it is now the absolute worst time ever to be an ordinary medicinal chemist in a high-wage part of the world. The days when you could make a reliable living doing methyl–ethyl–butyl–futile work in the United States or Western Europe are gone, and what mechanism will ever be found to bring them back? There’s still a lot of that work that needs to be done, but it is getting done somewhere else, and as long as “somewhere else” operates more cheaply and reasonably on time, that situation will not change.

This means that the best advice is not to be ordinary. That is not easy, and it is no guarantee, either, but it is the only semisafe goal for which to aim. Medicinal chemists have to offer their employers something that cannot be had more cheaply in Shanghai or Bangalore. New techniques, proficiency with new equipment, ideas that have not become commodified yet: Those seem to be the only form of insurance, and even then, they are not always enough.

I may be slightly biased as much of my work has been in the technology industry where large industry changes happen a little faster than in other industries so I’m particularly attuned to how those will impact companies, but very rarely do I notice people – in and out of the technology industry – give some careful thought to how their industries will change over time – and I think that’s a shame.

In the same way that the medicinal chemists from 5-10 years ago that Derek Lowe is writing about were caught off-guard by the impact of globalization, people in the postal service are watching technologies like email and internet advertising change the foundation of their jobs, people in the healthcare industry are watching new laws and regulations slowly come down the pipeline, and people in the book publishing industry are watching as eBooks and eReaders take off. I’m not claiming that these changes were obviously predictable – that’s what makes my job in venture interesting! — but, changes in science & technology, in globalization, and in demographics have and will dramatically impact every aspect of life/business and, frankly speaking, its the people who work in an industry (in the case of medicinal chemistry, it was guys like Derek Lowe) who have the best shot at gazing at a crystal ball, predicting and understanding the changes that will come down the pipeline, and, then, figuring out ways to get ahead of it (whether that means changing jobs, learning new skills, etc).

So, do yourself a favor 5-10 years from now – and gaze into your crystal ball.

(Image credit: PE2011 Facts)

Take the rapidly growing flash sales site Fab.com. They started as a social networking service focused on the gay population. But, when that did not work as well as they had hoped, they then attempted to reposition themselves as a review/check-in service also focused on the gay population.

Actually, it would be far more illustrative to use their words (see slide from Fab.com presentation below): they started as “Gay Facebook”, then tried to become a “Gay Yelp”, then shifted businesses to become a “Gay Foursquare” (after the popular social and location-based check-in service), and then tried to pivot again towards being a “Gay Groupon”.

But before they could try (and potentially falter again at) becoming the gay versions of the other major internet companies out there (Quora, Zynga, LinkedIn, Google, Pandora maybe?), they stumbled on something which really fit with their passions and interests – and that is the birth of the Fab.com that we see today.

So, successful changes can happen. Ideally, they wouldn’t need to take as many steps as Fab.com did, and we’re still a long way from ultimately calling Fab.com a success, but under the right reasons and with the right strategic thinking and operational chops, they can happen.

(Slideshare link)

For January I decided to blog a paper I heard about on the excellent Nature podcast about a deliciously simple and elegant experiment to test a very simple question: given how much time and effort boa constrictors (like the one on above, photo taken by Paul Whitten) need to kill prey by squeezing them to death, how do they know when to stop squeezing?

Hypothesizing that boa constrictors could sense the heartbeat of their prey, some enterprising researchers from Dickinson College decided to test the hypothesis by fitting dead rats with bulbs connected to water pumps (so that the researchers could simulate a heartbeat) and tracking how long and hard the boas would squeeze for:

• rats without a “heartbeat” (white)
• rats with a “heartbeat” for 10 min (gray)
• rats with a continuous “heartbeat” (black)

The results are shown in figure 2 (to the right). The different color bars show the different experimental groups (white: no heartbeat, gray: heartbeat for 10 min before stopping, and black: continuous heartbeat). Figure 2a (on top) shows how long the boas squeezed for whereas Figure 2b (on bottom) shows the total “effort” exerted by the boas. As obvious from the chart, the longer the simulated heartbeat went, the longer and harder the boas would squeeze.

Conclusion? I’ll let the paper speak for itself: “snakes use the heartbeat in their prey as a cue to modulate constriction effort and to decide when to release their prey.”

Interestingly, the paper goes a step further for those of us who aren’t ecology experts and notes that being attentive to heartbeat would probably be pretty irrelevant in the wild for small mammals (which, ironically, includes rats) and birds which die pretty quickly after being constricted. Where this type of attentiveness to heartrate is useful is in reptilian prey (crocodiles, lizards, other snakes, etc) which can survive with reduced oxygen for longer. From that observation, the researchers thus concluded that listening for heartrate probably evolved early in evolutionary history at a time when the main prey for snakes were other reptiles and not mammals and birds.

In terms of where I’d go next after this – my main point of curiosity is on whether or not boa constrictors are listening/feeling for any other signs of life (i.e. movement or breathing). Obviously, they’re sensitive to heart rate, but if an animal with simulated breathing or movement – would that change their constricting activity as well? After all, I’m sure the creative guys that made an artificial water-pump-heart can find ways to build an artificial diaphragm and limb muscles… right?

(Image credit – boa constrictor: Paul Whitten) (Figures from paper)

Paper: Boback et al., “Snake modulates constriction in response to prey’s heartbeat.” Biol Letters. 19 Dec 2011. doi: 10.1098/rsbl.2011.1105

We’ve blogged before about applying gaming technology to science, but much of that has been about using games or gaming system chips. A recent Wired magazine article reveals another interesting use case: taking the capabilities of something like Microsoft’s Xbox360 Kinect system and applying it directly to science research!

Apparently, a number of groups have decided to try out the Kinect as a “poor man’s” LIDAR (a tool that can be used to see and measure where things are in three dimensions)/complicated 3D camera setups which are expensive and require sophisticated calibration/post-processing analysis.

Of course, the Kinect is not a panacea: it has much more limited range, requires researchers to build their own analytical software, and the Kinect can’t do high-speed video (yet). But, because of its much lower price, its size, and the availability of drivers because of the active Kinect hacking/DIY community (and the support that even Microsoft is providing for people using Kinect beyond gaming), a number of researchers have decided to embrace the Kinect as a scientific tool.

The article profiles two potential use cases which only begin to scratch the surface of what this technology could be capable of: mapping meltwater lakes that form on top of glaciers (see images below) and studying small body impacts in space.

But, potentially the most valuable use of Kinect? As the Wired article puts it:

The Kinect’s best asset may be that it inspires students, Tedesco said. Rather than a daunting black box with convoluted cables and arcane software, the Kinect is something that many students are already familiar with.

“This creates a different mindset in students,” he said. “They’re not so scared about using the Kinect, and they can really get involved in learning and basic research.”

“I’m actually on my way to buy two of them right now,” he added.

(Image credit – Kinect) (Image credit – Kinect glacier map)

Because much has changed in the year and a half since I wrote that first epic post comparing my DROID2 with an iPhone 4 – for starters, my iPhone 4 now runs the new iOS 5 operating system and my DROID2 now runs Android 2.3 Gingerbread — I thought I would revisit the comparison, having had over a year to use both devices in various capacities.

Long story short: I still prefer my DROID2 (although to a lesser extent than before).

So, what were my big observations after using the iPhone 4 for two weeks and then switching back to my DROID2?

• Apple continues to blow me away with how good they are at
  • UI slickness: There’s no way around it – with the possible exception of the 4.0 revision of Android Ice Cream Sandwich (which I now have and love on my Motorola Xoom!) – no Android operating system comes close to the iPhone/iPad’s remarkable user interface smoothness. iOS animations are perfectly fluid. Responsiveness is great. Stability is excellent (while rare, my DROID2 does force restart every now and then — my iPhone has only crashed a handful of times). It’s a very well-oiled machine and free of the frustrations I’ve had at times when I. just. wished. that. darn. app. would. scroll. smoothly.
  • Battery life: I was at or near zero battery at the end of every day when I was in Asia – so even the iPhone needs improvement in that category. But, there’s no doubt in my mind that my DROID2 would have given out earlier. I don’t know what it is about iOS which enables them to consistently deliver such impressive battery life, but I did notice a later onset of “battery anxiety” during the day while using the iPhone than I would have on my DROID2.
• Apple’s soft keyboard is good – very good — but nothing beats a physical keyboard plus SwiftKey. Not having my beloved Android phone meant I had to learn how to use the iPhone soft keyboard to get around – and I have to say, much to my chagrin, I actually got the hang of it. Its amazingly responsive and has a good handle on what words to autocorrect, what to leave alone, and even on learning what words were just strange jargon/names but still legitimate. Even back in the US on my DROID2, I find myself trying to use the soft keyboard a lot more than I used to (and discovering, sadly, that its not as good as the iPhone’s). However:
  • You just can’t type as long as you can on a hard physical keyboard.
  • Every now and then the iPhone makes a stupid autocorrection and it’s a little awkward to override it (having to hit that tiny “x”).
  • The last time I did the iPhone/DROID comparison, I talked about how amazing Swype was. While I still think it’s a great product, I’ve now graduated to SwiftKey(see video below) not only because I have met and love the CEO Jonathan Reynolds but because of its uncanny ability to compose my emails/messages for me. It learns from your typing history and from your blog/Facebook/Gmail/Twitter and inputs it into an amazing text prediction engine which not only predicts what words you are trying to type but also the next word after that! I have literally written emails where half of my words have been predicted by SwiftKey.

     

• Notifications in iOS are terrible.
  • A huge issue for me: there is no notification light on an iPhone. That means the only way for me to know if something new has happened is if I hear the tone that the phone makes when I get a new notification (which I don’t always because its in my pocket or because – you know – something else in life is happening at that moment) or if I happen to be looking at the screen at the moment the notifications shows up (same problem). This means that I have to repeatedly check the phone throughout the day which can be a little obnoxious when you’re with people/doing something else and just want to know if an email/text message has come in.
  • What was very surprising to me was that despite having the opportunity to learn (and dare I say, copy) from what Android and WebOS  had done, Apple chose quite possibly the weakest approach possible. Not only are the notifications not visible from the home screen – requiring me to swipe downward from the top to see if anything’s there — its impossible to dismiss notifications one at a time, really hard (or maybe I just have fat fingers?) to hit the clear button which dismisses blocks of them at a time, even after I hit clear, I’m not sure why some of the notifications don’t disappear, and it is surprisingly easy to accidentally hit a notification when you don’t intend to (which will force you into a new application — which wouldn’t be a big deal if iOS had a cross-application back button… which it doesn’t). Maybe this is just someone who’s too used to the Android way of doing things, but while this is way better than the old “in your face” iOS notifications, I found myself very frustrated here.
• Cursor positioning feels a more natural on Android. I didn’t realize this would bug me until after using the iPhone for a few days. The setup: until Android’s Gingerbread update, highlighting text and moving the caret (where your next letter comes out when you type) was terrible on Android. It was something I didn’t realize in my initial comparison and something I came to envy about iOS: the magnifying glass that pops up when you want to move your cursor and the simple drag-and-drop highlighting of text. Thankfully with the Gingerbread update, Android completely closes that gap (see image on the right) and improves upon it. Unlike with iOS, I don’t need to long-hold on the screen to enter some eery parallel universe with a magnified view – in Android, you just click once, drag the arrow to where you want the cursor to be, and you’re good to go.
• No widgets in iOS. There are no widgets in iOS. I can see the iOS fans thinking: “big deal, who cares? they’re ugly and slow down the system!” Fair points — so why do I care? I care because widgets let me quickly turn on or off WiFi/Bluetooth/GPS from the homescreen in Android, but in iOS, I would be forced to go through a bunch of menus. It means, on Android, I can see my next few calendar events, but in iOS, I would need to go into the calendar app. It means, on Android I can quickly create a new Evernote note and see my last few notes from the home screen, but in iOS, I would need to open the app. It means that on Android I can see what the weather will be like from the homescreen, but in iOS, I would need to turn on the weather app to see the weather. It means that on Android, I can quickly glance at a number of homescreens to see what’s going on in Google Voice (my text messages), Google Reader, Facebook, Google+, and Twitter, but on iOS, I need to open each of those apps separately. In short, I care about widgets because they are convenient and save me time.
• Apps play together more nicely with Android. Android and iOS have a fundamentally different philosophy on how apps should behave with one another. Considering most of the main iOS apps are also on Android, what do I mean by this? Well, Android has two features which iOS does not have: a cross-application back button and a cross-application “intent” system. What this means is that apps are meant to push information/content to each other in Android:
  • If I want to “share” something, any app of mine that mediates that sharing – whether its email, Facebook, Twitter, Path, Tumblr, etc – its all fair game (see image on the right). On iOS, I can only share things through services that the app I’m in currently supports. Want to post something to Tumblr or Facebook or over email in an app that only supports Twitter? Tough luck in iOS. Want to edit a photo/document in an app that isn’t supported by the app you’re in? Again, tough luck in iOS. With the exception of things like web links (where Apple has apps meant to handle them), you can only use the apps/services which are sanctioned by the app developer. In Android, apps are supposed to talk with one another, and Google goes the extra mile to make sure all apps that can handle an “action” are available for the user to choose from.
  • In iOS, navigating between different screens/features is usually done by a descriptive back button in the upper-left of the interface. This works exactly like the Android back button does with one exception. These iOS back buttons only work within an application. There’s no way to jump between applications. Granted, there’s less of a need in iOS since there’s less cross-app communication (see previous bullet point), but when you throw in the ability of iOS5’s new notification system to take you into a new application altogether and when you’re in a situation where you want to use another service, the back button becomes quite handy.
• And, of course,  deluge of the he-said-she-said that I observed:
  • Free turn-by-turn navigation on Android is AWESOME and makes the purchase of the phone worth it on its own (mainly because my driving becomes 100x worse when I’m lost). Not having that in iOS was a pain, although thankfully, because I spent most of my time in Asia on foot, in a cab, or on public transit, it was not as big of a pain.
  • Google integration (Google Voice, Google Calendar, Gmail, Google Maps) is far better on Android — if you make as heavy use of Google services as I do, this becomes a big deal very quickly.
  • Chrome to Phone is awesome – being able to send links/pictures/locations from computer to phone is amazingly useful. I only wish someone made a simple Phone-to-Chrome capability where I could send information from my phone/tablet to a computer just as easily.
  • Adobe Flash performance is, for the record, not great and for many sites its simply a gateway for advertisements. But, its helpful to have to be able to open up terrible websites (especially those of restaurants) — and in Japan, many a restaurant had an annoying Flash website which my iPhone could not open.
  • Because of the growing popularity of Android, app availability between the two platforms is pretty equal for the biggest apps (with just a few noteworthy exceptions like Flipboard). To be fair, many of the Android ports are done haphazardly – leading to a more disappointing experience – but the flip side of this is that the more open nature of Android also means its the only platform where you can use some pretty interesting services like AirDroid (easy-over-Wifi way of syncing and managing your device), Google Listen (Google Reader-linked over-the-air podcast manager), BitTorrent Remote (use your phone to remote login to your computer’s BitTorrent client), etc.
  • I love that I can connect my Android phone to a PC and it will show up like a USB drive. iPhone? Not so much (which forced me to transfer my photos over Dropbox instead).
  • My ability to use the Android Market website to install apps over the air to any of my Android devices has made discovering and installing new apps much more convenient.
  • The iOS mail client (1) doesn’t let you collapse/expand folders and (2) doesn’t let you control which folders to sync to what extents/at what intervals, but the Android Exchange client does. For someone who has as many folders as I do (one of which is a Getting Things Done-esque “TODO” folder), that’s a HUGE plus in terms of ease of use.

To be completely fair – I don’t have the iPhone 4S (so I haven’t played with Siri), I haven’t really used iCloud at all, and the advantages in UI quality and battery life are a big deal. So unlike some of the extremists out there who can’t understand why someone would pick iOS/Android, I can see the appeal of “the other side.” But after using the iPhone 4 for two weeks and after seeing some of the improvements in my Xoom from Ice Cream Sandwich, I can safely say that unless the iPhone 5 (or whatever comes after the 4S) brings with it a huge change, I will be buying another Android device next. If anything, I’ve noticed that with each generation of Android, Android devices further closes the gap on the main advantages that iOS has (smoothness, stability, app selection/quality), while continuing to embrace the philosophy and innovations that keep me hooked.

(Image Credit – Android text selection: Android.com) (Image Credit – Android sharing: talkandroid.com)

The tradition of making a wrapup blog post continues… so what did I do in 2011 as reflected by my blog posts? Well, I…

• Foolishly made a list of 7 resolutions, the 3 easiest of which I completed… (I’ll let you decide which one those were) – hence learning not to do such a thing again
• Made a web-based tool to help glaucoma researchers compute AGIS visual field scores
• First ever trip to China and first ever trip to Tokyo
• Watched a movie about a certain social network which made me somewhat nostalgic for college
• Visited 1800s London, bought a new hat, and found out about my savage ancestors
• Made an impassioned plea to capital-seekers to stop sending horrible pitches to my inbox
• Continued my paper a month streak
• Was very thankful that nobody I knew personally was injured seriously during or immediately after the massive earthquake in Japan
• Changed web browsers (it’s a big deal!)
• Helped my firm kick off our Android focused A-Fund
• Found out I wasn’t the only one who adapted Hamlet into another format
• Said goodbye to a TV show that has kept me company since high school
• Bought a Android Honeycomb tablet and became a tablet convert
• Did some “serious thinking” at the De Young
• Made some recommendations for newbie comic book readers
• Started watching a new cartoon which scratched a certain superhero itch
• Bid farewell to Steve Jobs
• Mourned the loss of Google Reader’s social functionality and thus began using Tumblr (http://tumblr.benjamintseng.com/) as my poor man’s Google Reader substitute
• Read a military biography of one of my childhood heroes

All in all, a good year .

Happy New Year everybody! Here’s to a great 2012 and thank you from the bottom of my heart for reading (and continuing to read) my little corner on the internet!

(Image credit – Nassau Happening))

Like with the paper I blogged for last month, this month’s paper (from open access journal PLoS ONE) is yet again about the impact on our health of the bacteria which have decided to call our bodies home. But, instead of the bacteria living in our gut, this month is about the bacteria which live on our skin.

Its been known that the bacteria that live on our skin help give us our particular odors. So, the researchers wondered if the mosquitos responsible for passing malaria (Anopheles) were more or less drawn to different individuals based on the scent that our skin-borne bacteria impart upon us (also, for the record, before you freak out about bacteria on your skin, remember that like the bacteria in your gut, the bacteria on your skin are natural and play a key role in maintaining the health of your skin).

Looking at 48 individuals, they noticed a huge variation in terms of attractiveness to Anopheles mosquitos (measured by seeing how much mosquitos prefer to fly towards a chamber with a particular individual’s skin extract versus a control) which they were able to trace to two things. The first is the amount of bacteria on your skin. As shown in Figure 2 below, is that the more bacteria that you have on your skin (the higher your “log bacterial density”), the more attractive you seem to be to mosquitos (the higher your mean relative attractiveness).

The second thing they noticed was that the type of bacteria also seemed to be correlated with attractiveness to mosquitos. Using DNA sequencing technology, they were able to get a mini-census of what sort of bacteria were present on the skins of the different patients. Sadly, they didn’t show any pretty figures for the analysis they conducted on two common types of bacteria (Staphylococcus and Pseudomonas), but, to quote from the paper:

The abundance of Staphylococcus spp. was 2.62 times higher in the HA [Highly Attractive to mosquitoes] group than in the PA [Poorly Attractive to mosquitoes] group and the abundance of Pseudomonas spp. 3.11 times higher in the PA group than in the HA group.

Using further genetic analyses, they were also able to show a number of other types of bacteria that were correlated with one or the other.

So, what did I think? While I think there’s a lot of interesting data here, I think the story could’ve been tighter. First and foremost, for obvious reasons, correlation does not mean causation. This was not a true controlled experiment – we don’t know for a fact if more/specific types of bacteria cause mosquitos to be drawn to them or if there’s something else that explains both the amount/type of bacteria and the attractiveness of an individual’s skin scent to a mosquito. Secondly, Figure 2 leaves much to be desired in terms of establishing a strong trendline. Yes, if I  squint (and ignore their very leading trendline) I can see a positive correlation – but truth be told, the scatterplot looks like a giant mess, especially if you include the red squares that go with “Not HA or PA”. For a future study, I think it’d be great if they could get around this to show stronger causation with direct experimentation (i.e. extracting the odorants from Staphylococcus and/or Pseudomonas and adding them to a “clean” skin sample, etc)

With that said, I have to applaud the researchers for tackling a fascinating topic by taking a very different angle. I’ve blogged before about papers on dealing with malaria, but the subject matter is usually focused on how to directly kill or impede the parasite (Plasmodium falciparums). This is the first treatment of the “ecology” of malaria – specifically the ecology of the bacteria on your skin! While the authors don’t promise a “cure for malaria”, you can tell they are excited about what they’ve found and the potential to find ways other than killing parasites/mosquitos to help deal with malaria, and I look forward to seeing the other ways that our skin bacteria impact our lives.

(Figure 2 from paper)

Paper: Verhulst et al. "Composition of Human Skin Microbiota Affects Attractiveness to Malaria Mosquitoes." PLoS ONE 6(12). 17 Nov 2011. doi:10.1371/journal.pone.0028991

Quick primer for those of you not in the know/not as enthusiastic about Hannibal as I am : the Carthaginian general Hannibal fought in the Second Punic War – the second of three major wars between the two great Mediterranean powers of their day: Rome and Carthage. These wars were among the first true “world wars” that the world saw – in terms of bringing great powers to war and in terms of sheer devastation of life and property– and set the stage for Rome to eventually take over the entire Mediterranean.

So, why is Hannibal a childhood hero of mine? Well:

• He is the son of one of the greatest Carthaginian generals from the First Punic War – Hamilcar Barca — who, legend has it, made a young Hannibal swear to “never be a friend of Rome” (holy comic book origins, Batman!)
• He was a superb commander of men: whereas the Roman armies were made primarily of Roman citizens, Hannibal’s army consisted of people who spoke many different languages and had vastly different fighting styles: Carthaginian, Spanish, North African, Gallic tribesmen, Italian, Greek, etc.
• His army had elephants! I know that’s not too unique, but seriously – ELEPHANTS!
• He executed one of the boldest and most daring moves in antiquity, marching a massive multicultural army from Spain across the Alps and the Pyrenees into Italy.
• Then, for 15 years, he fought legion after legion in enemy territory, only once receiving very limited supplies and reinforcements from Carthage.
• One of those battles he fought was the famed Battle of Cannae – one of the greatest military victories ever achieved. There, Hannibal’s army of ~50,000 faced a Roman force of ~80-90,000. Despite being outnumbered, Hannibal crushed his Roman adversaries with a brilliant enveloping maneuver – losing some 5-8,000 soldiers (10-20% of Hannibal’s forces) while killing some 40-60,000 (50% of Rome’s forces) and capturing another 5-10,000! Among those killed included one of Rome’s two consuls (the equivalent to a Prime Minister or President), a previous consul, and a number of Roman Senators! In the course of three quick battles ending at Cannae, Hannibal’s forces had killed an estimated 100,000 Romans – believed to be 20% of Rome’s military age population.

I’ll admit, its not the most kid-friendly hero to have but when it came down to it, I was amazed by his life. It takes uncanny ability, stamina, and boldness to be able to operate within enemy territory for 15 years and still win victory after victory.

Its with that enthusiasm that I picked up Gabriel’s book. While I think it’s a wonderful book for anyone who is deeply interested in Hannibal and military history (like your humble blogger), this is not really a biography intended for popular consumption. The book should really be thought of as an academic close read of the works of Livy and Polybius, the two Romans who wrote the most detailed account of the Second Punic War – pointing out where Livy/Polybius’s nationalism or their lack of attentiveness to detail probably led to inaccurate or revisionist accounts of what happened. Its in those moments that the author is simultaneously the most compelling (as Gabriel clearly shows off his amazing knowledge of military history and of the ancient world) and also the most frustrating (as it interferes with the narrative of Hannibal’s life in the name of the academic purpose).

With that said, ancient/military history buffs will appreciate the attentiveness to detail from the author (and his dismantling of many commonly held beliefs about Hannibal’s failure such as the lack of naval control/siege equipment), and Hannibal devotees (which may just be me ) will appreciate the author’s almost stream of consciousness way of describing what must have been going through Hannibal’s head as he made decision after decision.

In particular, Gabriel’s dissection of why Hannibal was doomed to failure was very compelling. To Gabriel, Hannibal made a number of key mistakes. First, he did not understand that Rome did not view war the way that the Greeks did – where a large defeat or two on the battlefield would lead to one side capitulating – Rome viewed war as a life or death situation – there was no room for negotiation unless they were winning and there was no room for capitulating. Period. Secondly, he did not understand that he was just one front of a grander geopolitical chess game between Carthage and Rome: Carthage was not especially interested in Italy (it would never realistically be able to hold its territory there even if it gained it), it was interested in preserving its holdings in Spain and in the islands of the Mediterranean. It was those two errors which doomed Hannibal to failure especially once Rome realized it could not keep throwing legion after legion at Hannibal and waged a war of attrition.

So, ultimate verdict: this is great if you’re a military history buff or really want to get into the details of Hannibal’s exploits, but there are likely much more accessible reads if you just want to learn a bit more about Hannibal’s life/Punic Wars.

(Image credit – Summa Gallicana)

A few years ago, I blogged about an ingenious crowdsourced game called Fold.It. The concept was pretty simple:

• Use human intuition to help solve complicated three-dimensional protein folding challenges which is oftentimes as effective but significantly faster & cheaper than computational algorithms
• Pool together lots of human volunteers
• Turn the whole experience into a game to get more volunteers to spend more time

The result was a nifty little game which contributed findings which have made it, to date, into a number of peer-reviewed publications (see PNAS paper here and Nature Structure & Molecular Biology paper here)!

Well some researchers at McGill University in Canada want to take a page out of this playbook with a game they built called Phylo (HT: MedGadget) to help deal with another challenging issue in bioinformatics: multiple sequence alignment. In a nutshell, to better understand DNA and how it impacts life, we need to see how stretches of DNA line up with one another. Now, computers are extremely good at taking care of this problem for short stretches of DNA and for “roughly” aligning longer stretches of DNA – but its fairly difficult and costly to do it accurately for long stretches using computer algorithms.

People, however, are curiously intuitive about patterns and shapes. So, the researchers turned the multiple sequence alignment problem into a puzzle game they’ve called Phylo (see image below) where the goal is to line up multiple colored blocks. Players tackle the individual puzzles (in a browser or even on their mobile phone) and the researchers aggregate all of this into improved sequence alignments which help them better understand the underlying genetics of disease.

And how has it been doing? According to the McGill University press release:

So far, it has been working very well. Since the game was launched in November 2010, the researchers have received more than 350,000 solutions to alignment sequence problems. “Phylo has contributed to improving our understanding of the regulation of 521 genes involved in a variety of diseases. It also confirms that difficult computational problems can be embedded in a casual game that can easily be played by people without any scientific training,” Waldispuhl said. “What we’re doing here is different from classical citizen science approaches. We aren’t substituting humans for computers or asking them to compete with the machines. They are working together. It’s a synergy of humans and machines that helps to solve one of the most fundamental biological problems.”

With the new games and platforms, the researchers are hoping to encourage even more gamers to join the fun and contribute to a better understanding of genetically-based diseases at the same time.

Try it out – I have to admit I’m not especially good with puzzle games, so I haven’t been doing particularly well, but the researchers have done a pretty good job with the design of the game (esp. relative to many other academic-inspired gaming programs that I’ve seen) – and who knows, you might be a key contributor to the next big drug treatment!

Part of that ignorance is deliberate – chip companies exist to help electronics/product companies, not steal the spotlight. The only exception to that rule that I can think of is Intel which has spent a fair amount over the years on its “Intel Inside” branding and the numerous Intel Inside commercials that have popped up.

While NVIDIA has been good at generating buzz amongst enthusiasts, I would maintain that no other semiconductor company has quite succeeded at matching Intel in terms of getting public brand awareness – an awareness that probably has helped Intel command a higher price point because the public thinks (whether wrongly or rightly) that computers with “Intel inside” are better.

Well Qualcomm looks like they want to upset that. Qualcomm make chips that go into mobile phones and tablets and has benefitted greatly from the rise in smartphones and tablets over the past few years, getting to the point where some might say they have a shot at being a real rival for Intel in terms of importance and reach. But for years, the most your typical non-techy person might have heard about them is the fact that they have the naming rights to San Diego’s Qualcomm Stadium – home of the San Diego Chargers and former home of the San Diego Padres.

Well, on December 16th, in what is probably a very interesting test by Qualcomm to see if they can boost the consumer awareness of the Snapdragon product line they’re aiming at the next-generation of mobile phones and tablets, Qualcomm announced it will rename Qualcomm Stadium to Snapdragon Stadium for 10 days (coinciding with the San Diego County Credit Union Poinsettia Bowl and Bridgepoint Education Holiday Bowl) – check out the pictures from the Qualcomm blog below!

Will this work? Well, if the goal is to get millions of people to, overnight, buy phones with Snapdragon chips inside – the answer is probably a no. Running this sort of rebranding for only 10 days for games that aren’t the SuperBowl just won’t deliver the right PR boost. But, as a test to see if their consumer branding efforts raises consumer awareness about the chips that power their phones, and potentially demand for “those Snapdragon watchamacallits” in particular? This might be just what the doctor ordered.

I, for one, am hopeful that it does work – I’m a sucker for seeing enabling technologies and the companies behind them like Qualcomm and Intel get the credit they deserve for making our devices work better, and, frankly, having more people talk about the chips in their phones/tablets will push device manufacturers and chip companies to innovate faster.

(Image credit: Qualcomm blog)

One particular use case which fascinated me was in the non-consumer setting, what is mostly “fresh territory” for tablet manufacturers to pursue. But, whereas most manufacturers — like Lenovo and Toshiba — are taking on the non-consumer setting by chasing the traditional enterprise technology market, Motorola Solutions, which was spun out from the original Motorola alongside (but separate from) the consumer-oriented Motorola Mobility which was recently acquired by Google — they build things like hardware/IT systems for businesses and governments, has taken a much more customized approach (HT: EETimes) which really embodies some of the strengths of the Android approach.

Instead of building yet another Android Honeycomb tablet, Motorola Solutions has built a ruggedized Android tablet called the ET1 (Enterprise Tablet 1 – hey, they sell mainly to industrial and government customers where you don’t need catchy names ), with the emphasis on the word “ruggedized”. Yes, it has a 7” touchscreen, but this really wasn’t meant for casual consumer use at home: its meant to be used in the field/factory setting, built with a strengthened case and Gorilla Glass screen (so that it can survive drops/spills/impacts), support for external accessories (i.e. barcode scanners, printers, holsters/cases), a special hot-swappable rapid charge battery pack so that you can re-juice the device without interrupting the device function, and a “hardened” (translation: more secure by stripping out unnecessary consumer-oriented capabilities) Android operating system with support for rapidly switching between multiple user profiles (because multiple employees might use the same device on different shifts).

Will this device be a huge success? Probably not by any consumer electronic manufacturer’s metric. After all, the tablet isn’t meant for consumers (and won’t be priced that way or sold through stores/consumer eCommerce sites). But, that’s the beauty of the Android approach. If you’re not building a consumer tablet, you don’t have to. In the same way that Android phone manufacturers/software developers can experiment with different price points/business models in Africa, manufacturers can leverage (and customize) Android to target different use models and form factors entirely to satisfy the needs of specific market segments/ecosystem players, taking what they need and changing/removing what they don’t. I don’t know for sure what Motorola Solutions is aiming to get out of this, but maybe the goal isn’t to put as many of these devices out there as possible but simply to add a few key accounts with which to sell other services/software. I have no idea, but the point is that an open platform lets you do things like this. Or, to put it more simply, as I said before about Linux/Android: “go custom or go home”.

(Image credit)

What is the Dickens Fair, you ask? Apparently, it’s a Bay Area tradition dating to the 1970s where a group of performers, businesses, and cooks set up an imitation of the London which famous author Charles Dickens (1812-1870) wrote about and lived in.

And, like with Comicon, costumes and cosplaying are not only tolerated, but encouraged!

The entire experience was very fun. The shops were all period – selling period crafts and clothing and food. It was fun to just walk around and check out what people were dressed as, what they were doing, the accents they were assuming, and the various performances by singers/dancers. Feeling a little out of place, I decided to buy a hat to better blend in:

Another thing which turned out to be a fascinating experience was the antique book shop. While I didn’t buy anything, my girlfriend dug up a guide to the Japanese Empire written in 1914. At the time, the island of Taiwan was a part of the Japanese Empire so the book dedicates an entire chapter to describing it. While it was nice to hear good things about the island (about its beauty and nice climate), I was a little amused/shocked to hear the enormous amount of time the writer spent covering the “savage” aboriginal tribes and their practice of decapitation, and the extents to which the Japanese colonizers kept those practices at bay. Not really believing the writer, I turned to Wikipedia – and lo and behold, there apparently was widespread practice of headhunting amongst the aborigines!

That must explain why I’m so fierce and aggressive

November’s paper was published in Nature in 2006, and covers a topic I’ve become increasingly interested in: the impact of the bacteria that have colonized our bodies  on our health (something I’ve blogged about here and here).

The idea that our bodies are, in some ways, more bacteria than human (there are 10x more gut bacteria – or flora — than human cells on our bodies) and that those bacteria can play a key role on our health is not only mind-blowing, it opens up another potential area for medical/life sciences research and future medicines/treatments.

In the paper, a genetics team from Washington University in St. Louis explored a very basic question: are the gut bacteria from obese individuals different from those from non-obese individuals? To study the question, they performed two types of analyses on a set of mice with a genetic defect leading to an inability of the mice to “feel full” (and hence likely to become obese) and genetically similar mice lacking that defect (the s0-called “wild type” control).

The first was a series of genetic experiments comparing the bacteria found within the gut of obese mice with those from the gut of “wild-type” mice (this sort of comparison is something the field calls metagenomics). In doing so, the researchers noticed a number of key differences in the “genetic fingerprint” of the two sets of gut bacteria, especially in the genes involved in metabolism.

But, what did that mean to the overall health of the animal? To answer that question, the researchers did a number of experiments, two of which I will talk about below. First, they did a very simple chemical analysis (see figure 3b to the left) comparing the “leftover energy” in the waste (aka poop) of the obese mice to the waste of wild-type mice (and, yes, all of this was controlled for the amount of waste/poop). Lo and behold, the obese mice (the white bar) seemed to have gut bacteria which were significantly better at pulling calories out of the food, leaving less “leftover energy”.

While an interesting result, especially when thinking about some of the causes and effects of obesity, a skeptic might look at that data and say that its inconclusive about the role of gut bacteria in obesity – after all, obese mice could have all sorts of other changes which make them more efficient at pulling energy out of food. To address that, the researchers did a very elegant experiment involving fecal transplant: that’s right, colonize one mouse with the bacteria from another mouse (by transferring poop). The figure to the right (figure 3c) shows the results of the experiment. After two weeks, despite starting out at about the same weight and eating similar amounts of the same food, wild type mice that received bacteria from other wild type mice showed an increase in body fat of about 27%, whereas the wild type mice that received bacteria from the obese mice showed an increase of about 47%! Clearly, gut bacteria in obese mice are playing a key role in calorie uptake!

In terms of areas of improvement, my main complaint about this study is just that it doesn’t go far enough. The paper never gets too deep on what exactly were the bacteria in each sample and we didn’t really get a sense of the real variation: how much do bacteria vary from mouse to mouse? Is it the completely different bacteria? Is it the same bacteria but different numbers? Is it the same bacteria but they’re each functioning differently? Do two obese mice have the same bacteria? What about a mouse that isn’t quite obese but not quite wild-type either? Furthermore, the paper doesn’t show us what happens if an obese mouse has its bacteria replaced with the bacteria from a wild-type mouse. These are all interesting questions that would really help researchers and doctors understand what is happening.

But, despite all of that, this was a very interesting finding and has major implications for doctors and researchers in thinking about how our complicated flora impact and are impacted by our health.

(Image credit) (Figure 3 from the paper)

Paper: Turnbaugh et al., “An obesity-associated gut microbiome with increased capacity for energy harvest.” Nature (444). 21/28 Dec 2006. doi:10.1038/nature05414

But as my girlfriend once pointed out, the problem with asking academic advisors that question is that academic advisors tend to be academics – and in academia, you can make a career out of studying anything. Outside of academia, that is not so true. Look no further than the paradox of how we have record high unemployment for recent college graduates despite almost every startup I’ve spoken with expressing concerns about finding and retaining qualified employees?

Obviously, our education system is failing to meet the needs of our students and employers. But, other than hope that the system miraculously fixes itself, my advice to students is this: take classes that teach broadly employable skills. You don’t need to take a lot of them, and nobody’s asking you to major in a something that you don’t want to – college is, after all, about broadening your horizons and studying what interests you. But, in a competitive job market and a turbulent economy, the worker that is in the best position is the worker who can move between industries/jobs easily (getting out of bad jobs/industries and moving into better paid/more interesting ones) and who can quickly demonstrate value to their boss (so as to make them indispensable faster).

So what sort of skills am I referring to? Off the top of my head (I’m sure there are others), three come to mind:

• Accounting – All organizations that deal with money need people with accounting chops. From my experience, the executives/employees who are the most versatile across industries are the CFOs — they can plug into almost any business or organization and can quickly help their employers out. You may not want to be an accountant, but in a pinch, having those skills can help you get hired or find work as you figure out your next move.
• Programming – Programming as a skill is relatively generalizable. While I wouldn’t necessarily get an iPhone developer to write an operating system (or vice versa), folks with programming chops can quickly get up to speed on new projects at new companies, and, as a result, can quickly crank out functioning code to help with their employers.
• Statistics – You don’t need to be a math genius to be hireable. But, as computers become faster and more important, more organizations are turning to number crunching as a way to stay competitive. Not only will “data scientists” and statisticians become more in demand, individuals who have familiarity with those tools will be in a better position at their companies and be able to quickly help out a new employer.

The skeptic will point out that a lot of this can be outsourced. And, that’s certainly true – but in my experience, there is not only a limit on what companies are willing to outsource, there is also just huge value for any employee to tack those skills onto what they are already doing. A salesperson who is also good at crunching statistics on who to sell to next is far more valuable than a “regular” salesperson. A marketing guy with programming chops probably has a better understanding of a product or a technology than a “regular” marketing guy. And, a operations guy who also understands the nitty gritty financial details is going to be able to do a better job than an operations guy who doesn’t. Not to mention: the skills are broadly applicable; so if one company doesn’t have a good spot, there’s always another organization somewhere that will.

I tried using Google+ as a means of sharing for two weeks – I really did. But it didn’t stick. First, the sharing from within Google Reader was clunky at best – I had to hit the “+1” or the new “G+ share” button, then select the Reader circle I had made, and then do another click to share – awkward process. Secondly, Google+ just didn’t cut it with what I used Google Reader’s social functionality for. I use Google Reader to read. Google+ is great for sharing snippets and pictures and thoughts – but its not a reading platform, so treating it like a replacement for Google Reader’s sharing functionality was never going to make it. Lastly, the point I brought up from my previous post on different levels of interest on different types of content still rings true – the people who I shared with on Google Reader were opting in to my content shares – most of my friends on Google+ are opting in to my personal shares. The two aren’t always the same.

So, ultimately, I threw in the towel and decided to use Tumblr as an alternative. As you may know, Tumblr is a popular and fairly versatile mini-blogging tool – it lies somewhere between Twitter (where you are limited to 140 characters) and WordPress in terms of simplicity. But, it packs a ton of cool features to make it, from what I can tell, an okay substitute for Google Reader’s sharing functionality:

• a full-length RSS feed so that folks can subscribe to my “shares” from a reading platform like Google Reader
• packs a lot of compelling sharing features (liking, “re-blogging”)
• a browser bookmarklet pretty similar to what Google Reader had (so I can share things as I go)
• support for custom domain (so my Tumblr is now officially http://tumblr.benjamintseng.com/)
• support for Disqus (so it can do comments)
• pretty versatile HTML/CSS templating system so I can do further customizations later

Its not perfect. Its not integrated into Google Reader anymore – so all sharing/interaction will need to be done using the bookmarklet or on the site directly. But, the full-length RSS feed means we can keep reading and the sharing/Disqus functionality means we still can like, re-share, and comment.

I’m hoping my friends who once used Google Reader will join me on Tumblr, and I’m hoping my friends who were using Tumblr all along will welcome me to their world . I just started with the integration, but I am hoping to play around with the templating system to more tightly integrate the two sites in the near future.

(Image credit)

Flash forward a few years and one of my friends from college (who had to suffer through watching the thing because I was so proud I showed it to anyone willing to watch!) sends me an email with the subject line: “Why Didn’t Ben Do a Musical?”

Having seen the video she included, I can only respond: good question.

I now know what to make for my next video project!

Oh, and of course, my girlfriend has to throw in her own answer to that question: “because Ben can’t sing.” Also very true .

This month’s paper is about stem cells: those unique cells within the body which have the capacity to assume different roles. While people have talked at lengths about the potential for stem cells to function as therapies, one thing holding them back (with the main exception being bone marrow cells) is that its very difficult to get stem cells to exactly where they need to be.

With bone marrow transplants, hematopoietic stem cells naturally “home” (like a missile) to where they need to be (in the blood-making areas of the body). But with other types of stem cells, that is not so readily true, making it difficult or impossible to use the bloodstream as a means of administering stem cell therapies. Of course, you could try to inject, say, heart muscle stem cells directly into the heart, but that’s not only risky/difficult, its also artificial enough that you’re not necessarily providing the heart muscle stem cells with the right triggers/indicators to push them towards becoming normal, functioning heart tissue.

Researchers at Brigham & Women’s Hospital and Mass General Hospital published an interesting approach to this problem in the journal Blood (yes, that’s the real name). They used a unique feature of white blood cells that I blogged about very briefly before called leukocyte extravasation, which lets white blood cells leave the bloodstream towards areas of inflammation.

The process is described in the image above, but it basically involves the sugars on the white blood cell’s surface, called Sialyl Lewis X (SLeX), sticking to the walls of blood vessels near sites of tissue damage. This causes the white blood cell to start rolling (rather than flowing through the blood) which then triggers other chemical and physical changes which ultimately leads to the white blood cell sticking to the blood vessel walls and moving through.

The researchers “borrowed” this ability of white blood cells for their mesenchymal stem cells. The researchers took mesenchymal stem cells from a donor mouse and chemically coated them with SLeX – the hope being that the stem cells would start rolling anytime they were in the bloodstream and near a site of inflammation/tissue damage. After verifying that these coated cells still functioned (they could still become different types of cells, etc), they then injected them into mice (who received injections in their ears with a substance called LPS to simulate inflammation) and used video microscopes to measure the speed of different mesenchymal stem cells in the bloodstream. In Figures 2A and 2B to the left, the mesenchymal stem cell coated in SLeX is shown in green and a control mesenchymal stem cell is shown in red. What you’re seeing is the same spot in the ear of a mouse under inflammation with the camera rolling at 30 frames per second. As you can see, the red cell (the untreated) moves much faster than the green – in the same number of frames, its already left the vessel area! That, and a number of other measurements, made the researchers conclude that their SLeX coat actually got their mesenchymal stem cells to slow down near points of inflammation.

But, does this slowdown correspond with the mesenchymal stem cells exiting the bloodstream? Unfortunately, the researchers didn’t provide any good pictures, but they did count the number of different types of cells that they observed in the tissue. When it came to ears with inflammation (what Figure 4A below refers to as “LPS ear”), the researchers saw an average of 48 SLeX-coated mesenchymal stem cells versus 31 uncoated mesenchymal stem cells within their microscopic field of view (~50% higher). When it came to the control (the “saline ear”), the researchers saw 31 SLeX-coated mesenchymal stem cells versus 29 uncoated (~7% higher). Conclusion: yes, coating mesenchymal stem cells with SLeX and introducing them into the bloodstream lets them “home” to areas of tissue damage/inflammation.

As you can imagine, this is pretty cool – a simple chemical treatment could help us turn non-bone-marrow-stem cells into treatments you might receive via IV someday!

But, despite the cool finding, there were a number of improvements that this paper needs. Granted, I received it pre-print (so I’m sure there are some more edits that need to happen), but my main concerns are around the quality of the figures presented. Without any clear time indicators or pictures, its hard to know what exactly the researchers are seeing. Furthermore, its difficult to see for sure whether or not the treatment did anything to the underlying stem cell function. The supplemental figures of the paper are only the first step in, to me, what needs to be a long and deep investigation into whether or not those cells do what they’re supposed to – otherwise, this method of administering stem cell therapies is dead in the water.

(Figures from paper) (Image credit: Leukocyte Extravasation)

Paper: Sarkar et al., “Engineered Cell Homing.” Blood. 27 Oct 2011 (online print). doi:10.1182/blood-2010-10-311464

As corny as it sounds, my first thought after hearing about “Occupy Wall Street” wasn’t about right or wrong or even really about politics: it was about John Steinbeck and his book The Grapes of Wrath . It’s a book I read long ago in high school, but it was one which left a very deep impression on me. While I can’t even remember the main plot (other than that it dealt with a family of Great Depression and Dust Bowl-afflicted farmers who were forced to flee Oklahoma towards California), what I do remember was a very tragic description of the utter confusion and helplessness that gripped the people of that era (from Chapter 5):

“It’s not us, it’s the bank. A bank isn’t like a man. Or an owner with fifty thousand acres, he isn’t like a man either. That’s the monster.”

“Sure,” cried the tenant men, “but it’s our land. We measured it and broke it up. We were born on it, and we got killed on it, died on it. Even if it’s no good, it’s still ours. That’s what makes it ours—being born on it, working it, dying on it. That makes ownership, not a paper with numbers on it.”

“We’re sorry. It’s not us. It’s the monster. The bank isn’t like a man.”

“Yes, but the bank is only made of men.”

“No, you’re wrong there—quite wrong there. The bank is something else than men. It happens that every man in a bank hates what the bank does, and yet the bank does it. The bank is something more than men, I tell you. It’s the monster. Men made it, but they can’t control it.

And therein lies the best description of the tragedy of the Great Depression, and of every economic crisis that I have ever read. The many un- and under-employed people in the US are clearly under a lot of stress. And, like with the farmers in Steinbeck’s novel, its completely understandable that they want to blame somebody. And, so they are going to point to the most obvious culprits: “the 1%”, the bankers and financiers who work on “Wall Street”.

But, I think Steinbeck understood this is not really about the individuals. Obviously, there was a lot of wrongdoing that happened on the part of the banks which led to our current economic “malaise.” But I think for the most part, the “1%” aren’t interested in seeing their fellow citizen unemployed and on the street. Even if you don’t believe in compassion, their greed alone guarantees that they’d prefer to see the whole economy growing with everyone employed and productive, and their desire to avoid harassment alone guarantees they’d love to find a solution which ends the protests and the finger-pointing. They may not be suffering as much as those in the “99%”, but I’m pretty sure they are just as confused and hopeful that a solution comes about.

The real problem – Steinbeck’s “monster” – is the political and economic system people have created but can’t control. Our lives are driven so much by economic forces and institutions which are intertwined with one another on a global level that people can’t understand why they or their friends and family are unemployed, why food and gas prices are so expensive, why the national debt is so high, etc.

Now, a complicated system that we don’t have control of is not always a bad thing. After all, what is a democracy supposed to be but a political system that nobody can control? What is the point of a strong judiciary but to be a legal authority that legislators/executives cannot overthrow? Furthermore, its important for anyone who wants to change the system for the better to remember that the same global economic system which is causing so much grief today is more responsible than any other force for creating many of the scientific and technological advancements which make our lives better and for lifting (and continuing to lift) millions out of poverty such as those who live in countries like China and India.

But, even keeping that in mind, I — a firm believer in freer markets and globalization — am hard-pressed not to sympathize with the idea that the system has failed on its promise of expanding prosperity for a broad swath of the population. What else am I (or anyone else) supposed to think in a world where corporate profits can go up while unemployment stays stubbornly near 10%, where bankers can get paid bonuses only a short while after their industry was bailed out with taxpayer money, and where the government seems completely unable to do more than bicker about an artificial debt ceiling?

But anyone with even a small understanding of economics knows this is not about a person or even a group of people. To use Steinbeck’s words, the problem is more than a man, it really is a monster. While we may not be able to kill it, letting it rampage is not a viable option either — the “Occupy Wall Street” protests are a testament to that. They may not be generating any policy recommendations which can stop the problem, but their frustration is real and legitimate, and until politicians across both sides of the aisle and individuals across both ends of the income spectrum come together to find a way to “tame the monster’s rampage”, we’re going to see a lot more finger-pointing and anger.

(Image credit – Wikipedia)

“Omics” is the hot buzz-suffix in the life sciences for anything which uses the new sequencing/array technologies we now have available. You don’t study genes anymore, you study genomics. You don’t study proteins anymore – that’s so last century, you study proteomics now. And, who studies metabolism? Its all about metabolomics. There’s even a (pretty nifty) blog post covering this with the semi-irreverent name “Omics! Omics!”.

Its in the spirit of “Omics” that I chose a Science paper from researchers at the NIH because it was the first time I have ever encountered the term “antibodyome”. For those of you who don’t know, antibodies are the “smart missiles” of your immune system – they are built to recognize and attack only one specific target (i.e. a particular protein on a bacteria/virus). This ability is so remarkable that, rather than rely on human-generated constructs, researchers and biotech companies oftentimes choose to use antibodies to make research tools (i.e. using fluorescent antibodies to label specific things) and therapies (i.e. using antibodies to proteins associated with cancer as anti-cancer drugs).

How the immune system does this is a fascinating story in and of itself. In a process called V(D)J recombination – the basic idea is that your immune system’s B-cells mix, match, and scramble certain pieces of your genetic code to try to produce a wide range of antibodies to hit potentially every structure they could conceivably see. And, once they see something which “kind of sticks”, they undergo a process called affinity maturation to introduce all sorts of mutations in the hopes that you create an even better antibody.

Which brings us to the paper I picked – the researchers analyzed a couple of particularly effective antibodies targeted at HIV, the virus which causes AIDS. What they found was that these antibodies all bound the same part of the HIV virus, but when they took a closer look at the 3D structures/the B-cell genetic code which made them, they found that the antibodies were quite different from one another (see Figure 3C below)

What’s more, not only were they fairly distinct from one another, they each showed *significant* affinity maturation – while a typical antibody has 5-15% of their underlying genetic code modified, these antibodies had 20-50%! To get to the bottom of this, the researchers looked at all the antibodies they could pull from the patient – in effect, the “antibodyome”, in the same way that the patient’s genome would be all of his/her genes, —  and along with data from other patients, they were able to construct a “family tree” of these antibodies (see Figure 6C below)

The analysis shows that many of the antibodies were derived from the same initial genetic VDJ “mix-and-match” but that afterwards, there were quite a number of changes made to that code to get the situation where a diverse set of structures/genetic codes could attack the same spot on the HIV virus.

While I wish the paper probed deeper into actual experimentation to take this analysis further (i.e. artificially using this method to create other antibodies with similar behavior), this paper goes a long way into establishing an early picture of what “antibodyomics” is. Rather than study the total impact of an immune response or just the immune capabilities of one particular B-cell/antibody, this sort of genetic approach lets researchers get a very detailed, albeit comprehensive look at where the body’s antibodies are coming from. Hopefully, longer term this also turns into a way for researchers to make better vaccines.

(Figure 2 and 6 from paper)

Paper:  Wu et al., “Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing.” Science (333). 16 Sep 2011. doi: 10.1126/science.1207532