Recently in Biological Technology Category
I'm Berkeley getting ready to take the stage for a panel at the Open Science Summit. Meredith Patterson just read her Biopunk Manifesto.
Read it.
You don't have to agree with everything she says. But whether you agree or not, remember that Science Always Wins.
Viva Garagista!
Read it.
You don't have to agree with everything she says. But whether you agree or not, remember that Science Always Wins.
Viva Garagista!
Here are the archived video and slides from last week's meeting of the Presidential Commission for the Study of Bioethical Issues. And here is the session with presentations from Drew Endy, Bonnie Bassler, and myself, followed by questions and discussion with the Commission and public.
Browser warning: When I ran it, something about the combination of Flash and the slide viewer caused Safari to freeze; Firefox was just fine.
Browser warning: When I ran it, something about the combination of Flash and the slide viewer caused Safari to freeze; Firefox was just fine.
Here are the annotated slides (PDF) from my presentation this morning to the Presidential Commission for the Study of Bioethical Issues. (Update -- A word to the wise; a "crore" is an Indian unit indicating 10,000,000. We had an errant extra zero in our database, and I have now fixed the Indian biotech GDP number to reflect the correction.)
Now sitting in the audience, I've just heard Jim Thomas of ETC once again egregiously distort the Keasling-Amyris-malaria-artemisinin story. As usual he is quite well-spoken and reasonable sounding, and uses rhetoric well to his ends.
It may be true, as Thomas asserts, that switching artemisinin production to fermentation will harm the economic livelihood of "a few thousand" (his words) farmers in China and Africa. But he has left out of his calculation the 40% of the world's population that is at risk of malaria every year. He has left out the millions of children who die annually from malaria.
Quoting from my book (pg.98 -- I've left out the references as I am liveblogging from the meeting):
How's that for rhetoric?
Update: One other thought. Just one year of 1.3% GDP growth recovered by reducing (eliminating?) the impact of malaria would more than offset paying wormwood farmers to grow something else. There is really no argument to do anything else.
For a "Civil Society" organization, ETC is being decidedly uncivil on this issue.
Now sitting in the audience, I've just heard Jim Thomas of ETC once again egregiously distort the Keasling-Amyris-malaria-artemisinin story. As usual he is quite well-spoken and reasonable sounding, and uses rhetoric well to his ends.
It may be true, as Thomas asserts, that switching artemisinin production to fermentation will harm the economic livelihood of "a few thousand" (his words) farmers in China and Africa. But he has left out of his calculation the 40% of the world's population that is at risk of malaria every year. He has left out the millions of children who die annually from malaria.
Quoting from my book (pg.98 -- I've left out the references as I am liveblogging from the meeting):
The cost burden of the disease on individual families is highly regressive. The average cost per household for treating malaria may be in the range of only 3-7 percent of income, but total and indirect costs to poor households can amount to one-third of annual income. The disease also disproportionately affects the young. Approximately 90percent of those who are killed by the parasite are African children under the age of five; according to the World Health Organization (WHO), a child dies from malaria roughly every thirty seconds.So, Mr. Thomas, what about all the people who will benefit from inexpensive malaria drugs? It is, frankly, unconscionable and indefensible for you to continue beating this drum as you do. The human cost of not producing inexpensive artemisinin in vats is astronomical. If reducing the burden of malaria around the world on almost 2 billion people might harm "a few thousand" farmers, then we should make sure those farmers can make a living growing some other crop. We can solve both problems. Your ideological opposition to synthetic biology is is blinding you to the opportunities, and your version of reality would ignore the health and welfare of children around the world.
In addition to staggering personal costs, the disease harms whole societies by severely inhibiting economic development. In affected countries, malaria reduces GDP growth by about 1.3 percent per year. These countries, moreover, contain about 40percent of the world's population. Over the past forty years, the growth penalty has created a difference in GDP that substantially exceeds the billions in annual foreign aid they receive. In 2000 the World Health Organization estimated that eliminating this growth penalty in 1965 would have resulted in "up to $100 billion added to sub-Saharan Africa's [2000] GDP of $300 billion. This extra $100 billion would be, by comparison, nearly five times greater than all development aid provided to Africa [in 1999]."
Because there was no technical means to eliminate the parasite in the middle of the twentieth century, this is clearly a number calculated to impress or shock, but the point is that the growth penalty continues to balloon. As of 2008, the GDPs of countries in sub-Saharan Africa would be approximately 35 percent higher than they are today had malaria been eliminated in 1965. The World Health Organization reckons that malaria-free countries have a per capita GDP on average three times larger than malarious countries. The productivity of farmers in malarious countries is cut by as much as 50 percent because of workdays lost to the disease. The impact of producing an effective and inexpensive antimalarial drug would therefore be profound.
Improving access to other technologies, such as bed nets treated with insecticides, would also be of substantial aid in reducing the rate of infection. Yet infected victims will still need access to cures. Prevention might be found in a vaccine, which the Gates Foundation also funds. However, even the most promising malaria vaccine candidates are only partially effective and cost even more than artemisinin. Microbial production of artemisinin would completely change the impact of malaria on billions of people worldwide. Artemisinin is presently derived from the wormwood tree and has been used as an herbal remedy for at least two thousand years. Its antimalarial activity was first described by Chinese scientists in 1971. The existence of the drug and its physiochemical properties were announced to the world in 1979, although its precise molecular mechanism of action is still not understood. A method for chemical synthesis was published in 1983, but it remains "long, arduous, and economically nonviable."
Because natural artemisinin is an agricultural product, it competes for arable land with food crops, is subject to seasonal variations in supply, and its production costs are in part determined by the costs of fertilizer and fuel. As a result of the work of Keasling and his collaborators, it appears that, within just a few years, biological technology may provide a more-flexible and less-expensive supply of drugs than now exists. Commercial production of artemisinin should commence in 2010, with a continuous annual production sufficient to treat the 500million malaria cases per year.
How's that for rhetoric?
Update: One other thought. Just one year of 1.3% GDP growth recovered by reducing (eliminating?) the impact of malaria would more than offset paying wormwood farmers to grow something else. There is really no argument to do anything else.
For a "Civil Society" organization, ETC is being decidedly uncivil on this issue.
Years ago, I frequently commuted between Los Angeles and Seattle by air. The contrast between the two cities was always a bit jarring, particularly in July and August -- high summer on the west coast of North America -- when the lawns in Seattle are brown while all the residential yards in Los Angeles are a beautiful emerald green. Summer rainfall in Seattle is usually about 1.8 inches spread over those two months, while Los Angeles is essentially dry.
A couple of weeks ago I flew into LAX from the east coast and got another perspective on water use there. My first glimpse of the basin was the smog lapping up against the rim of the San Gabriel Mountains. I managed to snap a quick photo after we had flown over the ridge (the smog is on the lower left, though the contrast was more impressive when we were looking from the east side).
Even in May it looks a little dry 'round those parts.
A few minutes later, I noticed large green patches covering the sides (usually the west side) of hills. This continued all the way to downtown LA, and we were high enough for most of that time that I couldn't figure out why the locals were spending so much of their precious water keeping the sunset sides of hills green. Then, finally, we passed over one low enough that the purpose jumped out at me.
Cemeteries.
Even in death, Los Angelinos maintain their homage to William Mulholland by keeping him eternally damp. And in death, Los Angelinos continue to contribute to the smog shown above -- the grass covering the land of the dead is trimmed quite short. Many, many square miles of it. A cushy life, have those dead people. And to be fair to Los Angeles (which, admittedly, is hard for me), Seattle, too, uses a great deal of water and hydrocarbons to keep our decaying ancestors covered with a trim layer of green. It happens everywhere here. Welcome to America.
Even the way the US irrigates land to feed the living represents a profligate use of water. According to the USDA, 80% of the water consumed in this country goes to agriculture. (Note that "use" and "consumption" are often confused. Agriculture and thermoelectric power generation both "use" about 40% of the nation's freshwater, but while almost 100% of the water used for power generation is returned to where it was taken from -- albeit somewhat warmer than when it was taken -- much of the of water put on crops is does not reach the roots or is evaporated and lost to the atmosphere.) Notice that I did not use the word "waste", because some of the leakage winds up back in groundwater, or otherwise finds its way into the environment in a way that might be classified as "beneficial".
And pondering water use here in the US, and the impact on our economy, my thoughts turn to water use in Asia. Much ado was made in the last couple of years about the IPCC report of anomalous melting of Asian glaciers, followed by the discovery that there was no actual data behind the assertion.
A recent paper in Science adds some much needed analysis to the story. Walter Immerzeel and colleagues set out to understand the relative importance of meltwater and rainwater to river flows in Asia. It is interesting to me that this sort of analysis wasn't done before now: "Earlier studies have addressed the importance of glacial and snow melt and the potential effects of climate change on downstream hydrology, but these are mostly qualitative or local in nature."
For five large river basins the authors used a combination of precipitation data, snow melt models, and evaporation rates, to calculate the Normalized Melt Index (NMI). The NMI is the ratio of snow and glacier discharge to downstream discharge. If all the water in a river downstream is from melting, then this ratio is obviously one; if the ratio is less than one, rainfall contributes more than meltwater, and if it larger than one, more water is lost through evaporation or other processes (like agriculture) and meltwater is more important for total flow.
Here are the results. For each of the rivers, the authors calculated the percentage of the total discharge generated by snow and glacial melt:
In other words, water supplies in the Indus river valley are largely dependent on meltwater, whereas the large river systems in China appear to be less dependent on meltwater. That is a very interesting result, because the story told by lots of people (including myself) about the future of water in China is that they are in big trouble due to glacial melting in the Himalayas. Assuming this result holds up, China may be better off in a warmer world that I had anticipated.
The authors also used various projections of snow and rainfall to estimate what water supplies would look like in these rivers in 2050. As you might expect, a warmer world leads to less snowfall, more melting, and lower river flows. But as the warmer world brings increased rainfall, the impact is smaller than has been widely assumed. I am not going to bother putting any of the numbers in here, because, as the authors note, "Results should be treated with caution, because most climate models have difficulty simulating mean monsoon and the interannual precipitation variation, despite recent progress in improving the resolution of anticipated spatial and temporal changes in precipitation."
But they went one step further and tried to estimate the effects of potential decreased water supply on local food supplies. Couched in terms of crop yields, etc., Immerzeel et al estimate that the Brahmaputra will support about 35 million fewer people, the Indus will support about 26 million fewer people -- that's food for 60 million fewer people in India and Pakistan, if you are counting -- and the Yellow about 3 million more people. Finishing up, they write:
And even Lovett appears to acknowledge that reducing the human carrying capacity of the Brahmaputra and Indus river valleys by 60 million people is something to be concerned about. From Lovett:
A couple of weeks ago I flew into LAX from the east coast and got another perspective on water use there. My first glimpse of the basin was the smog lapping up against the rim of the San Gabriel Mountains. I managed to snap a quick photo after we had flown over the ridge (the smog is on the lower left, though the contrast was more impressive when we were looking from the east side).
Even in May it looks a little dry 'round those parts.A few minutes later, I noticed large green patches covering the sides (usually the west side) of hills. This continued all the way to downtown LA, and we were high enough for most of that time that I couldn't figure out why the locals were spending so much of their precious water keeping the sunset sides of hills green. Then, finally, we passed over one low enough that the purpose jumped out at me.
Cemeteries.
Even in death, Los Angelinos maintain their homage to William Mulholland by keeping him eternally damp. And in death, Los Angelinos continue to contribute to the smog shown above -- the grass covering the land of the dead is trimmed quite short. Many, many square miles of it. A cushy life, have those dead people. And to be fair to Los Angeles (which, admittedly, is hard for me), Seattle, too, uses a great deal of water and hydrocarbons to keep our decaying ancestors covered with a trim layer of green. It happens everywhere here. Welcome to America.
Even the way the US irrigates land to feed the living represents a profligate use of water. According to the USDA, 80% of the water consumed in this country goes to agriculture. (Note that "use" and "consumption" are often confused. Agriculture and thermoelectric power generation both "use" about 40% of the nation's freshwater, but while almost 100% of the water used for power generation is returned to where it was taken from -- albeit somewhat warmer than when it was taken -- much of the of water put on crops is does not reach the roots or is evaporated and lost to the atmosphere.) Notice that I did not use the word "waste", because some of the leakage winds up back in groundwater, or otherwise finds its way into the environment in a way that might be classified as "beneficial".
And pondering water use here in the US, and the impact on our economy, my thoughts turn to water use in Asia. Much ado was made in the last couple of years about the IPCC report of anomalous melting of Asian glaciers, followed by the discovery that there was no actual data behind the assertion.
A recent paper in Science adds some much needed analysis to the story. Walter Immerzeel and colleagues set out to understand the relative importance of meltwater and rainwater to river flows in Asia. It is interesting to me that this sort of analysis wasn't done before now: "Earlier studies have addressed the importance of glacial and snow melt and the potential effects of climate change on downstream hydrology, but these are mostly qualitative or local in nature."
For five large river basins the authors used a combination of precipitation data, snow melt models, and evaporation rates, to calculate the Normalized Melt Index (NMI). The NMI is the ratio of snow and glacier discharge to downstream discharge. If all the water in a river downstream is from melting, then this ratio is obviously one; if the ratio is less than one, rainfall contributes more than meltwater, and if it larger than one, more water is lost through evaporation or other processes (like agriculture) and meltwater is more important for total flow.
Here are the results. For each of the rivers, the authors calculated the percentage of the total discharge generated by snow and glacial melt:
|
Indus |
151% |
|
Brahmaputra |
27% |
|
Ganges |
10% |
|
Yangtze |
8% |
|
Yellow |
8% |
In other words, water supplies in the Indus river valley are largely dependent on meltwater, whereas the large river systems in China appear to be less dependent on meltwater. That is a very interesting result, because the story told by lots of people (including myself) about the future of water in China is that they are in big trouble due to glacial melting in the Himalayas. Assuming this result holds up, China may be better off in a warmer world that I had anticipated.
The authors also used various projections of snow and rainfall to estimate what water supplies would look like in these rivers in 2050. As you might expect, a warmer world leads to less snowfall, more melting, and lower river flows. But as the warmer world brings increased rainfall, the impact is smaller than has been widely assumed. I am not going to bother putting any of the numbers in here, because, as the authors note, "Results should be treated with caution, because most climate models have difficulty simulating mean monsoon and the interannual precipitation variation, despite recent progress in improving the resolution of anticipated spatial and temporal changes in precipitation."
But they went one step further and tried to estimate the effects of potential decreased water supply on local food supplies. Couched in terms of crop yields, etc., Immerzeel et al estimate that the Brahmaputra will support about 35 million fewer people, the Indus will support about 26 million fewer people -- that's food for 60 million fewer people in India and Pakistan, if you are counting -- and the Yellow about 3 million more people. Finishing up, they write:
We conclude that Asia's water towers are threatened by climate change, but that the effects of climate change on water availability and food security in Asia differ substantially among basins and cannot be generalized. The effects in the Indus and Brahmaputra basins are likely to be severe owing to the large population and the high dependence on irrigated agriculture and meltwater. In the Yellow River, climate change may even yield a positive effect as the dependence on meltwater is low and a projected increased upstream precipitation, when retained in reservoirs, would enhance water availability for irrigated agriculture and food security.I am perplexed by the take on these results over at Nature News by Richard Lovett. His piece carries the title, "Global warming's impact on Asia's rivers overblown". I'll give Lovett the out that he may not have written the actual headline (Editors!), but nonetheless he sets up the Immerzeel paper as a big blow to some unnamed group of doomsayers. Perhaps he imagines that Immerzeel completely undermines the IPCC report? This is hardly the case. As I wrote last January, sorting out the mistake over Himalayan melting rates is an example of science working through a blunder. Instead overturning some sort of vague conspiracy, as best I can tell Immerzeel is simply the first real effort to make quantitative assessments of something to which much more attention should have been paid, much earlier than it was.
And even Lovett appears to acknowledge that reducing the human carrying capacity of the Brahmaputra and Indus river valleys by 60 million people is something to be concerned about. From Lovett:
The findings are important for policy-makers, says Jeffrey Kargel, a glaciologist at the University of Arizona in Tucson. "This paper adds to mounting evidence that the Indus Basin [between India and Pakistan] is particularly vulnerable to climate change," says Kargel. "This is a matter that obviously concerns India and Pakistan very much."Indeed. As they should concern us all.
I'll be speaking at the first meeting of President Obama's Bioethics Commission is July 8-9 in Washington DC.
The topic is Synthetic Biology. Here is the agenda.
Location: The Ritz-Carlton Washington, DC 1150 22nd Street, NW Washington, DC 20037
The topic is Synthetic Biology. Here is the agenda.
Location: The Ritz-Carlton Washington, DC 1150 22nd Street, NW Washington, DC 20037
The press is all abuzz over the Venter Institute's paper last week demonstrating a functioning synthetic genome. Here is the Gibson et al paper in Science, and here are takes from the NYT and The Economist (lede, story). The Economist story has a figure with the cost and productivity data for gene and oligo synthesis, respectively. Here also are Jamais Cascio and Oliver Morton, who points to this collection of opinions in Nature.
The nuts and bolts (or bases and methylases?) of the story are this: Gibson et al ordered a whole mess of pieces of relatively short, synthetic DNA from Blue Heron and stitched that DNA together into full length genome for Bug B, which they then transplanted into a related microbial species, Bug A. The transplanted genome B was shown to be fully functional and to change the species from old to new, from A to B. Cool.
Yet, my general reaction to this is the same as it was the last time the Venter team claimed they were creating artificial life. (How many times can one make this claim?) The assembly and boot-up are really fantastic technical achievements. (If only we all had the reported $40 million to throw at a project like this.) But creating life, and the even the claim of creating a "synthetic cell"? Meh.
(See my earlier posts, "Publication of the Venter Institute's synthetic bacterial chromosome", January 2008, and "Updated Longest Synthetic DNA Plot ", December 2007.)
I am going to agree with my friends at The Economist (see main story) that the announcement is "not unexpected", and disagree strongly that "The announcement is momentous." DNA is DNA. We have known that for, oh, a long time now. Synthetic DNA that is biologically indistinguishable from "natural DNA" is, well, biologically indistinguishable from natural DNA. This result is at least thirty years old, when synthetic DNA was first used to cause an organism to do something new. There are plenty of other people saying this in print, so I won't belabor the point; see, for example, the comments in the NYT article.
One less-than-interesting outcome of this paper is that we are once again going to read all about the death of vitalism (see the Nature opinion pieces). Here are the first two paragraphs from Chapter 4 of my book:
Somewhat more intriguing will be the debate around whether it is the atoms in the genome that are interesting or instead the information conveyed by the arrangement of those atoms that we should care about. Clearly, if nothing else this paper demonstrates that the informational code determines species. This isn't really news to anyone who has thought about it (except, perhaps, to IP lawyers -- see my recent post on the breast cancer gene lawsuit) but it might get a broader range of people thinking more about life as information. What then, does "creating life" mean? Creating information? Creating sequence? And what sort of design tools do we need to truly control these creations? Are we just talking about much better computer simulations, or is there more physics to learn, or is it all just too complicated? Will we be forever chasing away ghosts of vitalism?
That's all I have for deep meaning at the moment. I've hardly just got off one set of airplanes (New York-DC-LA) and have to get on another for Brazil in the morning.
I would, however, point out that the recent paper describes what may be a species-specific processing hack. From the paper:
Since Gibson et al have in fact built an impressive bit of DNA, here is an updated "Longest Synthetic DNA Plot" (here is the previous version with refs.); alas, the one I published just a few months ago in Nature Biotech is already obsolete (hmph, they have evidently now stuck it behind a pay wall).
A couple of thoughts: As I noted in DNA Synthesis "Learning Curve": Thoughts on the Future of Building Genes and Organisms (July 2008), it isn't really clear to me that this game can go on for much longer. Once you hit a MegaBase (1,000,000 bases, or 1 MB) in length, you are basically at a medium-long microbial genome. Another order of magnitude or so gets you to eukaryotic chromosomes, and why would anyone bother building a contiguous chuck of DNA longer than that? Eventually you get into all the same problems that the artificial chromosome community has been dealing with for decades -- namely that chromatin structure is complex and nobody really knows how to build something like it from scratch. There is progress, yes, and as soon as we get a real mammalian artificial chromosome all sorts of interesting therapies should become possible (note to self: dig into the state of the art here -- it has been a few years since I looked into artificial chromosomes). But with the 1 MB milestone I suspect people will begin to look elsewhere and the typical technology development S-curve kicks in. Maybe the curve has already started to roll over, as I predicted (sketched in) with the Learning Curve.
Finally, I have to point out that the ~1000 genes in the synthetic genome are vastly more than anybody knows how to deal with in a design framework. I doubt very much that the JCVI team, or the team at Synthetic Genomics, will be using this or any other genome in any economically interesting bug any time soon. As I note in Chapter 8 of Biology is Technology, Jay Keasling's lab and the folks at Amyris are playing with only about 15 genes. And getting the isoprenoid pathway working (small by the Gibson et al standard but big by the everyone-else standard) took tens of person years and about as much investment (roughly ~$50 million in total by the Gates Foundation and investors) as Venter spent on synthetic DNA alone. And then is Synthetic Genomics going to start doing metabolic engineering in a microbe that they only just sequenced and about which relatively little is known (at least compared with E. coli, yeast, and other favorite lab animals)? Or they are going to redo this same genome synthesis project in a bug that is better understood and will serve as a platform or chassis? Either way, really? The company has hundreds of millions of dollars in the bank to spend on this sort of thing, but I simply don't understand what the present publication has to do with making any money.
So, in summary: very cool big chuck of synthetic DNA being used to run a cell. Not artificial life, and neither artificial cell nor synthetic cell. Probably not going to show up in a product, or be used to make a product, for many years. If ever. Confusing from the standpoint of project management, profit, and economic viability.
But I rather hope somebody proves me wrong about that and surprises me soon with something large, synthetic, and valuable. That way lies truly world changing biological technologies.
The nuts and bolts (or bases and methylases?) of the story are this: Gibson et al ordered a whole mess of pieces of relatively short, synthetic DNA from Blue Heron and stitched that DNA together into full length genome for Bug B, which they then transplanted into a related microbial species, Bug A. The transplanted genome B was shown to be fully functional and to change the species from old to new, from A to B. Cool.
Yet, my general reaction to this is the same as it was the last time the Venter team claimed they were creating artificial life. (How many times can one make this claim?) The assembly and boot-up are really fantastic technical achievements. (If only we all had the reported $40 million to throw at a project like this.) But creating life, and the even the claim of creating a "synthetic cell"? Meh.
(See my earlier posts, "Publication of the Venter Institute's synthetic bacterial chromosome", January 2008, and "Updated Longest Synthetic DNA Plot ", December 2007.)
I am going to agree with my friends at The Economist (see main story) that the announcement is "not unexpected", and disagree strongly that "The announcement is momentous." DNA is DNA. We have known that for, oh, a long time now. Synthetic DNA that is biologically indistinguishable from "natural DNA" is, well, biologically indistinguishable from natural DNA. This result is at least thirty years old, when synthetic DNA was first used to cause an organism to do something new. There are plenty of other people saying this in print, so I won't belabor the point; see, for example, the comments in the NYT article.
One less-than-interesting outcome of this paper is that we are once again going to read all about the death of vitalism (see the Nature opinion pieces). Here are the first two paragraphs from Chapter 4 of my book:
"I must tell you that I can prepare urea without requiring a kidney of an animal, either man or dog." With these words, in 1828 Friedrich Wöhler claimed he had irreversibly changed the world. In a letter to his former teacher Joens Jacob Berzelius, Wöhler wrote that he had witnessed "the great tragedy of science, the slaying of a beautiful hypothesis by an ugly fact." The beautiful idea to which he referred was vitalism, the notion that organic matter, exemplified in this case by urea, was animated and created by a vital force and that it could not be synthesized from inorganic components. The ugly fact was a dish of urea crystals on his laboratory bench, produced by heating inorganic salts. Thus, many textbooks announce, was born the field of synthetic organic chemistry.Care to guess where the nucleotides came from that went into the Gibson et al synthetic genome? Probably purified and reprocessed from sugarcane. Less probably salmon sperm. In other words, the nucleotides came from living systems, and are thus tainted for those who care about such things. So much for another nail in the vital coffin.
As is often the case, however, events were somewhat more complicated than the textbook story. Wöhler had used salts prepared from tannery wastes, which adherents to vitalism claimed contaminated his reaction with a vital component. Wöhler's achievement took many years to permeate the mind-set of the day, and nearly two decades passed before a student of his, Hermann Kolbe, first used the word "synthesis" in a paper to describe a set of reactions that produced acetic acid from its inorganic elements.
Somewhat more intriguing will be the debate around whether it is the atoms in the genome that are interesting or instead the information conveyed by the arrangement of those atoms that we should care about. Clearly, if nothing else this paper demonstrates that the informational code determines species. This isn't really news to anyone who has thought about it (except, perhaps, to IP lawyers -- see my recent post on the breast cancer gene lawsuit) but it might get a broader range of people thinking more about life as information. What then, does "creating life" mean? Creating information? Creating sequence? And what sort of design tools do we need to truly control these creations? Are we just talking about much better computer simulations, or is there more physics to learn, or is it all just too complicated? Will we be forever chasing away ghosts of vitalism?
That's all I have for deep meaning at the moment. I've hardly just got off one set of airplanes (New York-DC-LA) and have to get on another for Brazil in the morning.
I would, however, point out that the recent paper describes what may be a species-specific processing hack. From the paper:
...Initial attempts to extract the M. mycoides genome from yeast and transplant it into M. capricolum failed. We discovered that the donor and recipient mycoplasmas share a common restriction system. The donor genome was methylated in the native M. mycoides cells and was therefore protected against restriction during the transplantation from a native donor cell. However, the bacterial genomes grown in yeast are unmethylated and so are not protected from the single restriction system of the recipient cell. We were able to overcome this restriction barrier by methylating the donor DNA with purified methylases or crude M. mycoides or M. capricolum extracts, or by simply disrupting the recipient cell's restriction system.This methylation trick will probably -- probably -- work just fine for other microbes, but I just want to point out that it isn't necessarily generalizable and that the JVCI team didn't demonstrate any such thing. The team got this one bug working, and who knows what surprises wait in store for the next team working on the next bug.
Since Gibson et al have in fact built an impressive bit of DNA, here is an updated "Longest Synthetic DNA Plot" (here is the previous version with refs.); alas, the one I published just a few months ago in Nature Biotech is already obsolete (hmph, they have evidently now stuck it behind a pay wall).
A couple of thoughts: As I noted in DNA Synthesis "Learning Curve": Thoughts on the Future of Building Genes and Organisms (July 2008), it isn't really clear to me that this game can go on for much longer. Once you hit a MegaBase (1,000,000 bases, or 1 MB) in length, you are basically at a medium-long microbial genome. Another order of magnitude or so gets you to eukaryotic chromosomes, and why would anyone bother building a contiguous chuck of DNA longer than that? Eventually you get into all the same problems that the artificial chromosome community has been dealing with for decades -- namely that chromatin structure is complex and nobody really knows how to build something like it from scratch. There is progress, yes, and as soon as we get a real mammalian artificial chromosome all sorts of interesting therapies should become possible (note to self: dig into the state of the art here -- it has been a few years since I looked into artificial chromosomes). But with the 1 MB milestone I suspect people will begin to look elsewhere and the typical technology development S-curve kicks in. Maybe the curve has already started to roll over, as I predicted (sketched in) with the Learning Curve. Finally, I have to point out that the ~1000 genes in the synthetic genome are vastly more than anybody knows how to deal with in a design framework. I doubt very much that the JCVI team, or the team at Synthetic Genomics, will be using this or any other genome in any economically interesting bug any time soon. As I note in Chapter 8 of Biology is Technology, Jay Keasling's lab and the folks at Amyris are playing with only about 15 genes. And getting the isoprenoid pathway working (small by the Gibson et al standard but big by the everyone-else standard) took tens of person years and about as much investment (roughly ~$50 million in total by the Gates Foundation and investors) as Venter spent on synthetic DNA alone. And then is Synthetic Genomics going to start doing metabolic engineering in a microbe that they only just sequenced and about which relatively little is known (at least compared with E. coli, yeast, and other favorite lab animals)? Or they are going to redo this same genome synthesis project in a bug that is better understood and will serve as a platform or chassis? Either way, really? The company has hundreds of millions of dollars in the bank to spend on this sort of thing, but I simply don't understand what the present publication has to do with making any money.
So, in summary: very cool big chuck of synthetic DNA being used to run a cell. Not artificial life, and neither artificial cell nor synthetic cell. Probably not going to show up in a product, or be used to make a product, for many years. If ever. Confusing from the standpoint of project management, profit, and economic viability.
But I rather hope somebody proves me wrong about that and surprises me soon with something large, synthetic, and valuable. That way lies truly world changing biological technologies.
Tomorrow evening, May 19th, I will give a short talk about my recent book Biology is Technology at Reiter's Books in Washington DC, followed by discussion and refreshments. Among other issues, I will discuss updated figures for the impact of biotech and bioengineering on the US and world economies, the impact of the recent BRCA 1/2 gene patent decision, garage biotech, biosecurity, and regulation.
I look forward to seeing you there -- please bring hard questions.
Biology is Technology: The Promise, Peril, and New Business of Engineering Life
Robert Carlson
Harvard University Press, 2010
www.biologyistechnology.com
Where:
(Note that Reiter's has recently moved.)
Reiter's Books
1900 G St. NW
Washington DC 20006
www.reiters.com
When:
May 19, 2010
6:30 PM
I look forward to seeing you there -- please bring hard questions.
Biology is Technology: The Promise, Peril, and New Business of Engineering Life
Robert Carlson
Harvard University Press, 2010
www.biologyistechnology.com
Where:
(Note that Reiter's has recently moved.)
Reiter's Books
1900 G St. NW
Washington DC 20006
www.reiters.com
When:
May 19, 2010
6:30 PM
- Last January, the UPMC Center for Biosecurity published "U.S. Government Judgments on the Threat of Biological Weapons: Official Assessments, 2004-2009". If you are interested in bioterrorism, you should have a look.
- Also in January, the Belfer Center for Science and International Affairs at Harvard's Kenney School of Government released "Al Qaeda Weapons of Mass Destruction Threat: Hype or Reality?" (PDF) By Rolf Mowatt-Larssen. The document gathers together open source information regarding Al Qaeda's interest in WMD. Mowatt-Larssen is formerly the Director of Intelligence and Counterintelligence at the U.S. Department of Energy, and spent 23 years at the CIA. The introduction sets out the purpose of the document as dispelling the doubts of those skeptical there is a real threat.
- Former Senate Intelligence Committee chairman Bob Graham recently told the Washington Post that "India and Pakistan, as well as Syria and Israel, may have manufactured biological weapons." Graham said: "The extent to which they may have done it is classified, but it is a serious threat. ...A couple of weeks in the Middle East has given me a greater sense of urgency." Graham called out the lack of progress here at home in establishing "a response capability". In an update to the story, the Post then pointed to a description of a new "biosecurity" bill introduced in the House, which from the article sounds to be all about securing national labs rather than standing up any sort of real biodefense response capability.
This morning's biosecurity update from the Partnership for Global Security carried a mess of links I hadn't seen, including a story at the BBC entitled "Tech Know: Life hacking with 3D printing and DIY DNA kits". The embedded video has an interesting clip on a printed stainless steel Mobius strip with freely moving rings that can run around the perimeter -- interlinked complex shapes. Neat. (Not a new thing in plastics, but I hadn't seen it in metal before.)
Cambridge's James Brown gets the honor of introducing the Beeb's audience to synthetic biology, biobricks, and engineering methods for biological systems. The 3D-printed DremelFuge gets a photo and a significant mention. I explicitly pointed to this sort of application of 3D printing in my book, though it is happening even faster than I had imagined. Shapeways is now printing all sorts of interesting materials, though the resolution of most 3D printers and processes still doesn't make them useful for the sorts of objects I want to print. That said, there is clear improvement over time.
It will be interesting to see how long it takes before you can print mixed media functional objects, say something like a zero-dead volume, positive displacement membrane pump. Or better yet an entire pump block. (Which is usually milled from a piece of stainless steel -- see where this is going?) That gets you the most annoying bit of kit needed for a DNA synthesizer. At which point you can forget any regulations limiting access to DNA of any sequence.
Cambridge's James Brown gets the honor of introducing the Beeb's audience to synthetic biology, biobricks, and engineering methods for biological systems. The 3D-printed DremelFuge gets a photo and a significant mention. I explicitly pointed to this sort of application of 3D printing in my book, though it is happening even faster than I had imagined. Shapeways is now printing all sorts of interesting materials, though the resolution of most 3D printers and processes still doesn't make them useful for the sorts of objects I want to print. That said, there is clear improvement over time.
It will be interesting to see how long it takes before you can print mixed media functional objects, say something like a zero-dead volume, positive displacement membrane pump. Or better yet an entire pump block. (Which is usually milled from a piece of stainless steel -- see where this is going?) That gets you the most annoying bit of kit needed for a DNA synthesizer. At which point you can forget any regulations limiting access to DNA of any sequence.
