Rain clouds: From dust to lawn

Clouds turn to rain when water droplets and ice crystals that make them up get too big to resist the pull of Earth’s gravity. This is often caused by particles that disturb the maelstrom of droplets and crystals to become seeds around which cloud matter coalesces. Once this happens, the seeds grow rapidly and eventually fall to the ground.

The seeds can be caused by the passage of exotic things like cosmic rays. More often, though, they are dust particles lofted high into the air. A study in 2009 showed that dust from Taklimakan desert in China, whisked above 5,000 metres, circumnavigated the globe in just 13 days. Because dust needs large horizontal distances to attain sufficient altitude, it might then cause rainfall half-way across the world.

For example, the Rocky Mountains in America push water vapour to higher altitudes that help form clouds. At that point, the theory goes, the clouds run into particles swept in from Africa and Asia. To find if that is indeed what happens Kaitlyn Suski and her colleagues at the University of California, San Diego, examined dust and clouds in Californian skies, to the Rockies’ west. They report their findings in Science.

Ms Suski needed to confirm that dust particles reached heights of about 3,000 metres or more to be able to intercept rain clouds. She also had to verify that they originated in Asia and Africa. She collected samples in an aeroplane equipped with a mass spectrometer, which can accurately determine the dust’s chemical composition. These chemical signatures were then compared with those found in Asian and African deserts. As a cross-check, Ms Suski used data from satellites like CALIPSO, which tracks dust particles’ atmospheric peregrinations.

Perhaps more interesting, Ms Suski also found that rain clouds contained bacteria, though it proved impossible to pin down their origins. Tiny living organisms can float in the atmosphere for a long time, feeding on trace carbon and any other nutrients they bump into. They can also act as cloud seeds.

In 2010 researchers in Norway concluded that bacteria are not as important to rainfall as dust is. But calculations by Ms Suski and her colleagues suggest that their rainmaking powers are amplified when they mingle with desert dust. Deserts may be some of the harshest places on the planet to live, but, if Ms Suski is right, they may be the enablers of life everywhere else.

First published on economist.com.

Reference: Creamean et al. Science 2013. Dust and Biological Aerosols from the Sahara and Asia Influence Precipitation in the Western U.S. http://dx.doi.org/10.1126/science.1227279

Image credit: The Economist

Marine biology: Flea market

A newly discovered virus may be the most abundant organism on the planet

What is the commonest living thing on Earth? Until now, those in the know would probably have answered Pelagibacter ubique, the most successful member of a group of bacteria, called SAR11, that jointly constitute about a third of the single-celled organisms in the ocean. But this is not P. ubique’s only claim to fame, for unlike almost every other known cellular creature, it and its relatives have seemed to be untroubled by viruses.

As Jonathan Swift put it in a much-misquoted poem, “So, naturalists observe, a flea/Hath smaller fleas that on him prey”. Parasites, in other words, are everywhere. They are also, usually, more abundant than their hosts. An astute observer might therefore have suspected that the actual most-common species on Earth would be a “flea” that parasitised P. ubique, rather than the bacterium itself. The absence of such fleas (in the form of viruses called bacteriophages, that attack bacteria) has puzzled virologists since 1990, when the SAR11 group was identified. Some thought the advantage this absence conferred explained the group’s abundance. But no. As they report in this week’s Nature, Stephen Giovannoni of Oregon State University and his colleagues have discovered the elusive phages. Swift’s wisdom, it seems, still holds good.

Tracking down a particular virus in the ocean makes finding a needle in a haystack look a trivial task. A litre of seawater has billions of viruses in it. Modern genetic techniques can obtain DNA sequences from these viruses, but that cannot tie a particular virus to a particular host.

To do so, Dr Giovannoni (pictured) borrowed a technique from homeopathy: he diluted some seawater to such an extent that, statistically speaking, he expected a 100-microlitre-sized aliquot to contain only one or two viruses. The difference between his approach and a homeopath’s was that what homeopathy dilutes almost to nothing are chemicals, and thus cannot breed. A virus can, given a suitable host. So he mixed each of several hundred aliquots into tubes of water containing P. ubique. Then he waited.

The race is to the Swift

After 60 hours, he looked to see what had happened. In most cases the bacteria had thrived. In a few, though, they had been killed by what looked like viral infection. It was these samples that he ran through the DNA-sequencing machine, in the knowledge that the only viral DNA present would be from whatever it was had killed the bacteria.

His reward was to find not one, but four viruses that parasitise P. ubique. He then compared their DNA with databases of DNA found in seawater from around the world, to find out how abundant each is. The upshot was that a virus dubbed HTVC010P was the commonest. It thus displaces its host as the likely winner of the most-common-living-thing prize.

That does depend, of course, on your definition of “living thing”. Some biologists count viruses as organisms. Some do not. The reason is that a virus relies for its growth and reproduction on the metabolic processes of the cell it infects. This means viruses themselves are hard to parasitise, since they do no work on which another organism can free-ride. Which is why the next two lines of Swift’s poem, “And these have smaller fleas to bite ’em/And so proceed ad infinitum”, are wrong—and why, because HTVC010P itself can have no parasites, it probably really is the commonest organism on the planet.

First published in The Economist.  Also available in audio here.

References:

  1. Zhao et al., Abundant SAR11 viruses in the ocean, Nature2013.
  2. Brown et al., Global biogeography of SAR11 marine bacteria, Mol Syst Biol2012.
  3. Swift, Poetry: A Rhapsody, 1733.

Image credit: Lynn Ketchum

Drug development: Teaching old pills new tricks

Exploding research costs and falling sales: there seems to be no cure for the pharma industry’s two big afflictions. But it may have found a way to both cut costs and open up new markets: repurposing drugs already approved for treatment of one disease or those that failed to gain approval in the late stages of development. Alas, this is not as easy as it sounds—mostly for legal reasons.

Finding new uses for old or failed drugs is on average 40% cheaper than inventing a new drug from scratch: it allows to skip the early stages of development. Since coming up with a new drug can cost more than $1 billion, such savings are nothing to sneeze at. Repurposing also trims the risk of failure because new drugs hit a dead end mostly during the early stages of development.

In 2007, a report in Nature, a science journal, counted 41 drugs that have found new uses. But there should be many more, experts say. This is why America’s National Institutes of Health, the country’s biggest government agency financing drug research, and the Medical Research Council, its British counterpart, each have launched new grant programmes. Worth $20m and £10m ($15m) respectively, they are meant to allow university researchers analyse failed drugs from big pharma firms such as Pfizer, AstraZeneca and Eli Lilly and see whether they can be repurposed.

Yet such schemes are not enough, as work by Grant Churchill, a researcher at Oxford University, shows. In a recent paper in Nature Communications, another science journal, he describes how he and his colleagues looked for a drug to treat bipolar disorder, which causes uncontrollable mood swings. Instead of developing a new compound, they tested a library of known ones and found that ebselen, a drug first developed to treat stroke, was a candidate. Their claim, based on animal tests, is that ebselen is as good as and much safer than lithium, currently considered the best treatment for bipolar disorder.

But this was where things hit a hurdle that is hard to overcome. Universities do not have the money to further develop promising drug candidates that need to be tested on a large scale. Expensive human trials are usually carried out by pharma firms, which own the patent for a drug and thus can hope to make their money back. But in the case of many repurposed drugs, like ebselen, the patent has expired. Filing for a new one, which is possible, is not of much help: patients could simply buy versions of the drug which are already available from other makers.

One way of solving this problem would be to change the patent system, for instance by extending the length of patent protection, but this could hamper innovation in other ways. A better solution, argues Benjamin Roin, a law professor at Harvard University, is to have regulators grant the drugmaker that has repurposed the drug some exclusivity and thus time to recover research costs: it is rare that a drug is used in the same form and the same dosage for two different diseases; regulators could wait a few years before they allow other firms to offer the drug for the new purpose. If old drugs can learn new tricks, regulators should do so, too.

First published on economist.com.

References:

  1. Singh et al., A safe lithium mimetic for bipolar disorder, Nature Communications2013.
  2. DiMasi et al., The price of innovation: new estimates of drug development costs, Journal of Health Education2003.
  3. Chong & Sullivan, New uses for old drugs, Nature2007.
  4. Roin, Unpatentable Drugs and the Standards of Patentability, Texas Law Review2009.

Image credit: The Economist

Cancer drugs: Refusing to die

Suicide is a part of life. Whenever any of the 100 trillion or so cells that make up the human body malfunction, which happens all the time even in healthy tissue, they are programmed to provoke their own death. The mechanism hinges on a protein called TRAIL, which is produced by the damaged cell and binds to receptors on its surface, causing inflammation. That is a signal for the immune system to sweep in and, through a process called apoptosis, break down the damaged cell and recycle its parts to feed healthy ones. If this self-destruct is subverted, however, the result is a tumour.

When TRAIL’s tumour-suppressing ability was first discovered in 1995 researchers hoped that by discriminating between cancer cells and healthy ones, TRAIL would do away with the debilitating side-effects associated with traditional treatments like radio- and chemotherapy. These are good at destroying tumours but also cause lots of collateral damage. Unfortunately, it turned out that simply injecting a synthetic version of the molecule into the patient’s body provoked only a limited immune response in a handful of cancers.

That, says Joshua Allen from the Pennsylvania State Cancer Institute, was because people assumed that cancer’s subversion of TRAIL consisted merely in halting the molecule’s production within the cell. It turns out, however, that cancerous cells also suppress their TRAIL receptors, so no amount of synthetic TRAIL sloshing about would ever be enough. What you need, Dr Allen reasoned, is something to reboot the TRAIL-producing pathway within cells as well as to unblock their TRAIL receptors. Only then would the immune system be spurred into action.

So he and his colleagues sifted through a library of molecules maintained by America’s National Cancer Institute and found a molecule, called TIC10, whose biochemistry seemed to fit the bill. When enough of these molecules accumulate in a cancer cell, they activate a protein called FOXO3a. This binds to DNA and flips on many biological pathways, including those involved in the TRAIL mechanism that lead to the immune-system alerting inflammation.

As Dr Allen and his colleagues report in Science Translational Medicine, tests in mice with brain tumours confirmed the biochemical hunch. Murine subject given TIC10 lived twice as long as those that received no treatment. The drug also worked for lymphoma, as well as breast, colon and lung cancers. And it did not seem to cause the wasting side-effects typically associated with chemotherapy, suggesting that it can indeed tell cancer cells from healthy ones. As an added bonus, TIC10 is small compared to TRAIL, and cheaper to concoct than the complex protein is.

Last year Dr Allen secured a $1.3m grant from Pennsylvania’s department of health to begin clinical trials. These will be carried out in collaboration with Oncoceutics, a drug company. Nine out of ten promising molecules which work in mice fail in humans, so “Cure for cancer” headlines must wait. If TIC10 does live up to its promise, though, it would make one killer app.

First published on economist.com.

Image from here

A nebulous future

Before Apple launched iCloud in 2011, Steve Jobs allegedly offered to buy Dropbox, a file-sharing service founded in 2007, for $800m. When Dropbox declined, Apple’s late boss disparaged it as a feature, not a company. Soon after, Dropbox raised $250m, putting its value at over $4 billion. Earlier in December Dropbox concluded a promotional campaign that, in just a few weeks, added 2m new users, bringing the total to over 100m, roughly double the number when Jobs made his comment. Consumers, it seems, can’t get enough of the feature.

Dropbox dominates online file-sharing. It boast three times as many users as its closest direct rival, YouSendIt. (Its dominance is even more pronounced when it comes to the volume of data stored.) It eats up 20% of all bandwidth consumed globally by browser-based file-sharing services, against 1% for YouSendIt. Dropbox users save more than 1 billion files every day.

Most of them use the free version of the service. The company makes money by charging for extra storage. Around 4% of users plump for the premium version, though the proportion is growing, according to Arash Ferdowsi, one of the Dropbox’s co-founders. The recent campaign, called Space Race, gave away free space to university students in return for getting their peers to sign up to the service. The hope is that when access to this extra storage runs out after two years, the students, by then freshly-minted professionals, will pay to keep using it.

Dropbox relies on individuals and small firms, for whom its rudimentary security features are good enough; bigger businesses with sensitive information prefer more secure services like Box.net. The advent of competitors in the nebulous form of iCloud, Google’s Drive and Microsoft’s Skydrive, which come pre-installed on their respective makers’ gadgets, does not seem to have dampened enthusiasm for Dropbox. Unlike iCloud, which boasted 190m users by October thanks to its deep integration with Apple’s mobile devices, the service is “platform neutral”—ie, works across different devices and operating systems—and allows easy file-sharing, both useful traits in an increasingly connected world where few people hew devoutly to a single device-maker.

Google and Microsoft clouds emulate Dropbox in these respects. But at a little over 10m users each, they do not yet benefit from from the incumbent’s powerful network effect. If you are sharing files with a dozen other people on Dropbox, a move to Google or Microsoft would require all 12 to move with you.

Dropbox is also striving to make itself the default choice for smartphone users. In 2011 it struck a deal with HTC, a Taiwanese phonemaker, to preinstall Dropbox on its Android devices. In return it gives HTC users 5GB of space for free. HTC has been struggling of late, but Mr Ferdowsi says that his company is in talks with other manufacturers, hoping for similar arrangements.

A bigger long-term worry is the plummeting price of digital storage. With its vast scale, Amazon has driven down costs substantially for the likes of Dropbox, which leases server space from the e-commerce giant. But Google Drive already offers 100GB for $5 a month, half what Dropbox charges for the same amount of storage. And Google can advertise its cloud across its myriad online offerings. Dropbox’s margins are only likely to get wispier in the future.

First published on economist.com.

Image credit: Dropbox

Crowdsourcing ideas

What if you could use a lensless, portable microscope to detect microbes in the air? This did not occur to the designers of the apparatus, which cost hundreds of thousands of pounds to develop but was lying unused in a storeroom at Oxford University. But it did occur to James Dash, a 15-year-old pupil at John Hampden Grammar School in High Wycombe, Buckinghamshire. His winning proposal was one of 51 entries in a competition run by Marblar, a website for crowdsourcing ideas.

CyMap, researchers’ name for the device, is one of countless clever gizmos and techniques mothballed as solutions in search of a problem. An estimated 95% of all technologies coming out of universities never make it to the real world. Marblar, which was launched in September by a bunch of PhD students in Britain, aims to harness the collective imagination to prevent such waste. Other ongoing competitions invite people to come up with uses for a new kind of foam, a probe inspired by a wasp sting or paint-guns to squirt layers of paint just few molecules across.

The original inventors pay a small fee to post a challenge on Marblar’s website, using videos and slideshows to explain in plain English how their technology works. Geeks of all ages then submit their ideas about what it might be used for. Other users rate these before the inventors themselves pick the winner, who typically receives a cash prize of about £500 ($800). In future, says Daniel Perez, one of Marblar’s co-founders, winners may be invited to partner with the inventors and gain a stake in the commercialisation of their joint intellectual effort.

Marblar will not eliminate all waste. Many inventions have straightforward uses, says Lita Nelsen, director of the (rather busy) technology-licensing office of the Massachusetts Institute of Technology, all they need is better marketing. This is something technology transfer officers, often business-minded boffins who are able both to identify prospective licensees and explain the research to a non-scientist, may be better placed to do.

But Marblar is definitely onto something. IP group, a British venture-capital firm that invests in innovations spun out of universities, has ploughed about $600,000 into the start-up. It is already considering creating a company to commercialise a technology to glue strands of DNA without using an enzyme. In another challenge, a PhD student from Cambridge noticed that this is just the sort of thing he needed in his work on novel methods for drug delivery.

First published on economist.com.

Image credit: Marblar

A revolution in lens-making

Understanding of optics has changed no end since the world’s oldest known lens was ground nearly 3,000 years ago in modern-day Iraq. Yet its Assyrian maker would instantly recognise today’s lenses, which continue to be made much as they were then: by fashioning a piece of transparent material into a solid with curved surfaces. Just as invariably, the curves introduce optical aberrations whose correction requires tweaking the lens’s geometry in complicated ways. As a consequence, lenses remain bulky, especially by the standards of modern electronics.

Enter Federico Capasso, of Harvard University. He and his colleagues have created a lens that is completely flat and the width of two human hairs. It works because its features, measured in nanometres (billionths of a metre), make it a “metamaterial”, endowed with some weird and useful properties.

According to the laws of quantum mechanics, a particle of light, called a photon, can take literally any possible path between source A and point B. However, those same laws stipulate that the path of least time is the most likely. When a photon is travelling through a uniform medium, like a vacuum, that amounts to a straight line. But although its speed in a vacuum is constant, light travels at different (lower) speeds in different media. For example, it moves more slowly in glass than it does in air. So in a medium composed of both air and glass, light’s most likely path from A to B will depend on the thickness of glass it needs to traverse, as well as the total distance it needs to cover. That means that the light may sometimes prefer to bend. This is the quantum-mechanical basis of refraction.

In order to maximise the probability that photons from A will end up precisely at B, those going in a straight line need to be slowed down relative to those taking a more circuitous route, so that, in effect, all hit B the same time. This can be done by forcing the former to pass through more glass than the latter. The result is a round piece of glass that is thick in the middle, where the straight-line path crosses, and tapers off towards the edge, where the less direct routes do—in other words, a focusing lens, with its focal point at B.

Dr Capasso’s lens, described in Nano Letters, also slows photons down. But instead of using varying thickness of glass to do the job, he and his team created an array of antennae which absorb photons, hold on to them for a short time and then release them. In order for this trick to work, though, the distance between the antennae has to be smaller than the wavelength of the light being focused. In Dr Capasso’s case that means less than 1,550 nanometres, though he thinks that with tweaking it could be made to work with shorter-wavelength visible light, too.

Creating the array involved coating a standard silicon wafer, 250 microns thick, with a 60-nanometre layer of gold. Most of this layer was then stripped away using a technique called electron-beam litography, leaving behind a forest of V-shaped antennae arranged in concentric circles. By fiddling with their precise shape, after much trial and error, antennae lying on different circles could be coaxed into holding on to the photons for slightly different lengths of time, mimicking an ordinary glass lens. The whole fragile system can be sandwiched between two sheets of transparent material to make it more robust.

At present the new-fangled lens only works for monochromatic light and so is unlikely to replace the glass sort in smartphone cameras anytime soon. But it could revolutionise instruments that rely on single-colour lasers, by making further minaturisation possible while eliminating the optical aberrations inherent to glass lenses. Such devices include laser microscopes, which are used to capture high-resolution images of cells, or optical data storage, where a more accurate and smaller lens could help squeeze more information into ever less space.

First published on economist.com.

References: 

  1. Capasso et al., Aberration-Free Ultrathin Flat Lenses and Axicons at Telecom Wavelengths Based on Plasmonic Metasurfaces, Nano Letters2012.
  2. Capasso et al., Light Propagation with Phase Discontinuities: Generalized Laws of Reflection and Refraction, Science2011.

Also appeared in The Economist. Also available in audio here.

Image credit: Francesco Aieta