We, Beasties Sporulates

SalmonellaA little over 4 years ago, I joined up with three friends from grad school and launched a brand new science blog, "We, Beasties!" The name was meant to be a play on a phrase from Paul de Kruif's somewhat tongue-in-cheak translation of the first-ever microbiologist Antonie von Leeuwenhoek's term "Animacules." von Leeuwenhoek was the first human being to glimpse the world of life invisible to the naked eye, and de Kruif, 400 years later, dubbed those minuscule replicators "wee beasties." Of course, we now know much more about our microbial companions, including their immeasurable impact on our planet, on our ecosystems and on our own physiology. There are more microbes in each person's gut than there have been humans since we first came down from the trees. More microbes in our guts even than human cells in our bodies. As one of my PI's T-shirts says, we're 90% microbe, and this led, with a nod to Isaac Asimov, to the name "We, Beasties." The blog was planned as a collaboration between four microbe-obsessed scientists. I was focused on infectious disease and the immune system, Heather Olins studied microbial ecology in hydrothermal vents, Emily Gardel used microbes as tools to engineer biological fuel cells, and Dipti Nayak studied microbial evolution. From the beginning though, it was mostly me posting. Even when we got picked up by Scienceblogs less than a year into our effort (thanks mostly to Abbie's advocacy), Emily and Dipti were too busy with their research to devote much effort to writing. Heather wrote a number of great posts, and is also responsible for the post that got the most traffic in the blog's history (remember #arseniclife?), but several months-long trips to sea broke up the flow, and eventually she slowed down as well.

So for the past three years, it's been mostly an immunology blog. I've written about everything about the immune system I could think of, from autoimmune disease to serum sickness to semen allergies, Nobel prizes to parasites, the link between rock climbing and inflammation to the link between Brad Pitt's sexiness and his defense against pathogens. I've written explainers on allergies, medications, and how the immune system responds to a cut from start to finish. I've written about the problems with scientific publication and about Open Access.

Drip-Irrigation 200x135A few months ago, I wrote a guest-post for Scientific American's guest blog about allergies and genetically modified food. The community manager there, Bora Zivkovich (some of you may know him as the blogfather) has been planning to launch a group food-related blog for some time, and I suppose my post put me onto his radar, so I've been offered a spot on the team. Though GMOs are what got me in the door, I'm planning on sticking to my immunological and microbial roots. There's so much to talk about! From the effect of the microbes in our gut on metabolism, to autoimmune disorders, to food allergies and sensitivities, the list is endless. And I'll probably keep harping on the GMO controversy, but several of my fellow bloggers have much greater expertise in that realm.

Alas, my new position at SciAm means that I have to close up shop here at Scienceblogs. It's been an amazing experience. Scienceblogs.com was my first exposure to blogs about science (or indeed blogging generally), and the reason I wanted to do it. The idea that professional scientists could have an unmediated conduit to talk to people about their science was immediately appealing, even back in 2006 when I had just graduated from college and didn't really have "my" science.

But it's time for me to move on to other things. So, like a Bacillus anthracis bacterium deprived of nutrients, We, Beasties is sporulating. It's throwing out all non-essential functions and retreating into a dormant state, where it can live for centuries deprived of water and nutrients. Maybe some day, if the conditions are right and a new host wanders along, We, Beasties may hitch a ride, re-activate its metabolism and cause death and disease wherever...

Ok, the analogy isn't perfect.

As for me, I'll be at Food Matters on the SciAm network, along with a host of amazing writers focused on the science of what we eat. The science of food won't always sate me though, so for other musings about infectious disease, public health and the like, check out Red Wine and Lariam, a co-venture with my friend Todd Bixby. Come check them out, update your RSS feeds, and stay in touch!

Anti-science is not a state of mind

image Can you be skeptical about GM but believe in climate change? So asks Alice Bell in The Guardian. The answer is of course, "Yes," but you can also be a fundamentalist Christian while believing in evolution and being a great scientist, so being able to hold two things in your brain at the same time is not a useful measure of logical incompatibility. One can be right about one thing and wrong about the other.

But let's get to the real issue raised in Bell's piece, the use of the term "anti-science" to describe opponents of genetically modified organisms (GMOs):

When people use the term "anti-science", I want to know what definition of science they've based their concept of anti on.

Challenge accepted. When I use the term "anti-science," (and I have a couple times), I'm referring to the act of ignoring studies that refute your hypothesis without explaining their flaw, cherry-picking studies that support your hypothesis without regard to their rigor, ignoring the consensus of experts in peer reviewed literature, making claims that are not based in fact, shouting down people who point out those facts as shills, liars or worse etc.

Who'd be simplistic enough to be "pro" the whole of science? What sort of shallow, shampoo advert "science bit" approach to the complexities of modernity are they living by?

Who'd be simplistic enough to expand a term to it's most far-reaching interpretation, and sophistic enough to argue against that interpretation as if it meant anything. The opposite of being "anti-science" on GMO is not being "'pro' the whole of science." And what's so wrong about being pro-science? It doesn't take much nuance to accept that the scientific process is, as Carl Sagan said, "by far the most successful claim to knowledge accessible to humans," while also acknowledging, again as Carl Sagan said, "It is not perfect, it's just the best we have."

Still, I'm sympathetic with the idea that the term anti-science is, as Bell writes:

...all too often applied to close down debate.

As science communicators, we can't just say that someone is anti-science, dust off our hands and walk away. We need to explain the science, and explain why those people are wrong. The fact is, no one is really against science, which is why the anti-science criticism stings so much. Science is consistently rated among the most trusted professions, and people that don't believe in global warming or are against GMOs have to believe that their positions are grounded in scientific veracity.

I think that my main difference with Bell, and perhaps the source of the rest of my disagreement is this:

It's also a lot easier for the GM lobby to play a game of "you are wrong on science" rather than acknowledging that the bulk of the critique against them is economic and political. [emphasis mine]

It's simply not true that the bulk of objections to GMO are economic and political, and this is a huge problem. There *are* very reasonable political and economic arguments about the problems with modern agriculture, like industrial farming, monoculture and sustainability. But anti-GMO activists rail against "frankenfoods" as the boogyman for everything that ails agriculture, when most of these problems are not unique to genetically modified crops.

If my experience with people on the internet, family members, friends and acquaintances that oppose or are skeptical of GMOs is at all representative, the main objection is a vague feeling that GMO is unnatural, and therefore unsafe. For those that rise to the level of activism, economics and politics are almost never brought up, except as a last resort after I've addressed their other concerns.

But don't take my word for it, take a look at the literature published by groups supporting labeling laws in CA. They claim that GMO crops:

  • Are laboratory-made, using technology that is totally different from natural breeding methods, and pose different risks from non-GM crops

  • Can be toxic, allergenic or less nutritious than their natural counterparts

  • Are not adequately regulated to ensure safety

  • Do not increase yield potential

  • Do not reduce pesticide use but increase it

  • Create serious problems for farmers, including herbicide-tolerant “superweeds”, compromised soil quality, and increased disease susceptibility in crops

  • Have mixed economic effects

  • Harm soil quality, disrupt ecosystems, and reduce biodiversity

  • Do not offer effective solutions to climate change

  • Are as energy-hungry as any other chemically-farmed crops

  • Cannot solve the problem of world hunger but distract from its real causes – poverty, lack of access to food and, increasingly, lack of access to land to grow it on.

Now, I could spend days discussing many of these points, but that's a separate issue. I've bolded the points that I think could be classified as "economic and political," though the regulation and world hunger are really a mix of political and scientific questions. Still, that's 3/11 bullet points, hardly "the bulk" of criticism.

I would love to move to a discussion of economics and politics. There's a lot to be said, a lot of policy that could be changed. Despite my criticism of the Union of Concerned Scientists' position on GMO crops, their proposals around agriculture policy generally are excellent and deserve serious discussion. But having those discussions while people scream about non-existent allergens, toxins and health risks due to GMO is impossible.

For environmentalists that care about the health of the planet (I consider myself among them), agriculture is one of many 1,000 lbs gorillas in the room, but we're not having the right conversations. The anti-science of GMO activists is not a state of mind, not a philosophy or underlying motivation, it's an adjective for a subset of positions that is not based in experimental reality. And I for one will continue to call them out on it.

Living Factories: How Scientists Engineer Microbes to Make Useful Molecules

engineeringcells-imageA couple of weeks ago, I gave a talk for Tonight, I'm presenting at the Science In The News (SITN) Spring lecture series. If you're in the vicinity of Boston, you can come watch at 7pm in Pfizer Auditorium, located in the Mallinckrodt Chemistry Lab, 12 Oxford Street, Cambridge MA 02138.

If you can't show up in person though, SITN is now broadcasting live via google hangouts. Check out this page for details, and I'll try to upload the video feed here around 6:30 ET.

Start about 22min in

 

UCS response to my piece in SciAm

On Thursday, I had a post published on Scientific American's guest Blog about claims that genetically modified food crops could contain allergens. In it, I am critical of the Union of Concerned Scientists (a science advocacy and policy organization), for what I read as misplaced opposition to genetic engineering:

The UCS’s concern about the dire state of our food system is well-founded, and I applaud their efforts to get out in front of the policy debate. There’s just one problem: they oppose using all of our technology to help combat this problem. Specifically, I’m talking about genetic engineering (GE) and genetically modified organisms (GMO)

Via e-mail and on twitter, some folks from UCS made it clear that they believe I've mischaracterized their position. They haven't given me permission to publish the e-mails, so I won't, but I'll try to paraphrase. I was told that UCS does not oppose all uses of GMOs, but they believe that current policy does not do enough to regulate new GE varieties, that GMO companies have too much power to push past the regulation that does exist, and that there are alternatives to GE that should be pursued more aggressively. You should check out their website to read their position for yourself.

I largely agree with their position on agricultural issues - there isn't adequate regulation of new crops, large industrial farms have too much influence, and we're too reliant on monoculture (growing a single variety of a single crop year after year). However, none of these problems are unique to genetically engineered crops, and I think the fact that UCS has singled out GE as a problem confuses these issues. If GE crops were banned tomorrow, all of these same problems would remain.

I should be clear that I support UCS generally, and their work on agriculture specifically. Their roadmap for healthy farm policy is a wonderful and succinct explanation for what's wrong with the way we currently grow food, and policy proposals to make it better. But GE is a technology (among others) that can help us make it better. Yes, they should be regulated, but so should new varieties produced by techniques like mutation breeding. Yes, we need to move away from monoculture and industrial farming practices, but that's true of GE and organic farming alike.

Genetic engineering, like any other technology can be used for good and for ill. It can be helpful and it can be dangerous. New regulations and policies should be technology-neutral, and focus on outcomes.

This post was also published at my new blogging venture, Red Wine and Lariam

Science, Racism and Political Correctness

Two weeks ago, the Heritage Foundation (a conservative think-tank) released a position paper based largely on the academic research of one Jason Richwine. The conclusion (roughly paraphrased): Hispanic people have lower IQ's than white people, so an overly permissive immigration policy will drag down the US economy. Ethically, this conclusion is a deep affront to my liberal* sensibilities. The idea of basing our public policy on racism and bigotry is abhorrent.

Politically, this is dangerous territory. This is especially true after the 2012 election, when republican politicians were making noises about inclusiveness and reaching out to minorities - and in fact, the Heritage Foundation dropped Richwine almost as soon as the offending dissertation came to light (I'm not sure if they're disavowing the conclusions of their position paper though).

But what I want to talk about here is what this idea means academically. Jon Wiener at The Nation wrote a piece questioning why Harvard would award Richwine a PhD, and gave a fairly thorough accounting of why the conclusions are questionable based on recent scholarship. My friend and fellow Sbling Ethan Siegel wrote a post on Sunday going further, not just questioning why Richwine got his PhD, but flat out saying,

This. Is. Not. Okay.

This is the point at which my ethical and political sensibilities bump up against my academic principles, and for me, academic freedom wins. I don't think academics should be in the habit of silencing any scholarship, regardless of how much it offends our sensibilities. If Jason Richwine put in the work, met the requirements for his program and had his thesis approved by three independent faculty members (he did), then he deserves his PhD.

Both Jon Wiener at The Nation and Ethan here on ScienceBlogs assault Richwine's thesis based on the fact that "race" is an outdated term, "hispanic" is tough to define and doesn't actually represent a coherent group of people etc. This may be true - I largely agree with both of them on these points. Then again, I am not a sociologist, anthropologist or political scientist, and neither are Jon Wiener nor Ethan Siegel. Based on Wiener's reporting, the thesis was signed off on by three faculty members, one of whom is a strong liberal whose research specifically refutes the very premise of race as a valid category for scholarship.

The third member of the committee is the big surprise, and the big problem: Christopher Jencks, for decades a leading figure among liberals who did serious research on inequality—a contributor to The New York Review of Books, the author of important books, including Inequality: Who Gets Ahead?The Homeless and The Black White Test Score Gap. Christopher Jencks knows exactly what’s wrong with the studies purporting to link “race” with “IQ.” [emphasis mine]

Why is this a big problem? Wiener doesn't say, but I think it seems like a big problem because someone who likely disagrees strongly with the conclusions of this academic work still endorsed it. In fact,  that's a success, not a problem. If the thesis was empirically sound, I would consider it a scandal if Jencks had not signed off because the conclusions conflicted with his own work. This would be like someone in the 70's being blocked from doing a thesis that supported affirmative action. That's what's not OK. I'm not worried about Richwine and his thesis - his ideas are archaic and I'm confident that they will be relegated to the dustbin of history. What I worry about is other scholars, that have politically risky but correct ideas, being silenced for going against the prevailing wisdom.

Academic freedom, like freedom of speech, means that sometimes noxious ideas are going to be studied and espoused. To adapt a well-known phrase - The best defense against offensive scholarship is not to silence it, but is instead more scholarship.

----

*Here, I mean liberal in the philosophical sense, not the political one, though I am politically liberal as well.

OAS Wednesday - Activating immunity to suppress autoimmunity.

Every time I see an ad for some remedy that "Helps BOOST the Immune System!"  I die a little inside. It's not just that these products are often homeopathic bull*, but (as I've mentioned before), boosting the immune system can actually be a terrible idea. The immune system is a finely tuned instrument, and too much can be just as bad too little. Too much immune activation leads to allergies and autoimmune disorders like multiple sclerosis (MS) or lupus. We don't know exactly why, but the prevalence of  these "hyperinflammtory disorders," where the immune system is over-active, are on the rise. Unfortunately, most of our treatments (with a few notable exceptions) for these disorders are general blockers of the immune system, and can leave patients vulnerable to infection.

Inflammation scale

Consequently, there is enormous interest in trying to find ways to quiet the immune system to bring it back into balance, without crossing the line into immunosupression. The paper I want to talk about today took what at first glance seems like an odd approach - they activated the immune system in order to silence it.

ResearchBlogging.orgTreatment of Autoimmune Inflammation by a TLR7 Ligand Regulating the Innate Immune System

TLR7 is a receptor of the innate immune system - its normal job is to detect RNA from infectious viruses and activate an inflammatory response. However, the lab authoring this paper had previously shown that repeated stimulation with low doses of a chemical (called 1V136) that is detected by TLR 7 could actually suppress inflammation in the long-term. This isn't terribly surprising - a lot of biological processes have feedback inhibition mechanisms built in - in other words, activation of the system will lead to products that inhibit the system. The signaling pathway downstream of TLR7 is shared by a lot of the innate immune system, so blocking TLR7 signaling blocks all those other systems as well.

It works like this: TLR7 is activated by a low dose of  1v136, leading to some inflammation, but also a feedback signal that blocks future TLR7 signaling (as well as stimulation of other receptors that share the same pathway). The authors wondered whether this feedback could block inflammation coming from another source that normally leads to autoimmunity.

To test this, they used an animal model of multiple sclerosis - a disease in which the immune system attacks the brain. In order to induce this condition, mice are given a "vaccine" that trains the immune system to attack myelin, a critical protein of neurons in the brain. Five days after being given this vaccine, the authors gave some mice the drug 1v136 that triggers TLR7.

source: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0045860

I want to give these authors credit - many papers of this sort will start the treatment before they induce disease, which is a little bit disingenuous. We don't know who's going to have MS until they have it, so treatments that might help if taken before the onset of symptoms aren't really useful. These guys start giving the drug on day 5, which is still before the onset of symptoms, but at least it's after they've induced it. It would be more interesting to see what happens if the drug is given after symptoms begin, but this particular animal model probably isn't amenable to that kind of study.

As you can see from the white line in part B above, even the animals that were not given the drug seem to recover, and their recovery is pretty stable over the course of a couple of months. Most people with MS have a disease that is "relapsing and remitting," which means symptoms go away and then come back - usually each relapse is worse than the one before. Any human therapy is going to have to contend with the fact that many patients have had several relapses, and the disease has already progressed before they are diagnosed.

It's also worth noting that this treatment is NOT a selective immunosuppressive - it seems to block immune responses from a variety of sources, so it will likely suffer from the same problem as other drugs - increased susceptibility to infection. That's not necessarily a knock against it - the drugs we have don't work for all patients and having more arrows in the quiver to fight these diseases is always a good thing. And if you're suffering from autoimmunity, an increased susceptibility to infection is worth the relief. I say this as someone who's grandmother died of an infection - one she likely would have survived had she not been on are arthritis meds. But without those meds, the two decades leading up to her death would have been filled with horrendous pain in her joints.

Autoimmunity sucks, and it's on the rise, but thankfully we're getting better and better at dealing with it, one experiment at a time.

[OAS (open access science) wednesday is an attempt to highlight research published in Open Access Journals like PLoSeLife and PeerJHere are some reasons why I think OAS is important. Also check out the Open Science Federation]

Hayashi, T., Yao, S., Crain, B., Chan, M., Tawatao, R., Gray, C., Vuong, L., Lao, F., Cottam, H., Carson, D., & Corr, M. (2012). Treatment of Autoimmune Inflammation by a TLR7 Ligand Regulating the Innate Immune System PLoS ONE, 7 (9) DOI: 10.1371/journal.pone.0045860

Union of Concerned Scientists Failing on Farming

Ok, this is a little different, but it's annoying, so I'm going to talk about it. Let me begin by saying I love the Union of Concerned Scientists. They've been wonderful advocates on climate change for decades; they are media savvy, they train scientists to be media savvy, and they push the media and policy makers alike to understand the scientific consensus. When it comes to climate change, I trust them over just about any other source.

Which is why it's so disappointing that they are so wrong on genetically modified organisms.

Several years ago, UCS decided to branch out into the science of how we grow our food. This should be a wonderful thing - our agriculture system is badly broken, and there are scientific and technological solutions to help feed a growing human population while minimizing environmental impact.

There's a better way to grow our food. Working with nature instead of against it, sustainable agriculture uses 21st-century techniques and technologies to implement time-tested ideas such as crop rotation, integrated plant/animal systems, and organic soil amendments.

Sustainable agriculture is less damaging to the environment than industrial agriculture, and produces a richer, more diverse mix of foods. It's productive enough to feed the world, and efficient enough to succeed in the marketplace—but current U.S. agricultural policy stacks the deck in favor of industrial food production.

We need evidence-based advocates pressing this message, and UCS recently put out a big press release on a path to environmentally sustainable farming. They've got great information and resources, and I'd love to recommend them as a one-stop-shop for scientific information about the way we grow our food. But I can't, and it's because of this:

While the risks of genetic engineering have sometimes been exaggerated or misrepresented, GE crops do have the potential to cause a variety of health problems and environmental impacts. For instance, they may produce new allergens and toxins, spread harmful traits to weeds and non-GE crops, or harm animals that consume them.

There's so much here to address, but I'll just point you to others that make the points that genetically engineered crops are or can be more environmentally friendly, and there's never been a credible report of any pathology linked to GMOs.  There was recently an entire issue of the journal Nature (one of the most well-respected science journals in the world), in which even the most critical article basically exonerated GMO of any health impacts.

Yes, there are problems like herbicide resistant "superweeds," but this is not a problem unique to GMO - any strategy to stop pests, be they insects or weeds in agriculture, or infectious microbes in humans will lead to resistance. The mechanism is different but the end result is the same. It's also clear that there are bad uses of genetic engineering technology. And there are problems with monoculture and unsustainable farming and overuse of pesticides etc etc, but once again, these are not products of GMO technology, they are a products of industrial farming - practices used by farmers of organic and GE crops alike. UCS is right to advocate for reform of these practices, but genetic engineering is a technology that could help us escape from these practices, not a barrier to reform.

The scientific consensus on GMO may not be quite as clear as on climate change, but it's close, and it's upsetting that the UCS is joining in with the anti-science crowd on the potential risks.

List of links/phone #s for people in need of help (or offering help) #BostonHelp #bostonmarathon

Not going to report, since the facts will probably change before I hit publish, but these links should remain useful: Google people finder - for folks that can't get in touch with friends/relatives

Boston Globe-run form for people looking for or offering places in the city

Lots of folks offering help on twitter via #BostonHelp

Mayor's hotline for people looking for friends/family 617-635-4500 (via the globe)

Anyone with videos/pictures of the route (could be evidence) call 800-494-TIPS (also via Boston Globe)

Red Cross is not looking for blood donations now, but would love you to schedule for later (site was down when I checked, probably heavy traffic right now)

I've been following this almost since the news broke, and I'm beat. Gonna disconnect from social media for a bit... I'm OK, and everyone closest to me is OK, but a lot of people are not. Even setting aside the injured, there are a lot of runners stranded (many area hotels are shut down) and could probably use help. Pitch in if you can.

AskScience Live a Success! (I think) #askscilive

Ever wondered if we could identify someone by their breath? How fast you can propel a rocket using fusion power? If you can shoot at a plane with lasers and cause the pilot to burst into flame? Watch AskScience Live! Despite some technical hurdles with the G+ event, I'd say it went well last night. If you weren't able the join us live, the video is now up on youtube.

It's my birthday today, and if you didn't get me anything, you can make it up for me by just watching this :-)

Ask Science... Live! Thursday at 6pm EDT #askscilive

I'm trying something new. For several years now, I've been contributing to an online community called r/askscience. It's a place where curious people can ask questions, and have them answered - often with great, yet understandable detail - by expert scientists that have a passion for explaining their work. It's an amazing forum, and I'm continually astounded that so many scientists are so willing to donate their time and expertise to educate people, and that so many people are interested in hearing them do so.

Unfortunately, not everyone that would appreciate this sort of thing are using reddit, and so I decided to bring that ethos to another platform. I'm teaming up with some of the people from r/askscience to start a series of vcasts using Google Hangouts and Youtube. We'll be taking questions live on twitter and google+ with #AskSciLive, and answering them as best we can.

We're soliciting questions ahead of time as well - if you have something you've always wanted to ask an astrochemist, but didn't know where to turn, send us a tweet! And please tune in live at 6pm US Eastern time on Thursday April 11th. Let us know if you think this is awesome, or if you think it sucks and you have a better idea. And if you're a scientist that would like to get involved on a future panel, let us know too! We'd love to have a deep bench of expertise to draw on.

We're scientists, this is an experiment, but here's hoping it goes well!

The First Panel:

Chad Jones - graduate student at Brigham Young University studying physical chemistry, and blogger at thecollapsedwavefunction.com.

Matt Muckle - Completed graduate studies at the University of Virginia and specializes in molecular spectroscopy and astrochemistry.  His work has been published in science magazine and he now works designing novel instrumentation for analytical chemistry.

Andreas Lundberg - software engineer with experience in artificial intelligence and conventional software and a moderator at reddit’s AskScience subreddit

Kevin Bonham  - graduate student studying Immunology at Harvard, and blogger at scienceblogs.com/webeasties.

Facebook Event Google+ Event Youtube link

Friday Link Dump

Science - There's a new flu strain running around in China. As is often the case, Maryn McKenna over at Wired has the most important piece to read.

- Allie Wilkinson's piece in Ars Technica about a climate change's irreversibility, but not inevitability... it's a weird distinction, but it makes sense.

- Another good post from Keith Kloor on GMOs, but I'm not a fan of equating Monsanto with GMOs. One is a company, the other is a technology. Just because the technology is used by the company, that does not imply that the two are related.

Not Science

- The most important video I've seen in a while. Normally, I dislike TED - but this is important. Lawrence Lessig on money and politics

- Google bought up Nik Software (tools for editing photographs), and recently released them all for cheap. I've been using them for less than 24 hours and I am in love... absolutely amazing. You can try them for 14 days for free. Only downside is you can't use them for non-destructive editing, but still.

Music

Haven't been listening to much music lately, but this song is amazing:

Friday Link Dump

My blogging has been slacking, but I'm still reading a bunch that I just don't have time to comment on. So I'm going to experiment with a link dump at the end of the week. This first one features a couple week's worth of posts - feel free to start a discussion in the comments Science

- Keith Kloor has a couple of posts in the past few weeks about GMO scaremongering. I waded into the comments there, with varying levels of coherance. I'm working on an analogy about GMOs and rockets... more on that later maybe.

- Maryn McKenna continues in her tradition of being terrifying on the antibiotic resistant bacteria front - I would call it scaremongering if it weren't always completely scientifically accurate. Don't read before bed.

- Rob Dunn at SciAm's guest blog has an interesting post with predictions about how our understanding of our microbiome will change over the next decade. Bonus ideas from a number of great science bloggers in there too.

Not Science

Lots of good stuff on the sunsetting of Google Reader. Here's some good alternatives (I'm trying feedly personally). I'm a huge fan of Google Reader, but don't really understand all the fury and cries of "EVIL!" Google has a right to stop supporting products that don't fit into their business plan. I like the idea of open sourcing it, as there would undoubtably be people willing to take up the mantle, but as commenters noted, there could be a crap ton of work involved in doing that, and alternatives that already exist will be just as good.

- I rejiggered my personal website, and my girlfriend (she's a musician) got hers launched.

Music

My favorite song this week according to Last.fm:

BOY - Little Numbers from Grönland Records on Vimeo.

 

OAS Wednesday - Location, location, location

For this week's OAS Wednesday, I thought I'd try to highlight some research that's in my field. As a result, I will likely be more prone than usual to lapsing into jargon and assuming knowledge that I shouldn't (or maybe I'll over-correct and get too simplified). Please let me know if anything needs clarification. In real estate, they say that the three most important things to consider are location, location and location. The same could probably be said about many aspects of biology, including the immune system - if you get a cut on your toe, you don't want inflammation in your kidney. I've written before about the way that the cells of the immune system manage to navigate the body and arrive at the right location, but today we're getting smaller: how is it that proteins get where they need to go within an individual cell?

When talking about cells, we usually imagine a sac of fluid surrounded by a membrane. Maybe we imagine a separate sac on the inside that contains the DNA (the nucleus), but generally speaking, everything between the outer membrane and the nucleus is thought of as one homogenous mass - the cytoplasm.

In reality, the organization within cells is as vast and complicated as the organization of cells in the body, and many essential cell processes are entirely dependent on being in the right location at the right time. If you cast your memory back to high school biology, you may remember the term "organelle" (literally "little organ"), which refers to specific compartments within cells that each have different functions. Each of these organelles require a distinct set of proteins, and there's an elaborate set of processes that manage to direct these proteins to the right place.

ResearchBlogging.orgUnc93B1 mediates differential trafficking of endosomal TLRs

 

Toll-like receptors or TLRs, are proteins that our immune cells use to detect the presence of potentially infectious microbes. It's been known for several years that these TLR's are found in different locations in cells - either on the surface (plasma membrane), or inside compartments called "endosomes," which form when a cell engulfs a foreign particle or microbe (Cartoon 1).

Endocytosis cartoon_Figure 1Secretory pathway cartoon_Figure 2 It's been known for some time that another protein, called Unc93B, is required for those TLRs in endosomes to function. Unc93B is best thought of as a chaperone - it doesn't actively participate in signaling, but it gets the receptors to the right location. Since proper location is essential to the function of these receptors, removing Unc93B blocks the function of all of the endosomal TLRs. But this paper reveals that this chaperone's role in directing TLR localization is more extensive than previously thought.

All* proteins that end up in vesicles (like endosomes), on the cell surface, or secreted from the cells pass through a similar series of steps called "the secretory pathway." These proteins are translated (made) in the cytoplasm along with every other protein, but contain a signal that causes them to be threaded through a protein channel into the interior of the endoplasmic reticulum (ER). Once in the ER, they can be sent along in vesicles that bud from the ER and enter the Golgi apparatus, where they are further modified and sent off to their final destination (check out the video here... I can't figure out how to embed it).

If you think of a cell like a supply chain, the ER is the factory where products are assembled, but then they're sent off in trucks to a sorting facility, where the products receive their final packaging and are sent to their destinations. In this analogy, Unc93B is like a tracking bar code for TLRs, it stays with the package and makes sure it gets to the right place. ER to Golgi

For the endosomal TLRs, the "right place" is a compartment that merges with the endosomes formed when the cell pulls in some foreign particle - in this way, they are present in the best location to detect a possible threat. Actually, there are multiple different types of endosomes, and this paper by Lee et al demonstrates that Unc93B is responsible for sorting different TLRs into different endosomal compartments.

The paper is pretty heavy on the biochemistry, and I don't want to get too deep into the weeds looking at the actual data, but since this paper is open access, you should take a look and feel free to ask any questions that come up. I'm not sure if anyone understands exactly what the functional difference between these endosomal compartments is, even though we can tell that they are different. If anyone knows different, let me know.

*There are actually some exceptions to this rule, but talking about their trafficking would make things needlessly complicated

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[OAS (open access science) wednesday is an attempt to highlight research published in Open Access Journals like PLoSeLife and PeerJHere are some reasons why I think OAS is important. Also check out the Open Science Federation]

All figures in this post were created by me and licensed under a Creative Commons Attribution-ShareAlike 3.0 Unported License.

Creative Commons License

*There are actually some exceptions to this rule, but talking about their trafficking would make things needlessly complicated

Lee BL, Moon JE, Shu JH, Yuan L, Newman ZR, Schekman R, & Barton GM (2013). UNC93B1 mediates differential trafficking of endosomal TLRs. eLife, 2 PMID: 23426999

A few pounds of microbes, only ounces of insight

[This is my latest review for Download the Universe] Honor Thy Symbionts, by Jeff Leach. Kindle

In 2003, the Human Genome Project--an effort to sequence every gene in a human being--was completed. The success, announced to great fanfare, was supposed to herald a new era in health care. Unfortunately, the promises of personalized medicine, in which treatments are tied to a person's genetic sequence, have not yet come to fruition. A few of the reasons for this are obvious (at least in hindsight). Knowing the location and sequence of a gene is one thing, knowing what it does is quite another. And understanding the role that a gene or gene variant plays in a disease, especially when many afflictions are influenced by tens or hundreds of genes, is even harder.

Complicating matters further is the re-emerging realization that genes are not destiny, and now many new "-omics" projects are beginning to gain attention. From the transcriptome (what genes are actually expressed), to the proteome (proteins and protein modification), to the epigenome (modifications of the DNA that regulate gene expression), more and more researchers are attempting large-scale analysis of entire biological systems and trying to extract meaningful information from enormous data sets. In his new ebook, Honor Thy SymbiontsJeff Leach aims to tackle what is, in my opinion, the most fascinating of these new -omics revolutions: The Human Microbiome Project.

I desperately wanted to like Leach's book. Even though I've repeatedly heard the refrains, "There are 10 times more bacteria cells in your body than human cells," and "There are 100 times more bacterial genes in your gut than there are human genes," and "Bacteria account for 5 to 10 percent of your body mass," these facts never cease to amaze me. And I've been to enough microbiome-related research talks to know that the microscopic bugs that live in our guts can have profound impacts on our health--from metabolic disorders and type-II diabetes to multiple sclerosis and inflammatory bowel disease. The microbiome deserves a book-length discussion, but Honor Thy Symbionts falls short.

Problems

Problem 1 (I think this is the underlying reason for all of this book's problems): It's not a book, it's a collection of "essays" that are really just blog posts.

In fact, you can go to Leach's website and read almost all of the "chapters" for free on his blog. As I read his alleged book on my Kindle, it was abundantly clear that Leach simply did a large-scale copy-paste, without much additional effort. Spelling and grammatical errors abound, and phrases like "In a series of blog posts starting with this one[...]" only serve to call attention to the fact that I paid three dollars to download something I could just as easily have read on the Internet for free. In one chapter, the text refers to a graph that apparently didn't make it in the migration to Kindle. And since each chapter is really just a blog post, there's no cohesive narrative to tie the book together. Even the unifying "theme" of the microbiome is misleading, since several of the chapters don't even mention microbes.

 

Problem 2: A lot of the science is overstated.

Throughout this book, I had the same feeling of professional scientific unease I get when reading Malcolm Gladwell, without the benefit of Gladwell's ability to spin a narrative. For instance:

Though improved hygiene has many benefits, scrubbing soil from our bodies and food has thrown our immune system into an over reactive tailspin and is responsible for the skyrocketing increase in allergies and autoimmune disease.

There are several lines of evidence suggesting that hygiene may increase the risk for many inflammatory disorders, but there are plenty of other factors that may play a role, and a marginal increase in risk is a far cry from an "over reactive tailspin."

In another case, Leach describes compelling research suggesting that fiber intake can alter the levels of certain types of microbes. But then he leaps to a prescription how many grams of fiber we should eat each day (an amount significantly higher than current nutritional guidelines).

And in yet another case, Leach spends several pages discussing research on the protein consumption of spider monkeys. Based on this study, he draws conclusions about everything from human diets to agribusiness, sociology and the economics of poverty and health, finally concluding the chapter by pointing out that

This all assumes, of course, that the protein leverage theory plays any role in all of this. Maybe it doesn’t.

At least he admits the ambiguity this time. But then why all the self-assured conclusions? At times I wanted to pull my hair out.

Further complicating this scientific over-reach is Leach's failure to cite the research he's referring to. There's an extensive collection of references at the back of the book, but no link within the text to the reference itself. This seems to be another symptom of copy-pasting from a blog post. The blog posts have web links, but they were apparently were stripped out when the conversion was made.

Problem 3:  Inconsistency of style and complexity.

Leach jumps back and forth from lofty rhetoric:

It is at this interface between the terra firma of our evolutionary past and the enhanced material standard of living[...]

to colloquialisms that border on inanity. Sometimes he makes the jump within a single sentence:

In just a few thousand centuries, our kind has gone from nesting in trees, to making stone tools and digging roots, to kindling fires, to subduing flora and fauna, to erecting massive cities, and finally to downloading Angry Birds over 1 billion times (and counting).

Leach routinely throws in random and unnecessary digs at creationists. At one he point calls health-care workers who recommend baby formula "predatory." I found the constant movement between grandiosity and link-bait trolling to be jarring.

Leach also routinely mixes lay-accessible and jargon-laden writing. I know what 16S ribosomal RNA and shotgun pyrosequencing (misspelled as prosequencing) are, but I doubt the target audience of this book will. In some cases, the jargon is useful and adequately explained, but in others it just seems like Leach is trying to show off.

Redeeming Qualities

Despite these glaring problems, I don't think Leach should be written off entirely. A lot of the science he talks about is interesting and important. Our obsession with cleanliness probably does play some role in the increased prevalence of allergies and autoimmunity, even if it's not the only cause. People probably should be eating more fiber, even if we can't make a specific grams/day recommendation. The cheap cost of corn and expense of protein probably explains at least a portion of the paradoxical association of poverty and obesity, even if we can't draw a straight line between spider monkey diets and our own. And the main thesis of this book, that our dietary decisions need to be increasingly informed by our emerging understanding microbiome, is almost certainly correct.

Strangely, Leach himself makes much the same point in the introduction to this book.

While researchers are cautious and right not to oversell the microbiome (much work is still needed to confirm causation for many ailments), the direct or indirect implication of microbes in a staggering number of ailments and diseases of the modern world, reinforces that we are on the cusp of a paradigm shift from the orthodox notions of health and disease.

It's a shame that the author failed to exercise some of that caution himself.

Final Verdict

 There are too many problems for me to recommend this book. Prepare an enormous grain of salt and head over to Leach's blog instead. You'll get most of the same material, including web links to the relevant research so you can fact check any claims that seem overwrought. Meanwhile, I will anxiously await a book that tackles the microbiome and does justice to this amazing new field of research.

OAS Wednesday - Semen Boosts the Immune System! Helps HIV

One of the things that bugs me most in pop-sci and woo-woo science is the obsession with "boosting" the immune system. The immune system is in a constant balancing act - tip it too far one way and even normally harmless bacteria become life-threatening. But tilt it too far in the other direction, and you can end up with things like allergies and autoimmunity. And some pathogens have learned to take advantage of your normal immune responses, meaning that "boosting" your immune system can sometimes do more harm than good. A good case-in-point is a recent paper published in PLoS Pathogens:

IL-7 enhances replication of laboratory strains and primary isolates of HIV-1 in human lymphoid and cervico-vaginal tissues ex vivo

Background

Interleukin 7 (IL-7) is a type molecule called a "cytokine." Cytokines are chemical signals that cells of the immune system uses to communicate with each other. Some cytokines activate the immune system, some block the immune system, some act on particular cells to stimulate growth or activate one cell type while inhibiting others.

IL-7 is commonly thought of as a growth factor, specifically for T-cells, one of the major parts of the adaptive immune system. During HIV infection, one of the major problems leading to the disease AIDS is a dramatic decrease in T-cells that leaves people vulnerable to other infections. Because IL-7 increases the development of T-cells, several groups have been interested in using IL-7 as a therapy for HIV infected individuals to bring up their T-cell count. This idea seems rational enough: the problem with AIDS patients is a lack of T-cells. IL-7 increases T-cell counts. Therefore, we should use IL-7 as a therapy for AIDS patients. In fact, the company Cytheris is in a stage 2 clinical trial to do just that.

But if you know anything about HIV, you might have noticed a problem. HIV loooooves to infect T-cells. In fact, that's why AIDS patients have low T-cell counts: HIV has killed them all. This means that increasing T-cell counts may have the perverse effect of giving HIV more targets to infect and more factories in which to replicate.

As far as therapy goes, this probably isn't a concern. If a patient has so few T-cells that they need this therapy, it's clear that HIV is winning. In that case, reviving the patient's immune system is the most pressing concern, and the long term consequences of helping HIV are moot. If someone is bleeding out, you need to stop the bleeding, even if it means using your dirty hands that might give them an infection.

But the propensity of IL-7 to help out HIV is a concern in another realm - transmission. In someone that isn't already infected, having more T-cells around could make the difference between an infectious encounter and a non-infectious encounter. That's where this new research comes in. It seems that HIV positive men may actually prime their partner's immune system to make them more susceptible to infection with HIV.

See, semen is not just sperm in an innocuous fluid. It contains all sorts of other factors, including hormones that may improve mood*, stuff from food that the man has eaten (including allergens), and cytokines that modulate the partner's immune system. Scientists have long known that semen contains cytokines that dampen the immune response, a feature that makes sense from an evolutionary perspective (you don't want your partner's immune system attacking your sperm). But scientists have also noticed that semen contains IL-7, and that levels of IL-7 are higher in men with HIV.

So Andrea Introini et al decided to see what effect if any this might have on HIV transmission rates.

The concentration of interleukin (IL)-7, one of the most prominent cytokines in semen of healthy individuals, is further increased in semen of HIV-1-infected men. Here, we investigated the potential role of IL-7 in HIV-1 vaginal transmission in an ex vivo system of human cervico-vaginal tissue.

Methods

Since it would be tough to do experiments on couples in the wild, they instead turned to an experimental model, using explants of vaginal tissue** grown in a petri dish. Basically, they would take donations of tissue from patients that were undergoing hysterectomies, and keep that tissue alive in the lab. In this way, they could expose the tissue to HIV in the presence of experimentally controlled levels of IL-7. There are certainly problems with drawing conclusions from this system, but it's probably as close as you can get to doing controlled experiments in a natural system without actually infecting people. You'll lose some of the interactions with the rest of the immune system, but at least you've got an entire tissue instead of isolated cells.

Using this system, they then measured a number of different outputs, from HIV replication (literally counting the number of viruses produced), to the number of T-cells that are infected with HIV. Towards the end of the paper, they tried to explain a mechanism by which IL-7 could cause the results they see. I'll get to how that was done in the results section.

Results

The most notable result is probably evident from the title: IL-7 increases HIV infection and replication.

From http://goo.gl/f0alA

In the top graph, they are showing you the concentration of HIV virus particles found in the medium the tissues are bathed in. The dotted line is with tissue grown w/o IL-7, the dashed line is tissue grown in a low concentration of IL-7, and the solid line is tissue grown with a high amount of IL-7. The lower graph is basically the same data, but looking at the final concentration of HIV in each of the IL-7 conditions compared to the non-IL-7 condition. In other words, tissues in the presence of low dose IL-7 tended to have about twice as much HIV replication as tissue grown without IL-7, and the high dose tended to increase replication by 5-6 fold.

But why have both graphs if they're showing essentially the same thing?

When working with human tissue, you can often get wildly different results in terms of actual numbers, but scientists don't trust data that comes from a single experiment - you need to replicate it several times.  But if the authors had included multiple trials in that top graph, they could have had enormous error bars due to variation in the tissue that was used, so the top graph is showing a "representative" experiment. In the second graph, they normalize each experiment to the non-IL-7 control within that experiment, so they can graph them all together. Had they been using genetically identical mice, this might have raised some eyebrows, but when doing experiments with human tissue, it's totally acceptable.

In order to look at why IL-7 might be doing this, they decided to look at the effects of IL-7 on the T-cells present in the tissues that they were treating. T-cells that are infected with virus are often profoundly unhappy, and unhappy cells often commit cell-suicide. Cells committing suicide is often a good thing, because it prevents problems (like viral infections) from spreading, but IL-7 seems to prevent these infected T-cells killing themselves off, giving HIV more time to replicate and more opportunities to infect other T-cells.

This later result isn't terribly surprising, as IL-7 is known to be a growth factor , and several studies have shown that it can inhibit cell suicide, but it was important for these authors to demonstrate that it is still having this effect in the presence of HIV infection

Caveats / Discussion

I think this paper is an important advance, if for no other reason than highlighting a potential problem with using IL-7 as a treatment for HIV. It's important to understand factors that contribute to increasing HIV transmissiveness, and I was pleased that the authors did not suggest that this might lead to potential treatments or preventions, since blocking IL-7 during sex would be pretty impractical. Still, it's important to qualify what this paper does and doesn't show.

The paper does not show the effect of IL-7 in semen on the cells of an actual vagina. These are chunks of tissue floating in a bath of media, with a fairly high concentration of a cytokine present for long periods of time. The authors cite papers showing that semen from healthy men can contain 1-2 nanograms (1/1,000,000,000 of a gram) per milliliter, and that concentrations can be up to 100 times higher in HIV infected men. The lowest does the authors use in this study is 5 ng/mL, which seems reasonable until you realize that a typical ejaculate only contains a couple of milliliters of fluid, and that this would likely be significantly diluted out in the tissue. Further, I'm not sure anyone knows how long these cytokines are likely to persist before being used up or destroyed in the woman's genital track.

The authors did try to address that in Figure 3, where they showed that a brief treatment of IL-7 was enough to enhance replication of HIV. But it's still a fairly long pre-treatment (~16 hours), and it's hard to know if the concentrations are anywhere near what would be experienced in real life.

Shorter pre-treatment with IL-7 is sufficient to enhance HIV replication (Figure 3)

Another problem is that this study mostly evaluates the cytokine IL-7 in isolation. As I mentioned above, semen contains all kinds of stuff, including cytokines that dampen the immune system. Unfortunately, the authors note that seminal plasma from donors is toxic to cells in culture, so the best experiment (exposing tissue to seminal plasma from healthy vs HIV infected donors) is not really possible. The authors did experiments in lymphoid tissue (which contains A LOT of immune cells) with diluted seminal plasma, but I'm not convinced that these experiments add much.

I should emphasize that none of these caveats are deal breakers. Experimenting with HIV is hard, and every model we have has significant limitations. This is an interesting paper, filled with good experiments. There's definitely more to do, and more to know, but then again, that's always the case in science. It's also worth noting that the authors of this paper did not stretch their results to make grandiose claims based on their data. I don't know if this is because of the authors' restraint or good peer review, but it's always nice to see in papers with a high potential for exaggeration.

[OAS (open access science) wednesday is an attempt to highlight research published in Open Access Journals like PLoS, eLife and PeerJ. Here are some reasons why I think OAS is important. Also check out the Open Science Federation]

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*See this post for why the claims that hormones in semen probably don't affect mood.

**As an aside, the authors actually didn't restrict the study to vaginal tissue. They also looked at tonsillar tissue (representing the throat), and actually led with a figure on lymphoid tissue (part of the immune system). I'm guessing they did the initial experiments in lymphoid tissue because it's filled with immune cells and probably easier to get enough cells to measure. The results were essentially the same in all of the tissues that they looked at though.

Lecture 3a - Cell Biology and the Organization of Multicellular Life #SC-214

[This past fall, I taught a course at Emerson College called "Plagues and Pandemics." I'll be periodically posting the contents of my lectures and my experiences as a first-time college instructor] One of the biggest challenges in organizing this class was figuring out how to incorporate readings into the class material. Since I wanted to give the students a firm grounding in evolution as a way to understand infectious disease, one of the required textbooks I assigned was Carl Zimmer's excellent introductory textbook The Tangled Bank.

Unfortunately, I felt I only had a couple of days to give the introduction to evolution, and I ended up loading the kids up with way too much reading. If I teach this course again, I think it would work much better to spread the discussion of evolution out over several class periods, but weave it in to the discussion of infectious diseases right from the start. As it was, I came back to evolution over and over again, and I think the students had a fairly firm understanding of it (at least in the context of disease) by the end, but I could have started out better I think.

The other assigned texbook was Laurie Garrett's 1995 book The Coming Plaguewhich is phenomenal, but which I also didn't use effectively. I only ended up assigning 3 chapters out of the 20 or more, though at least two or three times that many were relevant to various parts of the course. This book is written more like journalism than a textbook, and the students enjoyed the chapters that I assigned. I'll definitely use both of these books again, but I think I can use them better.

Lecture 3a  (Readings: Zimmer - The Tangled Bank, chapters 4 and 6)

In the last lecture (part 1, part 2), I discussed the development of the two fundamental theories that underpin almost all of biology: evolution by natural selection and the gene theory of inheritance. These two advances of the 19th century were fused in the early 20th century into the modern synthesis (also sometimes called neo-Darwinism), and still govern how we think about biology today. With that as a backdrop, I'm going to step out of the history lesson a bit and talk about our current understanding of multicellular organisms, cell biology, and what we call the "central dogma."

Cells and their organization

It might seem obvious, but we are not made up of a single thing. Our bodies are composed of trillions of distinct entities, each with its own boundary, its own metabolism, and it's own blueprint for life. In 1665, Robert Hooke observed cork under a microscope, and named these entities "cells" for their resemblance to the living quarters of monks (what Hooke was actually observing was the outline made by the hard walls of these plant cells left over after the cell had died).

Hooke's drawing of cells in cork (source: wikipedia)

Many living things live as individual cells, and multicellular organisms run the gamut of complexity from dictyostelium, (a fungus that spends part of its life as a single cell, but then forms a multicellular structure to reproduce), to sponges (simple animals with less than 10 cell types), to people.

Fruiting stalks of dictyostelium (click for source)

Why have many cells, instead of just one? Scientists still aren't sure exactly what selective pressures first drove unicellular organisms to team up with one another into a larger aggregate, but it's clear in hindsight that multicellularity caries many benefits. For one, when many cells team up together, some of them can specialize. A single-celled yeast has to know how to move, find food, collect the food, digest the food, keep itself protected from predators and parasites, find mates (if it's sexual) etc etc etc. By contrast, a hepatocyte (liver cell) in a mammal has only a few functions, and can leave the rest of those jobs to others. Because of this, that hepatocyte can be really good at its limited functions.

Multicellular organisms thus have many different cell types, from less than a dozen in a sponge, to hundreds or thousands of different types in a human. These cells may have a lot of different functions, or be highly specialized, or have no other function than to give rise to other cell types. In any case, these cells must be organized into larger structures in order to carry out their function, and to contribute to the larger organism.

For instance, "columnar epithelial" cells line the inside of our gut, and function to provide a barrier, absorb nutrients, and secrete mucous to lubricate and protect from invading microbes. These cells are organized into a larger structure, or "tissue," that is comprised of several different cell types that all work together. The epithelial tissue is in turn organized with many other tissues (like smooth muscle), to form the "organ" of the small intestine. The small intestine is organized into an "organ system" - the digestive tract - along with the stomach, large intestine etc.

Close up of columnar epithelial cells (TL), these cells organized into villi, surrounding the lamina propria (TR), a cross section of the small intestine, showing the epithelium (dark pink) over the lamina propria (white), and smooth muscle (light pink) (BL), and the small intestine along with other organs of the digestive tract.

Likewise, the nervous system is composed of the brain, spinal chord and peripheral nerves, all of which can be further subdivided into different tissues and cells etc. In this way, many individual cell types can be organized at various levels to comprise a complex, multicellular organism like a human.

But how do individual cells do their thing?

Intro to Cell Biology

All* cells share a few basic requirements, and a few basic features. First, they need something to separate the outside of the cell from the inside. This is called the "plasma membrane," and is composed of a double layer of molecules that serve as a semi-permeable barrier. Imagine it like a chain-link fence surrounding a property - dogs and cats might be kept on one side or the other, but insects can pass back and forth without trouble. Actually, the membrane surrounding cells is much more selective, and prohibits movement based on more than just size, but the idea is the same.

Cell Membrane

But you wouldn't surround a property in a solid chain-link fence. Sometimes you want to allow things to pass from one side to the other that wouldn't fit through the fence. But you want to be able to control when, where, and how much goes in and out, so you build in gates and other portals. In the same way, cells have channels that can allow certain molecules to pass in one direction or the other in a controlled way, or pumps that actively push molecules to one side or the other.

Channels and Pumps

Cells also need ways to perceive the outside environment. Usually, this is accomplished by things called "receptors," which are basically sensors that span the membrane. These receptors can perceive the environment on the outside of a cell and communicate that information to the inside of the cell. We'll leave receptors as a black box for now, and get back to how they work in a later lecture.

The final basic feature that I want to talk about is the genetic material. This is the blueprint that every cell carries and that provides all of the instructions for how a cell behaves. You've probably heard of genes and DNA, but to go forward in this class, we need to put those things in context. But to understand what genes do, you first need to understand what proteins do.

Proteins do the work of the cell.

Proteins do everything (just about)! From carrying out chemical reactions, to communication between cells, to basic structural support, different proteins are responsible for almost every function in a cell. Those channels and pumps I mentioned above are proteins. If you're thinking of protein from a dietary perspective, the reason that meat tends to be high in protein is because it comes from muscle, and muscle contains high quantities of proteins that are able to contract and exert mechanical force. In the cell factory, every screw, gear and conveyer belt, and even the workers that operate the machinery are proteins.

Proteins can be quite large as molecules go, but at their core they are just long chains of smaller molecules called "amino acids." There are 20 different types of amino acids, and the order in which they are linked together influences their shape. Imagine a chain where each link is coated in either fuzzy or hooked velcro, or a positive or negative magnet. you could lay that chain out in a line, but if you put it in a box and shook it, what you pulled out of the box would be some tangled mess, but it would have some defined shape - each part of the chain may interact with other parts, repelling each other like two positive magnets, or sticking together like velcro or opposite-charged magnets.

In a long chain of amino acids, there are a lot of different types of interactions (not only 4 as in the example above). The order of those amino acids, as with the order of magnets and velcro, determines the final shape that the chain folds into, and that final shape determines the function of the protein. So how to determine that order? That's where genes come in.

But seeing as how this post is already super long, I'm going to put the explanation of how genes become proteins in a separate post... coming soon (I learned how to use Adobe Illustrator just to make the diagrams, it's going to be awesome!).

Stay tuned!

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* Any time I use categorical statements like "All cells..." or "Any time I..." when talking about biology, there's a good chance that there are a couple of examples that run contrary to the statement I'm about to make. For instance, even though all cells must have had genetic material at some point, red blood cells jettison their nucleus during development and carry out their function quite happy without any genomic DNA.

PeerJ - the science journal we need and deserve

I spend a lot of time thinking about the scientific method. I don't mean that thing you learned in high school, where you make an observation, form a hypothesis, design an experiment etc etc. That's certainly part of the scientific method, but the linear formula that freshmen are typically forced to memorize sucks the life and interest out of what it is that my colleagues and I do on a daily basis. Source: The fantastic "How Science Works" from UC Berkeley (click image)

The process of doing science is messy and complicated, and most of the time it doesn't work. There are false starts, bad experiments, bad interpretations, wrong or incomplete controls and sometimes you just forget to add salt to your buffer. But science is the only path to knowledge where all of these problems, the flaws of human planning, perception and cognition, are baked into the process and corrected for. One of the most important parts of that corrective influence, and what's missing from the scientific method as conceived in high school, is the discussion and debate that comes from sharing the results of our experiments with others.

Modified from "Understanding Science" - click for source

For the last hundred years at least, this has largely meant publishing findings in a journal. At their inception, journals were just ways to aggregate and disseminate the letters that scientists already sent around to each other - in other words, journals increased science communication. Not anymore.

These days, most published science remains locked in silos controlled by publishers. Even wealthy institutions like Harvard are being crushed under the weight of subscription fees, and if you don't belong to an institution, you're likely to pay around $30 for a single article! Scientific journals are now impediments to the free flow of scientific information.

However, as with so many things in the internet era, the old model is breaking down and the entrenched interests are kicking and screaming to hold onto their supremacy. Unfortunately for all of us, these entrenched interests have an advantage that other disrupted industries do not.

Because the rise of journals occurred in tandem with the rise of professional, publicly funded science, the two are now inextricably linked, to the point where the publication of discoveries in journals is necessary to maintain a career in academic science. Job prospects, grants and promotions all depend on the quality and quantity of publications.

Institutional barriers prevent individual researchers from innovating with publishing strategy because doing anything outside the standard model would hurt their ability to be promoted and more importantly, to get the grants they need to do science. The good news is that some enterprising people are starting to build journals that work within the current model of science publishing, but aim to disrupt it from the inside. Enter PeerJ, a new online-only journal that published its first papers today.

The Open Access movement has made great strides, but there is still a long way to go before all academic content can be freely read, broadly distributed and openly re-used by anyone, regardless of geography, education or wealth. A long way, but it is a worthy trip to undertake.

And so this is why we believe so strongly in the mission of PeerJ. We want to be a catalyst for change within the system of academic communication. We want  to publish science in an effective, efficient, rapid, innovative, respectful, professional and, above all ‘Open’ manner.

PeerJ has built a new open access journal, following the likes of the Public Library of Science (PLoS) and the much more recent journal eLife. However, where PLoS and eLife seem to be trying to build classic journals with an open access (OA) model, PeerJ seems to be trying to innovate on everything about the publishing process, from open peer review, to the integration of altmetrics, to the simple idea of publishing articles as they come in (like a blog) rather than in separate issues.

They're even planning to launch a pre-print server, which means that scientists will be able to upload their work to establish primacy (physicists have had something like this for a while), that can serve as an OA source, even for papers that eventually get published in a non-OA journal.

A little while ago, in response to a boycott of the publisher Elsevier, I wrote

We don’t need any academic journal’s services anymore. If you publish in any journal, you are making it easier for them to take action that harms academic institutions, so you shouldn’t[...]

[T]he truth is, journals add very little value to science, and impose huge monetary costs, as well as costs in terms of delayed publication and limited distribution[...]

In my idyllic world, every lab has their own blog, and publishes their results in real time, sharing them on a site like ResearchGate. Individual figures can be indexed on something like FigShare. Scientists can post their negative or confusing data and ask the entire world for help, or talk about their research plans and get critiqued. Meanwhile,altmetrics are being generated in real time to asses the validity of data, and scientists peer review on their own blogs or at some central location. The distribution of scientific knowledge returns to the model of the 19th century – free and openly distributed – but now also instantly and globally distributed at the same time.

My model of every scientist with their own blog may be too unwieldy, but PeerJ has built a journal that does almost everything I've been looking for, and are poised to show that this model can work and that it's better. I also wrote:

Science benefits when the flow of information is unrestricted and everyone benefits when scientific knowledge advances. Journals no longer assist in the distribution of knowledge, they only impede it, and no one benefits from this arrangement except the journals themselves. It’s time for something new.

PeerJ might be that something new. Here's hoping they prove me right.

Snow, cold, influenza and colds - Temperature and Infectious Disease

A "potentially historic" blizzard is barreling down on us here in New England, and is poised to drop up to two feet of snow on Boston. All of the schools in the area preemptively closed, our public transit system is shutting down at 3:30pm, and trying to buy groceries last night was bedlam. The snow is just now beginning to fall. Winter in New England can be rough, especially for a California-raised boy like me. It's not just because of the snow and cold, it's also the influenza and common colds. Source - Flickr user "Placbo"

The fact that the rate of some infections can vary by season is not controversial - actually, it was noted by Hippocrates over 2000 years ago - but in many cases, we still don't really know why. In some cases, it's obvious - the bacterium that causes Lyme disease is transmitted by deer ticks, so infections peak in the late spring and early summer when the ticks are active and people are going on hikes. But the winter-peak seasonality of infectious diseases like influenza is harder to pin down.

The first potential explanation is the temperature. After all, there's a disease called the cold for pete's sake. We know that cold temperatures can cause physical stress, and that stress can suppress the immune system. Another potential source of immunosuppression is vitamin D deficiency. Most of our Vitamin D comes from a process called "photoconversion" - ultraviolet radiation from sunlight causes a chemical reaction that produces vitD from 7-dehydrocholesterol. In the winter, especially at northern latitudes, the sun isn't out as long, you're not outside as much and more of your skin is covered up when you are outside. A number of recent studies have suggested many people are vitD deficient during the winter, and that this might have negative impacts on the immune system.

Both of these explanations seem straightforward enough, but neither explain why some pathogens are seasonal and some aren't. If it was just immunosuppression, we would expect all pathogens to be more prevalent or at least more severe in the winter, but this is not the case.

My favorite explanation is the human behavioral one. During the winter, people stay inside more, so they're in closer contact with more people. Infectious disease that spread via direct contact or because of sneezing etc like influenza and the common cold are precisely the pathogens that we'd expect to peak because of this behavior. Unfortunately, this explanation also isn't complete. Why woud there be seasonality in Florida or southern California for this reason? You could argue that people in northern latitudes are the main driver, and act as vectors for more southern populations (actually, I would argue that that's the case).

One of the least satisfying (but still totally valid) potential explanations is that the seasonality occurred by chance. Influenza infections occur in cycles of infection -> immunity -> mutation, where after one round, just about everyone that was susceptible is either immune or dead, and the virus must mutate to become infectious again. It's possible that this annual cycle just happened to peak in the winter. Because of the interactions between different pathogens, this would only have to happen to a single virus in order to get the whole thing going. In other words, the rhinovirus responsible for the common cold* might just be riding the coat-tails of influenza to hit people that are already knocked down by infection. There are issues with this hypothesis too. In the southern hemisphere, flu infection is also seasonal and also falls during the winter, which is off-set by 6 months from the northern hemisphere winter, but this alone does not rule out the "by chance" hypothesis.

There are other possible explanations as well, but all of them are very difficult to test. At best, we have plausible explanations with supporting correlations, but that's not enough to make a definitive claim. Even more problematic, it's possible that all of these explanations are true to some extent, and cooperate to give us the seasonality that we see.

In any case, my fellow East Coasters, bundle up, be safe, and try not to sneeze on anyone.

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Most of this information was learned at some point during my schooling, but for a source, check out this review

*There are actually several different viruses that cause the symptoms associated with "the cold," but the most common is Rhinovirus.

Women climbers are amazing too

It occurred to me after I posted my piece last week about rock climbing and arthritis that all of the photos of climbing were of men. This was purely coincidence - I was editing photos of last week's competition in reverse chronological order, and I'd only finished the photos of the Men's finals by the time I was done with the post. But I think it's important to note how amazing the women were as well (and it gives me an excuse to post more of my photography). In fact, this year, I thought that the women's bouldering problems were more interesting, and better demonstrated the skill and power of these climbers.

From the position you see here, the finalists had to scale to the top of that massive round thing with essentially nothing to hold on to. What you can't tell is that she's at least 15 feet off the ground.

Route 2 of the women's finals required a dyno (that's a move where all four points of contact leave the wall) for the first move.

From there, you actually have to traverse lower before dragging yourself up via some creative leg work...

... to finally reach the top by climbing the rear-sloped roof on tiny holds with ledges no more than a 1/2 inch wide.

On route 3, the climbers had to navigate out from underneath the low roof, hanging upside down holding crappy bars...

... to get out onto the main wall, where all you have to hold onto are, well, imagine doing pull-ups while palming a basketball.

Route 4, the last of the competition, was so crazy I'm just going to let pictures tell the story.

 

Unfortunately, none of the women were able to finish this problem. I will say that they left these routes up for the public to try after the competition, and I was able to get about as far that first picture in this series - I grabbed the first hold, got my feet off the ground and promptly fell. I think that once I got my foot to touch the next hold, but that's about it. I'm a fairly fit guy and I climb several times a week, but I couldn't hold a candle to these phenomenal athletes.

To see these gals (and the guys as well) in action, check out the official video (the finals climbing starts around the 3 minute mark.

Dark Horse 2013 Series 4 Championship Highlights from Louder Than Eleven on Vimeo.

<em>[All photos in this post were taken by me and are licensed under a <a href="http://creativecommons.org/licenses/by-sa/3.0/deed.en_US">Creative Commons Attribution-ShareAlike 3.0 Unported License</a>]</em> <a href="http://creativecommons.org/licenses/by-sa/3.0/deed.en_US" rel="license"><img style="border-width: 0;" src="http://i.creativecommons.org/l/by-sa/3.0/88x31.png" alt="Creative Commons License" /> </a>

 

Rock Climbing, Fat Fingers and Arthritis

In any physical activity, there is always the risk of acute injury - cuts, scrapes, bruises, and even broken bones are often par for the course. For some extreme sports like rock climbing, where you voluntarily drag your body hundreds of feet into the air on the side of a sheer rock wall, athletes are even willing to risk death.

Those acute sports injuries can sometimes grab headlines, but people are increasingly becoming aware of the long-term consequences of physical stress on the body. Football and hokey players can suffer from memory loss and depression as a result of swelling in the brain associated with repeated concussions, tennis players often get stress fractures on their spine (not to mention the aptly named tennis elbow), and many, if not all sports are thought to increase the risk of developing osteoarthritis - in which the cartilage in your joints breaks down, allowing bone to rub against bone and inducing inflammation.

This increased risk of arthritis is of particular concern for climbers - there are a lot of joints in the hands, and climbing tweaks them in all kinds of ways.

It's sort of accepted wisdom in climbing circles, and I never questioned whether or not it was true until a friend of mine told me that actually, climbers have a decreased risk of arthritis. So I decided to do some digging. 

First off, let's take a look at the increased risk of osteoarthritis for sports in general - it turns out, it's not that simple:

Participation in sports that cause minimal joint impact and torsional loading by people with normal joints and neuromuscular function may cause osteophyte [bone spur -kb] formation, but it has minimal, if any, effect on the risk of osteoarthritis. In contrast, participation in sports that subject joints to high levels of impact and torsional loading increases the risk of injury-induced joint degeneration. People with abnormal joint anatomy or alignment, previous joint injury or surgery, osteoarthritis, joint instability, articular surface incongruity or dysplasia, disturbances of joint or muscle innervation, or inadequate muscle strength have increased risk of joint damage during participation in athletics.

Let me translate: if you're not putting too much strain on your joints, a bit of sport isn't going to increase your risk. But sports that "subject joints to high levels of impact and torsional loading," does increase your risk. If hanging your entire body weight from two fingers doesn't count as high torsional loading, I don't know what does.

So then was my friend completely full of crap? It turns out, there have been a several medical studies on this very topic, and they offer up conflicting results. One study published in 2006 examined the hands of 26 recreational rock climbers and compared them to the hands of non-climbers. As you might expect, the hands of the climbers were much stronger than the hands of the non-climbers, and the climbers even had thicker bones, which the authors suggest might indicate that the bone is actively remodeled to make it more powerful. However, these researchers found no indication that the climbers had an increased risk for osteoarthritis.

By contrast, a study published 2 years earlier examined 19 members of the German Junior National Climbing Team (professionals), 18 recreational climbers and 12 non-climbers - these researchers determined that the climbers were at increased risk, since one member of each of the climbing groups had early signs of osteoarthritis and none of the non-climbers did. Another study published in 2011 supports this conclusion, showing that adult male sport climbers regularly get bone spurs and show significantly increased signs of osteoarthritis.

Finally, the study that I think has the best methodology, followed the 10 members of the German Junior National Team, 10 recreational climbers and 12 non-climbers over the course of 5 years. Their conclusion:

Intensive training and climbing leads to adaptive reactions such as cortical hypertrophy and broadened joint bases in the fingers. Nevertheless, osteoarthrotic changes are rare in young climbers.

 Unfortunately, all of these studies suffer from the same basic flaw - small numbers of test subjects. All of the bone-thickness stuff is pretty consistant - climbers' hands are structurally different - but the signs of osteoarthritis are so rare that they could have arisen by chance. Furthermore, all of the athletes in these studies were fairly young, and age could reveal problems (or lack thereof) that might not be apparent in the younger athletes.

Based on what we know about sports-related stress and osteoarthritis, it's reasonable to assume that there would be similar effects on the hands of climbers. But seeing as how we evolved from tree-climbing ancestors, it's also reasonable to predict that our hands might be better able to adapt to these stressors better than the stressors of swinging a racket (as far as I know, there's no evolutionary precedent for tennis). In fact, I don't even think it would have been unreasonable to predict that the increased strength attained from climbing might help you ward off osteoarthritis, though none of the studies I found suggested that (if any of you know the study my friend was referring to, please let me know in the comments). This type of intese climbing really started increasing in popularity about 30 years ago, so the first crop of climbers is starting to approach retirement age. It will be interesting to see if anyone begins to study these old timers to see how their hands and other joints are keeping up. As with so many things in science, the best I can say right now is that more research is needed to draw solid conclusions.

Well, I might be able to draw one conclusion: climbing is awesome!

[All photos in this post were taken by me* and are licensed under a Creative Commons Attribution-ShareAlike 3.0 Unported License] Creative Commons License

*Obviously, the picture of me wasn't taken by me, but it's still mine!