Bench Press

A few weeks ago, we posted a number of reasons why we believe the Pharmaceutical industry needs to pursue greater openness to accelerate innovation and reduce the cost and time of drug development. A few weeks after that, almost as if by magic, pharmaceutical giant GlaxoSmithKline made a very encouraging announcement which is hopefully a first step in the direction of openness and a promising boost to global health initiatives around the world working on Malaria:

GSK has screened its pharmaceutical compound library of more than 2 million molecules for any that may inhibit the malaria parasite P.falciparum, the deadliest form of malaria, which is found primarily in sub-Saharan Africa. This exercise took five scientists a year to complete, and has yielded more than 13,500 compounds that could lead to the development of new and innovative treatments for malaria, which kills at least one million children every year in Africa.

GSK will make these findings, including the chemical structures and associated assay data, freely available to the public via leading scientific websites. The release of these data will mark the first time that a pharmaceutical company has made public the structures of so many of its compounds in the hope that they could lead to new medicines for malaria.

Building upon its commitments to create a “knowledge pool” for neglected tropical diseases, GSK
today announced that governance of the “knowledge pool” will be taken over by an independent third party, BIO Ventures for Global Health (BVGH). GSK and BVGH have also signed a Memorandum of Understanding with the Emory Institute for Drug Discovery (EIDD) to join the pool and further open up knowledge, chemical libraries, and other assets in the search for new medicines for neglected tropical diseases. A second collaboration has also been established with South Africa firm iThemba Pharmaceuticals. This work will help research and discovery into new medicines to treat tuberculosis.

In addition to opening up its library of malaria hits to the public and creating a third-party administered “knowledge pool”, GSK is even promising to give 60 scientists access to its advanced facilities in Spain and a funding pool of $8 million to help fund malaria research.

While GSK is reaping (well-deserved) kudo’s for this, we believe (perhaps, more correctly, hope) that GSK is also using this to figure out if greater openness can help their underlying business and how best to do it. As a Nature editorial on the subject opines:

The move advances the pharmaceutical industry’s slow but steady shift towards more open sharing of data. At least for early-stage, precompetitive research, drug companies are finding it useful to lower the firewalls around their intellectual property and pool their resources. Making data public brings fresh eyes and minds to the problem, and has the potential to accelerate the discovery process.

Let’s hope this marks the beginning of a very productive move towards greater information sharing.

(GSK Press Release) (Image credit) (Nature editorial)

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)

As technology continues to advance the ubiquitous nature of certain devices prompts innovative people to come up with amazing new uses for everyday items. A perfect example of this is the cell phone. We’ve already shown you smartphones that can take and record ultrasound images as well as a nifty Android application that makes stargazing easy for the amateur astronomer in all of us. Now a team led by Dr. Daniel Fletcher at UC Berkeley in collaboration with researchers at UCSF have turned the smartphone into an incredibly effective microscopy device.

Light microscopy is a vital tool for the diagnosis and screening of various diseases. Unfortunately in many regions of the world access is limited due to availability or lack of portability. Dr. Fletcher’s group looked to solve this problem by taking off the shelf components and building a solution that would be cheap and effective. Fletcher’s group built a mobile-phone mounted light microscope, dubbed the CellScope, capable of providing images detailed enough to help diagnose diseases like malaria and tuberculosis. Using a mobile phone as the platform for the microscope also allows images to be saved and transmitted to clinical experts for further analysis.

The CellScope was put through it’s paces by Dr. Fletcher’s team as they tested it in various applications. As seen in the figure below sickle shaped red blood cells are clearly visible within the image of a blood smear sample allowing the diagnosis of malaria.

In addition to taking diagnostically clear images of blood smears, Dr. Fletcher’s group tested the CellScope with fluorescent filters to see if the CellScope could be utilized in an increasingly popular tuberculosis screening and monitoring assay.

As seen above the fluorescent staining of tuberculosis bacilli in spittum is remarkably clear for a microscope attachment on a mobile phone. In the C panel of the above figure, Dr. Fletcher’s group also attempted to harness the computational power of the mobile phone by developing software to automatically count and process the fluorescent image.

The CellScope’s effectiveness, portability, and low cost make it an incredible tool for health care providers throughout the world. More details available at PLoS ONE.

(PLoS ONE: Mobile Phone Based Clinical Microscopy for Global Health Applications)

In 2003 an unknown virus suddenly emerged in Guangdong China and proceeded to spread rapidly around the world. The SARS coronavirus disseminated around the world via the global air transportation network with stunning efficiency, highlighting one of the unintended consequences of the globe’s vast airline system. After the SARS outbreak, a group at St. Michael’s Hospital in Toronto, took it upon themselves to study the SARS outbreak in detail. The end goal to develop effective strategies to deal with future epidemics. Their project dubbed Bio.Diaspora took a multidisciplinary approach in analyzing air traffic patterns and the distribution of infectious diseases. Their self proclaimed mission:

Understand global patterns of human travel via commercial airlines as a way to predict how emerging infectious diseases are most likely to spread around the world – and consequently apply this knowledge to help the world’s cities and countries better prepare for and respond to global infectious disease threats of tomorrow.

The Bio.Diaspora team believed that not only more applied research into the impacts of global population mobility on public health and security is necessary, but access to quality data on global air transportation and traffic patterns is needed as well. They sought to fulfill this need by:

[D]eveloping a data warehouse for the sole purpose of conducting methodological and applied research on commercial air travel and emerging infectious disease threats. This report embodies rigorous analysis of these data from multiple scientific perspectives – medicine, infectious diseases, public health, health policy, biostatistics, geographic sciences, network analysis, computer sciences, and mathematical modeling.

Their thorough analysis accounted for numerous factors and yielded a report just prior to the emergence of the H1N1 influenza (Swine Flu) pandemic. One of the really interesting parts of the Bio.Diaspora report was the numerous simulations done on potential H5N1 avian influenza transmission from emergence in numerous potential cities around the world.

Click through for interactive version.

The above graphic illustrates the likelihood of importation of H5N1 avian influenza into various areas of the world with an epidemic beginning in São Paulo, Brazil. This caught my eye as it seemingly foreshadowed the H1N1 epidemic. After the emergence of H1N1, the Bio.Diaspora team went back to study the air traffic patterns of the initial stages of the spread (March and April 2009) from Mexico. Running simulations like those from the Bio.Diaspora project’s report they were able to produce predictions based on the flight itineraries (data shown below) that correlated highly with the observed transmission pattern. Their complete analysis is published in the New England Journal of Medicine.

Destination Cities and Corresponding Volumes of International Passengers Arriving from Mexico between March 1 and April 30, 2008.

The Bio.Diaspora project team’s work on both the SARS epidemic and now the H1N1 pandemic illustrate that there’s still much to learn about managing public health crises on a global scale thanks to the highly interconnected nature of today’s cities. It’s a much smaller world now and new tools and ideas will be necessary to deal with future emerging diseases.

(Bio.Diaspora)(Spread of a Novel Influenza A (H1N1) Virus via Global Airline Transportation)

A few weeks ago I wrote a post about the development of the Standoff Patient Triage Tool, an impressive use of lasers in order to make health critical readings of patients from a distance. Well one of the best things about science is that many people can utilize the same tools to come up with unique methods and solutions for any given problem. In this case, researchers have used lasers to develop a technology that could someday revolutionize imaging procedures in medicine.

Photoacoustic imaging of melanoma in vivo.

Photoacoustic tomography is the basis behind a new imaging technology being developed in hopes of providing more flexible and cost effective devices for physicians. The technique takes advantage of ultrasonic emissions produced when a non-ionizing laser pulse is directed towards a tissue. The emissions, resulting from transient thermoelastic expansion of the target tissue due to absorption of the laser energy, are detected and analyzed with various algorithms to construct an image (2D or 3D) of the targeted area. This differs from the reliance on the doppler shift produced by the reflected laser beam in the SPTT.

Images of vasculature like the one seen on the right can be produced by using photoacoustic tomography without the injection of contrast as differences between the molecular composition of the target can be used instead. In the example to the right, the difference between oxygenated and deoxygenated blood is an effective natural contrast. Photoacoustic tomography also presents other benefits over traditional imaging techniques as explained by The Economist:

CT scans also involve potentially harmful ionising radiation. And MRI and CT scans are very expensive, using machines that cost millions of dollars and require dedicated staff to operate them. Photoacoustic tomography, by contrast, could eventually be performed using portable hand-held devices, similar to those used for ultrasound scanning. This would allow doctors to diagnose and monitor patients in clinics, and reduce the need to refer them to consultants.

The adaptability of this nascent technology is also impressive as researchers are already looking at using it to detect specific ailments such as brain lesions and cancer. In the case of cancer, the ability to accurately image vasculature could allow doctors to monitor patients for the development of new blood vessels (angiogenesis) a hallmark of cancer development.

While there are some issues to work out with this new technique, such as the lack of imaging depth (ultrasound signal emitted is reduced the deeper the tissue lies) and ultrasound distortion from varying tissue types within the human body (e.g. bone vs muscle), photoacoustic imaging is a very promising new technology.

(Source)

Like my fellow Bench Press blogger Ben, I’m a fairly avid Star Trek fan. Having spent many hours during my formative years watching syndicated episodes I always wondered if we’d ever have some of the amazing devices in the show. One of the devices that captured my imagination was the Tricorder (pictured right). It amazed me that such a tiny device could provide so much utility throughout the show. The Tricorder’s versatility allowed it to do pretty much anything in the show, but what I always remembered was it’s medical utility. It allowed characters like “the Doctor” to analyze any number of ailments quickly and accurately.

While we don’t have the technology to make a Tricorder as effective as the ones used in Star Trek, the U.S. Department of Homeland Security’s Science and Technology Directorate (S&T) is developing a tool called the Standoff Patient Triage Tool (SPTT). The purpose of the SPTT is to aid first responders at a disaster triage patients quickly and accurately. Triaging patients with traditional methods can take 3-5 minutes per person. This can become an extremely difficult and time intensive task during a disaster, exactly the opposite of what we’d like. Therefore, the goal of the SPTT is to reduce triage time to 30 seconds per patient by providing accurate readings of pulse, body temperature, and respiration from up to twenty paces away all in a portable package about the size of a legal notebook.

A drawing of the proposed 15 inch by 8.5 inch x 6 inch Standoff Patient Triage Tool (SPTT) with the following features. 1) 4 x 6 display window; 2) Control button; 3) Infrared camera window; 4) Visible camera window; 5) Ranging subassembly window; 6) Shock bumpers. (Source: DHS S&T)

The SPTT takes advantage of Laser Doppler Vibrometry (LDV) in conjunction with a visual and infrared camera to make it’s readings. LDV takes advantage of the doppler shift produced when a laser bounces off a moving target. The shift in frequency upon return of the laser beam is measured and then analyzed in order to determine the velocity over time of the target. In this case, the SPTT’s vibrometer detects the movement of blood vessels and utilizes algorithms to extrapolate relevant data. So far researchers have found that the SPTT can produce strong readings from the head, chest, abdomen and foot. Currently, taking readings from the cartoid artery region of the neck appears to be the best option. Further testing needs to be done on patients in awkward positions, as well as with differing layers of clothing.

While the SPTT can’t do everything a tricorder can do, it appears to be taking a great first step in providing a portable device capable of providing first responders with accurate job critical data that will help them save lives. Maybe it’s only a matter of time before doctors start waving a small device around the patients while asking them what brings them into the office that day.

(Image Source)(DHS S&T Press Release)

During the past month’s global swine flu emergency providing health care professionals around the world with accurate information was critical to understanding and potentially containing the outbreak. The time sensitive nature of dealing with an emerging disease highlighted the importance of developing an effective communication channel that is quick, accurate, and accessible by numerous individuals. Traditional paper distribution channels, mailing notifications to primary care physicians, can delay the receipt of time sensitive materials by 72-96 hours. Thus, the question becomes how do you design a system that can be accessed quickly and easily by a maximum number of health care professionals, while still providing quality information.

A new web application developed by the Indiana Health Information Exchange (IHIE) interfacing with a service called Docs4Docs®, provided by the Regenstrief Institute, appears to have answered that question. The IHIE’s web portal allows electronic communication of public health messages to any registered health care provider. Registered users can also send messages back through the portal to be disseminated across the network. The web portal’s simplicity allows it to bridge the gap between paper-based and electronic-based medical offices thereby ensuring that even doctors in rural areas without advanced IT infrastructure can receive and contribute critical information.

Docs4Docs® also leverages the Indiana Network for Patient Care (INPC) which is a secure community health records system, providing patient data whenever needed. Dr. Shaun Grannis, a Regenstrief researcher, explains “[b]y working with our public health partners to seamlessly deliver public health alerts in precisely the same manner that physicians receive time-sensitive clinical information for patient care, we ensure that physicians have the right information at the time they need to see it”. This was exemplified by the first electronic health alert sent out across the Docs4Docs® network with regards to the emerging H1N1 crisis on April 29, 2009.

Last year Regenstrief scientists received a $10 million, 5 year contract from the Centers for Disease Control in order to continue working on developing electronic records and notification systems like those that make up the backbone of the Docs4Docs® service in Indiana. I for one believe that money is going to good use and look forward to seeing other states follow Indiana’s lead with regards to developing new electronic records and notification systems.

When most people think of laboratory/medical equipment, they think of massive machines full of sophisticated electronics and gear. But, thanks to Moore’s Law (which helps electronics get smaller, cheaper, and more power efficient), equipment that formerly required massive machinery, may be duplicated in the form of handheld devices, like this USB ultrasound gear from Laborie Medical Technologies (FDA approved):

LMT bundles software with their ultrasound probes to deliver images on PCs running Windows XP, but to use it on a phone you’ll need software from William Richard’s group from Washington University in St. Louis, who, with funding from Microsoft, have created a client allowing you to access ultrasound images on Windows Mobile devices! They’ve even released an SDK to help other enterprising researchers create other applications which can make use of these portable UltraSound devices and have them work on any Windows Mobile phone with a USB interface!

Such gear could bring ultrasound access to countries or regions lacking significant healthcare infrastructure, and similar devices could dramatically change how biomedical research is conducted.

For more information, read the presentation that David M. Zar gave at the Medical Records Institute’s TEPR+ (Towards the Electronic Patient Record) conference, and check out the live video demonstration as well as the UltraSoundUSB page on YouTube:

Let’s hope this is only the first in a long line of portable electronics interfacing with readily available mobile phone technology.

(Image credit – The Daily What)

Today modern medicine provides patients with numerous drugs for an enormous number of health issues. For example, getting relief from a headache can be as simple as popping open a bottle of aspirin and swallowing a couple pills. While to the patient the delivery of the drug begins and ends with swallowing those two pills with a glass of water, to the scientists working on the drug that’s simply the beginning of numerous steps that hopefully result in a drug surviving the trip through the body to it’s intended target and doing it’s job.

Drugs are therefore designed not just to solve a problem but to survive the human body’s natural mechanisms. The gauntlet of obstacles that a drug faces upon entry into the body is a major reason why many researchers continue to look into innovative techniques for delivering pharmaceuticals.

That’s where research being conducted by Drs. Stefan Franzen and Steve Lommel comes in. Working with the red clover necrotic mosaic virus (RCNMV), Drs. Franzen and Lommel have developed a potential revolutionary drug delivery platform.

Figure 1. Production of Drug Vector

Drs. Franzen and Lommel take advantage of a 17 nanometer space within the 38 nanometer icosahedral capsid of RCNMV in order to store therapeutics. The RCNMV infused with the drugs could then be used to deliver the drugs in a cell specific manner with the addition of targeting peptides.

The preparation of the drug carrying virus is elegant in it’s simplicity and produces a robust delivery mechanism (See Fig 1). First RCNMV is treated with EDTA to open pores in the capsid. Next therapeutics are infused through these open pores. The pores are then sealed with Ca²⁺ which is key in releasing the drug later upon viral entry to the cell. The prepared virus can then be purified via dialysis followed by adding target specific peptides.

The elegance of using Ca²⁺ to seal the pores lies in the fact that the human bloodstream is abundant in calcium. Inside cells, calcium levels are much lower, allowing the pores to open up thereby delivering the infused therapeutics only when the target cell has been entered.

In vitro work with Doxorubicin, a cancer drug, infused RCNMV shows promising results (see Fig 2.) promoting apoptosis only when provided with targeting peptides allowing the drug to be delivered to the interior of cells.

Figure 2. Delivery of Doxorubicin RCNMV to HeLa cells

A potential application of this research is in cancer treatment. Current chemotherapy treatments often result in dramatic side effects as the drugs do not distinguish between diseased and healthy cells. While these results are probably still years from resulting in a commercial therapy it provides hope that in the near future doctors will be able to prescribe chemotherapy treatments with dramatically reduced side effects thanks to target specific delivery of the drugs.

(Sources: NCSU – results. , NCSU News , Franzen Presentation – Plant Virus Nanotechnology)

IT Development Director Luke Bracegirdle demonstrates a virtual patient scenario.

After Ben’s post the other day about “the Doctor” from Star Trek Voyager it made me remember a news article I had read at ScienceDaily.com.

While in Star Trek Voyager a computer program was used to play the physician’s role, at Keele University in the UK they’ve developed “virtual patients” to train future pharmacists. These “virtual patients” are used to teach proper techniques in communicating and diagnosing patients. The overall program is called the Virtual Consultancy Program and focuses on providing digital avatar based training that rivals that of one on one interview training without the resource constraints of having faculty work one on one with every student.

The “virtual patients” behave quite believably throughout the example scenario displayed by the Keele University School of Pharmacy site. Most remarkably the program reacted quickly and realistically to questions spoken into a headset. The versatility and seeming ease of use makes this training tool particularly impressive.

What most impressed me most, was the potential that this “virtual patient” program illustrates. Keele University’s Virtual Consultancy Program ultimately uses computers to model certain human interactions in order to provide a learning tool for future pharamacists. Part of the parameters within the program include the patient’s basic physical statistics, symptoms, and even allergies in order to provide effective tests and examples for students. It seems to me that this software if developed properly could eventually be very useful in creating models with which doctors can practice and explore diagnosing difficult diseases/conditions.

It would be amazing to be able to model effects of various diseases within a “virtual patient” to determine the potential outcomes for a real patient. Risks could then be accurately assessed providing doctors with another method for screening potential therapies in various situations as well as potentially developing new diagnostic procedures. While I’m sure a lot of work would need to be done to produce a “virtual patient” of that sophistication not only with regards to software, but medical understanding as well. It’s nice to think about the possibilities.

(Read more – Virtual Consultancy Program)