Hypercolor T-shirts

I'm not really sure what our reader demographics are like here at the Bayblab, but I'm sure some of you remember Hypercolor T-shirts - the shirts that changed colour with heat. If you ever wondered how that worked, Wikipedia comes to the rescue:

The color change of Hypercolor shirts is based on combination of two colors: the color of the dyed fabric, which remained constant, and the color of the thermochromic dye. The dye is enclosed in microcapsules, tiny (few micrometers in diameter) drops of liquid sealed in a transparent shell, bound to the fibers of the fabric. The liquid is a leuco form of a dye (in this case crystal violet lactone), a weak acid (1,2,3-benzotriazole), and a quaternary ammonium salt of a fatty acid (myristylammonium oleate) dissolved in a solvent (1-dodecanol). At low temperatures, the weak acid forms a colored complex with the leuco dye, interrupting the lactone ring. At high temperatures, above 24-27 °C, the solvent melts and the salt dissociates, reversibly reacts with the weak acid and increases the pH. The pH change leads to closing of the lactone ring of the dye, which then regains its colorless (leuco) form.

Low temperatures allow a weak acid to react with the dye, converting it to its coloured form.

Whatever happened to those shirts anyhow? That they were easily ruined by washing them at higher than recommended temperatures didn't help, but I'm sure it had more to do with people not needing any more attention drawn to overactive armpits.

Cancer Carnival #22

Welcome to the June edition of the Cancer Research Blog Carnival - your monthly stop for cancer-related news and breakthroughs. I've been a bad keeper this month, both in soliciting hosts/posts and in timely delivery, so let's jump right in to the good stuff.

Omics! Omics!
Dr. Keith Robison ponders tumor supressors as he moves back into the cancer field, likening cancer researchers to the seven blind men who hasn't yet figured out the elephant in front of them

A great mystery for many such genes is why the tissue specificity of the tumor syndrome? In each of the genes mentioned above, the tumor syndrome appears to be very specific to a tissue type, yet in each of these cases the genes involved have been shown to be parts of cellular machinery used by every cell. Why does a failure of a general part manifest itself so specifically?

The Spittoon
Erin Cline Davis sends us a couple of links from the 23andMe blog's SNPwatch feature.

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals.

The first discusses new SNPs associated with testicular cancer, including one that may explain why the disease is more common among caucasians. The second involves a recent study that identifies genetic differences between benign and malignant neuroblastoma, including several SNPs in the BARD1 gene, also mentioned in Dr. Robison's post, above. 23andMe customers can browse their own data for these SNPs, which of course doesn't substitute for professional advice.

Bayblab
Here at the Bayblab, Bayman talks about new systems biology approaches to predicting anti-tumor activity of immune cells.

They fed the info into some sort of machine learning algorithim, which came up with some pretty clear-cut boolean style predictive rules that a mere organic being (aka tumor immunologist) could never have possibly concieved of with a million years of deductive reasoning and experimental testing.

As Bayman puts it: "It's Big Blue beats Kasparov all over again!"

Respectful Insolence
Orac at Respectful Insolence has a post up, Cancer research explained briefly, that explains why we'll never have "a cure for cancer". It's a simple explanation, and one that's important to be aware of. While there, be sure to click through to see the full comic in the post.

Framing Science
Have you ever wondered how accurate some of the information on medical dramas is? What about using a show like House to teach medical ethics? Matt Nisbet writes about misleading medical programs and the balance between raising issue awareness and getting medical facts right, citing the recent cancer-related Gray's Anatomy finale as an example.

"Many people view the cancer problem as much simpler than it actually is," Brawley says. "That's because they get their medical information from television shows. But television shows are by and large fictional, and much of the medical information there is also going to be fictional."

Hematopoiesis
Finally, our friend Alex at Hematopoiesis has written about stem cell derived cancer killing NK cells.

Dan Kaufman’s lab from University of Minnesota demonstrate for the first time efficient cancer killing activity in vivo, mediated by immune cells derived from hESC. They generated natural killer (NK) cells using previously published protocol and investigated their anti-cancer activity on the range of tumors in vitro and in mouse leukemia model.

He goes on to the results and the advantages of such an approach. For a Hematopoiesis bonus, check out this post about the cancer stem cell hypothesis complexity/controversy and how it's changed over the years.

That's it for this installment of the Cancer Research Blog Carnival. We always need hosts and posts so email the Bayblab to sign up, and get your posts in here. Visit the Carnival Homepage for previous editions.

And don't forget, the Cancer Research Blog Carnival now has subscription options; you can follow by email or RSS feed. An aggregated feed of credible, rotating health and medicine blog carnivals is also available.

Burger H&E

I imagine it played out like this:

An internist, a surgeon and a pathologist walk into a fast food joint and each order a burger. The internist says, "I wonder if there is any meat in there", the surgeon takes a bite, turns the pathologist and says: "can you tell me if there was meat in there tomorow?"...

So I guess after a bunch of H&E later and a manuscript sent to the annals of diagnostic pathology, we find out that the meat content on average barely breaks 15%. On the other hand you'll find connective tissues, blood vessels, bone, plant and intracellular parasites and lots of water. Thankfully, no neurons...

So the moral of the story is never bring a pathologist to a fast food joint if you want to be able to enjoy your burger.

Cow's milk allergy & recombinant proteins

A quick post about stuff I don't understand:
A friend of mine has an infant that is allergic to cow's milk. This is common and, who cares, since the infant is being breast fed. EXCEPT for the fact that the infant is allergic to the dairy products that the mother is consuming. This is somewhat uncommon but certainly not unheard of. My interpretation of this is that a protein antigen not only passes relatively intact from the GI tract of the mother into her blood, but is then incorporated into her breast milk without being completely broken down to amino acids and/or incorporated into human milk proteins. I always thought that proteins were almost completely broken down into, at most, a few amino acids long before absorption. The previous link suggests that relatively intact dietary protein is present in our blood.
Does this lend credibility to those who fear the biological activity from ingested proteins that are introduced into our food artificially as in the case of bovine growth hormone in cow's milk or Bt toxin in GE crops?
Anybody with some helpful information?

Wolfram|Alpha

A new search engine has recently gone online, though Wolfram|Alpha seems more a competitor to Wikipedia than to Google. The idea is to serve as a data search and computational engine.

Wolfram|Alpha's long-term goal is to make all systematic knowledge immediately computable and accessible to everyone. We aim to collect and curate all objective data; implement every known model, method, and algorithm; and make it possible to compute whatever can be computed about anything. Our goal is to build on the achievements of science and other systematizations of knowledge to provide a single source that can be relied on by everyone for definitive answers to factual queries.

It can solve equations for you, tell you notable events for a given date, or give you the current sky position of Pioneer 11. Try typing in your favourite gene, or even your first name. It's a cool little resource. I had fun playing around with inputs to see what it could do.

Extreme Mammals at AMNH

I was in New York City (and environs) this past weekend, and was fortunate enough to get an invite to a blogger preview of a new exhibit at the American Museum of Natural History. Unfortunately, my camera battery crapped out on me in the early going but luckily the press kit included in the blogger gift bag had some photos to share, so you won't have to suffer pics taken on a camera phone.

Extreme size: Indricotherium, the largest land mammal known, greets you at the exhibit's entrance

The exhibit is Extreme Mammals and is put on in collaboration with the California Academy of Sciences, San Francisco; Cleveland Museum of Natural History; and our own Canadian Museum of Nature here in Ottawa.

As you might guess, mammals were the order of the day, from the largest to the smallest and everything in between. And in between was key - the exhibit features fossils and models of some cool transitional forms as well as those of our stranger cousins such as the extinct Macrauchenia or the familiar platypus.

Macrauchenia is straight out of a Star Wars or fantasy movie

Among the fossils, taxidermy samples and models were the stars of the show: a colony of sugar gliders. Though they were napping while we were there (extreme laziness?), the sole live animal display definitely drew a crowd, particularly among the younger attendees. There were also a few simple interactive displays.

Ambulocetus, or "walking whale" is one of the transitional forms on display

The exhibit is unapologetic about evolution, which features heavily in both the displays and the educator guide as they discuss common ancestry, evolutionary trees and adaptation among other things including the requisite 'fun facts' and trivia. Did you know that a new species of striped rabbit was first discovered for sale in an Asian food market? (extreme deliciousness?)

Overall, Extreme Mammals is a cool exhibit, worth checking out if you're in the NYC area where it will be on display at the American Museum of Natural History until January of next year. After that, it will be on tour and if you're patient it's scheduled to arrive in Ottawa June 4 to November 6, 2011.

Local content: Puijila darwini, an early fin-footed mammal, was discovered in 2007 by a researcher from the Canadian Museum of Nature, Ottawa

Thanks to Brian from Laelaps who put me in touch with the museum for the blogger preview.

Images © AMNH

Rent-A-Bay?

Was looking at this article on the booming market for renting virtual office space for small business.

"I wanted to launch my company, but the cost of having a professional location was simply too high," says Mr. Gerochi. "This gave me the push to do it. I pay $300 a month and I can appear big-time to major clients.

"I use their reception staff -- they take all my calls -- office space, mailing service. The building address is advantageous. It's more professional than a home address and filters out unwanted solicitation. I can rent a cubicle for $15 an hour or a window office on the 57th floor at First Canadian Place in Toronto for $25 an hour instead of sitting in the food court with my laptop." He also uses the boardroom ($70/hour) to network with industry leaders."

Great way for entrepreneurs to overcome crippling infrastructure and basic staffing costs. It occurs to me that even higher infrastructure and start-up equipment costs pose a similar huge obstacle to the would-be biotech entrepreneur. Research space is like office space, except way more high-tech and costly. Rental lab space sounds like a great solution. Does your institute have any empty lab bays or equipment sitting unused? Let's see that shit up on Craigslist. Starving PhDs with great ideas are ready to put it to good use. You could even sell off those unused technical support staff people-hours. Like lunch.

Oh, cool. Apprently you can already do something like this. Like here. Not to be confused with here.

Kids! Sue your parents for defective genes!

This story is a bit old, and a bit odd. A 13-year-old girl born with Fragile X syndrome is suing a sperm bank after genetic tests showed the genetic condition was carried on the father's X chromosome. (Weirdness about a girl inheriting an X-linked condition from her father, and a Fragile X male as a sperm donor explained here. The short version is that it's a spectrum, repeat-expansion disease whose severity varies from generation to generation so a mildly affected father could have a more severely affected daughter, though it's rare)

The legal premise is based on product liability law that is usually applied to manufacturer defects such as faulty car brakes

Donovan does not have to show that Idant was negligent, only that the sperm it provided was unsafe and caused injury. "It doesn't matter how much care was taken," says Daniel Thistle, the lawyer representing Donovan, based in Philadelphia, Pennsylvania. Genetic tests have revealed that she inherited the disorder from her biological father.

The idea of sperm as a commodity subject to product liability laws raises some interesting questions. In this age of personal genomes and genetic testing, how much responsibility does a sperm bank have to screen for genetic disorders with every available test? If a child inherits Fragile X the old-fashioned way, could they sue their parents?

Should genetic disease even be considered 'injury' for the purposes of legal liability? This is quite different from suing a car manufacturer after suffering an injury caused by defective brakes. No defective brakes and you make it to your destination without a crash and a broken leg. No 'defective' sperm and you don't exist at all.

Either way, as more and more genetic tests come into existence and screening becomes more available there will be interesting legal issues to navigate. I should have gone to law school!

Systems Tumor Immunology: It's Big Blue Beats Kasparov All Over Again

One innovative approach to cancer therapy involves isolating immune cells (tumor-infiltrating lymphocytes or TILs) from a tumor, and then trying to expand and activate them against tumor antigens in the lab. It can work, but in practice, not an efficient practice. TILs are a mixed bag of cells with all sorts of different personalities, some of which may or may or not be interested in attacking tumor cells. Some, recruited by the ever-devious tumor cells, can even work to supress the activity of the good guys. So sometimes you get a bunch of TILs that work, sometimes not.

A new paper describes a systems biology approach to tackling the complexity of TIL populations with the aim of predicting anti-tumor activity. They profiled the reactivity of a ton of TIL populations, and correlated this inforamtion with a battery of surface markers. They fed the info into some sort of machine learning algorithim, which came up with some pretty clear-cut boolean style predictive rules that a mere organic being (aka tumor immunologist) could never have possibly concieved of with a million years of deductive reasoning and experimental testing.

Check it out:
Rule 1) If the CD8⁺CD28^-CD152^- subpopulation constitutes less than 43% of the entire TIL population AND the CD94+constitutes less than 0.4% of the entire TIL population, then the TIL population is tumor-reactive.

Also, by manipulating the relative proportions of different TIL subpopulations, they could affect reactivity as predicted by their adding machine.

Wicked. Who knew an abacus could do immunology?

See: Predicting and controlling the reactivity of immune cell populations against cancer

Nature Editors Still Concerned About Swine Flu

To their credit, they lay down some numbers. Most compelling, on the surface, is the following statement:

"There is ample reason for concern: a new flu virus has emerged to which humans have no immunity, and it is spreading from person to person. That has happened only three times in the past century."

That sounds kinda scary. Is it accurate? Would we have recognized the current H1N1 epidemic in its current form 100 years ago? Pinpointing flu strains down to the molecular level in thousands of patients worldwide, and integrated monitoring on the internet in real-time? It doesn't really seem reasonable to conclude there have only been three epidemics of this sort in the past century. Is our picture of the current, largely non-lethal flu epidemic not based entirely on technological revolutions of the past several years? How many swine or bird flu "pandemics" have gone totally unrecognized because of technological limitations? I guess we'll never know. Just like we have no idea when or if the swine flu will turn into some sort of apocalypse as most of the mainstream media would have had you believe a couple weeks ago. Of course there's always a chance. Like getting struck by lighting. Does anyone have the balls to put some numbers on this shit? I certainly don't.

I'd be surprised if our ability to predict the time of occurrence of a deadly flu pandemic has changed appreciably since 1909. How about we all agree that vigilant monitoring (as we are clearly already seeing) and balanced communication with the public (as we are often lacking) are important and leave the predictions, doomsday or otherwise, to Nostradamus?

See: Between A Virus and Hard Place

exhaustion hunt

I've read before about how the human body is supposedly evolved for running and that the earliest form of hunting may have been running after the prey until it collapsed of exhaustion. I always found that hard to believe. Why invest so much energy into a big brain when your survival depends on your ability to sweat and your endurance. But this video is simply amazing. I never imagined humans could be so much physically superior to other large mammals. Bonus points for David Attenborough narration.

Swine Flu Quote of the Week

"In the United States, Illinois had the most confirmed cases on Wednesday, with 122, surpassing New York with 97. Dr. Besser said that might be because Illinois was testing more. He said that Mayor Michael R. Bloomberg, on a visit to the C.D.C. earlier, had been asked by a reporter why New York had been surpassed, and had answered:

“You want 200 more cases? We’ll test 200 more people.”

More swine flu retrospective:
Global Flu Cases Top the 2,000 Mark

On "The Australasian Journal of Bone and Joint Medicine" (aka "The Merck Journal of Advertising Propaganda and other Bullshit"

This is really pathetic. TheScientist reports (Merck published fake journal):

"Merck paid an undisclosed sum to Elsevier to produce several volumes of a publication that had the look of a peer-reviewed medical journal, but contained only reprinted or summarized articles--most of which presented data favorable to Merck products--that appeared to act solely as marketing tools with no disclosure of company sponsorship."

Elsevier has pulled the journal from its roster, but you can bet there are many more so-called peer-reviewed biomedical journals out there that fit this bill. The only reason we're hearing about this one is that Vioxx gave some Australian guy a heart attack and he's suing.

Swine Flu Hits Ottawa

It's here. Via Mexico. That makes 140 cases in Canada. One girl sent to the ICU, recovering. No deaths.

Canadian Bacon Is Still Good to Go

Here in Canada we keep a close watch on our pigs. After all, Canadian back bacon is a national symbol. Nothing but the latest in molecular diagnostics for them. They minute they get infected, we know. For H1N1, that moment has arisen, sparking global interest in the fate of our little piggies:

"On Saturday, Canadian health officials said that the virus had been found in sick pigs on one farm in Alberta, the first report of the swine flu’s actually being found in swine. Previously, there had been heated debate about whether the virus could infect pigs, even though its genetic makeup clearly points to its having originated in swine at some point."

Ironically the pig in question got the flu from some dirty human:

"A worker at the farm had traveled to Mexico, fallen ill there and unknowingly brought the disease back to Canada last month. The worker has recovered."

Come on people, let's be a little more careful, this is our national treasure we're talking about. As for you consumers on the international market, not to worry; you can't get the flu from meat. So keep buying Canadian and stuffing your faces with our delicious bacon!

No Signs of Sustained Global Spread of Swine Flu

H1N1 Influenza Alert Upgraded to Level 17: "Bayman Has Concerns (But Mostly For Others)"

Why?

• The number of lab-confirmed cases is still rising, with Bayman's personal hazard ratio jumping up to 367/6,706,993,152 today, up about 6-fold or so since a couple days ago.
  
  
• This strain goes human-to human quite readily, something the wolf-crying bird flu never achieved.

• It's killed quite a few young people in Mexico. However Bayman suspects its lethality is still waaaay lower than our old friend the bird flu.

• Some flu people seem to think that making a vaccine could be difficult, as swine flu grows poorly in eggs.
  

The good news for Bayman: flu season in the northern hemisphere is almost over, so in all likelihood Bayman will get to sit this one out and see what happens in South America, before deciding whether or not to get really scared next winter.

Better information here.

National Cancer Research Month

May is National Cancer Research Month, and what better way to kick it off than with a fresh edition of the Cancer Research Blog Carnival. This month's host is Walter, at HighlightHEALTH, who has done a great job as always. head over there and check it out.

And don't forget, the carnival has subscription options; you can follow by email or RSS feed. An aggregated feed of credible, rotating health and medicine blog carnivals is also available.

Check out past editions here, and drop us a line if you're interested in hosting a future edition.

Investors keen on cancer vaccine

Reuters is reporting that several brokerages have upgraded the stock of a Seattle company, Dendreon, from 'hold' to 'buy'. The reason? Dendreon is the creator of Provenge, a prostate cancer vaccine expected to get FDA approval sometime late this year.

The reason for the excitement is recent data (presented at the American Urological Association annual meeting) showing a modest improvement in prostate cancer survival rates - a 4.1 month increase, with a 3-year survival rate of 42% compared to 23% for the control group. Oddly, the drug extends survival without shrinking tumours. However, Forbes reports that there is some concern over study design:

Much of the skepticism about Provenge until now has related to the perceived limitations of the 500-person study that Kantoff helped run. It was too small, some experts thought, and had an unusual design in which patients who did not receive Provenge and saw their cancer get worse would receive a frozen-then-thawed version of the vaccine.

This is unusual and may be unprecedented, says Donald Berry, head of biostatistics at the M.D. Anderson Cancer Center. It is possible that this frozen-then-thawed vaccine is actually different from Provenge; if it somehow harmed patients (there's no proof it does), it would actually make Provenge appear more effective. He asks how patients did after their cancer had progressed.

What's cool, though, is that if it works and is approved it will be the first cancer vaccine. The treatment itself is manufactured in part from a person's own antigen presenting cells (APCs, in this case dendritic cells). Patient APCs are extracted and co-cultured with a recombinant fusion protein. The now antigen-loaded APCs are then reinfused where they potentially activate a T-cell response against prostate cancer cells. The full course consists of 3 treatments over 4 weeks with only mild side effects compared to standard chemo treatments.

While the survival increase is quite small, it's encouraging and at least highlights the possibility of this kind of therapy. It would be interesting to know the duration of the immune response. Could this method be used as a preventative measure? How effective would it be against other cancers? (using a different antigen, of course)

Is Bayman Going to Get the Swine Flu?

64...current number of laboratory confirmed cases of flu strain H1N1 (most nonlethal) reported worldwide in the last week or so. Should I be scared? That's 64/6,706,993,152. Is that a lot? I dunno. What's normal for this time of year? I bet you could find 64/6,706,993,152 people who are postive for anything if you tried hard enough.

Thinking About Graduate Studies? Have You Considered A More Humane Form of Suicide?

This story is not really a new one to us graduate students, but I was surprised to find it at the top of the New York Times most emailed list: End the University as We Know It.

Columbia Prof Mark Taylor just comes right out and says it:

"GRADUATE education is the Detroit of higher learning. Most graduate programs in American universities produce a product for which there is no market (candidates for teaching positions that do not exist) and develop skills for which there is diminishing demand (research in subfields within subfields and publication in journals read by no one other than a few like-minded colleagues), all at a rapidly rising cost (sometimes well over $100,000 in student loans)."

Here from my fox hole at final-year PhD student ground zero, I can tell you Mark is not suffering from tenureship delusion. He's right on the money. The demise of graduate school spans disciplines, countries (at least in North America) and affects both core university departments and satellite institutes alike. This painful reality is worth a hard look if you're considering getting into graduate school:

"The dirty secret of higher education is that without underpaid graduate students to help in laboratories and with teaching, universities couldn’t conduct research or even instruct their growing undergraduate populations. That’s one of the main reasons we still encourage people to enroll in doctoral programs. It is simply cheaper to provide graduate students with modest stipends and adjuncts with as little as $5,000 a course — with no benefits — than it is to hire full-time professors.

In other words, young people enroll in graduate programs, work hard for subsistence pay and assume huge debt burdens, all because of the illusory promise of faculty appointments. But their economical presence, coupled with the intransigence of tenure, ensures that there will always be too many candidates for too few openings."

Kudos to Taylor for having the kahones to speak the truth in this rather public forum. I remember several years back an Ottawa journalist, Tom Spears ran a similar story on the plight of the graduate student/biomedical researcher after hanging around our research institute for a couple of days: "Hunting For Miracles at Minum Wage":

"A PhD student will work more than 60 hours a week in the lab, in return for a salary near $19,500, and sometimes payment of tuition. The salary portion is worth about $6.25 an hour -- less than minimum wage, for someone who might hold a key to heart disease, or cancer, or diabetes."

Needless to say, the Directorship of our institute tried to run him out of town. A flurry of follow-up discussion took place here on the Bayblab. See:

"Mr. T. Pities the Fool Who Does Graduate Studies"
"Are Graduate Students Exploited?", and
"More on the OHRI Salary Scandal"

I guess Spears can have the last laugh now with the knowledge he scooped the NYT.

Anyhow back to the original article. Taylor doesn't stop at just nailing down the problems. He proposes some reasonable ways to fix graduate programs. For example:

"Abolish permanent departments, even for undergraduate education, and create problem-focused programs."

"Transform the traditional dissertation. In the arts and humanities, where looming cutbacks will be most devastating, there is no longer a market for books modeled on the medieval dissertation, with more footnotes than text."

Good ideas but I don't think any of his proposals would address the most serious problem, which is the supply-demand/slavery issue.

At any rate, it's clear that research training is broken. We need to fix it. Any other ideas?