Bench Press

We have always sought out new frontiers and this generation is no different. Today’s frontiers can’t be found on a map. They’re being explored in our classrooms and our laboratories, in our start-ups and our factories. And today’s pioneers are not traveling to some far flung place. These pioneers are all around us — the entrepreneurs and the inventors, the researchers, the engineers — helping to lead us into the future, just as they have in the past. This is the nation that has led the world for two centuries in the pursuit of discovery.

-President Barack Obama,  Energy Speech at MIT October 23, 2009

As a candidate for President and throughout President Obama’s first year he has established himself as a friend of the scientific community. He has made many statements like the one above poignantly establishing the importance of innovation and scientific discovery in our nation’s goals. However, supportive statements don’t pay the bills and as I’ve had reiterated to me several times during my conversations with various professors at graduate school interviews; funding is king. Ultimately, the best way for President Obama to demonstrate his support of the sciences is to show us the money. He started off on the right foot with the science funding handed out in the stimulus package last year. The chart below illustrates President Obama’s proposed budgetary changes.

Minus the small decrease in funding for the CDC, many scientific organizations could potentially see sizable increases in funding. As I’ll be starting my graduate work in biosciences next fall I’m extremely happy to see the proposed increases. I’m quite surprised to see a reduction in funds budgeted to the CDC after the recent swine flu outbreak. However, the overall increase in funding is a huge step forward compared to the prior administration. Hopefully Congress will pass a budget with increases similar to the President’s proposed budget. These funds could be used to improve the financial status of many labs across the country that were affected by declining funding availability. I’ve got my fingers crossed that President Obama will continue supporting the sciences in not just his speeches but in his actions as well.

(Chart – Wired.com)

It is unfortunate that much of what we need to do to the human body to treat it requires that we cut it open, as this creates a whole set of risks and complications for science and medicine. Thankfully, science and technology march on in the quest to reduce our dependence on invasive surgeries. An interesting Economist article takes a look into some of the more unconventional tools that are being explored as potential non-invasive replacements.

Let’s take a classic problem which often has a surgical solution: the removal of a cancerous tumor. How could we solve this without resorting to the use of a scalpel?

• Of course, there’s radiation – which, as we’ve discussed before, is potentially dangerous if the radiation dosage isn’t calculated sufficiently well.
• The use of ultrasound as a means to visualize what’s going on under the skin is commonly known. But a small startup in Washington called Mirabilis Medica came up with a means to use ultrasound not only to see a tumor or blood clot, but also to focus it and generate enough heat to destroy the tumor/blood clot (what they’ve called High-Intensity Focused Ultrasound or HIFU; explanatory diagram below).

• Professor Weihong Tan at the University of Florida published a paper in PNAS in early 2009 a means of using light as a way of non-invasively activating blood clotting. The system is described in the picture below, but relies on a means of inhibiting the activity of Thrombin (a protein that helps control blood clotting) with short stretches of DNA (which they’ve cutely termed “Thrombin-binding Aptamers” or TBA) that have been chemically modified to be able to change shape in the light (cis-trans isomerization under photon stimulation). The vision is to one day be able to inject a patient with these Thrombin-TBA “molecular clasps” and hit the patient with a light source, cutting off the blood flow to the tumor and all without needing invasive surgery!

These only scratch the surface of what new technologies and scientific advances might be capable of. Son et lumiere (sound and light) as surgical tools indeed!

(Image credit) (Image credit – Mirabilis Medica) (Image credit – PNAS publication)

My talented girlfriend is both a science aficionado (currently a med student) and an avid knitter. So when she showed me the science-inspired knitting creations of one Etsy user CraftyHedgehog, I knew I just had to blog about it:

After all, who wouldn’t want knitted replicas of their favorite dissection specimens? And, the creative Ms. CraftyHedgeHog has taken her art a step beyond – behold, a knitted dissection of an Easter Bunny:

The fetal pig is 100% wool. The frog is made from a silk/wool blend with the organs made from 100% wool (and yes, that’s a real aluminum tray – don’t worry, Ms. CraftyHedgeHog assures us that they’re unused). The rat is hand-knit from an acrylic mohair, also with 100% wool organs. The Easter Bunny is made from soft nylon yarn and the insides are made from 100% wool (for the eggs) and the plastic grass used to line Easter baskets.

You can buy the specimens and learn more from CraftyHedgeHog’s Etsy page!

(Image credits – CraftyHedgeHog’s Etsy page)

While Bench Press is a big fan of open source, we realize that it can be intimidating for the lay-scientist (or layperson for that matter) to build code from an open source repository when asking a question might quickly get the asker labeled a n00b and not taken seriously. This problem is especially relevant to us Windows users who don’t have ready access to UNIX-style command line-fu and are dependent on kind open source community members to create Windows-specific installers.

This weekend, while working on integrating the open source database SQLite into some code I was writing for Benchside, I realized that the only way to integrate SQLite’s Full Text Search capability was to recompile it from source code, something I had never done before. As I ran a Windows system, I wasn’t able to use the UNIX command line instructions on from Michael Trier’s post on how to integrate SQLite’s Full Text Search capability into a Python program.

A few hours of research and trial and error later, I finally came up with how to do it on Windows in a way which hopefully generalizes to building other open source projects out there. Hopefully I can lay these out so that other “n00bs” out there no longer need to feel left out when someone gives them some source code:

1. Install MinGW and MSYS – MinGW is the Minimalist GNU for Windows software pack which allows Windows computers to implement the development tools (like gcc and make) that UNIX-style operating system users (Linux, Mac) take for granted. MSYS provides a command line interface which emulates directly the UNIX command line, at least up to the point where it is needed to build from source code. Both packages are open source and have Windows installers for download at their respective pages (to keep things simple). These installers are probably a sub-version or two behind (as the updated tools need to be packaged together in Windows installers), but with MinGW and MSYS, it should be relatively easy to download and build from source the new tools! In any event, install MinGW first, and afterwards when you install MSYS, it will ask where you placed the MinGW install and be able to link directly to those compiler tools
   • (optional step) Install GnuWin32 – GnuWin32 is, like MinGW, a set of tools which emulate many of the other commands that UNIX-style operating systems have. The primary use for these would be to do other command line tricks which the UNIX guys have access to (i.e. downloading and de-compressing source code files from the command line). This is unnecessary as most commercial compression software (or open source like 7zip) can handle most of the de-compressing that you need
   • (optional step) Install the Windows Open Command Window Here PowerToy which will let you right-click on a folder and open a command line window right there. Makes things more convenient many times.
2. Add MinGW and MSYS to your system path – Now that you’ve installed MinGW and MSYS (and possibly GnuWin32), you need to make sure that your tools can be accessed from anywhere by command line and not just in the folders that you installed them to. To do this, pull up the “System” panel in your Control Panel. You can do this by clicking on “Start”, “Run”, and typing in “control sysdm.cpl” and hitting [ENTER]. A window should pop up called “System Properties”. Click on the “Advanced” tab and then click on the “Environment Variables” button. Another window should pop up. In the System variables panel (the one on the bottom, see image below), select the row that has “Path” in the Variable column and click on the “Edit” button. This should bring up a text-editing dialog box where you should add the full directory paths to the MinGW bin and MSYS 1.0 folders separated by semicolons there. In my case, for instance, the paths to the bin folders were “C:\MinGW\bin” and “C:\msys\1.0” and so I added “C:\MinGW\bin;C:\msys\1.0;” to the end of the Variable Value text box.
3. Download and de-compress the source code – This usually comes in the form of a gzipped tarball file (*.tar.gz) which you can unpack with software like 7zip or at the command line (if you have the appropriate tools installed) using gzip and tar commands.
4. Run MSYS and use the cd command to go to the directory where you’ve de-compressed the source code – You should be able to do this, assuming you added MSYS to your path properly, from anywhere in the command line by just typing msys and hitting [ENTER]. Use the cd command (syntax: “cd <name of directory>”) to move to the directory where you unzipped the source code. In my case it was: “cd C:/sqlite3/sqlite-3.6.22/”
5. Set any compiler flags that need to be set and run ./configure: For SQLite, I had to set the DSQLITE_ENABLE_FTS3 and DSQLITE_ENABLE_FTS3_PARENTHESIS flags before compiling. To do this, I simply typed in: CFLAGS="-DSQLITE_ENABLE_FTS3=1 -DSQLITE_ENABLE_FTS3_PARENTHESIS =1" ./configure and hit [ENTER]. What this does is first, set the environment variable CFLAGS, which is what the compiler will look at to set any preprocessor flags (setting -DXXX=Y sets the preprocessor variable XXX the value of Y) that it needs before building, and second call ./configure which runs a quick diagnostic to see if your system has all the development tools it needs to compile. If an error pops up, this might be a sign that your MinGW installation is incomplete or that you did not set the system path correctly.
6. Follow any instructions in the README – Source code packs usually come with a README text file which gives instructions for how to build the software package. You should definitely read those (as they may also provide instructions for which compiler flags that you might want to set in step 5). These usually end with you entering the instruction “make” (and then [ENTER]) and subsequently “make install” (and then [ENTER]) to make sure that the compiled code is embedded in the system at its proper location.
7. Post-setup – Depending on the software, there may be further configuration/setup steps that need to take place. In the case of my custom SQLite build, I had to copy the Windows DLL file from the ./lib folder that was created by the build process (libsqlite3-0.dll) into my Python installation’s DLL folder and rename it sqlite3.dll to replace my old built-in Python-SQLite setup.

The process above is probably not 100% fool-proof and skims over some details which may be important for different source code types, but hopefully my painfully self-taught lessons in building from source in Windows-land will be helpful to those of you out there who find yourself needing to build something by compiling from source code.

(Image credit)

The Open Science movement is driven by the idea that collaboration and openness are good for innovation and discovery. After all, the logic goes, who is more likely to discover a cure for cancer: five research groups with different sets of skills and specializations who don’t share any information with one another, or five identical groups who actively pool their knowledge?

Ironically, that reasoning seems to have completely skipped over the biotech/pharmaceutical industry who seem intent on pursuing the “divided we fall” approach despite the escalating costs of drug development. The application of openness itself is especially relevant here, as a significant piece of the $800 million – $1.2 billion price tag that goes with bringing one drug to market is the cost of failed R&D projects.

This problem is one that is not only a burden on the shareholders and executives at these companies, but also a burden on the healthcare systems of people around the world, who have to pay more and wait longer for drugs to make it through a company’s pipeline.

About a month ago, the New York Times cast a spotlight on this problem:

Although many companies have committed to publishing the results of clinical trials, whether or not they succeed, drug makers don’t typically publish information about projects that fail at an earlier stage. A result is that companies waste many millions going down experimental paths that their competitors have already found to be dead ends.

M.I.T. is proposing dead-end drug disclosure, a concept that goes by a euphemistic mouthful: “precompetitive information sharing.”

Drug makers may realize that the financial and medical value of sharing such information outweighs the competitive risk, said Dr. Gigi Hirsch, the executive director of the M.I.T. Center for Biomedical Innovation, the locus of the drug project. “There should be more information available about failed compounds in the interest of the greater good,” Dr. Hirsch said.

The traditional response from the pharmaceutical industry is one that is familiar to Open advocates – that intellectual property and proprietary platforms are necessary for the returns which drive investment in these spaces. But, this ignores two things.

First, the act of sharing information on failed assay hits helps to reduce the cost and time of development. The investment decision is driven by returns, and returns are driven by costs and the delay in achieving revenues. While being more open about internal failures and successes will do little to change the cost of marketing, clinical trials, and many aspects of development, it will reduce a large portion of the time and cost of initial R&D (because of the wider availability of information) and the cost of failure (as there would be no need to pursue avenues of research on paths that have already been deemed a failure). So even if the price premium and number of drugs sold diminish slightly due to the inability of a company to hold on to some early-stage proprietary advantage or the release of some of the details on their compound library, the time to market and cost of development diminish as well, helping to preserve the return on investment necessary to provide for the level of drug innovation and discovery that patients and doctors desire.

Secondly, a move to openness does not necessitate unprofitability. It wouldn’t be realistic to ask companies to pursue a path which destroys the shareholder value they’ve been entrusted to protect. But, the fact that technology companies like Google and Nokia have been able to push open standards and open source yet retain profitability and innovativeness should hopefully signal to bio/pharmaceutical companies that it is possible to pursue shareholder value and a degree of openness.

The path to profitable openness that technology industry practitioners like Google pursue is no different than the path that any company pursues: specialization. Google, for example, has specialized on high quality search results, effective advertisement targeting, and its IT infrastructure management. As a result, there’s no reason for Google to prevent the broader technology industry from having access to the source code for its Chrome web browser, Android mobile operating system, and provides APIs to access almost all of the information you can find on its websites. In fact, Google seems to have understood that keeping its information closed would reduce innovation on the web, which would in the long-run hurt its own growth and profitability prospects.

I’d humbly wager that the value of protecting early stage failure and platform information is relatively minor in the grand scheme of pharmaceutical company value (and in fact some companies do publish failures, only years after the experiment), and that major drug companies probably have much more significant expertise and differentiation in the steps after initial R&D, such as in compound refinement, clinical trials operation, process development, and computational analysis, etc. Not to mention that healthcare worldwide and the state of drug development science in both academic and corporate settings would probably benefit significantly more from differentiation along these activities than any proprietary lock on compound failure information would enable.

Nobody is saying that this path will magically materialize and produce awe-inspiring levels of profitability and growth. But, when an industry is on the edge of a patent cliff (most blockbuster drugs are expected to become generic in the next couple of years), and its primary source of “value creation” seems to be in buying smaller companies, and nations around the world are struggling with healthcare costs, I’d assert that it needs to change its practices.

As for how – I would propose the following compromise.

1. First, the NIH, PhRMA, or some other neutral authority should define a set of standards for what information should be contributed (balancing the desire to foster innovation through openness and the desire for companies to maintain the closedness they need to build proprietary advantages along other dimensions), create a standard for secure information sharing (which protects any individuals and patients and proprietary pipeline-related information) and govern compliance.
2. This body should then set up an information exchange/database for participating companies, academic institutions, government research centers, and medical institutions to share information and prevent non-compliant companies from gaining access (it’s not a perfect solution, but it could help assure companies who are worried that they will give up all of their information but not receive any in return).

This road would likely be a long and difficult one, but given the stakes and the potential benefits, I think it is one well worth taking.

(Image credit) (Image credit)

With smartphones becoming more sophisticated and more popular, its only natural that there are a growing number of attempts to use them as a platform for scientific inquiry (pocket ultrasound, microscopy, and astronomy for example). This is especially useful in developing countries, where a relative lack of high-end computers and fixed broadband access make smartphones a very suitable alternative to the more expensive, bulkier solutions that are used in the developed world.

It should come as little surprise, then, that doctors in India are helping to pioneer a new “telemedicine” tool using the camera and processing capabilities of Apple’s popular iPhone to do remote diagnosis of Retinopathy of Prematurity (RoP), a condition which is more likely to afflict infants born underweight. While curable, RoP needs to be treated within days of detecting it as to prevent permanent damage to a child’s eyes, something which the iPhone’s camera, mobile broadband, and robustness of software and security platform allows pediatric eye surgeons to diagnose from remote locations, hundreds or even thousands of miles away.

But, the potential of smartphones to function as a tool for tele-medicine can probably go far beyond this. At least, that’s what i2i TeleSolutions, an Indian-based startup, is betting on. They provided part of the software solution for the RoP diagnosis tool, and are aiming to provide software and services to enable further telemedicine technology – mainly:

• Security – It is important that sensitive medical information is transmitted securely in a way such that only the appropriate medical professionals see the information.
• Data compression – As fast as 3G and the new LTE networks are (and will be), network coverage and data transfer rates will continue to be a limiting factor on the adoption of telemedicine. As such, a true telemedicine solution will require lossless compression techniques.
• IT support – Medical organizations are not especially well-suited for building sophisticated IT capabilities, nor do medical professionals necessarily have the time to learn an arcane user interface. For that reason, telemedicine solutions should aim to provide web-based access methods (in addition to any non-web based methods they may choose to push) to access and react to data.

i2i provides further details on the scope of their platform on their web page, but I think it represents a strong start for a solution. Going forward, I’d like to see them (and any competitors that emerge) provide support for:

• Additional types of data – i2i’s focus seems to be primarily on images, but the full range of capabilities on smartphones is massive – GPS, accelerometer, magnetometer, and even microscopy and other medical attachments – and I would hate to think that tele-medicine would be limited only to its imaging capability
• Deployment on more phones – The iPhone is unique in the maturity of the platform, but it would be nice to see similar applications on other operating systems like Android, Symbian, and Windows Mobile.
• Interactivity – The i2i platform appears to be very unidirectional: (1) take a picture, (2) send it to a remote surgeon. I think the true promise of telemedicine is something which allows for a greater level of flexibility and interactivity on both ends (to refine the view, or make a suggestion on some other place to scan, etc).
• Ability to tack on analytics – There is a significant amount of medical data that needs to be analyzed/processed before it can be acted upon. Building some sort of open protocol or extendability (a la Firefox or Salesforce or LinkedIn/Facebook model) would do a great deal towards enhancing the potential of a telemedicine platform

Anyone else have any other ideas?

In a world with flashy distractions like YouTube and Modern Warfare 2, how the heck do you get students to be interested in monocyte recruitment?

One idea that the Federation of American Scientists is piloting is the use of video games as tools for science education. To that end, the FAS developed, in conjunction with game studio Escape Hatch Entertainment, a game called Immune Attack (trailer below):

The premise of the game is pretty creative. A patient who suffers from a non-functioning immune system needs the player’s help to train her immune cells on how to fight off a bacterial infection. More detail can be found in the lesson plan on the Immune Attack website, but the game itself covers multiple phases showing:

• how leukocytes move from bloodstream to infection site
• how leukocytes are recruited by chemical signals
• how the immune system can recognize pathogen-associated molecular patterns
• phagocytosis (how white blood cells devour pathogens that they find)
• how white blood cells can recruit additional immune cells with chemokines
• how natural killers and MHC molecules can identify cells infected by viruses

While the game’s concept is original, the production value of the game is not quite up to a full-fledged professional studio. Although, to be fair, for only a ~500MB download and from an effort that wasn’t backed by a major game company, the quality was fairly impressive. The problem, though, is that the game mechanics are oriented around maneuvering about the 3D world to train the patient’s immune system how to respond to infection. The game is thus very dependent on the quality of the controls and the graphics. As I was playing on a Thinkpad T400 using a Trackpoint, it was actually fairly difficult at times to do the maneuvers necessary to move on to the next level.

The interface was also somewhat klunky – being similar enough to a standard first-person shooter controls but with enough variations to make the controls a little awkward (the need to hold down the right mouse button while steering with the mouse and the inability of the keyboard to change the pitch of motion were annoying). The software also didn’t feel complete bug-free. Just to see what would happen, I deliberately failed a mission requiring me to identify and destroy 5 infected cells before a viral infection destroyed 5 healthy cells. When I re-started the mission, the count of destroyed healthy cells began at 5 – is it any wonder that I failed the mission, again?

With all that said, I do believe that this was a very impressive effort that just needs a little polishing. The music and graphics were a little hokey, and the lesson plan materials need to be fleshed out a bit better, but the game mechanics were designed very well to ingrain visually and physically how monocyte transmigration worked, how white blood cells are recruited, and how basic viral and bacterial pathogens spread infection. While I wouldn’t say I’m yet fully convinced that this approach will work, I am optimistic that this is a good method to help scientists convey very complicated phenomena to students.

We’ve written a couple of times about the asteroid Apophis which, while unlikely to hit Earth, will make a very near pass of 18,300 miles above the planet’s surface in 2029. NASA’s Jet Propulsion Laboratory just released an excellent animation of just how close Apophis will be when it passes by.

Wow for some reason 18,300 miles doesn’t seem quite as far anymore.
(Video Credit – Wired Science)

Image depicting ant movements. Credit: University of Granada.

Its impressive how much humans can learn from biomimicry. Soldiers, for example, may soon owe their lives to the same pesky ants living in your own backyard. Researchers from the University of Grenada(UGR), under Antonio Miguel Mora García, Professor Juan Julián Merelo Guervós, and Professor Pedro Ángel Castillo Valdivieso, have taken inspiration from how ants find trajectories from their colonies to their food sources in order to develop a simulator that can devise the “safest” trajectory in a battlefield between any two points, given the necessary parameters.

Dubbed the “ant colony optimization (ACO),” this algorithm has already allowed Antonio to employ it to the videogame, Panzer General, with promising results. Currently, the University of Grenada has received participation from the Ministry of Defense to devise new strategies for them if its success continues.

The scientists of the UGR have developed a mini-simulator in order to define the settings (battlefields), locate the unit and their enemies, execute the algorithms and see the results. In addition, the software designed by them offers a few tools useful to analyze both the initial map and the results.

To prepare this system, Mora García started from the battlefields present in the videogame Panzer General, defining later the necessary properties and restrictions to make them faithful to reality.

While the ACO has immediate benefits to saving the lives of our soldiers, I’m also excited for its applications outside of the military. By extrapolating its uses, we could potentially use the ACO to optimize shipping orders, create shortest routes, plan airplane seating, etc, all by harnessing the creativity and intelligence of Mother Nature. So the next time you see an army of ants devouring your picnic basket, take some time to marvel at the beautiful tapestry of Nature before squashing all of them with your feet.

(Image Credit)

If you’re like me, and you’ve spent endless hours programming in front of your compute , you’d agree with me that sometimes it’s not the funnest thing to do. While the finished product might be really cool, getting there is oftentimes tedious, frustrating, and hair-splitting. What usually causes these problems is that coders get bogged down with the details due to the fact that certain blocks of code require unavoidably intricate and detailed logic. However, with the new EU-funded research project, ReDSeeDS, Michal Smialek and his team of researchers hope to lighten the burden for all coders and make coding enjoyable again.

What Smialek and his team discovered was that since most coders start from scratch when beginning a project, these programmers often need to code entire programs from the ground up despite the fact that other people have probably previously coded programs which accomplished similar tasks. As a result, programmers often re-write code simply because working on a project usually means starting from a blank screen. In order to avoid this, Smialek aims to create a repository which will house previously written code stored with a list of the program’s aims and requirements. Thus, when a user searches this database with a query of requirements, the database will return previously written code that is expected to produce similar outputs. These functionally equivalent snippets of code are called “artefacts,” and Smialek’s database is essentially a library of artefacts.

In a project, you may produce several artefacts which are design blueprints and then an artefact which is the code that tells the system how to work. The final program is also an artefact which is served by the other artefacts – that is the design and the code.

While most programs obviously will not completely overlap in terms of requirements, the fact that most programmers will not need to “re-invent the wheel” will greatly enhance productivity and allow them to not get so bogged down with the details. Not only does this allow for a more rapid rate of software releases, it vastly decreases the amount of time needed to fix problems within the code simply because the code within the database will be (we’d like to hope) error-free. Smialek notes that:

What it will do as a commercial product is to reduce considerably the amount of work required to develop a new software application, and that means the ability to develop more and larger systems using the same human resources.

(Image Credit)