Blinatumomab - BiTE antibodies

Just heard about this particular cancer therapeutic on the Science Magazine Podcast (link to mp3 of episode), called Blinatumomab. It is made by a US company called Micromet, who has a patent on this class of engineered proteins called BiTE antibodies. These proteins are a single polypeptide containing the variable regions from two antibodies with different specificities. BiTE stands for bi-specific T-cell engagers and are named such becuause one of the antibodies specificities is for CD3, a compentent of the T-cell receptor, while the other is specific for a tumour specific antigen. The idea is that these molecules attach to cells expressing the tumour antigen and then recuit Tcells (nonspecifically as they all have CD3) to kill these target cells. The mechanism of exactly how this works eludes me as the T-cells are not being activated in the conventional mechanism that I understand. However it is therefore suggested that the cancer cells would be more suseptable to this mechanism as they have managed so far to escape conventional immune control.
Check out the Micromet company backgrounder on BiTE antibodies. (pdf)
What makes these molecules Science magazine worthy is that Blinatumomab has demonstrated some impressive efficacy against non–Hodgkin's B cell lymphoma (NHL). Check out the publication from Science.

Banned Performace Enhancing Drug Classes

The IOC has banned participating athletes from using drugs to enhance their performance. What is the purpose of this policy? Surely technology offers athletes many ways to enhance their performance. If the issue is fairness, I can see similarities between the new speedo swim suits and performance enhancing drugs. If the issue is athlete health, which seems more reasonable to me, is there not health consequences of training to olympic levels in the first place? Young female gymnasts seem to experience at least some negative health consequences of training.
From the World Anti-Doping Agency (WADA):
"...Clean Athletes are the real heroes who make brave choices everyday by not doping. They deserve competition that is safe and fair. They deserve a level playing field."

In any case, back to science, here's a Ben Johnson's breakfast of all that you can't indulge in if your are an elite olympic athlete:
Anabolic Agents: Most importantly this includes small molecule steroids related to testosterone. These agents increase your muscle mass and red blood cell numbers. This makes them excellent for improving performance in strength requiring events. Obviously these agents have masculinizing effects. The scary side-effect of shrinking testicles is temporary, however the long term effects include undesirable cardiovascular effects. They can also cause you to start growing a beard if your are a woman and initiate male pattern baldness early. This category also includes steroids used to treat asthma, Beta-2 agonists. These drugs increase lean muscle mass, and also have some stimulant properties. A therapeutic use exemption can be obtained if you are asthmatic.
Blood doping: Blood doping means increasing the oxygen carrying capacity of your blood by increasing the number of red blood cells (RBCs) in your body. This is great for endurance sports. This can be done by harvesting RBCs, storing them, then re-administering to the athlete before competition. This is pretty old school now and more common is the use of erythropoeitin (EPO). EPO is a peptide hormone that stimulates growth of RBCs. It has medicinal uses and therefore is cloned and available. Detection is difficult but possible. Too much RBCs makes your heart work hard and apparently if you are an elite athlete with a low resting heart rate and too many RBCs you can die in your sleep.
Peptide hormones: There are many hormones that may give an athlete an unfair advantage. The previously mentioned EPO and additionally other growth hormones that increase muscle weight. This includes insulin, and surprisingly I didn't see a therapeutic use exception for exogenous insulin for diabetics. I would assume there is.
Stimulants: Caffine is fine, but go easy on the cocaine. These increase heart rate and thereby bloodflow and increase metal alertness. I would think the most commonly used stimulant as a performance enhancer is ephedrine, but only because I have heard about it the most.
Diuretics: Diuretics are used to increase urination to loose weight. Good for being the largest guy in the smallest weight category. These drugs are also used to eliminate drugs from your system also known as a masking agent.
Narcotic Analgesics: 'No pain, no gain', however without without the pain, it is all gain. Opiates are probably the most commonly used narcotics to overcome injury or train for longer periods that would normally cause pain.
Gene Doping: This is the newest category and I know if there are any examples. But my guess is that you could use some techniques to genetically increase EPO or another of the above protein products in an athlete. From WADA:
"The non-therapeutic use of cells, genes, genetic elements, or of the modulation of gene expression, having the capacity to enhance athletic performance, is prohibited."
If you are wondering about your particular prescription make sure to check the complete list of banned substances from the World Anti-Doping Agency. If it's on the list, increase your dose before any competitive event, winning is everything.

Do not drink liquid nitrogen

Because of safety reasons all my bottles of reagents on my shelf are labeled "do not drink" (except my ddH2O, that one is labeled "only drink if very thirsty"). I always thought it was a ridiculous precaution because who in their right mind would drink from a bottle in a lab. I mean if you're going write that, might as well add "do not use for enema". Well I guess I'm just not gifted:

August 15, 2008 -- A gifted 15-year-old student from India had to be rushed to the hospital after drinking liquid nitrogen during a science class at Princeton University.

The class was part of a program run by the Connecticut-based Summer Institute for the Gifted.

Werd (LHC rap)

WTF is transmission ratio distortion

So I had a mission this afternoon to figure out what the hell this "t-complex" was. I tried reading some papers about it, and quite frankly I couldn't get past the intro. The other strange thing is that there seems to be little to no paper on the subject that date from after the 80's. So I finally broke down and started reading reviews and what I found is an interesting and seemingly forgotten story. Apparently this was all the rage 70 years ago, and one of the biggest mysteries of mouse genetics.

It all started with mice that were captured in the wild and bred with "T mutant" lab mice which had short tails (the t in t-complex stands for tail). Somehow when you bred them together you got mice with no tail. There was some kind of "modifier" in one of the mice which was exacerbating the phenotype. People tried to map this supposed modifier, but the linkage was all messed up, and the heredity wasn't Mendelian.

Well this modifier wasn't in fact a gene it was a large region of chromosome 17. This region could either be wildtype (+) or be severely remodeled and called t-haplotype (t). The remodeling involved several rearrangements including multiple inversions which basically prevented the region from ever recombining with a normal (+) carrying chromosome 17. On top of that the region contains multiple mutant genes which are in a really strong linkage disequilibrium (IE you either get a bunch of mutants or the wt, no mixing at meiosis).

Males carrying two t-haplotypes are infertile, and so you would expect this anomaly to be quickly swept under the evolutionary rug. However there was a strange case of selfish gene interfering with the process. The het males (+/t) transmit the t to all the offsprings, and completely ignore poor Mendel and display a male transmission ratio distortion (TRD). How can this be? Obviously those genes where interfering with either meiosis or reproduction, and making sure they were passed on preferentially. Well it turns out that in that region there are a number of genes which affect sperm flagellar development.

It wasn't that the embryos getting the + allelle from the +/t father were dying, it wasn't that the +/t males were only producing t sperm, it was much more insidious. Somehow the t sperm is a better swimmer and the t-complex genes conspire to cripple the + sperm. How is that possible you may ask. Well through a quirk of sperm development: the syncithium. while the spermatocytes are maturing they share cytoplasm via bridges, so proteins and RNAs are free to flow between + spermatocytes and t spermatocytes. This way some problems of the mutants can be overcome by shared wt protein. This explain how the t survives but not how the + get crippled. Turns out that among the mutant genes being passed along together in the t-haplotype is a gain of function mutant which rescues the other mutants and is only expressed late in spermiogenesis, after the bridges between sperm have been burned. So the t spermatocyte share the poison to all connected sperm when the syncithium is present, but they save the antidote for later.

So this is how you get an entire selfish region to behave as a unit and be passed along preferentially despite being recessive lethal. Neat huh.

Cancer Carnival #12

The 12th Edition of the Cancer Research Blog Carnival has arrived! It's hard to believe it's been almost a year since the first edition. The carnival keeps getting bigger and better, and the latest edition is no exception. Click the link and check it out. Thanks to Ben for logo design, and for the awesome hosting job. Read it. Now.

As always, if you want to host a future edition, send us an email: bayblab[at]gmail.com

Fact or Fiction: Eclipse Blindness

Today, August 1 2008, a total solar eclipse will be visible in parts of northern Canada, Greenland, Russia, China and Mongolia, with a partial eclipse visible in other parts of the the country.

I remember in elementary school, a big deal was made of not looking directly at a solar eclipse. A very big deal. Even a quick, unprotected glimpse could cause blindness. At the time, it didn't make sense to me - why would looking at an eclipse be any worse than looking at an uneclipsed sun? Was the seemingly heightened paranoia because it's an event that people are likely to want to look at? Or is there something else about an eclipse that warrants the extra attention? Even NASA acknowledges that eclipse warnings may be a bit hyperbolic:

In the days and weeks preceding a solar eclipse, there are often news stories and announcements in the media, warning about the dangers of looking at the eclipse. Unfortunately, despite the good intentions behind these messages, they frequently contain misinformation, and may be designed to scare people from seeing the eclipse at all.

The fact of the matter is yes, you can do serious damage to your eyesight looking directly at a partial solar eclipse. During the period of total eclipse - when the moon completely obscures the sun - it's safe to observe with the naked eye (see also NASA link above). However, this isn't without risk since the shadow will continue to pass and without proper timing you could find yourself looking directly at a partial eclipse. Even when 99% of the sun is obscured, the remaining 1% is intense enough to cause serious retinal damage.

Is looking at a partially-eclipsed sun more hazardous than an unobscured sun? In a way, yes. Because even a mostly blocked sun can be damaging and the surrounding illumination in these conditions can actually be quite dim. In this case the eyes natural defense - constriction of the pupil - doesn't kick in right away. The pupil is exposed to the sun in a dilated state, allowing more of the damaging light to enter the eye. (Of course an unobscured sun will be sending that much more light to your eye, so this isn't a proper comparison.)

The bottom line is that there's nothing magical about a solar eclipse, and nothing special about the light it gives off, but after every eclipse there's a spike in cases of retinal injury and eyesight damage. Take proper precautions when viewing an eclipse and don't stare directly at the sun - eclipsed or not.

[Image source: Wikipedia]