Author: David Bradley

Planning for Disease – An international response

David Bradley at the Royal Society, January 2004

SARS appeared in a world that is plagued by many emerging and re-emerging diseases that occur on every continent not just the developing world, stated Dr David Heymann WHO’s Executive Director of Communicable Diseases. Keep the map of global map of outbreaks current is challenging. For instance, at the time of the meeting there were outbreaks of a high-mortality respiratory syndrome in Afghanistan, acute diarrhoea in Mozambique/Burundi, H5N1 influenza A, meningitis, measles, acute respiratory syndrome in China, and cholera in Zambia.

There is great concern, said Heymann, that one day there may be deliberate use of microbiological agents to cause serious harm. Today, the agents that worrisome are bacterial, fungal and viral agents, and rickettsial agents that cause typhoid and fevers.

Our concerns are not new; there have been concern about infectious diseases for centuries, if not millennia. Efforts during the 19th and 20th centuries to control the spread of infection culminated in 1969 with the little-known International Health Regulations, which provide the framework for disease surveillance and response. They are endorsed by WHO member nations and the aim is to prevent the spread of disease with minimal interference to world traffic.

Recently, WHO has begun to network with research groups creating everything from formal collaborative links between laboratories around the world and informal internet discussion groups. Information is constantly being brought in through these routes to WHO, such active information exchange is in stark contrast to the passive system with only three diseases listed as there was in 1969 and where disease reporting was not even compulsory.

Information allows WHO to decide whether a reported disease outbreak is of urgent international health importance. If it is not, the nation will be asked to contain it. If it is, then a collaborative risk assessment is undertaken. This amounts, said Heymann, to a new and active approach to disease.

The SARS epidemic illustrated this new coordinated global response to disease, relying on the world’s best laboratory scientists, clinicians, and epidemiologists to investigate and provide guidelines for care and containment. An extensive knowledge-base concerning SARS is now in the public domain, which will provide vital information for dealing with this and other diseases.

Introduction to emergent pathogens

Will we ever conquer infection?

Reporting from a January 2004 Royal Society meeting on infectious diseases – The myth of a germ-free utopia

Thirty years ago various experts pronounced that we had conquered infectious disease; we could thank better hygiene, sterilized food, vaccines, and antibiotics. But, in recent years there has been renewed anxiety about infectious diseases, said epidemiologist Tony McMichael of the Australia National University, Canberra.

We have been confronted with the emergence of legionnaire’s disease, lyme disease, HIV/AIDS, human “mad cow” disease, ebola and hantaviruses, SARS, and many other new diseases. Old adversaries, such as tuberculosis, dengue fever, cholera, and malaria have re-emerged. Cholera is a case in point. A bacterium once confined mainly to South Asia, cholera kills thousands from Asia to Europe and from Africa to North and Latin America.

Pathogens are spreading more freely. McMichael blamed increased personal mobility, greater international trade, and ever more densely populated cities. Greater poverty, changes in sexual practices, and intravenous drug use too, coupled with intensive food production and some modern medical procedures have created many new openings for evolving microbes.

Environmental changes have affected how humans come into contact with microbes while social changes, at the individual and community level, ensure human networks, technology choices, politics, and the distribution of disadvantage all create new opportunities for infection.

McMichael argued that new circumstances lead to unusual contact between people and pathogens. Millions of years ago our descent from the trees exposed us to the savannah’s disease-bearing insects. The advent of agriculture and civilization brought us into closer contact with animal diseases than ever before. War and invasions helped nations swap these diseases, and European expansion spread them to the New World.

McMichael proposed that we are living through a fourth transition – a global transition. Demographic, environmental, behavioural, technological, and other changes in human ecology created an environment well suited for the emergence of new diseases. Injudicious modern medicine is to blame for drug resistance in opportunistic microbes. Climate change and changes in river ecosystems are also influencing infectious disease emergence and spread.

Many factors influence the emergence of infectious diseases so what is the relative importance of environmental and social factors, asked McMichael. Having failed to achieve the germ-free Nirvana, we must recognize the increasingly globalised microbial world that will continue to produce infectious surprises. Rather than use the militaristic hyperbole of a war on microbes, we must approach the topic within an ecological framework. This will help us anticipate the effects of environmental and social change and act accordingly.
Read on… Emerging Viruses

Understanding Disease Transmission and Control

A very different disease - David Bradley at the Royal Society, January 2004

The SARS epidemic of 2002-2003 was rather unusual, began Professor Roy Anderson FRS of the Department of Infectious Disease Epidemiology, at Imperial College London. For instance, its transmission efficiency was low by comparison with viruses such as Influenza A, it had a high case fatality rate especially amongst the elderly, and there was a high incidence of infection and among health workers.

In regions badly affected by SARS there was much suffering, many deaths, serious disruption to social and work activities, and considerable economic losses. The isolation and quarantining of hundreds of thousands of people became essential to bring the disease under control as too were the tight restrictions on travel in some countries. The World Health Organization also played a vital role in co-ordinating the international response and helping to bring the disease quickly under control. We were very lucky this time round, he said. Draconian public health measures are relatively simple to implement in China and other neighbouring regions where this particular disease originated, but how would the people of North America and Western Europe cope with such restrictions on their liberties as mass quarantining? The cause of SARS was narrowed down to a single coronavirus and diagnostic tests of varying precision have been developed to help us detect it. Epidemiological research must now be carried out to help us understand how the disease spreads, especially given what is actually a very low transmissibility of the virus, compared with influenza. Data capture and information capture systems were put in place somewhat late during the epidemic. In future outbreaks this area needs to be improved so that researchers can gather knowledge about the disease’s epidemiology. During the SARS epidemic data capture systems were more effective in some regions and entirely ineffective in others. An international, centralised database would also allow doctors to record the effects of different medicines on the disease and so provide useful information for other doctors an in the longer-term epidemiologists.

We were extremely lucky with the SARS epidemic, said Anderson. SARS caused a around 800 or so deaths, influenza type A kills 30000 people in the USA every year. In the next global epidemic, we may not be so lucky in terms of biology or where the disease emerges. He suggested that we must keep SARS in perspective but not become complacent and assume that “we have been successful once, we will be again”.

The emergence of SARS

Professor Nan Shan ZHONG of the Guangzhou Respiratory Disease Research Institute suggested in his talk that he would probably raise more questions than he would make conclusions. The first case of SARS in China was recorded on 25th November 2002, and he saw his first definite case in December. The subsequent outbreak of the disease caught the world’s health systems unprepared. The worst Chinese epidemic was in Beijing with 2500 cases, while Guangdong province, where SARS first emerged, had some 1500 cases. The result was serious impact on social stability, particularly in China, and ultimately on the global economy.

From both the clinical epidemiological and virological points of view, SARS originated in the Guangdong province of China. Data showed that there may have been interspecies transmission between wild animals and humans, explained ZHONG, and a national campaign to kill rats as one possible source of infection was instigated by the government. As ZHONG pointed out, while rats harbour many diseases it is other animals, in particular the palm civet, which has been demonstrated to be the host of the emergent virus. The virus was found to be highly concentrated in the civets’ faeces and the first cases in 2002 occurred among animal traders. ZHONG believes it imperative these animals are culled and their use in cuisine be stopped.

ZHONG suggests that the health authorities must remain alert for the possible resurgence of SARS during the winter of 2003-2004 and into the spring. Indeed, the Provincial Department of Health in Guangdong has formulated a pre-warning policy based on early identification based on antibody lab tests. With early reporting, early isolation must be enforced to allow the health services to manage a resurgence.

Professionals have now been trained to identify the disease quickly and accurately and a report network has been established throughout mainland China to ensure a rapid response to new SARS cases. ZHONG told the meeting that in the previous three weeks three new cases of SARS had emerged.

Should the disease re-emerge, corticosteroid and non-invasive ventilation should be reiterated as the treatment of choice for patients with critical SARS. Traditional Chinese medicine (TCM) may also have use in early adjunctive therapy. An inactivated SARS vaccine is now in clinical trials and early results suggest it is safe and efficacious and may be available in an emergency.

Fighting SARS in China

Victory over the first SARS epidemic resulted from the efforts of the medical and scientific communities and the political commitment of the authorities in China with strong international support; the causative agent having been identified within two weeks of the outbreak, said Professor CHEN Zhu Vice President of the Chinese Academy of Sciences (CAS). Two weeks later, the SARS genome was unravelled.

Three programmes have now been implemented under the Chinese taskforce – research into causes and effects, diagnosis, treatment and prevention, and drug and vaccine development.

The initial SARS infections, which were seen among restaurant researchers in particular, were rather weak, and reminiscent of the state of play at the time of the meeting in the advent of a SARS second coming. It was then the infamous “Super-Spreader” event in Guangzhou Second Hospital, which evoked the epidemics in Guangzhou, the second phase, and then the Hotel M event that ultimately led to the massive scale of the SARS epidemic, the third phase to Northern China and other countries/regions in the world. Comparisons of the genome at each phase together with information about the relation between human SARS and the disease in the animal carriers, palm civets, is providing important clues about controlling SARS and vaccine development.

With regard to diagnosis, treatment, and protection, CHEN added that Guangzhou’s Prof. ZHONG Nan Shan is something of a hero in China for having first identified SARS as a new pathogen; he and his collaborators developed effective treatments using corticosteroids, antiviral drugs and non-invasive positive pressure ventilation, as well as integrating it with Traditional Chinese Medicine.

Diagnostic tools and kits have been developed in response to the first epidemic are now revealing themselves to be critical in controlling the recent appearance of SARS cases in 2004. Physical protective equipment for personal and hospital use are also being rapidly developed, added CHEN. The Chinese government has issued new security guidelines to help it cope with another outbreak. The scientific conservation of samples of the SARS coronavirus for further researchers is another important measure that CHEN mentioned briefly.

Beijing researchers had reported at the time of the meeting the effectiveness of inactivated SARS viral particle in laboratory tests, but says CHEN , many questions remain to be answered before a safe and effective vaccine will be ready.

The lessons of SARS have led to open reporting, especially in China, which means “next time”, the international health and research communities will be better equipped to respond.

The victims of SARS

Robert Maunder’s hospital, the Mount Sinai Hospital in Toronto, was on the frontline during the SARS epidemic. One aspect of such an epidemic that does not always immediately come to mind is the psychological impact on health workers.

The outbreak of SARS in 2003 provided a system-wide stress upon healthcare workers in the Toronto region, said Maunder, reminding us of when public-health messages were common and quarantine widely used. To understand the psychological impact on hospital staff and the wider community, we should recall the eighteenth century when hospitals were considered places to die rather than centres of healing.

The disease hit Toronto in two waves, said maunder. The first wave had a major impact on Mount Sinai Hospital allowing the researchers to survey of healthcare workers at three hospitals in late May. The effect of stringent controls put in place meant no visitors and non-essential staff ordered to stay home. The public perception of hospitals was severely affected, hospitals were seen as places with disease, and healthcare workers were seen as victims and carriers of disease.

Maunder’s team has studied data from two sources of information. First, observations by he and his colleagues of administrators and mental health professionals providing support during the SARS epidemic in March and April, and a survey of about 1600 healthcare workers at three Toronto hospitals in May and June. The results provide a picture of the factors which lead the SARS outbreak to be experienced as a psychological trauma.

Maunder described how more than 35% of those surveyed reported severe stress symptoms, including intrusive thoughts and feelings and avoidance and blunted feelings. The degree of risk of traumatic stress was related to degree and duration of exposure to SARS patients as well as other factors. These included isolation from family and colleagues, and the wider community as well as job stress, and problems with family life. Rules prevented colleagues shaking hands or eating in the hospital cafeteria compound the problems leading to poor sleep, anxiety, and preoccupation with signs of illness among many healthcare workers.

There is a psychological cost to controlling a disease like SARS, said Maunder. This must be considered when planning the public-health response and invaluable psychological support provided during the early stages of an outbreak.

New hosts for new diseases

Biologist Dr Diana Bell of the University of East Anglia, Norwich, immediately drew three conclusions about the nature of emerging diseases like SARS.

First, she suggested that the search for diseases of animal origin should be extended, not only geographically, but also to small carnivores other than the masked palm civet from which SARS emerged. Secondly, there are major ecological shifts favouring the emergence of zoonotic diseases, in South East Asia. Thirdly, new collaboration between conservation biologists and vertebrate ecologists would help in finding and controlling such diseases.

The search for disease has focused on the animal markets of Southern China, but many of the animals traded here are illegally imported. The animal reservoir for SARS and other viruses could extend far outside China. Moreover, China’s neighbours in the Indochina hotspot of biodiversity – Cambodia, Laos, Thailand – also exploit wild animals in the restaurant trades, traditional medicine, perfumes, skins for clothing, and as pets. The limelight has shone on three small carnivore species: the masked palm civet, Chinese ferret badger, and raccoon dog. Many other endangered species are also exploited.

Bell suggested that putative hosts must be screened across all routes from capture to marketplace and beyond. This would allow researchers to pinpoint at what point the animals first show signs of infection.

Wildlife trade is a global problem, not restricted to South East Asia. African civets are eaten as bush meat and should be screened. Moreover, the problem is very much a global one. Huge numbers of wild animals are imported into the USA each year, including 49 million live amphibians and 2 million live reptiles. The wildlife trade, Bell said, is not only a threat to biodiversity but seriously threatens human health.

To combat this trade, it is important to hit supply and demand, said Bell. Better law enforcement and community participation as well as education could be key to reducing the demand for wild meat.

Read on in Session 4: Planning for disease

Nanoparticles keep buses moving

The 7000-strong Stagecoach UK bus fleet is now using nanoparticles of the Envirox oxidation catalyst as a fuel additive.

Envirox is based on a well-established oxidation catalyst but has now been formulated for use in diesel fuel at just five parts per billion without any need to modify the engine. The result is a cleaner and more complete combustion, which the company claims produces an up to 12% fuel saving as well as reducing carbon deposits in the engine and lowering emissions.

The fuel-borne catalyst is composed of particles of cerium oxide 10 nm across, a material commonly used in conventional catalytic converters to clean up vehicle exhausts. Cerium oxide catalyses the conversion of carbon monoxide and hydrocarbon gases to carbon dioxide and water. It also reduces nitrogen oxides.

Researchers have attempted to formulate the compound as a fuel additive before but have generally failed to improve on fuel efficiency or cut emissions. Cerulean believe they have circumvented the problems with their nanoscale approach because at this size, the catalyst remains evenly suspended in the liquid fuel.

Stagecoach intends to try the product in up to 1000 of its buses across the UK. According to Chief Executive Brian Souter, “We believe this new product has huge potential and we are delighted to once again be leading the way in the UK bus industry in developing new ideas.”

Cerulean International Ltd is a subsidiary of Oxonica Ltd an Oxford University spin-out company. Oxonica’s Christopher Harris recently patented an improvement to the Envirox system that uses an organic solvent system to comminute, or coat the nanoparticles with an organic anhydride or acid, an ester, or a Lewis base. This coating is intended to help the particles disperse still more evenly in diesel fuel.

The permutations for nanoparticles additives are not to merely coating cerium oxide. In the initial nanoparticle patent, Gareth Wakefield describes how the particles might also be doped with a divalent or trivalent metal or metalloid. Doping might improve the properties further, although Stagecoach will be trialling only the undoped version.

The original version of this article by David Bradley originally appeared in The Alchemist in October 2003.

Mutant Venus Flytraps Catch TNT

Computation could allow new high-affinity and specific protein receptors and sensors to be designed for any number of small molecules of interest, thanks to researchers in the US. Such artificial receptors could ultimately find a role to play in medical diagnostics, drug design, and sensors.
According to biochemist Homme Hellinga and colleagues at the Duke University Medical Center, Durham, North Carolina, the formation of complexes between proteins and ligands is a fundamental interaction in molecular biology that lies at the heart of countless biological process.

Hellinga points out that manipulating the molecular recognition between ligands and their associated proteins is crucial to basic biological studies. From a technological standpoint though, improved understanding could also allow us to create bespoke enzymes, tailor-made biosensors, genetic circuits, and to carry out chiral separations very effectively. With such rewards in the offing it is not surprising that the systematic manipulation of binding sites is still “a major challenge”, Hellinga emphasises.

The team has taken a novel approach to improving our understanding of protein-ligand interactions. They have devised a structure-based computational method that can be used to redesign protein ligand-binding specificities, which can then be engineered into a microbial genome for fermentation-like protein manufacture. In a commentary on Hellinga’s research, William DeGrado of the University of Pennsylvania School of Medicine, Philadelphia, explains how organisms use many different small molecules that bind to proteins. Receptors, enzymes, and antibodies for instance all interact with small molecules to control cell communication, signalling, and protection against pathogens. Exploitation of these interactions has so far been limited, but diagnostics and new disease therapies could emerge from greater understanding of them.

The researchers have demonstrated how the approach works by constructing new soluble receptors for the explosive TNT (trinitrotoluene), the sugar L-lactate and the medically important hormone serotonin (5-HT). The new receptors have high selectivity and affinity for their ligands and could be used as the sensing component of a detector. Intriguingly, the team has also incorporated their new proteins into a synthetic bacterial signal transduction pathway, which means they can be used to regulate the switching on and off of various genes in response to the presence of TNT or L-lactate in a bacterial culture. “The aim is to create synthetic signal transduction pathways that may allow bacteria to function as biological sentinels to chemical threats and pollutants in the environment by switching on a reporter gene,” Hellinga told us.

They started with a series of bacterial periplasmic binding proteins (PBPs) from Escherichia coli, which DeGrado describes as “Venus-flytrap-like receptors”. These PBPs are composed of two protein domains that snap shut on their ligand, just as the fly-catching plant’s specialist leaves grab their prey. When the ligand binds, a signal is transmitted. “In vivo the signal is binding of the closed form of the protein to a transmembrane receptor that triggers a cytoplasmic phosphorylation cascade that ultimately results in transcriptional activation of a reporter gene,” explains Hellinga. The natural function is the control of chemotaxis or outer membrane protein expression, depending on the system, and the natural ligands include sugars and amino acids. The researchers wanted to redesign the PBP’s trap so that it would bind a range of other small molecules in order to engineer “biological sentinels”. They chose L-lactate, serotonin (5-HT), and TNT as their targets as these compounds demonstrate great molecular diversity structurally and chemically diverse, both from one another and the natural PBP ligands.

A computer model of the PBPs was then investigated by placing a “virtual” version of TNT, 5-HT or lactate in the trap. Their powerful algorithms then mutated the binding site amino acids one at a time and scanned for new protein sequences that had a surface into which the ligand would fit. The results are astounding, with just 12 to 18 amino acids being changed, 10^23 possible sequences are generated, many more than achievable with conventional methods. Moreover, if ligand approach is also considered the combinatorial possibilities rocket to between 10^53 and 10^76.
To screen such a vast array of virtual proteins, Hellinga’s team then used another algorithm – an enhanced version of “dead-end elimination”. The original algorithm was developed by Frank DeSmet of the Catholic University of Leuven, Belgium, but was then enhanced substantially by Hellinga’s team. Further work then allowed them to handle the design of ligand-binding sites needed for their research. The algorithm queries an entry in the library on the basis of hydrogen bonds, van der Waals interactions, electrostatic interactions and atomic solvation. However, rather than scanning each individual entry those library members lower down the diversity tree are pruned off if they don’t fit. The rationale for this being that if a lower member does not fit, then any twiglets further along its branch won’t either. In this way, only the mutant Venus fly traps with a global energy minimum are retained for further investigation. The result – from billions and billions of possibilities, the researchers have pruned down to a top seventeen.

The researchers synthesised these seventeen potential receptors and tested them in vitro against their target small molecules. Fluorescence measurements shed great light on each, revealing them to be highly specific and selective for their respective ligands.

Until now, explains De Grado, the proteins in question have been “developed” either through the generation of large libraries of proteins for testing and improved through evolutionary type methods. However, this is time wasteful and energy consuming. As De Grado points out the Hellinga team has now accomplished the task of creating such a library and screening it by a very rapid computational means.

References

Nature 2003, 423, 185; Loren L. Looger, Mary A. Dwyer, James J. Smith & Homme W. Hellinga
Nature 2003, 423, 132; William F DeGrado.

Acid reflux disease and diet

Almost half the chance of developing acid reflux disease, which doctors refer to as GERD, may be down to our genes, and not just a diet of lager and curry, a twin study in the journal Gut suggests.

Acid reflux disease (gastro-esophagal reflux disease) is one of the most common digestive disorders in the developed world, with about one in five people suffering from the characteristic heartburn and/or regurgitation of acid into the esophagus or mouth every week. Regular sufferers have an increased risk of esophagal cancer.

The findings (July, 2003) were based on 2000 pairs of identical and non-identical twins, who completed a questionnaire on the type and frequency of gastrointestinal symptoms and potential risk factors for acid reflux. These included smoking, excess alcohol, being overweight, and certain drugs, including some heart drugs, oral contraceptives, and drugs for anxiety.

On the basis of this study, and having taken account of known risk factors, the authors conclude that 43% of the chance of developing acid reflux is attributable to genes. Other research seems to back up their findings, say the authors, with previous studies recording several family members with GERD or even esophagal cancer.

The old ones are the best

An apocryphal story was doing the rounds of the chemistry discussion groups on the internet a while ago. You can substitute your own alma mater and personal weekend hobby for greater comic effect when relating the tale.

Two undergraduate chemists at Newcastle University did very well in their mid-term exams, their practical results were squeaky clean – both were headed for a first. In fact, the two friends were so certain of their chances they spent the weekend before the crucial final fell walking and partying at a hill-top youth hostel.

Either suffering from all the fresh air or one or two more beers than they should have had on the Sunday night they didn’t make it back to Newcastle until early Monday morning. Rather than taking the crucial final they spoke to Professor Bunsen after the exam and explained that their car got a flat tyre on the way back to University and the spare was dud.

flat-tyre

Bunsen was a lenient chap and agreed they could take the exam the following day. The friends were so relieved and studied hard that night. For the exam they were put in separate rooms and given the question booklet. Question One was a simple test of chemical reactions (5 points) and each thought the exam was going to be easy. They were unprepared, however, for what they saw on the next page. It said: “Which tyre? (95 points)”.

In the poo of Eden

We recently visited the Eden Project near St Austell in Cornwall and were impressed not only by the vast “biomes” and their horticultural contents but by the detail into which the designers of some of the exhibits have gone. Particularly intriguing was the Spindigo exhibit that is being undertaken with researchers at the University of Reading. Spindigo as the name might hint at, aims to find a sustainable way to supply the textile industry with the unique blue jeans dye indigo from natural renewable resources rather than synthetic chemicals. Certainly a worthwhile cause.

The Spindigo exhibit went into some detail about how all kinds of natural materials have been used to release the blue colouring from its natural plant sources. The seemingly endless list included dates, grapes, yeast, molasses, figs, papaya, green bananas. Our colleague began to wish he hadn’t visited the Eden Project’s restaurant for a “Cornish pastie” when he got further down the list. Rotten meat as well as urine (they don’t mention whose) have also been used to extract the blue. But, the last entry was the most off-putting – dog poo! On reflection though, perhaps this secret ingredient is part of what makes those shrink-to-fit jeans so trendy. Just don’t tell the marketing department.

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The Real Butterfly Effect

The tropical butterfly Morpho sulkowskyi flashes bright blue as its iridescent wings flutter by. Not only is it astonishingly beautiful, but Japanese chemists believe the secret of what gives these wings their brilliance could lead to a new approach to stay-clean coatings for cars and other surfaces.

Osamu Sato of the Kanagawa Academy of Science and Technology and colleagues have discovered the secret of why the butterfly’s shiny wings never seem to get dirty and intend to put their discovery to good use.

They already knew that butterfly wings have a special surface structure. This consists of an array of highly ordered microscopic scales, which produce colour by scattering and refracting light from the scales. This “structural colouring” is unlike the colourful pigments used elsewhere in the natural world which rely on reflecting light at different wavelengths. Structural colour, however, unlike a baboon’s rear, relies on keeping pristine, otherwise the butterfly would revert to a dull grey.

Sato and his team discovered that there are countless air-filled cavities within the scaly surface of the wing. These, he explains, carry out cleansing duties across the wing’s surface. Any minute droplets of water on the surface ride on a cushion of air and as they roll off they drag with them any clinging dirt particles. This helps maintains the scales’ smooth lustre.

Now, the team have copied the butterfly effect. First, they produced a liquid suspension containing finely divided polystyrene beads just a few micrometres across. They then added powdered silicate whose particles are a few tenths the diameter of the beads. A blast of ultrasound makes the particles disperse evenly throughout the liquid. The researchers then dipped a glass slide into this mixture and slowly withdrew it.

As the plastic beads stick to the slide, they pack together like so many apples on a tray into an arrangement known as hexagonal close packing. The beads act as a template for the silicate particles, which fill the gaps between the beads. “During the lifting process, the polystyrene beads self-assemble into a highly ordered structure,” explains Sato. It is the patterned silicate layer in which the researchers are interested though so they next burn off the polystyrene beads at 450 Celsius. This leaves behind a honeycomb of tiny hollow cells formed from the compacted silicate particles.

Size is important when it comes to hollow air pockets. To mimic the colourful effects of the butterfly wing, the holes have to have a diameter close to the wavelength of visible light so they can scatter incoming light waves, explains Sato. By changing the size of the templating beads, the researchers, can fine tune the diameter. In this way, they have made brilliant blue, green and red layers and could produce all the colours in between.

Their preliminary tests show that these silicate layers, are water repellent because of their air holes. Thus, like the butterfly’s wing any droplets of water are dispersed readily and dirt particles carried away with them. “The sample is not yet very tough, it will peel off if it is scratched,” confesses Sato, “but we are collaborating with Japanese companies to solve this problem.”

The researchers say their new materials might first find use in quantum dot devices, as optical materials for telecommunications, and as scaffolds for tissue engineering. More immediately commercial applications may be possible such as the self-cleaning car. Whatever colour it is to be, such a vehicle with its butterfly-wing coating is sure to cause a flap.