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50 ideas to change science: Genetics
COVER STORY
50 ideas to change science Part one Life and Earth What ideas are set to transform our understanding of the world around us and our relationship with it? Over the next two weeks, New Scientist looks at the advances that will really make a difference. We ask leading experts to tell us what will revolutionise their field and include some of our own ideas. We begin with the coming revolution in biology, life and Earth: ideas such as DNA origami, super-evolution, brain maps and ultrasounding the planet. Some of them are strokes of genius, some subtle slants on old problems, others just fundamentally new ways to make observations. All will change science beyond measure. Next week sees the turn of physics, space and technology – and your chance to tell us which of all the ideas will have the biggest impact on science, and why.
32 | NewScientist |9 October 2010
Artificial cells Life is membranes Jack Szostak
Brett rYDer
The exact nature of the first cell, the forerunner of all life today, is still a mystery. It is an exciting puzzle, but reconstructing events that took place 4 billion years ago is no mean feat. Fortunately, there is much to be learned from tackling a more modest goal, that of building simple artificial cells, beginning with their walls. Primitive membranes made from fatty acids seem to have all the right properties, such as allowing for spontaneous growth and division, as well as letting nutrients penetrate the cell. What drove the transition from such membranes to modern ones, which are based on the more complex phospholipids? A primitive RNA might have catalysed the synthesis of phospholipids, but what advantage would phospholipids have conferred on primordial cells? The answer may well be the first clue to the avalanche of events that eventually led to modern biology. If we can find it in artificial cells, we will be transported back to the onset of Darwinian evolution and the origins of life as we know it.
Jack Szostak is professor of genetics at Harvard Medical School and a co-recipient of the 2009 Nobel prize in physiology or medicine
9 October 2010 | NewScientist | 33
PART ONE Life and Earth
Super-evolution Change for the common good David Sloan Wilson
chip clark/smnh
In the study of evolution, the past half-century was the age of reductionism, when everything was explained in terms of individual self-interest and selfish genes. Now we are entering the age of holism, which recognises how colonies of social insects, human societies and at least some multispecies ecosystems can respond as a single “superorganism” to selective pressures. The turning point came in the 1970s, when biologist Lynn Margulis proposed that complex, nucleated cells originated as symbiotic associations of bacterial cells. Now it is known that every entity recognised as an organism is a highly organised group of individual cells, making it hard to deny that groups of organisms can themselves have organism-like properties and so can evolve in concert.
Impact assessment Revisiting Earth’s ancient trials
”We are beginning to recognise that societies can respond as a single ‘super-organism’ to selective pressures” 34 | NewScientist | 9 October 2010
alex wild
The history of life is littered with great upheavals: blooming diversity one epoch, mass wipe-outs the next. On that scale the Hangenberg event, an extinction 359 million years ago at the end of the Devonian period, was considered a minor blip. Not any more. The end of the Devonian was a crucial time for vertebrates. Many primitive lineages went extinct as sharks and bony fish became masters of the waters and tetrapods, the four-legged animals that eventually evolved into dinosaurs and mammals, conquered the land. We had seen this as a gradual change, one fuelled by a series of extinction pulses spread over 25 million years of the Devonian’s dog days. But now it seems they were piffling in comparison to the Hangenberg event, which all but wiped out the typical Devonian species and cleared the decks for the new world order (Proceedings of the National Academy of Sciences, vol 107, p 10131). We don’t know what caused this disaster. But the radical reassessment of its importance shows how ancient fossils remain a fertile field for new thinking.
The process of group selection through which this occurs seemed to have been authoritatively rejected during the age of individualism. But Darwin got it right: altruistic behaviours “for the good of the group” – whether that group is a species or an ecosystem – require a process of between-group selection to evolve, and tend to be undermined by individual selection within groups. What is new is the idea that higher-level selection is not invariably trumped by lower-level selection – and indeed sometimes wins out. Now we must pick through the implications of that insight, which span from the origin of life to the structure of ecosystems to the nature of religion and human biocultural evolution.
David Sloan Wilson is a professor of biology and anthropology at the State University of New York at Binghamton
Cognitive control Towards the seat of consciousness Allan Hobson The question “what is consciousness?” represents one of the great frontiers of contemporary science. Thanks to studies of humans and animals, we now know that it is a subtly nuanced state whose nature and intensity varies according to the brain’s intrinsic level of activity, its chemical microclimate and the information it receives from outside. By exploiting the normal vicissitudes of waking, sleeping and dreaming states, we are now beginning to explore how consciousness is expressed and controlled. For example, I have been involved in studies comparing brain activation in REM sleep with that in lucid-dreaming states, in which we retain much executive brain function. They seem to confirm the central importance of one specific area of the frontal brain – the dorsolateral prefrontal cortex – in regulating many key aspects of consciousness, including attention, decision-making and voluntary action. A combination of imaging techniques, judicious measures of subjective experience and detailed cellular and molecular-level studies will continue to deepen our understanding of our cognitive command centres in the coming years. With them we hope to crack the puzzle of consciousness, and perhaps correct the dysfunctional states of the brain we now call mental illness.
Allan Hobson is emeritus professor of psychiatry at Harvard Medical School in Cambridge, Massachusetts
Ocean observatories Wired up, deep down
Earth’s oceans are vast, unexplored regions full of unanswered questions. What part do the oceans play in climate change? How do earthquakes arise in undersea subduction zones, which account for 90 per cent of all seismic energy released worldwide? What does life look like on and below the sea floor? Grappling with these and other questions have been hindered by a paucity of data. A new project should change that. Rather than relying on the laborious traditional method of ship-based expeditions, the Ocean Observatories Initiative aims to wire up the ocean. Its network of sensors, strung from ocean surface to bottom in regions off the US coast and further out in the Pacific and Atlantic, will stream scientific and video data back not only to labs, but also to schools and homes via the internet. Work got under way late last year. Continuous, real-time interactions with the ocean could be the breakthrough we need to explore our planet’s final frontier.
Artificial enzymes
Molecules for all occasions Whether for a new drug or solar cell, we constantly strive to design and build intricate new molecules. Making them is one thing; making them efficiently enough for commercial production is quite another. If only we could take a leaf out of nature’s book, which uses highly specialised enzymes as catalysts to churn out vast quantities of the molecules life needs. Increasingly, we can. We can take natural enzymes and randomly tweak their structure until a variant efficiently produces the molecule we desire. For a rather less hit-and-miss strategy, we can use computer-led “rational design” modelling processes to make artificial enzymes from scratch. Ultimately, the aim is to trump nature. Compared with artificial catalysts, enzymes are wrapped around a relatively limited range of metals at their core. By combining the best of natural and artificial catalysis, we might be able to make enzymes – and final products – that are capable of simply anything.
The 1000 Genomes Project A catalogue of human variation The mapping of the human genome, largely completed 10 years ago, was a remarkable feat. But if genomics is to fulfil its potential, for example in combating disease, we need to know how much DNA sequences vary between individuals. Within the next few years we should do. The 1000 Genomes Project, a private-public consortium established in 2008, aims to create a detailed map of human genetic variation. Pilot projects involving 885 people were completed in June this year and identified about 16 million DNA variations, half of them not previously identified. That suggests there may be around 60 million such variations to be found. The full project, analysing the genomes of 2500 people from 27 populations across the world, is now under way. The growing dataset is freely available online at www.1000genomes.org. 9 October 2010 | NewScientist | 35
Jessica Peterson/getty
PART ONE Life and Earth
The web of life Darwin’s tree uprooted Ford Doolittle Bacterial genomes, we are coming to realise, are mosaics. Genes can come from different sources, not just a single common ancestor; even between two strains of the same species half of the genes may differ. The principal culprit is “lateral” gene transfer, in which genetic material from one bacterium passes to another, whether by expulsion into the environment and subsequent uptake or through the agency of viruses or bacterial sex. Transfer occurs within and between species and even between representatives of the bacterial equivalents of phyla or kingdoms. One consequence is that no simple pattern defines the relationships between microbial species. The tree of life with its tidily ramifying branches, a metaphor for the theory of evolution, has been uprooted. We now recognise that understanding the processes of evolution in no way depends on this “tree-thinking”. What’s more, the new discipline of metagenomics, which focuses on microbial communities and the differences in functional genes active at that level, is reducing the need for “species-thinking”. The upshot will be a sharper insight into the relationships of the tangled web of life.
Ford Doolittle is emeritus professor of biochemistry and molecular biology at Dalhousie University in Halifax, Nova Scotia, Canada
”Drawing a basic map of the brain would help us to understand how its regions interact to make behaviour”
36 | NewScientist | 9 October 2010
The connectome Mental maps Tim Behrens Understanding the routes by which populations of brain cells share information would be a major step towards understanding how our brains function. But although we can infer individual connections, we have no basic wiring diagram of the human brain. This is hardly surprising. The brain contains approximately 100 billion neurons, and a single neuron may connect to 10,000 others. Yet emerging techniques mean we are now making headway in this daunting task. Using electron microscopes, for example, we can probe animal brains neuron-by-neuron, connection-byconnection, in the hope of discovering
characteristic circuits that repeat themselves throughout the brain. From a wider perspective, brain imaging technologies can map the brain’s highways – large “cables” consisting of many thousands of connections between distinct brain regions. The US National Institutes of Health has begun to fund a major effort, the Human Connectome Project, to generate a comprehensive map of large-scale brain connections in humans. Following its directions, we might arrive at a better understanding of how the brain’s regions interact to produce behaviour.
Tim Behrens is a neuroscientist at the University of Oxford
Interactomes
Mapping cellular complexity Marc Vidal
Proteins and RNAs, the molecules encoded by genes, rarely act in isolation. Some proteins associate with other proteins, either to regulate them or to form larger cellular machines. Others perform specific tasks by binding to particular DNA sequences, or linking themselves tightly to RNA molecules. Throughout the 20th century, this incredibly dense web of interactions – dubbed the “interactome” in allusion to the genome – remained impenetrable. In the last decade, however, complete genome-sequence information and increasingly powerful bioinformatic tools have allowed us to generate and analyse draft interactome maps both for humans and for other model organisms. Although still far from complete, these maps are poised to serve as scaffolds for newly sophisticated models of how cells operate. Since many human diseases can be explained by perturbations of molecular interactions within cells, interactomes will drastically change how we think about human health, and how we set about designing drugs and preventive measures to counter illness.
HYBRID MEDICAL ANIMATION / SCIENCE PHOTO LIBRARY
Marc Vidal is a professor of genetics at Harvard Medical School and director of the Center for Cancer Systems Biology (CCSB) at the Dana-Farber Cancer Institute in Boston
Top-down processing
Our past determines our present The human eye is a camera that faithfully records everything in front of us, passing the information through the brain’s visual processor before it pops out as a conscious experience. This “bottom-up” process represents the textbook view. In truth, we are realising that our experience is closer to a form of augmented reality, in which our brain redraws what it sees to best fit our expectations and memories. The same goes for our other senses, and the growing suspicion is that kinks in this system of “top-down processing” might shed light on neurological disorders such as schizophrenia, autism and dyslexia. Whether or not that turns out to be the case, this idea is radically changing our view of how our past influences our here and now.
Dead oceans
Where climate change is really leading While we fret about the short-term effects of climate change on land-dwellers such as ourselves, global warming poses another, more insidious threat to the world’s oceans. Over the centuries, heat from the altered atmosphere will slowly seep into the sea. Warm water can hold much less dissolved oxygen than cool water, so across much of the ocean fish and other creatures could suffocate. Oxygen-deprived “dead zones” already exist in the oceans, including an area of thousands of square kilometres in the Gulf of Mexico. Simulations indicate that climate change could increase their total area sevenfold in the next couple of thousand years (Nature Geoscience, vol 2, p 105). Even if you don’t care about the fish, the oxygen-starved regions they vacate could come to host bacteria that emit nitrous oxide, a powerful greenhouse gas. Working out the likely extent of such feedback processes and devising strategies to fight them will be a major preoccupation for climate scientists in the coming years.
Phenomes
There’s more to life than genomes If we want truly to understand the living world, the genome won’t do. We need to get to grips with the “phenome”: the sum total of all traits, from genes to behaviour, that make up a living thing. If you think that sounds tough, you’d be right. Think about your own phenome. There are obvious traits such as eye colour, height and facial features. Then there are more intangible things such as your metabolic rate, personality, susceptibility to Alzheimer’s disease, and trillions of others. All of these came about through the interaction of your genome and your environment, starting from the moment you were conceived. That complexity perhaps explains why there is as yet no “human phenome project”, though such a thing was first mooted in 2003. But smaller-scale projects such as the Mouse Phenome Database are now springing up. From personalised medicine to our understanding of evolution, science will be the beneficiary. 9 October 2010 | NewScientist | 37
PART ONE Life and Earth
Earth scanning What lies beneath?
Biogenic climate change
We know more about outer space than we do about the interior of our planet. But geologists can now listen to the tiniest vibrations rumbling through the Earth. Analysing the speed and strength of these shudders is fleshing out our picture of what lies beneath us. In North America, for example, USArray – an ambitious rolling programme to scan the interior of the whole continent from west to east – has shown how the supervolcano beneath Yellowstone National Park gets its heat from a 1000-kilometredeep plume of hot, upwelling rock. Other projects have shown how the Indian continent is propping up the entire Himalayan mountain chain. By 2011 scientists aboard a Japanese deep-sea drilling ship called Chikyu hope to start drilling through a thin piece of oceanic crust to reach Earth’s mantle. For the first time we will be able to probe directly how rocks circulate around and mix in the mantle, and how this churning cauldron drives plate tectonics and ultimately shapes Earth’s surface – essential questions about our essentially unknown planet.
Evolution evolved Earth
Lloyd Cluff/CORBIS
Martin Brasier Travelling back to between a billion and half-a-billion years ago brings us to a curious passage in Earth’s history. At its beginning, modern eukaryotic organisms were thriving, but only as single cells. At its end, the world looked much like today, filled with large plants, invertebrates and fish. Between these two points, the geological record shows that Earth see-sawed wildly between periods of extreme heat and whole-planet glaciations – “snowball Earths”. The traditional view is that geological processes such as collisions between continents drove this climatic instability. Now, however, there is a growing realisation that feedbacks from life’s evolution played a pivotal part. Could it be, for example, that snowball glaciations were brought about by the evolution of multicellular algae and sponges?
Both could have fed upon greenhouse carbon from the atmosphere, reducing the air’s ability to hold onto heat, but when they died, that carbon would have fallen with them as sediments to the bottom of the sea. Was Earth then eventually saved from death-by-snowball through the invention of carbon recycling – the evolution of creatures with a “through gut”? It is certainly intriguing that snowball glaciations are found widely before the evolution of animals but never after the evolution of the anus. Such questions are more than whimsy. As we attempt to fathom our own impact on Earth’s climate, they give us a fundamental new perspective on our planet’s history and the role of life in it.
Martin Brasier is a professor of palaeobiology at the University of Oxford
Geoengineering More meddling – the solution to the planet’s ills? Steve Rayner
”For the first time we will be able to probe how the churning cauldron of the mantle ultimately shapes Earth’s surface”
38 | NewScientist | 9 October 2010
Geoengineering is “the deliberate large-scale manipulation of the planet’s environment to counteract climate change”, according to the UK’s Royal Society. It comes in two main varieties: approaches that seek to reflect incoming sunlight back into space, and those that aim to remove carbon dioxide from the air and store it underground. Of the first variety, injecting
sunlight-reflecting sulphate aerosols into the upper atmosphere is a relatively cheap, easy and quick option. Thanks to volcanic eruptions, we also know it works. But without drastic emission reductions in parallel, such a programme would have to be permanent for fear of a drastic temperature spike if discontinued. It might also disrupt the Asian monsoon upon which billions rely to bring rain for their crops. Such unknowns will make
CHRIS BUTLER / SCIENCE PHOTO LIBRARY
Nootropics
Food for thought You’ve got a big report to file, and the clock is ticking. If only you could concentrate harder, recall facts and figures more effectively, or just shake off that feeling of fatigue after yesterday’s late night. Soon a brain boost might follow a visit to your local pharmacy. Psychostimulant drugs such as Ritalin and Adderall, prescribed to treat attention-deficit hyperactivity disorder, and Aricept, used as a treatment for Alzheimer’s disease, have been shown to improve concentration and recall in healthy people, too. Such drugs are not currently available without a prescription, but some researchers say they should be. Multiply that extra brain power by the 7 billion members of the human race, they say, and the benefits to society and the pursuit of knowledge would soon start to add up. But is a race of drugged-up super-brains what we really want to be? Food for thought indeed.
Mirror neurons
The key to how we learn and think – possibly The saying “monkey see, monkey do” couldn’t be more true. Thanks to “mirror” neurons that fire not only when we perform an action ourselves but also when we see others perform it, our primate brains subconsciously mimic every behaviour they ever witness. That’s the theory, at least. Mirror neurons were first discovered in macaques in the 1990s, and brain scans using functional MRI had hinted that they exist in humans too. But it wasn’t until May this year that researchers measured the firing of mirror neurons in humans directly, using electrodes implanted in the brains of epileptic patients awaiting surgery (Current Biology, vol 20, p 750). While proponents of the power of mirror neurons claim they explain everything from empathy and compassion to a penchant for porn, their exact significance remains controversial. The next few years will see us homing in on what exactly they can and cannot explain about human cognition.
Palaeogenetics DNA blueprints from the past
international agreement on these measures difficult to achieve. By comparison, the political ramifications of capture and storage techniques seem slight. But these are distant and costly prospects compared with aerosol injection, and the benefits would take far longer to realise. Such dichotomies lie at the heart of the geoengineering problem. The possibility of geoengineering represents a fundamentally new frontier in the relationship between
science and nature. We should not dismiss it out of hand, but we should recognise that in the end social objections may be more binding than technological ones. We ignore the lessons of nuclear energy and genetically modified crops at our peril.
Steve Rayner is director of the Institute for Science, Innovation and Society at the Saïd Business School, University of Oxford
Until recently, we thought it would be impossible to decode the genetic blueprint of an extinct organism. In May this year, though, an international team published the full genome of a Neanderthal (Science, vol 328, p 710). What changed? Faster and cheaper DNA sequencing, mainly. Processing thousands or millions of sequences at once has allowed palaeogeneticists to piece together damaged DNA and discard degraded sections. They can also pull out the 5 per cent from a fossil sample that actually belongs to an ancient species, rather than subsequent bacterial contamination, by matching it up with DNA from a related, extant species. In the past five years, this has delivered genomes for several iconic species including a 40,000-year-old cave bear, a mammoth and now a Neanderthal. What does this tell us? A lot about our own family tree, for a start. The idea that ancient DNA sequences could be used to revive long-extinct beasts à la Jurassic Park is more fanciful, but we should never say never. 9 October 2010 | NewScientist | 39
PART ONE Life and Earth
DNA origami
Life as a template
”Converting solar energy into transportable and storable chemical fuels would set us on the way to clean energy for all”
REUTERS/Kim Kyung-Hoon
The stuff of life is sticky: put the right DNA base pairs together and they bond like Velcro. Take long single strands of DNA and throw in some shorter synthesised strands, and the bonds on the short strands can pull the long strands into specific shapes and hold them all together. This “DNA origami” technique is one of the most promising of many ways to make molecules self-assemble into 3D structures. It has been used to make a bewildering variety of objects, from toothed gears to 3D boxes with a lock-and-key mechanism. Ultimately, the hope is to use such boxes for drug delivery, and to exploit the folding and unfolding of biomolecules to make nanoscale computer components.
Artificial photosynthesis Energy out of thin air Nate Lewis A leaf is a beautiful thing. It is also a wonder of chemical engineering. Within it, photosynthetic reactioncentres collect solar energy to drive the transformation of water and carbon dioxide in the air into sugars that nourish and build the plant. Would that we could do something similar. The sun is by far the biggest energy source we know, but sunlight can’t be everywhere all the time. If we could find a cheap way to convert solar energy into storable, transportable chemical fuels available 24/7, we would be well on our way to clean energy for all. Some pieces of the jigsaw are already in place. Tiny light-collecting particles can be embedded on a
40 | NewScientist | 9 October 2010
membrane to absorb energy and split carbon dioxide and water molecules. The products are not sugars, but carbon-neutral transportation fuels: hydrogen, methanol and, in the future, high-energy-density fuels optimised for specific vehicles such as aircraft. This year, the US Department of Energy earmarked $122 million to set up the Joint Center for Artificial Photosynthesis in California. Here and across the world the race is on to develop new absorbers, catalysts and membranes that will permit the large-scale realisation of an idea that could change the world for good.
Nate Lewis is a professor of chemistry at the California Institute of Technology, Pasadena, and director of the Joint Center for Artificial Photosynthesis
Endogenous stem cells
Financial ecology
How does my organ grow?
Engineering the economic ecosystem Robert May Ecology is a young and still evolving subject. As it has moved from a largely descriptive science to one with a firmer conceptual underpinning, romantic notions of the “balance of nature” have given way to a detailed understanding of how the structure of food webs allows the richness of ecosystems to be maintained. Economics can learn something here. The recent banking crises have made it very clear that increasingly complex strategies for managing risk in individual financial institutions have not been matched by attention to risk in the system as a whole. And yet vague mantras about an economic equivalent of natural balance – invisible hands that efficiently produce “general equilibrium” if
sufficiently free from regulatory constraints – are still heard from many bonus-bloated bankers. Simple mathematical caricatures of “banking ecosystems” provide a fresh approach. They capture some of the essential dynamics of interacting financial networks, and have interesting parallels with – and significant differences from – earlier work on ecological stability and complexity. Such models will become increasingly important as we attempt to move towards financial systems engineered against systemic risk. But overturning entrenched ways of thinking won’t be easy.
Robert May is a professor of zoology at the University of Oxford, and was president of the UK’s Royal Society from 2000 to 2005
Competition Vote for your favourite big idea – and win a tablet PC
plainpicture/Johner
Full details of how to take part in our competition will be in next week’s issue to accompany the second batch of ideas, from physics, space and technology. Just tell us which of the 50 you think could radically change science, and why. An HP TouchSmart multi-touch tablet PC with 20-inch screen and 500 GB hard drive could be yours.
Stem cells are arguably the most exciting frontier in medicine right now. Most cells of the human body are irreversibly specialised or “differentiated” into roughly 200 types. Stem cells, on the other hand, are blank slates with the potential to develop in many different ways. That means they could be used to heal a myriad of damaged or diseased tissues. Most research so far has focused on creating them from embryos or adult tissues in the laboratory, manipulating their development using chemical “growth factors” and implanting them where needed. But there could be a cleverer way: to awaken our bodies’ own “endogenous” stem cells to achieve natural regeneration. Other animals do this. Amphibians, for example, can regrow entire lost limbs while hobbling about their daily business. Some day, the thinking goes, simply injecting the right chemicals might be enough to allow us to grow a new kidney or pancreas – or even a leg.
Neuronal recycling Culture is a parasite
The architecture of our brains far predates writing, religion and art. So how come we acquire these cultural traits and abilities with such ease? The standard answer is that our big, plastic brains have a uniquely flexible and generalised learning capacity. But is that true? The human brain is not homogeneous, after all, but organised into specialised areas. Moreover, brain imaging reveals that abilities such as reading and mathematics have distinct “neuronal niches”; they too are confined to specific brain circuits. That is compelling evidence for an idea known as neuronal recycling: that our cultural abilities invaded and parasitised brain circuits originally dedicated to evolutionarily older, but related functions. Reading, for example, seems to occupy circuits sensitive to complex shapes and with good connections to areas dealing with language (Reading in the Brain, Viking, 2009). If correct, it is our brains shape our culture, rather than our culture our brains. Human ingenuity is not unlimited, but fundamentally constrained by neural architecture.
A universal flu vaccine Taming a global killer
Bird and swine flu might have receded for now, but the top candidate for a global pandemic remains: a novel strain of flu. That is because flu mutates, so catching it one year may not stop you from catching it the next. This is why we make new flu vaccines year after year. It is also why every few decades a flu strain appears with the genetic novelty to evade our herd immunity and wreak global havoc. How to stop that? By developing a universal vaccine effective against all strains. Various possibilities that trigger an immune response against the parts of the virus that don’t mutate are in the works. Several have reached trials in people. If they prove effective, flu could soon become just one more half-forgotten disease that we vaccinate children against. 9 October 2010 | NewScientist | 41
50 ideas to change science Part one Life and Earth What ideas are set to transform our understanding of the world around us and our relationship with it? Over the next two weeks, New Scientist looks at the advances that will really make a difference. We ask leading experts to tell us what will revolutionise their field and include some of our own ideas. We begin with the coming revolution in biology, life and Earth: ideas such as DNA origami, super-evolution, brain maps and ultrasounding the planet. Some of them are strokes of genius, some subtle slants on old problems, others just fundamentally new ways to make observations. All will change science beyond measure. Next week sees the turn of physics, space and technology – and your chance to tell us which of all the ideas will have the biggest impact on science, and why.
32 | NewScientist |9 October 2010
Artificial cells Life is membranes Jack Szostak
Brett rYDer
The exact nature of the first cell, the forerunner of all life today, is still a mystery. It is an exciting puzzle, but reconstructing events that took place 4 billion years ago is no mean feat. Fortunately, there is much to be learned from tackling a more modest goal, that of building simple artificial cells, beginning with their walls. Primitive membranes made from fatty acids seem to have all the right properties, such as allowing for spontaneous growth and division, as well as letting nutrients penetrate the cell. What drove the transition from such membranes to modern ones, which are based on the more complex phospholipids? A primitive RNA might have catalysed the synthesis of phospholipids, but what advantage would phospholipids have conferred on primordial cells? The answer may well be the first clue to the avalanche of events that eventually led to modern biology. If we can find it in artificial cells, we will be transported back to the onset of Darwinian evolution and the origins of life as we know it.
Jack Szostak is professor of genetics at Harvard Medical School and a co-recipient of the 2009 Nobel prize in physiology or medicine
9 October 2010 | NewScientist | 33
PART ONE Life and Earth
Super-evolution Change for the common good David Sloan Wilson
chip clark/smnh
In the study of evolution, the past half-century was the age of reductionism, when everything was explained in terms of individual self-interest and selfish genes. Now we are entering the age of holism, which recognises how colonies of social insects, human societies and at least some multispecies ecosystems can respond as a single “superorganism” to selective pressures. The turning point came in the 1970s, when biologist Lynn Margulis proposed that complex, nucleated cells originated as symbiotic associations of bacterial cells. Now it is known that every entity recognised as an organism is a highly organised group of individual cells, making it hard to deny that groups of organisms can themselves have organism-like properties and so can evolve in concert.
Impact assessment Revisiting Earth’s ancient trials
”We are beginning to recognise that societies can respond as a single ‘super-organism’ to selective pressures” 34 | NewScientist | 9 October 2010
alex wild
The history of life is littered with great upheavals: blooming diversity one epoch, mass wipe-outs the next. On that scale the Hangenberg event, an extinction 359 million years ago at the end of the Devonian period, was considered a minor blip. Not any more. The end of the Devonian was a crucial time for vertebrates. Many primitive lineages went extinct as sharks and bony fish became masters of the waters and tetrapods, the four-legged animals that eventually evolved into dinosaurs and mammals, conquered the land. We had seen this as a gradual change, one fuelled by a series of extinction pulses spread over 25 million years of the Devonian’s dog days. But now it seems they were piffling in comparison to the Hangenberg event, which all but wiped out the typical Devonian species and cleared the decks for the new world order (Proceedings of the National Academy of Sciences, vol 107, p 10131). We don’t know what caused this disaster. But the radical reassessment of its importance shows how ancient fossils remain a fertile field for new thinking.
The process of group selection through which this occurs seemed to have been authoritatively rejected during the age of individualism. But Darwin got it right: altruistic behaviours “for the good of the group” – whether that group is a species or an ecosystem – require a process of between-group selection to evolve, and tend to be undermined by individual selection within groups. What is new is the idea that higher-level selection is not invariably trumped by lower-level selection – and indeed sometimes wins out. Now we must pick through the implications of that insight, which span from the origin of life to the structure of ecosystems to the nature of religion and human biocultural evolution.
David Sloan Wilson is a professor of biology and anthropology at the State University of New York at Binghamton
Cognitive control Towards the seat of consciousness Allan Hobson The question “what is consciousness?” represents one of the great frontiers of contemporary science. Thanks to studies of humans and animals, we now know that it is a subtly nuanced state whose nature and intensity varies according to the brain’s intrinsic level of activity, its chemical microclimate and the information it receives from outside. By exploiting the normal vicissitudes of waking, sleeping and dreaming states, we are now beginning to explore how consciousness is expressed and controlled. For example, I have been involved in studies comparing brain activation in REM sleep with that in lucid-dreaming states, in which we retain much executive brain function. They seem to confirm the central importance of one specific area of the frontal brain – the dorsolateral prefrontal cortex – in regulating many key aspects of consciousness, including attention, decision-making and voluntary action. A combination of imaging techniques, judicious measures of subjective experience and detailed cellular and molecular-level studies will continue to deepen our understanding of our cognitive command centres in the coming years. With them we hope to crack the puzzle of consciousness, and perhaps correct the dysfunctional states of the brain we now call mental illness.
Allan Hobson is emeritus professor of psychiatry at Harvard Medical School in Cambridge, Massachusetts
Ocean observatories Wired up, deep down
Earth’s oceans are vast, unexplored regions full of unanswered questions. What part do the oceans play in climate change? How do earthquakes arise in undersea subduction zones, which account for 90 per cent of all seismic energy released worldwide? What does life look like on and below the sea floor? Grappling with these and other questions have been hindered by a paucity of data. A new project should change that. Rather than relying on the laborious traditional method of ship-based expeditions, the Ocean Observatories Initiative aims to wire up the ocean. Its network of sensors, strung from ocean surface to bottom in regions off the US coast and further out in the Pacific and Atlantic, will stream scientific and video data back not only to labs, but also to schools and homes via the internet. Work got under way late last year. Continuous, real-time interactions with the ocean could be the breakthrough we need to explore our planet’s final frontier.
Artificial enzymes
Molecules for all occasions Whether for a new drug or solar cell, we constantly strive to design and build intricate new molecules. Making them is one thing; making them efficiently enough for commercial production is quite another. If only we could take a leaf out of nature’s book, which uses highly specialised enzymes as catalysts to churn out vast quantities of the molecules life needs. Increasingly, we can. We can take natural enzymes and randomly tweak their structure until a variant efficiently produces the molecule we desire. For a rather less hit-and-miss strategy, we can use computer-led “rational design” modelling processes to make artificial enzymes from scratch. Ultimately, the aim is to trump nature. Compared with artificial catalysts, enzymes are wrapped around a relatively limited range of metals at their core. By combining the best of natural and artificial catalysis, we might be able to make enzymes – and final products – that are capable of simply anything.
The 1000 Genomes Project A catalogue of human variation The mapping of the human genome, largely completed 10 years ago, was a remarkable feat. But if genomics is to fulfil its potential, for example in combating disease, we need to know how much DNA sequences vary between individuals. Within the next few years we should do. The 1000 Genomes Project, a private-public consortium established in 2008, aims to create a detailed map of human genetic variation. Pilot projects involving 885 people were completed in June this year and identified about 16 million DNA variations, half of them not previously identified. That suggests there may be around 60 million such variations to be found. The full project, analysing the genomes of 2500 people from 27 populations across the world, is now under way. The growing dataset is freely available online at www.1000genomes.org. 9 October 2010 | NewScientist | 35
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PART ONE Life and Earth
The web of life Darwin’s tree uprooted Ford Doolittle Bacterial genomes, we are coming to realise, are mosaics. Genes can come from different sources, not just a single common ancestor; even between two strains of the same species half of the genes may differ. The principal culprit is “lateral” gene transfer, in which genetic material from one bacterium passes to another, whether by expulsion into the environment and subsequent uptake or through the agency of viruses or bacterial sex. Transfer occurs within and between species and even between representatives of the bacterial equivalents of phyla or kingdoms. One consequence is that no simple pattern defines the relationships between microbial species. The tree of life with its tidily ramifying branches, a metaphor for the theory of evolution, has been uprooted. We now recognise that understanding the processes of evolution in no way depends on this “tree-thinking”. What’s more, the new discipline of metagenomics, which focuses on microbial communities and the differences in functional genes active at that level, is reducing the need for “species-thinking”. The upshot will be a sharper insight into the relationships of the tangled web of life.
Ford Doolittle is emeritus professor of biochemistry and molecular biology at Dalhousie University in Halifax, Nova Scotia, Canada
”Drawing a basic map of the brain would help us to understand how its regions interact to make behaviour”
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The connectome Mental maps Tim Behrens Understanding the routes by which populations of brain cells share information would be a major step towards understanding how our brains function. But although we can infer individual connections, we have no basic wiring diagram of the human brain. This is hardly surprising. The brain contains approximately 100 billion neurons, and a single neuron may connect to 10,000 others. Yet emerging techniques mean we are now making headway in this daunting task. Using electron microscopes, for example, we can probe animal brains neuron-by-neuron, connection-byconnection, in the hope of discovering
characteristic circuits that repeat themselves throughout the brain. From a wider perspective, brain imaging technologies can map the brain’s highways – large “cables” consisting of many thousands of connections between distinct brain regions. The US National Institutes of Health has begun to fund a major effort, the Human Connectome Project, to generate a comprehensive map of large-scale brain connections in humans. Following its directions, we might arrive at a better understanding of how the brain’s regions interact to produce behaviour.
Tim Behrens is a neuroscientist at the University of Oxford
Interactomes
Mapping cellular complexity Marc Vidal
Proteins and RNAs, the molecules encoded by genes, rarely act in isolation. Some proteins associate with other proteins, either to regulate them or to form larger cellular machines. Others perform specific tasks by binding to particular DNA sequences, or linking themselves tightly to RNA molecules. Throughout the 20th century, this incredibly dense web of interactions – dubbed the “interactome” in allusion to the genome – remained impenetrable. In the last decade, however, complete genome-sequence information and increasingly powerful bioinformatic tools have allowed us to generate and analyse draft interactome maps both for humans and for other model organisms. Although still far from complete, these maps are poised to serve as scaffolds for newly sophisticated models of how cells operate. Since many human diseases can be explained by perturbations of molecular interactions within cells, interactomes will drastically change how we think about human health, and how we set about designing drugs and preventive measures to counter illness.
HYBRID MEDICAL ANIMATION / SCIENCE PHOTO LIBRARY
Marc Vidal is a professor of genetics at Harvard Medical School and director of the Center for Cancer Systems Biology (CCSB) at the Dana-Farber Cancer Institute in Boston
Top-down processing
Our past determines our present The human eye is a camera that faithfully records everything in front of us, passing the information through the brain’s visual processor before it pops out as a conscious experience. This “bottom-up” process represents the textbook view. In truth, we are realising that our experience is closer to a form of augmented reality, in which our brain redraws what it sees to best fit our expectations and memories. The same goes for our other senses, and the growing suspicion is that kinks in this system of “top-down processing” might shed light on neurological disorders such as schizophrenia, autism and dyslexia. Whether or not that turns out to be the case, this idea is radically changing our view of how our past influences our here and now.
Dead oceans
Where climate change is really leading While we fret about the short-term effects of climate change on land-dwellers such as ourselves, global warming poses another, more insidious threat to the world’s oceans. Over the centuries, heat from the altered atmosphere will slowly seep into the sea. Warm water can hold much less dissolved oxygen than cool water, so across much of the ocean fish and other creatures could suffocate. Oxygen-deprived “dead zones” already exist in the oceans, including an area of thousands of square kilometres in the Gulf of Mexico. Simulations indicate that climate change could increase their total area sevenfold in the next couple of thousand years (Nature Geoscience, vol 2, p 105). Even if you don’t care about the fish, the oxygen-starved regions they vacate could come to host bacteria that emit nitrous oxide, a powerful greenhouse gas. Working out the likely extent of such feedback processes and devising strategies to fight them will be a major preoccupation for climate scientists in the coming years.
Phenomes
There’s more to life than genomes If we want truly to understand the living world, the genome won’t do. We need to get to grips with the “phenome”: the sum total of all traits, from genes to behaviour, that make up a living thing. If you think that sounds tough, you’d be right. Think about your own phenome. There are obvious traits such as eye colour, height and facial features. Then there are more intangible things such as your metabolic rate, personality, susceptibility to Alzheimer’s disease, and trillions of others. All of these came about through the interaction of your genome and your environment, starting from the moment you were conceived. That complexity perhaps explains why there is as yet no “human phenome project”, though such a thing was first mooted in 2003. But smaller-scale projects such as the Mouse Phenome Database are now springing up. From personalised medicine to our understanding of evolution, science will be the beneficiary. 9 October 2010 | NewScientist | 37
PART ONE Life and Earth
Earth scanning What lies beneath?
Biogenic climate change
We know more about outer space than we do about the interior of our planet. But geologists can now listen to the tiniest vibrations rumbling through the Earth. Analysing the speed and strength of these shudders is fleshing out our picture of what lies beneath us. In North America, for example, USArray – an ambitious rolling programme to scan the interior of the whole continent from west to east – has shown how the supervolcano beneath Yellowstone National Park gets its heat from a 1000-kilometredeep plume of hot, upwelling rock. Other projects have shown how the Indian continent is propping up the entire Himalayan mountain chain. By 2011 scientists aboard a Japanese deep-sea drilling ship called Chikyu hope to start drilling through a thin piece of oceanic crust to reach Earth’s mantle. For the first time we will be able to probe directly how rocks circulate around and mix in the mantle, and how this churning cauldron drives plate tectonics and ultimately shapes Earth’s surface – essential questions about our essentially unknown planet.
Evolution evolved Earth
Lloyd Cluff/CORBIS
Martin Brasier Travelling back to between a billion and half-a-billion years ago brings us to a curious passage in Earth’s history. At its beginning, modern eukaryotic organisms were thriving, but only as single cells. At its end, the world looked much like today, filled with large plants, invertebrates and fish. Between these two points, the geological record shows that Earth see-sawed wildly between periods of extreme heat and whole-planet glaciations – “snowball Earths”. The traditional view is that geological processes such as collisions between continents drove this climatic instability. Now, however, there is a growing realisation that feedbacks from life’s evolution played a pivotal part. Could it be, for example, that snowball glaciations were brought about by the evolution of multicellular algae and sponges?
Both could have fed upon greenhouse carbon from the atmosphere, reducing the air’s ability to hold onto heat, but when they died, that carbon would have fallen with them as sediments to the bottom of the sea. Was Earth then eventually saved from death-by-snowball through the invention of carbon recycling – the evolution of creatures with a “through gut”? It is certainly intriguing that snowball glaciations are found widely before the evolution of animals but never after the evolution of the anus. Such questions are more than whimsy. As we attempt to fathom our own impact on Earth’s climate, they give us a fundamental new perspective on our planet’s history and the role of life in it.
Martin Brasier is a professor of palaeobiology at the University of Oxford
Geoengineering More meddling – the solution to the planet’s ills? Steve Rayner
”For the first time we will be able to probe how the churning cauldron of the mantle ultimately shapes Earth’s surface”
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Geoengineering is “the deliberate large-scale manipulation of the planet’s environment to counteract climate change”, according to the UK’s Royal Society. It comes in two main varieties: approaches that seek to reflect incoming sunlight back into space, and those that aim to remove carbon dioxide from the air and store it underground. Of the first variety, injecting
sunlight-reflecting sulphate aerosols into the upper atmosphere is a relatively cheap, easy and quick option. Thanks to volcanic eruptions, we also know it works. But without drastic emission reductions in parallel, such a programme would have to be permanent for fear of a drastic temperature spike if discontinued. It might also disrupt the Asian monsoon upon which billions rely to bring rain for their crops. Such unknowns will make
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Nootropics
Food for thought You’ve got a big report to file, and the clock is ticking. If only you could concentrate harder, recall facts and figures more effectively, or just shake off that feeling of fatigue after yesterday’s late night. Soon a brain boost might follow a visit to your local pharmacy. Psychostimulant drugs such as Ritalin and Adderall, prescribed to treat attention-deficit hyperactivity disorder, and Aricept, used as a treatment for Alzheimer’s disease, have been shown to improve concentration and recall in healthy people, too. Such drugs are not currently available without a prescription, but some researchers say they should be. Multiply that extra brain power by the 7 billion members of the human race, they say, and the benefits to society and the pursuit of knowledge would soon start to add up. But is a race of drugged-up super-brains what we really want to be? Food for thought indeed.
Mirror neurons
The key to how we learn and think – possibly The saying “monkey see, monkey do” couldn’t be more true. Thanks to “mirror” neurons that fire not only when we perform an action ourselves but also when we see others perform it, our primate brains subconsciously mimic every behaviour they ever witness. That’s the theory, at least. Mirror neurons were first discovered in macaques in the 1990s, and brain scans using functional MRI had hinted that they exist in humans too. But it wasn’t until May this year that researchers measured the firing of mirror neurons in humans directly, using electrodes implanted in the brains of epileptic patients awaiting surgery (Current Biology, vol 20, p 750). While proponents of the power of mirror neurons claim they explain everything from empathy and compassion to a penchant for porn, their exact significance remains controversial. The next few years will see us homing in on what exactly they can and cannot explain about human cognition.
Palaeogenetics DNA blueprints from the past
international agreement on these measures difficult to achieve. By comparison, the political ramifications of capture and storage techniques seem slight. But these are distant and costly prospects compared with aerosol injection, and the benefits would take far longer to realise. Such dichotomies lie at the heart of the geoengineering problem. The possibility of geoengineering represents a fundamentally new frontier in the relationship between
science and nature. We should not dismiss it out of hand, but we should recognise that in the end social objections may be more binding than technological ones. We ignore the lessons of nuclear energy and genetically modified crops at our peril.
Steve Rayner is director of the Institute for Science, Innovation and Society at the Saïd Business School, University of Oxford
Until recently, we thought it would be impossible to decode the genetic blueprint of an extinct organism. In May this year, though, an international team published the full genome of a Neanderthal (Science, vol 328, p 710). What changed? Faster and cheaper DNA sequencing, mainly. Processing thousands or millions of sequences at once has allowed palaeogeneticists to piece together damaged DNA and discard degraded sections. They can also pull out the 5 per cent from a fossil sample that actually belongs to an ancient species, rather than subsequent bacterial contamination, by matching it up with DNA from a related, extant species. In the past five years, this has delivered genomes for several iconic species including a 40,000-year-old cave bear, a mammoth and now a Neanderthal. What does this tell us? A lot about our own family tree, for a start. The idea that ancient DNA sequences could be used to revive long-extinct beasts à la Jurassic Park is more fanciful, but we should never say never. 9 October 2010 | NewScientist | 39
PART ONE Life and Earth
DNA origami
Life as a template
”Converting solar energy into transportable and storable chemical fuels would set us on the way to clean energy for all”
REUTERS/Kim Kyung-Hoon
The stuff of life is sticky: put the right DNA base pairs together and they bond like Velcro. Take long single strands of DNA and throw in some shorter synthesised strands, and the bonds on the short strands can pull the long strands into specific shapes and hold them all together. This “DNA origami” technique is one of the most promising of many ways to make molecules self-assemble into 3D structures. It has been used to make a bewildering variety of objects, from toothed gears to 3D boxes with a lock-and-key mechanism. Ultimately, the hope is to use such boxes for drug delivery, and to exploit the folding and unfolding of biomolecules to make nanoscale computer components.
Artificial photosynthesis Energy out of thin air Nate Lewis A leaf is a beautiful thing. It is also a wonder of chemical engineering. Within it, photosynthetic reactioncentres collect solar energy to drive the transformation of water and carbon dioxide in the air into sugars that nourish and build the plant. Would that we could do something similar. The sun is by far the biggest energy source we know, but sunlight can’t be everywhere all the time. If we could find a cheap way to convert solar energy into storable, transportable chemical fuels available 24/7, we would be well on our way to clean energy for all. Some pieces of the jigsaw are already in place. Tiny light-collecting particles can be embedded on a
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membrane to absorb energy and split carbon dioxide and water molecules. The products are not sugars, but carbon-neutral transportation fuels: hydrogen, methanol and, in the future, high-energy-density fuels optimised for specific vehicles such as aircraft. This year, the US Department of Energy earmarked $122 million to set up the Joint Center for Artificial Photosynthesis in California. Here and across the world the race is on to develop new absorbers, catalysts and membranes that will permit the large-scale realisation of an idea that could change the world for good.
Nate Lewis is a professor of chemistry at the California Institute of Technology, Pasadena, and director of the Joint Center for Artificial Photosynthesis
Endogenous stem cells
Financial ecology
How does my organ grow?
Engineering the economic ecosystem Robert May Ecology is a young and still evolving subject. As it has moved from a largely descriptive science to one with a firmer conceptual underpinning, romantic notions of the “balance of nature” have given way to a detailed understanding of how the structure of food webs allows the richness of ecosystems to be maintained. Economics can learn something here. The recent banking crises have made it very clear that increasingly complex strategies for managing risk in individual financial institutions have not been matched by attention to risk in the system as a whole. And yet vague mantras about an economic equivalent of natural balance – invisible hands that efficiently produce “general equilibrium” if
sufficiently free from regulatory constraints – are still heard from many bonus-bloated bankers. Simple mathematical caricatures of “banking ecosystems” provide a fresh approach. They capture some of the essential dynamics of interacting financial networks, and have interesting parallels with – and significant differences from – earlier work on ecological stability and complexity. Such models will become increasingly important as we attempt to move towards financial systems engineered against systemic risk. But overturning entrenched ways of thinking won’t be easy.
Robert May is a professor of zoology at the University of Oxford, and was president of the UK’s Royal Society from 2000 to 2005
Competition Vote for your favourite big idea – and win a tablet PC
plainpicture/Johner
Full details of how to take part in our competition will be in next week’s issue to accompany the second batch of ideas, from physics, space and technology. Just tell us which of the 50 you think could radically change science, and why. An HP TouchSmart multi-touch tablet PC with 20-inch screen and 500 GB hard drive could be yours.
Stem cells are arguably the most exciting frontier in medicine right now. Most cells of the human body are irreversibly specialised or “differentiated” into roughly 200 types. Stem cells, on the other hand, are blank slates with the potential to develop in many different ways. That means they could be used to heal a myriad of damaged or diseased tissues. Most research so far has focused on creating them from embryos or adult tissues in the laboratory, manipulating their development using chemical “growth factors” and implanting them where needed. But there could be a cleverer way: to awaken our bodies’ own “endogenous” stem cells to achieve natural regeneration. Other animals do this. Amphibians, for example, can regrow entire lost limbs while hobbling about their daily business. Some day, the thinking goes, simply injecting the right chemicals might be enough to allow us to grow a new kidney or pancreas – or even a leg.
Neuronal recycling Culture is a parasite
The architecture of our brains far predates writing, religion and art. So how come we acquire these cultural traits and abilities with such ease? The standard answer is that our big, plastic brains have a uniquely flexible and generalised learning capacity. But is that true? The human brain is not homogeneous, after all, but organised into specialised areas. Moreover, brain imaging reveals that abilities such as reading and mathematics have distinct “neuronal niches”; they too are confined to specific brain circuits. That is compelling evidence for an idea known as neuronal recycling: that our cultural abilities invaded and parasitised brain circuits originally dedicated to evolutionarily older, but related functions. Reading, for example, seems to occupy circuits sensitive to complex shapes and with good connections to areas dealing with language (Reading in the Brain, Viking, 2009). If correct, it is our brains shape our culture, rather than our culture our brains. Human ingenuity is not unlimited, but fundamentally constrained by neural architecture.
A universal flu vaccine Taming a global killer
Bird and swine flu might have receded for now, but the top candidate for a global pandemic remains: a novel strain of flu. That is because flu mutates, so catching it one year may not stop you from catching it the next. This is why we make new flu vaccines year after year. It is also why every few decades a flu strain appears with the genetic novelty to evade our herd immunity and wreak global havoc. How to stop that? By developing a universal vaccine effective against all strains. Various possibilities that trigger an immune response against the parts of the virus that don’t mutate are in the works. Several have reached trials in people. If they prove effective, flu could soon become just one more half-forgotten disease that we vaccinate children against. 9 October 2010 | NewScientist | 41