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Jon Wiener at The Nation and Ethan here on ScienceBlogs assault Richwine’s thesis based on the fact that “race” is an outdated term, “hispanic” is tough to define and doesn’t actually represent a coherent group of people etc.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.

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.

Treatment 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 PLoS, eLife and PeerJ. Here 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

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.

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.

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

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

- 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:

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.

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.

Unc93B1 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).

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. 

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

——————–

[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]

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

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 Symbionts, Jeff 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.