synthetic genomics and genome engineering rewriting the blueprint of life

genomebiology |  Biology is now undergoing a rapid transition from the age of deciphering DNA sequence information of the genomes of biological species to the age of synthetic genomes. Scientists hope to gain a thorough mastery of and deeper insights into biological systems by rewriting the genome, the blueprint of life. This transition demands a whole new level of biological understanding, which we currently lack. This knowledge, however, could be obtained through synthetic genomics and genome engineering, albeit on a trial and error basis, by redesigning and building naturally occurring bacterial and eukaryotic genomes whose sequences are known. 

Synthetic genomics arguably began with the report from Khorana’s laboratory in 1970 of the total synthesis of the first gene, encoding an artificial yeast alanine tRNA, from deoxyribonucleotides. Since then, rapid advances in DNA synthesis techniques, especially over the past decade, have made it possible to engineer biochemical pathways, assemble bacterial genomes and even to construct a synthetic organism [1]–[11]. Genome editing approaches for genome-wide scale alteration that are not based on total synthesis of the genome are also being pursued and have proved powerful; for example, in the production of a reduced-size genome version of Escherichia coli[4] and engineering of bacterial genomes to include many different changes simultaneously [8]. 

Progress has also been made in synthetic genomics for eukaryotes. Our group has embarked on the design and total synthesis of a novel eukaryotic genome structure - using the well-known model eukaryote Saccharomyces cerevisiae as the basis for a designer genome, known as ‘Sc2.0’. The availability of a fully synthetic genome will allow direct testing of evolutionary questions that are not otherwise approachable. Sc2.0 could also play an important practical role, since yeasts are the pre-eminent organisms for industrial fermentations, with a wide variety of practical uses, including production of therapeutic proteins, vaccines and small molecules through classical and well-developed industrial fermentation technologies. 

This article reviews the current status of synthetic genomics, starting with a historical perspective that highlights the key milestones in the field (Fig. 1) and then continuing with a particular emphasis on the total synthesis of the first functional designer eukaryotic (yeast) chromosome, synIII, and the Sc2.0 Project. Genome engineering using nuclease-based genome editing tools such as zinc finger nucleases, transcription activator-like effector nucleases and RNA-guided CRISPR-Cas9 is not within the scope of this minireview (Box 1). Recent advances in gene synthesis and assembly methods that have accelerated the genome synthesis efforts are discussed elsewhere [12].

first computational genomics, now computational ethology...,

academia |  Abstract: For the past two decades, it has widely been assumed by linguists that there is a single computational operation, Merge, which is unique to language, distinguishing it from other cognitive domains. The intention of this paper is to progress the discussion of language evolution in two ways: (i) survey what the ethological record reveals about the uniqueness of the human computational system, and (ii) explore how syntactic theories account for what ethology may determine to be human-specific. It is shown that the operation Label, not Merge, constitutes the evolutionary novelty which distinguishes human language from non-human computational systems; a proposal lending weight to a Weak Continuity Hypothesis and leading to the formation of what is termed Computational Ethology. Some directions for future ethological research are suggested.

 Keywords: Minimalism; Labeling effects; cognome; animal cognition; formal language theory; language evolution

dna printing

NPR |  Here's something that might sound strange: There are companies now that print and sell DNA.

This trend — which uses the term "print" in the sense of making a bunch of copies speedily — is making particular stretches of DNA much cheaper and easier to obtain than ever before. That excites many scientists who are keen to use these tailored strings of genetic instructions to do all sorts of things, ranging from finding new medical treatments to genetically engineering better crops.

"So much good can be done," says Austen Heinz, CEO of Cambrian Genomics in San Francisco, one of the companies selling these stretches of DNA.

But some of the ways Heinz and others talk about the possible uses of the technology also worries some people who are keeping tabs on the trend.

"I have significant concerns," says Marcy Darnovsky, who directs the Center for Genetics and Society, a genetics watchdog group.

A number of companies have been taking advantage of several recent advances in technology to produce DNA quickly and cheaply. Heinz says his company has made the process even cheaper.

"Everyone else that makes DNA, makes DNA incorrectly and then tries to fix it," Heinz says. "We don't fix it. We just see what's good, what's bad and then we use the correct pieces."

left behind...,

guardian |  As science progresses the upgrades that become available will increasingly widen the gap between rich and poor. Research on implantable devices called brain-computer interfaces (BCIs) are in trials to help disabled people move their defunct limbs or robotic prosthetics.

More advanced devices could link people's brains directly to the internet, giving them vast and faithful memory storage, and seamless access to information, even if that does include endless footage of cats in hats.

Work is ongoing into BCIs that connect many brains at once, allowing animals to cooperate by accessesing each others' brain power - work which raises deep questions about the future meaning of identity.

Genetic engineering will be more disruptive still. A new genome editing procedure called Crispr has given scientists their first real hope of making safe, precise changes to the human genome. They have already used it to correct cells with genetic faults that cause cataracts and cystic fibrosis. Similar therapies might allow improvements to human performance.

Western history has made many of today's researchers flinch at studies into the genetic basis of intelligence. But the Beijing Genomics Institute, the world's largest genomics research centre, has taken on the job . If the project bears fruit, it might drive attempts to boost human intelligence by genetically modifying embryos.

George Church, a geneticist at Harvard University, suggests another radical possibility. He has developed tools that can scramble the genetic code leaving it functional but unrecognisable to invading viruses. His first goal is to engineer a bacterium that is resistant to viral infection. But he does not dimiss the possibility of changing human DNA too – leading to a biologically new kind of human.

"In the 21st century, there is a real possibility of creating biological castes, with real biological differences between rich and poor," said Harari. "The end result could be speciation. We're used to being the only human species around, but there is no law of nature that says there can only be one species of human. With this kind of upgrading treatment we could have, in the not too distant future, more than one human species on Earth again."

wade in the nytimes: adventures in very recent evolution

NYTimes |  Ten thousand years ago, people in southern China began to cultivate rice and quickly made an all-too-tempting discovery — the cereal could be fermented into alcoholic liquors. Carousing and drunkenness must have started to pose a serious threat to survival because a variant gene that protects against alcohol became almost universal among southern Chinese and spread throughout the rest of China in the wake of rice cultivation. 

The variant gene rapidly degrades alcohol to a chemical that is not intoxicating but makes people flush, leaving many people of Asian descent a legacy of turning red in the face when they drink alcohol. 

The spread of the new gene, described in January by Bing Su of the Chinese Academy of Sciences, is just one instance of recent human evolution and in particular of a specific population’s changing genetically in response to local conditions. 

Scientists from the Beijing Genomics Institute last month discovered another striking instance of human genetic change. Among Tibetans, they found, a set of genes evolved to cope with low oxygen levels as recently as 3,000 years ago. This, if confirmed, would be the most recent known instance of human evolution. 

Many have assumed that humans ceased to evolve in the distant past, perhaps when people first learned to protect themselves against cold, famine and other harsh agents of natural selection. But in the last few years, biologists peering into the human genome sequences now available from around the world have found increasing evidence of natural selection at work in the last few thousand years, leading many to assume that human evolution is still in progress. 

“I don’t think there is any reason to suppose that the rate has slowed down or decreased,” says Mark Stoneking, a population geneticist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.

Jablonski taking a sledgehammer to race - MUCH more impressed with this woman than I am with myself...,

Edge | Race has always been a vague and slippery concept. In the mid-eighteenth century, European naturalists such as Linnaeus, Comte de Buffon, and Johannes Blumenbach described geographic groupings of humans who differed in appearance. The philosophers David Hume and Immanuel Kant both were fascinated by human physical diversity. In their opinions, extremes of heat, cold, or sunlight extinguished human potential. Writing in 1748, Hume contended that, "there was never a civilized nation of any complexion other than white."

Kant felt similarly. He was preoccupied with questions of human diversity throughout his career, and wrote at length on the subject in a series of essays beginning in 1775. Kant was the first to name and define the geographic groupings of humans as races (in German, Rassen). Kant's races were characterized by physical distinctions of skin color, hair form, cranial shape, and other anatomical features and by their capacity for morality, self-improvement, and civilization. Kant's four races were arranged hierarchically, with only the European race, in his estimation, being capable of self-improvement.

Why did the scientific racism of Hume and Kant prevail in the face of the logical and thoughtful opposition of von Herder and others? During his lifetime, Kant was recognized as a great philosopher, and his status rose as copies of his major philosophical works were distributed and read widely in the nineteenth century. Some of Kant's supporters agreed with his racist views, some apologized for them, or—most commonly—many just ignored them. The other reason that racist views triumphed over anti-racism in the late eighteenth and nineteenth centuries was that racism was, economically speaking, good for the transatlantic slave trade, which had become the overriding engine of European economic growth. The slave trade was bolstered by ideologies that diminished or denied the humanity of non-Europeans, especially Africans. Such views were augmented by newer biblical interpretations popular at the time that depicted Africans as destined for servitude. Skin color, as the most noticeable racial characteristic, became associated with a nebulous assemblage of opinions and hearsay about the inherent natures of the different races. Skin color stood for morality, character, and the capacity for civilization; it had become a meme. The nineteenth and early twentieth centuries saw the rise of "race science." The biological reality of races was confirmed by new types of scientific evidence amassed by new types of scientists, notably anthropologists and geneticists. This era witnessed the birth of eugenics and its offspring, the concept of racial purity. The rise of Social Darwinism further reinforced the notion that the superiority of the white race was part of the natural order. The fact that all people are products of complex genetic mixtures resulting from migration and intermingling over thousands of years was not admitted by the racial scientists, nor by the scores of eugenicists who campaigned on both sides of the Atlantic for the improvement of racial quality.

The mid-twentieth century witnessed the continued proliferation of scientific treatises on race. By the 1960s, however, two factors contributed to the demise of the concept of biological races. One of these was the increased rate of study of the physical and genetic diversity human groups all over the world by large numbers of scientists. The second factor was the increasing influence of the civil rights movement in the United States and elsewhere. Before long, influential scientists denounced studies of race and races because races themselves could not be scientifically defined. Where scientists looked for sharp boundaries between groups, none could be found.

Despite major shifts in scientific thinking, the sibling concepts of human races and a color-based hierarchy of races remained firmly established in mainstream culture through the mid-twentieth century. The resulting racial stereotypes were potent and persistent, especially in the United States and South Africa, where subjugation and exploitation of dark-skinned labor had been the cornerstone of economic growth.

After its "scientific" demise, race remained as a name and concept, but gradually came to stand for something quite different. Today many people identify with the concept of being a member of one or another racial group, regardless of what science may say about the nature of race. The shared experiences of race create powerful social bonds. For many people, including many scholars, races cease to be biological categories and have become social groupings. The concept of race became a more confusing mélange as social categories of class and ethnicity. So race isn't "just" a social construction, it is the real product of shared experience, and people choose to identify themselves by race.

Clinicians continue to map observed patterns of health and disease onto old racial concepts such as "White", "Black" or "African American", "Asian," etc. Even after it has been shown that many diseases (adult-onset diabetes, alcoholism, high blood pressure, to name a few) show apparent racial patterns because people share similar environmental conditions, grouping by race are maintained. The use of racial self-categorization in epidemiological studies is defended and even encouraged. In most cases, race in medical studies is confounded with health disparities due to class, ethnic differences in social practices, and attitudes, all of which become meaningless when sufficient variables are taken into account.

Race's latest makeover arises from genomics and mostly within biomedical contexts. The sanctified position of medical science in the popular consciousness gives the race concept renewed esteem. Racial realists marshal genomic evidence to support the hard biological reality of racial difference, while racial skeptics see no racial patterns. What is clear is that people are seeing what they want to see. They are constructing studies to provide the outcomes they expect. In 2012, Catherine Bliss argued cogently that race today is best considered a belief system that "produces consistencies in perception and practice at a particular social and historical moment".

Race has a hold on history, but it no longer has a place in science. The sheer instability and potential for misinterpretation render race useless as a scientific concept. Inventing new vocabularies of human diversity and inequity won't be easy, but is necessary.

if it doesn't predict disease or illuminate neurodiversity, who cares?

This Dillweed Here

discover | It’s been a busy few days in the world of personal genomics. By coincidence I have a coauthored comment in Genome Biology out, Rumors of the death of consumer genomics are greatly exaggerated (it was written and submitted a while back). If you haven’t, please read the FDA’s letter, and 23andMe’s response, as much as there is one right now. Since Slate ran my piece on Monday a lot of people have offered smart, and more well informed, takes. On the one hand you have someone like Alex Tabarrok, with “Our DNA, Our Selves”, which is close to a libertarian cri de coeur. Then you have cases like Christine Gorman, “FDA Was Right to Block 23andMe”. It will be no surprise that I am much closer to Tabarrok than I am to Gorman (she doesn’t even seem to be aware that 23andMe offers a genotyping, not sequencing, service, though fuzziness on the details doesn’t discourage strong opinions from her). An interesting aspect is that many who are not deeply in the technical weeds of the issue are exhibiting politicized responses. I’ve noticed this on Facebook, where some seem to think that 23andMe and the Tea Party have something to do with each other, and the Obama administration and the FDA are basically stand-ins. In other words, some liberals are seeing this dispute as one of those attempts to evade government regulation, something they support on prior grounds. Though Tabarrok is more well informed than the average person (his wife is a biologist), there are others from the right-wing who are taking 23andMe’s side on normative grounds as well. Ultimately I’m not interested in this this argument, because it’s not going to have any significant lasting power. No one will remember in 20 years. As I implied in my Slate piece 23andMe the company now is less interesting than personal genomics the industry sector in the future. Over the long term I’m optimistic that it will evolve into a field which impacts our lives broadly. Nothing the United States government can do will change that.

Yet tunneling down to the level of 23andMe’s specific issues with the regulatory process, there is the reality that it has to deal with the US government and the FDA, no matter what the details of its science are. It’s a profit-making firm. Matt Herper has a judicious take on this, 23andStupid: Is 23andMe Self-Destructing? I don’t have any “inside” information, so I’m not going to offer the hypothesis that this is part of some grand master plan by Anne Wojcicki. I hope it is, but that’s because I want 23andMe to continue to subsidize genotyping services (I’ve heard that though 23andMe owns the machines, the typing is done by LabCorp. And last I checked the $99 upfront cost is a major loss leader; they’re paying you to get typed). I’m afraid that they goofed here, and miscalculated. As I said above, it won’t make a major difference in the long run, but I have many friends who were waiting until this Christmas to purchase kits from 23andMe.

Then there are “the scientists,” or perhaps more precisely the genoscenti. Matt Herper stated to the effect that the genoscenti have libertarian tendencies, and I objected. In part because I am someone who has conservative and/or libertarian tendencies, and I’m pretty well aware that I’m politically out of step with most individuals deeply involved in genetics, who are at most libertarian-leaning moderate liberals, and more often conventional liberal Democrats. Michael Eisen has a well thought out post, FDA vs. 23andMe: How do we want genetic testing to be regulated? Eisen doesn’t have a political ax to grind, and is probably representative of most working geneticists in the academy (he is on 23andMe’s board, but you should probably know that these things don’t mean that much). I may not know much about the FDA regulatory process, but like many immersed in genomics I’m well aware that many people talking about these issues don’t know much about the cutting edge of the modern science. Talk to any geneticist about conversations with medical doctors and genetic counselors, and they will usually express concern that these “professionals” and “gatekeepers” are often wrong, unclear, or confused, on many of the details. A concrete example, when a friend explained to a veteran genetic counselor how my wife used pedigree information combined with genomic data to infer that my daughter did not have an autosomally dominant condition, the counselor asserted that you can’t know if there were two recombination events within the gene, which might invalidate these inferences. Though my friend was suspicious, they did not say anything, because they were not a professional. As a matter of fact there just aren’t enough recombinations across the genome for an intra-genic event to be a likely occurrence (also, recombination likelihood is not uniformly distributed, and not necessarily independent, insofar as there may be suppression of very close events). And this was a very well informed genetic counselor.

back to stuff that matters - 4-D printing...,

foreignaffairs | In May 2010, the richest, most powerful man in biotechnology made a new creature. J. Craig Venter and his private-company team started with DNA and constructed a novel genetic sequence of more than one million coded bits of information known as nucleotides. Seven years earlier, Venter had been the first person in history to make a functioning creature from information. Looking at the strings of letters representing the DNA sequence for a virus called phi X174, which infects bacteria, he thought to himself, “I can assemble real DNA based on that computer information.” And so he did, creating a virus based on the phi X174 genomic code. He followed the same recipe later on to generate the DNA for his larger and more sophisticated creature. Venter and his team figured out how to make an artificial bacterial cell, inserted their man-made DNA genome inside, and watched as the organic life form they had synthesized moved, ate, breathed, and replicated itself.

As he was doing this, Venter tried to warn a largely oblivious humanity about what was coming. He cautioned in a 2009 interview, for example, that “we think once we do activate a genome that yes, it probably will impact people’s thinking about life.” Venter defined his new technology as “synthetic genomics,” which would “start in the computer in the digital world from digitized biology and make new DNA constructs for very specific purposes. . . . It can mean that as we learn the rules of life we will be able to develop robotics and computational systems that are self-learning systems.” “It’s the beginning of the new era of very rapid learning,” he continued. “There’s not a single aspect of human life that doesn’t have the potential to be totally transformed by these technologies in the future.”

Today, some call work such as Venter’s novel bacterial creation an example of “4-D printing.” 2-D printing is what we do everyday by hitting “print” on our keyboards, causing a hard copy of an article or the like to spew from our old-fashioned ink-printing devices. Manufacturers, architects, artists, and others are now doing 3-D printing, using computer-generated designs to command devices loaded with plastics, carbon, graphite, and even food materials to construct three-dimensional products. With 4-D printing, manufacturers take the next crucial step: self-assembly or self-replication. What begins as a human idea, hammered out intellectually on a computer, is then sent to a 3-D printer, resulting in a creation capable of making copies of and transforming itself. In solid materials, Skylar Tibbits of the Massachusetts Institute of Technology creates complex physical substances that he calls “programmable materials that build themselves.” Venter and hundreds of synthetic biologists argue that 4-D printing is best accomplished by making life using life’s own building blocks, DNA.

When Venter’s team first created the phi X174 viral genome, Venter commissioned a large analysis of the implications of synthetic genomics for national security and public health. The resulting report warned that two issues were impeding appropriate governance of the new science. The first problem was that work on synthetic biology, or synbio, had become so cheap and easy that its practitioners were no longer classically trained biologists. This meant that there were no shared assumptions regarding the new field’s ethics, professional standards, or safety. The second problem was that existing standards, in some cases regulated by government agencies in the United States and other developed countries, were a generation old, therefore outdated, and also largely unknown to many younger practitioners.

Venter’s team predicted that as the cost of synthetic biology continued to drop, interest in the field would increase, and the ethical and practical concerns it raised would come increasingly to the fore. They were even more prescient than they guessed. Combined with breakthroughs in another area of biology, “gain-of-function” (GOF) research, the synthetic genomics field has spawned a dizzying array of new possibilities, challenges, and national security threats. As the scientific community has started debating “human-directed evolution” and the merits of experiments that give relatively benign germs dangerous capacities for disease, the global bioterrorism and biosecurity establishment remains well behind the curve, mired in antiquated notions about what threats are important and how best to counter them. 

In the United States, Congress and the executive branch have tried to prepare by creating finite lists of known pathogens and toxins and developing measures to surveil, police, and counter them; foreign governments and multilateral institutions, such as the UN and the Biological Weapons Convention, have been even less ambitious. Governance, in short, is focused on the old world of biology, in which scientists observed life from the outside, puzzling over its details and behavior by tinkering with its environment and then watching what happened. But in the new biology world, scientists can now create life themselves and learn about it from the inside. As Venter put it back in 2009, “What we have done so far is going to blow your freakin’ mind.”

inside china's bio-google

technologyreview | BGI-Shenzhen, once known as the Beijing Genomics Institute, has burst from relative obscurity to become the world’s most prolific sequencer of human, plant, and animal DNA. In 2010, with the aid of a $1.58 billion line of credit from China Development Bank, BGI purchased 128 state-of-the-art DNA sequencing machines for about $500,000 apiece. It now owns 156 sequencers from several manufacturers and accounts for some 10 to 20 percent of all DNA data produced globally. So far, it claims to have completely sequenced some 50,000 human genomes—far more than any other group.

BGI’s sheer size has already put Chinese gene research on the map. Those same economies of scale could also become an advantage as comprehensive gene readouts become part of everyday medicine. The cost of DNA sequencing is falling fast. In a few years, it’s likely that millions of people will want to know what their genes predict about their health. BGI might be the one to tell them.

The institute hasn’t only initiated a series of grandly conceived science projects. (In January, it announced it had determined the DNA sequence of not one but 90 varieties of chickpeas.) It’s also pioneered a research-for-hire business to decode human genomes in bulk, taking orders from the world’s top drug companies and universities. Last year, BGI even started to install satellite labs inside foreign research centers and staff them with Chinese technicians.

BGI’s rise is regarded with curiosity and some trepidation, not just because of the organization’s size but also because of its opportunistic business approach (it has a center for pig cloning, dabbles in stem-cell research, and runs a diagnostics lab). The institute employs 4,000 people, as many as a midsize university—1,000 in its bioinformatics division alone. Like Zhao, most are young—the average age is 27—and some sleep in company dormitories. The average salary is $1,500 a month.

Ten years ago, the international Human Genome Project was finishing up the first copy of the human genetic code at a cost of $3 billion. Thanks to a series of clever innovations, the cost to read out the DNA in a person’s genome has since fallen to just a few thousand dollars. Yet that has only created new challenges: how to store, analyze, and make sense of the data. According to BGI, its machines generate six terabytes of data each day.

Zhang Yong, 33, a BGI senior researcher, predicts that within the next decade the cost of sequencing a human genome will fall to just $200 or $300 and BGI will become a force in assembling a global “bio-Google”—it will help “organize all the world’s biological information and make it universally accessible and useful.”

about the special relationship...,

archeologynewsnetwork | The genetic changes underlying the evolution of new species are still poorly understood. For instance, we know little about critical changes that have happened during human evolution. Genetic studies in domestic animals can shed light on this process due to the rapid evolution they have undergone over the last 10,000 years. A new study published today describes how a complex genomic rearrangement causes a fascinating phenotype in chickens.

In the study published in PLoS Genetics researchers at Uppsala University, Swedish University of Agricultural Sciences, North Carolina State University and National Chung-Hsing University have investigated the genetic basis of fibromelanosis, a breed characteristic of the Chinese Silkie chicken. This trait involves a massive expansion of pigment cells that not only makes the skin and comb black but also causes black internal organs. Chickens similar in appearance to the Silkie were described by Marco Polo when he visited China in the 13th century and Silkie chickens have a long history in Chinese cuisine and traditional Chinese medicine.

archeologynewsnetwork | The domestication of chickens has given rise to rapid and extensive changes in genome function. A research team at Linköping University in Sweden has established that the changes are heritable, although they do not affect the DNA structure.

Humans kept Red Junglefowl as livestock about 8000 years ago. Evolutionarily speaking, the sudden emergence of an enormous variety of domestic fowl of different colours, shapes and sizes has occurred in record time. The traditional Darwinian explanation is that over thousands of years, people have bred properties that have arisen through random, spontaneous mutations in the chickens' genes.

Linköping zoologists, with Daniel Nätt and Per Jensen at the forefront, demonstrate in their study that so-called epigenetic factors play a greater role than previously thought. The study was published in the high-ranking journal BMC Genomics.

archeologynewsnetwork | Dr Alice Storey, an archaeologist at the University of New England, is tracing the global migration routes of domestic chickens back through thousands of years towards their origins in the jungles of South-east Asia.

In doing so, Dr Storey is pioneering the use of DNA from ancient chicken bones recovered from well-dated archaeological sites around the world. This is enabling her to add a fourth dimension – that of time – to an emerging “map” of chicken dispersal. One of the ultimate goals of such research is identifying the original Asian centres of jungle fowl domestication.

“All of our domestic chickens are descended from a few hens that I like to think of as the ‘great, great grandmothers’ of the chicken world,” Dr Storey said.

Biological, linguistic, historical and archaeological data have all contributed to an understanding that chickens accompanied human movements from their Asian homeland west through the Middle East to Europe and Africa, and east through the islands of South-east Asia and the Pacific.

Dr Storey’s analysis of ancient DNA is disentangling complications in this broad picture caused by interactions later than the original dispersal. “Only ancient DNA provides a unit of analysis with the chronological control necessary to reconstruct and disentangle the signals of initial dispersals from those of later interactions,” she said. Hers are the first published reports on the use of ancient DNA in this context.

A paper by Dr Storey and her colleagues, titled “Global dispersal of chickens in prehistory using ancient mitochondrial DNA signatures”, is published today in the online scientific journal PLoS ONE.

thinking outside the genome...,

The Scientist | Not so long ago, the mention of any word with the two syllables “-ō-mics” tacked on the end was usually followed immediately with some response akin to, “Huh?” Today, we’ve gotten to the point where almost no biological phenomenon can escape “omics-ization,” and within the next 25 years, omics will be the biggest, if not the only, game in town. Why? Because we are about to undergo what experts call a phase shift, where a technology drives a fundamental change not just in what is known, but, more importantly, in how we think of ourselves. Put another way: omics is destined to change our patterns of living in ways that only technological revolutions can deliver.

Other technologies have already proven to have similarly deep effects on human culture. Consider the impact of the Internet on commerce, or the influence of GPS systems on travel and navigation. The reach of these technologies extended well beyond the information they generated. They redefined society.

In the last half century, the technology in genomics has provided us with a set of approaches initially as underappreciated as computers were in the early 1970s. “Exotic,” “finicky,” and “geeky” were terms used for mainframe computers that couldn’t even talk with each other. The same transformative technological advances that have turned computers into must-have personal accessories are inevitable for the nascent field of omics. Here are four ways in which omics will reshape the human experience.

genomic science: keeping it 100%

The Scientist | Meet the species whose DNA has recently been sequenced:

Species: The marijuana plants Cannabis sativa and Cannabis indica
Genome size: Around 400 million base pairs
Interesting fact: The marijuana plant is most well known for the high produced by THC, its active ingredient, which binds to cannabinoid receptors in the body. But Cannabis contains dozens of other active compounds, some of which are being studied as potential treatments for cancer and inflammation. Researchers at Medicinal Genomics hope that sequencing the entire genome will allow them to pinpoint therapeutic compounds while removing the psychoactive effects of THC.

The science dudes did some fungus and other stuff too....whatever.

ephaptic coupling

Cordis | Researchers believed neurons in the brain communicated through physical connections known as synapses. However, EU-funded neuroscientists have uncovered strong evidence that neurons also communicate with each other through weak electric fields, a finding that could help us understand how biophysics gives rise to cognition.

The study, published in the journal Nature Neuroscience, was funded in part by the EUSYNAPSE ('From molecules to networks: understanding synaptic physiology and pathology in the brain through mouse models') project, which received EUR 8 million under the 'Life sciences, genomics and biotechnology for health' Thematic area of the EU's Sixth Framework Programme (FP6).

Lead author Dr Costas Anastassiou, a postdoctoral scholar at the Californian Institute of Technology (Caltech) in the US, and his colleagues explain how the brain is an intricate network of individual nerve cells, or neurons, that use electrical and chemical signals to communicate with one another.

Every time an electrical impulse races down the branch of a neuron, a tiny electric field surrounds that cell. A few neurons are like individuals talking to each other and having small conversations. But when they all fire together, it's like the roar of a crowd at a sports game.

That 'roar' is the summation of all the tiny electric fields created by organised neural activity in the brain. While it has long been recognised that the brain generates weak electrical fields in addition to the electrical activity of firing nerve cells, these fields were considered epiphenomenon - superfluous side effects.

Nothing was known about these weak fields because, in fact, they are usually too weak to measure at the level of individual neurons; their dimensions are measured in millionths of a metre (microns). Therefore, the researchers decided to determine whether these weak fields have any effect on neurons.

Experimentally, measuring such weak fields emanating from or affecting a small number of brain cells was no easy task. Extremely small electrodes were used in close proximity to a cluster of rat neurons to look for 'local field potentials', the electric fields generated by neuron activity. The result? They were successful in measuring fields as weak as one millivolt (one millionth of a volt).

Commenting on the results, Dr Anastassiou says: 'Because it had been so hard to position that many electrodes within such a small volume of brain tissue, the findings of our research are truly novel. Nobody had been able to attain this level of spatial and temporal resolution.'

What they found was surprising. 'We observed that fields as weak as one millivolt per millimetre robustly alter the firing of individual neurons, and increase the so-called "spike-field coherence" - the synchronicity with which neurons fire with relationship to the field,' he says.

ideas of the microbiome and the virome...,

Sciencemag | Humans have been doing battle with bacteria since the 1800s, thwarting disease with antibiotics, vaccines, and good hygiene with mixed success. But in 2000, Nobel laureate Joshua Lederberg called for an end to the “We good; they evil” thinking that has fueled our war against microbes. “We should think of each host and its parasites as a superorganism with the respective genomes yoked into a chimera of sorts,” he wrote in Science in 2000.

His comments were prescient. This past decade has seen a shift in how we see the microbes and viruses in and on our bodies. There is increasing acceptance that they are us, and for good reason. Nine in 10 of the cells in the body are microbial. In the gut alone, as many as 1000 species bring to the body 100 times as many genes as our own DNA carries. A few microbes make us sick, but most are commensal and just call the human body home. Collectively, they are known as the human microbiome. Likewise, some viruses take up residence in the body, creating a virome whose influence on health and disease is just beginning to be studied.

Their genes and ours make up a metagenome that keeps the body functioning. This past decade we've begun to see how microbial genes affect how much energy we absorb from our foods and how microbes and viruses help to prime the immune system. Viewing the human and its microbial and viral components as intimately intertwined has broad implications. As one immunologist put it, such a shift “is not dissimilar philosophically from the recognition that the Earth is not the center of the solar system.”

This appreciation has dawned gradually, as part of a growing recognition of the key role microbes play in the world. Microbiologists sequencing DNA from soil, seawater, and other environments have discovered vast numbers of previously undetected species. Other genomics research has brought to light incredible intimacies between microbes and their hosts—such as a bacterium called Buchnera and the aphids inside which it lives. A study in 2000 found that each organism has what the other lacks, creating a metabolic interdependency.

One of the first inklings that microbiologists were missing out on the body's microbial world came in 1999, when David Relman of Stanford University in Palo Alto, California, and colleagues found that previous studies of bacteria cultured from human gums had seriously undercounted the diversity there. Turning to samples taken from the gut and from stools, the researchers identified 395 types of bacteria, two-thirds of them new to science.

In 2006, Steven Gill of the University at Buffalo in New York and colleagues did a metagenomics study of the gut, analyzing all the genes they could find in the 78 million bases sequenced. They found metabolic genes that complemented the human genome, including ones that break down dietary fiber, amino acids, or drugs, and others that produce methane or vitamins. This and a more comprehensive survey in 2010 by Jun Wang of BGI-Shenzhen in China and colleagues provided support for the concept of the microbe-human superorganism, with a vast genetic repertoire. Now, large-scale studies have surveyed the microflora in the gut, skin, mouth, nose, and female urogenital tract. The Human Microbiome Project has sequenced 500 relevant microbial genomes out of a planned 3000.

Some of these microbes may play important roles in metabolic processes. In 2004, a team led by Jeffrey Gordon of Washington University School of Medicine in St. Louis, Missouri, found that germ-free mice gained weight after they were supplied with gut bacteria—evidence that these bacteria helped the body harvest more energy from digested foods. Later studies showed that both obese mice and obese people harbored fewer Bacteroidetes bacteria than their normal-weight counterparts.

The microbiome is also proving critical in many aspects of health. The immune system needs it to develop properly. What's more, to protect themselves inside the body, commensal bacteria can interact with immune cell receptors or even induce the production of certain immune system cells. One abundant gut bacterium, Faecalibacterium prausnitzii, proved to have anti-inflammatory properties, and its abundance seems to help protect against the recurrence of Crohn's disease. Likewise, Sarkis Mazmanian of the California Institute of Technology in Pasadena showed that the human symbiont Bacteroides fragilis kept mice from getting colitis. And inserting bacteria isolated from healthy guts restored the microbial communities, curing chronic diarrhea in a patient infected with Clostridium difficile.

Herbert Virgin of Washington University School of Medicine finds a similar role for the virome. In mice, his team found that dormant herpesviruses revved up the immune system just enough to make the mice less susceptible to certain bacterial infections.

The ideas of a microbiome and a virome didn't even exist a decade ago. But now researchers have reason to hope they may one day manipulate the body's viral and microbial inhabitants to improve health and fight sickness.

science: the breakthroughs of 2010 and insights of the decade

AAAS | Until this year, all human-made objects have moved according to the laws of classical mechanics. Back in March, however, a group of researchers designed a gadget that moves in ways that can only be described by quantum mechanics—the set of rules that governs the behavior of tiny things like molecules, atoms, and subatomic particles. In recognition of the conceptual ground this experiment breaks, the ingenuity behind it, and its many potential applications, Science has called this discovery the most significant scientific advance of 2010.

Physicists Andrew Cleland and John Martinis from the University of California at Santa Barbara and their colleagues designed the machine—a tiny metal paddle of semiconductor, visible to the naked eye—and coaxed it into dancing with a quantum groove. First, they cooled the paddle until it reached its “ground state,” or the lowest energy state permitted by the laws of quantum mechanics (a goal long-sought by physicists). They then raised the widget’s energy by a single quantum to produce a purely quantum-mechanical state of motion. They even managed to put the gadget in both states at once, so that it literally vibrated a little and a lot at the same time—a bizarre phenomenon allowed by the weird rules of quantum mechanics.

Science and its publisher, AAAS, have recognized this first quantum machine as the 2010 Breakthrough of the Year. They have also compiled nine other important scientific accomplishments from this past year into a top 10 list, appearing in a special news feature in the journal’s 17 December 2010 issue. Additionally, Science news writers and editors have chosen to spotlight 10 “Insights of the Decade” that have transformed the landscape of science in the 21st century.

Science’s list of the nine other groundbreaking achievements from 2010 includes:

Synthetic Biology. In a defining moment for biology and biotechnology, researchers built a synthetic genome and used it to transform the identity of a bacterium. The genome replaced the bacterium’s DNA so that it produced a new set of proteins—an achievement that prompted a Congressional hearing on synthetic biology. In the future, researchers envision synthetic genomes that are custom-built to generate biofuels, pharmaceuticals, or other useful chemicals.

Neandertal Genome. Researchers sequenced the Neandertal genome from the bones of three female Neandertals who lived in Croatia sometime between 38,000 and 44,000 years ago. New methods of sequencing degraded fragments of DNA allowed scientists to make the first direct comparisons between the modern human genome and that of our Neandertal ancestors.

HIV Prophylaxis. Two HIV prevention trials of different, novel strategies reported unequivocal success: A vaginal gel that contains the anti-HIV drug tenofovir reduced HIV infections in women by 39% and an oral pre-exposure prophylaxis led to 43.8% fewer HIV infections in a group of men and transgender women who have sex with men.

Exome Sequencing/Rare Disease Genes. By sequencing just the exons of a genome, or the tiny portion that actually codes for proteins, researchers who study rare inherited diseases caused by a single, flawed gene were able to identify specific mutations underlying at least a dozen diseases.

Molecular Dynamics Simulations. Simulating the gyrations that proteins make as they fold has been a combinatorial nightmare. Now, researchers have harnessed the power of one of the world’s most powerful computers to track the motions of atoms in a small, folding protein for a length of time 100 times longer than any previous efforts.

Quantum Simulator. To describe what they see in the lab, physicists cook up theories based on equations. Those equations can be fiendishly hard to solve. This year, though, researchers found a short-cut by making quantum simulators—artificial crystals in which spots of laser light play the role of ions, and atoms trapped in the light stand in for electrons. The devices provide quick answers to theoretical problems in condensed matter physics and they might eventually help solve mysteries such as superconductivity.

Next-Generation Genomics. Faster and cheaper sequencing technologies are enabling very large-scale studies of both ancient and modern DNA. The 1000 Genomes Project, for example, has already identified much of the genome variation that makes us uniquely human—and other projects in the works are set to reveal much more of the genome’s function.

RNA Reprogramming. Reprogramming cells—turning back their developmental clocks to make them behave like unspecialized “stem cells” in an embryo—has become a standard lab technique for studying diseases and development. This year, researchers found a way to do it using synthetic RNA. Compared with previous methods, the new technique is twice as fast, 100 times as efficient, and potentially safer for therapeutic use.

The Return of the Rat. Mice rule the world of laboratory animals, but for many purposes researchers would rather use rats. Rats are easier to work with and anatomically more similar to human beings; their big drawback is that methods used to make “knockout mice”—animals tailored for research by having specific genes precisely disabled—don’t work for rats. A flurry of research this year, however, promises to bring “knockout rats” to labs in a big way.

Finally, to celebrate the end of the current decade, Science news reporters and editors have taken a step back from their weekly reporting to take a broader look at 10 of the scientific insights that have changed the face of science since the dawn of the new millennium. Here are their 10 “Insights of the Decade”:

genetic engineering of space travelers

Video - Twilight Zone Episode Third From the Sun

LiveScience | NASA's human spaceflight program might take some giant leaps forward if the agency embraces genetic engineering techniques more fully, according to genomics pioneer J. Craig Venter.

The biologist, who established the J. Craig Venter Institute that created the world's first synthetic organism earlier this year, told a crowd here Saturday (Oct. 30) that human space exploration could benefit from more genetic screening and genetic engineering. Such efforts could help better identify individuals most suited for long space missions, as well as make space travel safer and more efficient, he said.

"I think this could change the shape of what NASA does, if you make the commitment to do it," said Venter, who led a team that decoded the human genome a decade ago. Venter spoke to a group of scientists and engineers who gathered at NASA's Ames Research Center for two different meetings: a synthetic biology workshop put on by NASA, and Space Manufacturing 14: Critical Technologies for Space Settlement, organized by the nonprofit Space Studies Institute.

Astronauts with the right (genetic) stuff

Genetics techniques could come in extremely handy during NASA's astronaut selection process, Venter said. The space agency could screen candidates for certain genes that help make good spaceflyers — once those genes are identified, he added.

Genes that encode robust bone regeneration, for example, would be a plus, helping astronauts on long spaceflights battle the bone loss that is typically a major side effect of living in microgravity. Also a plus for any prospective astronaut: genes that code for rapid repair of DNA, which can be damaged by the high radiation levels in space.

Genetic screening would be a natural extension of what NASA already does — it would just add a level of precision, according to Venter.

"NASA's been doing genetic selection for a long time," he said. "You just don't call it that."

Last summer, the agency chose just nine astronaut candidates — out of a pool of 3,500 — for its rigorous astronaut training program based on a series of established spaceflight requirements and in-depth interviews.

A new microbiome
At some point down the road, NASA could also take advantage of genetic engineering techniques to make long space journeys more efficient and easier on astronauts, Venter said.

As an example, he cited the human microbiome, the teeming mass of microbes that live on and inside every one of us. Every human body hosts about 100 trillion microbes — meaning the bugs outnumber our own cells by a factor of at least 10 to one.

While humans only have about 20,000 genes, our microbiome boasts a collective 10 million or so, Venter said. These microbes provide a lot of services, from helping us digest our food to keeping our immune system's inflammation response from going overboard.

With some tailoring, the microbiome could help us out even more, according to Venter.

"Why not come up with a synthetic microbiome?" he asked.

Theoretically, scientists could engineer gut microbes that help astronauts take up nutrients more efficiently. A synthetic microbiome could also eliminate some pathogens, such as certain bacteria that can cause dental disease. Other tweaks could improve astronauts' living conditions, and perhaps their ability to get along with each other in close quarters.

Body odor is primarily caused by microbes, Venter said. A synthetic microbiome could get rid of the offenders, as well as many gut microbes responsible for excessive sulfur or methane production. Fist tap Nana.

everything else is merely conversation....,

NYTimes | Dr. Venter, now 63, made his name as a gene hunter. He was co-founder of a company, Celera Genomics, that nearly left the federally funded Human Genome Project in the dust in the race to determine the complete sequence of DNA in human chromosomes. He garnered admiration for some path-breaking ideas but also the enmity of some scientific rivals who viewed him as a publicity seeker who was polluting a scientific endeavor with commercialism.

Now Dr. Venter is turning from reading the genetic code to an even more audacious goal: writing it. At Synthetic Genomics, he wants to create living creatures — bacteria, algae or even plants — that are designed from the DNA up to carry out industrial tasks and displace the fuels and chemicals that are now made from fossil fuels.

“Designing and building synthetic cells will be the basis of a new industrial revolution,” Dr. Venter says. “The goal is to replace the entire petrochemical industry.”

a short course on synthetic genomics

Edge | On July 24, 2009, a small group of scientists, entrepreneurs, cultural impresarios and journalists that included architects of the some of the leading transformative companies of our time (Microsoft, Google, Facebook, PayPal), arrived at the Andaz Hotel on Sunset Boulevard in West Hollywood, to be offered a glimpse, guided by George Church and Craig Venter, of a future far stranger than Mr. Huxley had been able to imagine in 1948.

In this future — whose underpinnings, as Drs. Church and Venter demonstrated, are here already — life as we know it is transformed not by the error catastrophe of radiation damage to our genetic processes, but by the far greater upheaval caused by discovering how to read genetic sequences directly into computers, where the code can be replicated exactly, manipulated freely, and translated back into living organisms by writing the other way. "We can program these cells as if they were an extension of the computer," George Church announced, and proceeded to explain just how much progress has already been made. ... Click here to go to videos.

biologists finally catching on?

Video - Craig Venter on Genomics from Human to the Environment.

Bytesize Biology | An article published today in Science shows the first case of animals synthesizing carotenoids. Nancy Moran and Tyler Jarvik form the University of Arizona looked at the recently sequenced genome of the pea aphid. The pea aphid is known for having two different colors: green and red. It was not very clear though how the aphids got their color. Aphids feed on sap, and sap does not contain carotenoids. When looking at the genomes of the aphids, Moran and Jarvik found that they contained genes for synthesizing carotenoids: this is the first time carotenoid synthesizing genes are found in animals. The question they naturally asked is “where did those genes come from”? The animal kingdom does not contain genes for making carotenoids, so how come aphids have them? Indeed, when they looked for the most similar genes to the aphid carotenoid synthesizing genes they found that they came from fungi, which means they somehow jumped between fungi and aphids, in a process known as horizontal gene transfer. Horizontal gene transfer is not unheard-of in animals, and is actually quite common in plants (yeah, fungi are not plants, I know that), but this is the first time someone has shown a jump from fungi to animals, and that the trait that this gene conveys — color — became embedded and functional in the genome.

Aphid color is important: red aphids get picked easily by predators off green plants, and vice-versa. So there is an evolutionary aspect here: the carotenoid genes play a role in the predator-driven selection of aphids. So in the case of aphids, as opposed to puffins and flamingo, the selective pressure is that of predation, not of mating. (I’ll refrain from comments about Auntie Mae.)

"Long ago, an ancestor to today's pea aphid somehow internalized a large important chunk of DNA from a fungus. This DNA now allows the aphid to generate its own carotenoid molecules. All animals need carotenoids for body functions as important as eyesight. However this aphid is the only organism in the Animal Kingdom so far to have been reported capable of producing it internally. The rest of us must forage for foods such as carrots, containing carotenoids. The precise way the DNA transfer occurred is not yet understood; however patterns within the DNA conclusively show a link to a fungus. DNA transfer from fungus to animal is unprecedented." (text taken from the NSF announcement). Credit: Zina Deretsky, National Science Foundation

As an aside, many of our pseudogenes and other contents of “junk DNA” are thought to have been acquired by horizontal gene transfer. Still, this is the first time a case of gene transfer that is so clear between two different kingdoms. However, I have the sneaking suspicion that as we sequence more animal, plant, fungal and other genomes of multicellular organism, we would find more cases of “large-leap” HGT of functional genes happening: we just don’t have enough genomes yet to appreciate the frequency of these occurrences! Fist tap Dale.

genomics richard stallman?

The Scientist | In the future, Hubbard says that gene-prediction programs need to get good enough that they can find genes without the aid of experimental data or comparative genome analyses to guide them. “Because that’s cheating,” he says. “For example, an RNA polymerase does not go and look at the mouse genome when it’s working out whether to transcribe a particular stretch of human sequence. But that’s what many of our algorithms do now.” Instead, he says that annotation programs should take an RNA polymerase–eye-view of the sequence, modeling the biology closely enough to accurately locate and assess the activity of genes. As we move into an era of personal genomics, such an approach will be necessary for predicting the effect that a certain SNP variant might have on gene function. He and his team have had some early success, producing a transcription start-site predictor that nails about half the genes in a genome sequence with very few false positives.

Hubbard also spends quite a bit of time working on issues of open access and the economics of innovation. “Governments are spending all this money for research and then not maximizing its value because they’re not investing enough in making sure people can access and reuse that data,” says Hubbard, who has discussed these issues at meetings of the Organisation for Economic Cooperation and Development (OECD) and the World Health Organization. Much of this work he does in his spare time. “Other people go fishing,” laughs Birney. “Tim likes to reform international patent law and go to UN conferences to discuss how open-access agreements should be arranged to maximize the way science gets translated into meaningful outcomes.”

Those outcomes, of course, include potential improvements in the diagnosis and treatment of disease, which makes the issue more urgent and more fraught. “If you look at the health implications of all the work being done in genomics, the opportunities are tremendous and the obstacles are staggering—and a lot of those are political,” says Haussler. “I just have the ultimate respect for Tim, as he’s willing to move through those political hurdles and try to get things to happen.”

“In a way, Tim’s contribution to the scientific endeavor is a very interesting one and rather different from most scientists,” says EBI director Janet Thornton. “Although he’s had a hand in producing many of the big genome publications, his unique input lies in his broad perspective, his sense of fairness, and his openness to new ideas. His diplomatic efforts have really been fundamental in making these large-scale, collaborative genomics projects work—and in making the data available so that the science can be put to good use for biology and medicine around the world.”

“A lot of things can be done by one person with a computer,” adds Flicek. “If the Internet age taught us anything, it’s taught us that.”