Tag Archives: biology

BigBang

Pass the Nicotinamide Adenine Dinucleotide

NAD-moleculeFor those of us seeking to live another 100 years or more the news and/or hype over the last decade belonged to resveratrol. The molecule is believed to improve functioning of specific biochemical pathways in the cell, which may improve cell repair and hinder the aging process. Resveratrol is found — in trace amounts — in grape skin (and hence wine), blueberries and raspberries. While proof remains scarce, this has not stopped the public from consuming large quantities of wine and berries.

Ironically, one would need to ingest such large amounts of resveratrol to replicate the benefits found in mice studies, that the wine alone would probably cause irreversible liver damage before any health benefits appeared. Oh well.

So, on to the next big thing, since aging cannot wait. It’s called NAD or Nicotinamide Adenine Dinucleotide. NAD performs several critical roles in the cell, one of which is energy metabolism. As we age our cells show diminishing levels of NAD and this is, possibly, linked to mitochondrial deterioration. Mitochondria are the cells’ energy factories, so keeping our mitochondria humming along is critical. Thus, hordes of researchers are now experimenting with NAD and related substances to see if they hold promise in postponing cellular demise.

From Scientific American:

Whenever I see my 10-year-old daughter brimming over with so much energy that she jumps up in the middle of supper to run around the table, I think to myself, “those young mitochondria.”

Mitochondria are our cells’ energy dynamos. Descended from bacteria that colonized other cells about 2 billion years, they get flaky as we age. A prominent theory of aging holds that decaying of mitochondria is a key driver of aging. While it’s not clear why our mitochondria fade as we age, evidence suggests that it leads to everything from heart failure to neurodegeneration, as well as the complete absence of zipping around the supper table.

Recent research suggests it may be possible to reverse mitochondrial decay with dietary supplements that increase cellular levels of a molecule called NAD (nicotinamide adenine dinucleotide). But caution is due: While there’s promising test-tube data and animal research regarding NAD boosters, no human clinical results on them have been published.

NAD is a linchpin of energy metabolism, among other roles, and its diminishing level with age has been implicated in mitochondrial deterioration. Supplements containing nicotinamide riboside, or NR, a precursor to NAD that’s found in trace amounts in milk, might be able to boost NAD levels. In support of that idea, half a dozen Nobel laureates and other prominent scientists are working with two small companies offering NR supplements.

The NAD story took off toward the end of 2013 with a high-profile paper by Harvard’s David Sinclair and colleagues. Sinclair, recall, achieved fame in the mid-2000s for research on yeast and mice that suggested the red wine ingredient resveratrol mimics anti-aging effects of calorie restriction. This time his lab made headlines by reporting that the mitochondria in muscles of elderly mice were restored to a youthful state after just a week of injections with NMN (nicotinamide mononucleotide), a molecule that naturally occurs in cells and, like NR, boosts levels of NAD.

It should be noted, however, that muscle strength was not improved in the NMN-treated micethe researchers speculated that one week of treatment wasn’t enough to do that despite signs that their age-related mitochondrial deterioration was reversed.

NMN isn’t available as a consumer product. But Sinclair’s report sparked excitement about NR, which was already on the market as a supplement called Niagen. Niagen’s maker, ChromaDex, a publicly traded Irvine, Calif., company, sells it to various retailers, which market it under their own brand names. In the wake of Sinclair’s paper, Niagen was hailed in the media as a potential blockbuster.

In early February, Elysium Health, a startup cofounded by Sinclair’s former mentor, MIT biologist Lenny Guarente, jumped into the NAD game by unveiling another supplement with NR. Dubbed Basis, it’s only offered online by the company. Elysium is taking no chances when it comes to scientific credibility. Its website lists a dream team of advising scientists, including five Nobel laureates and other big names such as the Mayo Clinic’s Jim Kirkland, a leader in geroscience, and biotech pioneer Lee Hood. I can’t remember a startup with more stars in its firmament.

A few days later, ChromaDex reasserted its first-comer status in the NAD game by announcing that it had conducted a clinical trial demonstrating that a single dose of NR resulted in statistically significant increases in NAD in humansthe first evidence that supplements could really boost NAD levels in people. Details of the study won’t be out until it’s reported in a peer-reviewed journal, the company said. (ChromaDex also brandishes Nobel credentials: Roger Kornberg, a Stanford professor who won the Chemistry prize in 2006, chairs its scientific advisory board. Hes the son of Nobel laureate Arthur Kornberg, who, ChromaDex proudly notes, was among the first scientists to study NR some 60 years ago.)

The NAD findings tie into the ongoing story about enzymes called sirtuins, which Guarente, Sinclair and other researchers have implicated as key players in conferring the longevity and health benefits of calorie restriction. Resveratrol, the wine ingredient, is thought to rev up one of the sirtuins, SIRT1, which appears to help protect mice on high doses of resveratrol from the ill effects of high-fat diets. A slew of other health benefits have been attributed to SIRT1 activation in hundreds of studies, including several small human trials.

Here’s the NAD connection: In 2000, Guarente’s lab reported that NAD fuels the activity of sirtuins, including SIRT1the more NAD there is in cells, the more SIRT1 does beneficial things. One of those things is to induce formation of new mitochondria. NAD can also activate another sirtuin, SIRT3, which is thought to keep mitochondria running smoothly.

Read the entire article here.

Image: Structure of nicotinamide adenine dinucleotide, oxidized (NAD+). Courtesy of Wikipedia. Public Domain.

BigBang, Idea Soup

Thirty Going On Sixty or Sixty Going on Thirty?

By now you probably realize that I’m a glutton for human research studies. I’m particularly fond of studies that highlight a particular finding one week, only to be contradicted by the results of another study the following week.

However, despite lack of contradictions, this one published via the Proceedings of the National Academy of Sciences caught my eye. It suggests that we age at remarkably different rates. While most subjects showed a perceived, biological age within a handful of years of their actual, chronological age, there were some surprises. Some 30-year-olds showed a biological age twice that of their chronological age, while some appeared ten years younger.

From the BBC:

A study of people born within a year of each other has uncovered a huge gulf in the speed at which their bodies age.

The report, in Proceedings of the National Academy of Sciences, tracked traits such as weight, kidney function and gum health.

Some of the 38-year-olds were ageing so badly that their “biological age” was on the cusp of retirement.

The team said the next step was to discover what was affecting the pace of ageing.

The international research group followed 954 people from the same town in New Zealand who were all born in 1972-73.

The scientists looked at 18 different ageing-related traits when the group turned 26, 32 and 38 years old.

The analysis showed that at the age of 38, the people’s biological ages ranged from the late-20s to those who were nearly 60.

“They look rough, they look lacking in vitality,” said Prof Terrie Moffitt from Duke University in the US.

The study said some people had almost stopped ageing during the period of the study, while others were gaining nearly three years of biological age for every twelve months that passed.

People with older biological ages tended to do worse in tests of brain function and had a weaker grip.

Most people’s biological age was within a few years of their chronological age. It is unclear how the pace of biological ageing changes through life with these measures.

Read the entire story here.

Idea Soup

Cat in the (Hat) Box

google-search-cat

Cat owner? Ever pondered why your aloof, inscrutable feline friend loves boxes? Here are some answers courtesy of people who study these kinds of things.

From Wired:

Take heart feline enthusiasts. Your cat’s continued indifference toward her new Deluxe Scratch DJ Deck may be disappointing, but there is an object that’s pretty much guaranteed to pique her interest. That object, as the Internet has so thoroughly documented, is a box. Any box, really. Big boxes, small boxes, irregularly shaped boxes—it doesn’t matter. Place one on the ground, a chair, or a bookshelf and watch as Admiral Snuggles quickly commandeers it.

So what are we to make of the strange gravitational pull that empty Amazon packaging exerts on Felis sylvestris catus? Like many other really weird things cats do, science hasn’t fully cracked this particular feline mystery. There’s the obvious predation advantage a box affords: Cats are ambush predators, and boxes provide great hiding places to stalk prey from (and retreat to). But there’s clearly more going on here.

Thankfully, behavioral biologists and veterinarians have come up with a few other interesting explanations. In fact, when you look at all the evidence together, it could be that your cat may not just like boxes, he may need them.

The box-and-whisker plot

Understanding the feline mind is notoriously difficult. Cats, after all, tend not to be the easiest test subjects. Still, there’s a sizable amount of behavioral research on cats who are, well, used for other kinds of research (i.e., lab cats). These studies—many of which focused on environmental enrichment—have been taking place for more than 50 years and they make one thing abundantly clear: Your fuzzy companion derives comfort and security from enclosed spaces.

This is likely true for a number of reasons, but for cats in these often stressful situations, a box or some other type of separate enclosure (within the enclosures they’re already in) can have a profound impact on both their behavior and physiology.

EthologistClaudia Vinke of Utrecht University in the Netherlands is one of the latest researchers to study stress levels in shelter cats. Working with domestic cats in a Dutch animal shelter, Vinke provided hiding boxes for a group of newly arrived cats while depriving another group of them entirely. She found a significant difference in stress levels between cats that had the boxes and those that didn’t. In effect, the cats with boxes got used to their new surroundings faster, were far less stressed early on, and were more interested in interacting with humans.

Read the entire story here.

Image courtesy of Google Search.

BigBang

Syndrome X

DNA_Structure

The quest for immortality or even great longevity has probably led humans since they first became self-aware. Entire cultural movements and industries are founded on the desire to enhance and extend our lives. Genetic research, of course, may eventually unlock some or all of life and death’s mysteries. In the meantime, groups of dedicated scientists continue to look for for the foundation of aging with a view to understanding the process and eventually slowing (and perhaps stopping) it. Richard Walker is one of these singularly focused researchers.

From the BBC:

Richard Walker has been trying to conquer ageing since he was a 26-year-old free-loving hippie. It was the 1960s, an era marked by youth: Vietnam War protests, psychedelic drugs, sexual revolutions. The young Walker relished the culture of exultation, of joie de vivre, and yet was also acutely aware of its passing. He was haunted by the knowledge that ageing would eventually steal away his vitality – that with each passing day his body was slightly less robust, slightly more decayed. One evening he went for a drive in his convertible and vowed that by his 40th birthday, he would find a cure for ageing.

Walker became a scientist to understand why he was mortal. “Certainly it wasn’t due to original sin and punishment by God, as I was taught by nuns in catechism,” he says. “No, it was the result of a biological process, and therefore is controlled by a mechanism that we can understand.”

Scientists have published several hundred theories of ageing, and have tied it to a wide variety of biological processes. But no one yet understands how to integrate all of this disparate information.

Walker, now 74, believes that the key to ending ageing may lie in a rare disease that doesn’t even have a real name, “Syndrome X”. He has identified four girls with this condition, marked by what seems to be a permanent state of infancy, a dramatic developmental arrest. He suspects that the disease is caused by a glitch somewhere in the girls’ DNA. His quest for immortality depends on finding it.

It’s the end of another busy week and MaryMargret Williams is shuttling her brood home from school. She drives an enormous SUV, but her six children and their coats and bags and snacks manage to fill every inch. The three big kids are bouncing in the very back. Sophia, 10, with a mouth of new braces, is complaining about a boy-crazy friend. She sits next to Anthony, seven, and Aleena, five, who are glued to something on their mother’s iPhone. The three little kids squirm in three car seats across the middle row. Myah, two, is mining a cherry slushy, and Luke, one, is pawing a bag of fresh crickets bought for the family gecko.

Finally there’s Gabrielle, who’s the smallest child, and the second oldest, at nine years old. She has long, skinny legs and a long, skinny ponytail, both of which spill out over the edges of her car seat. While her siblings giggle and squeal, Gabby’s dusty-blue eyes roll up towards the ceiling. By the calendar, she’s almost an adolescent. But she has the buttery skin, tightly clenched fingers and hazy awareness of a newborn.

Back in 2004, when MaryMargret and her husband, John, went to the hospital to deliver Gabby, they had no idea anything was wrong. They knew from an ultrasound that she would have clubbed feet, but so had their other daughter, Sophia, who was otherwise healthy. And because MaryMargret was a week early, they knew Gabby would be small, but not abnormally so. “So it was such a shock to us when she was born,” MaryMargret says.

Gabby came out purple and limp. Doctors stabilised her in the neonatal intensive care unit and then began a battery of tests. Within days the Williamses knew their new baby had lost the genetic lottery. Her brain’s frontal lobe was smooth, lacking the folds and grooves that allow neurons to pack in tightly. Her optic nerve, which runs between the eyes and the brain, was atrophied, which would probably leave her blind. She had two heart defects. Her tiny fists couldn’t be pried open. She had a cleft palate and an abnormal swallowing reflex, which meant she had to be fed through a tube in her nose. “They started trying to prepare us that she probably wouldn’t come home with us,” John says. Their family priest came by to baptise her.

Day after day, MaryMargret and John shuttled between Gabby in the hospital and 13-month-old Sophia at home. The doctors tested for a few known genetic syndromes, but they all came back negative. Nobody had a clue what was in store for her. Her strong Catholic family put their faith in God. “MaryMargret just kept saying, ‘She’s coming home, she’s coming home’,” recalls her sister, Jennie Hansen. And after 40 days, she did.

Gabby cried a lot, loved to be held, and ate every three hours, just like any other newborn. But of course she wasn’t. Her arms would stiffen and fly up to her ears, in a pose that the family nicknamed her “Harley-Davidson”. At four months old she started having seizures. Most puzzling and problematic, she still wasn’t growing. John and MaryMargret took her to specialist after specialist: a cardiologist, a gastroenterologist, a geneticist, a neurologist, an ophthalmologist and an orthopaedist. “You almost get your hopes up a little – ’This is exciting! We’re going to the gastro doctor, and maybe he’ll have some answers’,” MaryMargret says. But the experts always said the same thing: nothing could be done.

The first few years with Gabby were stressful. When she was one and Sophia two, the Williamses drove from their home in Billings, Montana, to MaryMargret’s brother’s home outside of St Paul, Minnesota. For nearly all of those 850 miles, Gabby cried and screamed. This continued for months until doctors realised she had a run-of-the-mill bladder infection. Around the same period, she acquired a severe respiratory infection that left her struggling to breathe. John and MaryMargret tried to prepare Sophia for the worst, and even planned which readings and songs to use at Gabby’s funeral. But the tiny toddler toughed it out.

While Gabby’s hair and nails grew, her body wasn’t getting bigger. She was developing in subtle ways, but at her own pace. MaryMargret vividly remembers a day at work when she was pushing Gabby’s stroller down a hallway with skylights in the ceiling. She looked down at Gabby and was shocked to see her eyes reacting to the sunlight. “I thought, ‘Well, you’re seeing that light!’” MaryMargret says. Gabby wasn’t blind, after all.

Despite the hardships, the couple decided they wanted more children. In 2007 MaryMargret had Anthony, and the following year she had Aleena. By this time, the Williamses had stopped trudging to specialists, accepting that Gabby was never going to be fixed. “At some point we just decided,” John recalls, “it’s time to make our peace.”

Mortal questions

When Walker began his scientific career, he focused on the female reproductive system as a model of “pure ageing”: a woman’s ovaries, even in the absence of any disease, slowly but inevitably slide into the throes of menopause. His studies investigated how food, light, hormones and brain chemicals influence fertility in rats. But academic science is slow. He hadn’t cured ageing by his 40th birthday, nor by his 50th or 60th. His life’s work was tangential, at best, to answering the question of why we’re mortal, and he wasn’t happy about it. He was running out of time.

So he went back to the drawing board. As he describes in his book, Why We Age, Walker began a series of thought experiments to reflect on what was known and not known about ageing.

Ageing is usually defined as the slow accumulation of damage in our cells, organs and tissues, ultimately causing the physical transformations that we all recognise in elderly people. Jaws shrink and gums recede. Skin slacks. Bones brittle, cartilage thins and joints swell. Arteries stiffen and clog. Hair greys. Vision dims. Memory fades. The notion that ageing is a natural, inevitable part of life is so fixed in our culture that we rarely question it. But biologists have been questioning it for a long time.

It’s a harsh world out there, and even young cells are vulnerable. It’s like buying a new car: the engine runs perfectly but is still at risk of getting smashed on the highway. Our young cells survive only because they have a slew of trusty mechanics on call. Take DNA, which provides the all-important instructions for making proteins. Every time a cell divides, it makes a near-perfect copy of its three-billion-letter code. Copying mistakes happen frequently along the way, but we have specialised repair enzymes to fix them, like an automatic spellcheck. Proteins, too, are ever vulnerable. If it gets too hot, they twist into deviant shapes that keep them from working. But here again, we have a fixer: so-called ‘heat shock proteins’ that rush to the aid of their misfolded brethren. Our bodies are also regularly exposed to environmental poisons, such as the reactive and unstable ‘free radical’ molecules that come from the oxidisation of the air we breathe. Happily, our tissues are stocked with antioxidants and vitamins that neutralise this chemical damage. Time and time again, our cellular mechanics come to the rescue.

Which leads to the biologists’ longstanding conundrum: if our bodies are so well tuned, why, then, does everything eventually go to hell?

One theory is that it all boils down to the pressures of evolution. Humans reproduce early in life, well before ageing rears its ugly head. All of the repair mechanisms that are important in youth – the DNA editors, the heat shock proteins, the antioxidants – help the young survive until reproduction, and are therefore passed down to future generations. But problems that show up after we’re done reproducing cannot be weeded out by evolution. Hence, ageing.

Most scientists say that ageing is not caused by any one culprit but by the breakdown of many systems at once. Our sturdy DNA mechanics become less effective with age, meaning that our genetic code sees a gradual increase in mutations. Telomeres, the sequences of DNA that act as protective caps on the ends of our chromosomes, get shorter every year. Epigenetic messages, which help turn genes on and off, get corrupted with time. Heat shock proteins run down, leading to tangled protein clumps that muck up the smooth workings of a cell. Faced with all of this damage, our cells try to adjust by changing the way they metabolise nutrients and store energy. To ward off cancer, they even know how to shut themselves down. But eventually cells stop dividing and stop communicating with each other, triggering the decline we see from the outside.

Scientists trying to slow the ageing process tend to focus on one of these interconnected pathways at a time. Some researchers have shown, for example, that mice on restricted-calorie diets live longer than normal. Other labs have reported that giving mice rapamycin, a drug that targets an important cell-growth pathway, boosts their lifespan. Still other groups are investigating substances that restore telomeres, DNA repair enzymes and heat shock proteins.

During his thought experiments, Walker wondered whether all of these scientists were fixating on the wrong thing. What if all of these various types of cellular damages were the consequences of ageing, but not the root cause of it? He came up with an alternative theory: that ageing is the unavoidable fallout of our development.

The idea sat on the back burner of Walker’s mind until the evening of 23 October 2005. He was working in his home office when his wife called out to him to join her in the family room. She knew he would want to see what was on TV: an episode of Dateline about a young girl who seemed to be “frozen in time”. Walker watched the show and couldn’t believe what he was seeing. Brooke Greenberg was 12 years old, but just 13 pounds (6kg) and 27 inches (69cm) long. Her doctors had never seen anything like her condition, and suspected the cause was a random genetic mutation. “She literally is the Fountain of Youth,” her father, Howard Greenberg, said.

Walker was immediately intrigued. He had heard of other genetic diseases, such as progeria and Werner syndrome, which cause premature ageing in children and adults respectively. But this girl seemed to be different. She had a genetic disease that stopped her development and with it, Walker suspected, the ageing process. Brooke Greenberg, in other words, could help him test his theory.

Uneven growth

Brooke was born a few weeks premature, with many birth defects. Her paediatrician labeled her with Syndrome X, not knowing what else to call it.

After watching the show, Walker tracked down Howard Greenberg’s address. Two weeks went by before Walker heard back, and after much discussion he was allowed to test Brooke. He was sent Brooke’s medical records as well as blood samples for genetic testing. In 2009, his team published a brief report describing her case.

Walker’s analysis found that Brooke’s organs and tissues were developing at different rates. Her mental age, according to standardised tests, was between one and eight months. Her teeth appeared to be eight years old; her bones, 10 years. She had lost all of her baby fat, and her hair and nails grew normally, but she had not reached puberty. Her telomeres were considerably shorter than those of healthy teenagers, suggesting that her cells were ageing at an accelerated rate.

All of this was evidence of what Walker dubbed “developmental disorganisation”. Brooke’s body seemed to be developing not as a coordinated unit, he wrote, but rather as a collection of individual, out-of-sync parts. “She is not simply ‘frozen in time’,” Walker wrote. “Her development is continuing, albeit in a disorganised fashion.”

The big question remained: why was Brooke developmentally disorganised? It wasn’t nutritional and it wasn’t hormonal. The answer had to be in her genes. Walker suspected that she carried a glitch in a gene (or a set of genes, or some kind of complex genetic programme) that directed healthy development. There must be some mechanism, after all, that allows us to develop from a single cell to a system of trillions of cells. This genetic programme, Walker reasoned, would have two main functions: it would initiate and drive dramatic changes throughout the organism, and it would also coordinate these changes into a cohesive unit.

Ageing, he thought, comes about because this developmental programme, this constant change, never turns off. From birth until puberty, change is crucial: we need it to grow and mature. After we’ve matured, however, our adult bodies don’t need change, but rather maintenance. “If you’ve built the perfect house, you would want to stop adding bricks at a certain point,” Walker says. “When you’ve built a perfect body, you’d want to stop screwing around with it. But that’s not how evolution works.” Because natural selection cannot influence traits that show up after we have passed on our genes, we never evolved a “stop switch” for development, Walker says. So we keep adding bricks to the house. At first this doesn’t cause much damage – a sagging roof here, a broken window there. But eventually the foundation can’t sustain the additions, and the house topples. This, Walker says, is ageing.

Brooke was special because she seemed to have been born with a stop switch. But finding the genetic culprit turned out to be difficult. Walker would need to sequence Brooke’s entire genome, letter by letter.

That never happened. Much to Walker’s chagrin, Howard Greenberg abruptly severed their relationship. The Greenbergs have not publicly explained why they ended their collaboration with Walker, and declined to comment for this article.

Second chance

In August 2009, MaryMargret Williams saw a photo of Brooke on the cover of People magazine, just below the headline “Heartbreaking mystery: The 16-year-old baby”. She thought Brooke sounded a lot like Gabby, so contacted Walker.

After reviewing Gabby’s details, Walker filled her in on his theory. Testing Gabby’s genes, he said, could help him in his mission to end age-related disease – and maybe even ageing itself.

This didn’t sit well with the Williamses. John, who works for the Montana Department of Corrections, often interacts with people facing the reality of our finite time on Earth. “If you’re spending the rest of your life in prison, you know, it makes you think about the mortality of life,” he says. What’s important is not how long you live, but rather what you do with the life you’re given. MaryMargret feels the same way. For years she has worked in a local dermatology office. She knows all too well the cultural pressures to stay young, and wishes more people would embrace the inevitability of getting older. “You get wrinkles, you get old, that’s part of the process,” she says.

But Walker’s research also had its upside. First and foremost, it could reveal whether the other Williams children were at risk of passing on Gabby’s condition.

For several months, John and MaryMargret hashed out the pros and cons. They were under no illusion that the fruits of Walker’s research would change Gabby’s condition, nor would they want it to. But they did want to know why. “What happened, genetically, to make her who she is?” John says. And more importantly: “Is there a bigger meaning for it?”

John and MaryMargret firmly believe that God gave them Gabby for a reason. Walker’s research offered them a comforting one: to help treat Alzheimer’s and other age-related diseases. “Is there a small piece that Gabby could present to help people solve these awful diseases?” John asks. “Thinking about it, it’s like, no, that’s for other people, that’s not for us.” But then he thinks back to the day Gabby was born. “I was in that delivery room, thinking the same thing – this happens to other people, not us.”

Still not entirely certain, the Williamses went ahead with the research.

Amassing evidence

Walker published his theory in 2011, but he’s only the latest of many researchers to think along the same lines. “Theories relating developmental processes to ageing have been around for a very long time, but have been somewhat under the radar for most researchers,” says Joao Pedro de Magalhaes, a biologist at the University of Liverpool. In 1932, for example, English zoologist George Parker Bidder suggested that mammals have some kind of biological “regulator” that stops growth after the animal reaches a specific size. Ageing, Bidder thought, was the continued action of this regulator after growth was done.

Subsequent studies showed that Bidder wasn’t quite right; there are lots of marine organisms, for example, that never stop growing but age anyway. Still, his fundamental idea of a developmental programme leading to ageing has persisted.

For several years, Stuart Kim’s group at Stanford University has been comparing which genes are expressed in young and old nematode worms. It turns out that some genes involved in ageing also help drive development in youth.

Kim suggested that the root cause of ageing is the “drift”, or mistiming, of developmental pathways during the ageing process, rather than an accumulation of cellular damage.

Other groups have since found similar patterns in mice and primates. One study, for example, found that many genes turned on in the brains of old monkeys and humans are the same as those expressed in young brains, suggesting that ageing and development are controlled by some of the same gene networks.

Perhaps most provocative of all, some studies of worms have shown that shutting down essential development genes in adults significantly prolongs life. “We’ve found quite a lot of genes in which this happened – several dozen,” de Magalhaes says.

Nobody knows whether the same sort of developmental-programme genes exist in people. But say that they do exist. If someone was born with a mutation that completely destroyed this programme, Walker reasoned, that person would undoubtedly die. But if a mutation only partially destroyed it, it might lead to a condition like what he saw in Brooke Greenberg or Gabby Williams. So if Walker could identify the genetic cause of Syndrome X, then he might also have a driver of the ageing process in the rest of us.

And if he found that, then could it lead to treatments that slow – or even end – ageing? “There’s no doubt about it,” he says.

Public stage

After agreeing to participate in Walker’s research, the Williamses, just like the Greenbergs before them, became famous. In January 2011, when Gabby was six, the television channel TLC featured her on a one-hour documentary. The Williams family also appeared on Japanese television and in dozens of newspaper and magazine articles.

Other than becoming a local celebrity, though, Gabby’s everyday life hasn’t changed much since getting involved in Walker’s research. She spends her days surrounded by her large family. She’ll usually lie on the floor, or in one of several cushions designed to keep her spine from twisting into a C shape. She makes noises that would make an outsider worry: grunting, gasping for air, grinding her teeth. Her siblings think nothing of it. They play boisterously in the same room, somehow always careful not to crash into her. Once a week, a teacher comes to the house to work with Gabby. She uses sounds and shapes on an iPad to try to teach cause and effect. When Gabby turned nine, last October, the family made her a birthday cake and had a party, just as they always do. Most of her gifts were blankets, stuffed animals and clothes, just as they are every year. Her aunt Jennie gave her make-up.

Walker teamed up with geneticists at Duke University and screened the genomes of Gabby, John and MaryMargret. This test looked at the exome, the 2% of the genome that codes for proteins. From this comparison, the researchers could tell that Gabby did not inherit any exome mutations from her parents – meaning that it wasn’t likely that her siblings would be able to pass on the condition to their kids. “It was a huge relief – huge,” MaryMargret says.

Still, the exome screening didn’t give any clues as to what was behind Gabby’s disease. Gabby carries several mutations in her exome, but none in a gene that would make sense of her condition. All of us have mutations littering our genomes. So it’s impossible to know, in any single individual, whether a particular mutation is harmful or benign – unless you can compare two people with the same condition.

All girls

Luckily for him, Walker’s continued presence in the media has led him to two other young girls who he believes have the same syndrome. One of them, Mackenzee Wittke, of Alberta, Canada, is now five years old, with has long and skinny limbs, just like Gabby. “We have basically been stuck in a time warp,” says her mother, Kim Wittke. The fact that all of these possible Syndrome X cases are girls is intriguing – it could mean that the crucial mutation is on their X chromosome. Or it could just be a coincidence.

Walker is working with a commercial outfit in California to compare all three girls’ entire genome sequences – the exome plus the other 98% of DNA code, which is thought to be responsible for regulating the expression of protein-coding genes.

For his theory, Walker says, “this is do or die – we’re going to do every single bit of DNA in these girls. If we find a mutation that’s common to them all, that would be very exciting.”

But that seems like a very big if.

Most researchers agree that finding out the genes behind Syndrome X is a worthwhile scientific endeavour, as these genes will no doubt be relevant to our understanding of development. They’re far less convinced, though, that the girls’ condition has anything to do with ageing. “It’s a tenuous interpretation to think that this is going to be relevant to ageing,” says David Gems, a geneticist at University College London. It’s not likely that these girls will even make it to adulthood, he says, let alone old age.

It’s also not at all clear that these girls have the same condition. Even if they do, and even if Walker and his collaborators discover the genetic cause, there would still be a steep hill to climb. The researchers would need to silence the same gene or genes in laboratory mice, which typically have a lifespan of two or three years. “If that animal lives to be 10, then we’ll know we’re on the right track,” Walker says. Then they’d have to find a way to achieve the same genetic silencing in people, whether with a drug or some kind of gene therapy. And then they’d have to begin long and expensive clinical trials to make sure that the treatment was safe and effective. Science is often too slow, and life too fast.

End of life

On 24 October 2013, Brooke passed away. She was 20 years old. MaryMargret heard about it when a friend called after reading it in a magazine. The news hit her hard. “Even though we’ve never met the family, they’ve just been such a part of our world,” she says.

MaryMargret doesn’t see Brooke as a template for Gabby – it’s not as if she now believes that she only has 11 years left with her daughter. But she can empathise with the pain the Greenbergs must be feeling. “It just makes me feel so sad for them, knowing that there’s a lot that goes into a child like that,” she says. “You’re prepared for them to die, but when it finally happens, you can just imagine the hurt.”

Today Gabby is doing well. MaryMargret and John are no longer planning her funeral. Instead, they’re beginning to think about what would happen if Gabby outlives them. (Sophia has offered to take care of her sister.) John turned 50 this year, and MaryMargret will be 41. If there were a pill to end ageing, they say they’d have no interest in it. Quite the contrary: they look forward to getting older, because it means experiencing the new joys, new pains and new ways to grow that come along with that stage of life.

Richard Walker, of course, has a fundamentally different view of growing old. When asked why he’s so tormented by it, he says it stems from childhood, when he watched his grandparents physically and psychologically deteriorate. “There was nothing charming to me about sedentary old people, rocking chairs, hot houses with Victorian trappings,” he says. At his grandparents’ funerals, he couldn’t help but notice that they didn’t look much different in death than they did at the end of life. And that was heartbreaking. “To say I love life is an understatement,” he says. “Life is the most beautiful and magic of all things.”

If his hypothesis is correct – who knows? – it might one day help prevent disease and modestly extend life for millions of people. Walker is all too aware, though, that it would come too late for him. As he writes in his book: “I feel a bit like Moses who, after wandering in the desert for most years of his life, was allowed to gaze upon the Promised Land but not granted entrance into it.”

 Read the entire story here.

Story courtesy of BBC and Mosaic under Creative Commons License.

Image: DNA structure. Courtesy of Wikipedia.

BigBang, Idea Soup

DarwinTunes

Charles_DarwinResearchers at Imperial College, London recently posed an intriguing question and have since developed a cool experiment to test it. Does artistic endeavor, such as music, follow the same principles of evolutionary selection in biology, as described by Darwin? That is, does the funkiest survive? Though, one has to wonder what the eminent scientist would have thought about some recent fusion of rap / dubstep / classical.

From the Guardian:

There were some funky beats at Imperial College London on Saturday at its annual science festival. As well as opportunities to create bogeys, see robots dance and try to get physics PhD students to explain their wacky world, this fascinating event included the chance to participate in a public game-like experiment called DarwinTunes.

Participants select tunes and “mate” them with other tunes to create musical offspring: if the offspring are in turn selected by other players, they “survive” and get the chance to reproduce their musical DNA. The experiment is online – you too can try to immortalise your selfish musical genes.

It is a model of evolution in practice that raises fascinating questions about culture and nature. These questions apply to all the arts, not just to dance beats. How does “cultural evolution” work? How close is the analogy between Darwin’s well-proven theory of evolution in nature and the evolution of art, literature and music?

The idea of cultural evolution was boldly defined by Jacob Bronowski as our fundamental human ability “not to accept the environment but to change it”. The moment the first stone tools appeared in Africa, about 2.5m years ago, a new, faster evolution, that of human culture, became visible on Earth: from cave paintings to the Renaissance, from Galileo to the 3D printer, this cultural evolution has advanced at breathtaking speed compared with the massive periods of time it takes nature to evolve new forms.

In DarwinTunes, cultural evolution is modelled as what the experimenters call “the survival of the funkiest”. Pulsing dance beats evolve through selections made by participants, and the music (it is claimed) becomes richer through this process of selection. Yet how does the model really correspond to the story of culture?

One way Darwin’s laws of nature apply to visual art is in the need for every successful form to adapt to its environment. In the forests of west and central Africa, wood carving was until recent times a flourishing art form. In the islands of Greece, where marble could be quarried easily, stone sculpture was more popular. In the modern technological world, the things that easily come to hand are not wood or stone but manufactured products and media images – so artists are inclined to work with the readymade.

At first sight, the thesis of DarwinTunes is a bit crude. Surely it is obvious that artists don’t just obey the selections made by their audience – that is, their consumers. To think they do is to apply the economic laws of our own consumer society across all history. Culture is a lot funkier than that.

Yet just because the laws of evolution need some adjustment to encompass art, that does not mean art is a mysterious spiritual realm impervious to scientific study. In fact, the evolution of evolution – the adjustments made by researchers to Darwin’s theory since it was unveiled in the Victorian age – offers interesting ways to understand culture.

One useful analogy between art and nature is the idea of punctuated equilibrium, introduced by some evolutionary scientists in the 1970s. Just as species may evolve not through a constant smooth process but by spectacular occasional leaps, so the history of art is punctuated by massively innovative eras followed by slower, more conventional periods.

Read the entire story here.

Image: Charles Darwin, 1868, photographed by Julia Margaret Cameron. Courtesy of Wikipedia.

BigBang, Book Reviews

Biological Transporter

Molecular-biology entrepreneur and genomics engineering pioneer, Craig Venter, is at it again. In his new book, Life at the Speed of Light: From the Double Helix to the Dawn of Digital Life, Venter explains his grand ideas and the coming era of discovery.

From ars technica:

J Craig Venter has been a molecular-biology pioneer for two decades. After developing expressed sequence tags in the 90s, he led the private effort to map the human genome, publishing the results in 2001. In 2010, the J Craig Venter Institute manufactured the entire genome of a bacterium, creating the first synthetic organism.

Now Venter, author of Life at the Speed of Light: From the Double Helix to the Dawn of Digital Life, explains the coming era of discovery.

Wired: In Life at the Speed of Light, you argue that humankind is entering a new phase of evolution. How so?

J Craig Venter: As the industrial age is drawing to a close, I think that we’re witnessing the dawn of the era of biological design. DNA, as digitized information, is accumulating in computer databases. Thanks to genetic engineering, and now the field of synthetic biology, we can manipulate DNA to an unprecedented extent, just as we can edit software in a computer. We can also transmit it as an electromagnetic wave at or near the speed of light and, via a “biological teleporter,” use it to recreate proteins, viruses, and living cells at another location, changing forever how we view life.

So you view DNA as the software of life?

All the information needed to make a living, self-replicating cell is locked up within the spirals of DNA’s double helix. As we read and interpret that software of life, we should be able to completely understand how cells work, then change and improve them by writing new cellular software.

The software defines the manufacture of proteins that can be viewed as its hardware, the robots and chemical machines that run a cell. The software is vital because the cell’s hardware wears out. Cells will die in minutes to days if they lack their genetic-information system. They will not evolve, they will not replicate, and they will not live.

Of all the experiments you have done over the past two decades involving the reading and manipulation of the software of life, which are the most important?

I do think the synthetic cell is my most important contribution. But if I were to select a single study, paper, or experimental result that has really influenced my understanding of life more than any other, I would choose one that my team published in 2007, in a paper with the title Genome Transplantation in Bacteria: Changing One Species to Another. The research that led to this paper in the journal Science not only shaped my view of the fundamentals of life but also laid the groundwork to create the first synthetic cell. Genome transplantation not only provided a way to carry out a striking transformation, converting one species into another, but would also help prove that DNA is the software of life.

What has happened since your announcement in 2010 that you created a synthetic cell, JCVI-syn1.0?

At the time, I said that the synthetic cell would give us a better understanding of the fundamentals of biology and how life works, help develop techniques and tools for vaccine and pharmaceutical development, enable development of biofuels and biochemicals, and help to create clean water, sources of food, textiles, bioremediation. Three years on that vision is being borne out.

Your book contains a dramatic account of the slog and setbacks that led to the creation of this first synthetic organism. What was your lowest point?

When we started out creating JCVI-syn1.0 in the lab, we had selected M. genitalium because of its extremely small genome. That decision we would come to really regret: in the laboratory, M. genitalium grows slowly. So whereas E. coli divides into daughter cells every 20 minutes, M. genitalium requires 12 hours to make a copy of itself. With logarithmic growth, it’s the difference between having an experimental result in 24 hours versus several weeks. It felt like we were working really hard to get nowhere at all. I changed the target to the M. mycoides genome. It’s twice as large as that of genitalium, but it grows much faster. In the end, that move made all the difference.

Some of your peers were blown away by the synthetic cell; others called it a technical tour de force. But there were also those who were underwhelmed because it was not “life from scratch.”

They haven’t thought much about what they are actually trying to say when they talk about “life from scratch.” How about baking a cake “from scratch”? You could buy one and then ice it at home. Or buy a cake mix, to which you add only eggs, water and oil. Or combining the individual ingredients, such as baking powder, sugar, salt, eggs, milk, shortening and so on. But I doubt that anyone would mean formulating his own baking powder by combining sodium, hydrogen, carbon, and oxygen to produce sodium bicarbonate, or producing homemade corn starch. If we apply the same strictures to creating life “from scratch,” it could mean producing all the necessary molecules, proteins, lipids, organelles, DNA, and so forth from basic chemicals or perhaps even from the fundamental elements carbon, hydrogen, oxygen, nitrogen, phosphate, iron, and so on.

There’s a parallel effort to create virtual life, which you go into in the book. How sophisticated are these models of cells in silico?

In the past year we have really seen how virtual cells can help us understand the real things. This work dates back to 1996 when Masaru Tomita and his students at the Laboratory for Bioinformatics at Keio started investigating the molecular biology of Mycoplasma genitalium—which we had sequenced in 1995—and by the end of that year had established the E-Cell Project. The most recent work on Mycoplasma genitalium has been done in America, by the systems biologist Markus W Covert, at Stanford University. His team used our genome data to create a virtual version of the bacterium that came remarkably close to its real-life counterpart.

You’ve discussed the ethics of synthetic organisms for a long time—where is the ethical argument today?

The Janus-like nature of innovation—its responsible use and so on—was evident at the very birth of human ingenuity, when humankind first discovered how to make fire on demand. (Do I use it burn down a rival’s settlement, or to keep warm?) Every few months, another meeting is held to discuss how powerful technology cuts both ways. It is crucial that we invest in underpinning technologies, science, education, and policy in order to ensure the safe and efficient development of synthetic biology. Opportunities for public debate and discussion on this topic must be sponsored, and the lay public must engage. But it is important not to lose sight of the amazing opportunities that this research presents. Synthetic biology can help address key challenges facing the planet and its population. Research in synthetic biology may lead to new things such as programmed cells that self-assemble at the sites of disease to repair damage.

What worries you more: bioterror or bioerror?

I am probably more concerned about an accidental slip. Synthetic biology increasingly relies on the skills of scientists who have little experience in biology, such as mathematicians and electrical engineers. The democratization of knowledge and the rise of “open-source biology;” the availability of kitchen-sink versions of key laboratory tools, such as the DNA-copying method PCR, make it easier for anyone—including those outside the usual networks of government, commercial, and university laboratories and the culture of responsible training and biosecurity—to play with the software of life.

Following the precautionary principle, should we abandon synthetic biology?

My greatest fear is not the abuse of technology, but that we will not use it at all, and turn our backs to an amazing opportunity at a time when we are over-populating our planet and changing environments forever.

You’re bullish about where this is headed.

I am—and a lot of that comes from seeing the next generation of synthetic biologists. We can get a view of what the future holds from a series of contests that culminate in a yearly event in Cambridge, Massachusetts—the International Genetically Engineered Machine (iGEM) competition. High-school and college students shuffle a standard set of DNA subroutines into something new. It gives me hope for the future.

You’ve been working to convert DNA into a digital signal that can be transmitted to a unit which then rebuilds an organism.

At Synthetic Genomics, Inc [which Venter founded with his long-term collaborator, the Nobel laureate Ham Smith], we can feed digital DNA code into a program that works out how to re-synthesize the sequence in the lab. This automates the process of designing overlapping pieces of DNA base-pairs, called oligonucleotides, adding watermarks, and then feeding them into the synthesizer. The synthesizer makes the oligonucleotides, which are pooled and assembled using what we call our Gibson-assembly robot (named after my talented colleague Dan Gibson). NASA has funded us to carry out experiments at its test site in the Mojave Desert. We will be using the JCVI mobile lab, which is equipped with soil-sampling, DNA-isolation and DNA sequencing equipment, to test the steps for autonomously isolating microbes from soil, sequencing their DNA and then transmitting the information to the cloud with what we call a “digitized-life-sending unit”. The receiving unit, where the transmitted DNA information can be downloaded and reproduced anew, has a number of names at present, including “digital biological converter,” “biological teleporter,” and—the preference of former US Wired editor-in-chief and CEO of 3D Robotics, Chris Anderson—”life replicator”.

Read the entire article here.

Image: J Craig Venter. Courtesy of Wikipedia.

BigBang

Chromosomal Chronometer

Researchers find possible evidence of DNA mechanism that keep track of age. It is too early to tell if changes over time in specific elements of our chromosomes result in or are a consequence of aging. Yet, this is a tantalizing discovery that bodes well for a better understanding into the genetic and biological systems that underlie the aging process.

From the Guardian:

A US scientist has discovered an internal body clock based on DNA that measures the biological age of our tissues and organs.

The clock shows that while many healthy tissues age at the same rate as the body as a whole, some of them age much faster or slower. The age of diseased organs varied hugely, with some many tens of years “older” than healthy tissue in the same person, according to the clock.

Researchers say that unravelling the mechanisms behind the clock will help them understand the ageing process and hopefully lead to drugs and other interventions that slow it down.

Therapies that counteract natural ageing are attracting huge interest from scientists because they target the single most important risk factor for scores of incurable diseases that strike in old age.

“Ultimately, it would be very exciting to develop therapy interventions to reset the clock and hopefully keep us young,” said Steve Horvath, professor of genetics and biostatistics at the University of California in Los Angeles.

Horvath looked at the DNA of nearly 8,000 samples of 51 different healthy and cancerous cells and tissues. Specifically, he looked at how methylation, a natural process that chemically modifies DNA, varied with age.

Horvath found that the methylation of 353 DNA markers varied consistently with age and could be used as a biological clock. The clock ticked fastest in the years up to around age 20, then slowed down to a steadier rate. Whether the DNA changes cause ageing or are caused by ageing is an unknown that scientists are now keen to work out.

“Does this relate to something that keeps track of age, or is a consequence of age? I really don’t know,” Horvath told the Guardian. “The development of grey hair is a marker of ageing, but nobody would say it causes ageing,” he said.

The clock has already revealed some intriguing results. Tests on healthy heart tissue showed that its biological age – how worn out it appears to be – was around nine years younger than expected. Female breast tissue aged faster than the rest of the body, on average appearing two years older.

Diseased tissues also aged at different rates, with cancers speeding up the clock by an average of 36 years. Some brain cancer tissues taken from children had a biological age of more than 80 years.

“Female breast tissue, even healthy tissue, seems to be older than other tissues of the human body. That’s interesting in the light that breast cancer is the most common cancer in women. Also, age is one of the primary risk factors of cancer, so these types of results could explain why cancer of the breast is so common,” Horvath said.

Healthy tissue surrounding a breast tumour was on average 12 years older than the rest of the woman’s body, the scientist’s tests revealed.

Writing in the journal Genome Biology, Horvath showed that the biological clock was reset to zero when cells plucked from an adult were reprogrammed back to a stem-cell-like state. The process for converting adult cells into stem cells, which can grow into any tissue in the body, won the Nobel prize in 2012 for Sir John Gurdon at Cambridge University and Shinya Yamanaka at Kyoto University.

“It provides a proof of concept that one can reset the clock,” said Horvath. The scientist now wants to run tests to see how neurodegenerative and infectious diseases affect, or are affected by, the biological clock.

Read the entire article here.

Image: Artist rendition of DNA fragment. Courtesy of Zoonar GmbH/Alamy.

BigBang

Biological Gears

We humans think they’re so smart. After all, we’ve invented, designed, built and continuously re-defined our surroundings. But, if we look closely at nature’s wonderful inventions we’ll find that it more often than not beat us to it. Now biologists have found insects with working gears.

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From New Scientist:

For a disconcerting experience, consider how mechanical you are. Humans may be conscious beings with higher feelings, but really we’re just fancy machines with joints, motors, valves, and a whole lot of plumbing.

All animals are the same. Hundreds of gizmos have evolved in nature, many of which our engineers merely reinvented. Nature had rotating axles billions of years ago, in the shape of bacterial flagella. And weevil legs beat us to the screw-and-nut mechanism.

The insect Issus coleoptratus is another animal with an unexpected bit of machinery hidden in its body. Its larvae are the first animals known to have interlocking gears, just like in the gearbox of a car.

In high gear

I. coleoptratus is a type of planthoppers – a group of insects known for their prodigious jumping. It takes off in just 2 milliseconds, and moves at 3.9 metres per second. “This is a phenomenal performance,” says Malcolm Burrows of the University of Cambridge. “How on earth do they do it?”

Burrows first ran into the larvae of I. coleoptratus in a colleague’s garden. “We were poking around and there were these bugs, jumping around like crazy.” He took a closer look, and noticed that each larva had meshing gears connecting its two hind legs. The gears had been seen before, by a German biologist called K. Sander, but his 1957 paper isn’t even on the internet.

The bulb at the top of each hind leg has 10 to 12 teeth, each between 15 and 30 micrometres long. Effectively, each hind leg is topped by a biological cog, allowing the pair to interlock, and move in unison.

Working with Gregory Sutton of the University of Bristol, UK, Burrows filmed the gears at 5000 frames per second and confirmed that they mesh with each other (see video, top).

Great timing

The two hind legs moved within 30 microseconds of each other during a jump. Burrows and Sutton suspect that the gears evolved because they can synchronise the leg movements better and faster than neurons can.

Other animals have gears, but not gears that mesh, says Chris Lyal of the Natural History Museum in London. “When you look at [I. coleoptratus‘s gears], you wonder, why can’t anything else do that?” he says.

The German study from 1957 claims that all 2000-odd planthoppers have gears. “I’ve looked at about half a dozen, and they all have them,” says Burrows. “I’d be hesitant to say no other animal has them,” says Burrows. “But they haven’t been described.”

Read the entire article here.

Video courtesy of New Scientist.

Art, Environs, Idea Soup, Technica

En Vie: Bio-Fabrication Expo

En Vie, french for “alive” is an exposition like no other. It’s a fantastical place defined through a rich collaboration of material scientists, biologists, architects, designers and engineers. The premise of En Vie is quite elegant — put these disparate minds together and ask them to imagine what the future will look like. And, it’s a quite magical world; a world where biological fabrication replaces traditional mechanical and chemical fabrication. Here shoes grow from plants, furniture from fungi and bees construct vases. The En Vie exhibit is open at the Space Foundation EDF in Paris, France until September 1.

From ars technica:

The natural world has, over millions of years, evolved countless ways to ensure its survival. The industrial revolution, in contrast, has given us just a couple hundred years to play catch-up using technology. And while we’ve been busily degrading the Earth since that revolution, nature continues to outdo us in the engineering of materials that are stronger, tougher, and multipurpose.

Take steel for example. According to the World Steel Association, for every ton produced, 1.8 tons of carbon dioxide is emitted into the atmosphere. In total in 2010, the iron and steel industries, combined, were responsible for 6.7 percent of total global CO2 emissions. Then there’s the humble spider, which produces silk that is—weight for weight—stronger than steel. Webs spun by Darwin’s bark spider in Madagascar, meanwhile, are 10 times tougher than steel and more durable than Kevlar, the synthetic fiber used in bulletproof vests. Material scientists savvy to this have ensured biomimicry is now high on the agenda at research institutions, and an exhibit currently on at the Space Foundation EDF in Paris is doing its best to popularize the notion that we should not just be salvaging the natural world but also learning from it.

En Vie (Alive), curated by Reader and Deputy Director of the Textile Futures Research Center at Central Saint Martins College Carole Collet, is an exposition for what happens when material scientists, architects, biologists, and engineers come together with designers to ask what the future will look like. According to them, it will be a world where plants grow our products, biological fabrication replaces traditional manufacturing, and genetically reprogrammed bacteria build new materials, energy, or even medicine.

It’s a fantastical place where plants are magnetic, a vase is built by 60,000 bees, furniture is made from funghi, and shoes from cellulose. You can print algae onto rice paper, then eat it or encourage gourds to grow in the shape of plastic components found in things like torches or radios (you’ll have to wait a few months for the finished product, though). These are not fanciful designs but real products, grown or fashioned with nature’s direct help.

In other parts of the exhibit, biology is the inspiration and shows what might be. Eskin, for instance, provides visitors with a simulation of how a building’s exterior could mimic and learn from the human body in keeping it warm and cool.

Alive shows that, speculative or otherwise, design has a real role to play in bringing different research fields together, which will be essential if there’s any hope of propelling the field into mass commercialization.

“More than any other point in history, advances in science and engineering are making it feasible to mimic natural processes in the laboratory, which makes it a very exciting time,” Craig Vierra, Professor and Assistant Chair, Biological Sciences at University of the Pacific, tells Wired.co.uk. In his California lab, Vierra has for the past few years been growing spider silk proteins from bacteria in order to engineer fibers that are close, if not quite ready, to give steel a run for its money. The technique involves purifying the spider silk proteins away from the bacteria proteins before concentrating these using a freeze-dryer in order to render them into powder form. A solvent is then added, and the material is spun into fiber using wet spinning techniques and stretched to three times its original length.

“Although the mechanical properties of the synthetic spider fibers haven’t quite reached those of natural fibers, research scientists are rapidly approaching this level of performance. Our laboratory has been working on improving the composition of the spinning dope and spinning parameters of the fibers to enhance their performance.”

Vierra is a firm believer that nature will save us.

“Mother Nature has provided us with some of the most outstanding biomaterials that can be used for a plethora of applications in the textile industry. In addition to these, modern technological advances will also allow us to create new biocomposite materials that rely on the fundamentals of natural processes, elevating the numbers and types of materials that are available. But, more importantly, we can generate eco-friendly materials.

“As the population size increases, the availability of natural resources will become more scarce and limiting for humans. It will force society to develop new methods and strategies to produce larger quantities of materials at a faster pace to meet the demands of the world. We simply must find more cost-efficient methods to manufacture materials that are non-toxic for the environment. Many of the materials being synthesized today are very dangerous after they degrade and enter the environment, which is severely impacting the wildlife and disrupting the ecology of the animals on the planet.”

According to Vierra, the fact that funding in the field has become extremely competitive over the past ten years is proof of the quality of research today. “The majority of scientists are expected to justify how their research has a direct, immediate tie to applications in society in order to receive funding.”

We really have no alternative but to continue down this route, he argues. Without advances in material science, we will continue to produce “inferior materials” and damage the environment. “Ultimately, this will affect the way humans live and operate in society.”

We’re agreed that the field is a vital and rapidly growing one. But what value, if any, can a design-led project bring to the table, aside from highlighting the related issues. Vierra has assessed a handful of the incredible designs on display at Alive for us to see which he thinks could become a future biomanufacturing reality.

Read the entire article here.

Image: Radiant Soil, En Vie Exposition. Courtesy of Philip Beesley, En Vie / Wired.

BigBang

Building a Liver

In yet another breakthrough for medical science, researchers have succeeded in growing a prototypical human liver in the lab.

From the New York Times:

Researchers in Japan have used human stem cells to create tiny human livers like those that arise early in fetal life. When the scientists transplanted the rudimentary livers into mice, the little organs grew, made human liver proteins, and metabolized drugs as human livers do.

They and others caution that these are early days and this is still very much basic research. The liver buds, as they are called, did not turn into complete livers, and the method would have to be scaled up enormously to make enough replacement liver buds to treat a patient. Even then, the investigators say, they expect to replace only 30 percent of a patient’s liver. What they are making is more like a patch than a full liver.

But the promise, in a field that has seen a great deal of dashed hopes, is immense, medical experts said.

“This is a major breakthrough of monumental significance,” said Dr. Hillel Tobias, director of transplantation at the New York University School of Medicine. Dr. Tobias is chairman of the American Liver Foundation’s national medical advisory committee.

“Very impressive,” said Eric Lagasse of the University of Pittsburgh, who studies cell transplantation and liver disease. “It’s novel and very exciting.”

The study was published on Wednesday in the journal Nature.

Although human studies are years away, said Dr. Leonard Zon, director of the stem cell research program at Boston Children’s Hospital, this, to his knowledge, is the first time anyone has used human stem cells, created from human skin cells, to make a functioning solid organ, like a liver, as opposed to bone marrow, a jellylike organ.

Ever since they discovered how to get human stem cells — first from embryos and now, more often, from skin cells — researchers have dreamed of using the cells for replacement tissues and organs. The stem cells can turn into any type of human cell, and so it seemed logical to simply turn them into liver cells, for example, and add them to livers to fill in dead or damaged areas.

But those studies did not succeed. Liver cells did not take up residence in the liver; they did not develop blood supplies or signaling systems. They were not a cure for disease.

Other researchers tried making livers or other organs by growing cells on scaffolds. But that did not work well either. Cells would fall off the scaffolds and die, and the result was never a functioning solid organ.

Researchers have made specialized human cells in petri dishes, but not three-dimensional structures, like a liver.

The investigators, led by Dr. Takanori Takebe of the Yokohama City University Graduate School of Medicine, began with human skin cells, turning them into stem cells. By adding various stimulators and drivers of cell growth, they then turned the stem cells into human liver cells and began trying to make replacement livers.

They say they stumbled upon their solution. When they grew the human liver cells in petri dishes along with blood vessel cells from human umbilical cords and human connective tissue, that mix of cells, to their surprise, spontaneously assembled itself into three-dimensional liver buds, resembling the liver at about five or six weeks of gestation in humans.

Then the researchers transplanted the liver buds into mice, putting them in two places: on the brain and into the abdomen. The brain site allowed them to watch the buds grow. The investigators covered the hole in each animal’s skull with transparent plastic, giving them a direct view of the developing liver buds. The buds grew and developed blood supplies, attaching themselves to the blood vessels of the mice.

The abdominal site allowed them to put more buds in — 12 buds in each of two places in the abdomen, compared with one bud in the brain — which let the investigators ask if the liver buds were functioning like human livers.

They were. They made human liver proteins and also metabolized drugs that human livers — but not mouse livers — metabolize.

The approach makes sense, said Kenneth Zaret, a professor of cellular and developmental biology at the University of Pennsylvania. His research helped establish that blood and connective tissue cells promote dramatic liver growth early in development and help livers establish their own blood supply. On their own, without those other types of cells, liver cells do not develop or form organs.

Read the entire article here.

Image: Diagram of the human liver. Courtesy of Encyclopedia Britannica.

BigBang, Environs

Your Home As Eco-System

For centuries biologists, zoologists and ecologists have been mapping the wildlife that surrounds us in the great outdoors. Now a group led by microbiologist Noah Fierer at the University of Colorado Boulder is pursuing flora and fauna in one of the last unexplored eco-systems — the home. (Not for the faint of heart).

From the New York Times:

On a sunny Wednesday, with a faint haze hanging over the Rockies, Noah Fierer eyed the field site from the back of his colleague’s Ford Explorer. Two blocks east of a strip mall in Longmont, one of the world’s last underexplored ecosystems had come into view: a sandstone-colored ranch house, code-named Q. A pair of dogs barked in the backyard.

Dr. Fierer, 39, a microbiologist at the University of Colorado Boulder and self-described “natural historian of cooties,” walked across the front lawn and into the house, joining a team of researchers inside. One swabbed surfaces with sterile cotton swabs. Others logged the findings from two humming air samplers: clothing fibers, dog hair, skin flakes, particulate matter and microbial life.

Ecologists like Dr. Fierer have begun peering into an intimate, overlooked world that barely existed 100,000 years ago: the great indoors. They want to know what lives in our homes with us and how we “colonize” spaces with other species — viruses, bacteria, microbes. Homes, they’ve found, contain identifiable ecological signatures of their human inhabitants. Even dogs exert a significant influence on the tiny life-forms living on our pillows and television screens. Once ecologists have more thoroughly identified indoor species, they hope to come up with strategies to scientifically manage homes, by eliminating harmful taxa and fostering species beneficial to our health.

But the first step is simply to take a census of what’s already living with us, said Dr. Fierer; only then can scientists start making sense of their effects. “We need to know what’s out there first. If you don’t know that, you’re wandering blind in the wilderness.”

Here’s an undeniable fact: We are an indoor species. We spend close to 90 percent of our lives in drywalled caves. Yet traditionally, ecologists ventured outdoors to observe nature’s biodiversity, in the Amazon jungles, the hot springs of Yellowstone or the subglacial lakes of Antarctica. (“When you train as an ecologist, you imagine yourself tromping around in the forest,” Dr. Fierer said. “You don’t imagine yourself swabbing a toilet seat.”)

But as humdrum as a home might first appear, it is a veritable wonderland. Ecology does not stop at the front door; a home to you is also home to an incredible array of wildlife.

Besides the charismatic fauna commonly observed in North American homes — dogs, cats, the occasional freshwater fish — ants and roaches, crickets and carpet bugs, mites and millions upon millions of microbes, including hundreds of multicellular species and thousands of unicellular species, also thrive in them. The “built environment” doubles as a complex ecosystem that evolves under the selective pressure of its inhabitants, their behavior and the building materials. As microbial ecologists swab DNA from our homes, they’re creating an atlas of life much as 19th-century naturalists like Alfred Russel Wallace once logged flora and fauna on the Malay Archipelago.

Take an average kitchen. In a study published in February in the journal Environmental Microbiology, Dr. Fierer’s lab examined 82 surfaces in four Boulder kitchens. Predictable patterns emerged. Bacterial species associated with human skin, like Staphylococcaceae or Corynebacteriaceae, predominated. Evidence of soil showed up on the floor, and species associated with raw produce (Enterobacteriaceae, for example) appeared on countertops. Microbes common in moist areas — including sphingomonads, some strains infamous for their ability to survive in the most toxic sites — splashed in a kind of jungle above the faucet.

A hot spot of unrivaled biodiversity was discovered on the stove exhaust vent, probably the result of forced air and settling. The counter and refrigerator, places seemingly as disparate as temperate and alpine grasslands, shared a similar assemblage of microbial species — probably less because of temperature and more a consequence of cleaning. Dr. Fierer’s lab also found a few potential pathogens, like Campylobacter, lurking on the cupboards. There was evidence of the bacterium on a microwave panel, too, presumably a microbial “fingerprint” left by a cook handling raw chicken.

If a kitchen represents a temperate forest, few of its plants would be poison ivy. Most of the inhabitants are relatively benign. In any event, eradicating them is neither possible nor desirable. Dr. Fierer wants to make visible this intrinsic, if unseen, aspect of everyday life. “For a lot of the general public, they don’t care what’s in soil,” he said. “People care more about what’s on their pillowcase.” (Spoiler alert: The microbes living on your pillowcase are not all that different from those living on your toilet seat. Both surfaces come in regular contact with exposed skin.)

Read the entire article after the jump.

Image: Animals commonly found in the home. Courtesy of North Carolina State University.

BigBang

From RNA Chemistry to Cell Biology

Each day we inch towards a better scientific understanding of how life is thought to have begun on our planet. Over the last decade researchers have shown how molecules like the nucleotides that make up complex chains of RNA (ribonucleic acid) and DNA (deoxyribonucleic acid) may have formed in the primaeval chemical soup of the early Earth. But it’s altogether a much greater leap to get from RNA (or DNA) to even a simple biological cell. Some recent work sheds more light and suggests that the chemical to biological chasm between long-strands of RNA and a complex cell may not be as wide to cross as once thought.

From ars technica:

Origin of life researchers have made impressive progress in recent years, showing that simple chemicals can combine to make nucleotides, the building blocks of DNA and RNA. Given the right conditions, these nucleotides can combine into ever-longer stretches of RNA. A lot of work has demonstrated that RNAs can perform all sorts of interesting chemistry, specifically binding other molecules and catalyzing reactions.

So the case for life getting its start in an RNA world has gotten very strong in the past decade, but the difference between a collection of interesting RNAs and anything like a primitive cell—surrounded by membranes, filled with both RNA and proteins, and running a simple metabolism—remains a very wide chasm. Or so it seems. A set of papers that came out in the past several days suggest that the chasm might not be as large as we’d tend to think.

Ironing out metabolism

A lot of the basic chemistry that drives the cell is based on electron transport, typically involving proteins that contain an iron atom. These reactions not only create some of the basic chemicals that are necessary for life, they’re also essential to powering the cell. Both photosynthesis and the breakdown of sugars involve the transfer of electrons to and from proteins that contain an iron atom.

DNA and RNA tend to have nothing to do with iron, interacting with magnesium instead. But some researchers at Georgia Tech have considered that fact a historical accident. Since photosynthesis put so much oxygen into the atmosphere, most of the iron has been oxidized into a state where it’s not soluble in water. If you go back to before photosynthesis was around, the oceans were filled with dissolved iron. Previously, the group had shown that, in oxygen-free and iron rich conditions, RNAs would happily work with iron instead and that its presence could speed up their catalytic activity.

Now the group is back with a new paper showing that if you put a bunch of random RNAs into the same conditions, some of them can catalyze electron transfer reactions. By “random,” I mean RNAs that are currently used by cells to do completely unrelated things (specifically, ribosomal and transfer RNAs). The reactions they catalyze are very simple, but remember: these RNAs don’t normally function as a catalyst at all. It wouldn’t surprise me if, after a number of rounds of evolutionary selection, an iron-RNA combination could be found that catalyzes a reaction that’s a lot closer to modern metabolism.

All of which suggests that the basics of a metabolism could have gotten started without proteins around.

Proteins build membranes

Clearly, proteins showed up at some point. They certainly didn’t look much like the proteins we see today, which may have hundreds or thousands of amino acids linked together. In fact, they may not have looked much like proteins at all, if a paper from Jack Szostak’s group is any indication. Szostak’s found that just two amino acids linked together may have catalytic activity. Some of that activity can help them engage in competition over another key element of the first cells: membrane material.

The work starts with a two amino acid long chemical called a peptide. If that peptide happens to be serine linked to histidine (two amino acids in use by life today), it has an interesting chemical activity: very slowly and poorly, it links other amino acids together to form more peptides. This weak activity is especially true if the amino acids are phenylalanine and leucine, two water-hating chemicals. Once they’re linked, they will precipitate out of a water solution.

The authors added a fatty acid membrane, figuring that it would soak up the reaction product. That definitely worked, with the catalytic efficiency of serine-histidine going up as a result. But something else happened as well: membranes that incorporated the reaction product started growing. It turns out that its presence in the membrane made it an efficient scrounger of other membrane material. As they grew, these membranes extended as long filaments that would break up into smaller parts with a gentle agitation and then start growing all over again.

In fact, the authors could set up a bit of a Darwinian competition between membranes based on how much starting catalyst each had. All of which suggests that proteins might have found their way into the cell as very simple chemicals that, at least initially, weren’t in any way connected to genetic and biochemical functions performed by RNA. But any cell-like things that evolved an RNA that made short proteins could have a big advantage over its competition.

Read the entire article here.

BigBang

Grow Your Own… Heart

A timely article for Valentine’s Day. Researchers continue to make astonishing progress in areas of cell biology and human genomics. So, it should come as no surprise that growing a customized, replacement heart in a lab from reprogrammed cells will one day be on the horizon.

[div class=attrib]From the Guardian:[end-div]

Every two minutes someone in the UK has a heart attack. Every six minutes, someone dies from heart failure. During an attack, the heart remodels itself and dilates around the site of the injury to try to compensate, but these repairs are rarely effective. If the attack does not kill you, heart failure later frequently will.

“No matter what other clinical interventions are available, heart transplantation is the only genuine cure for this,” says Paul Riley, professor of regenerative medicine at Oxford University. “The problem is there is a dearth of heart donors.”

Transplants have their own problems – successful operations require patients to remain on toxic, immune-suppressing drugs for life and their subsequent life expectancies are not usually longer than 20 years.

The solution, emerging from the laboratories of several groups of scientists around the world, is to work out how to rebuild damaged hearts. Their weapons of choice are reprogrammed stem cells.

These researchers have rejected the more traditional path of cell therapy that you may have read about over the past decade of hope around stem cells – the idea that stem cells could be used to create batches of functioning tissue (heart or brain or whatever else) for transplant into the damaged part of the body. Instead, these scientists are trying to understand what the chemical and genetic switches are that turn something into a heart cell or muscle cell. Using that information, they hope to programme cells at will, and help the body make repairs.

It is an exciting time for a technology that no one thought possible a few years ago. In 2007, Shinya Yamanaka showed it was possible to turn adult skin cells into embryonic-like stem cells, called induced pluripotent stem cells (iPSCs), using just a few chemical factors. His technique radically advanced stem cell biology, sweeping aside years of blockages due to the ethical objections about using stem cells from embryos. He won the Nobel prize in physiology or medicine for his work in October. Researchers have taken this a step further – directly turning one mature cell type to another without going through a stem cell phase.

And politicians are taking notice. At the Royal Society in November, in his first major speech on the Treasury’s ambitions for science and technology, the chancellor, George Osborne, identified regenerative medicine as one of eight areas of technology in which he wanted the UK to become a world leader. Earlier last year, the Lords science and technology committee launched an inquiry into the potential of regenerative medicine in the UK – not only the science but what regulatory obstacles there might be to turning the knowledge into medical applications.

At Oxford, Riley has spent almost a year setting up a £2.5m lab, funded as part of the British Heart Foundation’s Mending Broken Hearts appeal, to work out how to get heart muscle to repair itself. The idea is to expand the scope of the work that got Riley into the headlines last year after a high-profile paper published in the journal Nature in which he showed a means of repairing cells damaged during a heart attack in mice. That work involved in effect turning the clock back in a layer of cells on the outside of the heart, called the epicardium, making adult cells think they were embryos again and thereby restarting their ability to repair.

During the development of the embryo, the epicardium turns into the many types of cells seen in the heart and surrounding blood vessels. After the baby is born this layer of cells loses its ability to transform. By infusing the epicardium with the protein thymosin ?4 (T?4), Riley’s team found the once-dormant layer of cells was able to produce new, functioning heart cells. Overall, the treatment led to a 25% improvement in the mouse heart’s ability to pump blood after a month compared with mice that had not received the treatment.

[div class=attrib]Read the entire article after the jump.[end-div]

[div class=attrib]Image courtesy of Google Search.[end-div]

BigBang

Orphan Genes

DNA is a remarkable substance. It is the fundamental blueprint for biological systems. It is the basis for all complex life on our planet, it enables parents to share characteristics, both good and bad, with their children. Yet the more geneticists learn about the functions of DNA, the more mysteries it presents. One such conundrum is posed by so-called junk DNA and orphan genes — seemingly useless sequences of DNA that perform no function. Or so researchers previously believed.

[div class=attrib]From New Scientist:[end-div]

NOT having any family is tough. Often unappreciated and uncomfortably different, orphans have to fight to fit in and battle against the odds to realise their potential. Those who succeed, from Aristotle to Steve Jobs, sometimes change the world.

Who would have thought that our DNA plays host to a similar cast of foundlings? When biologists began sequencing genomes, they discovered that up to a third of genes in each species seemed to have no parents or family of any kind. Nevertheless, some of these “orphan genes” are high achievers, and a few even seem have played a part in the evolution of the human brain.

But where do they come from? With no obvious ancestry, it was as if these genes had appeared from nowhere, but that couldn’t be true. Everyone assumed that as we learned more, we would discover what had happened to their families. But we haven’t – quite the opposite, in fact.

Ever since we discovered genes, biologists have been pondering their origins. At the dawn of life, the very first genes must have been thrown up by chance. But life almost certainly began in an RNA world, so back then, genes weren’t just blueprints for making enzymes that guide chemical reactions – they themselves were the enzymes. If random processes threw up a piece of RNA that could help make more copies of itself, natural selection would have kicked in straight away.

As living cells evolved, though, things became much more complex. A gene became a piece of DNA coding for a protein. For a protein to be made, an RNA copy of the DNA has to be created. This cannot happen without “DNA switches”, which are actually just extra bits of DNA alongside the protein-coding bits saying “copy this DNA into RNA”. Next, the RNA has to get to the protein-making factories. In complex cells, this requires the presence of yet more extra sequences, which act as labels saying “export me” and “start making the protein from here”.

The upshot is that the chances of random mutations turning a bit of junk DNA into a new gene seem infinitesimally small. As the French biologist François Jacob famously wrote 35 years ago, “the probability that a functional protein would appear de novo by random association of amino acids is practically zero”.

Instead, back in the 1970s it was suggested that the accidental copying of genes can result in a single gene giving rise to a whole family of genes, rather like the way animals branch into families of related species over time. It’s common for entire genes to be inadvertently duplicated. Spare copies are usually lost, but sometimes the duplicates come to share the function of the original gene between them, or one can diverge and take on a new function.

Take the light-sensing pigments known as opsins. The various opsins in our eyes are not just related to each other, they are also related to the opsins found in all other animals, from jellyfish to insects. The thousands of different opsin genes found across the animal kingdom all evolved by duplication, starting with a single gene in a common ancestor living around 700 million years ago (see diagram).

Most genes belong to similar families, and their ancestry can be traced back many millions of years. But when the yeast genome was sequenced around 15 years ago, it was discovered that around a third of yeast genes appeared to have no family. The term orphans (sometimes spelt ORFans) was used to describe individual genes, or small groups of very similar genes, with no known relatives.

“If you see a gene and you can’t find a relative you get suspicious,” says Ken Weiss, who studies the evolution of complex traits at Penn State University. Some suggested orphans were the genetic equivalent of living fossils like the coelacanth, the last surviving members of an ancient family. Others thought they were nothing special, just normal genes whose family hadn’t been found yet. After all, the sequencing of entire genomes had only just begun.

[div class=attrib]Read the entire article after the jump.[end-div]

[div class=attrib]Image: DNA structure. Courtesy of Wikipedia.[end-div]

BigBang

Curiosity’s 10K Hike

Scientists and engineers at JPL have Mount Sharp in their sites. It’s no ordinary mountain — it’s situated on Mars. The 5,000 meter high mountain is home to exposed layers of some promising sedimentary rocks, which hold clues to Mars’ geologic, and perhaps biological, history. Unfortunately, Mount Sharp is 10K away from the current home of the Curiosity rover. So, at a top speed of around 100 meters per day it will take Curiosity until the fall of 2013 to reach its destination.

[div class=attrib]From the New Scientist:[end-div]

NASA’S Curiosity rover is about to have its cake and eat it too. Around September, the rover should get its first taste of layered sediments at Aeolis Mons, a mountain over 5 kilometres tall that may hold preserved signs of life on Mars.

Previous rovers uncovered ample evidence of ancient water, a key ingredient for life as we know it. With its sophisticated on-board chemistry lab, Curiosity is hunting for more robust signs of habitability, including organic compounds – the carbon-based building blocks of life as we know it.

Observations from orbit show that the layers in Aeolis Mons – also called Mount Sharp – contain minerals thought to have formed in the presence of water. That fits with theories that the rover’s landing site, Gale crater, was once a large lake. Even better, the layers were probably laid down quickly enough that the rocks could have held on to traces of microorganisms, if they existed there.

If the search for organics turns up empty, Aeolis Mons may hold other clues to habitability, says project scientist John Grotzinger of the California Institute of Technology in Pasadena. The layers will reveal which minerals and chemical processes were present in Mars’s past. “We’re going to find all kinds of good stuff down there, I’m sure,” he says.

Curiosity will explore a region called Glenelg until early February, and then hit the gas. The base of the mountain is 10 kilometres away, and the rover can drive at about 100 metres a day at full speed. The journey should take between six and nine months, but will include stops to check out any interesting landmarks. After all, some of the most exciting discoveries from Mars rovers were a result of serendipity.

[div class=attrib]Read the entire article following the jump.[end-div]

[div class=attrib]Image: Base of Mount Sharp, Mars. Courtesy of Credit: NASA/JPL-Caltech/MSSS.[end-div]

BigBang

Telomere Test: A Date With Death

In 1977 Elizabeth Blackburn and Joseph Gall, molecular biologists, discovered the structure of the end caps, known as telomeres, of chromosomes. In 2009, Blackburn and colleagues Carol Greider and Jack Szostak shared the Nobel prize in Physiology or Medicine for discovering the enzyme telomerase, the enzyme responsible for replenishing telomeres.

It turns out that telomeres are rather important. Studies shows that telomeres regulate cell division, and as a consequence directly influence aging and life span. When a cell divides the length of its chromosomal telomeres shortens. Once a telomere is depleted its chromosome, and DNA, can no longer be replicated accurately, and the cell no longer divides, hastening cell death.

[div class=attrib]From the Independent:[end-div]

A blood test to determine how fast someone is ageing has been shown to work on a population of wild birds, the first time the ageing test has been used successfully on animals living outside a laboratory setting.

The test measures the average length of tiny structures on the tips of chromosomes called telomeres which are known to get shorter each time a cell divides during an organism’s lifetime.

Telomeres are believed to act like internal clocks by providing a more accurate estimate of a person’s true biological age rather than their actual chronological age.

This has led some experts to suggest that telomere tests could be used to estimate not only how fast someone is ageing, but possibly how long they have left to live if they die of natural causes.

Telomere tests have been widely used on experimental animals and at least one company is offering a £400 blood test in the UK for people interested in seeing how fast they are ageing based on their average telomere length.

Now scientists have performed telomere tests on an isolated population of songbirds living on an island in the Seychelles and found that the test does indeed accurately predict an animal’s likely lifespan.

“We saw that telomere length is a better indicator of life expectancy than chronological age. So by measuring telomere length we have a way of estimating the biological age of an individual – how much of its life it has used up,” said David Richardson of the University of East Anglia.

The researchers tested the average telomere lengths of a population of 320 Seychelles Warblers living on the remote Cousin Island, which ornithologists have studied for 20 years, documenting the life history of each bird.

“Our results provide the first clear and unambiguous evidence of a relationship between telomere length and mortality in the wild, and substantiate the prediction that telomere length and shortening rate can act as an indicator of biological age further to chronological age,” says the study published in the journal Molecular Ecology.

Studying an island population of wild birds was important because there were no natural predators and little migration, meaning that the scientists could accurately study the link between telomere length and a bird’s natural lifespan.

“We wanted to understand what happens over an entire lifetime, so the Seychelles warbler is an ideal research subject. They are naturally confined to an isolated tropical island, without any predators, so we can follow individuals throughout their lives, right into old age,” Dr Richardson said.

“We investigated whether, at any given age, their telomere lengths could predict imminent death. We found that short and rapidly shortening telomeres were a good indication that the bird would die within a year,” he said.

[div class=attrib]Read the entire article following the jump.[end-div]

[div class=attrib]Infographic courtesy of Independent.[end-div]

BigBang

Growing Eyes in the Lab

[div class=attrib]From Nature:[end-div]

A stem-cell biologist has had an eye-opening success in his latest effort to mimic mammalian organ development in vitro. Yoshiki Sasai of the RIKEN Center for Developmental Biology (CBD) in Kobe, Japan, has grown the precursor of a human eye in the lab.

The structure, called an optic cup, is 550 micrometres in diameter and contains multiple layers of retinal cells including photoreceptors. The achievement has raised hopes that doctors may one day be able to repair damaged eyes in the clinic. But for researchers at the annual meeting of the International Society for Stem Cell Research in Yokohama, Japan, where Sasai presented the findings this week, the most exciting thing is that the optic cup developed its structure without guidance from Sasai and his team.

“The morphology is the truly extraordinary thing,” says Austin Smith, director of the Centre for Stem Cell Research at the University of Cambridge, UK.

Until recently, stem-cell biologists had been able to grow embryonic stem-cells only into two-dimensional sheets. But over the past four years, Sasai has used mouse embryonic stem cells to grow well-organized, three-dimensional cerebral-cortex1, pituitary-gland2 and optic-cup3 tissue. His latest result marks the first time that anyone has managed a similar feat using human cells.

Familiar patterns
The various parts of the human optic cup grew in mostly the same order as those in the mouse optic cup. This reconfirms a biological lesson: the cues for this complex formation come from inside the cell, rather than relying on external triggers.

In Sasai’s experiment, retinal precursor cells spontaneously formed a ball of epithelial tissue cells and then bulged outwards to form a bubble called an eye vesicle. That pliable structure then folded back on itself to form a pouch, creating the optic cup with an outer wall (the retinal epithelium) and an inner wall comprising layers of retinal cells including photoreceptors, bipolar cells and ganglion cells. “This resolves a long debate,” says Sasai, over whether the development of the optic cup is driven by internal or external cues.

There were some subtle differences in the timing of the developmental processes of the human and mouse optic cups. But the biggest difference was the size: the human optic cup had more than twice the diameter and ten times the volume of that of the mouse. “It’s large and thick,” says Sasai. The ratios, similar to those seen in development of the structure in vivo, are significant. “The fact that size is cell-intrinsic is tremendously interesting,” says Martin Pera, a stem-cell biologist at the University of Southern California, Los Angeles.

[div class=attrib]Read the entire article after the jump.[end-div]

[div class=attrib]Image courtesy of Discover Magazine.[end-div]

Idea Soup

Culture, Language and Genes

In the early 19th century Noah Webster set about re-defining written English. His aim was to standardize the spoken word in the fledgling nation and to distinguish American from British usage. In his own words, “as an independent nation, our honor requires us to have a system of our own, in language as well as government.”

He used his dictionary, which still bears his name today, as a tool to cleanse English of its stubborn reliance on aristocratic pedantry and over-reliance on Latin and Greek. He “simplified” the spelling of numerous words that he believed were contsructed with rules that were all too complicated. Thus, “colour” became “color” and “honour” switched to “honor”; “centre” became “center”, “behaviour” to “behavior”, “traveller” to “traveler”.

Webster offers a perfect example of why humanity seems so adept at fragmenting into diverse cultural groups that thrive through mutual uncomprehension. In “Wired for Culture”, evolutionary biologist Mark Pagel offers a compelling explanation based on that small, yet very selfish biological building block, the gene.

[div class=attrib]From the Wall Street Journal:[end-div]

The island of Gaua, part of Vanuatu in the Pacific, is just 13 miles across, yet it has five distinct native languages. Papua New Guinea, an area only slightly bigger than Texas, has 800 languages, some spoken by just a few thousand people.

…

Evolutionary biologists have long gotten used to the idea that bodies are just genes’ ways of making more genes, survival machines that carry genes to the next generation. Think of a salmon struggling upstream just to expend its body (now expendable) in spawning. Dr. Pagel’s idea is that cultures are an extension of this: that the way we use culture is to promote the long-term interests of our genes.

It need not be this way. When human beings’ lives became dominated by culture, they could have adopted habits that did not lead to having more descendants. But on the whole we did not; we set about using culture to favor survival of those like us at the expense of other groups, using religion, warfare, cooperation and social allegiance. As Dr. Pagel comments: “Our genes’ gamble at handing over control to…ideas paid off handsomely” in the conquest of the world.

What this means, he argues, is that if our “cultures have promoted our genetic interests throughout our history,” then our “particular culture is not for us, but for our genes.”

We’re expendable. The allegiance we feel to one tribe—religious, sporting, political, linguistic, even racial—is a peculiar mixture of altruism toward the group and hostility to other groups. Throughout history, united groups have stood, while divided ones fell.

Language is the most striking exemplar of Dr. Pagel’s thesis. He calls language “one of the most powerful, dangerous and subversive traits that natural selection has ever devised.” He draws attention to the curious parallels between genetics and linguistics. Both are digital systems, in which words or base pairs are recombined to make an infinite possibility of messages. (Elsewhere I once noted the numerical similarity between Shakespeare’s vocabulary of about 20,000 distinct words and his genome of about 21,000 genes).

Dr. Pagel points out that language is a “technology for rewiring other people’s minds…without either of you having to perform surgery.” But natural section was unlikely to favor such a technology if it helped just the speaker, or just the listener, at the expense of the other. Rather, he says that, just as the language of the genes promotes its own survival via a larger cooperative entity called the body, so language itself endures via the survival of the individual and the tribe.

[div class=attrib]Read the entire article here.[end-div]

[div class=attrib]Image courtesy of PA / Daily Mail.[end-div]

BigBang

Remembering Lynn Margulis: Pioneering Evolutionary Biologist

The world lost pioneering biologist Lynn Margulis on November 22.

One of her key contributions to biology, and in fact, to our overall understanding of the development of complex life, was her theory of the symbiotic origin of the nucleated cell, or symbiogenesis. Almost 50 years ago Margulis first argued that such complex nucleated, or eukaryotic, cells were formed from the association of different kinds of bacteria. Her idea was both radical and beautiful: that separate organisms, in this case ancestors of modern bacteria, would join together in a permanent relationship to form a new entity, a complex single cell.

Until fairly recently this idea was mostly dismissed by the scientific establishment. Nowadays her pioneering ideas on cell evolution through symbiosis are held as a fundamental scientific breakthrough.

We feature some excerpts below of Margulis’ writings:

[div class=attrib]From the Edge:[end-div]

At any fine museum of natural history — say, in New York, Cleveland, or Paris — the visitor will find a hall of ancient life, a display of evolution that begins with the trilobite fossils and passes by giant nautiloids, dinosaurs, cave bears, and other extinct animals fascinating to children. Evolutionists have been preoccupied with the history of animal life in the last five hundred million years. But we now know that life itself evolved much earlier than that. The fossil record begins nearly four thousand million years ago! Until the 1960s, scientists ignored fossil evidence for the evolution of life, because it was uninterpretable.

I work in evolutionary biology, but with cells and microorganisms. Richard Dawkins, John Maynard Smith, George Williams, Richard Lewontin, Niles Eldredge, and Stephen Jay Gould all come out of the zoological tradition, which suggests to me that, in the words of our colleague Simon Robson, they deal with a data set some three billion years out of date. Eldredge and Gould and their many colleagues tend to codify an incredible ignorance of where the real action is in evolution, as they limit the domain of interest to animals — including, of course, people. All very interesting, but animals are very tardy on the evolutionary scene, and they give us little real insight into the major sources of evolution’s creativity. It’s as if you wrote a four-volume tome supposedly on world history but beginning in the year 1800 at Fort Dearborn and the founding of Chicago. You might be entirely correct about the nineteenth-century transformation of Fort Dearborn into a thriving lakeside metropolis, but it would hardly be world history.

“codifying ignorance” I refer in part to the fact that they miss four out of the five kingdoms of life. Animals are only one of these kingdoms. They miss bacteria, protoctista, fungi, and plants. They take a small and interesting chapter in the book of evolution and extrapolate it into the entire encyclopedia of life. Skewed and limited in their perspective, they are not wrong so much as grossly uninformed.

Of what are they ignorant? Chemistry, primarily, because the language of evolutionary biology is the language of chemistry, and most of them ignore chemistry. I don’t want to lump them all together, because, first of all, Gould and Eldredge have found out very clearly that gradual evolutionary changes through time, expected by Darwin to be documented in the fossil record, are not the way it happened. Fossil morphologies persist for long periods of time, and after stasis, discontinuities are observed. I don’t think these observations are even debatable. John Maynard Smith, an engineer by training, knows much of his biology secondhand. He seldom deals with live organisms. He computes and he reads. I suspect that it’s very hard for him to have insight into any group of organisms when he does not deal with them directly. Biologists, especially, need direct sensory communication with the live beings they study and about which they write.

Reconstructing evolutionary history through fossils — paleontology — is a valid approach, in my opinion, but paleontologists must work simultaneously with modern-counterpart organisms and with “neontologists” — that is, biologists. Gould, Eldredge, and Lewontin have made very valuable contributions. But the Dawkins-Williams-Maynard Smith tradition emerges from a history that I doubt they see in its Anglophone social context. Darwin claimed that populations of organisms change gradually through time as their members are weeded out, which is his basic idea of evolution through natural selection. Mendel, who developed the rules for genetic traits passing from one generation to another, made it very clear that while those traits reassort, they don’t change over time. A white flower mated to a red flower has pink offspring, and if that pink flower is crossed with another pink flower the offspring that result are just as red or just as white or just as pink as the original parent or grandparent. Species of organisms, Mendel insisted, don’t change through time. The mixture or blending that produced the pink is superficial. The genes are simply shuffled around to come out in different combinations, but those same combinations generate exactly the same types. Mendel’s observations are incontrovertible.

[div class=attrib]Read the entire article here.[end-div]

[div class=attrib]Image: Lynn Margulis. Courtesy edge.org.[end-div]

BigBang

Immaculate creation: birth of the first synthetic cell

[div class=attrib]From the New Scientist:[end-div]

For the first time, scientists have created life from scratch – well, sort of. Craig Venter‘s team at the J. Craig Venter Institute in Rockville, Maryland, and San Diego, California, has made a bacterial genome from smaller DNA subunits and then transplanted the whole thing into another cell. So what exactly is the science behind the first synthetic cell, and what is its broader significance?

What did Venter’s team do?

The cell was created by stitching together the genome of a goat pathogen called Mycoplasma mycoides from smaller stretches of DNA synthesised in the lab, and inserting the genome into the empty cytoplasm of a related bacterium. The transplanted genome booted up in its host cell, and then divided over and over to make billions of M. mycoides cells.

Venter and his team have previously accomplished both feats – creating a synthetic genome and transplanting a genome from one bacterium into another – but this time they have combined the two.

“It’s the first self-replicating cell on the planet that’s parent is a computer,” says Venter, referring to the fact that his team converted a cell’s genome that existed as data on a computer into a living organism.

How can they be sure that the new bacteria are what they intended?

Venter and his team introduced several distinctive markers into their synthesised genome. All of them were found in the synthetic cell when it was sequenced.

These markers do not make any proteins, but they contain the names of 46 scientists on the project and several quotations written out in a secret code. The markers also contain the key to the code.

Crack the code and you can read the messages, but as a hint, Venter revealed the quotations: “To live, to err, to fall, to triumph, to recreate life out of life,” from James Joyce’s A Portrait of the Artist as a Young Man; “See things not as they are but as they might be,” which comes from American Prometheus, a biography of nuclear physicist Robert Oppenheimer; and Richard Feynman’s famous words: “What I cannot build I cannot understand.”

Does this mean they created life?

It depends on how you define “created” and “life”. Venter’s team made the new genome out of DNA sequences that had initially been made by a machine, but bacteria and yeast cells were used to stitch together and duplicate the million base pairs that it contains. The cell into which the synthetic genome was then transplanted contained its own proteins, lipids and other molecules.

Venter himself maintains that he has not created life . “We’ve created the first synthetic cell,” he says. “We definitely have not created life from scratch because we used a recipient cell to boot up the synthetic chromosome.”

Whether you agree or not is a philosophical question, not a scientific one as there is no biological difference between synthetic bacteria and the real thing, says Andy Ellington, a synthetic biologist at the University of Texas in Austin. “The bacteria didn’t have a soul, and there wasn’t some animistic property of the bacteria that changed,” he says.

What can you do with a synthetic cell?

Venter’s work was a proof of principle, but future synthetic cells could be used to create drugs, biofuels and other useful products. He is collaborating with Exxon Mobil to produce biofuels from algae and with Novartis to create vaccines.

“As soon as next year, the flu vaccine you get could be made synthetically,” Venter says.

Ellington also sees synthetic bacteria as having potential as a scientific tool. It would be interesting, he says, to create bacteria that produce a new amino acid – the chemical units that make up proteins – and see how these bacteria evolve, compared with bacteria that produce the usual suite of amino acids. “We can ask these questions about cyborg cells in ways we never could before.”

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BigBang

The Search for Genes Leads to Unexpected Places

[div class=attrib]From The New York Times:[end-div]

Edward M. Marcotte is looking for drugs that can kill tumors by stopping blood vessel growth, and he and his colleagues at the University of Texas at Austin recently found some good targets — five human genes that are essential for that growth. Now they’re hunting for drugs that can stop those genes from working. Strangely, though, Dr. Marcotte did not discover the new genes in the human genome, nor in lab mice or even fruit flies. He and his colleagues found the genes in yeast.

“On the face of it, it’s just crazy,” Dr. Marcotte said. After all, these single-cell fungi don’t make blood vessels. They don’t even make blood. In yeast, it turns out, these five genes work together on a completely unrelated task: fixing cell walls.

Crazier still, Dr. Marcotte and his colleagues have discovered hundreds of other genes involved in human disorders by looking at distantly related species. They have found genes associated with deafness in plants, for example, and genes associated with breast cancer in nematode worms. The researchers reported their results recently in The Proceedings of the National Academy of Sciences.

The scientists took advantage of a peculiar feature of our evolutionary history. In our distant, amoeba-like ancestors, clusters of genes were already forming to work together on building cell walls and on other very basic tasks essential to life. Many of those genes still work together in those same clusters, over a billion years later, but on different tasks in different organisms.

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