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

Craig Venter's Revolutionary Biology: Unlimited Food and Fuel

Microbes will be the (human) food- and fuel-makers of the future, if J. Craig Venter has his way. The man responsible for one of the original sequences of the human genome as well as the team that brought you the first living cell running on human-made DNA now hopes to harness algae to make everything humanity needs. All it takes is a little genomic engineering.

"Nothing new has to be invented. We just have to combine [genes] in a way that nature has not done before. We're speeding up evolution by billions of years," Venter told an energy conference on October 18 at the New America Foundation in Washington, D.C. "It's hard to imagine a part of humanity not substantially impacted." _SciAm

La Jolla Algal Growth Facility Synthetic Genomics
Craig Venter wants to tweak algae and other microbes, so that humans can get most of their food, fuel, chemicals, plastics, medicines, and other high value items from microbial production. It is a matter of understanding the language of biology to a depth never before mastered. It is a difficult goal. But the payoff is almost inconceivably large.

Given algae's multibillion-year track record with photosynthesis and genetic experimentation Agradis's purpose is to turn that genetic cornucopia into improvements in agricultural crops, whether corn or canola—as well as use algae as a model for testing various new genetic combinations. A similar partnership between Monsanto and algae company Sapphire Energy will "use our algae platform that we developed to mine for genes that can transfer into their core agricultural products," explained Tim Zenk, Sapphire's vice president for corporate affairs in a prior interview with Scientific American. "When you do genetic screening in algae, you get hundreds of millions of traits in the screen and that accelerates the chances of finding something that can be transferred."

If that's not enough, Venter sees a role for synthetic biology in food beyond crops and livestock—specifically the growing hunger for meat around the world. "It takes 10 kilograms of grain to produce one kilogram of beef, 15 liters of water to get one kilogram of beef, and those cows produce a lot of methane," another potent greenhouse gas, Venter observed. "Why not get rid of the cows?" The replacement: meat grown in a test tube from microbes thanks to synthetic biology.

...look at the potential output from algae, and it's one to two orders of magnitude better than the best agricultural system. If we were trying to make liquid transportation fuels to replace all transportation fuels in the U.S. and you try and do that from corn it would take a facility three times the size of the continental U.S. If you try to do it from algae, it's a facility roughly the size of the state of Maryland. One is doable and the other's just absurd, but we don't have an algae lobby.

...We need three major ingredients: CO2, sunlight and seawater, aside from having the facility and refinery to convert all those things. We're looking at sites around the world that have the major ingredients. It helps if it's near a major refinery because that limits shipping distances. Moving billions of gallons of hydrocarbons around is expensive. But refineries are also a good source of concentrated CO2.

It's the integration of the entire process. [Synthetic Genomics] is not trying to become a fuel company. You won't see SGI gas stations out there, we're leaving that to ExxonMobil. We will help them shift the source of hydrocarbons to material recycled from CO2. _SciAm

Venter takes the "food vs. fuels" debate and turns it on its head: Why not make both, using the same type of platform?

Most journalists, energy analysts, policy makers, and academics have no concept of the biological potential of the planet Earth. Having fed their intuitions and imaginations on a steady diet of scarcity, they are at a loss in the larger world of actual possibilities.

But don't let the shortcomings of your overlords and masters in the media, government, and academia keep you from understanding the world as it is and as it could be. There is a whole new level of thought and existence coming. We simply need to survive until it gets here.

In the meantime: Hope for the best, prepare for the worst.

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.

Craig Venter Aims to Replace the Entire Petrochemical Industry

“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.” _NYT

NYT

Peak Oil will occur when humans no longer want to bother drilling into the ground to extract dark, gooey, messy liquids to turn into fuels. Instead, humans are slowly but surely developing other, more reliable and sustainable ways to fuel their industrial base and somewhat affluent lifestyles. Dieoff.orgiasts and other members of the Voluntary Human Extinction Movement hate to see any alternatives to Peak Oil Doom, or any skepticism to the orthodoxy of Catastrophic Anthropogenic Global Warming. But humans are innately a problem-solving and skeptical lot.

Craig Venter is one example of an unlikely problem solver. He was a poor student in his youth, and only after living through some harrowing experiences in Vietnam as a military medic was young Venter able to get his head on straight, and decide to do something with his life.

...Dr. Venter has a history of defying skeptics, and many people are betting that he will succeed this time as well. Dr. Walton, in fact, invested personally in Synthetic Genomics, and his venture firm, Oxford Bioscience Partners, recently wanted to sink a hefty sum into the company but was turned down when Dr. Venter found other investors offering better terms.

Exxon Mobil is giving Synthetic Genomics $300 million in research financing to design algae that could be used to produce gasoline and diesel fuel. (The new greenhouse will be used for that research.)

BP has invested in the company itself, turning to Synthetic Genomics to study microbes that might help turn coal deposits into cleaner-burning natural gas. Another investor, the Malaysian conglomerate Genting, wants to improve oil output from its palm tree plantations, working toward what its chief executive calls a “gasoline tree.”

...In the approach toward which Dr. Venter is driving, engineers would specify the entire genetic code of a cell — essentially the software that runs the cell — on computers, making design changes as if on a word processor. They would then press the “print” button, so to speak, and the DNA would be manufactured from its chemical components. The synthetic DNA would then be transplanted into an existing cell, where it would “boot up” and take control of the cell’s operations.

...Synthetic Genomics has about 130 employees. But much of its research, including the development of the synthetic cell, is done at the J. Craig Venter Institute. Synthetic Genomics pays for about 25 of the institute’s roughly 300 researchers, and has rights to their results. The rest of the institute’s funding comes mainly from federal grants and its endowment.... _NYT

Venter seems to love challenges and competitions. He lives to defy skeptics and to defeat rivals. And do you know the odd thing? The world is full of young Venters who have not yet -- and may never -- figured out what they want to do with their lives.

Pelted mercilessly with nightmarish predictions of doom and gloom, and instilled by governmenbt schools and indoctrinating universities with the futility of trying to fight their fate, hundreds of thousands of young Venters never amount to much -- when they might have done, given the right experiences in early life.

From an article published at Al Fin Energy

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.

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

Synthetic Biology Incorporated

An article at Biosingularity blog announces the formation of Synthetic Genomics, Inc., another Craig Ventner startup. Given the successful track record of Dr. Venter's enterprises, the prospects look pretty good for SGI.

Quoting from Biosingularity:
The ability to make extensive changes to the DNA of a chromosome, assemble it, and insert it into an organism is in its infancy, and the capability to assemble chromosome length strands of DNA will be key to the success of the company. Synthetic Genomics, Inc. is developing new scientific processes to enable industry to design and test desired genetic modifications. Using the genome as a bio-factory, a custom designed, modular “cassette” system will be developed so that the organism executes specific molecular functions. Synthetically produced organisms with reduced or reoriented metabolic needs will enable new, powerful, and more direct methods of bio-engineered industrial production.