A Quantum of Science

Happy Birthday, Internet

2009-10-29T18:30:00.001-07:00

A QUANTUM OF SCIENCE

Forty years ago today, the first message was sent on what would become "the internet."

The year was 1969. It was the years of the Cold War and the Cuban Missile Crisis. The average computer was the size of a Buick. The Department of Defense wanted a way to communicate in realtime across great distances with multiple sites simultaneously. And at the Advanced Research Projects Agency, someone decided they needed something called a "network."

Major communications companies were invited to bid on the project. IBM and Bell both declined. They could see no future in the technology. Finally a small company called BBN Technologies, originally started by two MIT professors as an acoustic consulting company, took the contract.

On October 29, 1969, BBN's creation - the IMP (Interface Message Processors) - used its ultrafast 24 kilobyte core memory and 50 kilobits per second speed as the world's first router. Researchers at UCLA sent the first message to the IMP that night. What was that message? Was it "One small step for man" or "What hath God wrought" like other significant advances in human technology?

No. The first real message sent over the nascent internet was:

LO

The IMP then crashed.

An hour later, the first FULL message sent over the nascent internet was:

LOGIN

It was a bold new world, and to this day the internet continues to crash in millions of places around the world, twenty-four hours a day.

Happy birthday, Internet!

For more information:

Internet Turns 40 Today: First Message Crashed System (National Geographic)

ARPANET (Wikipedia)

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

All Hail the Robot Armada!

2009-10-29T14:50:00.000-07:00

A QUANTUM OF SCIENCE

In the future, space exploration of distant worlds will be carried out not by humans, nor even by human-guided robots, but by robot-guided-robots.

Wolfgang Fink, visiting professor at California Institute of Technology, predicts a day when small, expendable robot teams would make the trek to Mars or Titan and explore independently, using generalized instructions and flexible programming to search extraterrestrial landscape in much the same way that astronauts have explored the surface of the moon.

All hall the Robot Armada!

For more information:

Robot armada might scale new worlds (R&D Magazine)

Visual and Autonomous Exploration Systems Research Laboratory

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

Airport liquid screening

2009-10-28T11:56:00.000-07:00

A QUANTUM OF SCIENCE

Soon you may be able to bring liquids on planes again thanks to a new spectroscopy technique

Since 2006 air travelers have been unable to bring liquids on board with them. Now a group of physicists from Germany may have found a way to sort the explosive liquids that airport security can’t currently detect from your bottle of Evian.

How does it work? Liquids are examined with a new form of spectroscopy known as Hilbert spectroscopy. Where previous methods used electromagnetic waves passing through a liquid to attempt to identify it – without success – Hilbert spectroscopy uses multiple wavelengths over a large range of frequencies to create a "fingerprint" for dangerous liquids that could be used by terrorists to create an explosion in-air.

While a prototype model is still several years away from being used in airports, continual progress means better and better detection of dangerous liquids – and less hassle for air travelers.

For more information:

Quick Test For Explosive Liquids (R&D Magazine)

Liquid identification by Hilbert spectroscopy (Lyatti et al)

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

FLU ATTACK!!!

2009-10-26T14:28:00.000-07:00

This is quite possibly the best video ever made showing exactly how the flu virus gets into your body and makes a gajillion copies of itself at your expense. You thought the movie theatre scene in "Outbreak" was bad? This is three minutes and thirty-nine seconds of pure infectious delight.

Recommended viewing times: while healthy, not in a crowded place, and *before* lunch.

How A Virus Invades Your Body (NPR)

© AQOS / P. Smalley (2009)
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Gene therapy brings the light to human eyes

2009-10-26T11:37:00.000-07:00

A QUANTUM OF SCIENCE

Gene therapy delivers on promise of better sight for congenital degenerative eye disorder

A recent AQOS post described the landmark success of gene therapy in curing congenital color-blindness in monkeys – the first primate study to achieve that success. Now, researchers have concluded a two-year study following the effects of similar gene therapy treatments for a congenital degenerative eye condition... in humans.

Twelve human volunteers with a condition known as Leber's congenital amaurosis agreed to be given gene therapy in one eye. Though multiple genes are responsible for the development of amaurosis, this study chose to replace the patients’ own copy of a gene called RPE65. The protein encoded by the RPE65 gene is located in the retinal pigment epithelium and is involved in the conversion of trans-retinol to 11-cis retinal during phototransduction (the molecular perception of light), which is then used in visual pigment regeneration in photoreceptor cells. Without a functioning copy of RPE65, humans suffer a steady decrease in vision and are often legally blind by the age of five.

In this study, twelve volunteers – five of them children – received a new copy of RPE65 in the cells of one eye. Within two weeks, the treated eyes began to become more sensitive to light, and within a few more weeks, vision began to improve. The younger the patients were, the better they responded. The youngest patient (age 9) had been legally blind before the study, and afterwards experienced a sufficient increase in sightedness that he is able to ride a bicycle and play softball. Older patients had less improvement because their eyes had greater degeneration in their retinal cells. Still, the improvement is marked and has persisted for the duration of the two-year study. Yet to be answered questions are whether the change is permanent, and what happens if the same therapy is given to the patients’ other eye.

Gene therapy is a field rapidly outstripping medical practitioners’ ability to conduct relevant trials, but this success augurs well for medical and financial support for future studies.

For more information:

Gene therapy transforms eyesight of 12 born with rare defect (LA Times)

Safety and Efficacy of Gene Transfer for Leber's Congenital Amaurosis (New England Journal of Medicine, Maguire et al)

Leber’s congenital amaurosis (Wikipedia)

RPE65 gene (Wikipedia)

Adenovirus-based gene therapy (Wikipedia)

© AQOS / P. Smalley (2009)
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Quantum: Science meets Social Networking

2009-10-23T15:54:00.000-07:00

A QUANTUM OF SCIENCE

FaceBook for scientists? Strange but true, a new software system called VivoWeb is attempting to use the tools pioneered by social networking to accelerate the pace of research and collaboration in the time-worn and somewhat stodgy halls of science, beginning with the biomedical field. What began at Cornell now has NIH funding to be expanded at the University of Florida and will soon be implemented at Scripps Research Institute (Juniper, FL), Ponce School of Medicine (Puerto Rico), Washington University of St. Louis, and the Weill Cornell Medical College (New York City).

No news so far on whether it has a Personals section.

VIVOweb may be the Facebook for researchers (R&D Magazine)

© AQOS / P. Smalley (2009)
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Chicks Dig Giant, errr, Tiny Robots!

2009-10-23T14:12:00.000-07:00

A QUANTUM OF SCIENCE

Microscopic robots might just be the next big thing.

Robots are cool. Giant robots are cooler. But robots measuring just a few micrometers (millionths of a meter) take the cake. At the National Institute for Standards and Technology, they might just do it literally. In May of 2010, the IEEE International Conference on Robotics and Automation to be held in Anchorage, Alaska will host the NIST Mobile Microrobotics Challenge pitting microbots from around the world against one another in such thrilling challenges as sprinting across a distance equal to the diameter of a pinhead! Operated by remote control and observed by judges literally watching them under a microscope, the microbots will perform tasks such as placing tiny pegs into holes or performing other feats of system reliability, level of autonomy, power management and task complexity.

Still not impressed? How about a rousing game of nanosoccer?

For more information:

Mobile microbots to face big challenge (R&D Magazine)

NIST Nanosoccer event

National Institute of Standards and Technology

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

Virtual Autopsies

2009-10-10T23:02:00.000-07:00

A QUANTUM OF SCIENCE

Ever wondered what you could do if the multitouch screen technology used in iPhones were combined with high-resolution MRI/CAT scan images?

Some Swedish researchers did. The result is called the Virtual Autopsy Table.

The name is literal. 3D images of a human body generated by MRI or CAT scans are digitally rendered and displayed on the surface of a table-sized multitouch screen, just like the surface of an iPhone. Observers can then manipulate the image, displaying only certain tissue types, zoom in and out or free-rotating the image, and even cut through the image to display interior regions.

Although it may seem more reminiscent of a certain Firefly episode than a tool of modern medicine, it is likely that VATs will soon be in most cutting-edge hospitals, where doctors can use them to more accurately diagnose illnesses and surgeons can study your particular body *before* you go onto the operating table.

For more information:

Virtual Autopsy Table brings multitouch to the morgue (Engadget)

The Virtual Autopsy Table (Norrkopings Visualseringscenter, Sweden)

[N.B. - the video presentation is well worth watching.]

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

Quotations: A Philosophy of Science

2009-10-10T21:56:00.000-07:00

The right of the scientist to investigate is akin to the academic freedom which our American standards demand for scholars in every field, and not too remote from the freedom of speech which we have come to believe constitutes one of the foundation stones of our American way of living. Each of these privileges, however, carries with it an obligation - an obligation, in the case of the scientist, to investigate honestly, to observe and to record without prejudice, to observe as adequately as human sense organs or the most modern instruments may allow, to observe persistently and sufficiently in order that there may be an ultimate understanding of the basic nature of the matter which is involved. These are the obligations which the scientist assumes when he contracts with society for the right to investigate.

But there is another obligation which is also implicit in the contract between scientist and the social organization which supports, protects and encourages his research. We believe that the scientist who obtains his right to investigate from the citizens at large is under obligation to make his findings available to all who can utilize his data. Any scientist who fails to report, or to place his findings in channels where they may serve the maximum number of persons, fails to recognize the sources of his right to investigate, and thereby jeopardizes the right of all scientists to investigate in any field.

- Alfred Charles Kinsey,
Sexual Behavior in the Human Female
(© 1953, renewed 1981)

© AQOS / P. Smalley (2009)
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That's a lot of flops

2009-10-09T10:11:00.000-07:00

A QUANTUM OF SCIENCE

Kraken supercomputer sets new computational standard

Peta. It’s the scientific prefix that means a thousand times bigger than a trillion – or to put it another way, "a million times a million times a thousand."

Question: How big is that?

Answer: Really, really big. A petasecond is eleven million years. A petainch is sixteen million miles. And a petaflop is a thousand trillion calculations per second. That record was just set by the Cray Xt5 supercomputer, better known as the Kraken.

Operated by the University of Tennessee for the National Science Foundation (NSF), the Kraken is the newest addition to the National Institute for Computational Sciences (NICS), and features more than 16,000 six-core 2.6-GHz AMD Istanbul processors with nearly 100,000 computer cores.

The new supercomputer will be used for scientific modeling studies, especially those requiring literally astronomical numbers of calculations – such as modeling core-collapse supernovas, believed to be responsible for over half the current elements in the galaxy. With the previous generation of high-performance supercomputers, astrophysicists had to make approximations that severely impacted the accuracy of their results. With the Kraken, new vistas in computational capability have opened up that will allow researchers to ask better questions and expand our understanding of the processes that shaped our universe.

For more information:

Kraken Achieves Petaflop (R&D Magazine)

NICS (Wikipedia)

Peta- (Wikipedia)

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

Sleep delays Alzheimer’s?

2009-10-06T14:47:00.000-07:00

A QUANTUM OF SCIENCE

Sleep-cycle neurotransmitters correlate with concentration of Alzheimer’s-causing protein

Alzheimer’s Disease (AD) is a form of late-adulthood dementia caused by brain matter deterioration. This process is associated with the accumulation of a protein called beta-amyloid. When functioning normally, beta-amyloid proteins are soluble and circulate throughout the brain institial fluid; but sometimes their concentration rises to the point where the amyloid protein precipitates, forming insoluble plaques in the brain that lead to necrosis and loss of neuronal function – the classic Alzheimer’s symptoms. But what causes beta-amyloid concentrations to rise to the point where they begin to accumulate as brain-killing plaques?

While the root cause is still unknown, scientists at Washington University in St. Louis have found an unprecedented correlation between beta-amyloid concentration and sleep. Using mice, this study followed beta-amyloid concentrations in brain fluid over the course of multiple sleep cycles. Their findings, just published in the journal Science, show that beta-amyloid concentrations in the brain fell sharply during sleep, only to rise against during waking hours. In additional experiments, researchers showed that sleep deprivation (with or without orexin, a neurochemical that promotes wakefulness) also artificially maintained a high concentration of beta-amyloid, while a chemical that prevents orexin from binding to brain receptors artificially decreased beta-amyloid concentrations.

While the causes of this association are not yet clear, the study points to a potent and previously unknown link between sleep and the pathogenesis of Alzheimer’s disease.

For more information:

Amyloid-Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle (Kang et al)

Beta-amyloid protein (Wikipedia)

Alzheimer’s Disease (Wikipedia)

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

WiFi-Proof Paint

2009-10-05T11:07:00.000-07:00

A QUANTUM OF SCIENCE

Nanoscale metals in paint block WiFi signals - with big implications for mobile users

WiFi is everywhere these days, but less than a decade ago it was rare - and less than two decades ago it did not exist at all. Wireless technology was invented in 1991 by AT&T/Lucent (now Agere) but the current standard technology was not patented until 1996 by an Australian company called CSIRO. The Wi-Fi Alliance, a loose affiliation of over 300 companies manufacturing wireless products or services, was formed in 2000 to ensure standardization of WiFi technologies. The first fully-wireless campus was Carnegie-Mellon in 1994 and the first free-WiFi airport was Pittsburgh International in 2003. In 2005 an undergraduate communications class at the University of Washington mapped all the wireless networks in the Seattle area (5,225 at that time). But what is WiFi?

Though the term suggests "Wireless Fidelity" by analogy to Hi-Fi, the WiFi Alliance (who owns the term) officially states that the term is just a brand name and means nothing. In practice, WiFi is a short-range radio signal, an electromagnetic wave that propagates through space in all directions over a distance that decreases quadratically from its source. Depending on the power of the signal it could travel as little as 120 feet (the average home router) and as much as several kilometers using outdoor line-of-sight directional antennas. The power of the signal is limited by the FCC and is generally up to 1 Watt (compare this with an AM radio station at around 50,000 watts for a sense of scale). The frequency is set by industry standard: 2.4 gigahertz (2.4 billion waves per second) is the current standard. As a consequence, the wavelength of WiFi is in the low millimeter range.

Despite the fantastic growth in WiFi hardware and accessibility over the last decade, little attention has been given to controlling WiFi broadcasting. Some information should not be shared freely, such as for businesses who use WiFi internally but which would rather not share their internal emails with the world. This is especially true for businesses who handle confidential information, such as banks and hospitals. Governmental WiFi networks are obvious targets for WiFi hacking as well, and increasing home WiFi network prevalence makes identity theft from unsecured routers a growing concern for millions of consumers.

While many software security solutions exist to protect networks from illicit access, no system is hack-proof, so methods of preventing the propagation of wireless signals beyond a certain boundary are increasingly important. WiFi "jammers" are devices that function by transmitting a signal in the same wavelength range as WiFi (millimeter) but with opposite sign, creating destructive interference with the WiFi signal. They are illegal in many countries (including the US) nominally because they interfere with emergency-response but more likely because they could theoretically prevent law enforcement communications.

Recently, researchers at the University of Tokyo published a paper detailing their work at blocking wireless transmissions with nanoscale magnets – tiny metallic crystals that can be suspended in an oil/latex matrix (AKA paint) and coated onto walls or other surfaces. These tiny magnetic particles absorb electromagnetic energy in the millimeter wavelength (the same range as wireless signals) and a process called gyromagnetic resonance (or "natural" resonance) results, effectively dissipating the wireless signal into tiny, random magnetic resonances that block further propagation of the electromagnetic wave through space. In this case the nanoscale magnets are composed of aluminum-doped iron oxide crystals, which are unique in that they have the highest gyromagnetic coefficient recorded to date. The researchers also noted that both iron oxide and aluminum were inexpensive, non-toxic materials and thus eminently suitable for this application. Additionally, this nanomagnetic paint will block cell phone signals as well, since those operate at a lower frequency than WiFi.

One area that is not affected by this innovation is human health. The World Health Organization did a study on the impact of radiofrequency emanations on human health in 2007, with the finding that normal levels of RF permitted by most industrialized nations have no measurable impact on health or development - so don’t order a few gallons of anti-WiFi paint thinking it will protect you from cancer. Still, while movie theatres, restaurants and museums might hail this "quiet" technology as a welcome breakthrough, consumers’ ever-increasing use of wireless devices is unlikely to wane any time soon – even if some Wi-Fi hotspots will soon become No-Fi coldspots.

For more information:

Anti-Wi-Fi paint keeps your wireless signal to yourself (Yahoo Tech)

University of Washington WiFi map of Seattle (2005)

Synthesis of an Electromagnetic Wave Absorber for High-Speed Wireless Communication (Namai et al)

A Millimeter-Wave Absorber Based on Gallium-Substituted -Iron Oxide Nanomagnets (Ohkoshi et al)

World Health Organization report on Health Consequences of Wireless Networks

WiFi (Wikipedia article)

Electromagnetic interference in the 2.4GHz range (Wikipedia)

The Physics of WiFi (WiFi Forum)

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

Who Killed T-Rex?

2009-10-01T15:22:00.000-07:00

A QUANTUM OF SCIENCE

The King of the Dinosaurs may have been done in by a microscopic parasite

When paleontology researchers from major universities and museums around the world started to compare notes on the bone structures of particular specimens, they noticed something strange: cavities. In specific, Tyrannosaurus Rex cavities. Of the 61 specimens examined, 15% had significant lesions in the mandible (jaw bone), most of them occurring on both sides of the jaw. The earlier interpretation – that these were the result of intraspecies predation – was ruled out by comparison to the jaws of crocodiles, which form significant scar tissue when punctured by the teeth of other crocodiles. There was no sign of scarring, the cavities were simply eroded into the jaw bone, characteristic of a microbiological agent.

Researchers concluded that based on the similarities between the morphology and pattern of lesions in the T-rex specimens to those found in modern falcons, a protozoan known as Trichomonas gallinae was most likely responsible. The protozoan could have been transmitted either from infected prey or through violent contact between T-rex muzzles such as might be imagined in instance of either displays of dominance or outright cannibalism. Once the disease progressed to the stage found in many of the examined fossil specimens, feeding would become problematic or even impossible. In another modern equivalent, the Tasmanian Devil is actually starving itself into extinction following a face-biting behavior that spreads an oral cancer between individuals. While not conclusive in their theory that trichomonosis starved the T-rex to death, evidence is accumulating that it may have been the case for some populations of the dinosaur, and the potential exists that scientists may be able to extract DNA from these fossils and provide a more solid conclusion in the near future.

For more information:

Common Avian Infection Plagued the Tyrant Dinosaurs (Wolff et al)

Trichomonas gallinae (Wikipedia)

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

Building Blocks

2009-09-30T11:51:00.000-07:00

A QUANTUM OF SCIENCE

Geopolymers turn industrial wastes into energy-efficient super-building materials

Ordinary Portland Cement (OPC) is among the most common building materials on earth. Originating in the early British Industrial Revolution, it is used today in concrete, mortar, stucco and grout. An estimated 2.6 billion tons of it are made worldwide every year. Portland cement manufacture is a highly energy-intensive process involving high-temperature kilns, uses vast amounts of natural resources such as limestone, and produces not only considerable environmental damage in the form of alkaline run-off but also 5-8% of the total carbon emissions worldwide. But is there an alternative for this critical industrial material?

Geopolymers might just be that alternative. This new branch of industrial science explores methods for turning industrial waste products into highly energy-efficient materials with advanced properties. One of those industrial wastes is fly ash, the black powder left over from coal-burning power plants. At present, fly ash disposal is a tremendous industry problem with tremendous environmental impact. Recently, however, scientists have developed ways to use fly ash instead of limestone or other silicas and carbonates for the manufacture of concrete. These materials, known as geopolymers, not only make use of an abundant raw material but also present unique advantages for industrial use. Geopolymer concrete sets much faster than OPC, shows greater mechanical strength, shrinks less, is more resistant to corrosion and can withstand far higher temperatures without breaking down. Perhaps best of all, the production of geopolymer concrete reduces carbon emission by 90% compared to an equivalent amount of OPC.

Geopolymers are poised to provide other advantages as well. The mechanical strength and improved resistance to corrosion and heat make geopolymers ideal for sequestering environmentally harmful compounds such as arsenic, cadmium, chromium, lead, dioxins and even radioactive wastes. Challenges remain, however. Most importantly, long-term durability and stability data has yet to be generated, though ongoing tests suggest favorable performance compared to OPC. There are also existing regulations for OPC-based concrete products that would have to be modified if geopolymers are to gain acceptance and use worldwide, especially in the European Union where such regulations are strict. Still, the prospect of using industrial waste to make one of the most-used building materials on earth with improved characteristics while using less energy and adding less carbon to the planet seems an ideal solution.

For more information:

New Geopolymer Concrete Technology Created (R&D Magazine)

The role of inorganic polymer technology in the development of 'green concrete' (Duxson et al)

Geopolymerisation: A review and prospects for the minerals industry (Komnitsas et al)

Reaction mechanisms in the geopolymeric conversion of inorganic waste to useful products (Van Deventer et al)

Portland Cement (Wikipedia)

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

Prostate cancer - STD?

2009-09-28T14:47:00.000-07:00

A QUANTUM OF SCIENCE

Mouse virus is implicated in causation of #2 male cancer killer

Prostate cancer strikes one in six American men, and is the second most likely cancer to cause death in men. New research now suggests that prostate cancer may in fact be linked to a virus that could be sexually transmitted.

The suspect is xenotropic murine leukemia-related virus (XMRV), a gammaretrovirus similar to viruses known to cause cancer in animals. Retroviruses are known cancer-causing agents because they integrate themselves into the host’s genetic material; when this takes place in or near a segment of DNA associated with a gene that controls growth, cancer – unrestricted cell growth – can result. Some retroviruses also contain cancer-causing genes of their own, such as the src gene in Rous sarcoma virus. The three most common cancer-causing viruses are human papilloma virus (HPV), Hepatitis B virus (Hep B), and the Eppstein Barr Virus (EBV).

Scientists working in collaboration between Columbia University and the University of Utah found XMRV in over 25% of prostate tissue samples, especially malignant ones. Moreover, the virus was found to be significantly more infective when present in semen. Another semen component, acid phosphatase, increased XMRV infectivity of human prostate cells by over 100-fold.

The strongest theory at present for the biology of XMRV-linked prostate cancer suggests that an infected man has viral particles present in his genital tract and deposits them in his partner when he has unprotected intercourse. The acid phosphatase in the semen activates the viral particles and makes them substantially more infective, making the partner at risk of transmitting the virus during future intercourse.

More research is needed to substantiate this theory, but this discovery could also lead to new treatments based on anti-retroviral therapies already known to medicine.

For more information:

Viral Cause For Prostate Cancer? (New Scientist)

Retroviruses (Wikipedia)

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

Lunar Oasis

2009-09-28T11:57:00.000-07:00

A QUANTUM OF SCIENCE

Three separate space probes find spectral evidence of lunar water

In October 2008, India launched the Chandrayaan-1, its first lunar probe. The Chandrayaan-1 was designed to spend the following two years mapping the surface of the moon, but on August 31, 2009 contact with the probe was lost. Before then, however, the probe generated over 70,000 high-resolution images covering almost the entirety of the moon’s surface. Even more importantly, its sensors revealed a curious observation: ice.

Light absorbance is the characteristic interaction of different wavelengths of light with particular chemical elements. If a specific element is present in a material, it will absorb light of a characteristic wavelength. The same is true for simple compounds, such as water. With this technique, specific elements and often simple compounds can be detected even at interstellar distances, allowing scientists to deduce the chemical composition of distant stars. One compound that has a particularly characteristic absorbance spectrum is water. The Chandrayaan’s sensors reported a spectrum containing absorbance peaks consistent with water, and soon afterwards the observations were repeated by NASA’s Cassini and Deep Impact space probes.

Isn’t the moon a dry desert, though? Apollo astronauts certainly believed so when they landed on the moon in 1969, and "moon rocks" brought back from the lunar landing seemed to confirm it – except that it was assumed that any humidity found in the samples were the result of earth water contamination. Now, scientists theorize that water exists on the lunar surface in extremely thin layers just millimeters below the surface. The source and amount of water are still matters for further investigation, but scientists theorize that water on the surface of the moon might "migrate" as the moon is alternately warmed and cooled by exposure to the sun, until it ends up in deep lunar craters. These craters were recently found to be at a lower temperature than the surface of Pluto, so water ending up there would be "stuck" and accumulate over time.

The existence of water on the moon is particularly exciting not only because it was contrary to decades-old assumptions but also because it creates new possibilities. If it could be effectively harvested, lunar water could help sustain a human outpost on the lunar surface. Even more daringly, some have suggested that hydrogen and oxygen derived from electrochemically "splitting" this water could serve as rocket fuel. Rockets launched from the moon would require substantially less fuel because the moon’s gravity is so much less than that on Earth, leading to speculation that lunar launches could facilitate a new era in the exploration of the solar system, especially Mars.

For more information:

India's first lunar probe fails after less than a year (New Scientist)

Widespread water may cling to moon's surface (New Scientist)

How astronauts could 'harvest' water on the moon (New Scientist)

What Do Spectra Tell Us? (NASA)

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

Gene Therapy cures color-blindness in adult primates

2009-09-16T19:52:00.000-07:00

A QUANTUM OF SCIENCE

This is the single biggest success story for gene therapy to date. Instead of reiterating, I will simply say: go read the linked articles and marvel that this could have come to pass in your lifetime.

"Looking back on this in 50 or 100 years, it will be a landmark paper even then."
-David Williams, director of the University of Rochester’s Center for Visual Science

FOR MORE INFORMATION:

Gene Therapy Cures Color-Blind Monkeys (Wired Science)

Original article: Gene therapy treatment of color blindness in adult primates (Mancuso et al)

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

Antioxidants Curb Cancer's Spread

2009-09-16T13:41:00.000-07:00

A QUANTUM OF SCIENCE

New research shows reactive oxygen breaks down cell walls and helps cancer spread

Malignant cancer tumors have a unique characteristic: they can release tumor cells into the lymphatic system and cause tumors to grow elsewhere in the body, even in tissues or organs totally unrelated to those that were the original source of the tumor. This process is called metastasis, and sometimes forces doctors to use whole-body or systemic anti-cancer treatments when a localized treatment targeting a single tumor would be both more effective and far easier on the patient. Now scientist are advancing understanding of how metastasis occurs, and how to prevent it.

Researchers at Burnham Institute for Medical Research in La Jolla, California recently reported that reactive oxygen species were key players in the cellular process of metastasis. Reactive oxygen species (ROS) include superoxide, hydrogen peroxide and other forms of oxygen generated by the body’s normal functions. Some uses of ROS are beneficial, such as when the immune system generates ROS to kill invading cells. In cancerous cells, however, ROS help form lesions and break down cell walls, aiding in the spread of tumor-forming cells. Researchers have isolated a scaffold protein called Tks5 (for Tyrosine Kinase Substrate) which is concentrated in extruded lesions of tumor cells, called podosomes (or invadopodia in some papers). Tks5-rich cells rapidly produce ROS and form lesions that facilitate the spread of tumorous cells throughout the body. In their paper, Burnham scientists show that cells lacking the gene for Tks5 production are substantially inhibited from forming metastatic tumors, and treating the tumor cells with antioxidants similar suppresses the activity of Tks5, resulting in smaller tumors, fewer lesions/podosomes and a substantial decrease in extruded (metastatic) cells.

An example of tumor size reduction in cells lacking the Tks5 gene (4.20 and 4.24):

This paper is an exciting advance in the understanding of the basic processes of malignant cancer. If podosome formation and metastasis can be reduced by either antioxidant treatments or drugs that target Tks5, huge advances can be made in reducing the mortality associated with highly-metastatic malignant cancer.

For more information:

Reactive Oxygen’s Role in Metastasis

A role for the podosome/invadopodia scaffold protein Tks5 in tumor growth in vivo (Blouw et al)

Metastasis (Wikipedia article)

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

Old Flu Drug, New Hope

2009-09-15T15:19:00.000-07:00

A QUANTUM OF SCIENCE

When vaccines fail, antiviral drugs might make the difference between life and death

The seasonal flu vaccine is already being administered and a special vaccine targeting H1N1 will soon follow, but for some people a vaccine may not be enough. Children, the elderly and immunocompromised individuals are at high risk for complications from influenza. For those already infected a vaccine does no good, but fortunately, antiviral medications are available when the flu turns life-threatening.

The most well-known anti-influenza drug is TamiFlu (its official name is Oseltamivir). TamiFlu is taken orally, usually for a five-day course of treatment. Approved in 1999, it has been used to treat 50 million people to date. Currently, TamiFlu is usually reserved for serious, potentially life-threatening cases in an attempt to prevent the flu virus from mutating into a form resistant to the drug. Indeed, five cases of TamiFlu-resistant H1N1 have already been reported but overall the rate of resistance flu cases remains low (around 1.2%).

Recently, a drug called Peramivir has been developed and is on the fast track to approval by the FDA. This is not a new drug – it was abandoned in 2001 by Johnson and Johnson due to low oral availability – but in 2005 concerns over Avian flu caused drug-makers to reexamine the compound and begin testing it as an intravenous medication. Recent studies show a single intravenous dose of Peramivir is as effective as the full five-day course of oral treatment with TamiFlu. Additionally, adverse drug reactions were less common with Peramivir.

Both TamiFlu and Peramivir act by inhibiting the same viral enzyme, neuraminidase. This enzyme allows viral particles to escape infected cells and go out in the bloodstream where they can find new cells to infect. When TamiFlu or Peramivir inhibit the viral neuraminidase, viral particles remain trapped inside infected cells until the body’s immune system can respond, usually with macrophages (literally "big eaters") that engulf the infected cell and digest it, destroying the viral particles along with the cell.

Additional advantages of Peramivir include its single-dose effectiveness. There have been reports of individuals hoarding TamiFlu pills and threatening the supply of the drug, but that cannot happen with a drug which can only be administered intravenously.

For more information:

Study: New Drug Fights Flu as Well as TamiFlu

TamiFlu (Wikipedia article)

TamiFlu-resistant H1N1 cases reported

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

Toward Better Vaccines

2009-09-15T10:51:00.000-07:00

A QUANTUM OF SCIENCE

Making vaccines both optimally effective and optimally safe may be an easier task in the near future

Vaccines have an overwhelming track record when it comes to preventing illness, and thanks in part to conservative rules put in place by the federal agencies regulating them vaccines have also been extremely safe. Still, there’s an unadvertised trade-off in that compromise: vaccines would be even more effective than they are today if they could be made with heat-inactivated pathogens rather than highly purified microbial proteins generated in non-toxic bacteria, but that elevates the risk of possible immune reactions and side effects in those who take the vaccine.

To help improve the effectiveness of vaccines even when not using the heat-inactivated pathogens, scientists have long used compounds known as adjuvants to "boost" the body’s immune response. In essence, adjuvants are sensitizers that tell the body to be ready for an invader; when given as part of a vaccination, adjuvants significantly increase the vaccine’s protective effects both in duration and potency. But the only adjuvant ever approved for use in humans, aluminum hydroxide (or alum), is far from the most effective compound for the job. To date the FDA has been extremely reluctant to approve other, more powerful adjuvants for use with vaccines because of concerns about toxicity and possible side-effects.

Now scientists at Oregon State University have developed an adjuvant based on lecithin, a common food product, that shows six-fold greater immune response when administered as part of a vaccine as compared to alum-based treatments. Lecithin is part of a category of food products termed "generally recognized as safe" by the FDA, meaning that it is non-toxic in almost any dosage. This could mean a fast track to approval and, very possibly, vaccines that would be more effective, for longer periods of time, with smaller doses and fewer injections.

For more information:

New adjuvant could hold future of vaccine development

Adjuvant (Wikipedia article)

Strong antibody responses induced by protein antigens conjugated onto the surface of lecithin-based nanoparticles (Sloat et al)

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

A Weed No Longer

2009-09-11T12:14:00.000-07:00

A QUANTUM OF SCIENCE

Latex production finds an unlikely source: dandelions

Latex is a complex emulsion of proteins, alkaloids, starches, sugars, oils, tannins, resins, and gums. In most plants, latex is white, but some have yellow, orange, or scarlet latex. Latex rubber comes from rubber trees, mostly found in South America, where industrial production of this common material has been severely impacted by fungal infections that threaten the entire industry.

The alternative? Dandelions.

The milky white juice that comes out of the stem when picked is a latex not unlike that found in rubber trees, except that it polymerizes immediately on contact with air. With some careful genetic work, scientists have developed a strain of dandelions lacking the enzyme that causes that polymerization, leading to the very real promise of industrial dandelion latex farms in the next five years. The best part of all is that latex from dandelions exhibits none of the immune rejection observed in latex rubber products, making it safe for use by hospitals and other important applications.

Dandelions: a weed no longer.

For more information:

Dandelion’s natural latex now used for rubber production

Latex (Wikipedia article)

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

Quantum: Tree Power!

2009-09-09T14:43:00.000-07:00

A QUANTUM OF SCIENCE

"Green power" takes on a whole new meaning

Researchers at the University of Washington have discovered a way to "tap" the small but renewable electrical currents found in trees by investigators at MIT in 2008. Usually these microcurrents (200 millvolts or less) would be incapable of running even small circuits, but electrical engineers from the UW have built special "boost converters" that take a low incoming voltage and store it to produce a greater output.

This is an entirely new and very exciting field where much is currently unknown but the potential exists for a wide range of low-voltage devices that might one day help with everything from early wildfire alerts to climate-change sensors to methods for measuring tree vitality.

For more information:
News article from the UW

Source of Sustained Voltage Difference between the Xylem of a Potted Ficus benjamina Tree and Its Soil (Love et al, 2008)

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

Genetic Pastorale

2009-09-09T10:48:00.000-07:00

A QUANTUM OF SCIENCE

Are cows responsible for the spread of a gene allowing humans to digest their milk?

Lactase is an enzyme that breaks down lactose, the disaccharide found in cow milk, into glucose and galactose.

This is important because lactose itself cannot serve as a source of energy for the human body, but glucose and galactose can. The gene encoding lactase can have either one or two copies and still produce enough lactase for carriers to process milk – humans lacking a copy cannot digest cow milk and are called lactose intolerant. Another term, "lactase persistence," refers to the strange stubbornness of the lactase gene, which is inherited in some human populations with far more frequency and fidelity than in other human populations.

Now a new publication shows statistical attempts to model the spread of lactase persistence in European populations as a correlate with how common dairying – raising cows for their milk – is in that region over the last, say, ten thousand years.

While it might seem intuitively obvious that intensive dairying would provide a strong selective pressure for a gene that makes cow milk digestible, this model shows exactly how strong that pressure is. Think about it this way: dairy cows were first domesticated around 9,000 years ago in the early Neolithic age. Since then, their presence has managed to exert a strong influence on human genetics, making those who raise them and care for them much more able to benefit from their milk. Before cattle were domesticated for milk (as opposed to for meat) there was little advantage for humans to possess even a single copy of the lactase gene; today, there is a sharp genetic profile between human populations associated with dairying and those that are not. This map, taken from the statistical modeling publication, shows how sharp that genetic profile is.

Researchers suggest, based on this model, that lactase persistence originated somewhere in the red area on the map around 7,500 years ago. This matches archeological evidence as well, showing the value of the model for predicting genetic drift over time and distance.

As much as human civilization has impacted the genetic destiny of the cow, the reverse is true as well. This begs the question: how many other creatures in our environment are shaping us, even now? It is easy to believe that Homo sapiens is the apex of the evolutionary ladder, but even the humble cow has some say in our genetic path.

For more information:

The Origins of Lactase Persistence in Europe (Itan et al)

Lactase (Wikipedia article)

Lactose intolerance (Wikipedia article)

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

Cut, cut, cut

2009-08-25T12:55:00.000-07:00

A QUANTUM OF SCIENCE

Are HIV rates in the US substantial enough to merit a policy of circumcision?

Following evidence of the protective effect against HIV infection, recent news articles report that the CDC is mulling the idea of endorsing circumcision for all male infants born in the United States. But will it have that much impact?

First, the science: how does circumcision prevent HIV infection? HIV infections occur when the virus gains entry to cells by binding to a protein called CD4, found on the surface of cells. Cell types rich in CD4 are thus easier targets for a successful HIV infection. One such cell type is the Langerhans cell, a part of the primate epidermal tissue related to defending the body against invading microbes. As it happens, primate foreskin is rich in Langerhans cells, meaning plenty of CD4 protein for the AIDS virus to bind to and invade the body. By removing the foreskin through circumcision, an easy point of entry for the virus is blocked.

(Interestingly, CD4-rich Langerhans cells are found in human foreskin and vaginal tissues, but not in oral or rectal tissues. This suggests that HIV infections use a different biochemical route when introduced into the body through those tissues.)

The idea of reducing the risk of contracting HIV through circumcision is far from new. In 1987 a letter was published in the New England Journal of Medicine suggesting exactly that, and studies done in the last fifteen years bear out that theory. While the methods used and areas studied (largely in Africa) varied, the conclusions were so striking that in at least one case a circumcision/HIV infection study was halted years early so the findings could be considered for public policy discussions. Depending on the area studied and the risk factors of those involved in the study, HIV infection rates were found to be as much as 50% lower among circumcised African men than their intact counterparts. Various attempts have been made to expand the conclusions of individual studies through meta-analysis papers and their conclusions found an even greater protective effect of circumcision when those studied were from high-risk populations.

So why not support a policy of encouraging circumcision in the United States? The same studies being reviewed by the CDC have some counterindications that are well worth considering in any kind of policy discussion.

First, the benefits of circumcision are greatly enhanced among high-risk populations. This means that for the average American man (whose risk is far, far lower than the average African man) the benefits are considerably lessened. This could well have something to do with the fact that an estimated 79% of American men are already circumcised – though as rates of circumcision have fallen to around 65% in the most recent surveys, that number is now trending downward. Secondly, use of barrier protection is far more prevalent in America among all demographics, another factor that reduces the positive impact of circumcision protection. Another risk factor related to the need for additional preventative measures against HIV infection – the rate of STDs causing lesions or ulcers, such as herpes or syphilis, which help HIV enter the body during sexual contact – is lower in America than in most African nations, and treatment for those afflictions is considerably more available. Finally, almost all the research done in this area has been performed in Africa. This means there is a possibility that things could be different among Caucasian populations, simply because they are biochemically distinct from non-Caucasians.

The need for additional research is clear. Until scientists can repeat the highly successful African studies in America, Europe, or ideally both – since circumcision is much less common in European nations than in America – the benefits of circumcision for Western populations will remain a question too open for a substantive policy debate to take place.

For more information:

CDC mulls routine circumcision of infants to reduce spread of HIV (NY Daily News, 25-Aug-09)

Circumcision and heterosexual transmission of HIV infection to men. (Fink, 1987)

Comparative investigation of Langerhans' cells and potential receptors for HIV in oral, genitourinary and rectal epithelia. (Hussain, 1995)

Male circumcision and risk of HIV infection in sub-Saharan Africa: a systematic review and meta-analysis. (Weiss, 2000)

Male circumcision for HIV prevention in young men in Kisumu, Kenya. (Bailey, 2007)

Langerhans cells.

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

Comets: Interstellar Johnny Appleseeds?

2009-08-20T15:35:00.000-07:00

A QUANTUM OF SCIENCE

Are comets the disseminators of the seeds of life?

It was January 2, 2004. The NASA space probe known as Stardust passed through the tail of the Wild-2 comet, five years after the craft was launched on its mission to collect interstellar dust and particle samples from the tail, or coma, of the comet – particles that might well come from beyond Earth’s solar system. A specially-designed collector called an extra low density aerogel was used to capture the particles, and the probe’s camera took high-resolution images of the comet’s nucleus.

On January 15, 2006, the Stardust probe returned to Earth. A sonic boom and a fireball heralded its return over Utah’s Great Salt Lake desert. It was travelling at almost 29,000 miles per hour – the fastest re-entry speed into Earth's atmosphere ever achieved by a man-made object.

Since then, scientists in the Stardust Mission of NASA’s Jet Propulsion Laboratory have been hard at work analyzing the microscopic dust and particles it collected on its seven-year, three billion mile journey. And the results of that analysis are breathtaking.

Some things were expected. Silicate crystals had been predicted based on spectroscopic observations, but their presence confirmed not only those predictions but also the belief that the comet contained matter from outside the solar system.

Even more exciting, organic materials were detected. Astrobiologists have long been aware of aliphatic hydrocarbons (long chains of carbon and hydrogen) diffused throughout space, but the hydrocarbons found in the coma of Wild-2 were much longer than standard interstellar chains, indicating greater complexity. Methylamine and ethylamine, while simple molecules, were an exciting find as well because the nitrogen they contain is essential for life.

But on August 16, 2009, Dr. Jamie Elsila of NASA's Goddard Space Flight Center in Greenbelt, Maryland announced something astonishing. Scientists analyzing the Stardust samples had detected the presence of glycine, the simplest amino acid – and one of the critical building blocks of almost all life on Earth.

Rigorous testing was required in order to confirm this result. Every effort was made to ensure that "earth grime" did not contaminate the samples. The Johnson Space Center in Webster, Texas maintained the comet particles (it is also the home of most of the moon rocks recovered by the Apollo missions) and over 150 scientists from some of the most prestigious laboratories in the world helped with the analysis.

Among the tests they performed as confirmation of the results was an isotopic analysis. Isotopes of an element contain different numbers of neutrons than the most common version of that element, and the prevalence of different isotopes of a given element are well characterized. Using that information, scientists were able to confirm that the isotopic prevalence found in the glycine detected in the comet particles was not terrestrial contamination.

Where did the glycine come from, then? Theories abound, but the one with the greatest antiquity is the theory of panspermia (also known as exogenesis). First proposed in ancient Greece, many respected scientists since the Renaissance have expressed support for the idea that life came to Earth from outer space. This is one of the core areas of study in the field known as astrobiology, a multidisciplinary science that has existed formally since NASA established the first astrobiology program in 1960. Combining physics, astronomy, chemistry, biology and even more specialized sciences, astrobiology concerns itself with the study of the origin, evolution, distribution, and future of life in the universe.

The presence of even the simplest amino acid in the tail of a comet is a profound piece of evidence supporting the idea of panspermia. If this theory is correct, comets might well be the Johnny Appleseeds of the universe, slowly sowing their seeds of complex pre-biotic molecules throughout the galaxy – and suggesting that life on other worlds may be far more common than scientists once thought.

For more information:

NASA article on the discovery
http://www.nasa.gov/mission_pages/stardust/news/stardust_amino_acid.html

SCIENCE Magazine article on Wild-2 analysis (2006)
http://xray.physics.sunysb.edu/research/pdf_papers/2006/sandford_science_2006.pdf

More on the Wild-2 comet
http://en.wikipedia.org/wiki/Comet_Wild_2

More on Panspermia
http://en.wikipedia.org/wiki/Panspermia

More on Astrobiology:
http://en.wikipedia.org/wiki/Astrobiology

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

BS-o-meter: Detecting Pseudoscience

2009-07-31T11:01:00.001-07:00

A QUANTUM OF SCIENCE

Pseudoscience is no joke.

While some of its claims may be laughable, countless otherwise intelligent people are taken in by claims of better health, extended life, or superior male equipment. Some of these "miracle cures" are harmless (except perhaps to your wallet) but others can be deadly – for instance, "energized water" made by adding the radioactive element radium! As consumers of not just materials but also of information, it is critical for everyone to be able to spot science scams when they come your way.

The single best piece of advice is simply this: Question. Be skeptical. Don’t believe everything you read, or take it at face value. Ask for references. Check the background. Read a book, or talk to an expert. Ask if someone is trying to make a buck – or a convert. And never forget that if it seems too good to be true, it probably is.

Common sense aside, here are some of the hallmarks of pseudoscience:

Use of vague, exaggerated or untestable claims. The language of science is that of objective, measurable quantities or verifiable characteristics. Good science also requires a narrow scope for its claims, and uses negative controls and blind tests to prevent it from reaching unjustified conclusions. Just what type of energy has been added to "energized water" anyway? Any claim that cannot be objectively measured or independently quantified is suggestive of pseudoscience.

Absence of authoritative references or citable sources. Scientists build on the work of those who came before them, and reference those sources extensively to show where their predecessors’ work ends and their own begins. By listing their sources, scientists establish their contribution in the context of previously tested and verified work in the same field, and present it for testing and verification by others. Any theory or claim lacking citations from established scientists in the same field should be viewed with extreme skepticism.

Unrepeatability or lack of openness to testing by other experts. The hallmark of science is reproducibility. If other scientists cannot replicate an experiment using the same conditions and materials described by the claimant, the claim is refuted. Pseudoscience often seeks evade this by making claims that are difficult or impossible to test and thus refute. Pseudoscience will sometimes make claims of "ancient knowledge" or "secret practices" from far-off lands, but these should be recognized as ways to convince the reader to be uncritical and accept the source’s claims without question.

Reductionism. In science, the simplest explanation is usually the correct one. This principle, known as Occam’s Razor, can be applied to any possible pseudoscientific claim as a way of discerning its value. If the explanation seems unduly complicated and unlikely, it is probably untrue.

Absence of progress. Science is constantly growing, learning, self-correcting and progressing. If a field does not constantly add to its body of knowledge, correct imperfections or errors in itself, or add further instances and explain further phenomena, chances are it is pseudoscience. For example, astrology today is almost identical to that of the last two millennia, and phrenology has not changed in the last 150 years since it first gained popularity.

Use of misleading language. Pseudoscience often seeks to cloak itself in the language of science and thus mislead the unsuspecting. This can be difficult for a non-scientist to detect or dispel, but overly-general terms such as "energy/energized" or overly-scientific terms such as "dihydrogen monoxide" (also know as H2O or water) are a sign of obfuscation and an attempt to mislead the reader. "Psi," "aura," "miracle," "natural" and "holistic" are other classic terms frequently misused in pseudoscientific claims.

Personalization of issues. Any theory that attracts extremists, the dogmatic, the charismatic, or that characterizes those who dispute it as enemies, is likely founded on pseudoscience. Often this is true of “scientific theories” propounded by extreme religious groups seeking to support a particular theology with something that sounds like science. Intelligent Design is one of the best examples of this – ultimately, this theory is not testable and thus cannot be the province of science, but rather of faith.

Claims of suppression, or of conspiracy to conceal or refute. Science is an open, peer-reviewed, transparent process – as it must be, in order to be cumulative and build upon itself. Real science is eagerly tested by others in the field, since it is either an innovation to be adopted or a fallacy to be exploded. It is only pseudoscience that shies away from peer review and independent testing. If a theory is supposedly being suppressed by the scientific establishment, it is likely to be in hiding from it instead.

Confirmation rather than refutation. In science, the burden of proof rests on those making a claim, not on the skeptic. Any theory that defies science to disprove it is likely to be pseudoscience.

Self-appointed experts and single-source theories. Successful scientific theories are tested by credentialed scientists and then used in their own work, leading to many examples and instances where it holds true. Often pseudoscience comes from someone lacking appropriate scientific credentials, or someone with unverifiable or obscure degrees from unlikely places. Also, if a theory is held only by a single person or a single group, and especially if that has been the case for an extended period of time, it is strongly suggestive of pseudoscience.

Association with financial gain. The adage ‘if it seems too good to be true, it probably is’ should be applied whenever claims of beneficial discoveries are purported. If a theory or claim is followed by an attempt to sell you a product or service purported to help you, especially in some subjective or non-quantifiable way, it is almost certainly pseudoscience and should be viewed with extreme skepticism.

For more information:

What is Pseudoscience?

H2O dot con: water-related pseudoscience, scams and quackery

Dowsing for Dollars – Fighting High-Tech Promises with Low-Tech Critical Thinking Skills

Crank dot net – a collection of scams and popular falsities on the web

© AQOS / P. Smalley (2009)
Reproduction with attribution is appreciation

Telemedicine: Cell Phone Microscopy

2009-07-27T15:32:00.000-07:00

A QUANTUM OF SCIENCE

Can technical innovations bring medical diagnostics anywhere a cell phone can go?

It is increasingly common for medical professionals to use images generated by light microscopy in the rapid evaluation and dissemination of a diagnosis of disease. This practice is so widespread that a medical communication standard has been adopted for using transferring digital images between doctors and institutions. This has resulted in improvements in rapid diagnosis of disease, but rural areas and developing nations lag far behind this due to the prohibitive cost of equipment and training required. Light microscopes and their more exotic cousins (dark-field, fluorescence microscopy, etc) are far from universal medical devices. Worse still for underserved regions, microscopy is an essential tool for diagnosis of diseases endemic to such areas. Tuberculosis, malaria and sickle-cell anemia are just a handful of the afflictions most easily characterized by microscopy, and which are also extremely common in developing nations.

What is strange and in this case fortunate is that rural areas and developing nations are being more quickly served by mobile phone providers, and thanks to this fact researchers in Berkeley, California were able to engineer a device that could interface with a standard cell phone to capture, analyze and transmit high-resolution microscopic images such that positive diagnoses could be made.

Using a Nokia phone equipped with only a 3.2-megapixel CMOS camera, scientists and engineers were able to construct a device consisting of two filters and three lenses that was capable of capturing high-quality microscopic images of blood (allowing positive diagnosis of malaria and sickle-cell anemia) and sputum (allowing positive diagnosis of tuberculosis). The latter required the addition of an LED emitting in the ultraviolet spectrum, permitting fluorescence microscopic images to be captured by the cell phone’s camera. While minimal image modification was required for the light microscopy images, even the fluorescence microscopy images needed only minor processing before they could be analyzed successfully.

The power and utility of this innovation of science and engineering cannot be easily overstated. For a relative pittance, the power of expensive and complex instruments requiring trained technicians to operate is now available to anyone with a cell phone. Soon, underserved rural areas and developing nations will have the possibility of rapid and high-accuracy diagnoses. With this piece of technical know-how the scientists, engineers and medical professionals of Berkeley have pushed back the darkness a little farther and paved the way for a better quality of life for many who suffer only because of where they happen to have been born.

For more information:

Mobile Phone Based Clinical Microscopy for Global Health Applications (Breslauer et al)

© AQOS / P. Smalley
Reproduction with attribution is appreciation

Biomining: Panning for Gold with Viruses

2009-07-23T12:49:00.000-07:00

A QUANTUM OF SCIENCE

How can viruses solve an industrial mining problem?

One of the most abundant forms of life on earth is a humble virus called a bacteriophage. Phage for short, it exists only to infect bacteria; they are harmless to plants and animals. But scientists have long used phage as a way to search for special protein sequences with unique properties – in this case, the ability to selectively bind to specific metal ores.

An emerging technology, gold- and silver-binding phages were known in the literature but only as curiosities until a scientist at the University of British Columbia Institute of Mining Engineering wondered if he could find a phage that bound copper sulfide.

Industrial mining practices typically grind ore into a fine powder to aid in separating the ore of interest from other minerals. Special chemicals called flotation aids are added to this liquid slurry of various minerals and make the copper sulfide particles hydrophobic. These particles then adhere to bubbles in the slurry and float to the top, making a solid layer of the desired ore that can easily be extracted.

The problem comes in when very similar ores are present in the same slurry. To solve this problem, Dr. Scott Dunbar of UBC decided to search for a phage that selectively bound the mineral chalcopyrite (CuFeS2). In collaboration with scientists at the UBC’s Centre for Blood Research and the Department of Biochemistry and Molecular Biology, Dunbar found three unique phages that bound tightly and selectively to chalcopyrite, sphalerite (ZnS), or both. Using these selective phages, researchers were able to enrich ore slurries for the desired mineral ore, even in the presence of the other – in effect, panning for gold among the sand.

From this similarity the term biomining was coined.

Not only the mining industry may benefit from this advance. In addition to the reduction or elimination of flotation reagents from the industrial mining process (a potent source of environmentally unfriendly chemicals), this achievement demonstrates the potential for ore-binding phages as a powerful bioremediation technology. Heavy metals such as lead and cadmium could be more easily removed from contaminated soils using similar phages, and even some nuclear wastes might be amenable to biomining remediation. As an innovative technology, biomining has capabilities that are only just beginning to be imagined, let alone tapped.

For further information:

Virus may lend a hand in copper mining

Biomining with bacteriophage: Selectivity of displayed peptides for naturally occurring sphalerite and chalcopyrite (Curtis et al)

© A Quantum of Science / P. Smalley
Reproduction with attribution is appreciation

Quantum: Get Stung and Get Paid

2009-07-21T08:55:00.000-07:00

A QUANTUM OF SCIENCE

Dr. Duffy wants to give you malaria.

Well, sort of.

Researchers at the Seattle Biomedical Research Institute have developed a weakened version of the malaria bug (Plasmodium falciparum) by deleting from its genome the genetic instructions that allow it to invade the liver and to reproduce. Now SBRI has been approved to conduct human trials using this "neutered" malaria, testing various drugs and vaccines for their effectiveness at blocking the parasite.

And volunteers will get paid somewhere between $2000 and $4000 for their trouble.

For more information:

Seattle Times article "You can get paid to catch malaria"

SBRI press release on the approval to conduct human trials with malaria vaccine

© A Quantum of Science / P. Smalley
Reproduction with attribution is appreciation

Quantum: Less Antibiotique, merci

2009-07-20T09:54:00.000-07:00

A QUANTUM OF SCIENCE

French government program educates about the danger of overuse of antibiotics

From 2002-2007 the French government has operated a program aimed at reducing the use of antibiotics for flu-like symptoms after a report came out showing that France used more antibiotics per capita than any other European nation. Called "Antibiotics are not Automatic" this program targeted overuse of antibiotics for flu-like symptoms, especially among the young. Now a report has been released showing the results of this program. Briefly, overall antibiotic use was down an average of 26% in all regions of the country and for all antibiotic categories (except quinolones). Remarkably, this reduction was even more pronounced among children (35%) and most of all in instances of those complaining of flu-like symptoms (45%). The important thing about this study is that broad health education can work on an entire population and over a reasonable period will result in major adjustment of behavior. Also worth noting is that the information used in the study was obtained through the online electronic database of French medical records, a system not unlike that which is being built by US government funding at present.

For more information:

Significant Reduction of Antibiotic Use in the Community after a Nationwide Campaign in France, 2002–2007 (Sabuncu et al)

© A Quantum of Science / P. Smalley
Reproduction with attribution is appreciation

Quantum: Obesity fueled by reward-behavior gene

2009-07-14T15:51:00.000-07:00

A QUANTUM OF SCIENCE

Obesity risk factor gene found to act in an unlikely place: our minds

Researchers analyzed the DNA of over 30,000 humans in 8 different studies and found three separate localed regions (or "loci") in their DNA where many of those studied had very similar subtle differences ("single-nucleotide polymorphisms"). The presence and number of copies of these genes with subtle differences correlated almost precisely with measurements of waist circumference, body mass index, and obesity. Two of these genes were known from other studies, but the newest gene, NRXN3, has a surprising role in the body. Instead of regulating the growth and proliferation of fat cells, or guiding the metabolic rate up or down, it acts on the central nervous system to modulate so-called "reward behavior," in which the brain receives positive feedback stimulation when a particular behavior is performed.

While these results are enlightening, they are not a genetic test for obesity risk nor even necessarily an indication that science is racing to "cure" obesity. But by understanding the underlying factors better, new strategies to address the expanding epidemic of obesity may be hastened. Moreover, NRXN3, is also associated with susceptibility to addiction and further research may reveal additional therapies to help affected individuals overcome that as well. What is more frightening is the knowledge of how similar those two scourges truly are - obesity as an addiction to food is a chilling idea.

For more information:

NRXN3 Is a Novel Locus for Waist Circumference: A Genome-Wide Association Study from the CHARGE Consortium (Nancy L. Heard-Costa et al)

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Reproduction with attribution is appreciation

You Give Me Fever

2009-07-09T16:03:00.000-07:00

A QUANTUM OF SCIENCE

Emergent viral outbreaks show Ebola is not the only "hot zone" virus worth fearing

Sub-Saharan Africa has long been known as the Hot Zone, a place from which some of the world’s most deadly viruses originated. Among them are the well-known Ebola and Marburg viruses, members of the viral hemorrhagic fever (VHF) family that cause extreme fever, internal and external bleeding and rapid death among a frighteningly high percentage of those infected. Other "Old World" (i.e. African) hemorrhagic viral diseases include dengue and yellow fever. Most VHF viruses are carried by rodents – which seem largely immune – and are spread to humans by liquid contact, though some are capable of aerosol infections. (This latter category includes the Marburg virus, which was weaponized by the former Soviet Union in the 1980’s.) Less well-known cousins in this same family are the so-called New World viruses such as hantavirus, as well as the Argentine, Bolivian, and Venezuelan hemorrhagic fevers.

Late last fall an African travel agent was flown from the city of Lusaka to Johannesburg, South Africa, suffering from high fever and external bleeding. She died a few days later. Within the next several days, the paramedic who received her into the hospital, a nurse who cleaned the room following the travel agent’s death, and a nurse who attended the paramedic after he became ill, all perished from the same virus. Another nurse who treated the paramedic was given an antiviral treatment and survived. This was the beginning and end – for now – of an outbreak of the Lujo Virus, named for the two cities where it was first observed (Lusaka and Johannesburg). A member of the VHF family, it has more in common with the New World branch than it does Ebola or Marburg. Genetic analysis by researchers at Columbia University showed that the Lujo virus was a member of the arenaviridae genus (the name comes from the Latin word for sand, referring to the way viral particles of this genus appear when viewed under a microscope). Strangely, arenaviruses are almost unknown in Africa but have several species native to South America. Comparing the genetic sequence of Lujo to other VHF species from Africa showed significant differences, strongly suggesting that Lujo was not a simple mutant or even a more virulent strain caused by reassortment of viral chromosomes (such as is often the case for the influenza virus). Instead, Lujo appears to be the first high-morbidity, high-mortality VHF virus to emerge from Africa’s hot zone in the last thirty years.

In 2006 a paper was published by Dr. C.J. Peters, a member of the University of Texas Medical Branch, discussing the factors that affect the accelerating rate of emergence of new viruses and increasingly deadly outbreaks. He referenced the Emerging Microbial Threats reports issued by the Institute of Medicine in 1992 and updated in 2002, in which all the data pointed to two major factors at play in the increasing danger of deadly microbial outbreaks: multiple ecologic niches and ever-accelerating human travel and transport. In this paper he describes an arenavirus outbreak in a small village in Bolivia in 1962. The village suffered an outbreak of "black typhus" and out of 600 villager there were 107 cases, of which more than four out of ten perished. This is roughly the same morbidity and mortality rates recorded for the medieval scourge of bubonic plague, better known as the Black Death.

Since the 1960's, large sections of the Amazonian plateau have been deforested, and human activity in those regions has reached levels never before seen. The same is true of sub-Saharan Africa, where the Lujo virus emerged in 2008; had the Lujo virus not been caught before it spread thanks to current medical expertise not available in 1962, the "black typhus" outbreak may well have paled in comparison to the devastation Lujo might have wrought.

The story of ecological niches created through human activity has become hauntingly familiar, and authorities predict that the problem will only worsen as population pressures push humans deeper into the hot zones of viral reservoirs in both the Old World and the New.

For more information:

Viral hemorrhagic fever (overview)

Googleblog article on early news of the Lujo outbreak

News article on Columbia researcher’s efforts to analyze Lujo

Genetic Detection and Characterization of Lujo Virus, a New Hemorrhagic Fever–Associated Arenavirus from Southern Africa (Lipkin et al).

NOVA interview discussing Soviet weaponization of Marburg virus

© A Quantum of Science / P. Smalley
Reproduction with attribution is appreciation

Quantum: the Cute-Baby Effect

2009-07-09T11:33:00.001-07:00

A QUANTUM OF SCIENCE

This just in: women like looking at "attractive" babies more than men do. That's unlikely to make any headlines, but the reverse case is where the surprise comes in: if a baby is "unattractive" through some objective standard, women like looking at it *less* than men do.

Researchers at the Clinical Psychopathology Laboratory or McLean Hospital and Harvard Medical School in Boston report that the length of time that women vs. men spent looking at "normal" babies versus those affected by cleft palate, Down's Syndrome or other congenital birth defects were reversed: women spent longer looking at the "normal" babies than men did, but much less time looking at "unattractive" babies than men did. The authors of the study suggest that this might reflect an evolutionary bias on the part of women to spend less time and attention on the less viable of their offspring, correlating subjective lack of aesthetic appeal with decreased potential for viability.

For more information:

Gender Differences in the Motivational Processing of Babies Are Determined by Their Facial Attractiveness (Yamamoto et al.)

© A Quantum of Science / P. Smalley
Reproduction with attribution is appreciation

Food Safety Overhaul: Chickens and Eggs

2009-07-08T11:45:00.000-07:00

A QUANTUM OF SCIENCE

Sweeping and ambitious, administration regulations would enact mandatory oversight and tracking of critical foods

Today the Obama administration announced a major overhaul of the US food safety system. Overseen almost entirely by the FDA, some 150,000 individual commercial food producers would be subject to sweeping new regulations that would require traceability for all food and food additives sold in the US. This is a significant increase in the level of government oversight of the food industry and is a response to several high-profile outbreaks of food poisoning in the last several years. These include recent E. coli and Salmonella outbreaks leading to the recall of tremendous amounts of food throughout the US. Notably, Salmonella in peanut products and E. coli in ground beef both originated in US commercial food manufacturers as a result of poor hygiene and lack of mandatory safety regulations. Worse still, it took unconscionably long for the FDA to track down exactly where the problem started, leading to a much larger outbreak than necessary.

To prevent this from happening again, the new legislation calls for a Reportable Food Registry to be established and overseen by the FDA. This registry would ensure that any outbreak of food poisoning or adulterated food would be instantly reported to the FDA, which would then be able to use the registry to track down where the adulterated food came from, what other foods it might have come in contact with or been used in, and what distributors to alert. Not only would this increase the response time of the FDA, it would also allow traceability for the agency such that random testing of large numbers of those 150,000 individual commercial food manufacturers would not be required. If a tomato in Denver turned up positive for Salmonella, FDA scientists could quickly determine that it came from a wholesaler in Texas who purchased it from a grower in Louisiana. From there, all tomatoes that came from that grower or that passed through that wholesaler would be identified and the distributors notified to pull the tomatoes off their shelves.

This is a massive undertaking but a significant benefit to the food safety network in the US. Previously it might have taken FDA scientists weeks to trace a single infected tomato back to that grower in Louisiana, and in that time panicked distributors might destroy untold volumes of perfectly safe tomatoes, costing the food industry huge amounts of money. With the Registry, that process might take less than 48 hours, and the cost savings to distributors and wholesalers is the reason that the food industry generally supports this legislation.

One particular area of concern for the Obama administration is eggs – specifically, chickens, eggs, and Salmonella. It has been known for twenty years that infected chicks produce Salmonella-laden eggs that cannot be detected easily by the current food safety inspection systems in place. The new legislation mandates that egg growers take steps to eliminate rodents (a prime source of Salmonella contamination) and only purchase chicks from growers who also take steps to monitor Salmonella among their stock. Additional regulations require refrigeration during more of the lifespan of an egg, something that about half of all egg producers already do voluntarily and which would reduce the potential for Salmonella growth. As mentioned above, egg growers are generally in favor of these regulations – even though it will cost them some money for testing and prevention, they believe the increase in public confidence will more than make up for the estimated one-cent per dozen increase in the cost of eggs.

They’re almost certainly right. In this case, it doesn’t matter whether the chicken or the egg came first, so long as both of them come before the Salmonella.

For more information:

FDA Reportable Food Registry

Article from The Washington Post on the new legislation

New York Times article focusing on egg safety regulations

© A Quantum of Science / P. Smalley
Reproduction with attribution is appreciation

Newest Alzheimer's Drug: Coffee?

2009-07-06T12:31:00.000-07:00

A QUANTUM OF SCIENCE

New research suggests caffeine may not only protect but can also reverse Alzheimer's Disease symptoms

Today's issue of the Journal of Alzheimer's Disease contains two reports involving the effects of caffeine on mice bred to mimic the biochemical degeneration of cognition found in human Alzheimer's disease. Briefly, the major source of this neural degeneration is the accumulation of a protein called Amyloid-β (or Aβ). A natural protein, Aβ can sometimes mis-fold and in that state becomes impervious to the normal cellular processes that break down aging proteins for recycling. Because it cannot be broken down, mis-folded Aβ accumulates and eventually causes cell death in the tissues surrounding it. Alzheimer's disease results when this takes place in brain tissue.

Researchers are interested in the process by which Aβ mis-folds, accumulates and - just possibly - might be eradicated. In the studies published today in the Journal of Alzheimer's Disease, researchers found that caffeine can not only protect Alzheimer's-prone mice from the accumulation of Aβ, but can even reduce Aβ levels in the brains and blood of mice who already have advanced Alzheimer's conditions. This is not the first report of caffeine's effects, but the two studies are back-to-back illustrations of the growing body of evidence linking caffeine to treatment for Alzheimer's even after the condition is diagnosed. Additionally, the levels of caffeine used in this study are relevant - the equivalent of about five cups of coffee per day for a human. This is exciting as it suggests that caffeine treatment might be possible without resorting to levels so high as to cause dangerous side-effects to humans.

For more information:

Caffeine Reverses Cognitive Impairment and Decreases Brain Amyloid-β Levels in Aged Alzheimer’s Disease Mice (Arendash et al)

Caffeine Suppresses Amyloid-β Levels in Plasma and Brain of Alzheimer’s Disease Transgenic Mice (Chuanhai et al)

© A Quantum of Science / P. Smalley
Reproduction with attribution is appreciation!

Music Gene

2009-07-02T09:00:00.000-07:00

A Genetic Basis for Music?
A QUANTUM OF SCIENCE

Musical legacy found in a gene associated with social interaction traits – including love

Researchers in Finland recently reported a study in which 19 Finnish familes (343 individuals) with many professional or active amateur musicians among them were studied for genetic similarities. The study found that a single gene, AVPR1A (for arginine vasopressin receptor 1A), held a strong statistical correlation to creative musical abilities such as pitch, tempo and composition, especially when members of multiple generations all shared musical ability. So what is arginine vasopressin?

Peptide hormones, of which the vasopressins are a subfamily, are composed of short cyclic chains of amino acids (nine, in this case) and regulate a number of physiological functions. Arginine vasopression (abbreviated AVP) controls hydration through kidney function, including the stimulation of urine dilution and concentration in balance with the body’s need for extra water. For this activity it is secreted into the bloodstream, but some AVP is also found in the brain, where it binds to a specialized receptor – the one encoded by the gene AVPR1A. Binding of AVP to AVPR1A stimulates the brain to release neurotransmitters that play into "social behavior" responses, including the mate bonding behavior found in voles and, to a greater or lesser extent, in humans. Some studies have even suggested that these same neurotransmitters play a role in feelings of altruism, or love.

Is there a single gene that determines who is musical and who is not? These findings are preliminary and far from exhaustive, but they point to a biological function encouraging the spread and preservation of the AVPR1A gene. If, as suggested, the AVP/AVPR1A peptide hormone receptor plays a role in social behavior and other emotional attachment activities in higher mammals, it could easily be linked to the development of early human societies via the universal language: music.

For more information:

Original PLOS article

© A Quantum of Science / P. Smalley
Reproduction with attribution is appreciation

Newest AIDS drug: Sugar?

2009-06-30T16:13:00.000-07:00

A QUANTUM OF SCIENCE
Common polysaccharide prevents HIV infection in mice

Researchers at Meharry Medical College School of Medicine in Nashville recently reported that HIV-1 infections were blocked in mice by a surprising compound: cyclodextrin, a common cyclic sugar used extensively in food, pharmaceuticals and commercial products such as dryer sheets and Febreze.

The structure of cyclodextrin is a hollow ring, perfect for complexing hydrophobic molecules (such as fragrances, in the case of Febreze) and binding them tightly. This also makes cyclodextrin a good carrier molecule for pharmaceuticals, encapsulating drugs and aiding their delivery to different parts of the body. Surprisingly, the use of cyclodextrin in the food industry held the key to its role in preventing HIV infection. In the food industry cyclodextrins are employed for the preparation of cholesterol free products, allowing cholesterol to be sequestered inside the hollow ring of cyclodextrin and more easily removed from the food matrix.

Researchers have known for some time that there was a link between cholesterol and HIV infection. Cholesterol is an essential part of cell membranes, helping them stay fluid and permeable for normal trans-membrane traffic. Lipid rafts, a specialized structure rich in cholesterol, is required for HIV-1 to infect new cells. Though the research is still preliminary, cyclodextrin’s ability to bind and sequester cholesterol appears to play a role in preventing successful HIV infections. Trials in mice demonstrated a transient, reversible protective effect when female mice were challenged with HIV-laden semen. Similar experiments in primates have not fared as well, but issues with those studies have sparked several more extensive trials and the scientific community is abuzz with the possibilities.

Among the most exciting properties of cyclodextrin from a pharmaceutical standpoint is its safety. Discovered in 1891, cyclodextrins have been used for decades in foods and medicines. Its toxicity is extremely low, even when used in high dosages, and since it is composed entirely of sugar molecules there is little chance of complications or immune reactions. Only time will tell whether this humble molecule will find a new role in the prevention of HIV infections, but pharmaceutical giant Johnson & Johnson is already pursuing it as a therapeutic and prophylactic.

For more information:

http://www.the-scientist.com/templates/trackable/display/blog.jsp?type=blog&o_url=blog/display/55807&id=55807

© A Quantum of Science / P. Smalley (2009)
Reproduction with attribution is appreciation!

Quantum: Ancient immunity

2009-05-28T11:45:00.000-07:00

A QUANTUM OF SCIENCE

New findings show adaptive immune system may not be new invention

Recently, scientists at Emory University in Atlanta reported that lampreys - a cartilaginous fish which evolved around 500 million years ago - is the oldest organism yet found to possess an adaptive immune system like that of humans. Previously, the adaptive immune system was believed to have originated in sharks, which evolved around 400 million years ago. This extra 100 million years is a big deal because the lamprey is a much earlier splinter from the vertebrate branch of the tree of life, and could mean that other even more ancient predecessors had already figured out how to "record" microbial invaders and repel them better in future infections.

Another interesting note: the age of cartilaginous fishes was known as the Silurian period, a time culminating in the so-called Law Event in which approximately 60% of aquatic species became extinct through a series of rapid climatic changes. Could the adaptive immune system have helped lampreys and sharks survive?

For more information:
The Scientist: Ancient organism, modern immunity

© A Quantum of Science / Peter Smalley (2009)
Reproduction with attribution is appreciation

Curing the Mosquito

2009-05-26T14:13:00.000-07:00

A QUANTUM OF SCIENCE

How can bacteria help protect humans from malaria?

Malaria is a deadly but neglected tropical disease that has received more money and attention in the last decade than in perhaps the preceding century. The disease is spread by mosquitoes in whose gut live one or more of five protozoan species of the Plasmodium genus. As a protozoa, it is neither a virus nor a bacteria but more like an amoeba or an algae, and thus it is more difficult to fight because its cells look more like human ones than either viruses or bacteria. Malaria is contracted by 350-500 million people every year, and approximately 1-3 million die of it annually - mostly sub-Saharan children. Now a scientist at the Johns Hopkins University Malaria Research Institute think he might have a unique way to help break the cycle of malarial infection.

The answer? Cure the mosquito.

For a long time it was thought that malaria could be controlled by using insecticides and bed screens to keep the mosquitoes away, but these approaches have both proven only partially effective. Insecticides also have their own toll on both human health and the environment, and rapidly become ineffective. But Dr. George Dimopoulos has found a species of bacteria living in the gut of the mosquito whose presence seems to inhibit the growth of the malaria protozoa. When he treated mosquitoes with an antibiotic, the bacteria died and the protozoa multiplied manyfold, making the mosquito a much deadlier vector for the disease. By helping this specific bacterium to stimulate the mosquito's immune system and cure it of the protozoans it carries, Dr. Dimopoulos believes, the spread of malaria could be controlled more effectively than with insecticides or bed screens alone.

If so, this could be a new and unprecedented breakthrough in fighting malaria, one of the great scourges of Africa.

For more information:
VOA News article

Public Library of Science article by Dr. Dimopoulos

Wikipedia entry on protozoa

© A Quantum of Science / Peter Smalley (2009)
Reproduction with attribution is appreciation

A Cure for the Common Cancer

2009-05-24T08:46:00.000-07:00

A QUANTUM OF SCIENCE

What can the common cold do to help fight cancer?

Behold one of the most successful organisms in the history of the world: the humble adenovirus, better known as the cold. Human have recorded suffering from this virus since at least Hippocritas, and likely much earlier. Every year humans around the world come down with runny noses, coughs and fevers associated with the cold. And then they spread it to others, and recover - until the next round. Adenoviruses are among the handful of true success stories in biology. Now, scientists have found a way to harness the infectivity of the common cold to make it serve a therapeutic function, not an epidemiological one.

Recently, a group of scientists led by Dr. Leonard Seymour of Oxford University reported successfully removing the "disease" genes from a adenovirus and replacing them with genes for cancerous proteins. Why would this help? In the same way that your body's immune system eventually learns to recognize and attack normal adenoviruses that manage to infect you, the modified adenovirus contains cancer-linked genes that provide the immune system with the opportunity to "learn" that these proteins are invaders to be fought, potentially turning the immune system into the most potent and selective anti-cancer fighter possible.

Scientists have managed similar feats before but to do so they have had to weaken the virus, making it less effective at stimulating the immune system and teaching it to recognize cancer proteins as invaders to be fought. With this achievement, Dr. Seymour and his collaborators have taken a large step forward into a burgeoning field of therapeutics drawn from biological strategies older than humanity itself.

For more inforation:
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1000440

(C) AQOS / Peter Smalley (2009)

A single amino acid

2009-05-21T15:43:00.000-07:00

A QUANTUM OF SCIENCE

Why does the more lethal H5N1 Avian flu not infect humans more readily?

Several references have been made now to the "nightmare scenario" in which genes from the more lethal Avian flu (H5N1) reassort with the less dangerous but more infective Swine flu (H1N1), generating a hybrid that is both lethal and infective. We have yet to talk much about why the H5N1 strain is harder for people to catch – so hard that in some years there are only a single-digit number of cases.

Certainly, the lethality of H5N1 inhibits its spread. In epidemiological terms, the virus kills faster than it spreads, leading to a reproduction number at or below one. In a recent paper, researchers show that a single amino acid change in the sequence of the viral polymerase gene (PB2) results in a dramatic difference in both temperature tolerance and infectivity.

Scientists at University of North Carolina at Chapel Hill found that the H5N1 virus required the higher temperatures found in its bird hosts (around 40 degrees Celsius) in order to be highly infective. At 32 degrees Celsius - the temperature of the cells found in human nasal passages called HAE, or human airway epithelium – the H5N1 virus became sticky and did not effectively infect those cells. The reason for this? A single amino acid at position 627 of the polymerase protein of the H5N1 virus was changed, allowing it to be glycosylated - chemically modified to bear a particular sugar residue. Researchers were able to prove this by genetically altering a human influenza virus (which infected cells optimally at 32 degrees Celsius) at position 627, changing just that one amino acid to one that could be glycosylated. The resulting human virus was not capable of creating an infection in human airway epithelial cells, demonstrating an attenuation of the formerly infective human influenza virus. Further modification of viral coat proteins fully attained an "avian" level of temperature sensitivity.

This research is important because it significantly adds to our understanding of the molecular process by which the influenza virus mounts a successful infection in either of its principal hosts (birds or humans). Scientists who sequence previously unknown strains of influenza isolated from patients can now rapidly assess the polymerase gene (PB2) and determine quickly whether it is an avian strain or one more evolved for humans. Not only the treatments recommended but also the course of a widespread epidemiological event could be affected by this. Further, scientists searching for the molecular keys to understanding the mutations of various influenza strains can now look more effectively for such alterations, granting insight into the process of interspecies spread of the virus.

Perhaps most importantly, these findings help to partially allay fears that H5N1 is likely to reassort with H1N1 – since avian flu infects HAE cells poorly due to their intolerance for colder temperatures, we are less likely to endure that kind of hybrid virus.

For more information:
Avian Influenza Virus Glycoproteins Restrict Virus Replication and Spread through Human Airway Epithelium at Temperatures of the Proximal Airways.

© A Quantum of Science / Peter Smalley (2009)
Reproduction with attribution is appreciation

Mapping H1N1

2009-05-20T10:34:00.001-07:00

A QUANTUM OF SCIENCE

Where in the world is H1N1?

The spread of H1N1 around the world has significant implications for the etiology and epidemiology of the disease, as well as the global health infrastructure’s response to it. Raw numbers alone do not tell the story as well as this single image, taken from the WHO pandemic alert and response website.

This map is current: as of today there are a global total of 10,243 laboratory-confirmed cases of H1N1 influenza that have been reported to the WHO, including 80 deaths (making the global mortality rate one death out of every 128 cases). While the actual number of total cases is inevitably somewhat higher due to the lagging nature of lab confirmations and reporting, what is more interesting is the distribution of the cases – and deaths – and what this might tell us about the past and future of H1N1.

Originally dubbed as Swine Flu, the official name for this strain of H1N1 is North American influenza, and indeed the overwhelming majority of the cases are in North America (93.8%). What is interesting to note is that 79 of the 80 confirmed deaths are also in North America (98.75%). Digging a little deeper into the distribution of deaths, we find that this is due to the large contribution of deaths from H1N1 in Mexico, where the mortality rate is one death for every 50.6 cases. That is two and a half times the global mortality rate, and eighteen times the mortality rate in the adjacent United States. With the sequencing of the H1N1 genome in Canada that was announced yesterday, no significant differences were found in strains isolated in Mexico versus those in the United States or Canada. While this is somewhat reassuring because it means there is not a more virulent strain on the loose in Mexico, it requires a different explanation. Some authorities have suggested Mexico has deficiencies in its health infrastructure, but others cite a cultural inhibition that may play a more pervasive role in preventing infected persons from seeking help until it is too late. In either case, however, countries with similar health infrastructures and cultures would be expected to have a similar mortality rate, and this has not yet been borne out (as the map’s number for Central and South America show).

Another point of interest brought out by the map of H1N1 cases to date are the non-North American hot spots. Japan is the leader of these, with 210 cases, followed almost evenly by Spain (107) and the United Kingdom (102). What is interesting about this is the far-flung locations of the hotspots outside North America. Nothing like the close distribution of cases in Mexico-US-Canada have been seen in these Asian and European hotspots. This could mean that there is something particular to North America that supports the infectivity of the viral strain; or it could mean that it is simply too soon, and the neighbors of these hotspots will soon show a commensurate rise in cases. It is worth noting that strains of influenza are known to show a strong geographical preference; the deadly Bird flu (H5N1) is almost unknown outside of the Far East, for reasons that scientists are still trying to elucidate. This also brings up the potential for reassortment of viral genes between H1N1 and H5N1, now that the former has entered the latter’s territory. Still, Japan has been aggressive about treating flu cases and currently Roche (the maker of Tamiflu) estimates that 35 million of the 50 million people who have been treated with Tamiflu are in Japan. It can be hoped that this aggressive treatment schedule will be effective in containing the possible hybridization of H1N1 with H5N1.

For more information:
WHO Epidemic and Pandemic Alert and Response

WHO H1N1 map (20-May-2009 version)

Tamiflu (Oseltamivir) information, including use in Japan

© A Quantum of Science / Peter Smalley (2009)
Reproduction with attribution is appreciation

Canadian scientists sequence H1N1 genome

2009-05-19T14:42:00.000-07:00

A QUANTUM OF SCIENCE

Now we know the complete blueprint for H1N1; now what?

Today it was announced that scientists in Canada have fully sequenced the entire genome of the H1N1 influenza virus. While it's not the first viral genome to be fully sequenced, it is a landmark achievement and all the more so for having been completed in one week of around-the-clock work by scientists at Canada's National Microbiology Laboratory in Winnipeg. This is, as the saying goes, kind of a big deal.

These findings shed some intriguing light on the outbreak of H1N1 but raises even more questions, as most scientific discoveries do. For example, researchers found virtually no difference between the Mexican strains and those occurring in the US or Canada. Why, then, have so many more cases in Mexico proven fatal? The answers may not lie in the genes themselves, but rather in differences of health infrastructure and health policy. Benefits of this breakthrough include faster analysis of future strains, a better understanding of how and why H1N1 mutations or reassortments occur, and a better H1N1 vaccine - with this last being of crucial importance as major pharmaceutical companies begin the laborious process of choosing which sequences to use for their vaccines. With an improved understanding of the variations in the H1N1 genome, conserved sequences can be selected for use vaccines, resulting in a stronger, more robust protection against future infection.

Perhaps it is a little cynical, but one might consider that the timing of this announcement seems a little too convenient considering that today is the second day of the 62nd World Health Assembly, the annual meeting of the World Health Organization whose handling of the H1N1 outbreak has been criticized by many science and health professionals. Then again, maybe it is simply a case of serendipity; regardless, it is good news and that's worth remembering.

Plus, if you want to apply for the position of Viral Genome Curator at a company in Bethesda, MD, you now have one more fully-sequenced genome to add to the list.

For more information:
http://www.canada.com/Health/Canadian+completes+sequencing+virus/1569084/story.html

© A Quantum of Science / Peter Smalley (2009)
Reproduction with attribution is appreciation

Quantum: Influenza tutorial (powerpoint)

2009-05-19T10:38:00.000-07:00

A QUANTUM OF SCIENCE

This powerpoint presentation may be a little advanced in places but there is some great information to be extracted even with just a casual viewing, especially among the pictures. The author, Dr. Mustafa Ababneh, is a molecular virologist at the Department of Veterinary Clinical Sciences, Jordan University of Science and Technology.

For more information:
Dr. Ababneh's publication record on PubMed

© A Quantum of Science / Peter Smalley (2009)
Reproduction with attribution is appreciation

Quantum: flu expert fears H5N1 nightmare

2009-05-19T10:16:00.000-07:00

A QUANTUM OF SCIENCE

What happens when the lethal but less-infective H5N1 strain of influenza mingles with the relatively benign but more-infective H1N1?

Dr. Yi Guan of Hong Kong Kong University is one of the leading flu experts in the world. His claim to fame was the isolation of the SARS virus in wild civets in 2003; his recommendation to eliminate the population of captive civets may have prevented a re-emergence of SARS since then. Now he has some strong criticisms of the World Health Organization's handling of H1N1, and worries about the potential for a sharing of lethal H5N1 genes with H1N1, which has proven itself far better at spreading itself around than H5N1.

The difference between the two strains' ability to infect may be in the gene encoding hemagglutinin, the protein that helps the virus get into cells and infect them. Recently published data shows that the genetic sequence for the hemagglutinin (HA) gene is only 9.7% similar between H5N1 and H1N1, by far the largest difference between their genetic codes. Because influenza is capable of rapid reassortment - the shuffling of genes like decks of cards - it may only be a matter of time before the HA gene from H1N1 is adopted by H5N1. That could have profoundly dire effects if experts like Dr. Guan are to be believed. So far the only ray of hope that nightmare scenario will not happen is the H1N1 seems restricted to North America, while H5N1 is only found in Asia. Critics of the WHO like Dr. Guan seem to be quite justified in calling for increased attention to transcontinental spread of H1N1 and more aggressive use of TamiFlu and other treatments to curb the spread of H1N1 into Asia.

More information:
http://blogs.sciencemag.org/scienceinsider/2009/05/exclusive-meet.html

© A Quantum of Science / Peter Smalley (2009)
Reproduction with attribution is appreciation

Quantum: Counting H1N1

2009-05-18T15:08:00.000-07:00

A QUANTUM OF SCIENCE

First let's tackle the jargon.

Prevalence is the total number of cases of a disease or infection in a given population. The important thing to remember about prevalence is that it is all the cases, not just the new ones, so the longer it takes to recover from a particular infection, the higher the prevalence will be. Most of the H1N1 figures you hear or read about are prevalence numbers, and as such are not as accurate a reflection as they might be.

Incidence is the rate at which new cases occur in a population, and is a better measure of how fast a disease is spreading because it takes out the duration-of-illness factor included in prevalence. Incidence is usually reported per capita ("3 new infections per 1000 people") or even with a time-element ("14 per 1000 persons-years"). The latter is useful because it lets researchers compare the instantaneous rate of a disease’s spread even in disparate time periods (for example, an incidence of 14 per 1000 persons-years could mean 14 cases would be expected for 1000 persons observed for 1 year, or 50 persons observed for 20 years). The only caveat to this use of incidence is the assumption that the rate will always be linear over the period in question, so longer time periods are more susceptible to incidence errors.

Finally there is the reproduction ratio, which is a measure of how many people each infected person will spread the disease to before they recover. In order for a disease to spread at all that ratio has to be greater than 1 (such that each infected person infects at least one more person). Up to now the ratios estimated for H1N1 Swine flu have been between 1.4 and 1.6. Recently, however, researchers at the National Institute of Health and Medical Research in Paris have re-estimated the ratio using some different assumptions and found it to be between 2.2 and 3.1 in Mexico, well within the range of numbers required for a pandemic. With the recent report of 135 new cases of H1N1 in Japan, the World Health Organization still denies an official pandemic is underway but evidence is mounting that H1N1 may have a higher incidence than previously thought.

For more information:
http://blogs.sciencemag.org/scienceinsider/2009/05/swine-flus-rate.html

http://blogs.sciencemag.org/scienceinsider/2009/05/h1n1-rocks-japa.html

http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19205

© A Quantum of Science / Peter Smalley (2009)
Reproduction with attribution is appreciation

Smoking AIDS

2009-05-16T15:42:00.000-07:00

A QUANTUM OF SCIENCE

Anti-retrovirals are now drugs of abuse in South Africa; will this lead to resistant HIV?

The newest chapter in the AIDS saga in Africa is unfolding in the townships of South Africa, where the demographic of 15-21 year olds are engaging in a new practice: grinding up anti-retroviral drugs designed to suppress HIV and prevent it from becoming AIDS, mixing the powder with tobacco or marijuana, and smoking it to achieve hallucinogenic and anxiolytic effects.

A recent BBC article goes into further detail, but mainly focuses on the social aspect of the new form of drug abuse. Doctors and health care policy activists in South Africa are gravely concerned about not only the interruption of the intended use of the drugs - which has led to shortages and long lines in many areas - but also the possibility that this abuse of the drugs will cause resistant strains of HIV to arise.

This seems unlikely for several reasons. First, smoking a pharmaceutical innately changes the molecular structure of the drug. The heat involved might well be expected to break down the structure into inactive forms, or combine key parts of the molecule with oxygen and likewise eliminate its antiviral activity. Without activity, the drug cannot cause resistance to arise. The second reason this fear is ungrounded is that in order to cause resistance, those abusing this drug must also be HIV-positive. While there is likely to be some overlap in a country whose HIV-positive population is 3.2% among that age/sex demographic [LINK], it is unlikely to be enough to cause undue concern from a health policy standpoint.

Clearly there is a health policy crisis in South Africa regarding the proper administration of anti-retroviral drugs. Concerns about drug abuse aside, the phenomenon is preventing those who really need such drugs from obtaining them, and this alone is sufficient reason to take action. But fears of a super-HIV, resistant to the anti-retroviral cocktails of drugs currently capable of controlling (though not eradicating) HIV, are overblown in this case.

© AQOS / Peter Smalley (2009)
Reproduction with attribution is appreciation

Quantum: Tracking H1N1 mutations in real time

2009-05-13T16:10:00.000-07:00

A QUANTUM OF SCIENCE

How do scientists around the world collaborate rapidly in real time when a pandemic looms?

Today marks a departure from the established format of longer, more detailed essays with the first "quantum" post designed to provide a short, sweet snapshot of a small corner of Science. The intent of such quantum posts is to give readers tools to make use of on their own to extend their knowledge of the cutting edge of science and technology.

Today's quantum is the Human/Swine A/H1N1 Influenza Origins and Evolution project: a wiki site maintained by Oliver Pybus of Oxford University and Andrew Rambaut of the University of Edinburgh. The purpose of this wiki is to provide a place for scientists around the world to post and discuss the genetic sequences of H1N1 influenza strains they have isolated and characterized. Based on these sequences, scientists can build a more accurate picture of where the flu virus is spreading and - most importantly - how fast it is mutating... in real time. This is key because a mutation that increases virulence could make the difference between a regular annual flu season and a global pandemic.

Of particular note: the phylogeography link has a great discussion of how fast different strains of the virus are spreading, and where. This ties in nicely with the phylogenetic analysis of the virus, a look at the genetic history of H1N1 as it has spread over time.

© AQOS / Peter Smalley (2009)
Reproduction with attribution is appreciation

The End of Antibiotics

2009-05-12T16:34:00.000-07:00

A QUANTUM OF SCIENCE

As antibiotic after antibiotic becomes useless, where will we turn to fight the advancing tide of bacterial infection?

Most American adults are aware of the problem of antibiotic resistance: the rapid and aggressive evolution of pathogenic bacteria capable of tolerating even the most potent antibiotics that Western medicine has come up with. Less than a century ago penicillin would knock out any bacterial infection known; today we live in the age of MRSA, a strain of Staphylococcus aureus resistant to not just one but multiple antibiotics. Doctors are running out of ways to prevent even mild infections from becoming life-threatening because bacteria develop resistance can share genetic information with one another, spreading the resistance even further. While there are things we can do to slow the advance of antibiotic resistance, the pace of resistance is accelerating far beyond the ability of pharmaceutical companies to develop new drugs. Is there no hope?

One source of hope may be simpler - and far older - than we think. Mammals have a powerful adaptive immune system to protect them, but what about the lower animals, insects, and plants that lack a sophisticated immune system? How do they avoid succumbing to microbial infections? In the last thirty years scientists have begun to discover that living things have long since developed ways to fight bacteria. One of the most ancient and endemic of these are a class of proteins call antimicrobial peptides (AMP).

First a bit of nomenclature. The majority of your body is made of protein: a polymer of up to 21 different amino acids strung together in long chains. A shorter chain of amino acids (less than a hundred) is called a peptide. Both peptides and proteins have their sequence determined by genes: deoxyribonucleic acid (DNA), which is made up for four basic nucleic acids in repeating sequences. Antimicrobial peptides are encoded by special genes that first evolved, scientists estimate, over a hundred million years ago.

Scientists now know of over nine hundred antimicrobial peptides, and the number is growing at an exponential rate. The diversity of these peptides is astounding: even closely related species have a different set of AMP that little resemble those of even their closest evolutionary siblings. And almost every animal or insect examined has not merely one, but a palette of antimicrobial peptides in their genome, expressed as peptides found in epithelial tissues, blood cells, haemolymph and saliva. Not only the sequence of these peptides is diverse. Their structure also spans an amazing range of shapes, sizes and architectures. Some resemble a helix, others form two-dimensional sheets, and still others form complex rings and branches through multiple internal bonds. Further, many of these AMPs are processed by the cell after being translated from genes into peptides: glycosylation, amidation, halogenation and proteolytic cleavage are common modifications. Given the diversity of genes and structures, scientists have spent a long time trying to understand the unique effectiveness of AMP in combating microbial infections.

The first question that arose after the discovery of antimicrobial peptides was why resistant strains of bacteria had not evolved, especially since AMP genes were so evolutionarily ancient. The first key to this is the very diversity that has confounded scientists. Imagine if each species of plant and animal had evolved the genetic ability to produce between five and twenty broad-spectrum antibiotics, all of which were available for use as a kind of antibiotic "cocktail" whenever infection threatened! This diversity makes it very hard for bacteria to evolve resistance – just when it figures out how to evade one AMP, nineteen more are there to make sure it doesn't pass on that knowledge. Further, the target of antimicrobial peptides is almost impossible for bacteria to avoid: the bacterial membrane itself.

Bacterial membranes are made up of a double layer of molecules called phospholipids. Briefly, the "phospho" part of the membrane molecule is hydrophilic and prefers to be in water, thus facing both the inside and the outside of the bacterium. The "lipid" part of the membrane molecule is hydrophobic, preferring not to be exposed to water, and so gets sandwiched in the middle of the membrane. (Touch your four fingertips together in front of you; the fingers are like the lipid part of the membrane, the palms are like the phospho part. To the left of your hands is inside the cell, to the right is outside.) This makes an effective barrier because most molecules are either overall-hydrophilic or overall-hydrophobic; either way, the phospolipid bilayer will prevent both kinds of molecules from crossing into (or out of) the cell.

The exception, of course, are antimicrobial peptides. Regardless of the diverse sequences they possess, all AMP have the characteristic of being "amphipathic" – possessing both hydrophobic and hydrophilic sequences of amino acids in the same peptide. Carefully spaced, these amino acids first carpet the bacterial membrane, merging with the hydrophilic phospho exterior of the membrane and thinning it. The AMP then swing around so that their hydrophobic amino acids can merge with the lipid layer of the membrane. As this happens, pores begin to form in the membrane and more AMP are able to slip inside the bacterium, repeating the process from the inside. Pores expand and soon the membrane collapses, destroying the bacterium and freeing the AMP to find another target.

Because the target of the AMP is the bacterial membrane, this strategy has been effective for a remarkably long time – more than a hundred million years in some cases (Nicolas, 2003). The phospholipid membrane was one of the earliest innovations of the primordial unicellular world, and unlike genes and protein, it is not easily susceptible to evolutionary advance. While bacteria have learned how to add or subtract elements from their membranes – and do, often, to disguise themselves from the immune system – they cannot alter the basic phospholipid building block of their membranes.

There is even more to the story. In higher animals, their repertoire of AMP work in concert with their immune systems, giving T-cells and antibodies greater access to invade bacterial cells and defeat them – and more importantly, to recognize them and store that memory against future invasions. Additionally, commensal bacteria (the "helpful bacteria" that do things like help humans digest their food) seem to be considerably more tolerant of AMP and even play a role in stimulating the body to produce AMPs and keep the defenses active. This is part of why you are more likely to develop an infection after a course of treatment with broad-spectrum antibiotics that kill these commensal bacteria as well as the pathogenic ones.

So if antibiotics are unable to keep up with the rate of resistance and AMP are so much better, why aren’t we already using them? The answer is that pharmaceutical companies are exploring many potential AMP therapies but their nature makes them difficult to use as drugs. AMPs work in a mass-action fashion, mobbing a single bacterium with hundreds of copies and dozens of different specific AMPs; because of this, effective dosages of AMP are quite high and can result in potentially toxic side-effects. Still, topical uses of AMP are the most accessible application and several are in clinical trials or consideration by the FDA. Oral and systemic AMP drugs are still in development as scientists search for molecules with high activity that could be supplied in lower dosages, but the use of AMP in combination with antibiotics has resulted in some exciting drug cocktails of considerable potency.

AMP also have an array of very exciting applications even outside direct use as drugs, however. AMP molecules have been used as imaging probes, allowing doctors to better visualize the spread of a bacterial infection in the body. Biofilms of AMP have been shown to protect surgical instruments against airborne bacteria that could infect patients on the operating table. AMP genes have been introduced into crops such as tobacco and potatoes to noticeable improvement in their disease resistance. AMP constructs have also been shown to aid considerably in combating STDs, as well as the pulmonary infections associated with cystic fibrosis. A novel class of human therapeutics is even being explored that works by stimulating natural AMP production.

Antibiotics are powerful tools, but more and more doctors and researchers are turning to alternatives as resistance to antibiotics renders them ineffective. In the future, expect to see greater emphasis placed on peptide pharmaceuticals as an expanding answer to the threat of pathogenic bacterial infections – an answer that Nature has already tried and found effective for the last hundred million-odd years.

For more inforation:
Molecular strategies in biological evolution of antimicrobial peptides. P Nicolas, D Vanhoye, M Amiche – Peptides, 2003 [Link]

Antimicrobial Sequences Database (Tossi group, University of Trieste)

Antimicrobial peptides of multicellular organisms. Zasloff, Nature, 415 (24) 2002 [Link]

Antimicrobial Activity and Stability to Proteolysis of Small Linear Cationic Peptides with D-Amino Acid Substitutions. Hamamoto et al. Microbiology and Immunology
Vol. 46 (2002) , No. 11 pp.741-749 [Link]

© AQOS / Peter Smalley, 2009
Reproduction with attribution is appreciation

The Upside of Food Poisoning

2009-05-07T15:43:00.000-07:00

A QUANTUM OF SCIENCE

In the future, food poisoning might keep you from developing cancer

Food poisoning occurs when a microbial pathogen enters the food supply and multiplies, leading to a high enough concentration of viable cells to cause an infection when the food is consumed. Most frequently this is a gastrointestinal infection, leading to nausea and diarrhea as the body tries to flush the invader out of its system. In severe cases, especially among the very young and very old, severe cases of dehydration can result in death. This was the case during the recent outbreak of Salmonella in peanut butter, where hundreds were sickened around the US. But is there any upside to food poisoning?

Surprisingly, yes. One particular food-borne pathogen is a common bacterium known as Staphylococcus aureus. Most strains of this microbe are harmless and actually help protect you by competing with the more sinister strains and effectively out-growing them. A few strains are deadly, however, such as the growing frequency of hospital infections of MRSA (multiply-resistant S. aureus, strains that are resistant to all but the newest antibiotics). In between these two extremes are those strains of S. aureus that produce a special protein called staphylococcal enterotoxin. This protein, belonging to a class known as superantigens, is the immune system equivalent of shouting "BOMB!" in an airport. All the body’s defensive systems are activated and a red alert is sounded, sending active T-cells scrambling to produce antibodies and hopefully fight off whatever invader has come calling. But recent research has shown that this is not always a bad thing, at least in small, controlled doses. Enterotoxins have been shown to stimulate the immune system in novel ways, even to generating protective antibodies against unusual targets – targets such as the body’s own cancerous cells.

In their review article "Superantigens: The Good, the Bad, and the Ugly," researchers at Duke and the University of Florida tested the protective effect of superantigens when healthy mice were vaccinated with melanoma cells that had been chemically inactivated – making them unable to grow and become tumors, but allowing the mouse immune system to make antibodies against them. Some of these mice were then given a dose of superantigen (equivalent to a case of food poisoning, roughly speaking) and all the mice were exposed to live, infective melanoma cells. The usual result of this is death after 14 days from massive skin cancer tumors. In this study, however, the results were startling: 100% of the untreated mice in the study expired after 14 days; 100% of vaccinated mice after 17 days; but after 136 days only 40% of the vaccine+superantigen mice had expired, and none of these mice displayed any sign of melanoma tumors. The mice who survived to this stage were given another dose of live melanoma cells and 80% of them survived for another 50 days, showing that the protective antibodies were now a permanent part of their immune repertoire.

Does this mean you should go eat some potato salad that has sat at room temperature on the counter overnight? Well, no. First of all, only the T-cells that are actively making antibodies are stimulated by the superantigen; all others are switched off, the better to concentrate the body’s resources on making protective antibodies. This means that unless you are currently being exposed to an invader and making antibodies against it, receiving a dose of superantigenic staphylococcal enterotoxin isn’t going to do you any good (and while food poisoning won't kill you, the symptoms are far from pleasant). On the other hand, superantigen therapy has the potential to help the human body fight off infections that even modern antibiotics are helpless against. Imagine a patient infected with MRSA – now, his own immune system could be revved up by administration of superantigen and potentially mount a much stronger offense against the current, active infection. The irony here is that MRSA is also a member of the S. aureus species from which the superantigenic enterotoxin is derived, meaning that the invader itself has helped teach us how to fight off its more virulent sibling.

The potential for superantigenic anti-cancer vaccine therapies in humans is still a ways off, but not so far that it cannot be seen. Many researchers are looking for the most effective way to balance the protection gained from superantigenic treatment against the potential harms – which include a range of autoimmune diseases (such as multiple sclerosis and other degenerative disorders). Clearly the potential exists to improve human health and longevity against one of the most prevalent causes of mortality; and with a healthy dollop of caution, the downside of superantigens can be avoided.

Pass the potato salad.

Want to know more? Full text of the cited article can be found here:

http://www.ebmonline.org/cgi/reprint/226/3/164

© A Quantum of Science / Peter Smalley, 2009
Redistribution with attribution is appreciation!

Down With the Sickness

2009-05-06T19:59:00.001-07:00

A QUANTUM OF SCIENCE

Down With the Sickness,
or why you should be glad to have the flu now (as opposed to later)

Being sick is no fun. Congestion, fever, coughing – there’s nothing good about it. Or is there? For a single human being the answer may be "no" but for large groups of humans the grim reality of a multi-stage pandemic makes beating the rush a smart strategy.

First let’s talk about the adaptive immune system. Every time your body encounters a foreign protein such as a virus, your immune system kicks in and starts the process of identifying the invader, teaching other cells how to recognize it, and systematically degrading the virus wherever it is found in the body. There are many different cells involved in this process but the big players are the special white blood cells known as T-cells, B-cells, and macrophages. Just a few words about each will be sufficient for our later discussion.

T-cells mature in the thymus (hence "T") and are responsible for several important immune activities: secretion of cytokines (small chemical triggers that turn on various parts of the immune system), destruction of infected cells, and eventual suppression of immune response (if your immune system doesn't know when to turn off it eventually attacks itself). B-cells are maintained in the bone marrow (hence "B") and work by engulfing an invader, chewing it up and displaying bits and pieces of it on the cell surface. T-cells that are already on alert for the same invader bind to the B-cell and secrete cytokines telling the B-cell to multiply and mature, after which it churns out antibodies that bind to the invader and signal its destruction. B-cells that survive this process through multiple rounds are called memory B-cells and are the repository of much of humans’ adaptive immune repertoire. Finally, macrophages ("big eaters") literally swallow viral particles and even whole bacteria, digesting them and displaying bits and pieces of them in much the same way that B-cells do, eventually recruiting T-cells to flag the invader and make it easier to find and consume. A single macrophage can consume a hundred bacteria before its own digestive enzymes break it down from the inside.

Now that we now a bit more about the major players of the immune system, let’s talk about one particular invader: the influenza virus. A virus is a small bundle of proteins that can be thought of as a kind of microscopic mosquito, with long "legs" that latch onto a target cell and a dense "body" containing its own genes for making more copies of itself.

The influenza virus is a rough sphere or filament coated with proteins that bind to human cells using a protein called hemagglutinin (abbreviated HA) that works by binding to a particular sugar modification called sialic acid. Once bound, the cell "ingests" the virus in a special bubble called an endosome, the purpose of which is to isolate the virus and fuse the endosome with an acidic lysozome in order to degrade the virus down to harmless nuts and bolts. HA is specifically adapted to this use strategy against the cell, however; the acidic environment causes it to alter its shape and helps the virus escape the lysozome, where its RNA genes can be released directly into the cell and the copying process can begin. Once this happens, the cell cannot tell which RNA is viral and which is its own, so its cellular machinery begins turning viral RNA into protein – new copies of the virus – and the battle is effectively over for that cell.

The other major player for the influenza virus is called neuraminidase (NA), an enzyme that is critical for release of the many-times-copied virus out of the cell. The HA part of these copied viruses would like nothing better than to bind to the sialic acid in the cell wall once again, just as it did when entering the cell; in order to prevent that, NA cleaves the sialic acid off of sugar molecules in the cell membrane and helps the viral copies escape the cell and spread out to look for new cells to infect. Some of the most potent anti-influenza drugs currently available, including TamiFlu, specifically inhibit viral neuraminidase, a perfect target because humans do not possess that enzyme.

Because these two enzymes (hemagglutinin and neuraminidase) are so critical for the activity and pathogenicity of the influenza virus, virologists classify strains of influenza based on which versions of those two enzymes characterize that strain. There are 16 types of HA and 9 types of NA, meaning that there is a range of 144 individual influenza strains in this group. Strains of related pairings of these two enzymes compose the major classifications of the flu virus, such as the avian flu that was the specter of the 1990’s (H5N1) as well as the current strain of interest: H1N1 swine flu.

H1N1 is a subtype of the Influenza A class, and is composed of eight single-stranded RNA molecules that code for eight individual proteins. Unlike many viruses, however, these eight genes are not all part of a single long string of nucleic acid; and because they are physically separate, they lend themselves well to a process called reassortment in which a cell infected by different strains of the influenza virus will package genes from different viruses together into a new, hybrid virus. By analogy, imagine the cell as a car manufacturing plant: viral proteins are assembled into cars (viruses), all of which look pretty similar. The owner’s manual (RNA genes) that goes into each car, however, might be made up of pages taken from two different models (viral strains), so when a particular car (virus) later infects a new cell, the hybrid owner's manual it comes with gives rise to an entirely new model of car (virus). Reassortment is what allows influenza viruses from different species to commingle and generate new, more pathogenic hybrid strains of the virus, as well as helping them continue to elude the best efforts of the immune system to recognize and eradicate the virus. It also makes it difficult for scientists to predict which strain of influenza should be included in this year's flu shot. The current H1N1 model is what is known as a triple reassortment - a virus carrying genes from avian, swine and human influenza strains.

So what about the H1N1 model? Scientists are concerned about the current outbreak of H1N1 that began in Mexico in March 2009 because this model is also responsible for one of the worst pandemics in human history, the 1918 "Spanish Flu" epidemic. In just two years, between 70 and 100 million humans died due to this strain of flu, largely due to a specific pathogenicity that turned the human immune system into its own worst enemy. Remember the T-cells, the immune system player that secretes cytokines and stimulates the overall immune response? The 1918 strain of H1N1 was incredibly good at causing T-cells to secrete cytokines, to such an extent that the victims were overcome by what is now termed a "cytokine storm" in which a positive feedback loop was created between cytokines and immune cells. This is why the majority of victims of the 1918 epidemic were not the very young and very old, but rather healthy adults – their immune systems were the strongest, and thus most easily turned against them.

So far the North American H1N1 shows no signs of being capable of creating a cytokine storm effect in its victims. So we’re home free, right? As it turns out, it’s not that simple. Researchers who have charted the progression of the 1918 epidemic show a peculiar three-stage pattern in which the H1N1 strain killed 5 people per thousand in July of 1918, then 25 per thousand in November of that year, and finally 12 per thousand in March 1919. The current scientific explanation of this pattern, based on viral RNA extracted from well-preserved victims who died at different stages of the epidemic, is that there was a critical mutation of the strain in just four brief months between the first and second emergence of the H1N1 virus. Normally when a virus gains in strength its victims are more likely to stay home and not spread it, but in late 1918 World War I was still raging, and it is theorized that the concentration of military personnel around the world fostered the spread of the more pathogenic mutant. Because the mutant was so lethal, it actually inhibited its own reproduction and thus the third emergence showed another new mutant, this one less pathogenic. By that time the war was over and sociological pressures that favored the spread of the virus were far reduced; there was no fourth emergence.

So what does this teach us regarding the current H1N1 outbreak? Quite a bit, actually. Our world today is much different than the world of 1918. Air travel can now spread a virus around the world literally overnight, exposing vast numbers of people in a far shorter span than was ever true in the crowded field hospitals and trenches of World War I. The speed at which a pandemic could take hold in many major cities around the world means the window for an effective response time is also much shorter. On the other hand, we now know about cytokine storms and how to prevent them using a variety of drugs like corticosteroids, free radical scavengers and TNF-alpha inhibitors. Further, powerful drugs like TamiFlu provide an effective answer to pandemics, especially among healthcare professionals who are on the front lines in any major public health threat. And most reassuringly of all, epidemiologists are well aware of the possibility of pandemic and are, if anything, overeager in their efforts to spread the word about that possibility. This may create some annoying overdramatization in the media, but considering that electronic media now encircle the globe far faster even than air travel, any increase in public awareness remains the first, best line of defense against a pandemic outbreak.

And one more thing about the 1918 H1N1 pandemic: those who caught the earliest, least pathogenic strain of the virus were largely immune to later mutants. So if you’re a parent thinking about keeping your child out of school, or if the guy next to you at work keeps coughing in your direction, just remember that if things go bad, you’re probably better off catching that flu now when it’s in the mildest form – just in case.

For more information:

http://www.newscientist.com/article/dn17072-first-genetic-analysis-of-swine-flu-reveals-potency.html

http://www.newscientist.com/article/dn17077-flu-outbreak-the-pig-connection.html

http://www.cnn.com/video/?/video/health/2009/04/28/am.gupta.swine.flu.model.cnn

© AQOS, Peter Smalley (2009)
Distribution with attribution is appreciation

How now, brown cow?

2009-04-23T18:20:00.000-07:00

A QUANTUM OF SCIENCE

What do cows now have in common with dogs, guinea pigs, armadillos, lemurs, the platypus, slime molds and wild mustard?

Bessie is the latest member in the club of organisms with sequenced genomes.

At present this club consists of approximately twenty single-celled organisms, twenty-two plants and thirty-six animals (not to mention 360 bacterial species). The club was founded in 1995 with the sequencing of the bacterium Haemophilus influenzae. Humans joined in 2000, fashionably late. The bovine genome has taken six years of work by 300 scientists at a cost of a quite modest $53 million (compared to the Human Genome Project at a bit over $3 billion). The project was spearheaded by researchers at Baylor College of Medicine in Houston, Texas and the results are provoking a level of interest far in excess of other organisms recently sequenced. The last "big" genome to be sequenced was the mouse, whose importance as a research tool can hardly be overstated. Almost all pharmaceuticals and therapies used on humans are tested on mice, so understanding their genetic variability was a huge milestone. So why is the cow genome making such a stir?

Unsurprisingly, it has to do with money. The cow is the first animal to be sequenced that has a significant commercial value associated with it. And ranchers and dairy farmers are already starting to queue up to have their herds genotyped, hoping to find out which ones carry genes associated with increased milk production, better tissue-building properties (read: faster meat) and improved resistance to pathogens. From a scientific basis this latter trait is among the most fascinating: even though cows diverged from the evolutionary tree before mice and well before humans, they share more genes in common with humans than they do with mice. In part this may be due to the far faster reproduction of mice giving them more generations to evolve, but there is some suggestion that humans and cows evolved more along similar tracks because of their symbiotic relationship over the last 10,000 years – in other words, domestication.

There were some definite surprises when the full map of the bovine DNA record was analyzed. Of particular note is the degree of repetition in their genome. Genes coding for immune defenses exist in myriad copies in the bovine genome compared to humans, perhaps due to the significantly greater exposure they have to microbes associated with digestion of cellulose. Curiously, the same thing may have caused cows to lose the genes for certain digestive enzymes from their genome that humans retained – since microbes were doing the digesting for them, cows did not need to retain those genes.

What good can come from this project? The significant benefit of knowing the blueprint for cows lies primarily in breeding. Currently most cattle breeding centers on bulls, and the cost to bring a single bull to an age where it can be bred is between $25,000 to $50,000 – and there are no guarantees a particular bull will make good breeding stock. Now, breeders can test bulls shortly after birth and determine which ones will make the best stock for particular desirable traits, saving tremendous amounts of money and making the process far less fraught with uncertainty and error. Best of all, breeding programs can now begin to reduce the dairy industry’s reliance on additives like rBST, the recombinant bovine somatotropin (better known as bovine growth hormone), a product used since 1993 as a means of increasing milk production but which has caused considerable controversy regarding the health of the animals in which it was used.

As a result of the sequencing of the bovine genome, the beef and dairy industries are poised for a potential rebirth as modern genetic techniques become available and better decisions can be made to improve the health of the industry, the consumer, and the cows.

For more information:

http://sciencenow.sciencemag.org/cgi/content/full/2009/423/2

http://en.wikipedia.org/wiki/List_of_sequenced_eukaryotic_genomes

© AQOS, Peter Smalley (2009)
Distribution with attribution is appreciation

A Quantum of Science

2009-04-22T18:55:00.000-07:00

"No subject must be taught as if it were a quantum of science to be learnt by heart; it would become a dead weight in the memory of students, engendering nothing but boredom and a desire to get rid of it as soon as possible. It does not matter whether the pupils know or do not know a great amount of detail; they must participate with their very soul in the truth they are being taught."

- Bacelli, Italian Minister of Education (1919)