Streamlining the Bio-Production of Fuels, Chemicals, and Pharmaceuticals

This article is adapted from an article published on Al Fin Energy blog

The team's method can be compared to understanding both the chemical reactions and the machinery that are required to refine crude oil into petrol in a large, industrial factory. Modeling metabolism tells you what biochemical reactions need to take place. Modeling the organism's gene expression tells you what kind of machinery you need. The team's method specifically accounts for the expression of enzymes, which are the molecular machines responsible for the biochemical processes of life. With this knowledge, it is possible to explore how an organism distributes its resources to promote growth and how genetic manipulation of these organisms alters this distribution. _SD

This new approach devised by UCSD researchers is likely to expedite the creation of biological organisms capable of producing high volumes of fuels, chemicals, pharmaceuticals, etc. in a fast and profitable manner.

A biochemically accurate model of molecular biology and metabolism will facilitate comprehensive and quantitative computations of an organism's molecular constitution as a function of genetic and environmental parameters. Here we formulate a model of metabolism and macromolecular expression. Prototyping it using the simple microorganism Thermotoga maritima, we show our model accurately simulates variations in cellular composition and gene expression.

Moreover, through in silico comparative transcriptomics, the model allows the discovery of new regulons and improving the genome and transcription unit annotations. Our method presents a framework for investigating molecular biology and cellular physiology in silico and may allow quantitative interpretation of multi-omics data sets in the context of an integrated biochemical description of an organism. _NatureCommunications

Nature Communications 3, Article number: 929 doi:10.1038/ncomms1928

UCSD researchers have taken an important step toward the general ability to custom design the genome of organisms, in order to produce synthetic fuels, chemicals, pharmaceuticals, on a commercial scale.

"What you could hypothetically do with our model is simulate the total cost of producing a value-added product, such as a biofuel. That includes all the operating and maintenance costs," said Daniel Hyduke, a project scientist in Palsson's lab. Hyduke said the method has the potential to help streamline industrial metabolic engineering efforts by providing a near complete accounting of the minimal material and energy costs associated with novel strain designs for biofuel, commodity chemicals, and recombinant protein production.

Hyduke and Lerman prototyped the method on the minimal, yet metabolically versatile, hyperthermophile Thermotoga maritima. Because T. maritima is not currently ready for use in industrial applications, Hyduke and Lerman are working as part of a larger team to produce similar models for industrially relevant microorganisms, such as E. coli.

"We've built a virtual reality simulator of metabolism and gene expression for Thermotoga maritima, and shown that it much better approximates phenotypes of cells than modeling metabolism in isolation," said Lerman.

...Their method accounts, in molecular detail, for the material and energy required to keep a cell growing, the research team reported in the journal Nature Communications.

"This is a major advance in genome-scale analysis that accounts for the fundamental biological process of gene expression and notably expands the number of cellular phenotypes that we can compute," said Bernhard Palsson, Galetti Professor of Bioengineering, at the UC San Diego Jacobs School of Engineering.

"With this new method, it is now possible to perform computer simulations of systems-level molecular biology to formulate questions about fundamental life processes, the cellular impacts of genetic manipulation or to quantitatively analyze gene expression data," said Joshua Lerman, a Ph.D. candidate in Palsson's Systems Biology Research Group. _SD

This approach provides more useful information in advance, to researchers considering various approaches to the design of custom chemicals-producing organisms -- particularly microbes, but eventually plants and animals as well.

In summary, the development of this tool should streamline the design and development of organisms capable of producing commercially valuable chemicals and fuels in an economical and timely manner. It should also prevent much wasted energy on the part of researchers, by pointing out dead-end research approaches in advance.

Full article in Nature Communications

Tools such as this will take us closer to the world where fast-growing weeds can be transformed into complete nutrient food crops capable of growing virtually anywhere, or life saving pharmaceuticals grown in one's own garden or window sill. High value "inks" for 3D printing will likely be produced from organisms designed by this or similar methods. And you can count on clever criminals learning to create tomato plants that produce cocaine, or squash that produce opium.

These tools will not stay in laboratories. They will migrate into garage biohacking facilities in short order. And then we will see disruptive change. Slowly at first, and then more rapidly.

An Explosion of Experimentation in Synthetic Biology

The cost of both decoding DNA and synthesizing new DNA strands... is falling about five times as fast as computing power is increasing under Moore's Law, which has accurately predicted that chip performance will double roughly every two years. Those involved in synthetic biology, who often favor computer analogies, might say it's becoming exponentially easier to read from, and write into, the source code of life. These underlying technology trends... are leading to an explosion in experimentation of a sort that would have been inconceivable only a few years ago. _Technology Review

This rapid improvement in the tools of synthetic biology is making it much easier to re-program living organisms, and to eventually generate a wide range of entirely new creatures -- custom-made for specific purposes.

Among its many projects, [George] Church's lab [at Harvard's Center for Computational Genetics] has invented a technique for rapidly synthesizing multiple novel strings of DNA and introducing them simultaneously into a bacterial genome. In one experiment, researchers created four billion variants of E. coli in a single day. After three days, they found variants of the bacteria in which production of a desired chemical was increased fivefold.

The idea, Church explains, is to sort through the variations to find "an occasional hopeful monster, just as evolution has done for millions of years." By mimicking in lab experiments what takes eons in nature, he says, he is radically improving the odds of finding ways to make microbes not just do new things but do them efficiently. _TechnologyReview

It is only natural to devise ways of speeding up evolution. But synthetic biologists are not likely to remain satisfied within the confines of nature, regardless of the speed of evolutionary change.

The new breed of scientists in this field will want to colour outside the lines.

[James] Collins wanted to study cellular processes by constructing gene networks rather than taking them apart. As a first step, he built a biological toggle circuit. A toggle is a mechanism with two possible states—in the case of a light switch, on or off. In the switch he and his colleagues built from DNA, two genes next to each other in a bacterial genome both produced proteins when they were "on." But Collins set things up so that each protein would block production of the other—if gene 1 was on, it would keep gene 2 off, and vice versa. With the aid of chemicals or a thermal pulse, Collins could flip between the two states. The DNA toggle switch was analogous to an electronic transistor, able to store a single bit of information. It was also an engineered example of the kind of feedback loop that often determines whether cells grow, divide, or die. "The idea that you could build a circuit out of biological parts helped launch the field of synthetic biology," says Collins. The results were published in January 2000. Soon Collins's toggle was joined by an expanding list of DNA circuits, including biosensors, oscillators, bacterial calculators, and similar molecular gadgetry. Researchers even established a Registry of Standard Biological Parts: 7,100 different DNA structures are available to order. Scientists were excited by the idea that biology might be modular and predictable, like something made with Lego blocks or computer code. Many scrambled to found companies that they hoped would commercialize the technology to produce fuels, drugs, or other products.

...[George Church's] Warp Drive Bio... combines computer science, chemistry, and genetic engineering in ways that would not have been possible until recently. It aims to use ultrafast DNA sequencing and synthetic-biology techniques, some of which Church pioneered, to hunt for potential medicines by scouring the DNA of millions of environmental samples that drug companies have collected and stored over several decades. Warp Drive is, in effect, searching for genetic parts that nature has already programmed to make particularly potent, useful chemicals. Church's technology will be used to generate copies of those parts, incorporate them into bacteria, and optimize their performance. Then the bacteria can be used to produce chemicals that, if all goes according to plan, have new and interesting therapeutic properties.

... If Church and Collins are intent on creating new synthetic parts and bioengineering techniques, [Gregory] Verdine is hoping to use many of the same techniques to unwrap the mysteries of how nature does it. Over the decades, he explained to me, pharmaceutical researchers have collected and stored tens of thousands, and more likely millions, of environmental samples, including dirt and pond scum. The idea was to discover some potent chemical in these mixtures by dripping extracts onto cancer cells or into petri dishes of bacteria. But that process is laborious and subject to chance. Most drug companies have scaled back such research.

The answer, Verdine decided, was to search for DNA instead. Given the plummeting cost of DNA sequencing, it's now feasible to simply decode all the genetic material present in, say, a drop of pond water teeming with microörganisms. Verdine says many of the natural drugs that have already been identified have similar DNA signatures—clusters of genes that often occur together in a microbe's genome. The trick, he adds, is to scan the samples' DNA to locate familiar-looking clusters that might be recipes for synthesizing a natural product—ideally, an important one that hasn't been found before.

Once identified, the DNA sequences will need to be engineered into a bacterium so that the company can produce the chemical and study the potential drugs. This is where the synthetic-biology techniques developed by Church will be crucial: in transforming the code into actual compounds. "We use genomics and informatics to find a gene cluster. But that's an information unit," Verdine says. "We have to get the molecule. Synthetic biology involves coaxing the cluster into biosynthetic factories, which then produce the molecules. If we don't have the molecule, the cluster is useless." _TechnologyReview

It is a very competitive field, with potential payoffs for commercialisation easily into the billions of dollars, and higher.

It is difficult to find and properly train minds capable of spanning the vast conceptual distances between the molecular, the genetic, the cellular, the physiologic, the pharmacologic, and the business / economic / legal /ethical issues.

And that is the crux of the issue: What the best human minds can do, with the assistance of the best tools that they can conceive and create.

This is one area where the contrast between dynamists and stasists could not be clearer.

Venter Tries to Put the Genomics Revolution in Perspective

Craig Venter has done some amazing things. Follow the link to read the Wired interview in full, and you will see an abbreviated bio for the disruptive scientist. In the excerpts from the interview below, Venter attempts to describe what will be required before society can expect to reap all the benefits from the coming genomic revolution.

Venter has to simplify the challenge for the sake of the public, but there is no minimising the promise. Life is hackable, and we are developing the tools that will be able to hack just about any genome. More exciting than that, is the challenge of creating entirely new genomes, which function on different principles, using different nucleic acids, amino acids, carbohydrates, and lipids. Now that will be biohacking.

Venter's Synthetic Algal Farm

Venter: ...what most people think about when it comes to genetics is personalized medicine. If we sequence your genome or my genome, what can we interpret, what can we predict for the future, what can we change? That’s in its absolute infancy. We’re at the point where we don’t need one genome or just a few genomes to interpret your genome. We need tens of thousands of genomes as a starting point, coupled with everything we can know about their physiology. It’s only when we do that giant computer search, putting all that DNA together, that we will be able to make sense in a meaningful statistical manner of what your DNA is telling you. We’re just at the start of trying to do that. So the fact that it’s 10 years out and we’re able to start on that project—that, I think, is pretty exciting.

Goetz: There is some perception, though, that in terms of human health the genomics revolution has overpromised and underdelivered.

Venter: Well, it depends on whose promises you’re talking about. Some people were saying that 10 years out we’d have every disease cured. I think that was overpromising. I always said it was a race to the starting line. Once we got the first genome, that’s when genomics would really start.

Goetz: I’m curious about your own interest in human health. Where does that stand on the spectrum of what you’re doing?

Venter: I turned 65 last year, and each year I get more and more interested in human health. For most people it happens around age 50, but I’ve always been a slow learner. It’s critical in terms of the cost of health care. If we can actually do this experiment of getting at least 10,000 human genomes and then get the corresponding phenotype information, we can show that this data set could make preventative medicine possible and thereby reduce health care costs. And one of the things about genetics that has become clearer as we’ve done genomes—as we’ve worked our way through the evolutionary tree, including humans—is that we’re probably much more genetic animals than we want to confess we are.

Goetz: What do you mean by that?

Venter: We’re much more genetically determined in terms of our physiology. We have 200 trillion cells, and the outcome of each of them is almost 100 percent genetically determined. And that’s what our experiment with the first synthetic genome proves, at least in the case of really simple bacteria. It’s the interactions of all those separate genetic units that give us the physiology that we see.

Goetz: So on a cellular level, since the genes control the function of the cell, no matter what happens in that cell’s environment, we’re more the product of our genes than our environment.

Venter: Yes. And that has important consequences when it comes to reading our genomes, trying to understand the basis of disease, and then trying to alter those features. We’re a country that seems to love drama and disasters. We’re not so good at preventing them. But preventing disease is the future of medicine. That’s the only way to lower costs and improve outcomes.

Goetz: You mentioned synthetic life. This is another area that you have helped pioneer. It’s built on the same raw material—DNA—as your work on the human genome, but it leads us in a very different direction, toward energy solutions, things like that.

Venter: The term synthetic life means different things to different people. For some it’s green monsters, for others synthetic means plastic. Most people didn’t know what to make of it when we announced that we had created synthetic life. We’re talking about chemical synthesis.

...Goetz: But it’s not like just asking a cell to start making furniture. You’re trying to get them to do something that’s close to what they already do naturally.

Venter: Right. We’re trying to harness photosynthesis. A key part of photosynthesis is what happens when the sun goes down. Cells convert CO2 into sugar and fat molecules. And they store the fat to burn as energy to get them through the night—the same way we store fat, only that’s just to get us through TV shows. We’re trying to coax our synthetic cells to do what’s happened to middle America, which is store far more fat than they actually were designed to do, so that we can harness it all as an energy source and use it to create gasoline, diesel fuel, and jet fuel straight from carbon dioxide and sunlight. This would shift the carbon equation so we’re recycling CO2 instead of taking new carbon out of the ground and creating still more CO2. But it has to be done on a massive scale to have any real impact on the amount of CO2 we’re putting into the atmosphere, let alone recovering from the atmosphere.

“There are not enough scientists on the planet to look at all the genes that we’ve discovered.”

Goetz: A massive industrial scale.

Venter: We envision facilities the size of San Francisco. And 10 or 15 of those in this country. We need sunlight, seawater, and non-agricultural land, but you need a lot of photons to drive this. You need a lot of surface area of sunlight to do that. It’s a great use for Arizona. Lots of sunlight there.

Goetz: You’ve been working on synthetic life for 15 years or more. How long until we reach scale? There must be many experiments between here and there.

Venter: We’re looking at this as a 10-year problem, not a 10-month problem.

Really? You think that we can get to industrial-scale energy production in just 10 years?

Venter: If we can’t get some key scientific breakthroughs within the next couple of years, it probably won’t happen in 10 years. So it’s something that’s really dependent on fundamental science. But we’re already able to do things that were once seen as impossible.

Goetz: Just to put a couple of things together: The part of this that involves genetic sequencing is figuring out what different genes can do so you can plug them in for specific outputs. And when you have cataloged thousands and millions of these genes and what proteins they create, then those are potential building blocks to synthesize new organisms that produce specified outputs. Is that it?

Venter: That’s right. And there are new functions being discovered all the time. But there are not enough scientists on the planet to look at all the genes that we’ve already discovered. From the ocean expedition alone, we have about 60 million to 80 million genes. We don’t know what most of them do.

What’s needed is an automated way to discover what they do. And then we can actually make substitutions starting with the digital world and converting that into these analog DNA molecules, then transplant them automatically and get cells out. It’s a matter of scoring the cells based on knowing what the input information is, to work out what that gene does, what impact it has. Do you get a living cell or not? I think we can make a robot that learns 10,000 times faster than a scientist can. And then all bets are off on the rate of new discovery.

Goetz: And energy is just one of your targets. You believe DNA is a code that can be used to solve all sorts of problems: health, energy, food.

Venter: I think of it as an equation: Water equals food equals energy. It doesn’t matter where you start in that equation, you need cheap renewable energy to produce food and clean water, and vice versa. Biology is a natural part of many of those, certainly the food part. And it’s been a part of energy. Oil is ancient biology, very ancient biology, as is coal, but we need to not take that ancient biology out of the ground, burn it, and put it into the atmosphere. We need a way to recycle the biology. So biology will be a key part of the solution. Will it be the only solution? No. We need lots of solutions. We can now start with the code, the digital code of DNA, convert that into chemical DNA, and convert that into new living organisms that have the potential to do what we need them to do. Producing these very necessary things for society.

... _Venter Interview in Wired

A Video Worth Watching from Time's Man of the Year 2010

Note: Since I posted the NASA Ames video, someone has pulled permission for both embedding and public viewing. But here is the "60 Minutes" interview filmed just after the achievement of creating a strain of mycoplasma mycoides. I'll leave the locked video here for now -- just in case the owners come to their senses.

J. Craig Venter on Synthetic Biology at NASA Ames from Ben Howard on Vimeo.

Craig Venter is Time's Man of the Year for 2010 for his team's "plug and play" creation of the first synthetic cell, Mycoplasma mycoides. This "minimal cell", a parasitic organism which can only live inside other living cells, is meant as a starting point for the creation of microscopic factory-cells.

The aim of the Venter team was.....to build a prototype for a microscopic production line. Back in May, here is what the team had to say in Science:

If the methods described here can be generalised, design, synthesis, assembly and transplantation of synthetic chromosomes will no longer be a barrier to the progress of synthetic biology … the approach we have developed should be applicable to the synthesis and transplantation of more novel genomes as genome design progresses.

So, if a microorganism could be engineered to include genes that direct the cell to do a number of functions, it would be possible to use this cell for a range of industrial tasks, such as making proteins or carbohydrates or any compounds to order, depending on demand. Theoretically, it might be possible to make biofuels, vaccines, drugs, foodstuffs and anything else genetic engineers can program the new genomes to produce.

What Venter's team really set out to do, and achieved, was show it's possible to build the world's smallest production line, inside the world's smallest factory.

Venter was not so much playing God, but following in the tradition of the great industrial pioneers of last century. He's closer to a latter day Henry Ford - the man who in the 1910s developed the production line that eventually put a car in almost every home in the Western world and became the de novo engineering tool for the mass production of everything from ice cream to tweezers.

What happens next depends on how Venter and others working in this new field can tool up this tiny production line. _Cosmos

"Synthetic Biology" is a far more clever and descriptive term than "metabolic engineering." The word "synthetic" does double duty, since not only are new biological factories to be synthetically generated, but these biological factories are to be used to synthesise valuable chemicals, materials, fuels, and drugs.

We are seeing the preface to the first chapter of a multi-volume work. Much more to come.

What Is Metabolic Engineering and Why Should We Care?

LBLNewsMetabolic Engineering is one of those bastard terms which is often spawned by science-savvy folks in academia who are functionally illiterate. For example, MIT has a lab department of Bioinformatics and Metabolic Engineering. Rice has studies in Biological Chemistry and Metabolic Engineering. Harvard teaches Systems Metabolic Engineering. Cornell has a lab for Biomolecular and Metabolic Engineering. At Berkeley, the subject falls under the Department of Chemical and Biomolecular Engineering... and so on. When will we be given entire departments of Respiratory Engineering, Mitochondrial Engineering, Liposome Engineering, or Cholesterol Membrane Engineering? There truly is no end to the number of departmental classifications that could be spawned by the postmodern twits of academia who have acquired a little bit of specialised scientific training.

Forgive me, I got a bit sidetracked. Chemical engineer Jay Keasling has published an article in Science discussing the "Future of Metabolic Engineering," in which he looks at the possibilities of creating designer molecules, cells, and micro-organisms.

In a paper published in the journal Science titled “Manufacturing molecules through metabolic engineering,” Keasling discusses the potential of metabolic engineering – one of the principal techniques of modern biotechnology – for the microbial production of many of the chemicals that are currently derived from non-renewable resources or limited natural resources. Examples include, among a great many other possibilities, the replacement of gasoline and other transportation fuels with clean, green and renewable biofuels.

“Continued development of the tools of metabolic engineering will be necessary to expand the range of products that can be produced using biological systems, Keasling says. “However, when more of these tools are available, metabolic engineering should be just as powerful as synthetic organic chemistry, and together the two disciplines can greatly expand the number of chemical products available from renewable resources.”

...Metabolic engineering is the practice of altering genes and metabolic pathways within a cell or microorganism to increase its production of a specific substance. Keasling led one of the most successful efforts to date in the application of metabolic engineering, when he combined it with synthetic organic chemistry techniques to develop a microbial-based means of producing artemisinin, the most potent of all anti-malaria drugs. He and his research group at JBEI are now applying that same combination to the synthesis of liquid transportation fuels from lignocellulosic biomass. In all cases, the goal is to engineer microbes to perform as much of the chemistry required to produce a desired final product as possible.

“To date, microbial production of natural chemical products has been achieved by transferring product-specific enzymes or entire metabolic pathways from rare or genetically intractable organisms to those that can be readily engineered,” Keasling says. “Production of non-natural specialty chemicals, bulk chemicals, and fuels has been enabled by combining enzymes or pathways from different hosts into a single microorganism, and by engineering enzymes to have new function.”

These efforts have utilized well-known, industrial microorganisms, but future efforts, he says, may include designer molecules and cells that are tailor-made for the desired chemical and production process. _LBLNews_via_BrianWang

Sound familiar, this metabolic engineering? Like a contrived illegitimate offspring of genetic engineering, synthetic biology, and metabolomics? It's bad enough to have a proliferation of -omics, such as genomics, proteinomics, metabolomics, glycomics, lipomics . . . It is almost enough to turn a person homicidalomic.

Psychiatry with its DSM is almost as insane. But these irrational and cumbersome systems of classification tend to evolve by the method of poorly punctuated disequilibrium, leaving those downstream to deal with the offalness of it all.

Does Keasling simply want to excel in a field that another researcher -- Craig Venter -- has already staked out -- synthetic biology? Venter has long since founded a company called Synthetic Genomics. Is it possible that Keasling is unwilling to share the same field with a person such as Venter, who is already hot on the trail of the very things that Keasling claims to be pursuing in the name of Metabolic Engineering? Fine. Do the same thing, but call it something different. No one will ever know.

Controlling Microbial Genes: Beyond Synthetic Biology

While other gene-expression techniques need to be engineered for a particular gene, Collins says, the RNA-based switch "can be used to control any gene of interest." Other switches rely on proteins to regulate gene expression. But the use of proteins requires several steps, which means they're not as fast to make as the RNA switches. _TR

Kill switch: From top left to bottom right, these images show bacteria dying over the course of a few minutes. Researchers flip a genetic switch that causes the bacteria to make proteins that cause them to burst.
Credit: PNAS
Scientists at Boston University have developed the ability to control the activity of any microbial gene -- reducing or even stopping any gene's protein synthesis activity.

...researchers at Boston University, led by biomedical engineering professor James Collins, have developed a highly tunable genetic "switch" that offers a greater degree of control over microbes. It makes it possible to stop the production of a protein and restart it again. The switch, which could be used to control any gene, can also act as a "dimmer switch" to finely tune how much protein a microbe would produce over time.

The researchers made a highly effective microbe "kill switch" to demonstrate the precision of the approach. For years, researchers have been trying to develop these self-destruction mechanisms to allay concerns that genetically engineered microbes might prove impossible to eradicate once they've outlived their usefulness. But previous kill switches haven't offered tight enough control to pass governmental regulatory muster because it was difficult to make it turn on in all the cells in a population at the same time.

...Collins's switch, described online in the Proceedings of the National Academy of Sciences, turns a modified gene on and off. The switch is created by sequences of DNA that can be added to any gene that a bioengineer wants to regulate. When the cell takes the first step toward expressing that gene--making an intermediate molecule of RNA that can be "read" to make the relevant protein--it also creates the RNA switch. When the first, "off" RNA switch is made, it latches onto the ribosome, preventing it from making a particular protein. When the second, "on" switch is made, it pulls the first RNA switch off of the ribosome and binds to it the switch, freeing the ribosome to resume production.\

Depending on how they're designed, production of the RNA switches can be regulated by exposing the bacteria to a particular chemical. By controlling how much of the "on" and "off" RNAs are made, it's also possible to regulate protein production over a continuum, not just turn it totally on or off.

...Such a kill switch could be useful in microbes designed to, for example, break down environmental toxins. Once the microbes have cleaned up a toxin, "you could spray the area with an innocent compound that triggers cells to expire on command," says Collins. The kill switch could also be coupled to other synthetic biology tools such as genetic clocks in order to design bacteria that live for a given number of days.

These switches make it possible "to do the kinds of things people like me struggle to do," says Robertson. One of the main challenges for a company like Joule, he says, is complying with regulations about environmental containment of genetically modified organisms, and Collins's switch could help.

Collins is currently working to combine the switches to make what he calls tunable "switchboards." "We want to tune genes like a rheostat," he says. Such a switchboard might be used to control a population of cells so that they first put their energies toward growing their population. Then, when engineers deem it timely, they can administer chemical signals that cause the cells to gradually ramp up production of a fuel, for example. _TechnologyReview

By starting with a gene-packed bacterium, the scientists could conceivably "tune" the cell to behave just like a wide range of other bacterial species -- depending upon which genes were "switched on or off" at the time. The only thing missing would be a means to generate new controllable genes on the fly.

This type of development will actually be blended into the field of synthetic biology -- but it will extend the field significantly. Now, instead of simply designing new life forms which will behave as designed, synthetic biologists can design "programmable life forms" which can serve as flexible test beds for a wide range of genetic experiments.

The possibility for the transfer of such techniques to mammalian cells should be setting off warning klaxons among the dieoff.orgy lefty-Luddites from Berkeley to Manhattan to Brussels. And to think they're worried about genetically modified foods!

Synthetic Biology: One Bright Doorway Into the Future

If you want self-replicating nano-assemblers, you do not need to look further than your own body and bodily excretions. Biology is the proof of concept of self-replicating nano-machines, and synthetic biology is rapidly becoming an rocketing ride into a future of diminishing limits.

Brian Wang presents an interview with synthetic biologist Andrew Hessel (featured in the video above). Excerpts:

Question: What is the main purpose of the singularity university?
Answer: I am the co-chair of bioninformatics and biotechnology at the Singularity University. Singularity has a very unique business model when it comes to education. We focus on training students in technologies that can go exponential. I emphasize to the students that the reading and writing of genetics code is an exponential technology in the same way for biogenetics that Moore's law is for computing. We are hitting the knee of the curve of that technology.
....
Question: Craig Venter’s team recently created a new prokaryotic life form. How important is this accomplishment?
Answer: I believe Venter’s accomplishment will have profound ramifications. I see DNA as a programming language, and like any language there are three components - reading, writing, and comprehension. Craig has been at the forefront of reading and understanding DNA code, and today he is a leader in synthetic technologies. The creation of an artificial prokaryotic life form only scratches the surface of the greater potential of synthetic biology. The ability to easily engineer living organisms is perhaps the most powerful technology humans have made to date.
....
Question: What will be the first mainstream application to be introduced that is dependent on synthetic biology?
Answer: That is the billion dollar question. If I had an answer to this question, I would be locked in a lab developing it. There are some clues, though. Historically, biotech has focused on treating illnesses, but the average consumer isn’t sick. This limits the marketplace. In health, people spend money on things that gives them tangible value in their everyday lives, at affordable prices. This means energy, building materials, household products, cosmetics, foods, pets, sensor and diagnostic technologies, and perhaps even smart drugs and intoxicants, like beer or wine. Whoever successfully brings biotechnology innovation to the masses will generate a fortune that rivals Google.

Question: When will the first human organs be created using synthetic biology?
Answer: Human organ cloning is actually more about stem cell engineering than synthetic biology per se. I predict rapid advancements in that area, due to rapid 3D printing technologies. The leader in that space is a company called Organovo, which has just announced the first commercial cell printer. Once we can print cell-based structures, we can produce everything from synthetic foods to organs. Given an aging population, it’s only a matter of time before fully functional cloned human organs become commercially available.

Question: How much progress can be expected in the field of synthetic biology by 2020?
Answer: This technology is in the knee of the s-curve and will grow exponentially for decades. By 2020 we will be able to engineer simple living systems routinely, whether it be a single protein, a metabolic pathway, or simple multicellular creatures. Eventually, testing and measurement of what we’re programming will become the limiting factor. Overall, the potential of synthetic biology is comparable to the potential of computers. We’re going to see it broadly applied in human endeavors. _NextBigFuture

A lot of resources are being shunted toward the several areas of science that intersect with synthetic biology. The potential is enormous, but the eventual outcome is anything but certain. With so many different transformative offshoots likely to spring up, it will be easy to overlook some incredibly profound possibilities lying within the technology.

Is there anything that biology cannot do over time and with assistance? We may soon find out.

What Use is a New-Born Baby?

On a Friday in March, scientists inserted over 1 million base pairs of synthetic DNA into Mycoplasma capricolum cells before leaving for the weekend. When they returned on Monday, their cells had bloomed into colonies.

“When we look at life forms, we see fixed entities,” said J. Craig Venter, president of the Institute, in a recent podcast. “But this shows in fact how dynamic they are. They change from second to second. And that life is basically the result of an information process. Our genetic code is our software.” _Wired

Wired
"Impressive!", you may say, "but what good is it?" Yes, what good is a newborn baby? Only time can tell. Here is a look at the coverage of the Venter Institute's achievement from a few prominent websites:

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. _NewScientist

"It is a big deal," geneticist and technology developer George Church of Harvard Medical School says of the achievement. "It's not incremental, but it's not final either," noting that other groups are already delivering useful products from partially reengineered genomes, such as biofuels from engineered E. coli.

Biological engineer Drew Endy of Stanford University clarified how to think of this creation. "It's not genesis, it's not as if mice are coming from a pile of dirty rags in a corner," he says. "The correct word is poesis, human construction. We can now go from information and get a reproducing organism. It lays down the gauntlet for us to learn how to engineer genomes." _SciAm

Using a method developed in 2008, the researchers, led by genomics pioneer Craig Venter, synthesized the genome of a tiny bacterium called Mycoplasma mycoides, containing just over a million DNA base pairs. Next they transplanted the synthetic genome into a related bacterium, Mycoplasma capricolum, in a process they had previously perfected using nonsynthetic chromosomes.

Once the recipient cells incorporated the synthetic genome, they immediately began to carry out the instructions encoded within the genome. The cells manufactured only M. mycoides proteins, and within a few rounds of self-replication, all traces of the recipient species were gone. The results were published Thursday in the online edition of the journal Science.

To distinguish their synthetic genome from the naturally occurring version, the researchers encoded a series of watermarks into the sequence. They began by developing a code for writing the English alphabet, as well as punctuation and numbers, into the language of DNA--a decoding key is included in the sequence itself. Then they wrote in their names, a few quotations, and the address for a website people can visit if they successfully crack the code. _TechnologyReview

This publication represents the construction of the largest synthetic molecule of a defined structure; the genome is almost double the size of the previous Mycoplasma genitalium synthesis. With this successful proof of principle, the group will now work on creating a minimal genome, which has been a goal since 1995. They will do this by whittling away at the synthetic genome and repeating transplantation experiments until no more genes can be disrupted and the genome is as small as possible. This minimal cell will be a platform for analyzing the function of every essential gene in a cell. _GCC

What we now need are ways to construct and test billions of genome combinations using protein and RNA biosensors for many or all metabolic intermediates and cell-signalling states. In combination with the sort of techniques that the JCVI has just demonstrated — but at much lower cost — this would enable researchers to select for important products such as pharmaceuticals, fuels, chiral chemicals and novel materials.
_NextBigFuture

Ever since Watson and Crick, biologists and biochemists have known that it was only a matter of time before humans learned to bend biological mechanisms to the will of humans. The journey has just barely begun. It is likely to be a very wild ride.

Do Not Bet Against Craig Venter

Craig Venter has true grit. He came by it honestly over his lifetime, and continues to display true grit in all of his ventures.

Since mapping the human genome 10 years ago, J. Craig Venter has found plenty of work. The biologist now is burrowing into DNA in as many forms as he can discover, in organisms from the sea and deep underground. His goal: to use the building blocks found in naturally occurring DNA to make synthetic cells. He and his partners at Exxon Mobil Corp. and BP PLC believe genetically engineered life forms hold great promise for energy and other industries. _WallStreetJournal

Fuels-from-microbes is a topic of interest to scientists, venture capitalists, and technologists around the world. It is no wonder that Craig Venter finds himself at the center of the cyclone that involves finding the replacement for fossil fuels and finding the keys to biological magic both at the same time.

In July of last year, Synthetic Genomics announced a $300 million agreement with Exxon to research and develop next generation biofuels using photosynthetic algae. That investment will occur over a number of years -- but that's still a lot of cash. It's more than the total amount of venture capital invested in algae startups since 2005. A drop in the bucket for Exxon but still, big money.

Here's what Venter had to say: "We are at the early stages of seeing what biology can do."

Venter has come up an idea to trick algae into pumping more lipids out. He also claims to have "engineered algae to continuously pump out hydrocarbons," which eliminates much of the cost and energy-intensity of conventional algae oil farming. If that can be done, economically and at scale -- it is absolutely disruptive.

...Venter speaks in a matter-of-fact manner about his activities but beneath that calm tone are mind-bending ideas straight out of science-fiction novels. Venter has already created the first cell with a synthetic DNA gene. If not exactly creating life, Venter is bending the genetic code to do his bidding. He said that he is "going from the four-letter genetic code of A, C, G and T to the binary codes of ones and zeros."

He is "amassing a genetic database...continually learning to write the genetic code" and "treating the genetic code as a raw material." By "changing the DNA software in the cell, the cell converts to a new species." In Venter's words, "The concept of life is changing."

In Venter's "optimistic" estimation, it will take roughly a decade to get to scale on CO2 to fuel. But "once the proof of concept is done, this will move rapidly."

There remain many problems with algae -- it's not just a matter of tricking the algae to pump more lipids out or to secrete hydrocarbons. There's an entire process chain in algae farming that needs to be optimized -- algae growth, water issues, nutrient issues and more.

But Venter is a man of action and it's not a good bet to wager against him. _BiofuelsDigest

Venter is the Vietnam war veteran who beat the Human Genome Project to the human genome. Venter understands the stakes that are involved in learning the secrets of the gene -- whether for humans or for algae. Once these secrets are out of the box, there is no replacing them.

Programming algae to replace fossil fuels will be a trivial achievement in comparison to finding the genetic keys to nurturing smarter humans. Whatever Venter may say, there is little doubt that he would like to be at the center of that cyclone as well.

Venter is a man of grit, accomplishment, and great ambition. Such men aim high, and once they reach great heights of achievement, they tend to aim even higher.

Always the Doom You Don't Expect That Gets You

Synthetic biology involves the production of novel living organisms that are self-replicating and potentially uncontrollable if something goes wrong.....

QUEST on KQED Public Media.
A .... concern is the deliberate construction and release of a pathogen more virulent and transmissible than anything in nature. The perpetrator might be a malevolent individual with a knowledge of synthetic biology or a terrorist group seeking the ultimate bioweapon. Fuelling such fears is the rapidly growing availability of BioBricks and other “standard biological parts”, which enable even undergraduates to engineer their own microbes.

We probably have at least five years grace before synthetic biology has reached the point... FT

.... where it can destroy our current gullible faith in the safety of the commons. We may have five years. Sooner or later, resentful child-men and child-women will have the power to turn the life-giving air, water, food, and biosphere of the planet into agents of certain death -- or worse.

Synthetic biology will have to learn how to manipulate much more than DNA and genomes to become truly dangerous, of course. Without the epigenome and other components of life, the genome is an empty shell.

Epigenetics, a relatively new endeavor in science, refers to the control of the patterns of gene expression in cells, which gives rise to the necessary differences responsible for creating the complex and interacting tissues in the body.

Scientists globally have begun working on a Human Epigenome Project in a bid to compile detailed data documenting, within a person, the epigenetic changes in different types of cells and tissues, something that will complement the already-completed Human Genome Project. _Source

Links and video via Machines Like Us

We are accustomed to breathing from a common air supply, drinking from a common water supply, eating from a common food supply, and immersing ourselves in a common biosphere. In the not-so-distant future, humans may have to jettison this childlike faith in the safety of the bio-commons, and take steps to assure the safety of our own food, water, and air supplies. On a local -- even household -- level. Mass society could become a thing of the past, as multiple existential threats simultaneously sever the threads of trust that presently hold cultures and societies together.

Who will prevent this dissolution of trust and safety? Not the clueless clowns of the present US governmental reich. They are too busy destroying political enemies and grabbing as much political power as possible, to even consider attending to real world existential threats. The type of competence required to anticipate, interdict, and prevent such threats, is in very short supply -- and little valued in the current political / academic / media climate.

It is up to individuals and groups working outside the mainstream, to devise protective solutions to these somewhat probable threats. Fortunately, many genuinely useful preventative measures apply almost equally to a wide range of existential threats.

Not Just Beer -- Yeast Factories For Everyone!

The Venter Institute has just published a PNAS paper detailing their work to turn beer yeast (Saccharomyces cerevisiae) into multi-use factories. These yeast factories can be made to crank out components for completely artificial organisms which the Venter Institute are developing. Artificial organisms that can make synthetic fuels, valuable chemicals and chemical feedstocks, new pharmaceuticals -- a veritable cornucopia of biologically produced treasure.

Senior author Clyde Hutchison added, "I am astounded by our team's progress in assembling large DNA molecules. It remains to be seen how far we can push this yeast assembly platform but the team is hard at work exploring these methods as we work to boot up the synthetic chromosome."

Venter and his team continue to work towards creating a living bacterial cell using the synthetic genome sequence of the Mycoplasma genitalium bacteria.
_AFP

More from Green Car Congress:

The JCVI team continues to explore the capacity for DNA assembly in yeast, and the various applications of this particular method. They conjecture that a variety of combinations of DNA molecules and genetic pathways could be manufactured in yeast, in essence turning yeast into a genetic factory for specifically designed and optimized processes. This advance is being used by scientists at the company SGI in making next generation biofuels and biochemicals more efficiently. _GCC

Venter's team is not the only group working on the genetic transformation of organisms to create biofuels. This Al Fin Energy piece describes the work of the Chromatin-Monsanto alliance.

A South Korean scientific team has just completed the sequencing of the genome of a Korean scientist Kim Seong-jin, as the genomics revolution spreads worldwide. The tools of genomics will soon be inexpensive and ubiquitous enough so that garage hobbyists will be able to sequence various genomes, and experiment by inserting gene stacks -- "artificial chromosomes" -- into plants and animals.

Synthetic Biology and BioSynthetic Fuels

The best time to work on alternatives to fossil fuels is while fuel prices are temporarily low. Better prepare now, because when those prices start rising again it may be too late to block another energy-recession.

Synthetic biology is in its early bloom. Soon, it will begin offering a greater abundance of products such as fuels, plastics, chemicals, pharmaceuticals, and other things unimaginable now. Unless the ever-lurking Luddites burn the bridges before they are built. That is a danger under the current political current. But the need for alternative fuels is so apparent, that it is possible the Luddites in political control will overlook this one shining promise.

Synthetic biology refers to both the design and fabrication of biological components and systems that do not already exist in the natural world, and the redesign and fabrication of existing biological systems. As tools are developed to hone and refine this technology, researchers across multiple disciplines are finding novel applications for it.

...One company that provides the raw material for the creation of biofuels is Agrivida, an agricultural biotech firm that creates renewable, biomass-based alternative fuels and raw materials. “We are working upstream, making plants that are more easily degradable, primarily switchgrass, sugar cane, and corn,” states R. Michael Raab, founder and president. “We are focused on nonfood crops and crop residues that are degradable into fuel.”

...Gevo develops advanced biofuels technology based on butanol and its derivatives. “The magic isn’t in the biology alone,” according to Pat Gruber, Ph.D., CEO. “It’s in the chemistry, fermentation, processing, and genetic engineering all together; knowing what tools you need, and having the tools to make it happen.”

Dr. Gruber points out that three critical pieces of technology have helped Gevo produce these on a commercial scale. “We have a group that’s been working on this for 20 years or longer. Metabolic engineering of suitable host organisms make it possible to use carbon and energy efficiently for fuel production. Process engineering makes it possible to lower product separation costs and chemistry to produce valuable hydrocarbons.”

...Two other companies working in the metabolic engineering space are Mascoma and LS9. Mascoma recently received $26 million in DOE funding, which will be applied toward the development of a cellulosic fuel production facility that uses nonfood biomass to convert woodchips into fuel. Mascoma’s production facility is expected to produce 40 million gallons of ethanol and other valuable fuel products per year.

LS9 developed new metabolic pathways that efficiently convert fatty acids to a broad portfolio of petroleum replacements. It also discovered and engineered a new class of enzymes and their associated genes that catalyze the efficient conversion of fatty acids to hydrocarbons. They recombinantly produce hydrocarbons (oxygen-deficient biocrudes), fatty acid alkyl esters (biodiesel), and a variety of industrial chemicals from sugars via fatty acid biosynthesis.

...Codexis’ technology enables solutions for cost-effective, efficient, and environmentally sound production of pharmaceuticals, transportation fuels, and industrial chemicals, reports David Anton, Ph.D., vp, bioindustrials R&D. The company focuses on biocatalysts—enzymes or microbes that initiate or accelerate chemical reactions. At Codexis, biocatalysis is used to design faster, less costly, and greener chemistry-based manufacturing processes in the life science and energy industries.

According to Dr. Anton, Codexis’ technology makes it possible to customize enzymes capable of selectively and efficiently performing a desired chemical process that doesn’t exist in nature.

...SunEthanol was recently awarded a $750,000 Phase II Small Business Technology Transfer Program contract. This award, made as a follow-up for successfully completing a year-long Phase I grant, will allow SunEthanol to continue pioneering a process that converts plant waste into clean ethanol fuel in one simple step, saving time and money over the traditional two-step cellulosic conversion process, the company claims.

... _GenEngNews

Several more companies are mentioned and linked in the above Genengnews article. It is impossible to keep track of all the research efforts in synthetic biology that will influence biosynthetic fuels development. Every university biology or agriculture department with a significant research program will be working on this problem, in all likelihood. Whether or not the world economy improves, fuel prices will rise. If the Luddites in control suppress energy technologies, energy prices will rise out of scarcity. If the Luddites are given a well-deserved boot in the arse, energy prices will rise as economies improve. Those who are prepared will prosper. Those who are not prepared, will dieoff.org. It is the harsh way of the universe.

Artificial DNA: Creating Alien Life on Earth

All life on Earth is based upon the same basic DNA template. Now Japanese chemists have succeeded in building double stranded DNA (even triple stranded DNA!) from artificial nucleic acids.

Until now, scientists have only been able to craft DNA molecules with one or a few artificial parts, including certain bases.

The researchers used high-tech DNA synthesis equipment to stitch together four entirely new, artificial bases inside the sugar-based framework of a DNA molecule. This resulted in unusually stable, double-stranded structures resembling natural DNA. Like natural DNA, the new structures were right-handed and some easily formed triple-stranded structures. The unique chemistry of these structures and their high stability offer unprecedented possibilities for developing new biotech materials and applications, the researchers say.

...The finding could lead to improvements in gene therapy, futuristic nano-sized computers, and other high-tech advances, they say. Their study is scheduled for the July 23 issue of the Journal of the American Chemical Society, a weekly publication __Nanowerk

In order to create an entirely new system incorporating the new DNA, the researchers would need to create artificial RNA and artificial ribosomes that work together to produce artificial peptides and proteins--or protein analogs.

Artificial systems of DNA / RNA / Ribosomes / Proteins / Glycoproteins etc. could be an important bridge to a more versatile and prolific molecular nanotechnological assembler complex. It should be possible to get around some of the greatest limitations of current enzymes using specially designed artificial amino acids and amino acid analogs.

It took nature a billion years or so to work out the system we have. Only about 55 years have passed since Watson and Crick announced their discovery. I expect significant progress toward integrated systems of artificial DNA, RNA, and protein analogs before 2030.

First Trillion Dollar Company? Synth-Bio

Yesterday we discussed trillion dollar ($Trillion) industries, and from which industry the first $Trillion company may come from. Consider the goal of Craig Venter's synth-bio research: to replace the entire petrochemical industry! According to Fortune, Venter's company would easily be a $Trillion company if it fulfills Venter's promise.

Geneticist Craig Venter disclosed his potentially world-changing "fourth-generation fuel" project at an elite Technology, Entertainment and Design conference in Monterey, California.

"We have modest goals of replacing the whole petrochemical industry and becoming a major source of energy," Venter told an audience that included global warming fighter Al Gore and Google co-founder Larry Page.

"We think we will have fourth-generation fuels in about 18 months, with CO2 as the fuel stock."

Simple organisms can be genetically re-engineered to produce vaccines or octane-based fuels as waste, according to Venter.

Biofuel alternatives to oil are third-generation. The next step is life forms that feed on CO2 and give off fuel such as methane gas as waste, according to Venter.

"We have 20 million genes which I call the design components of the future," Venter said. "We are limited here only by our imagination."___Source_via_NextEnergy

The problem with creating a $Trillion company is that there will likely be a lot of competitors trying to imitate your success. For most industries, there is only so much market share to go around.

But as I said yesterday, in the future, we are likely to see $Trillion companies the same way we see $Billion companies today. As the norm for large companies and corporations. We merely need to remove the artificial bottlenecks that cause humans to continue thinking "small".

Craig Venter Is Not God! Claims Biologist Helen Wallace -- Venter's Wife Declined Comment

Scientists at the Craig Venter Institute were able to synthetically reproduce the genome of a Mycoplasma bacterium--the simplest of life forms. While not the same thing as actually creating a new life form, the feat did require developing genome assembly techniques that will be very useful later when novel lifeforms are actually created.

A team of 17 researchers at the J Craig Venter Institute in Rockville, Maryland, describes in the journal Science how it has successfully created the largest man-made DNA structure, indeed the largest synthetic molecule, the circular genetic code of an artificial bacterium that it is now trying to breed in the lab.

The scientists led by the human genome pioneer Dr Craig Venter want to create new kinds of bacterium, living chemical factories if you like, to make new types of bugs which can be used as green fuels to replace oil and coal, digest toxic waste or absorb carbon dioxide and other greenhouse gases from the atmosphere....the team specially designed fragments of lab-synthesised DNA to build 101 "cassettes", each consisting of 5,000 to 7,000 letters (base pairs, in the scientific jargon) of genetic code.

Dr Venter's team, notably Clyde Hutchison and the Nobel laureate Ham Smith, also created "watermarks" in the synthetic genome - which had no purpose other than to show it was man made - and knocked out a gene to render it harmless. Essentially, however, the team was trying to make a copy of a natural genome, not design one from scratch.

From here, the team developed novel methods and techniques to assemble the genome, which are the subject of patent applications. "One reason it took so long is that we were trying to develop techniques that were highly robust," says Dr Venter.

They devised a five stage assembly process where the cassettes were joined together in the correct order in sub-assemblies to make larger and larger overlapping pieces that would eventually be combined to build the whole synthetic M. genitalium genome, a ring of DNA consisting of 582,970 letters. At each stage of assembly, the growing pieces were sequenced to make sure they were accurate.

Telegraph

The techniques of genomic assembly that will be patented by the Venter Institute should be the source of lucrative licensing agreements between Venter's Institute and Universities, other labs, and biotech/ chemical /pharmaceutical companies for decades to come.

Other scientists hastened to state that Venter's group did not create new life:

Eckard Wimmer, professor of molecular biology at New York University, said it was clear from Venter's study that the team had not yet created artificial life.... His fears were echoed by Helen Wallace, a biologist and spokesperson for GeneWatch UK, who said that while Venter's team has managed a technical feat, it is some way from being artificial life. "Venter is not God ... He's a long way from creating life," she told AFP.

Source

Here is Venter's first person account.

More from LA Times and NY Times

Programming DNA : Basics -- One Hour Video

This talk will introduce current best practice in biological engineering, including an overview of how to order synthetic DNA and how to use and contribute standard biological parts to an open source collection of genetic functions. The talk will also discuss issues of human practice, including biological safety, biological security, ownership, sharing, and innovation in biotechnology, community organization, and perception across many different publics.

Video's Google Page

If you do not have a technical background, this video may require more than one viewing to get an understanding of most of the basics.

H/T Biosingularity

Once you start to get a feeling for what can be done, what cannot be done--but will be done soon, what cannot be done--and will probably never be done . . . etc., you will begin to understand that a trillion dollars a year is being spent to wage and defend against the last millenium's weaponry.

When the technology described in this video (along with advanced nanotechnology) begins to kick in, all bets will be off. It will be easier for a motivated lone fanatic to commit mass mayhem and murder than it is for you to open a bank account.

In Israel they have bomb shelters and gas masks, because they understand their bad neighbors' tendencies and unneighborly wishes.

We in the west live in a public society, where much is shared commonly. We take such public activity and openness for granted, and assume it is our right. An occasional workplace, school, or shopping mall shooting does not dampen our naive expectation of safety in the public sphere. The new terrorism, when this technology matures, will not allow us this easy confidence. No security force or agency in the world is prepared.

Information about Adventures in Synthetic Biology comic here. Full pdf of Adventures in Synthetic Biology. To view the Adventures in Synthetic Biology Comic go here.

Peak Oil: Meet Synthetic Micro-Organisms that Produce Petroleum

Creating micro-organisms that can synthesise renewable hydrocarbons for fuels and feedstocks, is one aim of synthetic biology.

The process is the same as making cellulosic ethanol insofar as cellulosic feedstocks are converted into fermentable sugars, and those sugars are placed in a fermentation vat. The difference comes in the microbes doing the fermenting. With ethanol, it's generally some form of yeast. The researchers at LS9 have engineered their own microbes, lifting genes from other microbes and recombining them into an organism that does just what they want. In this way they can precisely tweak the characteristics of the resulting fuel.

Yeast fermentation produces ethanol, which mixes with water and subsequently has to be extracted via distillation. LS9's microbes produce -- via fatty acid metabolism, in a process I won't claim to understand -- hydrocarbons (the building blocks of petroleum). These hydrocarbons are immiscible, i.e., they don't mix with water. Instead, they float to the top of the vat, where they can essentially be skimmed off. That allows LS9 to skip the distillation process, which saves a whole boatload of energy. (That's where most of the claimed 65% energy savings comes from.)

Source

David Berry, one of the brains behind LS9, has won the Young Innovator of the Year award from MIT's Tech Review.

Berry's goal was nothing less than "to develop a novel and far-reaching solution to the energy problem." In col­laboration with genomics researcher George Church of Harvard Medi­cal School and plant biologist Chris Somerville of Stanford University, Berry and his Flagship colleagues set out to do something that had never been attempted commercially: using the tools of synthetic biology to make microörganisms that produce something like petroleum. Berry assumed responsibility for proving that the infant company, dubbed LS9, could produce a biofuel that was renewable, better than corn-derived ethanol, and cost-­competitive with ­fossil-based fuels.

I understand that Chris Somerville -- a leading figure in the plant biology field -- is also at work on plants that are genetically engineered to produce biodegradable plastics. Now if they could just integrate that idea with these petroleum-producing microbes, we'd really have something to celebrate.

Source

If synthetic biologists can create microbes that efficiently create "petroleum" in an industrial environment--out of renewable materials and skipping any energy-wasting distillation process--the economics of the future of energy might change a bit.

After Synthetic Biology: Comes the Plague?

Synthetic biologists such as Craig Venter, are optimistic about their future. They believe that once they have mastered the art of forcing nature to do their will, the good life will follow--for everyone.

Synthetic biologists, as they survey all the new genes and control elements whose DNA sequences are now accumulating in data bases, seem to feel extraordinary power is almost within their grasp.

“Biology will never be the same,” Thomas F. Knight of M.I.T.’s Computer Science and Artificial Intelligence Laboratory wrote recently in describing the new engineering discipline he sees as emerging from it.

....“Grow a house” is on the to-do list of the M.I.T. Synthetic Biology Working Group, presumably meaning that an acorn might be reprogrammed to generate walls, oak floors and a roof instead of the usual trunk and branches. “Take over Mars. And then Venus. And then Earth” —the last items on this modest agenda.

Most people in synthetic biology are engineers who have invaded genetics. They have brought with them a vocabulary derived from circuit design and software development that they seek to impose on the softer substance of biology. They talk of modules — meaning networks of genes assembled to perform some standard function — and of “booting up” a cell with new DNA-based instructions, much the way someone gets a computer going.

The first practical applications of synthetic biology may not be so far off. “The real killer app for this field has become bioenergy,” Dr. Collins says. Under the stimulus of high gas prices, synthetic biologists are re-engineering microbes to generate the components of natural gas and petroleum. Whether this can be done economically remains to be seen. But one company, LS9 of San Carlos, Calif., says it is close to that goal. Its re-engineered microbe “produces hydrocarbons that look, smell and function” very similarly to those in petroleum, said Stephen del Cardayre, the company’s vice president for research.

Synthetic biologists are well aware that, like any new technology, theirs can be used for good or ill, and they have encouraged open discussion of possible risks at their annual meetings.

One possible danger is bioterrorism.

Source

Bioterrorism. For western scientists looking for all the good things in life for themselves and others, bioterrorism is not first on their minds. Yet for hundreds of millions of religious fanatics and apocalyptics, the possibility of ending man's reign on earth offered by a perverted synthetic biology must be too strong to resist.

Most of us simply do not want to think about it. Why not simply dwell on all the good things biotech, nanotech, advanced computing, robotics, and molecular fabs will bring to our living rooms and workshops? Why think about a potential hell when we could be thinking about a potential utopia?

Because we like to think about the apocalypse. There is no apocalypse like a "plague apocalypse." Remember 12 Monkeys, or 28 Days Later? How about the classics Earth Abides, No Blade of Grass, or Andromeda Strain?

In a plague apocalypse, the victims can die as long and as painfully as the author desires. Victims can even pass into a zombie state to prey on survivors and the uninfected. Or instead of humans dying from plague, they can die from starvation when diseases attack food crops--destroying the entire food chain from the bottom up.

The White Plague is a revenge tale, about a scientist who loses his wife to terror and embarks on a far more lethal campaign of terror himself. Why not? Scientists are as human as anyone else. Anyone who has not witnessed the passion of a scientist probably just doesn't know any scientists very well.

The point is, synthetic biology makes synthetic plagues--aimed at people or plants--possible. And given the rampant religious apocalyptic fanaticism that possesses the young burgeoning populations of certain countries, it is likely that many of these fanatics will take up biological science as a profession. In other words, it will happen if we let it.

What will our world be like if we get sloppy, and allow the secrets of synthetic plague to slip into the hands of fanatic apocalyptics? To visualize that, you must use your imagination. Reading some of these books might help. Or you may want to read some of these. After all, apocalypses share many consequences among them.

Facing these possibilities is what organisations such as the Lifeboat Foundation and the Society for Creative Apocalyptology are all about.

It is not inconceivable that the future will belong to the city-state, rather than to the nation-state. A city-state can trade with other city-states and with the surrounding countryside, but is more defensible than the nation-state--having shorter borders.

The US-Mexican border will not keep out a deadly plague. Neither will the long border of the Mediterranean Sea between much of the third world and Europe. Chinese military officials have threatened to devastate the US west coast with nuclear weapons, but why bother when a simple microbe will do even more damage?

Round the world cruises and air travel are custom made for spreading deadly plagues. It is quite possible that we will look back on these days as a time of extraordinary freedom to travel and experience the world. In the future, many unknown perils wait.

This is not a time for academic lobotomies or psychological neotenates. It is a time for teaching children basic skills of living and survival, as a matter of course. Think of life in an orbiting colony or on a moonbase. Think of how children would have to be raised in order to deal with the deadly hazards existing right outside the door.

Then start thinking realistically about what life on Earth could easily be like in a decade or two. And stop wasting generations of human life by dooming them to incompetent neoteny and frivolous helplessness.

Bacterial Genome Transplanted, Next Step--Synthetic Organism?

After replacing DNA in mycoplasma capricolum organism with the chromosome from mycoplasma mycoides, scientists at the Ventner Institute are planning work on a completely synthetic organism.

Scientists at the J. Craig Venter Institute (JCVI), a genomics research facility, transplanted a bacterial chromosome from one type of bacteria into another, and have completely replaced an entire bacterial genome and its expression. The work of Carole Lartigue, Ph.D. and colleagues was published in the latest issue of Science:

The JCVI team devised several key steps to enable the genome transplantation. First, an antibiotic selectable marker gene was added to the M. mycoides LC chromosome to allow for selection of living cells containing the transplanted chromosome. Then the team purified the DNA or chromosome from M. mycoides LC so that it was free from proteins (called naked DNA). This M. mycoides LC chromosome was then transplanted into the M. capricolum cells. After several rounds of cell division, the recipient M. capricolum chromosome disappeared having been replaced by the donor M. mycoides LC chromosome, and the M. capricolum cells took on all the phenotypic characteristics of M. mycoides LC cells.

As a test of the success of the genome transplantation, the team used two methods -- 2D gel electrophoresis and protein sequencing, to prove that all the expressed proteins were now the ones coded for by the M. mycoides LC chromosome. Two sets of antibodies that bound specifically to cell surface proteins from each cell were reacted with transplant cells, to demonstrate that the membrane proteins switch to those dictated by the transplanted chromosome not the recipient cell chromosome. The new, transformed organisms show up as bright blue colonies in images of blots probed with M. mycoides LC specific antibody.

The group chose to work with these species of mycoplasmas for several reasons -- the small genomes of these organisms which make them easier to work with, their lack of cell walls, and the team's experience and expertise with mycoplasmas. The mycoplasmas used in the transplantation experiment are also relatively fast growing, allowing the team to ascertain success of the transplantation sooner than with other species of mycoplasmas.

According to Dr. Lartigue, "While we are excited by the results of our research, we are continuing to perfect and refine our techniques and methods as we move to the next phases and prepare to develop a fully synthetic chromosome."

Source

Synthetic biology is one of many approaches to studying the mechanisms of life. Craig Ventner says that he will create an organism that will solve the energy crisis. Perhaps he will. As long as western civilisation survives the onslaughts of anti-enlightenment thinking, I suspect that organisms that can produce unlimited energy will be the least of achievements from synthetic biology, nano-biology, biologic computing etc.

Because western educational systems do not teach students to use their broad intellectual capacities, most humans--even in the developed world--do not have a clue about the multiple revolutions in scientific discovery that are teetering on the very brink of the activation energy hump. Some students of the singularity believe that the true revolution will require the creation of a friendly superhuman machine intelligence.

Personally, I believe that machine augmentation of human intelligence will be enough--once humans learn to use the intellects they possess. But since the educational establishments are incapable of helping humans learn about their intrinsic capacity, there may be some delay.

DNA "Computer" Works Inside Living Cells, Suggests Possibilities

Although DNA computers have been made that can play simple games like tic-tac-toe, programming DNA computers to work inside living cells is much more interesting.

The goal is to inject human cells with DNA that can determine whether a cell is cancerous or otherwise diseased, based solely on the mix of molecules inside the cell. Sensing disease, the DNA might trigger a pinpoint dose of treatment in response. That technology, however, is a long way off. For now, researchers are testing different ways of turning DNA into versatile computers that can detect certain combinations of molecules and respond by producing other molecules.

...RNAi is something that cells do naturally. Cells produce what are known as short interfering RNA (siRNA) molecules, which recognize corresponding DNA sequences in genes and cause them to shut down.

Benenson and colleagues engineered a target gene to be sensitive to several different siRNAs of their own design. In the simplest case, they introduced a single siRNA molecule to switch off a target gene that encoded a fluorescent protein. In more complex cases, a pair of siRNAs or either of two siRNAs switched off another target gene, which in turn switched off a gene for a fluorescent protein. To make sure the system worked as intended, the researchers based their siRNAs on those of other species, they report in a paper published online today by Nature Biotechnology.

In principle, the RNAi technique can reach great heights of complexity, Benenson says, by making genes sensitive to more and more siRNAs in various combinations. "The scalability is very important, because eventually you want to make complex decisions," he says.

He says the next step is figuring out how to make the molecules inside a cell—such as those that are overproduced in cancer—trigger the production of siRNAs.

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This is a very simple approach to DNA "computing", but for all its conceptual simplicity it suggests possibilities that are much more complex. It is best to go very slowly and carefully. The type of control of gene expression hinted at here is not only promising as a cure for cancers, it is threatening.

This type of research appears ideal for a synthetic biological organism. At this time synthetic biologists are attempting to design the simplest possible cells, from other species, by including the smallest possible gene set for viability. Presumably, as the synth biologists master the simpler life forms, they will attempt to create more complex organisms.

Synthetic organisms could potentially become ideal biological models for studying various human diseases. Eventually, synthetic organisms and biological systems could replace most animal models--eliminating much of the need for animal research and testing.

This is yet another research field that bears close watching.