2012: Year in review

C&I Issue 11, 2012

Medicines on chip

It could be the future for drug delivery: an implantable microchip that releases a patient’s medication at the push of a remote-controlled button. In February, researchers in Denmark reported the results of the first clinical trial of such a wirelessly controlled microchip – to deliver an osteoporosis drug (Science Transl. Med., doi: 10.1126/scitranslmed.3003276). The team implanted the pacemaker-sized chip just below the waistlines of seven women with the disease, aged between 65 and 70, and reported that the implant delivered the drug teriparatide just as effectively as daily injections for 12 months. Biomarkers indicated improved bone formation and a reduced risk of bone fracture.

The microchip could be an alternative to daily drug injections for severe osteoporosis sufferers and may boost quality of life and patient compliance. It could have much wider application beyond teriparatide, and may one day allow doctors to adjust a patient’s medication by computer or smartphone.

Electricity from wastewater

A compound similar to baking powder could be the key to producing electrical energy from wastewater, researchers reported in March 2012. Their findings suggest that sewage treatment plants could one day be harnessed to produce energy rather than consuming it as they do today. The group from Pennsylvania State University in the US combined two types of energy-producing technologies in a bid to improve efficiency: a microbial fuel cell and a reverse electrodialysis system (Science, doi: 10.1126/science.1219330).

In a microbial fuel cell, microbes consume plant or human waste and generate an electrical current. In reverse electrodialysis, solutions of saltwater and freshwater are pumped across specialised membranes that allow only positively or negatively charged ions through; movement of these ions towards their respective electrodes generates an electrical current. By using ammonium bicarbonate as the fuel for reverse electrodialysis, rather than the usual seawater, the researchers were able to regenerate the salt solution continuously by harnessing small amounts of heat such as are produced by waste treatment. The group reported that their microbial reverse-electrodialysis cell (MRC) produced 0.94kWh of electricity/kg of wastewater organic matter, against an energy consumption of 1.2kWh/kg on treatment with activated sludge.

Insecticide harms bees

It had long been suspected, but in March 2012, two groups of researchers finally reported evidence that neonicotinoid insecticides, among the world’s most widely used pesticides, are harmful to bees. Both honeybee and bumble populations have declined rapidly in recent years, with multiple causes blamed for the fall in numbers. In the first study, researchers at the universities of Stirling and Lancaster exposed developing colonies of bumblebees to low levels of the insecticide imidacloprid, then placed them in an enclosed field site for six weeks (Science, doi: 10.1126/science.1215025). Compared with the control bee colonies that had not been exposed to imidacloprid, the treated colonies were on average 8 to 12% smaller than the control colonies at the end of the experiment – and produced about 85% fewer queens.

In the second study, researchers in France tagged free-ranging honeybees with tiny RFID microchips that were glued to each bee’s thorax. They then gave some of the bees a sub-lethal dose of the pesticide thiamethoxam and tracked the insects as they came and went from their hives (Science, doi: 10.1126/science.1215039). They reported that the treated bees were two to three times more likely to die while away from their nests and predicted by mathematical computation that honeybee populations exposed to the pesticide would drop to a point from which it would be difficult to recover – putting them at risk of colony collapse disorder.

However, subsequent research by the UK’s University of Exeter and the Food and Environment Agency, reported in the autumn, argues that the calculations in the latter study included an inappropriately low birth rate (Science, doi: 10.1126/science.1224930). When the experiment was repeated with a higher birth rate value, the researchers found the risk of colony collapse disorder disappeared.

Gene therapy for smokers

Gene therapy with an anti-nicotine antibody may one day help smokers to kick the habit by stopping the drug from reaching the brain and activating pleasure receptors, US researchers reported in June. The group, from Cornell University and Scripps Research Institute, slipped the genetic sequence of the antibody into a gene therapy carrier or vector and injected it into nicotine-dependent mice (Sci. Transl. Med., 2012, 4, 140ra87). Animals given the therapy continuously made antibodies to mop up any circulating nicotine before it reached the brain. Their brains were claimed to have only 15% of the level of nicotine seen in untreated mice. The approach may be an alternative to an anti-nicotine vaccine, which has proved difficult to make as nicotine is too small to be recognised by the immune system.

A cracking answer

Materials cracking or fracture is a phenomenon that is generally best avoided. But in May 2012, researchers at Ewha Womens University in Seoul, Korea, demonstrated how cracks may be controlled and potentially put to good use in nanofabrication (Nature, doi: 10.1038/nature11002). The group described producing straight, oscillating and stitch-like cracks in a thin brittle film deposited on a silicon wafer. They were even able to control the direction of the cracks and bend them around corners – and terminate the fracture process at special stop structures engineered into the silicon structure.

The researchers were able to control crack formation by etching notches on the silicon wafer that produce stress points in the overlying brittle film, and by choosing the appropriate crystal orientation of the underlying silicon. The method could lead to the development of a cheaper and quicker route to produce nano-patterns for lab-on-a-chip type applications, such as single-molecule sensing, and can be easily scaled-up without affecting the cost and processing time, they say.

Biofuel cells from roaches

It sounds like something that surrealist writer Franz Kafka might have dreamed up, but researchers have created a living biofuel system by generating electricity from a live cockroach, they reported in early 2012 (JACS, doi: 10.1021/ja210794c). The scientists, from Case Western Reserve University in Cleveland, US, inserted a pair of electrodes into the insect’s circulatory system, which carries nutrients including the sugar trehalose around the insect’s body. One of these electrodes, the anode, was impregnated with two enzymes that break down trehalose, while the other electrode, the cathode, contained an oxidase enzyme. Electrons released at the anode after the breakdown of trehalose travelled to the cathode where they combined with oxygen from the atmosphere to generate water. The resulting biofuel cell was able to generate a current density of up to 460µA/cm2, with potential applications including rechargeable insect sensors for detecting atmospheric pollutants.

World’s toughest material

Wonder material graphene got even more wonderful this year with the development in February of a new graphene composite claimed as the world’s toughest fibre – tougher even than Kevlar or spider silk (Nature Communications, doi: 10.1038/ncomms1661). Produced by a team of international researchers, the fibre comprises sheets of graphene interlocked by carbon nanotubes and surrounded by chains of polyvinyl alcohol polymer. While the polymer chains allow for elongation of the material, the nanosheets and graphene provide a stiffening effect and help to stop the growth of cracks. As well as being useful for reinforcing advanced composites as in aircraft, the researchers speculated that they may be woven into vehicle safety belts where they could potentially absorb ‘enormous’ amounts of energy during a collision.

Self-healing hydrogels

Whe curious jelly-like properties of hydrogels have made them widely useful for medical implants such as contact lenses, among other applications. In March, researchers reported the creation of a potentially even more useful self-healing hydrogel that repairs itself in seconds upon simply changing the surrounding pH (Proc. Nat. Acad. Sci., doi: 10.1073/pnas.1201122109).

The trick was to arm the hydrogel with dangling side chains capable of interlocking separate pieces of hydrogel by hydrogen bonding, the researchers at the University of California, San Diego, US, reported. ‘The dangling bonds were designed to have an optimal length to mediate hydrogen bonds across two hydrogel pieces like interlocking fingers in a clasped hand,’ said report author Shyni Varghese. However, they were not so long that they collapsed back into the hydrogel, she added. The group coated various surfaces with the resulting hydrogel and then damaged them with cracks, which healed rapidly on exposure to low pH solutions and over a range of temperatures, light and humidity conditions. New applications for self-healing hydrogels could include drug delivery devices.

Drug grown in carrots

The first approval for a drug grown in genetically engineered plant cells was granted by US regulators in early summer 2012 – a development that could pave the way for more drugs produced in plants.

The drug, taligluciferase alfa (Elelyso), replaces an enzyme lacking in people with type 1 Gaucher’s disease, a rare genetic disorder that leads to the accumulation of lipids and fats inside cells (C&I, 2012, 6, 9). Pfizer/Protalix’s Elelyso fared at least as well as another commercially available enzyme replacement therapy in clinical trials.

It is the first approved plant-cell expressed drug derived from Protalix’s proprietary manufacturing system, ProCellEx. The company is also developing another protein produced in carrot cells to treat another enzyme-related disorder, Fabry disease.

Vaccine for hay fever

Those afflicted with the seasonal curse of severe hay fever may be able to look forward to a time when they can go outdoors without fear of an attack, judging by the results of new vaccine trials reported this summer (C&I, 2012, 7, 15). The vaccine’s developers at Vienna, Austria-based biopharma company Biomay claim that it will offer a big improvement over current immunotherapy approaches, used where antihistamines or nasal steroids fail, as it will only require three to four annual injections. Conventional immunotherapy typically requires 60 to 100 injections.

The vaccine, BM32, is made by fusing B-cell peptides from the grass pollen allergen with an immunogenic carrier protein from a virus. In a Phase 2a study, patients receiving three doses of either 20µg or 40µg of BM32 over two months showed a significant reduction in their nasal symptoms and a boost in immunoglobulin antibody levels, it was claimed. Lindsey McManus of Allergy UK described the therapy as ‘a very exciting prospect.’

Element 113 nailed

Researchers in Japan got the first fleeting glimpses of element 113 back in 2004 and 2005. However, it was not until September 2012 that the same group finally obtained enough evidence to support their claims to name the element. The new results, produced in experiments at the RIKEN Radioisotope Beam Factory (RIBF) near Tokyo, identify the element conclusively through connections to well-known daughter nuclides formed on decay of element 113 (Journal of Physical Society of Japan, doi: 10.1143/JPSJ.81.103201).

While the group’s earlier work had observed only four decay events followed by spontaneous decay of dubnium-262 (element 105), the new data indicate that dubnium decayed into lawrencium-258 (element 103) and finally into mendelevium-254 (element 101). It was this alpha decay to lawrencium that provided proof of element 113 as the origin of the chain.

To carry out the experiment, RIKEN’s Kosuke Morita and colleagues accelerated zinc ions towards a thin layer of bismuth in a linear accelerator to produce the heavy ion, and then tracked the ensuing decay processes. The group had been looking for evidence of element-113 for over nine years, Morita commented. ‘At last we have it. It feels like a great weight has been lifted from our shoulders.’

Google map for genome

DNA has become even more interesting after researchers have discovered how much more of it is useful than was first thought. The Human Genome Project produced an almost complete order of the 3bn pairs of chemical letters in life’s genetic blueprint. However early researchers suggested that all but a tiny percentage of this material was redundant junk.

In September 2012, studies by the worldwide Encode (Encyclopaedia of DNA elements) consortium – involving more than 440 researchers in 32 labs around the globe – overturned that idea for good by linking more than 80% of the human genome sequence to a specific biological function and mapping more than 4m regulatory regions where proteins specifically interact with DNA.

‘The Encode catalogue is like Google Maps for the human genome,’ said Elise Feingold, one of the Encode project founders. ‘The Encode maps allow researchers to inspect the chromosomes, genes, functional elements and individual nucleotides in the human genome in much the same way.’

The findings are published in 30 papers in Nature, Genome Research and Genome Biology (www.nature.com/encode).

Polymers that resist bacteria

Infections caused by medical devices are estimated to cost the UK’s NHS around £1bn/year. But in August 2012, scientists at the UK’s University of Nottingham reported a new class of polymers – weakly amphiphilic acrylates – that are resistant to the attachment of the bacteria responsible for many of these hospital-acquired infections and device failures.

The group hit upon the polymers after screening hundreds of materials simultaneously using high throughput technology developed by researchers at Massachusetts Institute of Technology in the US. In laboratory experiments, the polymers were able to reduce the number of bacteria attached to their surfaces by up to 96.7% compared with a commercially available silver-containing catheter – and succeeded in resisting microbial attachment in a mouse implant model (Nature Biotechnol., 2012, doi: 10.1038/nbt.2316).

Biobutanol takes first steps

The world’s first commercial-scale biobutanol plant came onstream in May 2012, in Luverne, Minnesota, US. The firm was highlighted as the front-runner of a ‘wave of companies’ that have either begun or are about to start manufacturing a variety of novel chemical products – distinct from bioethanol and biodiesel – derived from plants (C&EN, 2012, 90, 38, 10). Titled Biobased summer, the feature also lists LS9, Reverdia, Rivertop Renewables, Solazyme and ZeaChem as among the firms with production facilities scheduled to start-up biobased chemicals operations this year.

Biobutanol is regarded as a superior motor fuel compared with ethanol as it has a considerably higher energy density – more than 80% that of gasoline. Unlike ethanol, which is more miscible with water, it is more compatible with existing fuel infrastructure and could be blended with petrol to higher concentrations, potentially up to 15-16% by volume. Biobutanol was made at Luverne by retrofitting Gevo Integrated Fermentation technology (GIFT), including its proprietary yeast, to the firm’s ethanol plant.

Like all fledgling technologies, however, things can sometimes go wrong. Seventeen weeks into production, at the end of September Gevo announced that it had halted biobutanol manufacture to sort out fermentation issues. It expects to restart production in 2013.

Temporary fix for blindness

Scientists have discovered a chemical that offers a temporary fix for blindness, they reported in July 2012. The chemical, AAQ (acylamide-azobenzene-quaternary ammonium), is a photoswitch that binds to protein ion channels on the surface of retinal cells. When switched on by light, AAQ alters the flow of ions through the channels and activates neurons similarly to the light sensitive cells – rods and cones – in the retina.

After injecting tiny amounts of AAQ into the eyes of blind mice, UC Berkeley professor of molecular and cell biology Richard Kramer and colleagues observed that the mice’s pupils contracted in bright light, and they showed light avoidance, which would have been impossible before the treatment (Neuron, 2012, 75(2), 271).

The group is hopeful that the approach could one day be extended to restore vision in people with retinitis pigmentosa, the most common inherited form of blindness, and age-related macular degeneration, the most common cause of acquired blindness in the developed world. In both cases, the rods and cones in the retina die, leaving the individual without functional photoreceptors.

The team is now working on new versions of AAQ that restore vision for days rather than hours in the original paper. A chemical could offer a safer alternative to gene or stem cell therapies, which permanently alter the retina, and is less invasive than implanting light-sensitive electronic chips in the eye.

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