Vaginas (May not be suitable for children and some adults)

In case you missed it, vaginas were all the rage last week…

Kangaroos have not 1, not 2, but 3 vajayjays.

     Just when you thought the human vagina was complicated. The sexual reproductive plumbing of kangaroos (and all marsupials) uses 3 vaginas as “one-way streets,” two side roads for sperm and one main road that functions as the birth canal. How do the sperm know to go down the side roads? As it turns out, male marsupials have 2-pronged penises to accommodate the 2 side (lateral) vaginas while the external opening of the middle vagina (also called the pseudovagina or medial vagina) opens and closes at each birth.

     As Ed Yong points out, “With its complicated reproductive set-up, a female kangaroo can be perpetually pregnant. While one joey is developing inside the pouch, another embryo is held in reserve in a uterus, waiting for its sibling to grow up and leave. Indeed, a mother kangaroo can nourish three separate youngsters at a time – an older joey that has left the pouch, a young one developing inside it, and an embryo still waiting to be born.”

Red is the color of lust…and baboon butts.

     One speculation as to why the color red turns men on is rooted in the hypothesis that there is an ancestral attraction to red, evolutionary baggage held over from when the genitalia of our female ancestors still flushed and swelled when they were ready to tango–much like they do in Old World primates that are in “heat.” This doesn’t happen in modern humans so instead, women could attract men by wearing red as an indicator “to announce impending ovulation and sexual proceptivity.” Researchers tested this hypothesis in a study recently published in PLoS One, which is pretty well broken down in this Slate article. They reasoned that if the hypothesis were true, then men would prefer redder vaginas. To test this the researchers asked men to rate the attractiveness of images of vaginas that varied in color: pale pink, light pink, dark pink, and red. The results indicated that men had a “relative preference for pinker genital images with redder genitalia rated significantly less sexually attractive” and therefore did not support the hypothesis.

     The study, however, did not come without problems as the researchers had a hard time getting photos of vaginas. As they put it, “Explicit images of anatomically normal, un-retouched, non-pornographic, similarly oriented female genitals were surprisingly difficult to obtain.” So the study participants were shown digitally recolored images of vaginas. As Jesse Bering of Slate points out, “Perhaps I’m wrong, but to my untrained, homosexual eyes, the colors do indeed appear to capture a natural-looking variation—though the red does look a bit raw and painful.” To me the red one looks more brown. That might skew the attractiveness scale toward the pinker ones. You can have a gander at Figure 1 of their paper and decide for yourself.

     The paper also left me wondering how might social and cultural norms override biology in this context. Different cultures may attach different meanings to colors, for instance in the West the color of mourning is black. For Vietnamese culture it’s white. Unfortunately, this applies to skin tone as well–some cultures “prefer” lighter skin. Case in point: the availability of supposed vaginal bleaching products in India. (Can anyone confirm for me if Clean and Dry Intimate Wash is in fact a skin lightener?)

Related Reading:

Further scientific insight on lipstick colour?

A seductive trap that looks like a vagina but smells like poop

     Looking like part vagina, part venus fly trap, the flower of Hydnora africana, an underground-growing plant that parasitizes the roots of other plants, emits an “eau de poop” to attract and then trap dung beetles. Unlike the venus fly trap, the Hydnora africana flower doesn’t capture the beetle for food, but rather to cover it in pollen. In addition to a pollen shower, the flower provides the beetle temporary housing complete with meals–the beetle feeds on the flesh of the flower. After a few days, the flower fully blooms allowing the dung beetle to leave and carry out pollination.

Piranha plant or Audrey II? You decide.

The ongoing G-Spot controversy

     This just came in this morning in my Twitter feed. Looks like someone is claiming to have found the anatomical existence of the ever elusive G-Spot. Read this interesting take on how the media infatuation and perpetuation of the G-spot debate is counterproductive to women’s sexual health. The blog post also points out some in failures of the research, some interesting conflicts of interests, and also points out that there is no corresponding controversy/debate/focus on male orgasms despite the fact that many men have reported sexual gratification through different means such as anal and prostate stimulation. 

Condemned to a Skeletal Prison

ResearchBlogging.org

     Imagine going to sleep and waking up the next morning not able to bend your elbow or knee. Or imagine having difficulty drawing breath because your rib cage is starting to fuse. Imagine being unable to enjoy your favorite cut of steak because your jaw has locked into place. Even worse, imagine having a limb amputated because you’ve been misdiagnosed with cancer. This is the harsh reality facing patients with fibrodysplasia ossificans progressiva (FOP), a rare, genetic disease affecting 1 in 2 million people (700 known cases worldwide, 185 in the US), where soft tissues–like muscle and connective tissue–are progressively replaced by bone. Often beginning in the neck, ribbons of bone, spread through the shoulders, along the back, trunk, and limbs of the body eventually freezing patients in a skeletal cage.

     Curiously, FOP patients are born by and large symptom free, the only consistent tell-tale sign being malformed great toes:

Extraskeletal bone formation occurs sometime in the first two decades of life, usually during childhood. Bone formation is preceded by a painful, inflammatory flareup, the cause of which is unknown. A particularly insidious feature of the disease is that trauma or injury can induce these flareups, meaning that undergoing surgery to remove the extra bone only exacerbates the problem. Bumps and bruises we typically overlook cause alarm for FOP patients. Even injections, such as vaccinations, are a source of concern. Currently, while there is no cure, treatment revolves around reducing inflammation and controlling pain using corticosteriods, NSAIDS, or COX-2 inhibitors such as Vioxx (before it was pulled from the market).

A mystery unraveled

     While the earliest description of FOP dates back to the late 17th century, the cause of the disease remained an enigma for centuries until 2006, when researchers at the University of Pennsylvania linked the disease to a mutation found in FOP patients (1). The mutation affects one copy of the ACVR1(ALK2) gene, which encodes a protein important in relaying communication between cells. In the body, cells can send signals to instruct other cells to start forming bone via Bone Morphogenetic Proteins (BMP)–thus named for their ability to induce bone growth. ACVR1 is a type I receptor for BMPs and, with the help of the BMP type II receptor, acts like an antenna that receives these signals and transmits the encoded instructions to the cell.

Cellular messaging. Cells communicate with each other by sending proteins “messages” that are received by receptors on the cell surface. BMPs are just one of many types of different protein messages. These messages can instruct other cells to grow, divide, transform into other types of cells, or even self-destruct. This is analogous to people communicating by text message. BMPs and the ACVR1 receptor can be thought of as the text message and the cell phone receiving the text message, respectively.* 

     Studies in zebrafish, fruit flies and mammalian cell culture all indicate that the mutant ACVR1 receptor linked to FOP has gone rogue, capable of transmitting the instructions without having to receive the initial BMP signal (2-4). The mutant receptor acts as though its power switch has been permanently flipped to the “on” position. More recently, scientists have provided even more direct evidence that the mutant form of ACVR1 is responsible for FOP. Through a trick of genetic engineering known as “gene knock-in”, the researchers at UPenn were able to replace one copy of the normal ACVR1 gene in mice with the mutant form associated with FOP. The resulting mutant mice displayed many of the hallmarks of FOP: “malformed first digits in the hind limbs and post-natal extra-skeletal bone formation” that occurs both spontaneously and as a result of injury (5).

Adapted from Figure 2 (5). (A) Characteristic great toe malformation in FOP patient. (B) FOP mutant mice (right panels) displayed malformation of the first digits of the hind-limbs (circled) at birth. (C) Skeleton of FOP mouse with arrows to indicate extra-skeletal bone formation. Fusion of cervical vertebrae (C3-C5) (D), fusion of costovertebral malformations and fusion of vertebrae (asterisks) (E), and abnormal bone growth (arrows) (F) are observed in the mouse and FOP patients.

One of the limitations of their knock-in technique, however, was that the replacement of the normal ACVR1 gene with the mutant version was incomplete–it occured in most, but not all, of the cells in the mice. This produced chimeric mice, which were mosaics of cells that had one copy of the mutated ACVR1 gene (“FOP” cells) and cells that had two normal copies of the ACVR1 gene. Exploiting this mixed nature of the mice, the researchers were able to study how “FOP” cells interacted with normal cells. Surprisingly, they found that in the presence of “FOP” cells even normal cells were turning into bone. This suggests that cells that have the faulty ACVR1 receptor can also instruct normal cells to turn into bone through an unidentified mechanism.

Marching toward a cure

     With these findings scientists are beginning to devise strategies and design drugs that can either specifically turn off the expression of the mutant ACVR1 gene or turn off the aberrant activity of the mutant, providing hope that a cure or, at very least, an effective treatment is on the horizon. While some of these avenues are promising, a viable treatment is far from reaching the market. To find a cure will require more research, which in turn requires money. Because FOP is such a rare disease it often flies under the radar when it comes to research funding. Currently, an estimated $1.5 million a year is spent on FOP research, 25% of which is funded by institutions like the NIH and the Orthopaedic Research and Education Foundation. Incredibly, the remaining 75% is generated through donations and FOP family fundraising. If you would like to help or find out more about FOP, please visit the International FOP Association website.

Featured Image: Harry Eastlack, a man who lived with FOP, donated his skeleton to science. His skeleton is on display at the Mütter Museum.

1. Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ, Choi IH, Connor JM, Delai P, Glaser DL, LeMerrer M, Morhart R, Rogers JG, Smith R, Triffitt JT, Urtizberea JA, Zasloff M, Brown MA, Kaplan FS. A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet. 2006 May;38(5):525-7

2. Shen Q, Little SC, Xu M, Haupt J, Ast C, Katagiri T, Mundlos S, Seemann P, Kaplan FS, Mullins MC, Shore EM. The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ventralization. J Clin Invest. 2009 Nov;119(11):3462-72. doi: 10.1172/JCI37412

3. Le VQ, Wharton KA. Hyperactive BMP signaling induced by ALK2(R206H) requirestype II receptor function in a Drosophila model for classic fibrodysplasiaossificans progressiva. Dev Dyn. 2012 Jan;241(1):200-14. doi: 10.1002/dvdy.22779

4. van Dinther M, Visser N, de Gorter DJ, Doorn J, Goumans MJ, de Boer J, ten Dijke P. ALK2 R206H mutation linked to fibrodysplasia ossificans progressiva confers constitutive activity to the BMP type I receptor and sensitizes mesenchymal cells to BMP-induced osteoblast differentiation and bone formation. J Bone Miner Res. 2010 Jun;25(6):1208-15

5. Chakkalakal, S., Zhang, D., Culbert, A., Convente, M., Caron, R., Wright, A., Maidment, A., Kaplan, F., & Shore, E. (2012). An Acvr1 R206H knock-in mouse has fibrodysplasia ossificans progressiva Journal of Bone and Mineral Research DOI: 10.1002/jbmr.1637

*7.10.12 – Updated figure. See this post.

NASA in the News

It was a pretty eventful March for NASA. The MESSENGER space probe wrapped up its mission to Mercury, a project that has yielded new maps that support the hypothesis that there may be ice lurking in the innermost planet’s craters:

The mission also revealed a new estimate for how much of the planet is actually core: 85% (Earth is about 17% core). There also appears to be a solid layer of iron sulfide wrapped around Mercury’s core:

The MESSENGER space probe was initially launched in 2004 and first encountered Mercury in 2008 and entered its orbit around the planet in 2011. The probe could have reached Mercury earlier if it had taken a direct course to the planet but such an approach vector would have put the probe under the influence of the sun’s gravitational pull which would have made orbital insertion nearly impossible. Instead, MESSENGER used gravitational assistance from Earth and Venus as it flew by these planets to slingshot the probe into its circuitous trajectory to reach Mercury:

http://messenger.jhuapl.edu/the_mission/movies/encounters/od131cruiseorbitsandtimeline.mov

This, of course, was preceded by the announcement that NASA and Finland-based Rovio Entertainment cooperated on the game Angry Birds Space, a collaboration aimed at not only entertaining but also educating about concepts such as microgravity:

NASA closed out the month by firing 5 sub-orbital rockets to study the upper jet stream.  

April, however, was a different story as NASA found itself connected to two controversial topics. The Huffington Post published an uneven and journalistically (is that a word?) lazy article covering the “story” of 49 former NASA scientists and astronauts who signed a letter “blasting the agency for making unwarranted claims about the role of carbon dioxide in global warming.” The reactions from around the web were less than enthusiastic. This prompted the Huffington Post to publish a more in-depth post, a mea culpa of sorts, two days later exposing the holes in the climate change denialism argument while also pointing out the political agendas and connections of some of the former NASA astronauts and scientists. Then, just earlier this week came allegations that an ex-NASA employee was fired over his beliefs in intelligent design.

Here’s to a controversy-free May for NASA.

Carl Zimmer comes to Brown and schools me in the art science writing.

     When it came to science writing, I made a gross miscalculation. Two months ago, the idea of of science blogging came with the naive notion that it would be easy. I assumed that I would be effortlessly writing about endless topics. It wouldn’t take long before I found myself humbled by the quality of writing by other science writers or paralyzed by writer’s block. My confidence inevitably gave way to doubt.

     So I was understandably excited earlier this month when I discovered* that Carl Zimmer was coming to Brown to share his experiences as a science writer in a lecture titled, Viruses and Whales: Adventures in Science Writing. I was doubly excited when I caught wind that there would be an open discussion for students and postdocs to meet with Carl Zimmer before his talk. For those of you who don’t know, Carl Zimmer is a popular science writer and blogger who has been described “as fine a science essayist as we have” by The New York Times Book Review. He is the author of 12 science books, an essayist for Discover and The New York Times, and a frequent guest on the radio programs Radio Lab and This American Life. For any aspiring science writer trying to find both voice and audience, this was an excellent opportunity to pick the brain and learn from one of the best.

     To be honest, I wasn’t quite sure what to expect from this open discussion. My friend and I arrived at the conference room a little bit on the early side and felt too awkward to be the first ones to enter while Carl Zimmer was working on what appeared to be his talk for later that evening. Slowly but surely students started to trickle in and we took our seats. After a round of introductions, what followed was a candid and enlightening, informal discussion on popular science writing.

     When asked whether journalists should read or understand the research papers they write about (a topic explored by Alice Bell and James Randerson), he explained that he always goes to the primary literature and refers to experts in the field to fill in the gaps of his understanding. Characterizing the journalistic argument against having to read research papers, Carl quipped, “I find the argument lame.” Having sound understanding of the research you are writing about is important, particularly because, as Carl noted, news about a scientific discovery traveling from a research lab, to university press release, to print media and finally to the public can be like a game of telephone. At each stop the discovery gets a little bit more sensationalized. He also went onto say that certain constraints however, such as deadlines, would dictate the length and depth that a journalist could delve into a particular research paper.

     And just when I thought I had an encouraging leg up on journalists given my scientific training, Carl swoops in to crush that notion by pointing out that the years scientists spend on Ph.D and postdoctoral training, writers devote to honing their craft. Scientists are handicapped because the style of writing used in grants and research papers are highly inaccessible, jargon heavy, and written, much to the disgust of Carl, in passive voice–made clear by the fact that when he uttered the word “passive” it was accompanied by a pantomime of vomiting. Scientists, because of their nature, also can get bogged down in details, which derails their writing. So for scientists transitioning to popular science writing, not only do we have to retrain ourselves to unlearn “bad” habits, we also have to become good self-editors.

     The most relevant insight Carl shared that afternoon, however, dealt with story selection. The largest obstacle and primary source of writing paralysis for me is deciding on a topic to write about. I’ve spent many hours either staring at a blank document trying to figure out a different and fresh angle on a much-covered scientific discovery or surfing through countless websites and Google searches for a potentially interesting but overlooked story. This is the most challenging aspect of science writing for me because on one hand I don’t want to write about something everyone else is writing about and on the other hand overlooked stories are probably overlooked for a reason–they’re just not that interesting to a wider audience. So how does one decide? The answer in part, explains Carl, depends on where you work. If you’re working in-house for a magazine or newspaper than you have to be versatile enough to cover a wide range of topics since many of them will be assigned. You have much more flexibility as a freelancer and can write about the more obscure stories but then the burden is on you to prove that you are an expert. If you’re a blogger, then that onus is even greater–you’ve got to use your blog well and be sure to make a point. Regardless of whether your in-house, freelancing or blogging  you have to find a balance between engaging and informing your audience. While not all scientific discoveries or topics will have mass appeal, great science writers can make the public care by identifying the point they are trying to get across and weave all the relevant information into an overarching narrative or compelling story.

     I wish I could say that I left Carl Zimmer’s office hours feeling inspired. But the reality was that I felt overwhelmed. Maybe it was the fact that I had a thesis committee meeting right after the open discussion, but more likely it was because I realized that the amount of work that goes into being a good science writer was daunting. For some, writing is effortless. For me it requires work. Later that night, after Carl’s talk, I reflected on the advice and insight he shared. One thing he said stuck out. “Emulate good writers,” he advised. Luckily for me, Carl has published 12 books and countless essays for me to use as source material. That night I cracked open my girlfriend’s copy of Parasite Rex and got to work…

* For those of you who are still reluctant to join Twitter and complained that this event was not well advertised: I found out about this event from my Twitter feed.

Related Reading

You can read live tweets of Carl’s talk here.

Check out Katie PhD’s post and artful sketchnote of Carl’s visit and talk:

Probing the Passions of Science: An Interview with Carl Zimmer on the Art of Science Writing

A voyage of discovery: how the best science writers keep you enthralled

Image Credits:

http://taishimizu.com/320/NECSS-2011

http://writingworkshop.blogs.wesleyan.edu/2011/04/29/tips-for-writing-your-first-science-paper/

Patents On Nature

by Youssef Rizk, Esq.

     Most people are aware that having a patent on an invention, process, or business method is a powerful benefit granted by the government that creates an exclusive right of use to the inventor. Translation: “My idea, not yours! Hands off!”  What people often forget, however, is that in exchange for that right, the government insists that all of the details surrounding the patentable material are revealed to the public.  This requirement is an attempt to balance the individual’s right against the rights of the general public.  It encourages new invention, but promises that eventually those new inventions will become accessible to the public domain (often after 20 years).

     The requirements for obtaining a patent, which reflect the intent of the government to reward invention, but then to have the invention benefit the public interest are that:

1. The invention must be patentable (i.e. fall under the statutory definition of what is patentable

2. The invention must be new/novel (i.e. does not exist prior to the patent process);

3. The invention must be useful; (i.e. it needs to have a beneficial function);

4. The invention must be non-obvious (i.e. it should not be something that someone with a similar set of skills or background could come up with easily); and

5. The invention must be adequately described to the point that someone following the instructions could re-create the invention

 

     Two recent decisions by the U.S. Supreme Court have shaken things up in the scientific community.  First, there was the decision in the Mayo Collaborative Services, DBAMayo Medical Laboratories, Et al. v. Prometheus Laboratories, Inc. case where the court denied patents held by Prometheus.  The patents protected a testing “method” used to determine whether or not a person’s body had absorbed too little or too much thiopurine drugs (used to treat autoimmune diseases) by analyzing the metabolites in the blood after ingenstion.  The case concludes (and I am heavily summarizing the legaleze) that Prometheus could not patent a process that simply told doctors to check the levels and then compare those levels to a scale of what is considered too high or too low.  The court determined that there was nothing novel about performing tests that doctors already performed, especially because the metabolites are a naturally occurring phenomena in the human body that result from metabolizing thiopurine drugs (which the drugs themselves have been in existence long before the patent).  The process also did not instruct the doctors to do anything specific.  For example, the (loosely paraphrased) instruction: “Check the levels of the patient’s metabolites,” was not followed with a description of how to do so.  Instead it was left up to the doctor to determine the correct procedure for measuring the metabolites.  This alone does not transform Prometheus’ process into anything patentable because it relies on the doctor’s innate knowledge to check the blood levels and measure them properly.

     In the more recent case of Association for Molecular Pathology v. Myriad Genetics, No. 11-725, the U.S. Supreme Court did not deny the patents, but rather remanded the decision to the Appellate court for reconsideration in light of the Prometheus decision.  Many in the legal community view this sort of thing as essentially a message from the Supreme Court to the Appellate court implying that they change their decision.  Others feel that it may simply be that the Supreme Court needs more to go on after the Appellate Court includes Prometheus in its analysis.  Regardless, the decision has many in an uproar. 

     For starters, in the Myriad case, the issue mainly concerns actual physical materials that Myriad patented rather than a process like that in Prometheus.  Myriad’s patents are for genes found in human DNA that when examined for mutations can indicate whether or not a woman is at high risk for breast or ovarian cancer.  Some argue that the Appellate court need not consider the Prometheus case because it simply has to do with a process that was poorly defined whereas Myriad has patents on actual physical materials.  In opposition to that reasoning some argue that the Supreme Court intends the Appellate Court to analyze the decision not in terms of the patented subjects, but in terms of whether or not one can patent a natural phenomena.

     DNA is something that occurs in nature.  Patenting genes in DNA could be akin to patenting an organ found in a newly discovered insect or the liquid form of oxygen, which does not exist on Earth naturally, but is a form of a natural element.  Simply put, these physical things cannot belong to any one person because no person created them.  However, a unique process for using the new insect organ or creating liquid oxygen could be patentable (In Diamond v. Diehr, 450 U. S. 175, 185, the Supreme Court found that a mathematical formula itself was not patentable, but a unique process that used the formula was.).  What complicates the matter is that Myriad claims that the mutations when analyzed outside the body are a new and transformative creation different from what occurs naturally.  Further (and this is where Prometheus may apply more strongly), Myriad purports to have a process for determining whether or not the genes carry a mutation.  The question is whether Myriad’s process to “determine if there is a mutation” is specific enough or whether it is as general as that in Prometheus.

     Many bio companies consider these U.S. Supreme Court decisions detriments that create disincentives for companies or inventors to continue with their research when there is potentially no patent reward.  Others consider the decisions a win for the scientific community in general because restricting access to naturally occurring phenomena or obvious diagnostic testing would impede scientific progress more greatly.  The courts must consider striking a balance between the openness that benefits communal knowledge and the individual protections that reward ingenuity.  Until we see how the Appellate court further analyzes the Myriad case in light of the decision in Prometheus, we will have to wait to see how these decisions ultimately affect scientific research generally and specifically with bio companies in the long run.  

Featured image credithttp://farmwars.info/wp-content/uploads/2011/11/money.gif

Related Reading:

Gene Patenting: Ethical and Legal Issues

Rethinking the War on Cancer 4.11.12

Bang for our buck

    Last month, Nature published a damning article on the state of cancer research. In it, a former Amgen researcher C. Glenn Begley details how experiments from 47 out of 53 “landmark” cancer-related publications were irreproducible, prompting headlines such as In cancer science, many “discoveries” don’t hold up. Many of these highly-cited publications identify potential genetic targets for cancer treatment and drug research–“druggable” targets that now fall under a looming shadow of doubt. While Begley concedes that some of the failure in replicating experiments may be due to “technical differences or difficulties,” he also raises a more concerning factor: “What reasons underlie the publication of erroneous, selective or irreproducible data? The academic system and peer-review process tolerates and perhaps even inadvertently encourages such conduct.” Similarly, this system offers no incentives to confirm the scientific discoveries of others. Under pressure to win grant funding (publish or perish), researchers might be tempted to make biased and inaccurate conclusions. This not only jeopardizes the integrity of science but also wastes taxpayer funding, playing right into the narrative of the recent spate of science denialism and skepticism.

     Given the inherent flaws with this system in combination with the astronomical costs of developing drugs and a less than stellar 4.7% success rate of bringing cancer drugs to market, are we just throwing money down the drain? An article published in Science Translational Medicine would suggest that a paradigm shift is long overdue: 

More than half of the cancer occurring today is preventable by applying knowledge that we already have. Tobacco, obesity, and physical inactivity are the modifiable causes of cancer that generate the most disease. Cancer burden can be reduced by alterations in individual and population behaviors and by public health efforts as long as these changes are driven by sound scientific knowledge and social commitment to change. The obstacles to these efforts are societal and arise from the organization of institutions, including academia, and in the habits of daily life. To achieve maximal possible cancer prevention, we will need better ways to implement what we know and improved infrastructure that will better incentivize and support transdisciplinary, multilevel research and successful intervention. 

(also quoted at the The Finch and Pea)

     Prevention, of course, comes with its own obstacles. As the authors note, only 1.5% of current biomedical research is dedicated to “health services and implementation of effective prevention programs.” Furthermore, legislation and policy that encourage changes to individual and population behaviors are often met with charges of social engineering. And frustratingly, when research does yield effective vaccines to prevent cancers you can always rely on the ol’ culture wars to derail science, as was the case with Gardisil. It should be noted that the rate of new cancer cases in the US have dropped at an annual clip of 0.5% since 1998 thanks in part to better preventative measures (although this comes with a rise in obesity- and skin-related cancers). I think we can do much better than 0.5%.

New cancer test and treatment recommendations

     Our reevaluation should also not be limited to cancer research. A two-year effort by the American Society of Clinical Oncology has culminated in new recommendations for cancer tests and treatments, mirroring recent, controversial recommendations for prostate and breast cancer screenings. Whereas part of these guidelines are driven by studies indicating that certain tests and treatments will not improve the prognosis of some cancer patients, they are also driven by financial considerations as many of these procedures are costly. While, understandably, it is often the case that patients and doctors will exhaust every avenue to find effective treatment, we cannot ignore the rising cost of cancer care. (And predictably, the specter of death panels rises…)

So Crazy It Just Might Work

     Last November, I caught a captivating episode of This American Life that relates to the idea of rethinking how we approach “curing” cancer:

One day a successful cancer researcher named Jonathan Brody gave a talk at his alma mater, about how people in his field need to think outside the box if they’re going to find a cure. Afterward Jonathan’s old music teacher Anthony Holland shared an idea that was way out of the box: Killing cancer cells with electromagnetic waves.

     The idea was simple, if you could break glass with a certain frequency of sound, maybe you could target cancer cells with a certain frequency that would leave normal cells unharmed. This story works on many levels: an interesting hypothesis, an unlikely collaboration between a scientist and music professor, how outside-the-box thinking can reinvigorate science, it even touches on the ethics of disseminating unvetted scientific data (open science anyone?). But what I found very compelling about the piece was that it illustrated the apparent gulf of understanding that the public has regarding the scientific method and why science often proceeds at a maddeningly slow pace. For, although, Anthony Holland initially observed cancer cells getting obliterated by EM waves, his experimental design turned out to be improperly controlled for and the experiments could not be successfully repeated. The segment does an excellent job of chronicling Professor Holland’s toiling and frustrating attempts to replicate his experiments, proving that it takes a certain kind of masochism to be a scientist. In the end, the story for me really highlights a cultural clash that underscores the public’s perception that “seeing is believing” while in science “convincing needs repeating.” It’s worth a listen.

     You can also find out more about Anthony Holland’s documentary film in the making here.

A man, a mouse, and a fruit fly walk into a bar: Genetic approaches in understanding Alcohol Use Disorder (AUD)

ResearchBlogging.org     The recent buzz surrounding the drinking habits of Drosophila, from dealing with rejection to killing parasites by self-medicating, got me thinking: How might fruit flies be used for research in understanding the cause of alcohol use disorder (AUD)?  AUD, which encompasses both alcohol abuse and dependency, affects millions of Americans and is a complex disorder influenced by a myriad of environmental and genetic factors. Not surprisingly, efforts to identify the genes responsible for AUD in human and animal models are fraught with limitations. Human studies comparing the genetic variability between affected and unaffected individuals have identified many potential genes responsible for AUD, but only with weak statistical support, thus leaving scientists to ponder which genes are bona fide candidates. On the other hand, more feasible experiments performed in animals and cell culture have identified genes involved in ethanol response, but whether these genes are relevant to a complex, human disorder such as AUD is unknown.

     In a study published last December in G3: Genes, Genomes, Genetics, biologists from UCSD and UCSF used a multispecies approach to work around these obstacles to identify and test potential genes involved in alcohol-induced behavioral responses (Josyln et al., 2011). Behavioral changes in response to ethanol can be indicative of later AUD development. To prune the list of potential genes from the entire genome, the researchers analyzed available mouse genetic data to identify regions of the mouse genome associated with ethanol-induced ataxia (loss of coordination). These genomic regions represent clusters of genes that could influence AUD. Despite differences in overall structure and number of chromosomes, many of these gene clusters have been maintained in the genomes of many organisms–this is known as synteny. The researchers exploited this fact to cross-reference the mouse-identified regions to the corresponding sections in the human chromosomes, allowing them to focus on smaller regions rather than the daunting task of searching across the entire human genome.

Corresponding genomic regions between mouse and human genomes are color-coded.

     Next, an alcohol challenge study was performed in human subjects. Study participants were given ethanol to consume and the researchers then measured how much ethanol affected the participants inclination to sway to the left and right (another measure of coordination similar to ataxia). Using DNA collected from participants, a genetic association analysis of the human genome corresponding to the regions of the mouse genome associated with ethanol-induced ataxia was performed to identify genes linked to ethanol-induced body sway. The logic behind genetic association is that differences in DNA sequence (genetic variability) amongst individuals underly the variability in human traits (phenotypes, i.e. hair color, eye color, and in this case disease). Thus the researchers looked for a change in DNA sequence (genetic variant) that was common to individuals with the most pronounced ethanol-induced body sway (phenotype). This analysis revealed glypican 5 (GPC5) as a candidate gene involved in ethanol response in humans. GPC5 belongs to a class of genes that encode cell surface proteins, known as glypicans, that act like cellular antennas to receive protein-encoded messages from other cells (see figure below). These protein messages can induce specific responses in the cell, such as turning on the expression of specific genes or alter cellular metabolism. This form of cellular communication is known as signal transduction and is vital for the proper development of an organism.

Adapted from U. Häcker et al., 2005

     To test whether glypicans can affect ethanol response the researchers turned to Drosophila. The researchers found that mutations in the equivalent (homologous) Drosophila glypican genes, dally and dally-like (dlp), affected fruit fly behaviors sensitive to ethanol exposure. Normally, when exposed to ethanol vapor, fruit flies are initially startled and display elevated locomotor activity that becomes increasingly uncoordinated until the flies eventually becomes sedated. Mutations in both dally and dlp affected ethanol-induced locomoter activity and decreased the time it took for the fruit flies to become sedated. Interestingly, wildtype Drosophila become tolerant to ethanol since a second exposure to ethanol vapor takes a longer time to induce sedation. Only the mutation in dally displayed an inability to develop this second exposure tolerance suggesting that dally and dlp have different roles in developing tolerance to alcohol. These results confirmed that glypicans influenced alcohol-induced behaviors in Drosophila.

Bar Fly from Science News on Vimeo.

     The authors of the study reasoned that the convergence of data obtained from their mouse, human and fly studies “provides strong support to the hypothesis that GPC5 is involved in cellular and organismal ethanol response and the etiology of alcohol use disorders in humans.” In further support of their hypothesis, they point to other research indicating that the signal transduction pathways regulated by glypicans are also involved in ethanol response. While the role of GPC5 in the etiology of AUD requires further study, this research provides an example of a powerful, combinatorial genetic strategy that may prove useful in identifying causative genes in the context of other complex, multifactorial diseases such as cancer, metabolic syndrome, or heart disease.

* April is Alcohol Awareness Month

Joslyn, G., Wolf, F., Brush, G., Wu, L., Schuckit, M., White, R., & Hall, I. (2011). Glypican Gene GPC5 Participates in the Behavioral Response to Ethanol: Evidence from Humans, Mice, and Fruit Flies G3: Genes|Genomes|Genetics, 1 (7), 627-635 DOI: 10.1534/g3.111.000976