Craig Venter

Has synthesized a megabyte chromosome. Everything in the cell was derived from the chromosome and the natural traces were all deleted. They are digitizing biology. Converting analog genetic code to digital. Now they can go the other way, from ones and zeros to living organisms. Huge progress over past two decades. Big breakthrough new algorithm in 1995. New approach to sequencing pieces by breaking them down and putting into the computer. Government review process said it couldn’t work, so they had to find their own money. After it proved they worked, more money than they knew what to do with. Worked from microbes to humans in five years. First published in Science about ten years ago. First diploid genome in 2007. Used his own to avoid having to get permissions. It has now become de rigeur to put your genome on the Internet. Found that there is 1-3% difference between unreleated humans, which is ten times more than previously thought.

Had hoped for first synthetic species last year, but was wrong. Needed proofreading software. Had a sequence that could boot with ten synthetic sections and one natural one, so they knew where the problem was.

44% of genes have more than one heterozygous variant. Amazing that we have so much in common, and that things work as well as they do. Now can buy a small machine for half a million dollars that will sequence a genome in a couple days. Seeing more variation in Africa than between African, Venter, and Chinese.

NASA has been doing selection for a long time, but not calling it that, by screening for things like inner-ear changes, rapid bone regeneration, DNA repair, strong immune system, small stature, high energy utilization, low risk for genetic disease, etc. Have more microbes than human cells (we have several trillion bacteria), and their gene population exceeds ours by orders of magnitude. Millions of genes in mouth, intestinal tract, vagina, etc., and we don’t know much about them. Thousands of new ones brought up to ISS every trip. Have to understand out own genetic code, the codes of the microorganisms, and the interactions between them and the environment. Starting to make progress as we learn more. Esophageal cancer fastest growing one since seventies, and don’t know if microbes are causal, or symptom. Studying metabolomics of microbes. Ten percent of chemicals in our bloodstream are bacterial metabolites, and we don’t know if they help, hurt, cause or suppress disease, cause mood, etc. Need to know microbes and correlate. Important for space trips, and more important for long ones. Synthetic biome community might eliiminate disease organisms (infections and dental decay). Eliminate methanogens and sulfur producers. Body odor primarily caused by microbes. Best way to eliminate smell of armpits is to kill microbes (alcohol works better than perfume). Add cells that help metabolize algae-based food. There is an abundance of microbes (half of earth’s biomass). Has taken samples every two hundred miles in the ocean by filtering seawater, and sequence everything on the filters. Don’t know what they look like, but know what their genomes look like. Expected limited diversity in each area, but discovered great amount, and discovered many new organisms from sequencing. Also looked at deep-sea microbes near volcanic vent. Don’t need organic compounds, make everything from CO2 and hydrogen as energy source. Found same level of diversity deep in the earth, but more clusters like people expected in the oceans, perhaps because of radiation protection and less mutations. No point in sequencing new mammals to look for new genes — have probably seen it all, but microbes can provide new genes from any new sample.

Minimal life — smallest genome, 482 protein-coding genes and 43 RNA, discovered in 1995. Don’t know how small one can go, how many are essential for cellular life. Did gene knockouts, but discovered that only way to get there was synthesis. Comparative genomics can only take us so far. Over half of human genome are transposons, that can randomly insert in the cell. If cell survives gene replacement, defined as non-essential, but what’s essential and non-essential depends on context (e.g., sucrose and glucose can keep alive, but one or the other can’t). Knocking out a gene doesn’t tell you whether its function is essential, because there may be redundancy. Questions: could they make a synthetic DNA, and could they boot it up? Longer the genes, more errors, so needed error-correction methods. Discovered that the software could build its own hardware for virii. Thought it would be harder to boot up a full bacterium than a virus. Converted one species into another by reprogramming DNA. Isolated DNA, figured out ways to inject in a related cell. Thought would have to eliminate chromosome in recipient cell, but discovered that enzymatic processes in the cells would do it for them. Cell briefly has both chromosomes, it starts to make new enzymes, including restriction enzymes that chew up the original DNA, and a new cell with the coding of the donor cell. This allowed transplants (2007). They could then start to build up a new organism, piece by piece.

D/ radiodurans: “the ultimate DNA Assembly Machine.” Highly radiation resistant, but couldn’t get it to work outside the cell. Based on yeast, managed to assemble 600,000 base-pair organism, but couldn’t boot it up. Breakthrough was simple in-vitro recombination, with three enzymes, and one-step reaction at 50 degrees centigrade, allowing automation (just synthesized mouse genome). Can imagine robot that can “learn” how to do this, accelerating learning rate. Problem was assembling in a eucharyot, but having problem getting the chromosome from yeast and transplanting into another organism. Discovered that they had to methylate it. Now can modify things with yeast, isolate it, methylate it, and transplant into target organism. DNA synthesis no longer the barrier.

Now they’re watermarking the genes with things like quotes from James Joyce (got complaints from his estate for copyright violation). Idea is to put stop-codes in to not overrwrite critical parts.

They’re now up to a millions base pairs, and now that things are automatable, entering a new era. 40 million genes discovered to date, are the design base for the future. Will be able to specify metabolism to design future organisms. Because so much gene diversity, and so few scientists, need more approaches for rapid screening, and pass results on to the humans. select for chemical production, viability, etc.

Could use for mitigating carbon buildup, provide medicine, food, clean water as population grows. Three people alive on the planet for every person in 1946 when he was born, and soon four. Need new approaches. Plants not very productive systems, very limited, but microalgae has good potential (orders of magnitude better for fuel production). Only making ethonol from corn because there is a corn lobby, not because it’s smart. Designing fuels with CO2 as a carbon source. Instead of squeezing cells, getting them to pump the fuel out continuously. Exxon has put $600M on the line to do this. Expect useful economic processes in ten years. Have to design new algae strains to get there, because no natural ones will do the job. Food production for spaceflight very inefficient, but new designs can improve. Totally within the realm of the next few years. Microbial fuel cells also key application, with drinking water as output. Some bacteria use nanowires that can interface with the metal. Also working on reverse vaccinology, focusing on meningitus B and flu. Could help with rapid production of new vaccines, no longer grow them in chicken eggs.

Many reviews of the ethics of this: first priority of the Obama bioethics committee. This is likely to be the number one wealth generator for the next century. At early stages — first stage took fifteen years (longer than expected). What took years can now be done in a day, and shortly will be able to do millions of times per day.

For spaceflight, need to look at human genetic code, sequence microbiome to understand their influence on health and disease, and then all the issues from food, recycling waste, and perhaps even improve on stem cells to make us more radiation resistant/protective.

17 thoughts on “Craig Venter

  1. Trent Waddington

    I can beat that:

    Make a new organism that can grow in the atmosphere of Venus, storing nitrogen and oxygen internally and use the resulting buoyancy to maintain an internal/external pressure of 1 atm. Over years, a planetary canopy forms providing a new “surface” at ~50km with an Earth-like atmosphere. As an added bonus the canopy can grow fruit and other food crops.

  2. danae

    Outstanding synopsis! This man’s ingenuity and optimism are inspiring.

    You’re creating a monster–my book list. But your sacrifice is greatly appreciated.

  3. kurt9

    Its about time we start to see some developments in biotechnology. I like the radiation resistant stem cell regeneration therapy. I wonder if they can make synthetic stem cells that can function normally in micro-gravity.

  4. Tony (UK)

    Thanks for the writeup Rand!
    This is impressive stuff-he comes across as a very optimistic guy, who is in a position to really help people, and on a vast scale. I’ve not been following the biosciences so much, preferring the nano (appropriately named or not), non-standard fission and non-tokomak fusion efforts to create a better world. And space of course, always space…

    Its clear I need to do some more reading in this area.

    Now, all we need to do is get rid of the fascists and we’re good to go…

  5. Paul D.

    Very exciting stuff.

    Organisms spend a lot of energy just error-checking their DNA, so I wonder how much crop yields could be improved by editing out all the nonfunctional junk (assuming it *is* junk) DNA from their genomes.

    I’d also like to see organisms in which the genetic code has been shuffled. These would be immune to current viruses, kind of like a chip with a different set of opcodes.

  6. Mike K

    The most impressive thing about Venter, besides his intellect, is that he is doing all this with a private organization. This is free enterprise leaping ahead of government research. Biotech is probably the solution for energy eventually. We are also learning that a huge biomass extends deep, very deep, into the earth and probably the other terrestrial planets.

  7. paul breed

    Mr Venter is on avery short list of people w
    ho single handedly change the world.Im in awe.(sent from my phone)

  8. Bennett

    I read somewhere that the key is to live another 10-20 years. By then this science will have progressed to the point where one could live forever.

    Population pressures will probably keep it out of the hands of almost everyone, however…

    Great write up, Rand. Thanks!

  9. Joe Silva

    Another avenue to pursue: Understand the genetic basis of strength loss (bone, muscle,etc) due to low G, with an eye towards interventions at that level. It could be all in the regulatory networks. Being able to stem the loss due to lack of stress, for instance being bed ridden on earth, would have huge spin-offs.

  10. Pete

    Very impressive – thank you for writing this up.

    I am interested in the health implications, which are potentially huge (including radiation resistance, self repair, longevity, etc.).

    I doubt it will have much benefit on the energy front, improving on four billion years of evolution is not that easy – physics still applies, although better selecting specific traits will have a significant impact.

    It is difficult to compete with mechanical systems for performance, standard plants are typically only 1-2% efficient, algae up to maybe 7% with elevated CO2. Global biomass production is around 90TW per year, world energy use is around 18TW, but it would be nice to increase this say fivefold in the next 50 years (get everyone up to US levels plus some). Considering only a small proportion of this biomass is harvestable, biomass has significant limits, even if only desired for transport fuels. In contrast global wind is around 870TW and solar around 86PW. An area of 1000km by a 1000km of solar could serve the world’s energy needs and a 100TW of southern ocean wind is not an entirely economically inconceivable prospect. Nuclear is also a reasonable possibility.

    The problem is actually more carbon capture than energy. A 1.5MW wind turbine sweeps around 100kW worth of carbon dioxide (as converted into say methane). Extracting carbon from the atmosphere for conversion into hydrocarbons currently seems prohibitive at the scales desired – makes batteries and LH2 look good.

  11. Brock

    I’ve become jaded with the advances in computer-related technologies. Faster processors? Smaller phones? Ho hum.

    But this stuff? Synthetic life? Rearranging the genome of existing species? This reignites the feeling I am living in a sci-fi world.

    Pete said:
    Considering only a small proportion of this biomass is harvestable, biomass has significant limits, even if only desired for transport fuels. In contrast global wind is around 870TW and solar around 86PW.

    Apples & oranges. The only things that can be directly powered by thermal wind are dirigibles and politicians. The trick is that we need portable power.

    That means either liquid fuels (either put into an internal combustion engine or fuel cell) or much better batteries. Since no one is proposing a battery that can drive a car 500 miles or recharge in two minutes, liquid fuels are the way to go. And algae is the best way to do that.

  12. Pete

    Apples & oranges. The only things that can be directly powered by thermal wind are dirigibles and politicians. The trick is that we need portable power.

    That means either liquid fuels (either put into an internal combustion engine or fuel cell) or much better batteries. Since no one is proposing a battery that can drive a car 500 miles or recharge in two minutes, liquid fuels are the way to go. And algae is the best way to do that.

    There are a number of battery technologies under development that can likely do 500 mile ranges, if desired (silicon nanowire, lithium air, etc.). Similarly there are some rather fast recharge batteries under development, 10min is already available.

    Current CO2 waste streams are limited, Algae production using them can scale up only so far. Developing an economically viable method of mining CO2 for higher yield algae production seems very difficult. Note that the 90TW of global biomass includes all agricultural, natural and oceanic sources (it includes all the algae that grows in the oceans of the world). If algae is the best way to produce liquid fuels, where is it going to come from?

    Currently the world perhaps needs 10TW worth of liquid fuels, but that really needs to increase many times over the next few decades as the rest of the world catches up to the US in energy consumption and the US consumption continues to grow.

    This is one of the most useful global energy resource charts around – a good starting point to understanding the world’s energy options:

    http://gcep.stanford.edu/pdfs/GCEP_Exergy_Poster_web.pdf

  13. Brock

    Pete,

    Cool chart. I hadn’t seen that before.

    Just a couple points-

    1. Even if those ultra-dense, quick-charging batteries (or ultra-capacitors) come to market, I understand that handling that much concentrated electrical current is pretty dangerous. Having super-high-voltage sub-stations at every Exxon station seems pretty dangerous. Maybe it’s a manageable danger, but I’d still be very concerned. If the future of energy works out that there’s just no alternative to batteries I think it would be safer to have “swap out” technology rather than quick recharge.

    Either that or hybrid vehicles which run on batteries “most of the time” and only use liquid fuels for long distance driving. That ought to cut down demand for liquid fuels to a reasonable level.

    2. There are waste streams of CO2 that are currently not being tapped, such as the 250 million tons of waste Americans produce each year. A high temperature plasma furnace could reduce that all to constituent gases, including enough H2 to power the plasma furnace and CO2 for algae. And that’s just one example. Think of America’s lawn clippings.

    I’m not worried about CO2 sources. And if worse comes to worse, we can always get it from the same place trees do. It’s not concentrated, but it’s damn near infinite.

    3. I expect the algae to come from vertically stacked farms. They can get light and heat from nuclear power if sunlight isn’t good enough (which I expect it would be). Set aside a bit of Arizona or New Mexico (as a percentage of their land mass it would probably be less than the percent of Indiana used for growing corn), and you’re golden.

  14. Pete

    First steps will likely be to replace coal and natural gas with solar/wind/nuclear which frees up this carbon for conversion to liquid fuels. Transitioning to renewables would likely happen over many decades.

    If you have the carbon source (coal, natural gas, forestry/agricultural/animal waste), then algae does not actually gain that much. Most of these feed stocks are halfway to liquid fuels and they can probably be hydrogenated directly to use the rest of the carbon (say using nuclear energy). But beyond this batteries and LH2 (for larger applications) present themselves.

    Energy is actually potentially cheap, as is waste CO2, but beyond these supplies CO2 actually gets rather expensive – it is just so diffuse in the atmosphere. Extracting carbon from the atmosphere using plants has limits (90TW global total), artificial methods are similarly limited – this is a very nasty surface area problem.

    I would want to assume a future a few generations hence with almost ten times the global energy use of today, finding the energy to support this seems quite doable, finding the carbon to support a hydrocarbon future currently seems fundamentally problematic – hence looking for alternative mobile energy sources.

  15. Sam Dinkin

    Venter should focus on mastering clinical immortality rather than food. Food represents 6% of world GDP. I imagine Venter and his immitators could get a good fraction of the $150T in money and credit if they manage to hold on to the intellectual property associated with each increase in life expectancy. I would happily take out a loan for 20 years of my income to pay for it if I could live twice as long.

    Source of stats above: World Factbook

    Carbon is also a small part of the economy. Power from low carbon fossil fuels and nuclear cost only about $4/ton of CO2 more than coal power. In a time scale long enough to retire the coal plants in an orderly fashion, that’s a cost of only $60B/year to cut emmissions to half of 1990 levels (0.1% of world GDP). Even if the brass ring he goes for is all energy production, that’s still on the order of 10% of GDP ($6T/year).

    Doubling life expectancy ought to be worth 100% of GDP for 20 years. I.e., everyone in the world would might be willing to take out a mortgage for 20 years worth of wages in order to double their life expectancy.

  16. Jonathan Card

    This will probably get me into the Reactionary Hall of Fame (and it’s well after the post is old; it’s taken me some time to catch up on my Transterrestrial Musings after the last few weeks), but this presentation gave me the creeps. At one point, he compared a diagram of his genome and the one from nature they were mimicing. The natural one had a bunch of gray areas that weren’t genes, and his didn’t have any of them; he said that his was more efficient because they didn’t have any of the useless bits in them. It so happens that I was in the middle of the section of The Black Swan where he discusses the “Round Trip Fallacy”; he talks about how doctors sometimes mistake “I find no evidence of cancer” with “you don’t have cancer” and, more relevantly, how doctors in the 1960s made claims that breast milk was not more healthy than bottled milk because they found no evidence of difference between the two. A whole generation grew up with greater incidence of breast cancer and childhood diseases because of differences the doctors didn’t know to look for. So when he says things like, “removing these bits made the genome more efficient,” I’d be very impressed with how he really found “evidence of no function” rather than “no evidence of function”.

    I was also non-plussed by the fact that, while I can think of dozens of things to do with this technology in space, his first impulse was to engage in a Gattaca-like eugenics program, in defiance of the medical research recently finding that older people are much more resilient to launch-level G forces than expected (and possibly more than young people), rather than focusing on technologies like life-support and others.

    I’d be happy if he’d done the same work, but said, “we haven’t seen these sections do anything, so we removed them and we haven’t seen any difference is survival rates” or something, rather than, “ours is better because it doesn’t have this stuff”. I like the technology; I’m not advocating that he’s going to launch a plague of accidental pathogens upon mankind, but I wish he, personally, was as impressed by his ignorance as I was just listening to him.

    So, probably no one will read this, being posted so late, but I was a little disturbed.

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