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

Clicked off

Doom beckons for online ads

They pop up without warning, distract attention and clog computers. Users have many reasons to shun online ads—and find it easy to do so. Though global online-advertising revenues rose by 22% in 2011, websites that depend on selling their viewers’ eyeballs are worried. Around 9% of all online page views come from browsers armed with ad-blocking software, such as Adblock Plus, downloaded nearly 180m times since 2007, and 3.5m times in October alone.

Few sites have tried to fight back. In 2010 Ars Technica, a technology-news outlet, found that 40% of its users were blocking its ads. So it blocked their access for a day, but signed up only 200 users (out of 5m a month) for its ad-free version. Media firms are now opting for paywalls. Press+, a paywall provider set up in 2010, now has over 300 clients.

Till Faida, co-founder of Eyeo, which owns Adblock Plus, agrees that ads are needed to pay for content. Users of his plug-in can choose to allow “acceptable ads”: no animation and no tiresome clicking to dodge them. “You cannot annoy someone into liking you,” says Norm Johnston of Mindshare, a media-buying agency. But for many users the only good ad is an invisible one.

First published in The EconomistAlso available in audio here.

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Grim and bear it

 

The subjective study of suffering

 

Controversy about pain relief is usually between those who worry about addiction, black markets and over-prescription, and those who just want patients with long-running or fatal diseases to get the best pills. But a lesser-known issue is gaining attention, too: the treatment of acute pain.

 

Despite big advances in medical care in most other respects, pain relief after surgery has not improved in the past 60 years. A study in 2003 found that 80% of adults reported moderate to severe pain after surgery, just as many did in 1950. Pain does not just cause anguish: the stress-hormone cortisol it releases can damage the body. The end result may be heart attacks or internal blood clots.

 

The dispute is not about the drugs themselves, but concerns their type, quantity and timing. Medical opinion is surprisingly divided on this, chiefly because it is so hard to measure pain accurately. Attempts to determine a global pain scale have failed, because pain tolerance varies from country to country. In nations with stiff upper lips, a dose may be too high. In those with trembling lower ones, the same amount may be too little. Stereotypes are misleading: on average Germans, for instance, rate pain for similar conditions worse than Spaniards or Italians do.

 

Such comparisons are rare, but a global study called Pain Out is trying to make them more systematic. It records data across 16 rich and poor countries. Patients fill in forms after operations and doctors make notes of given treatments. The data are fed into a central server and can be accessed freely by researchers. In Berlin this month Ruth Zaslansky, of the Jena Medical Centre in Germany, will present the results of the study and actions taken.

 

One finding is that Rwandan women undergoing Caesarean sections get worse therapy than those in any other rich or poor country. As a result, says Antoine Bahati Kabeza, an anaesthetist at Kigali University Hospital, the medical staff are changing its pain-relief policies, and the university is changing the way it teaches pain management.

 

Medical care inevitably varies between rich and poor countries. But pain relief, administered correctly, costs relatively little given the good it does. The psychology of national character does not feature in pharmacological thinking. Perhaps it should.

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

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Gene therapy

A technique intended to eliminate mitochondrial diseases would result in people with three genetic parents

Is it possible for a child to have three parents? That is the question raised by a paper just published in Nature by Shoukhrat Mitalipov and his colleagues at Oregon Health and Science University. And the answer seems to be “yes”, for this study paves the way for the birth of children who, genetically, have one father, but two mothers.

The reason this is possible is that a mother’s genetic contribution to her offspring comes in two separable pieces. By far the largest is packed into the 23 chromosomes in the nucleus of an unfertilised egg. In that, she is just like the child’s father, who provides another 23 through his sperm. But the mother also contributes what is known as mitochondrial DNA.

Mitochondria are a cell’s power-packs. They convert the energy in sugar into a form usable by the cell’s molecular machinery. And because mitochondria descend from a bacterium that, about 2 billion years ago, became symbiotic with the cell from which animals and plants are descended, they have their own, small chromosomes. In people, these chromosomes carry only 37 genes, compared with the 20,000 or so of the nucleus. But all of the mitochondria in a human body are descended from those in the egg from which it grew. The sperm contributes none. And it is that fact which has allowed doctors to conceive of the idea of people with two mothers: one providing the nuclear DNA and one the mitochondrial sort.

The reason for doing this is that mutations in mitochondrial DNA, like those in the nuclear genes, can cause disease. These diseases especially affect organs such as the brain and the muscles, which have high energy requirements. Each particular mitochondrial disease is rare. But there are lots of them. All told, there is about one chance in 5,000 that a child will develop such an inherited disease. That rate is similar, for example, to the rate of fragile-X syndrome, which is the second-most-common type of congenital learning difficulty after Down’s syndrome. Mitochondrial disease is thus not a huge problem, but it is not negligible, either.

New batteries, please

To find out whether mitochondrial transplantation could work in people (it has already been demonstrated in other species of mammal) Dr Mitalipov collected eggs from the ovaries of women with mutated mitochondria and others from donors with healthy mitochondria. He then removed the nuclei of both. Those from the healthy cells, he discarded. Those from the diseased cells, he transplanted into the healthy cells. He then fertilised the result with sperm and allowed the fertilised eggs to start dividing and thus begin taking the first steps on the journey that might ultimately lead to them becoming full-fledged human beings.

Nearly all of the experimental eggs survived the replacement of their nuclei, and three-quarters were successfully fertilised. However, just over half of the resulting zygotes—as the balls of cells that form from a fertilised egg’s early division are known—displayed abnormalities. That compared with an abnormality rate of just an eighth in control zygotes grown from untransplanted, healthy eggs.

This discrepancy surprised—and worried—Dr Mitalipov. The abnormality rate he observed was much higher than those seen when the procedure is carried out on other species. That, though, could be because this is the first time it has been attempted with human eggs. Each species has its quirks, and if mitochondrial transplants were to become routine, the quirks of humans would, no doubt, quickly become apparent. With tweaks, they could be fixed, Dr Mitalipov predicts.

However, turning this experiment into a medical procedure would be a long road, and not just scientifically. Dr Mitalipov has little doubt that his zygotes could be brought to term if they were transplanted into a woman’s womb. That experiment, though, is illegal—and, in the view of some, rightly so. But the fact that it now looks possible will surely stimulate debate about whether the law should be changed.

Two kinds of question arise. One kind is pragmatic: would the process usually work and, if it did, would it always lead to a healthy baby who would have a normal chance of growing into a healthy adult? The second kind of question is moral, for what is being proposed is, in essence, genetic engineering. Not, perhaps, as classically conceived because no DNA is artificially modified. But it is engineering nevertheless. And that might worry some people.

On the first kind of question, the auspices are good. When Dr Mitalipov tested his zygotes, he could find no trace of mutated mitochondrial DNA in them, so the purpose of the procedure seems to have been achieved. And an experiment on monkeys that he began three years ago has produced four healthy offspring that are not apparently different from any other young monkey of their age. These are preliminary results, but they are encouraging.

It is on the moral questions that things may stumble. There is no consensus. Some people oppose such genetic tinkering in principle. Some worry about the consequences of a third adult being involved in the traditionally two-person process of parenthood—though the mitochondrial contribution is restricted to genes for energy-processing proteins and is unlikely to have wider ramifications on, say, family resemblance. Some worry that three-parented individuals may themselves be worried by knowledge of their origin. But until recently such questions have been hypothetical. Now they are real. In September, for example, Britain’s Human Fertilisation and Embryology Authority, which deals with such matters, launched a public consultation to discuss the ethics of creating three-parent offspring of the sort Dr Mitalipov proposes. This consultation runs till December 7th and the results will be given to the government in the spring.

In the end, whether three-parent children are permitted will probably depend on the public “uggh!” factor. There was once opposition to in vitro fertilisation, with pejorative terms like “test-tube baby” being bandied about. Now, IVF is routine, and it is routine because it is successful. In the case of mitochondrial transplants what will probably happen is that one country breaks ranks, permits the procedure, and the world will then see the consequences. If they are good, you will never find anyone who will admit to having opposed the transplants in the first place. If they are bad, the phrase “I told you so” will ring from the rafters.

First published in The Economist. Also available in audio hereThis article also had an editorial that ran with it.

This story was mentioned on the cover page of the print issue and made it to the front page of  Reddit and Digg, receiving over 250,000 views in two days.

Image credit: The Economist

Genetic medicine

A new technique to help cure mitochondrial diseases should be permitted by the law

In September Britain’s Human Fertilisation and Embryology Authority launched a public consultation on what sounds like a crackpot idea: to create children with three genetic parents. Yet this could be a way to eliminate a set of rare but nasty diseases caused by problems with pieces of cellular machinery called mitochondria. According to research published this week (see article), the basic technique of substituting problem-free mitochondria has now been tested in a laboratory and the researchers seem confident that, given the green light, they could bring a healthy child into the world.

Most of a child’s genes would come from the couple it would learn to call mum and dad. A tiny fraction of the DNA, however, would come from a female donor who would provide part of the egg from which the child grew. At present the law in Britain, like that in most other places, prohibits any genetic modification of embryos. It should be changed.

An in-gene-ious idea

Mitochondria turn the energy in sugar into a form a cell can use, so if they go wrong the consequences are dire. The brain, the nerves and the muscles, all huge consumers of energy, are the organs that suffer most. Mitochondria are also special, because they contain their own genes, completely separate from those in the cell nucleus, which are thus transmitted from mother to child in the egg.

Some mitochondrial disease is caused by mutations in these genes and is thus also inherited solely from the mother. Such diseases affect one person in 5,000 during his or her lifetime. But the separateness of mitochondrial genes means that by moving the nucleus from an afflicted egg into a healthy one, the mutated, disease-causing genes can be left behind. In effect, the nucleus would receive a mitochondrial transplant.

This incorporation of the DNA of two women might be seen by the nervous as a step down the slippery slope towards the genetic engineering of people. But that is unlikely.

The principal worry about genetic engineering is that it will lead to “designer babies” with customised DNA. But mitochondrial transplants involve no tinkering with the DNA itself. Though on a microscopic scale, the process is quite like a heart, liver or kidney transplant, with the caveat that the transplant will be passed on to the recipient’s children, if she is female. Any organ transplant introduces new genes into the body. Mitochondrial genes are ubiquitous, it is true, but this difference is one of degree, not kind.

Another reason not to worry is that the mitochondria carry only 37 genes, compared with about 20,000 in the cell nucleus, and these genes are exclusively concerned with energy metabolism. Pushy parents will not be picking mitochondrial donors on the basis of looks, personality or intelligence.

Non-biological objections are sometimes raised as well. Some worry, for instance, that a person with three genetic parents might suffer an identity crisis. But that seems less likely than in the case of people conceived by in vitro fertilisation using sperm donated by strangers who have contributed half of their offspring’s genes, not a paltry three dozen. And for that reason mitochondrial donors are even less likely than sperm donors to want to be involved with bringing up children in whom they have but a fractional genetic interest.

But is the process safe? Doing the experiment is the only way of finding out. It should be preceded by a lot of tests in Petri dishes and laboratory animals. But in the end, you just have to try it and see.

First published as a Leader in The Economist. Also available in audio hereThis editorial also had an accompanying article with it.

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Stay sharper for longer

With the advent of old age, incidences of misplaced keys and embarrassing moments of forgotten names occur more often. As you inch closer to becoming a senior citizen, certain cognitive skills start to decline and others improve. But you can still find some 70-year-olds who can beat those at 50 on a memory test. How do they retain such abilities and how can that knowledge be used to our advantage? Results emerging from unique studies show that there might indeed be ways to slow down the inevitable slide.

Stay sharper for longereu:sci, Autumn 2012 issue.

A list of main references here. Free image from here.

Crowdfunding science: Many a mickle makes a muckle

Necessity, so the proverb has it, is the mother of invention. And science is nothing if not inventive. So, as conventional sources of money get harder to tap (the success rate enjoyed by those applying for research grants from the National Institutes of Health, America’s biggest science-funding agency, has fallen from 30% in 2003 to 18% in 2011), some of science’s more creative minds are turning elsewhere.

Philanthropic sponsorship of science, particularly in the form of expensive pieces of kit such as large telescopes, or sponsorship for expeditions to far-off places, has been around for centuries. But the internet now permits what might be thought of as microphilanthropy. Through a technique called crowdfunding, in which members of the public donate small sums to projects they like the look of (sometimes in the knowledge that the donation will be taken up only if sufficient other pledges are made to surpass a stated target), the possibility of scientific philanthropy has been extended to those of more slender means.

On October 4th, for example, Ethan Perlstein, a pharmacologist at Princeton University, launched a bid on a site called RocketHub to collect $25,000 to study the effect of drugs such as methamphetamine on the brain. He has until November 18th to raise the money.

Kristina Killgrove, an anthropologist at the University of West Florida, has already raised over $12,000 on RocketHub to examine the DNA of Roman skeletons. And on another crowdfunding site, Petridish, the California Academy of Sciences (CAS) offered to name any new species of ant discovered during a conservation project in Madagascar after those who donate more than $5,000 to the enterprise.

Although the crowdfunding of science is not raising the sorts of sums sometimes attracted by those with ideas for things like video games, it has already spawned a couple of specialised platforms of its own. Petridish is one. Another is called Microryza. And academic institutions are starting to follow the lead taken by the CAS. The University of California, San Francisco, has made a deal with a site called Indiegogo that will allow the university’s charitable status to make money donated via Indiegogo tax deductible. It will launch the first such project later this month.

Donors can expect no revenue if a crowdfunded science project is successful, of course. But they can expect to be kept up to date with progress. Dr Perlstein has promised to upload all data from his experiments onto a website, for his sponsors to look at. And even those who are not immortalised in the myrmicine literature, as the CAS proposed, may still get a warm glow from the feeling that they are making a contribution to the advancement of knowledge in a way which was previously open only to philanthropists with rather fatter wallets.

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

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