Friday, August 31, 2007

FAN DEATH!!


A extremely infrequent reader of the bayblab returned from Korea recently and informed me of the dangers of electric fans. According to many professionals, including police, media and doctors, there are many deaths due to electric fans. What is curious is the mechanism of death by fan, aka Fan death. Apparently sleeping with a fan on in a room with no open doors or windows can kill. The death is by suffocation as the fan steals oxygen in the room whilst you sleep, or possibly hypothermia as the fan cools your core body temperature.
Your probably laughing but this is a real belief held by many people in Korea.
Check out the comprehensive FanDeath.net. From the site:
"When I first heard about fan death, I discussed it with my Korean friends and students. I was the foreign skeptic and they were the loyal natives. I was shocked at how powerful their belief was and at the lack of critical thinking about the issue. All you have to do is bring up the issue of fan death with a Korean and it would be difficult to get them to accept the fact that fan death might not be true. Especially when talking to a foreigner, they are more likely to defend their cultural belief than question it. So, unable to have a semi-neutral discussion, I turned to the internet. After checking the internet for more information about fan death, I became greatly frustrated. I could not find any detailed information about fan death. So, I decided to make this site to encourage others to tell their stories and share their knowledge about the issue."
Makes the aquatic ape seem like a really believable hypothesis.


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The sex files: cavemen, monkeys and beetles

Bayman recently pointed out that he finds Neanderthals sexy, and thinks that maybe different hominids experimented with interspecies sex, perhaps while in college. Yet he may not be alone with these views, some people have proposed that red hair for example was a Neanderthal trait introduced into our gene pool. One of the long-standing problem with that theory is that no hybrid bones were ever uncovered, although a recent finding in Gibraltar may change that... Still according to wikipedia:

"On November 16, 2006 Science Daily published scientific test results demonstrating that Neanderthals and ancient humans probably did not interbreed. Scientists with the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) and the Joint Genome Institute (JGI) sequenced genomic nuclear DNA (nDNA) from a fossilized Neanderthal femur. Their results more precisely indicate a common ancestor about 706,000 years ago, and a complete separation of the ancestors of the species about 376,000 years ago. Their results show that the genomes of modern humans and Neanderthals are at least 99.5-percent identical, but despite this genetic similarity, and despite the two species having cohabitated the same geographic region for thousands of years, there is no evidence of any significant crossbreeding between the two."

Of course this makes sex with monkeys even less probable. In fact, Dave Chapelle once pointed out that AIDS could not have come from someone having sex with monkeys, because anyone who would have sex with a monkey, probably doesn't have sex with woman. Yet there has been experiments by a Russian scientist in the past:

"Dr. Il'ya Ivanov was a world-renowned expert on veterinary reproductive biology, but he wanted to do more in life than breed fatter cows. So in 1927 he traveled to Africa to pursue his vision of interbreeding man and ape. Thankfully his efforts weren't successful. To a great degree this was due to the native staff of the West Guinea research facility where he worked, from whom he constantly had to conceal the true purpose of his experiments. If they had found out what he was really doing, he wrote in his diary, "this could have led to very unpleasant consequences." The necessity of carrying out his work in secrecy made it almost impossible to do anything, although he did record two unsuccessful attempts to artificially inseminate female chimpanzees with human sperm."

He eventually tried to implant an orangutan embryo into a human womb, but the ape (Tarzan) died before the experiment could be performed, and he was sent to prison.

Still, sex with monkeys is probably more pleasant than sex with Bruchid beetles, at least for females. In this species the males unfurl an impressive penis covered with spikes and impales the female's reproductive tract. The female tries to kick the male to end copulation early and minimize damage. However she does get something out of it, she uses the copious amount of ejaculate to rehydrate and nourish herself. So the perfect female in beetles likes it quick and swallows...

In humans, kissing may also be a way for females to rehydrate: "Males, however, were more likely than females to initiate open mouth kissing and kissing with tongue contact. The researchers speculate that the exchange of saliva during kissing may have biological consequences in its own right. Male saliva contains measurable amounts of the sex hormone testosterone which can affect libido."


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Thursday, August 30, 2007

Another blow to the stem cell hypothesis

You know the immortal strand hypothesis, which says that stem cells keep the "template" DNA when they replicate asymmetrically and send off the new and therefore mutation ridden strand to the daughter cell. Well it turns out to be wrong, thus undermining the use of BrdU as a way to isolate stem cells. These findings were published in the latest Nature: "Sequential administration of 5-chloro-2-deoxyuridine and 5-iodo-2-deoxyuridine indicated that all HSCs segregate their chromosomes randomly. Division of individual HSCs in culture revealed no asymmetric segregation of the label. Thus, HSCs cannot be identified on the basis of BrdU-label retention and do not retain older DNA strands during division, indicating that these are not general properties of stem cells."

In fact this article quotes the researchers as saying:

[BrdU is] ... "a very insensitive and nonspecific marker."

and

"This study suggests that researchers should test BrdU label retention as a marker before assuming it can be used to identify stem cells in other tissues"


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Even your moma thinks you're ugly

Every year, Medical Hypotheses, an Eselvier publication, gives out a prize to honour those who think outside of the box. In 2006 the prize was given for this paper "Parental selection: a third selection process in the evolution of human hairlessness and skin color". Now the first part of that title actually makes sense, parental selection undoubtedly plays a role in evolution, including human evolution. Often in birds, parents will favor one of the offspring and let the others die. It's all a matter of opportunity cost. The metabolic cost of making a second egg, while high for the female, is still outweighed by the potential cost of losing one egg and not being able to reproduce for one season, especially if life expectancy is short. In other words, two birds in the nest is better than none in the bush. For birds, this selection may depend on cracking out of the egg a few minutes earlier, or being noisier, or having a bigger redder beak. In humans the situation is quite different. For one, twin births are relatively rare so there is no competition for milk. This means the most likely mechanism of parental selection would probably be infanticide. It is not hard to imagine that this could happen on the basis of the sex of the baby, or perhaps if there is a malformation or mental retardation. But the authors go further, much further, and they crossed the line, in fact they are so far from the line, they can't even see the line. They argue that babies had to look cute otherwise their mothers would abandon them, so they became all pink and lost their hair, so has to not be confused with Neanderthals. WHAAT? First of all, if anything, genes that would make mothers find their baby attractive no matter what are more likely to be positively selected than genes which makes them choosy. For eutherian mammals, the maternal investment leading to birth is huge, they wouldn't just throw the baby with the bathwater because he is too hairy, or not pink enough. In fact the stupidity is even greater, because if you assume that our ancestors started out hairy, then the difference in hair compared to Neanderthals does not help to discriminate the two. I mean you just have to look at the face, that's enough to differentiate them. Some people even argue that the two species might have interbred. That also seems odd to me, I mean when I see a monkey, the last thing I want is to have sex with it. I don't know about you. Plus, imagine how technically difficult that would be, first you would have to catch it in the trees. Anyways, there are definitely better theories for hairlessness such as having less parasites, especially since we humans are such poor social groomers... So I'll put that theory in the same garbage bin as the we're hairless because we had an "aquatic ape" phase bullshit.


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Wednesday, August 29, 2007

HPV vaccine program

A pretty decent article in Macleans on the HPV vaccine. Gardasil is a human papilloma virus vaccine that is scheduled to be part of a massive vaccination program of young girls starting this September. The vaccine targets strains 16 & 18 which account for causing 70 percent of cervical cancer cases. It does a poor job of talking about the percentage of adverse events associated with inoculation (probably exceedingly low), however, it still makes one wonder about whether this is really the health priority that we are being led to believe. It also explains a bit of the politics that surround the approval of this vaccination program. I also hope that the makers of the vaccine, Merck & Co., have learned their lesson with Vioxx. On the scale of a vaccination program even rare problems could have serious financial consequences for the pharma giant.


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The Wisdom of Monks

Monks are undeniably cool: from their melodic chants, to brewing history, to kung-fu skills (don't forget monks don't take a penalty on unarmed attacks). Their contributions to beer and champagne production aside, they have been active in many other areas of science. Here are just a few throughout history:

Albertus Magnus (1193-1280) - "Albert the Great" was a Dominican monk who was also a reknowned scholar. He wrote many treatises on a wide variety of topics - from astronomy to zoology - and was well known for his encyclopaedic knowledge in these areas. Like so many of his contemporaries he was also a philosopher with views on the nature of science: "Natural science does not consist in ratifying what others have said, but in seeking the causes of phenomena." Also a strong advocate for the co-existence of science and religion, he was made a saint by the Catholic church in 1931, and named the patron saint of scientists (as well as students, medical technicians and, uh, Cincinnati, Ohio) ten years later. St. Albertus also dabbled in alchemy (hey, nobody's perfect) and legend has it that he discovered the philosopher's stone, as well as creating a mechanical automaton (see entry for 'androides') that can answer questions. A saint building androids, turning lead into gold - all sounds pretty cool. In terms of REAL scientific acheivement, in addition to his voluminous writings, Albertus Magnus is also credited with being the first person to isolate the element arsenic.

William of Ockham (1288-1348) - Not quite a scientist, but definitely an early contributer to the philosophy of science, William of Ockham was an English friar of the Franciscan order. He wrote physics commentary but is most widely known for coining Occam's Razor which states "entia non sunt multiplicanda praeter necessitatem" (or, for those who don't read latin, "entities should not be multiplied beyond necessity") While not a scientific law, the idea is often invoked in scientific discussion and forms an integral part in many philosophies on the scientific method including those of Popper and Kuhn. Consciously or not, we all rely on it from time to time in it's form "All things being equal, the simplest solution/hypothesis/explanation tends to be the best one."

Gregor Mendel (1822-1884) - Born Johann Mendel, the 'father of modern genetics' was a member of the Augustinian order of monks. Mendel is a common name in any high school biology classroom because of his ideas about inheritance. He was an avid gardener and spent 7 years of his life cultivating and testing close to 30 000 pea plants, developing ideas about dominant and recessive traits and giving us the classic ratios anybody who has done a Punnett square should be familiar with. His paper "Experiments in Plant Hybridization", describing the work, was roundly criticized (the prevailing idea at the time that pangenes were responsible for inheritance, a view Darwin himself held) and received little attention until well after Mendel's death. His legacy? Mendelian genetics and Mendel's Laws.

Georges Lemaître (1894-1966) - OK, I'm cheating on this one. Lemaître wasn't a monk, but he was a Roman Catholic priest and a member of the Pontifical Academy of Sciences where he was asked by the Pope to investigate the subject of birth control. But birth control wasn't his claim to fame, nor is it why he makes this list. Georges Lemaître is famous for postulating the Big Bang Theory, and formulating an early version of Hubble's Law (before Hubble himself). Hubble's observations suggesting an expanding universe support the Big Bang theory. Though it is a widely accepted explanation of the origins of the universe, the Big Bang isn't without controversy, mostly regarding it's theological implications. At the time of it's publication in Nature in 1931, theists interpreted the Big Bang as a creation event and the religious implications that went along with it. Lemaître, however, was an advocate for the co-existence of science and religion and had this to say on the subject:

"As far as I can see, such a theory remains entirely outside any metaphysical or religious question. It leaves the materialist free to deny any transcendental Being. He may keep, for the bottom of space-time, the same attitude of mind he has been able to adopt for events occurring in non-singular places in space-time. For the believer, it removes any attempt at familiarity with God, as were Laplace’s chiquenaude or Jean’s finger. It is consonant with the wording of Isaias speaking of the “Hidden God”, hidden even in the beginning of creation."

Robo-monk (1999-present) - While the above examples are of monks contributing to science, Robo-monk is an example of science (well, engineering really) contributing to monkdom. Made out of recycled parts (from bicycles, washing machines, etc.), Robo-monk spends most of his time in silent meditation. When it detects a worshipper approaching, the praying tin-man rhythmically beats a wooden drum while leading a prayer. The only question is, does it have a soul? Leave it to the Japanese to come up with something like this, but with robot priests maybe I'll convert to Buddhism.

So there you have it, a small sampling of science that was the product of monks, and one monk who was the product of science. Who says science and religion can't mix?


5 comments:

Red Bull makes chicks smarter

I'm sorry I just had to post this story so that I could write that headline.


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On open-access and peer review

We've covered this topic often on both this blog and on the podcast but it may be time to revisit it one more time. Open access (OA) publishing has won the heart of most scientists. By definition our work only gains value by sharing, and sharing is easier when it's free. As an author of papers, I can also retain copyrights over my own work so that I am free to do whatever I please with it, including reproducing it in my thesis or posting it on my blog. I mean what's not to love. Well some people actually oppose it, obviously people who have a vested interest in the multi-million dollar publishing business. PLOS, one of the pioneers in open-access, has basically proven that not only can the idea work, but it can make for a high profile journal. But with the introduction of PLOS-ONE it may have shown its Achilles' heel. See the opponents of open-access always pointed out that openness would destroy peer review. Obviously a ridiculous assertion, since peer review is already open and free. But with PLOS ONE peer review was changed from outside "random" assigned expert to "in-house" academic editors. In fact I strongly suspect that Nature's precedings, was built to fail, an exercise in futility, to show how openness equals lack of peer review and craptacular creationist papers published. And while the opponents of open access like PRISM might have an axe to grind, they also make a good point, what is peer review, and who oversees peer reviewers?

First lets check out what they say one their site: what's at risk?

  • undermining the peer review process by compromising the viability of non-profit and commercial journals that manage and fund it;

  • opening the door to scientific censorship in the form of selective additions to or omissions from the scientific record;

  • subjecting the scientific record to the uncertainty that comes with changing federal budget priorities and bureaucratic meddling with definitive versions; and

  • introducing duplication and inefficiencies that will divert resources that would otherwise be dedicated to research.
The first point could have been better formulated. But what I think they are trying to say is "hold-on you guys can't police yourself, you need publishers to manage peer review". I mean they don't actually fund peer review since it's free but they do manage it. I don't see why editors of OA journals can't do the same, but it does raise the need for a peer-review watchdog (more on that later)

The second point is even more asinine. They're saying "Hold-on you can't choose what can and cannot be published, that's censorship, let corporations do that job". This is ironic since the purpose of journals like PLOS ONE is to let people publish based on the quality of the science not the importance of the findings. Importance is subjective, and often Nobel winning discoveries like PCR or antibodies were rejected from publication.

The third argument is also flawed because funding shouldn't affect OA journals, they are run by the publication costs defrayed by the authors. In fact one could argue that traditional private publishing is at the mercy of investors, stock market crashes and economic conditions.

Finally duplications could actually be a problem, especially for journals like PLOS ONE. If papers are not discriminated upon the basis of importance, very small incremental findings could be published which do not really lead the field forward. That being said, I would rather have more information than less. In fact if information is freely available, perhaps you would be less likely to unknowingly duplicate someone's work that was published in an obscure journal to which your institution doesn't have access.

Then what's the answer?:

Well one big step in the right direction was the creation of BPR3 an acronym coined by none other than Kevin Z (of bayblab podcast fame). Bloggers for peer review reporting aims to overview the peer review process, and check out their take on PLOS ONE. Ultimately we need some kind of watchdog, a "peer-review watch", and that it could be born in a blog just shows you the power of web 2.0 and openness.

In the mean time, why not check out this spoof of PRISM (the axis of evil publishers), called PISD (I think it is pronounced [piss]-t):
"We don't believe it's a publisher's place to make the value judgment that dissemination of scientific information is a greater social good than the increase in capital associated with charging higher subscription rates. That judgment should be made by politicians, ethicists, economists, and other valuable members of society. If you would like to know more, we suggest you consult review articles on the theory of utility or the laws of supply and demand. If your institution doesn’t provide access to such articles, we'll be happy to sell them to you at a reasonable price."


6 comments:

Monday, August 27, 2007

Obesity IS a Disease

Stem cells are at it again, but this time they're responsible for obesity. At a recent meeting of the American Chemical Society, data was presented demonstrating that infection with with a common virus - Adenovirus-36 - caused adult stem cells from adipose tissue to change into fat storing cells. Animals infected with the virus pack on the pounds, and obese people are 3 times as likely to have been infected by Ad-36 according to the report. Adenovirus-36 has also been shown to increase insulin sensitivity and reduce leptin expression - two other factors that can influence obesity. Researchers are talking about coming up with an 'obesity vaccine' to combat this form of obesity, further chiseling away at the notion of personal responsibility when dealing with one's health.


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Whiskey Science

Congeners are by-products of the fermentation process and are responsible for the taste and aroma of alcholic beverages (and some say for hangover symptoms as well). The maturation process alters the congener composition which is why a 20-year old whiskey has a different taste and aroma than a 5-year old single malt. Recent research has shown that the altered congener content also alters pharmacokinetics and neurological effects of ethanol. Using mice as their test-subjects, researchers found that the older (20-year) whiskey slowed ethanol metabolism and prolonged the neurodepressive effects of ethanol causing a longer period of drunkenness (measured by duration of loss of righting reflex). The evidence points to increases in the amount of nonvolatile congeners in the more mature whiskeys. If this is true, it means that states of drunkenness would be different among spirits with the same alcohol content - a vodka (low congener content) would give you a shorter buzz than a bourbon whiskey (higher congener content).


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Meet the Opposition to Open Access Scientific Publishing

Alex Palazzo's daily transcript has some nice info on the publishing industry's anti-open access lobby group, PRISM. What a bunch of spineless bums.


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New superior RFP cloned?

Well I can't seem to find a better reference and the article is dumbed down, but apparently some russian scientist cloned a better "turbo-RFP" from an unusually bright anemone he spotted at a pet shop. It sounds like it has a different excitation frequency than regular RFP, and that it emits further into the near-infrared, thus making it more penetrating...


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Wine science

What happens when you combine two things that I love: wine and science? Well you just have to listen to our latest podcast to find out (hint: it's not pretty). But please let me elaborate on this topic... The wine industry has dramatically changed in recent years. It's been a difficult process. Once a local product, from small traditional wineries, wine producers have had to adapt to globalization. First demand for wine began to grow worldwide, as new markets opened up in Anglo-Saxon countries (Canada, United-States, Australia, UK), and increasingly more in Asia. Wine was making producing countries, mostly France, Spain and Italy, very rich, and they felt unstoppable. Then new-world wines came in and spoiled their party. The European view of wines, as having secret traditional recipes, where the soil and region is what matters most was replaced with the "Australian" way, were productivity and reproducibility of the taste were the modus operandi. We may have lost something in the way, but wine-making was ripe for some technology. The Australians perfected mass production, and figured out ingenious ways to reproducibly create tastes that would appeal to mass markets. The French as usual, were unimpressed and accused the new wines as being catered to the lowest common denominator, to lack subtle aromas and regional variability, yet they were left unable to compete. It looks like they are now ready to fight back, and reclaim their former wine-making glory. The French teamed up with the Italians to sequence the grape genome. Even the cultivar is meaningful, they chose pinot noir which is the current darling of winos out there (curse you Sideways). Even Affymetrix now has a pinot noir gene array. And what they found was interesting, by agricultural selection, genomic loci encoding taste, and smell have been amplified. This opens up the door to transgenic grapes, with new and improved flavours and pest resistance (yay, no more sulfites). Or why not skip the grape and go straight to synthetic wines. In any case, a bold step from countries which have traditionally been very anti-GMO...


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Friday, August 24, 2007

Science Journalism Critics

Just ran into an interesting website, stats.org, that analyzes science journalism and critiques use and abuse of data in mainstream media articles. Some really good articles are on the website and it seems to me after reading a few articles that their reporting is unbiased and fair. Although, of course, they probably feel they have an obligation to be highly critical to pretty much all science reporting since they provide service to journalists writing scientific stories. They also have some books for sale that actually sound interesting for those who care about how science ends up being digested by the general public.
The one that most attracted my attention was the article entitled "Anatomy of a health scare: PCBs in Salmon." Basically I'm going to pig out on wild salmon before it's all gone.


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Queen Rockstar gets His PhD

Here's a nice feel-good story for those of us who may have entered into a deep depression after reading some of the bayblab's latest postings - Queen guitarist Brian May has proven there is life after Freddy Mercury and just completed his dissertation in astrophysics, entitled "Radial Velocities in the Zodiacal Dust Cloud". Apparently he had started his research at Imperial College in 1974 but just kind of got side-tracked when his rock band sort of became popular.

"It's a bit like an album — you've got to live with it for the rest of your life, so you want it to be perfect," said the rock star.

May also said he intends to stay in research, and has already written a science book for children. As well, BBC news reports, May " is also preparing a concert to mark the inauguration of a telescope at the Observatory of the Roque de Los Muchachos in La Palma in the Canary Islands, where he completed his studies last month."

Now this is a guy who knows how to live life.


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Cancer Research Blog Carnival

The bayblab is proud to host the first ever blog carnival on cancer research. The purpose of the exercise was two-fold: Find out who blogs about cancer research, and share ideas on this topic. Hopefully this will be the first step in creating a community of cancer research bloggers and readers. So please visit the links and share your comments!

Synthetic biology:
The first story comes from our very own bayman. Bayman is the original founder of the bayblab blog, part philosopher part mad scientist he's done some great work on oncolytic viruses and is dreaming up methods to engineer smart cells to deliver virus payloads. In this post he tells us how synthetic biology may carve the way to create bacteria that essentially function as organic computers capable of discriminating between cancer and normal tissue: "The gate integrates two environmental inputs to produce a phenotypic output. As an example, they show how their circuit can be used to program bacteria to invade mammalian cells when the concentrations of two different extracellular chemicals fall within a certain range."

Imaging:
Our next story comes from Ramūnas Janavičius a clinical genetics doctor from Vilnius University in Lithuania. He maintains a blog about cancer genetics and is particularly interested in a personalized approach to treatment. In this post he tells us how a recent study in Lancet has shown that MRI scans are vastly superior at detecting ductal carcinoma in situ compared to standard mammograms: "What is a connection between MRI, DCIS and cancer genetics, you may wonder? It is now well established, that BRCA1-positive breast tissue has different histopathological appearance and course - its usually G3, estrogen negative and expressing basal-like phenotype. Recently published studies from Canada, Italy, Germany (btw, by the same author), the Netherlands and UK (MARIBS study) all similarly showed, that MRI outperforms mammography in BRCA1 breast cancers and annual MRI is now included as addition to mammography for TP53, BRCA1 and BRCA2 mutation carriers screening programs, performed from 30 till 49 years in UK and other countries. Cost effectiveness of MRI is also proven." Check also his post about a novel biomarker for prostate cancer...

Diet:
Next we have Ruth from the Biotech Weblog. Ruth originally from the Philippines studied paddy soil microbiology at the international rice research institute. She is now a freelance writer based in Singapore. In her post she talks about how some green tea components may be protective against cancer: "epigallocatechin gallate (EGCG) equivalent to 8-16 cups of green tea, might help some people strengthen their metabolic defense against toxins capable of causing cancer by boosting the production of enzymes which belong to the glutathione S-transferase (GST) family."

Smoking:
Next we have Ben, who is a medical/PhD student in Chicago studying lung cancer and lately RNAi. He is mostly famous for having been mentioned on the bayblab podcast. In this post he tells us how Phillip Morris had troves of unpublished data about side effects of smoking. Also does a good job of explaining how second hand smoking is worse than toking, which had always been a mystery to me: "While the group that published this article had previously shown that secondhand smoke is fourfold more toxic than mainstream smoke (that is, the smoke to which a smoker is exposed), the primary findings of the present paper indicate that NNK formation increases rapidly in the local surroundings over a period of several hours after a cigarette is put out. That is, secondhand smoke clearly is harmful, and it becomes worse, and potentially more carcinogenic, even after that which is generating it is eliminated. This suggests that the dangers of smoking extend far beyond the localized duration of a single lit cigarette and the time it takes to smoke it—specifically, up to 11 hours’ worth of danger, according to Philip Morris themselves, over 20 years ago"

Clinical trials:
Next we have Joe, from the Joe Oncology blog. Joe is the leader of two cancer centers in the southeast United States. Joe shares with us the difficulties of running clinical trials, with all the agency red tape and patient recruitment nightmares: "Another problem we have is recruiting enough patients to go on trial. Patients like the idea of clinical trials but they don't like the idea of possibly receiving a placebo. I wouldn't either. Thus many opt for traditional treatment until there are no other options. Many by then don't have the will, the energy, or the qualifications to go on a clinical trial."

Pharmaceuticals:
Next we have Konstantinos Vougas, a molecular biologist from Greece who specializes in proteomics and maintains the life sciences blog. In his post he wonders what will happen with overpopulation if a cancer sure is found, and whether pharmaceutical companies are going to share it with the less fortunates: "If you were the CEO of a pharmaceutical industry giant and your R&D team came up to you one day and said “We have the perfect anti-cancer vaccine and we can get rid of cancer once and for all”, would you give this vaccine to the public? In other words would you give up on a $75 billion/year market in the US only?"

Diagnostic:
Finally we have Lim from Singapore who maintains the wacky Fresh Brainz blog. Lim is a frequent commenter on the bayblab and quite a joker. He tells us how early diagnosis can cut mortality rates: "Current work is focused on DNA-based therapeutics. Prof. Hartwell gave an example of how this is helpful: in esophageal cancer, which used to have a very poor prognosis. This is because by the time clinical symptoms appear, the patient has already entered the late stage of the cancer. Now, the outlook for patients has improved because of the availability of new screening techniques. Samples are taken from people who suffer from Barrett's esophagus and examined for DNA changes, allowing a much earlier diagnosis of cancer. "

Well that concludes our first ever blog carnival on cancer research, I hope you've enjoyed these links. I want to thank all the bloggers who submitted posts, and hope we can do this again sometime!


7 comments:

Thursday, August 23, 2007

Nature precedings?

I was catching up on the latest Nature, reading about mice with OCD and how we graduate students are all doomed because only 30% of PhDs have jobs in academia (or if you really want to be depressed read the comments on pharyngula), when I noticed an add for nature precedings. Now there is a small explanation on the site of what the purpose of nature precedings is, but judging from the content it resembles PLOS ONE. Except there is no peer review.

"Nature Precedings is a place for researchers to share pre-publication research, unpublished manuscripts, presentations, posters, white papers, technical papers, supplementary findings, and other scientific documents. Submissions are screened by our professional curation team for relevance and quality, but are not subjected to peer review."

It seems you can just submit a paper and then people can vote on it, and discuss it. Most of the popular papers are about H5N1. I can see the usefulness of rapidly sharing some information, such as polymorphisms and possible antigens. Information sharing is key if an epidemic is ever to occur. And this type of information can probably get away with not having been peer reviewed. But when I perused the cancer section I noticed some strange papers. Take this one for example "metastasis as a faulty recapitulation of ontogeny". It reads more like an OP-ED than a review or paper. The premise is that transforming somatic cells with oncogene is like bringing back the cell to its original progenitor-like state. For example some lung cancer cells look like the embryonic cells that give rise to the alveolar epithelium. Well nothing new here. He author argues that these "progenitor-like" cells will behave like their embryonic counterparts and migrate in a similar fashion. Well nothing outlandish here either. He also argues that some of the metastases may implant in different organs and assume the identity of that organ and maybe remain unnoticed. While this is all somewhat interesting I doubt any of the ideas are novel enough to actually get published in one of the "real" nature journals. In fact that paper could have easily been published on a blog . Is this the future of science publishing? Is it a good thing?


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Science blogger gets sued: for once it's not me!

PZ Myers, over at the pharyngula blog, is getting sued for libel to the tune of $15M by Stuart Pivar. The story is eerily familiar, Pivar is a businessman who thinks geneticists have it all wrong and has his own version of evolution and developmental biology. He decided to write a book about it called Lifecode, which he sent for review to PZ Myers. Myers being a developmental and evolutionary biologist called the book for what it is, bullshit, exposed all of the factual scientific errors and called Pivar a "crackpot". Now Pivar's feelings are hurt and he is suing, and he has the money to do so. I don't know yet if the World Court is involved.

Speaking of crackpots, PLOS has a good article exposing some of the HIV deniers, including our favorite character Duesberg:

"Interestingly, alternative hypotheses for AIDS causation depend on where the patient lives. In Africa, HIV deniers attribute AIDS to a combination of malnutrition and poor sanitation, i.e., they believe that AIDS is simply a relabeling of old diseases. In America and other wealthy countries, they claim AIDS is caused by drug use and promiscuity. Duesberg has long been an advocate of the idea that the use of “poppers,” or amyl nitrate, is a cause of AIDS in the gay community [31]. With the identification of AIDS in individuals who have never used poppers, this hypothesis has been widened by HIV deniers to implicate a number of recreational drugs (cocaine, crack, heroin, methamphetamines) as well as prescription drugs such as antibiotics and steroids in the etiology of AIDS. HIV deniers have criticized the idea that immunosuppression due to infection with HIV could result in all of the different infections that characterize AIDS, and yet they support the idea that poppers or other drugs—including many that have not been shown to cause severe immune deficiencies—could cause AIDS. In the past decade, the very drugs used to treat HIV/AIDS have come under fire by HIV deniers, who have suggested that the medicines themselves are a cause of AIDS"

You know I've never figured out why pharyngula is so popular, it's always the same creationist bashing, with a picture of a cephalopod thrown in from time to time. I mean I dislike creationists as much as the next scientist, but man it gets old quickly, the bayblab is soo much better.


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Wednesday, August 22, 2007

Corporate Profits Take Priority over Breast Cancer Prevention?

A recent Nature article describes the cancellation of a planned NIH trial (STELLAR) that would have compared the effects of newcomer drug Letrozole to the older Raloxifene in preventing breast cancer in post-menopausal women. While many potentially valid reasons were offered for the cancellation, other issues raised give cause to question whether the North American approach to cancer drug development is fatally flawed:

"the panel was strongly influenced by the fact that letrozole, made by Novartis, goes off-patent in 2011."

Translation: Who cares if letrozole prevents breast cancer if a corporate monopoly won't have the chance to exploit for ridiculous profits?

Hopefully this statement was issued by a disgruntled colleague and the Novartis bottom line doesn't really determine NIH trial funding decisions. Did Novartis threaten to drop their $30M/free drug contribution to the US government's $55M investment? Why should Novartis' interests be the only priority here? Once the drug is off-patent, it would available for generic production and even more accessible to patients. Must we always look for financial "returns" to justify investment in medical research? Isn't improving human health enough of a payback? Maybe it's about time North American governments reclaim some capital from the private sector to support publicly-funded research that benefits human beings instead of accountants.


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Aneuploidy Hampers Yeast Cell Proliferation

We recently discussed on the bayblab whether gross chromosomal abnormalities such as aneuploidy, frequently observed in cancer cells, are cause or consequence of tumor formation. A new paper from Torres et al. shows that yeast with extra chromosomes actually grow slower, suggesting that the relationship between aneuploidy and cancer might be a bit more complex (if the phenomenon holds true on human cells). Then again, maybe yeast are just, well...yeast.


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Virtual Epidemiology

The PS3 Folding at Home project harnesses the distributed processing power of idle playstations to use computational methods to understand protein folding, misfolding and related diseases. (The project isn't limited to the playstation - anybody with a PC and an internet connection can donate spare processor cycles). Now scientists are considering using World of Warcraft (WoW) to model infectious diseases. They think the natural interactions of a massively multiplayer online game (MMORPG) community (including travel and social interaction) can be harnessed to test hypotheses about disease spread. How well teleporting from Teldrassil to Durotar mimics an airline flight from New York to Toronto remains to be seen, but it's an interesting idea. A couple of years ago a virtual plague swept through the WoW land of Azeroth and the behaviour of the virtual population mimicked that of real populations during historical epidemics. An analysis of the 'Corrupted Blood' plague and commentary on the usefulness of MMORPGs for epidemiological studies can be found in a recent issue of the journal Epidemiology. Forget Bayman's facebook PhD... I'm majoring in World of Warcraft.


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Tuesday, August 21, 2007

Histone Code Cracked?

This report in Nature presents genome-wide CHIP maps of a variety of histone modifications in a few types of embryonic and stem cell lineages. Seems like they found some very interesting signatures that correlated well with gene expression status. For example, trimethylation at lysines 4 and 27 could discriminate expressed versus inducible versus repressed genes, whereas the same modification at lysines 4 and 9 marks imprinted regions. Very cool. Of course we'll have to see what the AC has to say for the expert opinion.

I once proposed a similar project in a mock post-doc grant proposal for a systems biology grad class I took (except with the added minor step of cloning mice by somatic cell nuclear transfer). It got pretty bad reviews. Apparently some people thought it was too ambitious. Go figure. This one only took 15 authors...


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Monday, August 20, 2007

Biofuels

Every time I read about the economics of producing ethanol fuel, it seems that it is doomed from the start. The problem is that producing ethanol from food crops, such as corn, creates additional problems, such as increasing the demand and price of a basic food staple, and using up energy to grow the crop vs how much energy you can produce. The energy balance of producing an intensive agricultural crop like corn is negative. The reason it is being pushed so hard, especially by the Bush administration (and also in Canada) is that corn production is subsidized, and we produce excess corn. Yet corn takes a lot of fertilizer and a lot of energy to grow and process. It's a win/win situation for politician, they can appear to be pro-environmental, and keep farmers in business by throwing money at them, and pretend they are fighting foreign oil dependency. But any forward thinking rational person would point out this is very short-sighted.
One way to get around this is to use a non-food crop to produce the ethanol, for example in Ottawa we have a company (Iogen) which produces enzymes to digest cellulose (dead wood) into ethanol. It's unclear wether that energy balance is positive yet, and many areas in the third world don't have wood to spare. But the problem may be ethanol itself. It is a very toxic product for cells, and we may have already reached the ethanol capacity of microorganisms.

An alternative is to produce oils instead of alcohols. The Jatropha produces seeds that are 40% oil, the plant itself is resistant to drought and pests, and it is not edible. Basic chemestry will tell you that oils are much more energy dense than sugars or alcohols. Again I'm not sure what the energy balance is for this plant but I can tell you it's superior to corn. Corn produces about 18 gallon equivalent per acre, while Jatropha produces 202 gal/acre. Already in India, the Mumbai-Delhi train uses a 20% biodiesel mix from Jatropha planted along the tracks. Oils form coconuts and palm are also very energy rich, and have great yields, but the agriculture is more energy intensive, and you are competing with food usage.

Another alternative are algae. They are relatively easy to grow, and there is a lot of space to grow them in the open ocean. Some figures based on a very generous 60% oil content estimate a maximum capacity at about 5000gal/acre. These microorganisms might also lend themselves to genetic manipulation and maybe even synthetic biology one day.

One of the most expensive steps in producing ethanol is the distilling. When it comes to oils, separating them from water is really easy, but it's the transformation into diesel that is limiting. But once again you can count on biology to provide the answer: enzymes found in fungi. Metarhizium anisopliae produces copious amounts of lipase, prefect for transforming the oils.


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Biotechnology is SO 19___

Recently the AC questioned the novelty of human genome sequencing (albeit from fossilized specimens), the work of one of Discover magazine's picks for last year's scientist of the year. He has inspired me to also question the novelty of their other two picks, just for old time's sake:

1. Using microorganisms to produce fossil fuel alternatives is SO 1934 (and probably even older).
William J. Hale of Dow Chemicals discussed this idea as a part of his broader plan for increasing the scope of agricultural manufacturing in his 1934 classic The Farm Chemurgic. I'm sure the notion had been floating around before, as it was well-known by this time that ethanol is a natural product of fermentation. But hey, who wants to burn it when you can get hammered and take off on a gasoline-guzzling joyride instead. Of course the synthetic biology approach in the context of this problem is still sexy - but doesn't necessarily change the economics of the approach, unless it increases efficiency or allows new types of starting materials to be converted.

2. The Man-Machine Interface is SO 1948.
Craig Taylor was one of the founders of one of the world's first biotechnology programs at UCLA, and kick-started the field of man-machine interfaces (and apparently liked to participate in his own experiments). Military and aeronautical engineers took a particular interest in the nascent field. I think this picture of him from Life magazine really shows that the technology of the day just cannot be beat (I that an egg he's frying with the power of his brain??):(Reproduced from R. Bud, The Uses of Life: A History of Biotechnology, 1993.)

As always, find these stories and more in The Uses of Life: A History of Biotechnology, .by Robert Bud (1993).


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The Psychology of Obvious

The human brain is an excellent pattern-recognition machine. When it comes to an 'obvious' detector, it can fall short - tricking a person into thinking something is obvious when it's not. How a toilet works seems obvious, until you're asked to explain it, for example. The idea that the obvious isn't necessarily so is an important one in science. After all, why test for something if it's a forgone conclusion? This seems particularly true for psychology - a field where many conclusions seem obvious after the fact. (I've been guilty of accusing a psychology-major roommate that "It's all just common sense" in my undergrad days. After all, it's not *real* science, right?) There's a nice little article in The Psychologist discussing the nature of obviousness, some examples of non-obvious findings and the importance of testing 'obvious' ideas. If you're interested in reading other examples of counter-intuitive science, Lim at Freshbrainz has been running a series on his blog.


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Brain size is proportional to the number of friends you can have


Perhaps this is old news to most bayblabbers but I just found out about this recently.
Apparently, group size is a function of relative neocortical volume in nonhuman primates. Meaning larger brained primates hang out in larger numbers. This correlation was first described in 1990. It is thought that a larger brain size allows an individual to keep track of its social network to which it must use to the best of its ability in order to be as reproductively successful as possible. Social interactions among primates are maintained by social grooming. And the time devoted to social grooming is linearly related to group size among the Old World monkeys and apes.
So then based on my human brain size, how much time should I be grooming my friends and indeed how many friends can I have??
Awesome questions, answered by Dunbar, R.I.M. In a paper published in 1993, Dunbar explains how language enables us to more efficiently groom our friends, because based on our brain size, we should be grooming about 150 people. Especially with modern humans grooming obsession this would be extremely time consuming without just being able to chat. Dunbar suggests in fact that 60% of human conversations are about personal experiences and gossip, thus fulfilling its role as a social networking tool.
One hundred and fifty friends then is also known as Dunbar's number. I ran into a very interesting article that discusses the concept of Dunbar's number and how it applies to modern society. Apparently just through trial and error the military has been aware of Dunbar's number before it was proposed. And some companies, like Gore-Tex, use this number for company structuring.
An absolute KILLER blog entry at http://www.lifewithalacrity.com does an awesome job of discussing Dunbar's number and attempts to challenge it using data from online networks and massive multiplayer online games and their guild sizes. Check the ganked graph I ganked from that website.
On a podcast I remember stating that I thought that language evolution was all about the meme ie. being able to learn survival abstractly from others in the group and being able to pass on behaviors that can evolve faster than biology. I guess I was wrong and it's all about being able to gossip so that you can have a bigger group with which to beat down the smaller groups.


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Sunday, August 19, 2007

PLOS tv?

Man my love for PLOS never ceases to grow. Along with a bunch of other partners they've set-up Scivee, a kind of youtube for science. In there you can find lectures and presentation from the authors of papers that have appeared in various PLOS journals. Genius!


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Global Warming Still Happening: James Hansen Strikes Back on Climate Data, Scores Points for Team God

In a newly-released statement, James Hansen, NASA scientist responsible for their temperature data, explains "what's really going on" with recent headlines that described errors in reported climate data and raised concerns regarding the realities of global warming. Yes, says Hansen, we made errors, the blogger told us about them, and we corrected them. The corrections are insignificant he claims, (see fig.) and were blown out of proportion by the conservative media in an effort to enable "the royalty" in power to go on destroying the Earth. In fact, he says, we already knew that 1998 wasn't the warmest year on record, and they reported this previously. He should've just stopped with the data ("Just shut up James. You had me at no significant difference). But no. The latter half of the letter is a fervently emotional rant about, "usufruct (WTF?), gorillas, captains of industry, court jesters and how Hansen is just working to save "Creation". Freaky.

Hey, I appreciate the man's passion and I'm all in favor of individuals and industries taking responsibility for their impact on the environment. But it would be nice to see scientists approach the issue with a balanced, objective perspective, not as Crusaders fighting to protect God's creation from Satan's evil oil-hungry minions. I don't care what God or Satan think. I just want some reality please. And don't tell me your too busy defending God's domain to get your data straight.


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Discover's scientist of the year

Discover magazine came out with their scientist of the year selection, with two runner-ups. While the scientists themselves are interesting, it's the fields that I'm most curious about. What's the sexiest science in 2007? Well the first scientist is Jay Keasling, working in, you guessed it, synthetic biology. He's famous for making a bug that spits out artemisin, a natural anti-malarial drug. He's now set his sights on making biofuel. Synthetic biology + biofuels is definitely the sexiest science right now. I must admit it wouldn't be my first thought to apply synthetic biology to producing fuel, it doesn't seem like a natural fit to me, and there is so much to figure out before making something as complex as a fuel. maybe it's just me.

The second runner up is John Donoghue, who works on brain/machine interface. Also sexy sexy science. He's working on wireless chips to implant in the brains of paraplegics to allow fine motor control. There has been a lot of progress lately in this field, with artificial retinas etc... A good choice.

The third runner up is Svante Pääbo, who wants to sequence the entire Neanderthal genome. To date, they've only managed 30Mb, still it's no small feat. However it's not the sexiest field, I mean 1999 called and they want their genome project back.

So whatever happened to stem cell biology, the former darling of hot science?


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Saturday, August 18, 2007

Man vs Wild: Japan


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Friday, August 17, 2007

Drug Marketing Regulations

Bayman previously touched upon advertising regulation in his comments here. The Globe and Mail has an article about the history of pharmaceutical advertising laws and some of the surrounding issues (sorry, subscription required). Believe it or not, ads for prescription drugs are illegal in Canada (over-the-counter meds can still be marketed). Since 1954, the Food and Drugs Act has banned the advertising of prescription drugs "to protect the purchasing consumer against injury to health, and against deception." CanWest Global is currently launching an assault on these laws in the courts, claiming they violate free speech. So why do we see so many horny elderly couples on TV, sneaking away for some afternoon delight under the shadow of a Cialis or Viagra logo?

The answer lies in a loophole built into the act, also under the guise of consumer protection. An exemption was included to allow pharmacies to post price comparisons, so buyers could get the best deal, but only the name and the price could be included in the ad - no medical conditions or claims of effectiveness. So now, as Canadians, we're treated to two kinds of 'reminder' ads: The Guy Lafleur erectile dysfunction type, that mention a condition but no drug (talk to your doctor about ED) and the Viagra type that mention a drug but no condition (Viagra...ask your doctor) and leave the rest to inference and innuendo. Be careful, though, about running the two too close together: a few years ago, Health Canada cracked down on Wyeth for running acne awareness ads in the same commercial block as their drug Alesse - a birth control and anti-acne drug, using similar themes to link the two in consumers minds.

While Canadian drug marketers have to rely on coy and uninformative (though imaginative) advertising, our neighbours to the south face a different situation. The United States is one of only two nations that allow direct to consumer pharmaceutical advertising (New Zealand is the other). Instead companies can advertise their wares, but must include extensive information about negative side-effects.

Which system is best? That's a tough call. If we must be at the mercy of advertisers, my inclination would be a US system that includes both positive and negative about the drug. It's a rare person that doesn't know what Viagra is for, but probably far fewer are aware of the side-effects. In this sense, the uninformative Canadian ads may be more harmful. However, it's been argued that allowing all-out drug advertising increases the cost of pharmacare since drug companies pass the ad expenses on to consumers. (I fail to see how allowing only Canadian-style ads reduces this expense). Finally, with all drug advertising, there's the issue of mis-prescribing. Studies have shown that if a specific drug is asked for, the chances of it being prescribed increase, regardless of whether they manifest the correct symptoms: "The fact that they asked for the antidepressant was a stronger determinant of treatment than whether they had the conditions the drug was meant to treat."


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Hiding From the Noise - Essential Genes Cluster in Open Chromatin?

We've previously discussed on the bayblab how the same transgene can provoke different murine phenotypes depending on which genomic locus it is expressed from. We've also discussed work demonstrating how noisy gene expression seems to be caused by stochastic bursts of mRNA transcription. A new paper in Nature Genetics ties together these ideas with the observation that essential genes tend to physically cluster within specific regions of genomes.

Based on the reasoning that transcriptional noise arises from the stochastic relaxation of otherwise closed chromatin, Batada and Hurst argue that essential eukaryotic genes tend to cluster within regions of open chromatin because these regions are relatively free from transcriptional noise. This would minimize the possibility of random fluctuations in expression that would kill the cell and therefore provide a selective advantage to those cells whose essential genes cluster together in less noisy regions. They present bioinformatic analyses of yeast data that seem to support this idea.

I like the idea, but am not totally sold on the notion of "essentialness". Yeast essential genes are based on those which are lethal when mutated in yeast grown under the warm and loving conditions of laboratory culture. However, the yeast genome did not evolve in the lab, it evolved in much harsher and variable natural environments. The the real set of essential genes is likely to be much larger than defined here, in fact it may include the whole genome as it is likely that each gene was essential at some point in yeast evolution. This said, even in natural environments, there maybe a spectrum of gene essential-ness, with some genes essential over a broader range of conditions, or longer evolutionary time-span than others. Thus the lab essential genes may actually reflect the core set of "most essential genes". But can we take this for granted?


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Science: Coming to a Cafe near you

All the best scientific discussions happen over a beer (just look to the Bayblab podcast for proof), but they don't have to occur just between scientists. In an effort to make science more accessible and increase public understanding of science, there's a program called Science Cafes (think Let's Talk Science for the pub set). Modelled after the British Cafe Scientifique, this program lets the general public engage in scientific discussion, ask questions, participate in debate and generally educate themselves on the latest science issues, all in an informal setting. Unfortunately the Canadian version doesn't seem to have been very active in the past couple of months - the last one in Ottawa was June 12. Maybe the Bayblab crew should host one (and podcast it, of course).


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I swear that's how it happened


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The Stem Cell Delusion: Are They Still Stem Cells If They're Bacteria?

On a previous episode of the bayblab podcast, I argued (rather poorly) that so-called mammalian "stem" cells are not so magical and deterministic as we think (ie they do not "exist"). Rather, I attempted to argue, the stem cell illusion is an emergent property of fundamental cell population dynamics and is even exhibited by the lowly unicellular prokaryotes, as exemplified by the phenomenon of bacterial persistence. A new PLOSone paper explores the theoretical basis of bacterial persistence as population bet-hedging:

"Within a population of bacteria there exists a subgroup of cells that do not grow at the normal rate but exists in a quiescent, non-growing or slow-growing state. These cells are sometimes called persister cells [1], because they are able to persist in the face of catastrophic events such as antibiotic treatment...A key aspect of persister cells is that their resistance to antibiotic treatment is not genetically determined. Consequently, following antibiotic treatment, persisters give rise to new populations that have the same vulnerability to antibiotic treatment as the ancestral population [9]."

Sound familiar stem-cell believers? Slow growth, resistance to insult, and capable of repopulating diverse cell types. OK, so maybe bacteria have stem cells too. Maybe we should even think of them as multicellular organisms. But wait, now for the challenge to faith:

"The resistance of persister cells is therefore determined phenotypically, with cells switching between the alternative phenotypic states of persistence and normal growth [7], [11]."

What the !@#$& ?? Cells shape-shifting back and forth? Stem cell one minute, non-stem cell the next? Clearly mammalian cells are different. Once a stem cell always a stem cell. Right? Wrong. The stochastic outcome of asymetric stem cell division was one of the first properties described by McCulloch and Till soon after they discovered mammalian stem cells waaaaay back in the day.

Obviously then, "stem" cells do not exist....then they do....then they don't, then they do....

Wave....particle.....wave....no, particle....no it's a wave....

Maybe it's not that bad. At least one might say there's a certain probability that a given cell will be "stem" at a certain point in space-time?


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Thursday, August 16, 2007

Bartholomew Cubbins' RNA Comedy

I gotta hand it to BC from Bartholomew Cubbins on RNA for taking science blogging to a new level with his homemade video entries. Not only does he post video reviews of the latest RNA papers, but more importantly he makes videos that will make you laugh. Check out what not to do during your lab meeting presentation, and famous RNA investigator fun to get started. Then read the rest of his blog. Please.



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The gender bending urbisexuals

No I'm not talking about metrosexual urbanites but of the hypothetical ancestor of animals with bilateral symmetry (as opposed to radial symmetry like sea urchin). The urbilateria is one of my favorite ideas in evo-devo. I like it because this mystical beast is purely a construct of inference, much like particle physic's Higgs Boson. The idea is that by looking at existing clades and phyla of protostomes and deuterostomes we can imagine what the common ancestor might have looked like. For example, maybe it had segments, and antennae, a mouth, two eyes. But what I really wonder is how did it have sex? Was the urbilateria a hermaphrodite? did it have external or internal fertilization? But the question I'm most interested in, is how his germ cells and stem cells operated. See there are two ways of making germ cells: preformation and epigenesis. In the former it is the asymetric distribution of germ plasm (coming from the oocyte) during cell division that makes the germ cell, while in the latter it is signals (BMPs) coming from the epiblast which directs dedifferentiation into germ cells. Extavour and Akam think that our ancestor used epigenesis, and that preformation reevolved several times, by simply maintaining maternal expression of germ cell genes like nanos and vasa in the zygote.

There must however be a tradeoff in keeping totipotent stem cell genes expressed in germ cells such as nanog, sox2, oct4. Quite likely that tradeoff is the risk of teratocarcinoma, which is the bizarre cancers deriving from germ cells. Great measures are taken to control germ cells and stop them from either differentiating into somatic cells or turning into cancers. Primordial Germ Cells (PGCs) are mostly transciptionally silent. They have vast changes in their chromatin structure, and very specific changes in histone and DNA methylation. In fact their embryonic precursors don't even express the stemness genes, those need to be reactivated by the BMP signal. To simplify, the stemness of the ES cell is a great liability and is quickly erased by down regulating master genes, only later does the germ cell regain this ability but at the cost of becoming transcriptionally silent. Futhermore, the migration of PGCs to the gonadal ridge acts as a second barrier to weed out potentially defective germ cells. Many germ cells get lost and die during that process. They must get there to be rescued by paracrine signals within a very narrow time. Futhermore even within the adult most female germ cells remain transcriptionally silent. Male germ cells which must remain active and divide have evolved a special DNA methylation system to keep retrotransposons in check, and they are particularly prone to apoptosis at pachytene if anything goes wrong, which means males are more susceptible to acute environmental exposure to sterilizing substances. Interrestingly germ cells also lack interferon sensitivity which has led to the evolution of a whole gamut of non-coding RNA regulation. There are about 50 000 piRNAs which regulate germ cells and we know almost nothing about. I've been looking at a possible link between large scale changes in chromatin that occur in germ cells and piRNA as a potential comprehensive exam topic. It really blows my mind.

So where does that leave our poor urbilateria. Well perhaps it had only one type of stem cell interspersed through its body and those stem cells were mostly silently waiting for an injury, but also capable of producing germ cells. We wont know for sure until synthetic biology as grown enough for us to recreate hypothetical ancestors...


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Case for Man-Made Global Warming Made Up By NASA Scientists?

Blogger Steve McIntyre has apparently discovered what seems to be a blatantly fraudulent presentation of NASA temperature data which has been used to make the case for global warming:

"NASA has now silently released corrected figures, and the changes are truly astounding. The warmest year on record is now 1934. 1998 (long trumpeted by the media as record-breaking) moves to second place. 1921 takes third. In fact, 5 of the 10 warmest years on record now all occur before World War II."

NASA's
Reto Ruedy and James Hansen, the scientists responsible for the data, are blaming a Y2K data glitch. How convenient. Hansen made headlines previously, when he publicly denounced the US government for trying to censor his data. Sorry guys, but you're scientists. Not really cool to blame the computer for your hugely massive "mistake" of misinforming the world on global warming. Hard to believe they never even took a glance at the final data...

Despite this fiasco regarding the US data, it seems that long-term global temperatures are indeed on the rise as previously believed.

The science on this issue has become so corrupted by politics I find it pretty much impossible to know what to believe. Hopefully the scientific community will take this as a lesson that the ultimate price of compromising objectivity by selling out to political and corporate interests is the loss of the public trust. Once this happens, the benefits and freedoms science can provide are lost to society altogether. Maybe I'm naive to hope we haven't yet reached that point...


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Cancer and Aging


A pretty common theme here on the bayblab. For those of you with Nature access there is an informative (at least for me) review on the connections between cancer and aging.
"The relevance of senescence for cancer protection can be rationalized if senescence is considered as a stress-induced barrier that limits the proliferative potential of damaged cells. In keeping with this notion, recent data have shown that there are abundant senescent cells within tumours, thus moving these observations from the realm of the plastic plate into the arena of real cancer biology"


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Sea pineapple

So my japanese labmates have started this little game which consists on feeding me things and seeing if I'll eat them. To their great amusement I will pretty much eat anything. To anyone who knows me this is not a great surprise, Bear Grylls from the show Man Vs. Wild has nothing on me, plus I think he's a buffoon. The next thing they are going to feed me is the sea pineapple. Sea pineapples are an edible ascidian or sea squirt. Here is what wikipedia has to say:

"Sea pineapples are known for both their peculiar appearance, described by journalist Nick Tosches as "something that could exist only in a purely hallucinatory eco-system"[1] and their peculiar taste, described as "something like iodine"[1] and "rubber dipped in ammonia."[2] However, aficionados claim that the taste is well suited to serving with sake.[3] The flavor has been attributed to an unsaturated alcohol called cynthiaol, which is present in minute quantities.[3]"

Maybe this one will make it to my top 3 of Icelandic rotten shark, Kyrgyz fermented horse milk, and Chinese century eggs. So If Kevin is right, and sea squirts just want to have fun, there is a party in my mouth and they are invited.


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Wednesday, August 15, 2007

Creating cancer stem cells

Ok maybe I'm thick, but this latest paper still doesn't make it clear to me that static cancer stem cells exist. A team at MIT has developed a kind of media that promotes the growth of cancer stem cells. When growing identical breast tissue samples in normal or "special" media and then transforming them with the same oncogene, two types of cells are formed. Each line produced different tumours when xenografted, with the cells growing in the "special" media forming more agressive, metastasis prone cancers. Furthermore those special cells were 4 orders of magnitude more likely to form tumours (i.e. it took 10^4 less cells). The researchers concluded that they had a found a way to make cancer stem cells.

Lets get back to the definition of cancer stem cell: it's a cell which has the ability to initiate a tumour. So it should really be called a tumour initiating cell. It this respect it is more akin to an ES cell. ES cells are destroyed in the process of forming a human being. Conversely adult stem cells cannot form an organ, but they are needed for tissue homeostasis. These properties are, I think, what most people imagine a cancer stem cell has. It's the replicative compartment of the tumor.

This leads to an ambiguity: is the tumour initiating cell the same as the tumour homeostasis cell?

Take these facts into consideration:

-Many tumours only grow in the periphery and have a necrotic core, does it mean tumour homeostasis cells always migrate to the periphery, or are self-renewing at a high rate on the exterior. Would the explanation that any cancer cell in the periphery has a probabilistic ability to act as a homeostatic cell be more parsimonious?

-The authors suggest that normal cell lines have much lower abilities to form tumours than their "super" cells. They say it usually takes a million cells in a xenograft versus as little as 100 of their cells. So they argue that only about a cell in a million can hold the proliferative potential of a cell line. We know that's not true, all the cells are dividing, and you can easily start a new culture flask with 100 cells, I've done it countless times. The limiting factor here, I think, is the ability to implant and survive in the hypoxic and growth factor poor environment of a mouse, after having lived in the easy condition of growth media.

-Finally the authors argue that their media selects stem cells. Obviously that's not true, otherwise both culture conditions would create the same tumours but at different rates depending on the selection stringency. Here they get 2 types of tumour. More likely they've either selected for two types of cells or changed the phenotype of the cell with their media. They do acknowledge they have two cell types, but they argue that they have enhanced stemmness, when all they show is they have a different cell with a different probabilistic ability to initiate a totally different cancer type.


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