31 July, 2009


For the first time in a long time, I looked at the Google Keywords that are leading people to this site. I was very amused. In fact, I'm still amused, and also bewildered. Since this is a happy state of being, I thought it might be polite of me to share it with you.

fire breathing chicken
mass haul optimization algorithm
belgian blues
20 flirty questions for scientists
a scientist and makeup blog
adiponectin the scientist
bass player scientist
bigger cecum
can bacteria grow on oreos
cartoon word
do llamas have breasts?
ear toasters
friends flirting bad side
fucking awesome toasters
guild of mad scientists
hats that a scientist would wear
hungry leptin
igf-1 before after pics
in vitro system to create apoptotic cells
invader zim gir mens sneakers
luciferin problem
mad to breast
moshing as a woman
picture of a mad scientist
pipette tips in nostril funny
read the fucking manual cartoon
silk muscle
tesla jr
there's a llama
vampire ass
was i flirting
weakness of a men to a woman
zombies cooler than vampires
leptin ghrelin adiponectin resistin milk

Of all these terms, it's "there's a llama" that worries me the most. I picture someone nervously googling that term while an angry llama stares inside their bedroom window, chewing oh-so-patiently whilst waiting for the full moon to rise! Because that's what llamas do, right?

Also, I do not recommend ear toasters. Use muffins instead; they are thermally dense and edible!

30 July, 2009

On Animal Research

The recent venal response to Dr. Isis' very reasonable worry regarding animal-rights activists posing as university inspectors to gain access to her lab and wreak harm upon herself, her employees, her research, or her livelihood. In response, implied threats against her family were made.

Let's be clear: Toaster supports animal research. I do not support inhumane treatment of animals or unnecessary cruelty, but I will defend the necessity of animal research whenever it called into doubt. I do not undertake animal research lightly, and I seek to treat the rodents I use as humanely as possible. Some persistently argue that animal research is inherently inhumane and cruel, but I find that it is far more cruel to perpetuate human suffering that may be preventable due to animal research by sitting back and doing nothing.

Nonetheless, the recent debate got me wondering how far I would be willing to go to further research that alleviates human suffering. Adult humans aside, I suspect that if taking on a silverback gorilla armed with nothing more than a 22-blade scalpel was guaranteed to save a stranger's child, I would do so. And if that child were family, I'd forfeit the scalpel for a potato.

29 July, 2009

Dueling Clarification/FAQs

What is a Scientists' Duel?

As opposed to a traditional gentlemens' duel in which the participants try very hard to wound or kill each other, a Scientists' Duel is a rather gentler sport. In this, 2 scientists agree upon a paper to read and publicly explain (e.g., through research blogging). The public then gets 100 points to divide between the participating scientists as they see fit based upon the quality of their explanations. After a set time period of voting, points are added up and a winner is declared.

How do the participating scientists choose a paper?

However they wish to and feel it fair, but it must be mutually agreed upon. In my duel with Hermitage, we chose the brain-machine interface paper because it is far outside each of our respective expertise, which we felt would make the competition fair. At the same time, a duel between scientists within closely related expertise upon a paper from their field would also be fair.

How do readers judge the Dueling Scientists?

However they want to. But generally comprehension, intelligibility, and accessibility are good benchmarks.

What benefits are there to Scientists' Duels?

Not only do these duels get more than 1 interpretation of otherwise unpublicized research out into the ether for knowledge and consumption, but it also adds a fun element of competition. Concurrently, Scientists' Duels accord an inherent worth upon a scientist's ability to concisely and clearly explain complicated research, which is a win for both their readers and the scientist's skills.

I want to Duel a Scientist. How do I do so?

Contact the scientist in question, let them know what you're about and see if they're up for it. This would be where you challenge them. At that point you can invite submissions for dueling material from your readers or work it out with the scientist you challenged. Either way, for the duel to be fair, the material must be mutually agreed upon. Then you read the paper, write about it, and post that. Let your readers know it's part of a duel and provide a link to your opponent's entry. It would also help to aggregate it into Research Blogging. Then sit back and let your readers vote.

Add other unclear questions in comments and I shall amend this post to include them.

28 July, 2009

Let's Have a Duel!

I would like to see more Scientists' Duels.

Kinda like that, but sciencier. Maybe they have rancors attached to the end of those ropes.

Sure, dueling was widely regarded as a vile gentlemen's sport in the 19th century, but that, I suspect, was primarily because it involved rather a lot of pistols, sabres, death, and fluffy shirts*. Nonetheless, dueling was a visceral bloodsport that involved honor and competition. I'm not advocating that we turn to scientific bloodsport** for amusement and funding, but rather that we start competing intellectually. Yes, we as scientists already compete upon the scientific edge, trying desperately sometimes not to be scooped as we race to publish data and inadvertantly grind graduate students' free will*** to dust in the process. But at the same time, friendly, rigorous competition is a good thing as it raises standards and adds a slight sheen of adrenalin to even the most esoteric of topics.

If future Scientists' Duels were to take place in the form of competing research blogging, the benefits would be manifold. Namely:
1) Intellectual competition is fun.
2) Important research is disseminated.
3) An inherent value in explaining complicated science for uninvested audiences emerges.
4) More scientists communicate outside of their fields, thereby increasing their explanatory flexibility.
5) Research gets explained more than one way in each Duel, which would allow those with different knowledge-absorbing patterns to more effectively learn what it means.

I am not explicitly saying that I will take on any and all comers in challenging me to a Scientists' Duel, but I am implying it while trying to encourage others to square off and Duel for themselves.

Thoughts, ideas, encomium, and/or**** excoriation?

*Which I do believe I could pull off admirably, the shirts, I mean, not the pistols. Anyone up for a bout with quarterstaves?
**Like writing grants, but with sharp, pointy things. Come to think of it, an actual duel may be easier, and preferable for both parties, than endless traction of 2 closely scored grants in study section. But I digress.
***That's a joke, I think...
****The English language really needs an "and/or" functionality. "Else" is inexact. Therefore I propse "twick" and/or "andort". The added "t" makes it cooler.

Scientists' Duel Outcome

Hermie won*.

The final score was 205 Hermitage, 195 Toaster.


But at least I only lost by 10 points instead of only getting 10 points!!! She graciously extended the offer to me to not count the midnight dark horse Erk, which would have resulted in me winning, but as I am a Mad Scientist with integrity, I decided that responsibility to the rules was more important than my own ego and we counted their votes anyway.

However, let it be known that this is far from my last duel!

*Gloating can be found here.

24 July, 2009

Optimizing Algorithms for Brain-Machine Interfaces

ResearchBlogging.orgImagine waking up trapped in a prison of your own flesh, blinking awake in the dull glow of a softly bleached hospital room. Your arms and legs are unresponsive to the will to move them, to the simple desire to reach up and scratch the itchiness of morphine from your eyes. Nothing happens, nothing responds, nothing moves, nothing feels. You are an immobile head trapped on an unresponsive body, and no matter how loudly you scream against the walls of your confinement from inside your head, nothing happens.

Luckily many quadriplegics retain the ability of speech and independent respiration. However, their quality of life, and that of the more unfortunate patients who are fully lucid but cannot communicate with the outside world by anything more than eye-blinking Morse code, remains severely compromised due to poor rehabilitation prospects and dependency upon caretakers. Perhaps one day we'll be able to repair injured nerves and restore connectivity with the rest of the body, but for now we're beginning to work out how to directly interface the brain with mechanical actuators. The goal is to develop an interface through which a paralyzed patient could control a machine that would augment their standard of living using nothing more than their mind and some technology.

Nerves and computers and both conveniently electrical. The problem is that they each operate on very different electrical schema. With computers we more or less know which transistor is storing which bit of information and have discrete units of conductors, resistors, capacitors and such. But it is very difficult to isolate the behavior of a single neuron in situ, so instead we use mass behavior of relatively large numbers of neurons to try to approximate functional firing chains. To translate the chaotic, non-discrete signal from neurons into discrete signals for machines, we need an algorithm. And to develop that algorithm, we need electrode-implanted animal models (unrestrained monkeys in this case) and scientists who can do math.

Li and Nicolesis et al have developed a novel modification of pre-existing brain-machine interface algorithms in "Unscented Kalman Filter for Brain-Machine Interfaces". Previous brain-machine interface algorithms were either linear approximations or non-linear particle filters. Linear filters (such as the Wiener and standard Kalman filters) didn't do as well approximating the behavior of neurons as particle filters, but they were much faster and computationally cheap enough that they could be used in real time. In general, particle filters (such as SSPPF) were very good at modeling the behavioral input of neurons, but they were so cumbersome that each iterative point required computing time that put it outside the range of useful real-time applications. Li and Nicolesis et al have modified a Kalman filter such that it uses a nonlinear tuning method (a quadratic model instead) and adds historical regression with multiple time offsets to help predict future behavior patterns. The quadratic tuning model integrates previous neural activity to arm movement models (the cosine tuning model, tuning to speed, tuning to distance of reach) into one cohesive and flexible equation. The historical regression with time offsets gives the model a short memory that allows it to quickly predict possible future states of neural activity to arm movement correlates and optimize them based on current neural activity input.

Implementing the quadratic neural tuning model greatly improved the accuracy of predicted neuron firing behavior, which means that the algorithm was better at interpreting the noisy signals from the neurons. At the same time, the historical regression made brain-activity-guided movement of the prosthetic hand* smoother and also helped to tune the monkeys' training on the algorithm by operating as a sort of continuous optimization that kicked out inefficient processes to improve overall performance. This quadratic model also significantly improved the reconstruction of the monkeys' desired hand movements during real-time tests in comparison to standard Kalman and Wiener filters.

In effect, this new algorithm construction allows for more accurate control of a prosthesis, with low tuning demands and progressive learning of efficient movement correlates. Ideally, this will one day allow paralyzed patients to accurately control mouse cursors (better than existing technology, anyway) or robotic prostheses that will greatly improve their quality of life. This technology may still be crude, but it is progressing rapidly and with great potential. I, for one, welcome the prospect of an auxiliary robotic arm. It would be great for my benchwork productivity.

*In this case, a cursor on a computer screen.

Li, Z., O'Doherty, J., Hanson, T., Lebedev, M., Henriquez, C., & Nicolelis, M. (2009). Unscented Kalman Filter for Brain-Machine Interfaces PLoS ONE, 4 (7) DOI: 10.1371/journal.pone.0006243


This is my entry in the Scientists' Duel that Hermitage and I are fighting for the title of Most Nefarious. Her entry is here. You, dear reader, will decide who wins. As of 12:00AM, 7/24/09, you have 72h to vote. You get 100 points to divide between Hermitage and I as you see fit. Report your scoring in comments. At the end of 72h we will tally up the points and determine the winner.

21 July, 2009


This Thursday a 5pm EST a mighty and fierce battle will break out in the sciencey blogosphere. I know this because I will be one of the combatants, and I intend to kick some serious arch-nemesis ass! This will not be any ordinary flame-war or troll-con, no, this will be far more violent, far more bruising, and inflict far more collateral damage on the surrounding countryside.

This will be the duel for the TITLE OF MOST NEFARIOUS!!!

and I dispute and have fought at great length to determine which of us is more nefarious. Indeed, entire dinosaur armies (my shock troops) have been obliterated into smushiness by her trout-gore spewing bento cannons (her favorite weapon) and I have fried literally tons of her self-replicating bunny robots with the stabby teeth with my mighty Tesla coil cannons! The countryside can not support such vicious and scientific warfare for too much longer, so Hermitage and I agreed to settle this dispute like proper scientists: a paper duel.

Because each of us is rather fond of all of you, we chose an open-source PLoS ONE paper upon which to wage war: Unscented Kalman Sensor for Brain-Machine Interfaces. This way each of you can see the original source.

The battle will not be over the paper itself, but rather for your hearts and minds. Hermitage and I are each going to blog about the paper cited above. Then you, our lovely readers, will each get 100 points to assign between us as you see fit. Whomever has more points after 72h for voting will be declared the winner.

I tap out this announcement in order to give you fair warning. Shore up the walls of your own individual Internet homesteads, put the fine china in the cellar, and get yourself a hammer to beat at us if we encroach too closely to your territory in the blushing heat of the battle.

Watch out, it's coming!

Dear Hermitage,


20 July, 2009

Book Meme

DuWayne Brayton has tagged me with the book meme. I didn't follow the rules precisely. There are probably more than 15 books below, and I took something like 20odd minutes to write and hyperlink all this together. The books that follow are in no particular order of favor. I don't necessarily agree with the viewpoints espoused in all of these books, but they nonetheless seem to be persistent sticks in the mud of my mind.

In the Name of Science: A History of Secret Programs, Medical Research, and Human Experimentation, Andrew Goliszek
Mutants: On Genetic Variety and the Human Body, Armand Marie Leroi
The Language of Life: How Cells Communicate in Health and Disease, Debra Niehoff
Janeway's Immunobiology
Neuromancer, William Gibson
The Complete Essays of Mark Twain
Maus I + II, Art Spiegelman
Percy Gloom, Cathy Malkasian
The Brief and Wondrous Life of Oscar Wao, Junot Diaz
One Hundred Years of Solitude, Gabriel Marcia Marquez
American Psycho, Bret Easton Ellis
Ender's Game, Orson Scott Card
Green Eggs and Ham, Dr. Seuss
Stiff: The Curious Lives of Human Cadavers, Mary Roach
Sex, Time and Power: How Women's Sexuality Shaped Human Evolution, Leonhard Shlain
Grimm's Fairy Tales
A Scanner Darkly, Phillip K. Dick
American Pastoral, Philip Roth
Catharsis, Andrzej Szczeklik
Lord of the Rings trilogy, J.R.R. Tolkien
Amor y Cohetes (Love and Rockets), the Hernandez Bros.
The Jungle, Upton Sinclair
1984, George Orwell
The Grapes of Wrath, John Steinbeck
Alice in Wonderland, Lewis Carroll
The Futurological Congress: From the Memoirs of Ijon Tichy, Stanislaw Lem
Frankenstein, Mary Shelley
Watchmen, Alan Moore and Dave Gibbons
The Portrait of Dorian Gray, Oscar Wilde
James and the Giant Peach, Roald Dahl

Now then, I tag Arikia Millikan, Hermitage, Science Bear, Hexadecimal, Tig, Stephanie Zvan, Ktbug Ladydid, Lost Marbles, and Quietandsmall. Let's see what all of you have!

AHAA Addiction

Every day we labor in the lab, hoping to build knowledge into a coherent and publishable narrative, pursuing understanding. Often I have heard scientists speak of the "A-HAAAA!!!!!" moment where months' worth of laborious experiments snap into place and reveal a new bit of truth, and how addicting that moment is, how it is akin to pure joy or The Perfect Cookie. This is a wonderful goal, and somehow it keeps us working long hours for little pay and even less respect. But, admittedly, it's hard work.

I have found that every once in a while, as I'm reading along through some papers, I come across a well-supported point or elegant experiment that is just SO DAMN AWESOME that my mind has to stretch a little farther to accommodate the new view of the Entire Frickin' Universe that that paper has just jammed into my eye sockets. It's like licking lightning*, but less painful. And these papers don't have to be recognized across the scientific sea as revolutionary to make that difference. I still know approximately nothing, inasmuch as my scientific knowledge is but a 5uL drop in a 3L pond of ignorance. And as such, papers that fasten together what were previously disparate informations (for me, although that may have already been old hat to the greybeards) can be just as mind-boggling.

Apparently I have a knack for finding these papers. The other day in the lab after his committee meeting, the grad student turns to me and sez, "You failed me there! You're my Master Downloader, and you didn't catch the paper that completely changes 1/5th of my thesis!". He was kidding, I think. I have yet to read the paper in question. From the abstract, it's been recently found that IL-12Rp35 doesn't just participate in IL-12 signaling, but also in IL-35 signaling, which has an antagonistic effector function against IL-12 (IL-12 is pro-TH1 T-cell response, IL-35 is pro-Treg T-cell response). This is on top of previous knowledge that the IL-12Rp40 subunit is also part of the IL-23R complex (IL-23 is involved in TH17 T-cell differentiation and function).

These frequent revolutions of our understanding are unequivocally Good Things. Sure, it makes our lives difficult and increases the range of possibilities in which we make asses of ourselves in front of our colleagues, but at the same time it's the very stuff Science is made of. If we cling to out-dated theories and disproven information, we will not produce accurate new information and we will fail as scientists. This necessary nimblemindedness is sometimes frustrating, but at the same time it allows us to have those A-HAAA!!!!! moments all the more often without doing all the benchwork ourselves.

To date, there are 3 papers that stick out in my mind as having been particularly eye opening:

1) Käfer J, Hogeweg P, Marée AFM (2006) Moving Forward Moving Backward: Directional Sorting of Chemotactic Cells due to Size and Adhesion Differences. PLoS Comput Biol 2(6): e56. doi:10.1371/journal.pcbi.0020056

I didn't see this when it first came out, but when I finally read it and worked through the differential equations it really made a huge difference in how I view organogenesis. I wasn't much interested in the functional dynamics of Dictyostellium morphology, but the work on cell sorting and migration based entirely on size and net kinetic energy was really really really cool. Blogged here.

2) Venegas J, Winkler T, Musch G, Vidal Melo M, Layfield D, Tgavalekos N, Fischman A, Callahan R, Bellani G, Harris R (2005) Self-organized patchiness in asthma as a prelude to catastrophic shifts. Letters to Nature. doi: 10.1038/nature03490

This was some major computational sweetness wrapped up in massive physiological awesomeness. It integrated all the separate physical forces at work on individual alveoli to integrate them into a model of whole-lung pathology. This was tight work, very well-done, and immediately relevant to clinical practice as their model revealed that inhaled anti-asthma drugs would likely affect only the non-spasming portions of the lung airways, although it also didn't exactly make an alternative recommendation. Anyway, still relevant. Blogged here.

3) Artis D. Epithelial-cell recognition of commensal bacteria and maintenance of immune homeostasis in the gut. Nat Rev Immunol. 2008 Jun;8(6):411-20. doi: 10.1038/nri2316

This paper assembled a major heap of evidence and thoroughly blasted the simple view of intestinal epithelial cells as humble nutrient transporters that I had been taught to ragged shreds. Intestinal epithelial cells aren't just lining for the gut, they actively interact with the massive volume of microorganisms inhabiting our guts and modulate both the ecology thereof as well as the responsiveness of the innate and adaptive immune systems. Intestinal epithelial cells even express MHCII! As far as I can discern, this paper has helped to provoke a flurry of gastroenterology papers that discuss the rapidly evolving view of the microbiome, even going so far as to label our intestinal microbiome another metabolic organ**. Blogged here.

So, dear reader, what papers have changed your world-view and why?

*Don't try that at home. It tastes terrible.
**If you want to look smart to a gastroenterologist, drop "TSLP" casually into conversation. TLSP = thymic stromal lymphopoeitin, it's secreted by intestinal epithelial cells to attenuate inflammatory TH1-type immune responses to the bacterial antigenic signal from the gut microbiota. It kinda skews the response towards TH2 effectors instead.

19 July, 2009

Of Superheroes and Pirates

Each summer, Ann Arbor, Michigan subjects itself to a massive art fair that usually draws 350-500,000 people into town to view and buy stuff. Naturally, since it was a crowded environment with delicate and expensive stuff crammed tightly together, Toaster thought it'd be an excellent idea to get a large-ish group together to dress up as charmingly pathetic superheroes and play Tag. So we did.
Toaster, The Superhero, having a blissfully unaware Spiderman 3 moment.

Left to right: P-par, Tie Fighter, The Cloaked Librarian, Punkupine, Zebragirl, Toaster, Hufu Transformer, and Skrull. It may dismay (or delight) you to know that 5 of the people present here are actually scientists by day. If it dismays you, dismiss us as Mad Scientists.

Left to right: The Cloaked Librarian, Toaster, and Hufu Transformer. We know we're badass.

Childrens' reactions to seeing us (excitedly jumping up and down, staring and grinning, asking their parents whether we could really fly) just reaffirmed my empirical knowledge that too many adults are stuffy dunderheads. Sure, be responsible and stuff, but it's silly--very silly--to be so full of yourself, and so vain, that you deny yourself fun for fear of looking like an ass. Or maybe we're just weird.

And then tonight there was a concert with a pirate song band followed by a burlesque show, which had a Star Trek-in-the-ocean theme. I watched Dr. Spock get mobbed by stingrays in pasties, and the ribbon encircling my hat (because, of course, I was also dressed as a pirate*) was part of the North Pacific Trash Gyre's costume that she abandoned throughout the course of her routine. This was all followed by a massive dance party that had us dodging glitterbombs and slipping on bubbles.

*You may wonder what kind of pirate wears a top hat. Well, to put it simply, fancy motherfucking pirates wear fancy motherfucking hats.

18 July, 2009

In Defense of Cliches

Bora Zivkovic of A Blog Around the Clock and Ed Yong of Not Exactly Rocket Science alerted me via Twitter to an article in Wired Science by Betsy Mason entitled "5 Atrocious Science Cliches to Throw Down a Black Hole". In short, the article claims that "Holy Grail", "Silver Bullet", "Shedding Light", "Missing Link", and "Paradigm Shift" are overplayed, tired terms that should be banned from scientific reportage.

Betsy Mason is wrong.

We need cliches. We depend upon cliches, and cliches are quite useful in the proper context. While it may be true that the above terms do get thrown about quite a bit, they're still quite useful. Science journalism is already a convoluted field that must continually walk the line between being too esoteric for its mainstream, non-scientist audience and maintaining proper accuracy to satisfy its scientific constituents, which keeps information flowing. Banning the use of any widely understood vehicles for explanation just raises the barrier to effective communication between science and the public. And when we, as a scientific community, have already made it clear that we're not usually pleased by the transmission of our findings to the public through the prism of science journalism, do we really need to throw in even more barriers?

This article indulges in a great deal of unfortunate professional myopia. From the perspective of a scientist, calling research, such as active in vivo RNAi therapy, the Holy Grail of cancer research will seem inaccurate given the breadth of other therapies being developed to combat cancer. It may be more accurate to place RNAi therapy in the context of all the other therapies, from advanced laser ablation at the level of individual cells to cytolethal fusion proteins, but with this accuracy comes a great sacrifice in public comprehensibility. Science is detailed, science is convoluted, and science is very nuanced. But unless we're willing to write and peer-review multi-chapter articles for the popular press, if those outlets would even carry the required tomes, we must tell a complex story simply and linearly in order for anyone but the most educated and avidly interested members of the public to understand it. Using widely understood cliches as vehicles to convey that comprehension is not just necessary, it's laudable.

I do not mean to impugn the intelligence of the general population. Perhaps naively, I still believe that the public is usually smarter than we give them credit for. But at the same time, scientific communication is a form of technical communication with clearly defined words and standards. We use "attenuated", "potentiated", "significantly", "stochastically", "sufficient", and "necessary" in very specific ways that don't necessarily* translate into normal, everyday public usage. We can't well use these standards to communicate effectively to the public, instead we must speak to the public on the public's terms, which by and large will involve either sports analogies or cliches. The above maligned cliches are here to stay, and they remain quite useful. If they continue to help convey broad understanding of scientific concepts, then I will continue to welcome them and their use.

*Like that.

UPDATE (tweets):
[@ToasterSunshine] @BoraZ @edyong209 | In defense of the "5 atrocious science cliches": http://bit.ly/15vgZL | Must speak to the public on the public's terms.

edyong209@ToasterSunshine You present false choice between cliches and jargon. Entirely possible to write lay-friendly copy w/o cliches.
edyong209@ToasterSunshine Or at the very least, without seriously misleading cliches.

ToasterSunshine@edyong209 Yes, sometimes cliches may be overused/misleading. But to call for a ban takes tools away from communicating scientists.
ToasterSunshine@edyong209 Scientists get jargon + don't need cliches or analogous metaphors as vehicles for understanding research. Public probably does.

edyong209@ToasterSunshine If tools are crap, they won't be missed. Good writers/communicators ought not to rely on cliches *anyway*.
edyong209@ToasterSunshine Neither article nor I calling for end to analogy/metaphor but end to MISLEADING ones.
edyong209@ToasterSunshine Again, I think you're presenting false choice between jargon and cliches. Metaphors are good but we can do better.

betsymason@toastersunshine I don't advocate a ban on metaphors for science, just the most overused, hyperbolic & annoying cliches. We can do better.

ToasterSunshine@edyong209 @betsymason I don't dispute that "paradigm shift" is overplayed. I do stand firmly against anything that attenuates science comm.

edyong209@ToasterSunshine Not attenuation. Sci-com benefits if misleading terms are lost, writers forced to think creatively. Atten'g BAD comm= good.

ToasterSunshine@edyong209 Agreed less bad comm good, but cliches not always misleading/bad. Cliches often help capture interest and sustain story reading.
ToasterSunshine@edyong209 See rec Herceptin research: "Herceptin magic bullet against breast cancer stem cells" vs. "Herceptin inhibits even HER2- tumors".
ToasterSunshine@edyong209 HER2 = jargon, but HER2 also absolute key to story. Accurate inclusion in headline turns general audience away. Need interest.

17 July, 2009


Aside from scientific papers and comic books*, I don't do much reading any more. I can't remember the last new thing I read for fun. Maybe it was World War Z by Max Brooks, and that was well over a year ago. I mean, I have read Neuromancer by William Gibson since then, but I tend to do that annually, so it doesn't really count.

The problem is that whenever I sit down to read anything, even a comic book, which is quick and awesome, I feel guilty that I'm not off reading scientific literature instead. I've got a stack of unread papers rapidly approaching the thickness of my head, and I have a large noggin. I see something that looks really interesting, read the abstract, and print it off to read later. Problem is that all too often it doesn't actually get read later, it just gets buried under everything else I've been meaning to analyze and forgotten.

But at the same time I really miss curling up with a good book and reading away.

So, dear reader, what do you recommend? Any great books you've recently parsed?

*Although I am also reading "Makers" by Cory Doctorow as it comes out, serializedy, on Tor's website. It's what made me realize I miss reading stories.

16 July, 2009

The Invisible Hand

The current global recession notwithstanding*, I have some major beef with economics in general. Economics exists to describe, regulate, and predict the markets, yet it inevitably fails to recognize reality and only perpetuates an unfortunately narrow self-interest in the majority of its participants. I posit:

1) The self-regulating "invisible hand" of the markets that supposedly guides consumers en masse to the best possible outcomes is nothing more than a foolish myth.

2) Economics pretends that it is uniquely exempt** from basic thermodynamic principles.

The invisible guiding hand is a convenient white lie that humanizes the volatility of markets, which amplify human indecisiveness and greed, and makes them seem comprehensible. This is pure fluffery at its least ingenious. The invisible hand's actions throughout history have, by and large, only served to increase the wealth of those who could afford to speculate within the markets, those who had money to risk and milk. It is entirely true that the invisible hand will guide consumers to purchase equivalent goods at lower costs and thereby benefit the producer who is able to manufacture those goods at the lowest marginal cost. But the same time this effect will not increase the purchasing parity or real wealth of the consumers themselves unless we insist on qualifying wealth by measurement of cheap plastic tchotkes. The invisible hand excludes benefit to the poor by marginalizing their purchasing to the necessities and using them as labor. The latter effect is especially apparent in third-world sweat shops churning out luxury items for industrialized nations' consumption. This disparity between benefit to the rich and cost to the poor is starkly visible in material trade and manufacturing between wealthy consumer nations and poor producer nations.

The North American Free Trade Agreement (NAFTA) effectively removed all barriers to trade between the United States of America, Canada, and Mexico. Large businesses in the USA and Canada have benefited from the cheaper labor available from Mexico even as their own working classes have suffered. Consumption intensive (defined as consumption relative to income) middle class families have certainly benefited from this with the rise of Walmart-type stores. But at the same time, large agricultural businesses, through chemical-heavy agricultural practices, can produce more corn per acre and do so more cheaply than Mexican farmers, and as such cheap USA grain flooded the North American market and dropped the bottom out of the smaller local markets that Mexican farmers depended upon. This bankrupted Mexican farmers, which in turn benefited large USA and Canadian businesses by providing hungry labor and mass immigration to urban centers (e.g., maquiladoras). Ironically enough, this has greatly increased the benefit to risk ratio of illegal immigration into the USA or Canada, something that the very politicians who championed NAFTA are now bemoaning and demonizing.

The invisible hand also fails to take into account individual greed. For the most part, most people will always hew true to one law and one law only: serve thy immediate needs! It is very difficult, sometimes even nigh impossible, to convince people to care about anything beyond their own immediate surroundings and even then it has to have a benefit to them. This is especially true in the relationship of the economy to the environment, and by proxy, peoples' apathy to caring about anything to do with the environment (or people far away, for that matter).

This brings me to my second point: economics acts as though it is independent of the physical laws that govern all things and organizations. The economy treats the environment, and the mineral, biological, and human resources contained therein, as infinite. Our entire global economic system is predicated on the assumption that infinite growth is posssible, practical, and inevitable. Barring the development of cost-effective space colonization and mineral extraction, this is only absolute madness! The Earth has a finite mass and a finite chemical composition and as such there is an absolute limit to the volume of materials we can extract and use. We can only move so much, and at that relatively little, amounts of stuff around before we start to poision our own garden. We've been quite tidily moving the carbon in fossil fuels to carbon dioxide in the atmosphere for the past 2 centuries, which is now incontrovertibly linked to global warming and ocean acidification.

Economics also ignores the very real and deadly costs of waste products. Manufacturing waste, whether steel slag, arsenic extractant for gold, or simple office paper trash, take up space and, because its toxic more often than not, poisons its immediate environment. Waste represents an energy sink, a huge cost that is magicked away from the accounting sheets because it is long-term and distant and will be someone else's problem before we are willing to take responsibility for it. Economics treats waste as just another commodity, pretending that the Earth contains infinite space for landfills, infinite fresh water to pollute, and infinite poor nations to dump toxic waste upon. While this does indeed maximize profits for the already-affluent shareholders, it does nothing to increase the average standard of living for the human race. If anything, it just makes it worse.

If nothing else, we can at least conclude that the invisible hand is not only invisible, but also blind, venal, and utterly unwilling to acknowledge its limitations. Funny how an invisible hand can look so hard at itself preening in the mirror.

*Seriously, who thought it'd be a good idea to sell debt around? That's like selling someone a cookie before the flour has even been ground, and if you sold me a cookie before you so much as even had the ingredients you'd have a very unhappy and possibly angry Toaster on your hands.
**Politics, however, does operate independently of thermodynamic principles.

13 July, 2009

On Apoptosis in Development

ResearchBlogging.orgApoptosis means doom for an individual cell. As such we tend to automatically assume that apoptosis is a Bad Thing, but in reality apoptosis often is quite necessary for normal physiological function at the organism level. In order for our bodies to maintain the homeostasis that defines so many of our cellular processes, we have to sacrifice some cells. As it turns out, we actually wind up sacrificing enormous numbers of cells every day. Worn out red blood cells, dangerously self-reactive lymphocytes, individual columnar epithelial cells and others. These processes are tightly regulated, so much so that most cell types actually require biochemical signals from neighboring cells, tissues, or even distant organs just to tell them to keep living. The anti-apoptotic survival signals can fall below a threshhold value and/or be overridden by pro-apoptotic stimuli, which normally results in swift induction of the apoptotic program. When individual cells develop mutations that deafen them to these signals, they become dangerous proliferation-happy pre-cancerous cells more interested in their own survival than that of their constituent organism.

Figure A: TUNEL histochemical staining in murine liver, brown cell is apoptotic.

The apoptotic program ultimately results in highly oxidative and degradative enzymes (such as proteases) hidden away in the mitochondria being released into the cytoplasm to wreak havoc. Usually the raw material of a dying cell is tidily absorbed by its neighbors to be recycled. I've always imagined mitochondria as pulsing with a low, gentle buzz in normal cellular physiology with occassional metallic pings as statistical flucuations in the net free energy of electrons falling down the electron transport chain is captured in ATP. Following this, I think the sound of caspase-8 et al slicing open the mitochondria would be like the initial panicked braking shriek of a train loaded with Furbies who are quickly drowned out in the self-amplifying roar like a tornado grinding through a gravel pit as the apoptotic effector enzymes set to work dissolving the cell from within.

Apoptosis is absolutely essential not just to adult homeostasis, but also to normal ontogeny. Without apoptosis organs would fail to separate, fingers would remain stuck together, and many other things would go very, very wrong. There are 2 families of intracellular proteins that battle to determine whether or not a cell will become apoptotic: the (generally) pro-apoptotic Bcl-2 family and the (generally) anti-apoptotic IAP family. Conveniently, IAP stands for Inhibitor of Apoptosis Protein. A recent review by Dr. O'Riordan et al discussed the diverse and essential roles for IAP proteins in normal tissue development across a wide range of model organisms. From ablated organ development in the absence of Diap1 in Drosophila larvae to stunted hematopoeitic developmental repertoire in the abscence of Survivin in mice, IAPs seem to be evolutionarily conserved signal transducers that integrate diverse extracellular signals into a coherent cellular action. Developmentally, the IAP proteins seem to be involved in everything from proper vascularization to chromosome stability, although it is important to note that direct modulation of apoptosis in developmental processes has only been established in invertebrates. Lack of any one of several IAPs in higher chordates has not been directly linked to developmental apoptosis, but several abnormal embryonic phenotypes and attenuated adult functional capacities have been demonstrated.

IAPs are grouped by the prescence of BIRs (baculovirus IAP repeats) and many also have RING domains. Both motifs have been found to have zinc-finger conformations and the interaction of different sections of adjacent BIR motifs in some proteins, such as direct inhibition of pro-apoptotic caspases-3 and -7 by BIR2 of XIAP (X-linked inhibitor of apoptosis protein), has been found to modulate a number of diverse effects. These diverse effects are potentiated by the ubiquitin ligase activity that some RING domains have demonstrated. IAPs help the organism balance necessary apoptosis and unnecessary apoptosis, and because apoptosis is required for the homeostasis of most tissues the IAP family has been evolutionarily conserved and biochemically diversified. IAPs remain an active and engaging area of research that holds great promise in the treatment of pathologies from cancer to intracellular bacterial infections and underscore how a little sacrifice for the team by one cell can make a massive impact on the constituent organism's overall fitness.

IAPs have also been found to modulate innate immunity, which will be discussed in another post.

ORIORDAN, M., BAULER, L., SCOTT, F., & DUCKETT, C. (2008). Inhibitor of Apoptosis Proteins in Eukaryotic Evolution and Development: A Model of Thematic Conservation Developmental Cell, 15 (4), 497-508 DOI: 10.1016/j.devcel.2008.09.012

Additional Source: Molecular Biology of the Cell; Alberts et al; 4th ed.; pages 1010-1014

11 July, 2009

Against Megalomania

The public has an odd image of scientists are reclusive loners with deep eclectic streaks and megalomaniacal tendencies. Eclecticism aside, it should most vehemently noted that megalomaniacs are, by their very nature, doomed to failure, so as a scientist you shouldn't even try. Yes, it may be tempting to ponder as you blearily load Blue Juice into agarose wells and wonder why you bothered to crawl out of bed. And yes, you may know, in your data-ey heart of hearts that the world would be a better place if it was ruled by a rational scientist*, but the truth is that each and every megalomaniac aspirant begins their path to conquering the world with grand visions of uniting the world as one cohesive and peaceful society. Then they inevitably make 2 mistakes:

1) Try to invade Russia.
2) Fail to take into account that people actually live in the world.

First of all, it should be noted that unless you've found a way to animate snow men as soldiers, you will never successfully conquer a very cold, wintery Northern country (except maybe Canada). The people that live there are used to the staggeringly brutal winters and know how to use it as an advantage against you. To understand that this is true, you only have to look to the historical examples (of which there are relatively few) where one Northern country tried to whup another militarily instead of just economically. In the Winter War of 1942, Finland and Russia fought a nasty border war. The Russians attacked on snow mobiles, and the native Finns who knew the land ambushed them, guerilla-style, on skis. Russia tried to use tanks, but really should have known better: they got stuck in freezing mud. Moscow may be flat, but Karelia and Finland are full of lakes, and what looks like dry ground between lakes is usually actually a swamp. Finland eventually lost this battle because they didn't have the supplies to keep fighting, and they wound up losing a substantial amount of territory in Karelia and also lost the important industrial city of Viipuri (now Vyborg).

Secondly, in almost everywhere on the planet, in every little nook and cranny where you'd least expect to find them, are people. Living there. With histories, and traditions, and individual languages and land rights that make the task of being their benevolent ruler aggravatingly complex and bureaucratic. You're stuck with them. You have to deal with them, regardless of whether or not you want to because, if you're in charge and decide to ignore them and focus elsewhere, you'll have a steaming pile of rebellion dropped right into your fancy oatmeal. And let's face it: rebellions are an expensive pain in the ass. You've got to send soldiers to keep them from taking it out on any vulnerable scapegoats, you've got to rebuild whatever they manage to destroy (never underestimate the sheer raw power of 10,000 angry people with hammers), and then you've got to figure out whatever the hell it was they wanted in the first place. Pain. In. The. Ass. Instead of eating exquisite grapes off the juicy bodies of your servants and having your wine washed in fancy feet, you've got to rule the people.

Alternatively, you could conquer the world and set up a Parliament so that the people you now have to rule would feel like they had some say in things, but then you'd also have to deal with Parliament interfering in your wishes. And if you decide to go even further and let Parliament actually rule and be a figurehead emporer instead, well, let's just say you're setting yourself up for a coup d'etat, and once the whole world is pissed off at you there's no where for you to flee to.

Isn't this sounding like a massive bother? Wouldn't a nice cup of tea and a cookie be better instead? I mean, if you're going to rule something absolutely, start somewhere where you can decide who gets to live there. Like the Moon. If anyone tries to rebel you can politely tell them to go walk it off outside.

*Because if we let an engineer run the world everything would suddenly have 3X as many buttons, 1/2 as many useful functions, and nothing would be properly labeled.

10 July, 2009

Ready For Conference

Toaster is ready for the conference. Are you?

08 July, 2009

Notes From The Sprawl #5

A song, entitled "Suburban Dirge 1", may be found here. Maybe not so much Notes From The Sprawl as Excoriation Thereof. This one is from my archives, and I think it illustrates the topic at hand quite well.

06 July, 2009

A Proposal

PROBLEM: At conferences and meetings of scientists, it is difficult to differentiate the academic ranks of the various attendees. This greatly complicates politeness and increases the risk of disrespecting a big shot who will then sabotage the entire rest of your career for your unwitting slight.

SOLUTION: Conference attendees shall wear hats, with the fanciness of said hats increasing as their academic rank increases.

Undergrads = berets of various colors (by lab or school)
Grad students, pre quals = Fezs
Grad students, post quals = bowlers
Post-docs = tri-corner hats, add 1 feather to hat/successive post-doc
Profs w/out tenure = princess cone hats, add 1 sequin per publication
Profs w/ tenure = princess cone hats w/ gauze streamers, add 1 sequin/publication
Departmental chairs = fruit baskets with real fruit
Journal editors = appropriate hat + bling
Techs = top hats, fancier ribbons indicating greater experience
Lab managers = fedoras
Core facility staff = cowboy hats
Journalists = cat-earred head bands

And Now For Something Unrelated

For anyone who believes classical music is outdated and boring, or that it's an antiquated and dead genre that is not relevant to modern times, I present this rebuttal:

04 July, 2009

Notes From The Sprawl #4

The acrid stench of bleach kept the bristling green riot at bay behind the well-polished kitchen windows. She sniffed, momentarily satisfied, and rubbed blearily at the caffeinated caverns stretching beneath her itchy eyes. A sudden twitch brought her shoulders about her ears as a birdsong clarion echoed faintly through the vinyl siding. With a moist sigh, she turned to rummage through her obese bag for the earbuds that made her daily penance upon the treadmill more bearable and shuffled away on the fresh linoleum.

Later that day, after she’d bit her tongue while he complained about his boss—forgetting, as always, to remember to ask how her presentation that morning had gone—over a skillet-warmed stir fry with no monosodium glutamate, she curled into the squeaky couch and nursed a gingerly spiked cranberry juice as a dull parade of local news and commercials marched past her flickering thoughts. There was a knot somewhere, something not quite right, but she thumbed a pregnant sniffle away from her nose and lost the mustering concentration to put her finger on it.

The next morning, bleary from being woken at dawn by seven friendly sparrows and one erstwhile loon (which she thought was an owl), groping for her probiotic yogurt breakfast as she backed her sedan out of the oil-smelling garage, she suddenly stopped. Two of the dozen mole traps scattered about her patchy front yard had been sprung. Knowing that he would leave 5 minutes too late to bother noticing or doing anything about, she jammed the car into neutral and clattered out into the yard, cursing the tiny stones that persisted amid the rooting sod. With a fragrant mixture of revulsion and curiosity, she reached down to pull the first sprung trap out of the proud mole hill he’d punched it into.

It wouldn’t budge.

She pulled.

It resisted.

So she pulled harder, kneeling down in her favorite floating yoga position to grasp and tug with both hands. With an organic wet suck, the trap abruptly came free of the dew-drenched earth and she reeled backwards, crashing onto the thick sod with a disgruntled thud. The trap was empty. Snarling invectives against the undeveloped patch of forest that hemmed in her orderly cul-de-sac, she lunged forward and peered into the hole she’d just opened up, just in enough time to see the hairy, tapered rear end of something brown retreating down into the wormy murk. With a cavalcade of searing oaths, she stomped back into the gingerbread house to change her newly grass-stained blouse.

Now she was going to be late, and she was pissed.

03 July, 2009

Notes From The Sprawl #3

I am back in Michigan. I have nothing particularly profound or insightful to say regarding my week-long trip back to my Ozarkian whelping grounds, except that it became painfully, perhaps even absurdly, obvious just how pale I have become since moving to Teh North. I am delighted to report that the cliffs of the Meramac River do indeed amplify one mightily, especially when one sneezes whilst floating below them in a kayak. I thought I was being shot at.

This little series, "Notes From The Sprawl", will continue a little while longer until it dries up. I go back to the place that I used to call home, that I fought so hard to get out of, and I see how much has changed. Not for the better, just more of the same. It seems like almost every single fucking one of the wild places I inhabited growing up has been plowed over for more bland tract homes or been walled away behind fanciful shrubbery. The fingers of wilderness that the developers couldn't profit from are being razed anyway, plowed under for more vacuous consumption as new construction techniques are magicked into thin air. I still think it's stupid to try to build houses in a swamp.

But it remains gut-wrenching to behold. The swampy forest with the deep ravines that I used to carry my bike across a fallen tree to get to, where I could ride wherever and however I wanted, every green tree blurring past my handlebars climbable, has been felled, filled in, and paved over. I wonder where the salamanders I used to chase down the streams have gone now that those same streams are heavy and swollen with the mud running off of the clear-cut land while small-minded box homes are put up in their place. The ponds I used to chase tadpoles in have been fenced off and labeled as dangerous. The hollers are being swept away underneath the bluffs being rudely shoved into them by bulldozer armies, replaced by pesticide lawns and asphalt parking lots that ooze malodorously in the summertime heat. Every piece of the wild, every part of the real, is being torn apart or boxed away. The proud old oaks with their gnarled roots hiding years' of birdsong are being pulled down to make way for plastic ficus trees and cheap lawn frappery. The birches, the elms, the hickorys, the careful slow dogwood and the stodgy firs: my friends, our family.

Sure, maybe it's the American Dream to own your own piece and house and fill it with whatever you like; but at the same time, we're doing so en masse and completely losing the authenticity of the red clay earth that holds that land up, losing reality when we truck in manufactured top soil and sod instead. I wonder, perhaps cynically, how many of the people who dwell in these cookie cutter houses have ever actually dug in the earth, gotten the lovely reek of it up to their elbows and ingrained its grit in every tiny whorl of their fingertips. I wonder who among them has ever tried to jump a creek and failed laughing among the startled turtles. I wonder whether any of them have ever looked down and seen the tiny, ancient shells that run through the area's red flint stones like fire through our veins and felt small and insignificant in the sheer scope of what the earth is and has been and will continue to be long after they've ceased to be, and just wondered at the sheer marvel of it all.

We're rushing to trade this*:
For this:

What are we losing?

Damn near everything that matters.

*Yeah, it's blurry. I apologize, but I was rolling backwards when I took it.

02 July, 2009

Notes From the Sprawl #2

The Sprawl is the flabbiest of all civil structures. It represents the ultimate in chaotic decentralization driven entirely by the profit motive of land developers who raze forest and farm alike to plane the earth and replace them with rows of standard plan houses and pear trees*. Cloned subdivisions with timber frames and false brick facades spring up from the Caterpillar wreckage of the land. Many have argued that decentralization increases resilience of almost any system, including the suburbs, but I strongly disagree with this. In order for decentralization to have a net positive effect upon the structure in question, adequate infrastructure must first be in place. Suburbs are spawned on old county roads that once only served farms and light traffic, suddenly jammed full of SUVs and minivans as people wend about on their daily multitudinous commutes. Developers benefit from this tangibly, consumers nominally, and society pays the remaining negative balance through the continual development of catch-up infrastructure: new roads and new schools, new strip malls and parks to accommodate the shifting needs of an ever-pancaking population. Fundamentally, barring the development and implementation of efficient and unlimited energy, The Sprawl is entirely unsustainable.

Living in The Sprawl, one must drive everywhere. There are no other options. Sidewalks and bike lanes are rare; the logistics and cost of trying to implement mass transit in the landscape of streets designed to maximize profit through over-indulgence in cul-de-sacs and curving lanes is an absolutely Sisyphean nightmare. The creation of this curiously inefficient arrangement of society has been enabled and perpetuated by the development of the personal automobile. Without dependable, affordable personal transportation, people would never have been able to sever their dependency upon centralized mass transit in the more densely populated cities and begin to commute. Without relatively cheap energy, the absolutely massive scale of material trafficking required to sustain suburban patterns of consumption would be untenable. Even with cheap energy from gasoline, the traffic of the wheat from field to factory to face is fragile and easily disrupted. This is not resilience, this is absurdity!

With a city, the population is concentrated, and so are the infrastructures that distribute solutions to their needs. The environmental footprint, as quantized in gross inputs and outputs, is easily measured and containable. Suburbia spreads out over the farmland that once fed the city it is creeping out of, over the forest that once purified that city’s waste. Suburbia replaces these with new needs, spread thinner and spread farther. And through it all, the personal automobile reigns supreme. We’ve come to view driving as a right, and not an economic privilege. The reality of it is that driving is massively subsidized by the public through the creation and maintenance of roads, and this is one of the truthisms that lies sharp behind the seductive veil of the American Dream. It ain’t nearly so cheap as we’d like to believe, not for our wallets our the surrounding environment.

*Pear trees seem to be a favorite in the Midwest because they grow quickly and make a nice, dense shape. However, the most popular variety planted doesn’t even bear fruit and has a common habit of falling apart in a strong storm. It also doesn’t even have the decency to smell nice.

How Not to Flirt #4

If you are going to take the risk of consuming food in the presence of the object of your affection, it is recommended that you take care not to place a volume of food larger than that of your mouth into said mouth, regardless of whether or not you also try to continue speaking through it.

01 July, 2009

Llamas Against Breast Cancer

ResearchBlogging.orgWe all knew llamas were kind of weird. They're fluffy. They're smelly. They spit. They're like Sanrio (the Hello Kitty company) tried to make over a camel. But that's not all. Llamas are also immunologically strange. Whereas most all other organisms with a humoral immune system produce large, multi-domain antibodies with several distinct genetic and structural motifs, llamas instead make nanobodies. Nanobodies are, basically, tiny little antibodies. Normal antibodies contain 2 heavy chains and 2 light chains, which each have V (variable, where the epitope binds) and J (joining) regions; and the heavy chains also have C (constant, these make up the Fc fragment) regions. All of those chains are bound together by disulfide bonds and the resulting antibody typically has 2 binding sites, each at the tip of the Y shape. Nanobodies dispense with all of that and only retain a functional binding site with a single variable light chain domain. As a result, nanobodies are much much smaller and can access and bind to sequestered epitopes or complex 3D epitopes that may otherwise be hidden inside a molecular cleft.

Figure A: Structual phylogenetic picture, much like a family picture. This is only an approximation as Good Images are copyrighted and Photoshopping ribbon-style molecules is difficult.

The point of this study is not that nanobodies are weird and cool. Instead, Alvarez-Rueda et al harnessed the complex 3D structural variability of nanobodies to mimic the immunogenic structure of HER2. HER2 is a surface protein normally only expressed in fetal development that is reexpressed in 20-40% of breast cancers and 30% of ovarian cancers. It is a member of the epidermal growth factor (EGF) family and is suspected to help cancerous cells proliferate more rapidly and aggressively. Tumor expression of HER2 correlates strongly with increased metastatisis and decreased survival. We've known about HER2 for a while now and it has been a target of intense research. There are now genetic tests available for HER2 alleles that correlate with increased morbidity from breast cancer. There was also a passive immunotherapeutic treatment against HER2 approved for use in combination with chemotherapy in 1998 called Trastuzumab (marketed as Herceptin(R) and manufactured by Roche). Trastumuzab is a humanized antibody therapy that targets HER2 directly; it is thought that it mimics the natural humoral immune response to HER2, which is observed to slow down tumor growth in early tumors but unfortunately sometimes fails to stop it. The primary problem with Trastuzumab is that it must be repeatedly administered over the course of cancer treatment to have any effect. While Trastumuzab is an invaluable tool in the fight against these cancers, it has long been recognized that inducing a robust host immune response would help to combat the tumor itself, and subsequent induction of a host immune memory against HER2 would help to prevent relapse of the cancer.

The best way to do this is with a vaccine.

Simply injecting HER2 with an adjuvant could produce a strong immune response, but the HER2 itself could make the cancer worse meanwhile. The ideal vaccine would be a molecule that mimics the structure of HER2 closely enough to induce cross-reactive immunity but that doesn't have the biological activity of HER2.

Enter the llama and its nanobodies.

Alvarez-Rueda et al injected Trastuzumab into a llama and the llama kindly produced nanobodies. Because Trastuzumab is an antibody against HER2, the llama's immune system produced a molecule against it that is somewhat structurally similar to HER2. When this nanobody molecule was isolated and expressed via transgenic clone library, it was found to strongly bind both Trastuzumab as well as isolated human anti-HER2 antibodies. So they then took the nanobody (called 1HE) and injected it into mice (along with Freund's adjuvant). As expected, the mice produced antibodies against the nanobody. These antibodies then, in turn, bound strongly to both 1HE and the HER2 protein. This strongly implies that immunization of a human with the 1HE nanobody and adjuvant would induce a strong anti-HER2 antibody response, effectively immunizing them against HER2-expressing breast or ovarian cancers or arresting the growth of existing tumors as part of chemotherapy*. Additionally, the polyclonal antibodies produced by the mice in response to the nanobody were found to inhibit growth of HER2-expressing carcinoma cell lines. The data have not yet been validated in vivo.

Either way, this is a cool advance in the fight against breast cancer, and I sincerely hope that something therapeutically useful in humans will soon come out of this. Thank you, llamas.

*This is technically known as an anti-idiopathic vaccine.

Alvarez-Rueda, N., Ladjemi, M., Béhar, G., Corgnac, S., Pugnière, M., Roquet, F., Bascoul-Mollevi, C., Baty, D., Pèlegrin, A., & Navarro-Teulon, I. (2009). A llama single domain anti-idiotypic antibody mimicking HER2 as a vaccine: Immunogenicity and efficacy Vaccine DOI: 10.1016/j.vaccine.2009.05.067