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

Biohacking In Every High School Curriculum

Biohacking is growing in popularity among amateur bio-hobbyists, but government overseers of biological threats are concerned. The government is worried about dangerous organisms being created in basements, garages, and walk-in closets in ordinary neighborhoods -- perhaps your own. But should the same government efficiency that makes air travel such a pleasure, has totally eliminated drug and human smuggling across the border, and is currently destroying the private sector of the economy be applied to the close oversight of every closet, garage, and basement in America?

These hobbyists represent a growing strain of geekdom known as biohacking, in which do-it-yourselfers tinker with the building blocks of life in the comfort of their own homes. Some of them buy DNA online, then fiddle with it in hopes of curing diseases or finding new biofuels.

But are biohackers a threat to national security? ... biohackers argue that Mother Nature is more likely than any home hobbyist to create dangerous new pathogens. They cite the current A/H1N1 "swine flu" virus, which is a made-in-the-wild brew of human, bird and pig influenzas. Mackenzie Cowell, a founder of DIY Bio, says members aim to do good and are committed to working safely.

The movement has made big strides recently thanks to the commercial availability of synthetic DNA. This genetic material, normally found inside the nucleus of cells, can now easily be purchased online. That provides any amateur with the ingredients for constructing an organism....So far, most garage biologists playing around with synthetic DNA are simply adding a gene or two to an existing organism, a fairly standard scientific practice involving some test-tube mixing, and not something biosecurity experts are very worried about. But technology promises to allow the creation of entire organisms from scratch -- something academics are aiming to do in university labs -- and that has some experts worried. _WSJ

The government's instinct is to shut everything down that it conceives as the least threat. Far more rational, would be to train students from the earliest age in the science and safety of bio-research of all types.

The best answer to any kind of serious threat is an educated and informed public that has learned the competencies to respond effectively. Currently, government schools produce helpless incompetent sheep that must be protected and cared for at every turn. The pampering and coddling continues at every stage, so that instead of an informed and effective citizenry, the end result is a horde of confused, milling zombies capable of electing a government of smoothly deceptive clowns in hopes of being well taken care of.

Sorry, zombies, it doesn't work that way. Once the clowns are elected, they are obligated to do favours for their big money supporters. Trial lawyers, labour unions, billionaire bankers and speculators, eco-extremists.... And so it goes until it can't go any longer.

Al Fin is going on record in support of the training of children and youth to be truly competent across a wide range of skills -- some of them quite deadly. Make them smart, strong, and formidable. The ongoing experiment of turning children into lifelong pets isn't working out very well.

Grow Your Own Zombie Monkeys at Home!

The Apple computer was invented in a garage. Same with the Google search engine. Now, tinkerers are working at home with the basic building blocks of life itself...Using homemade lab equipment and the wealth of scientific knowledge available online, these hobbyists are trying to create new life forms through genetic engineering... _LAT

A lot of things are becoming possible for home hobbyists. You can build your own computers, brew your own beer, make your own lathes and mills, set up home sound and video recording studios, build your own rapid prototypers... But have you considered building your own genetic engineering lab at home -- and the things you might be able to grow in it?

In her San Francisco dining room lab, for example, 31-year-old computer programmer Meredith L. Patterson is trying to develop genetically altered yogurt bacteria that will glow green to signal the presence of melamine, the chemical that turned Chinese-made baby formula and pet food deadly.

...In Cambridge, Mass., a group called DIYbio is setting up a community lab where the public could use chemicals and lab equipment, including a used freezer, scored for free off Craigslist, that drops to 80 degrees below zero, the temperature needed to keep many kinds of bacteria alive.

Co-founder Mackenzie Cowell, a 24-year-old who majored in biology in college, said amateurs will probably pursue serious work such as new vaccines and super-efficient biofuels, but they might also try, for example, to use squid genes to create tattoos that glow.

Cowell said such unfettered creativity could produce important discoveries.

"We should try to make science more sexy and more fun and more like a game," he said. _LAT

One thing that home hobbyists may possess, is an unfettered imagination, without the need to publish peer-reviewed papers or to submit grant applications to brain-dead foundations and funding agencies. Humans enjoy playing games, from the earliest age. Making science and learning more like a game may bring astounding results.

Of course, growing your own army of zombie-monkeys to take over the world, is a bit beyond current technology. We cannot all be like the narcissist elect -- at least not yet. But soon. Study your biology, join your local "home brew" club, play life as a game. Imagine what you might achieve.

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.

Pimp My DNA---Biology in the Digital Age

This is a nice accessible 1 hour Google Tech video that explains the impact of high speed automation and data analysis in biomedical research. If you want to better understand where the genomic revolution is heading, take a look. ( Via Eye on DNA)

The video includes an introduction to "Systems Biology", a dynamic new field in biology that promises to radically alter most of the things we think we know about biology. It also looks at the historical background of DNA science, at the state of the art, at DNA engineering, and at open source genomics.

Highly provocative and mind-stretching.

Genetic Engineering: Drew Endy's Edge Interview

Drew Endy is one of the young and edgy bio-engineers who as an MIT professor is shaping the next generation of bio-engineers to be even edgier. Dizzy times? Even dizzier times coming!

Programming DNA is more cool, it's more appealing, it's more powerful than silicon. You have an actual living, reproducing machine; it's nanotechnology that works. It's not some Drexlarian (Eric Drexler) fantasy. And we get to program it. And it's actually a pretty cheap technology. You don't need a FAB Lab like you need for silicon wafers. You grow some stuff up in sugar water with a little bit of nutrients.

...in 2003 I taught a course at MIT, the Synthetic Biology Lab with some colleagues, and we had 16 students. For the last four years this course has been doubling every year, and it's now taught independently at about 60 schools in 30 or 40 countries worldwide, it's called IGEM, the International Genetically Engineered Machines competition. There are teams of teenagers from Germany programming DNA happily there, as well as Australia, Russia, Japan, China. The competition was won by the team from Peking University this year, and six or seven hundred students participated....How do you recognize this exponential and serve it and bring more people to participate in it?

...the previous generation of people working in biotechnology are scientists, and the ones coming up now are engineers. We're going to have to invent our new world of biotechnology and I suspect we'll learn lessons around biological safety from the past generation, but all the other lessons are up for grabs. The bio-security framework is going to collapse. The IT framework based on patents isn't going to scale, and the questions of playing God or not are so superficial and embarrassingly simple that they're not going to be useful in discussion.

There are some people who understand what's going on, and who are in a position, or who have comfort acting on time scales that are relevant. It is interesting for me to learn how difficult it is for folks to appreciate what an exponential technology really implies. The fact that sequencing goes from approximately zero to human genomes in ten years. The same thing is happening with construction of genomes. And with the parts collection—the standard biological parts doubling every year. And the same thing is happening with the number of teenagers who would like to do genetic engineering; it's doubling every year. How do you actually live in a world where you're surfing that exponential in a way that's constructive and responsible? Very few people get that.___Edge.org

Anyone trying to predict the future beyond the next 5 or 10 years in bio-medicine, bio-energy, bio-weapons, bio-nanotech, etc. is clearly at a disadvantage. Because there is absolutely no way of knowing what this djinn is going to do, now that it is out of its bottle.

New technology is allowing the talented and skilled youth of today and tomorrow entry into worlds of power and performance previously limited to only a few. The need for wise oversight and guidance has never been greater.

Radical DNA Future--Genetic Engineering Squared

Now that scientists are learning to insert artifical nucleic acid bases into DNA sequences, we are off for a wild ride in genetic engineering. Combining artificial nucleic acids with artificial amino acids should yield radically new peptides and enzymes, with designable shapes and characteristics.

Two artificial DNA "letters" that are accurately and efficiently replicated by a natural enzyme have been created by US researchers. Adding the two artificial building blocks to the four that naturally comprise DNA could allow wildly different kinds of genetic engineering, they say.

Eventually, the researchers say, they may be able to add them into the genetic code of living organisms....The unnatural but functional new base pair is the fruit of nearly a decade of research by chemical biologist Floyd Romesberg, at the Scripps Research Institute, La Jolla, California, US.

Romesberg and colleagues painstakingly created a library of nearly 200 potential new genetic bases that are slight variations on the natural ones. Unfortunately, none of them were similar enough in structure and chemistry to the real thing to be copied accurately by the polymerase enzymes that replicate DNA inside cells....The team is now eager to find out just what makes it work. "We still don't have a detailed understanding of how replication happens," says Romesberg. "Now that we have an unnatural base pair, we are continuing experiments to understand it better."

In the near future, Romesberg expects the new base pairs will be used to synthesize DNA with novel and unnatural properties. These might include highly specific primers for DNA amplification; tags for materials, such as explosives, that could be detected without risk of contamination from natural DNA; and building novel DNA-based nanomaterials....Romesberg notes that DNA and RNA are now being used for hundreds of purposes: for example, to build complex shapes, build complex nanostructures, silence disease genes, or even perform calculations. A new, unnatural, base pair could multiply and diversify these applications.

The most challenging goal, says Romesberg, will be to incorporate unnatural base pairs into the genetic code of organisms. "We want to import these into a cell, study RNA trafficking, and in the longest term, expand the genetic code and 'evolvability' of an organism."

New Scientist
Initially, the new DNA's will be used to study replication, then altered transcription and translation. But soon, all bets are off. Other artificial base pairs will be designed and built, and we will be off to the races.

Such discoveries illustrate how limited our understanding of basic life processes have been. If the enemies of genetic engineering thought they understood "the enemy," they could not have been more wrong.

More information at links at Brian Wang's NextBigFuture

The Body Becomes Accessible

Once it was difficult to target specific cells, and to insert proteins or genes into these cells. Now scientists are using nanotubes to open the door. From Stanford chemist Dai: "Dai's team also showed that carbon nanotubes could carry proteins and DNA into cells potentially to help deliver drugs or therapeutic genes. Compared with a solid spherical nanoparticle, a hollow nanotube has more surface area with which to carry molecules, explained biomolecular engineer Michael Strano at the University of Illinois at Urbana-Champaign. " Further, "Dai and his colleagues in August reported that by tagging carbon nanotubes so that they would specifically latch onto cancer cells and shining near-infrared lasers on them, they could kill just cancer cells without harming normal tissue."

Biosingularity blog is a rich field of information on biological advances. Recent reports of insertion of growth factors into failing heart muscle, and differentiation of heart myocyte stem cells are encouraging.

Using viruses to insert genes into cells caused problems, including the death of a child. Scientists backed off from that avenue of research until they could be assured that it was safe. Other types of forced entry into the cell were explored and found less risky, for the time being.

With the emergence of more accessible biohacking, and safer methods of gene insertion into cells, the scale of unregulated animal (mice, rats etc) experimentation into gene therapies may grow larger than the published and regulated experimentation. If ALF commandoes raid a university lab and "liberate" the animals, will they be making a dent in the overall structure of experimentation? Probably not.

Here is a simple manual to introduce an understanding of genes and gene therapy.