杏吧原创

The mysteries of life

From sex and sleep to ageing and aliens, there's still an awful lot we don't understand about the living world. But what are the biggest unanswered questions, and how close are we to solving them? Here are New 杏吧原创's top 10, plus the experts' choice

1 How did life begin?

IN 1953 an iconic set of experiments showed that some of the chemical building blocks of life, such as amino acids, could form spontaneously in the atmospheric conditions thought to prevail on the primordial Earth. This gave rise to the idea that the early oceans were a 鈥減rimordial soup鈥 from which life somehow emerged.

The idea still holds a great deal of water, but 50 years on the details remain sketchy. It is still unclear, for example, how a primordial soup of simple molecules could give rise to today鈥檚 system of DNA and proteins. It is a classic chicken-and-egg problem: DNA codes for the proteins that catalyse the chemical reactions that replicate DNA. How could one exist before the other?

One theory proposes that the first genomes were actually made of RNA. Like DNA, RNA consists of chains of nucleic acids, but due to its slightly different chemical properties, RNA can catalyse some reactions without the need for proteins. This self-sufficient RNA world could then have been superseded by our present DNA one.

Another idea currently in vogue is 鈥渕etabolism first鈥, in which the chemical reactions necessary to liberate energy and support life arose before self-replicating molecules did. According to one version of the model this could have started out at deep-sea hydrothermal vents with the formation of pyrite from iron sulphide and hydrogen sulphide.

Another bone of contention among biologists is how the basic chemical building blocks of life could have become sufficiently concentrated to meet, react and form more complex molecules such as proteins and nucleic acids. Researchers have speculated that the chemically 鈥渟ticky鈥 surfaces of certain minerals 鈥 clays are a particular favourite 鈥 could have been life鈥檚 first incubator. Or alternatively it might have been droplets of seawater thrown into the atmosphere, or perhaps small chambers inside rocks.

One of the key issues is to work out when life began 鈥 do that and you have a better idea of the conditions under which it formed. Easier said than done. Some researchers think there are chemical signs of life in rocks 3.8 billion years old, a 鈥渕ere鈥 0.2 billion years after the Earth became habitable. Others believe that signs of life do not show up until 2.7 billion years ago.

Yet another idea has it that life did not originate on Earth at all, but arrived from space cocooned in asteroids or comets. Experiments have confirmed that the basic chemicals of life, including amino acids, exist in space and that microorganisms could survive an interplanetary trip. But, wherever it came from, this still does not explain how life began in the first place.

Claire Ainsworth

2 How many species are there?

LIFE on Earth remains largely uncharted territory. In the two and a half centuries since Carl Linnaeus devised his system for naming and classifying organisms, scientists have formally described and named about 1.7 million species. (No one knows the exact number, because there is no central clearing house for this type of information.) Everyone agrees that many unknown species remain, but just how many is anyone鈥檚 guess. Estimates range from 5 million to 100 million.

In the past couple of years, evolutionary biologists have begun to clamour for a Big Science project to provide an answer.

Not because the final count itself makes much difference, but because the real prize lies in understanding who lives where. That knowledge 鈥 woefully incomplete so far 鈥 forms the bedrock on which much of conservation biology, evolutionary biology and ecology are built.

So is it 5 million or 100 million species? Biologists have tried to get nearer an answer by extrapolating from detailed samples. More than 20 years ago, entomologist Terry Erwin of the Smithsonian Institution in Washington DC fogged 19 trees of one Panamanian rainforest species with insecticide and counted the insects that rained down. If other tree species hosted a similar number of insect species, he estimated the world might hold upwards of 30 million insect species alone. But more recently, researchers in New Guinea have shown that the same insects often feed on several different tree species, leading them to a make a lower estimate of around 5 million insect species.

Microbes, though, are the real terra incognita. Just a few thousand species of bacteria have been described, largely because they are so featureless to the eye. But when geneticists compare gene sequences among a collection of microorganisms, they find vastly more diversity hidden there. Two years ago, Thomas Curtis of the University of Newcastle upon Tyne, UK, used this diversity to calculate that a single gram of soil might contain between 6400 and 38,000 species of bacteria, and a tonne of soil might hold as many as 4 million.

A better count of the world鈥檚 biodiversity might at last be in the offing. Several groups are making plans to collect and classify species, using both molecular and more traditional physical characteristics, on a scale never attempted before. This mass-production approach should reveal the diversity of obscure groups as well as taxonomists鈥 favourites. If the plans are put into practice, the question of how many species inhabit Earth may have a better answer in 20 years鈥 time.

Bob Holmes

3 Are we still evolving?

HUMANS are not like other animals. We have contraceptives to control the number of children we produce, aspirations beyond reproduction, medicines to sustain life and postpone death, and the potential to engineer our own DNA. It is tempting to think that we have moved beyond the clutches of evolution. Tempting, but wrong.

Evolution is built on two cornerstones: heritable variation and selection. Plainly, humans vary. The source of that variation is genetic mutation, which still occurs at around the same rate today as it has throughout our evolution.

But what about selection? In the west we certainly seem to have wriggled free of natural selection. It is no longer just the fittest who survive and reproduce. Modern medicine allows people to overcome diseases and injuries that would once have killed them. Birth control and reproductive technology make reproduction a matter of choice, not adaptive quality. Likewise, the power of sexual selection has been blunted because the mass media has a strong influence on who we find attractive, and because 鈥渂eautiful鈥 people do not necessarily have the most children.

But that still leaves artificial selection, the force more usually associated with the domestication of animals and plants. Obviously, we do not systematically direct the evolution of our own genome in the way our ancestors did to produce high-yield wheat or miniature poodles, but there is a parallel: many human traits only exist because they have been selected for artificially. The invention of spectacles has allowed myopia to proliferate, dairy farming has given many adults the ability to digest milk sugar, and stone tools allowed our earliest ancestors to extend their physical abilities without evolving bigger muscles. These and countless other innovations have affected our gene pool.

Other forces are at work, too. Humans are changing the environment, altering the climate, filling the world with pollution and creating the conditions for new diseases to emerge 鈥 changes that are almost certainly driving human evolution.

And while we may think that genetic technology will give us control over our future, it may actually send human evolution in unexpected directions. It is hubris to think that we can engineer our genome to a particular end. We know so little about how our genes interact that any attempts at engineering sperm or eggs may well have unpredictable results. All we can say for sure is that our gene pool is changing, perhaps faster than ever. But where evolution will take us remains a mystery.

Kate Douglas

4 Why do we sleep?

THE average person spends a third of their life asleep, and going without it kills you quicker than starvation. Sleep seems to be fundamental in biology: all animals do it, and even cultured neurons in a Petri dish spontaneously enter a sleep-like state. Yet we don鈥檛 know what sleep is for.

There are several ideas, of course, ranging from obvious ones about restoration and recovery to more elaborate theories dealing with memory processing. But none has been confirmed, and the only thing sleep researchers can agree on is that there is no satisfactory answer.

Part of the problem is that sleep comprises two very different states: rapid eye movement sleep (REM), when the eyes flick from side to side, the brain is very active and most dreaming occurs, and non-REM, which is a deeper state of unconsciousness. These are so unlike one another that they surely cannot have the same purpose. But they are somehow intertwined. In natural sleep, non-REM is always followed by a bout of REM, so their functions are probably linked in some way.

Amid the confusion, one thing is clear 鈥 sleep is for the brain. One reason we know this is that animals sleep but plants do not. And other organs, such as muscles and liver, do not sleep. This might seem trivially obvious, but it was only this year that a large region of the brain called the cerebellum was shown to participate in sleep.

Armed with the knowledge that sleep is a whole-brain phenomenon, researchers are starting to unite behind the idea that non-REM sleep, at least, is when the brain makes good the damage done by free radicals, the toxic chemical by-products of metabolism. Other organs repair this damage by sacrificing and replacing injured cells, but this is not an option for the brain. So it switches itself off and, like a highway-repair team working at night, gets on with the job when things are quiet.

Several pieces of evidence have emerged to back this up. One is that animals with a high metabolic rate, and hence a faster rate of free radical damage, sleep more than those with a slow metabolism. Another is that the brains of sleep-deprived rats suffer unusually high levels of oxidative damage. And earlier this year gene-expression studies confirmed that the brain actively switches on genes involved in protein synthesis and membrane repair during sleep.

But what of REM? Some researchers have proposed that this is the brain booting up to test out the repairs it made during non-REM. Others suggest it has something to do with early brain development. But we don鈥檛 really know. Looks like we鈥檒l have to sleep on it some more.

Graham Lawton

5 Is intelligence inevitable?

IT IS comforting to think of human intelligence as the pinnacle of evolution. But cast that anthropocentric snobbery to one side and consider this: intelligence is just another adaptation. It evolved because it is the best way to survive in a particular ecological niche.

Intelligence is evolution鈥檚 answer to unpredictability. If an organism lives in an environment that is predictable then it can get by on instinct and hard-wired responses. But animals that live in shifting environments need to be flexible, they need to be able to weigh up new situations and act accordingly. That is where intelligence can come in handy.

But hang on, does that mean that once life appears, the evolution of intelligence is inevitable? It鈥檚 not as simple as that. Natural selection only favours a trait if the benefits outweigh the costs. And there are some serious costs associated with intelligence. For a start, the brain is a gas guzzler. In humans it accounts for 20 per cent of our energy requirement, while making up just 2 per cent of our body mass. There is also the cost of being naive. A newborn animal with hard-wired survival responses will be at an advantage in some situations compared with one that must work out the best way to react. And intelligence seems to carry other as yet unidentified handicaps, as suggested by a study published last year showing that fruit flies bred for braininess survive less well if food is scarce.

Nevertheless, during the evolution of life on Earth, the benefits of intelligence have undoubtedly outweighed the costs on many occasions. That is why even very simple animals often show behavioural flexibility that denotes a level of intelligence. But our own creative intelligence is qualitatively different. Is this type of intelligence inevitable?

Maybe. As well as being evolution鈥檚 solution to unpredictability, intelligence creates unpredictability of its own through the complex behaviour it generates. So there is positive feedback. This is particularly strong where one animal鈥檚 behaviour affects the survival of others 鈥 which might explain why intelligence is common in social animals such as bonobos and Caledonian crows.

Humans are the ultimate social animals. We manipulate the world to such an extent that we create our own fast-changing environment. But positive feedback is surely not the whole story. There must also be an element of serendipity involved. So, if you were to rerun the tape of evolution would the world inevitably end up with a creature with our unique blend of mental skills, from complex language and tool use to symbolism and morality? The odds against all of them coming together in one species, in less than 4 billion years of evolution, are extremely long. That is not to say it couldn鈥檛 happen again, though, given enough time.

Kate Douglas

6 What is consciousness?

IT IS fairly easy to describe what consciousness feels like. Being conscious is all about being awake and aware, having a sense of self and a feeling of embodiment, of knowing the difference between you and the world around you. It is also about having a history or narrative made up of a continuous flow of thoughts, images and sounds 鈥 your stream of consciousness. But most importantly it is about how it feels to be you.

But herein lies the problem. Consciousness is a really difficult question for science, because it is entirely subjective. That is why the study of consciousness has long belonged in the realms of philosophy and religion. But now biologists, especially neuroscientists, are getting in on the debate. Some hope that brain imaging and electrical recording will reveal the 鈥渘eural correlate of consciousness鈥. That is, we should be able to find what is going on in the brain when people are conscious, but not while they are unconscious.

Researchers are making progress with this. But it is still not at all clear what it is about brain activity that makes us conscious. There is certainly no single brain area that is active when we are conscious and quiet when we are not. And there doesn鈥檛 seem to be a simple threshold of neuronal activity above which we are conscious, nor a type of activity or neurochemistry that always accompanies consciousness.

But even if you accept that consciousness is something that comes from the brain (and not quite everyone does), and you find a pattern of brain activity that correlates with a conscious experience, there is still a problem. Why should the activity of a mass of neurons feel like anything? Why does pricking your finger feel like pain? Why does a red rose appear red?

This has been dubbed the 鈥渉ard problem鈥 of consciousness, and some people have tried to explain it away by calling it an emergent property of active networks of neurons 鈥 in other words, something that arises from the interactions between these neurons, but which is not found in the neurons by themselves. That, however, seems a bit of a cop-out. What is more, this 鈥渆xplanatory gap鈥 has attracted a number of oddball theories proposing weird quantum states that produce consciousness, mathematical explanations as to why synchronous oscillating brain waves may be the key, and so on.

Some say that the gap will never be bridged because our brains are ill-equipped to understand their own consciousness. And some researchers argue that consciousness is just an illusion anyway.

Helen Phillips

7 What is sex for?

SEX sells, and not just in popular culture. Biologists have been fascinated with it for more than 100 years and there鈥檚 no danger of them losing interest.

Why sex? Surely there is no mystery there 鈥 the reason 99.9 per cent of multicellular species reproduce sexually is because it is the best way of passing on your genes while ensuring there is plenty of variation in the next generation. But this argument has a fundamental flaw, which is the immediate and short-term wastefulness of sexual reproduction.

Imagine a population of fish living in a lake and competing for limited food. The fish reproduce sexually so each new generation contains both females and males, all competing for the same resources. Now imagine that one fish discovers how to reproduce asexually. All her offspring are females, and in time they will all produce their own female offspring, without the wasteful need for males. In just a few generations the descendants of this single fish will outnumber their sexual rivals and drive them to extinction. In the day-to-day battle for survival, sex is a seriously losing strategy.

In the long term, of course, this does not hold true. Without sex to shuffle the genetic pack, species accumulate harmful mutations and quickly go extinct. The majority of asexual species last only a few tens of thousands of years. But this is not a satisfactory explanation for the near-ubiquity of sex. Natural selection doesn鈥檛 care what happens many generations into the future. To win the day, sex must confer benefits right here, right now. And that鈥檚 where things get sticky.

How does sex win? There have been dozens of suggestions, most of them focusing on its ability to generate variety. Because the environments in which species live can vary so much in space and time, the argument goes, only those that can adapt rapidly survive. One of the most popular versions of this idea concerns the never-ending arms race between hosts and parasites. Problem solved. Except that no one has been able to prove that this accounts for the overwhelming dominance of sex in nature.

Perhaps there is a way out of this conundrum. Sex may be everywhere not because it confers short-term advantages, but because it is difficult to give up once it has evolved. Some biologists believe that the type of cell division that gives rise to sperm and eggs evolved very early in the history of life and was only later incorporated into reproduction. They argue that sex is etched so deeply into life鈥檚 operating system that abandoning it is all but impossible. It is a promising answer, but not a complete one. In some ways all it does is transfer the mystery to another area: how sex evolved in the first place. And that one will keep us guessing for at least another 100 years.

Graham Lawton

8 Can we prevent ageing?

NO ONE seriously believes they can live forever, but most people would gladly forego the tribulations of ageing. The problem is, we don鈥檛 know enough about why ageing occurs to be able to intervene.

The orthodox view is that ageing is due to an accumulation of random damage. Among the main suspects for inflicting this damage are free radicals, toxic by-products of the chemical reactions that release energy from food.

Some researchers are testing this idea by developing anti-ageing strategies based on fighting free radicals. Vitamins and natural antioxidants in food seem to help, a fact that has led to a buoyant food-supplement industry. Another school of thought is that simply eating less will cut the number of free radicals produced over a lifetime. Semi-starved mice can live up to half as long again as well-fed animals. Some people are trying this out on themselves by permanently cutting their calorie intake by up to a third. A recent small study showed this strategy does seem to improve cardiovascular health, but its long-term effectiveness is unknown, and few people want to feel hungry and tired most of the time.

An alternative view of ageing is that it is a programmed degeneration that evolved to reduce competition with offspring. Supporters of this theory point to recent research showing that knocking out a gene called daf-2, or its equivalents, makes worms, flies and even mice live longer. The gene encodes a hormone receptor that controls numerous functions, suggesting this pathway is the 鈥渕aster switch鈥 of programmed ageing. But a gene could affect ageing without having evolved specifically to cause it, so the daf-2 findings remain compatible with the random-damage theory.

However it is interpreted, daf-2 is sparking a good deal of excitement in longevity research, as it suggests there may be a relatively simple way of boosting lifespan. Of course, what works for animals will not necessarily work for people. But it鈥檚 a good sign that the pathway exists in mice.

Steven Austad of the University of Idaho in Moscow certainly thinks so. He famously bet a colleague $500 million that someone living in 2001 would still be alive and sentient by 2150. 鈥淚鈥檓 feeling very good about my bet,鈥 he says.

Clare Wilson

9 What is life?

IT SEEMS such a simple question. After all, we know life when we see it, don鈥檛 we? But just try to pin down a precise definition.

We can certainly describe what living things do, but that is not enough. For example, living things take in nutrients and excrete wastes, but so do cars. Living things replicate and participate in evolution, but so do certain computer programs, while some life forms such as mules and post-menopausal women do not. The best minds of biology and philosophy have tried for decades, and failed, to agree on a universal set of criteria for life on Earth, or wherever else we might find it.

If you took a vote today, the most popular definition would probably be the one proposed 10 years ago by Gerald Joyce of the Scripps Research Institute in La Jolla, California. He describes life as a self-sustaining chemical system capable of evolving through Darwinian natural selection. This definition captures the essence of life on Earth, but critics worry that, broad as it is, it may not be broad enough to encompass absolutely everything we would want to call life.

The reason the task is so difficult is that we only have one example to work with. All life on our planet is descended from common ancestry, so no one knows whether its fundamentals 鈥 membranes, proteins, carbon-based biochemistry and the like 鈥 are necessary, or merely accidents of history. As some experts have noted, it is a bit like trying to generalise about what makes a mammal when you only have a zebra. We need a second, alien life form for comparison.

And we might have one within a few years, not from another planet, but from test tubes here on Earth. Several groups are trying to synthesise life from scratch, and some of their efforts bear little resemblance to our familiar life forms. One under development by Steen Rasmussen at Los Alamos National Laboratory in New Mexico, for example, is based on fat droplets rather than watery, membrane-bound cells. Another, by the Venice-based company ProtoLife, aims to repeatedly select the most 鈥渓ife-like鈥 features from a chemical smorgasbord, essentially letting life reinvent itself. If either of these efforts succeeds, we may suddenly gain a totally new perspective on what it means to be alive.

Bob Holmes

10 Is there life on other planets?

TOUGH one. So let鈥檚 rephrase the question: do you want there to be? If your view is that there is something special about the Earth, then there is plenty of scientific scope for saying the answer is no, there is no evidence of life on other planets. If, on the other hand, you do not subscribe to the idea that a pale blue dot in a humble corner of an ordinary galaxy should be bestowed with such significance, there is evidence, of a kind, for you too.

But it鈥檚 not just a matter of taste or opinion. The UK鈥檚 Astronomer Royal, Martin Rees, considers this the most important question facing science today.

Finding an answer comes down to resolving the issue of how 鈥 and how easily 鈥 life gets started in the first place. Is it a freak event, or an inevitable consequence of the laws of physics? As yet, we don鈥檛 know.

Of course, science abhors a vacuum, and so scientists have formed opinions based on whichever set of proofs they like the sound of. Asking for the received wisdom is rather like asking what length a skirt should be. A couple of decades ago, the fashionable opinion was that life is pretty hard to kick off, and thus probably not widespread beyond Earth. These days it is more in vogue to say that life is inevitable, and the universe is probably crawling with living things.

What has changed, scientifically speaking, in those 20 years? Very little. But using the mathematics of probability to reach your conclusions happens to be all the rage. Given the vastness of the universe, the diversity of its environments, and the fact that life has certainly evolved once, you can argue that the chances are pretty small that Earth is the only place life exists.

The fact remains, however, that the search for extraterrestrial intelligence (SETI) operating out of the SETI Institute headquarters in Mountain View, California, has found nothing conclusive in 40 years. And Tau Ceti, a star system that was considered a frontrunner to host life, was recently declared too comet-ridden. Even if we discover life on Mars we cannot draw any conclusions because the Red Planet regularly trades rocks with Earth.

Anyway, what kind of life do we mean? We don鈥檛 know whether we should be looking for the carbon-based life so familiar on Earth, or some other form. And if we can鈥檛 agree on a definition of life, and what it might need to evolve and exist, the argument just gets woollier and woollier. So, at the moment, it all seems to boil down to a different question: do you want us to be alone?

Michael Brooks

The experts鈥 choice

Although New 杏吧原创 came up with the 10 questions presented here, we wanted to know what the experts think. So we canvassed some of the world鈥檚 leading biologists. Here is a selection of the answers we received:

Chris Stringer

Palaeoanthropologist at the Natural History Museum in London, UK. He is known for his work on the 鈥淥ut of Africa鈥 theory of human origins

鈥淚 think the biggest unanswered question in biology is whether life is unique to Earth. Evidence from Mars may help to answer this question, even in the next few years. As for my own field, I think the biggest question is: what was the last common ancestor of humans and chimpanzees like? Knowing the answer would help solve many questions about our origins. I would also like to discover the key factors that led to the success of our species. Why are we here and not people like the Neanderthals?鈥

Tom Kirkwood

Gerontologist at the University of Newcastle upon Tyne, UK. He proposed the 鈥渄isposable soma鈥 theory of ageing

鈥淲hy are people living longer and longer at the moment? What we are seeing is something quite extraordinary. In the 20th century, life expectancy began to climb for all the obvious reasons, such as improved healthcare, vaccines, antibiotics and sanitation. Since most of these measures stop people from dying young, everyone predicted that the rate of increase in life expectancy would plateau as the benefits of keeping young people alive pushed up average lifespan. But the rate has not slowed. What seems to be happening now is that we are beginning to change the nature of old age itself. What is driving this and how far will it go?鈥

Simon Conway-Morris

Professor of evolutionary palaeobiology at the University of Cambridge. He is known for his work on the early evolution of animals, particularly the fossils of the Burgess shale

鈥淥ne big question concerns convergent evolution 鈥 the finding that life comes up with remarkably similar solutions to the same problem more than once. The camera eye is a good example. What is it that makes life navigate towards particular solutions? Is there a deeper pattern or set of principles at work, some kind of underlying 鈥渓andscape鈥 across which life is forced to move? If we could discover that landscape, we would have a general theory of evolution.鈥

Frans de Waal

C. H Candler Professor of Primate Behavior at Emory University in Atlanta, Georgia. He studies social intelligence in apes and monkeys

鈥淚 want to understand why we empathise with others, and why we do so automatically. A one-day-old baby already cries when it hears another baby cry, and few adults keep a dry eye while watching a sad movie. Our closest relatives, the great apes, show similar emotional sensitivity. It must mean that we are programmed to be highly cooperative. People seem to interact against a background of emotional connectedness, the evolution of which biology has not even begun to explain.鈥

Susan Greenfield

Professor of pharmacology at the University of Oxford and director of the Royal Institution of Great Britain. She is particularly associated with research into neurodegenerative diseases

鈥淚 think the biggest unanswered question is how the brain generates consciousness. It is the question I would most like to solve and the one I would tackle if I were starting out again. In my own field, I think the key question is what is the critical mechanism triggering Alzheimer鈥檚 disease?鈥

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