A few notes to keep in mind with the interpretation of the results:
1. The macronutrient consumption data are based on food frequency questionaires, a somewhat unreliable means to measuring food consumption. How accurate do you think you'd be if asked about how much of each type of food you ate over the past few months? For more disucssion of problems with food frequency questionaires and other general issues with studies on nutrition see: http://fivethirtyeight.com/fea...
2. The study is an observational study that can only assess correlation, not causation. People who reported eating more carbohydrates had higher mortality. Was eating more carbohydrates the cause of the higher mortality, or were there other differences between people who ate more carbohydrates and those who ate less? A common problem with these studies is that people who follow dietary guidelines are more likely to follow other guidelines for healthy living, so one could just be picking up a signal from decreased mortality of those who pay attention to their health in general. Socioeconomic factors are another potential confounding factor in the results. In many of the third world countries studied, a diet higher in animal protein would likely be more expensive than a diet higher in carbohydrates. These confounding variables make inferring causation difficult. Randomized controlled trials would provide a gold standard for assessing whether there is a causal relationship between carbohydrate intake and mortality, though these are notoriously difficult to perform (how do you get a large cohort of people to change their diets for long periods of time?).
3. Even if the differences in diet are causally related to the changes in mortality and CV events, the exact mechanism is unclear. For example, in a commentary published in the Lancet along side the research paper (I would recommend reading the commentary if you are interested in the subject), the authors note:
Micronutrient malnutrition is an important problem in many of the countries included in PURE. Animal products are rich sources of zinc, bioavailable iron, vitamin K2, and vitamin B12, which might be suboptimal in populations consuming high carbohydrate diets. Therefore, one potential explanation for the PURE results is that nutrient-dense meats corrected one or more nutrient deficiencies
If the results are partly due to consumption of animal products alleviating micronutrient malnutrition, it is unclear whether the results would be as applicable in populations where micronutrient malnutrition is not an issue.
Overall, the study is a very important piece of evidence in determining the best amount of carbohydrates, proteins and fats to include in one's diet. However, it is not a definitive study, so one needs to consider the entire body of evidence including observational studies (such as this one) done in a number of different populations, randomized clinical trials, and laboratory experiments that get at the mechanisms involved.
Other physicists have expressed skepticism over the Harvard group's claims of making metallic hydrogen. Importantly, the claim is made on the basis of one single experiment that has not yet been replicated by the group reporting the claims. From a news article published in Nature:
Other researchers aren't convinced. It’s far from clear that the shiny material the researchers see is actually hydrogen, says geophysicist Alexander Goncharov of the Carnegie Institution for Science in Washington DC. Goncharov has criticized the Silvera lab’s methods before. He suggests that the shiny material may be alumina (aluminium oxide), which coats the tips of the diamonds in the anvil, and may behave differently under pressure.
Loubeyre and others think that Silvera and Dias are overestimating the pressure that they reached, by relying on an imprecise calibration between turns of the screw and pressure inside the anvil. Eugene Gregoryanz, a physicist at the University of Edinburgh, UK, adds that part of the problem is that the researchers took only a single detailed measurement of their sample at the highest pressure — making it hard to see how pressure shifted during the experiment.
I can think of a certain group of American Republicans who would do exactly that...
Indeed, some conservatives in America have taken on the practice of coal rolling, outfitting diesel trucks to spew black smoke as protest against environmental regulations.
Here is probably the biggest difference in terms of a drug-development perspective: HIV relies on enzymes that are not normally found in the human body, so it is relatively easy to find drugs that can target these proteins without causing significant side effects. Cancer cells, however, are human cells themselves, so the proteins that drive tumor growth and malignancy are found in healthy cells as well. Thus, developing anti-cancer drugs is not just a matter of finding and inactivating the proteins that drive cancers, but also making sure that inactivating these targets does not harm other non-cancerous cells in the body.
We have had the ability for quite some time to synthesize viruses from scratch (the first report in the scientific literature came from the laboratory of poliovirus from scratch, published in 2002). So, there is no reason to keep smallpox stocks around because we can just synthesize the virus if we need it. While this technology means that anyone with sufficient resources could download the (publically available smallpox genome, and synthesize it, the same technology also enables scientists to more rapidly generate vaccines without having to start with a physical sample of the virus.
The selfish genetic elements used in this technology are called "gene drives" because they drive their own inheritance through a population. I probably did not make that clear enough in the summary.
When I mentioned DNA from millenia ago, I was referring to scientists being able sequence DNA from the remains of dead, extinct animals (like the woolly mammoth genome). In the Science paper, they print the DNA onto a microchip which can be easily read out with standard DNA sequencing machines. Storing information in the DNA of a living organism would, of course, not work very well because of the low but significant error rate of DNA replication.
Last year George Church and colleagues published a paper in Science describing data storage using DNA (Church, Gao, and Kosuri. 2012. Next-Generation Digital Information Storage in DNA. Science 337: 1628. doi:10.1126/science.1226355) . While perhaps not lasting billions of years, given that we've been able to read DNA from creatures that existed millenia ago (whose DNA was definitely stored in non-ideal conditions), DNA data storage could potentially preserve data for very long periods of time.
Lobster, crab, shrimp and other crustaceans are much more closely related (evolutionarily) to insects than to fish or other animals that we commonly eat. So in a way, many Americans are already eating insects.
A similar situation occurred with the papaya ringspot virus threatening to devastate the papaya industry in Hawaii. However, in 1998, researchers developed a genetically modified papaya resistant to the virus, and this scientific development has been credited with saving Hawaii's papaya industry. Perhaps this offers some hope for a good outcome in using genetic modification to solve the problem of citrus greening.
When you insert a new gene (such as an herbicide resistance gene in Monsanto's Roundup Ready crops) into a plant, you also need to insert a piece of DNA called a promoter that tells the plant to turn the gene on. The scientists who created the GMOs chose to insert the promoter from the cauliflower mosaic virus (CaMV), as it is particularly good at this task and is very well studied. This promoter also happens to include part, but not the entirety, of gene VI from the virus.
* 2. Was it put there by accident or by purpose?
* 2(a). If by accident, how, when, what happened?
* 2(b). If by purpose, why, and by whom?
As stated above, the fragment of gene VI was placed into the GMOs on purpose. Because fragments of genes are generally inactive, the presence of the gene fragment is not expected to be problematic and showed no evidence of causing problems during the testing of the GMOs. Furthermore, because cauliflower mosaic virus is a naturally occurring virus, the full gene VI can be found in many non-GMO crops (for example, see this 2004 study).
3. How come the American scientists never detected this viral gene?
* 3(a). Was it because of incompetence, or was it because the American scientists were not allowed to publish their finding, if they had found it before the Europeans?
These findings were not published before because we already knew that many GMOs contain a fragment of CaMV gene VI. In fact, in the Podevin and du Jardin study, the authors "found" the gene VI fragments by simply querying a database. A more substantial finding would have been if they found evidence that the gene VI fragments are actually made into functional protein (a prerequisite for the gene VI fragment to cause any deleterious effects), but this study did not investigate this issue. Rather, the study simply looked at what proteins might be produced in the worst case scenario and concluded that any possible proteins made from the gene VI fragments are unlikely to be human allergens or toxins. The authors speculate these possible proteins could be harmful to the plant itself, but because many of these GMOs are very productive plants that produce high yields in commercial settings, this possibility seems unlikely.
Sydney Brenner, who won the Nobel Prize in Physiology or Medicine for his work on programmed cell death, wrote a nice essay in the journal Science (subscription required) describing what he saw as a major paradigm shift in the 1950s and 60s that created modern molecular biology. Prior to the discovery of the structure of DNA by Watson and Crick, biologists had been focusing on how DNA and its associated proteins might be carrying out the functions of the cell. The discovery of the structure of DNA, however, fundamentally changed how researchers approached these questions by revealing that DNA is really just carrying information. Brenner writes:
"We can now see exactly what constituted the new paradigm in the life sciences: It was the introduction of the idea of information and its physical embodiment in DNA sequences of four different bases. Thus, although the components of DNA are simple chemicals, the complexity that can be generated by different sequences is enormous. In 1953, biochemists were preoccupied only with questions of matter and energy, but now they had to add information. In the study of protein synthesis, most biochemists were concerned with the source of energy for the synthesis of the peptide bond; a few wrote about the “patternization” problem. For molecular biologists, the problem was how one sequence of four nucleotides encoded another sequence of 20 amino acids."
Indeed, following this paradigm shift, Watson and others quickly worked out the question of how the information encoded in DNA gets read by the cell and their work now forms the central dogma of modern molecular biology. Therefore, Kuhn's concept of paradigm shifts does indeed apply to biology.
William Press and Freeman Dyson recently published a very interesting paper showing that the optimal IPD strategy depends on whether your opponent is mindlessly following a particular algorithm or is actually sentient. In particular, if you who can figure out your opponent's algorithm, you can then game the opponent's algorithm for your benefit. You may find reading the paper (http://www.pnas.org/content/109/26/10409) and the accompanying commentary by Stewart and Plotkin (http://www.pnas.org/content/109/26/10134) to be useful.
You've got it backwards. The cost of materials for sequencing is dropping to $1k, but the data analysis (stitching together all of the short DNA reads to assemble a full genome sequence) still costs well in excess of $1k. For example, a 2011 Chemical and Engineering News article suggests that the cost of the analysis was still ~$100k.
A molecule like this has already been made by Frasier Stoddart in 1994 (https://en.wikipedia.org/wiki/Olympiadane). The 1994 version, unlike the olympicene synthesized here, actually has interlocking rings versus rings that are simply juxtaposed.
The same group of researchers published a paper in 2009 in the journal Science using a technique called atomic force microscopy (AFM) rather than the scanning tunneling microscopy (STM) approached used here. This technique allowed them to resolve the atomic structure of pentacene, showing the classic ring structure as one might see drawn on a chalk board in their chemistry class. Combined with their means of imaging molecular orbitals by STM, these researchers have developed some really nice tools for studying molecules. Here's the citation for the AFM paper:
Gross et al. (2009) The Chemical Structure of a Molecule Resolved by Atomic Force Microscopy. Science, 325: 1110. doi:10.1126/science.1176210
Well, let's say these engineered worms escape into the environment. 1) the paper does not show whether the changes they made to the worm's genome are heritable, so the worm's offspring might not be able to incorporate the unnatural amino acids and the trait might go away after the escaped engineered worms die. Even if the trait is heritable, the paper suggests that the gene cassette they engineered into the worm gets lost from the genome over time, so after a few generations, the trait would likely be lost. 2) these worms do not have the ability to synthesize the unnatural amino acids on their own. They incorporate the unnatural amino acids into their proteins only when the researchers feed the worms large amounts of the unnatural amino acid. Without a source of unnatural amino acids, they are just slightly broken versions of a normal C. elegans worm.
In the case of this study, the researchers are tricking the worm to incorporate an unnatural amino acid in the place of a stop codon (TAG to be specific). The researchers created an reporter gene that codes for a red fluorescent protein (mCherry) after a TAG stop codon. If the worm is not able to incorporate the unnatural amino acid, the cell will stop producing the protein once it encounters the TAG stop codon and not produce the red fluorescent part of the reporter gene. Successful incorporation of the unnatural amino acid, however, allows the cell to bypass the TAG stop codon and produce the red fluorescent part of the reporter gene. So, even though the unnatural amino acid is not directly producing the fluorescence, seeing the worms glowing red means that the worm's cells were able to incorporate the unnatural amino acid successfully.
You actually wouldn't need to even start with Vaccinia virus. In 2008, scientists at the J Craig Venter Institute synthesized and assembled the genome of an entire bacterium from scratch (Gibson et al. 2008. Complete Chemical Synthesis, Assembly, and Cloning of a Mycoplasma genitalium Genome. Science 319: 1215 - 1220. doi:10.1126/science.1151721) . The bacterial genome they synthesized was 580,000 base pairs compared to the 186,000 base pair size of the smallpox genome. Of course, commercial gene synthesis companies would never sell anyone any sequence resembling a smallpox sequence, but given enough resources, a government or even some well funded group could conceivably resurrect smallpox without needing a sample of the virus.
With new gene synthesis technologies (such as the ones used by Craig Venter to create his "synthetic" bacteria), one could fairly easily resurrect smallpox from DNA chemically synthesized in the lab along with some engineered cell lines. This was demonstrated with poliovirus nearly a decade ago (Cello, Paul, and Wimmer 2002 Chemical Synthesis of Poliovirus cDNA: Generation of Infectious Virus in the Absence of Natural Template Science 297: 1016. doi:10.1126/science.1072266). So, even eliminating every remaining sample of smallpox on Earth would not guarantee that the virus could not one day be resurrected as a bio-weapon.
Here's a small detail that the article leaves for the last paragraph:
“The next step will be to differentiate between different DNA samples and, ultimately, between individual bases within the DNA strand,” said study co-author Dr. Tim Albrecht. “I think we know the way forward, but it is a challenging project and we have to make many more incremental steps before our vision can be realized.”
In other words, they can zip DNA through this device quickly and measure some signal as the DNA passes through, but no one knows yet whether it is possible to extract accurate sequence information from the signal they get. Similar implementations (that admittedly have a less sensitive way of getting a signal from the different DNA bases) have so far failed to see significant enough differences between the DNA bases to be useful for sequencing. It's not clear that this method will work as advertised
It's typical of mathematicians. They construct a well posed problem and convincingly show that a solution exists, but make no effort at finding the actual solution to the problem.
There are existing techniques that give ~tens of nanometers resolution using fluorescence microscopy (discussed in a feature in Nature Methods). Techniques such as PALM/FPALM/STORM (developed by Betzig, Hess, and Zhuang, independently) use photoswitchable fluorophores to image and localize single fluorescent molecules with high precision then reconstruct the image from these single molecule images. Another technique, STED (stimulated emission depletion, developed by Hell) uses stimulated emission to effectively shrink the size of the point spread function of a fluorescence microscope. Yet another technique, structured illumination microscopy (developed by Gustafsson), plays tricks with moiré patterns to extend the resolution of optical microscopy. All would, in theory, be applicable on Smith's array tomography samples.
On issue with superresolution fluorescence microscopy, however, is that the spatial resolution of an image is dependent on the density of antibodies bound to the sample. The Nyquist criterion defines how frequently one must sample the underlying structure (the neuron) in order to achieve a specific spatial resolution. In this case, each antibody that binds to the neuron is one sampling event. Therefore, achieving very high resolution requires binding more antibody to the sample than typical for standard immunohistochemistry. This can be difficult, especially in samples that are embeded in resin (as is required to get the 70 nm sections used in the array tomography method), as the embeding process can drastically reduce the antigenicity of the sample.
Slashdot Mirror
A few notes to keep in mind with the interpretation of the results:
1. The macronutrient consumption data are based on food frequency questionaires, a somewhat unreliable means to measuring food consumption. How accurate do you think you'd be if asked about how much of each type of food you ate over the past few months? For more disucssion of problems with food frequency questionaires and other general issues with studies on nutrition see: http://fivethirtyeight.com/fea...
2. The study is an observational study that can only assess correlation, not causation. People who reported eating more carbohydrates had higher mortality. Was eating more carbohydrates the cause of the higher mortality, or were there other differences between people who ate more carbohydrates and those who ate less? A common problem with these studies is that people who follow dietary guidelines are more likely to follow other guidelines for healthy living, so one could just be picking up a signal from decreased mortality of those who pay attention to their health in general. Socioeconomic factors are another potential confounding factor in the results. In many of the third world countries studied, a diet higher in animal protein would likely be more expensive than a diet higher in carbohydrates. These confounding variables make inferring causation difficult. Randomized controlled trials would provide a gold standard for assessing whether there is a causal relationship between carbohydrate intake and mortality, though these are notoriously difficult to perform (how do you get a large cohort of people to change their diets for long periods of time?).
3. Even if the differences in diet are causally related to the changes in mortality and CV events, the exact mechanism is unclear. For example, in a commentary published in the Lancet along side the research paper (I would recommend reading the commentary if you are interested in the subject), the authors note:
Micronutrient malnutrition is an important problem in many of the countries included in PURE. Animal products are rich sources of zinc, bioavailable iron, vitamin K2, and vitamin B12, which might be suboptimal in populations consuming high carbohydrate diets. Therefore, one potential explanation for the PURE results is that nutrient-dense meats corrected one or more nutrient deficiencies
http://www.thelancet.com/journ...
If the results are partly due to consumption of animal products alleviating micronutrient malnutrition, it is unclear whether the results would be as applicable in populations where micronutrient malnutrition is not an issue.
Overall, the study is a very important piece of evidence in determining the best amount of carbohydrates, proteins and fats to include in one's diet. However, it is not a definitive study, so one needs to consider the entire body of evidence including observational studies (such as this one) done in a number of different populations, randomized clinical trials, and laboratory experiments that get at the mechanisms involved.
Other physicists have expressed skepticism over the Harvard group's claims of making metallic hydrogen. Importantly, the claim is made on the basis of one single experiment that has not yet been replicated by the group reporting the claims. From a news article published in Nature :
Other researchers aren't convinced. It’s far from clear that the shiny material the researchers see is actually hydrogen, says geophysicist Alexander Goncharov of the Carnegie Institution for Science in Washington DC. Goncharov has criticized the Silvera lab’s methods before. He suggests that the shiny material may be alumina (aluminium oxide), which coats the tips of the diamonds in the anvil, and may behave differently under pressure.
Loubeyre and others think that Silvera and Dias are overestimating the pressure that they reached, by relying on an imprecise calibration between turns of the screw and pressure inside the anvil. Eugene Gregoryanz, a physicist at the University of Edinburgh, UK, adds that part of the problem is that the researchers took only a single detailed measurement of their sample at the highest pressure — making it hard to see how pressure shifted during the experiment.
I can think of a certain group of American Republicans who would do exactly that...
Indeed, some conservatives in America have taken on the practice of coal rolling, outfitting diesel trucks to spew black smoke as protest against environmental regulations.
Here is probably the biggest difference in terms of a drug-development perspective: HIV relies on enzymes that are not normally found in the human body, so it is relatively easy to find drugs that can target these proteins without causing significant side effects. Cancer cells, however, are human cells themselves, so the proteins that drive tumor growth and malignancy are found in healthy cells as well. Thus, developing anti-cancer drugs is not just a matter of finding and inactivating the proteins that drive cancers, but also making sure that inactivating these targets does not harm other non-cancerous cells in the body.
But as it can be synthesised, that refutes the argument that "if we destroyed it, it would be gone forever"
Yes. While destroying existing stocks would not eradicate the virus forever, it would still help minimize the risks of accidental releases.
We have had the ability for quite some time to synthesize viruses from scratch (the first report in the scientific literature came from the laboratory of poliovirus from scratch, published in 2002). So, there is no reason to keep smallpox stocks around because we can just synthesize the virus if we need it. While this technology means that anyone with sufficient resources could download the (publically available smallpox genome, and synthesize it, the same technology also enables scientists to more rapidly generate vaccines without having to start with a physical sample of the virus.
The selfish genetic elements used in this technology are called "gene drives" because they drive their own inheritance through a population. I probably did not make that clear enough in the summary.
When I mentioned DNA from millenia ago, I was referring to scientists being able sequence DNA from the remains of dead, extinct animals (like the woolly mammoth genome). In the Science paper, they print the DNA onto a microchip which can be easily read out with standard DNA sequencing machines. Storing information in the DNA of a living organism would, of course, not work very well because of the low but significant error rate of DNA replication.
Last year George Church and colleagues published a paper in Science describing data storage using DNA (Church, Gao, and Kosuri. 2012. Next-Generation Digital Information Storage in DNA. Science 337: 1628. doi:10.1126/science.1226355) . While perhaps not lasting billions of years, given that we've been able to read DNA from creatures that existed millenia ago (whose DNA was definitely stored in non-ideal conditions), DNA data storage could potentially preserve data for very long periods of time.
Lobster, crab, shrimp and other crustaceans are much more closely related (evolutionarily) to insects than to fish or other animals that we commonly eat. So in a way, many Americans are already eating insects.
A similar situation occurred with the papaya ringspot virus threatening to devastate the papaya industry in Hawaii. However, in 1998, researchers developed a genetically modified papaya resistant to the virus, and this scientific development has been credited with saving Hawaii's papaya industry. Perhaps this offers some hope for a good outcome in using genetic modification to solve the problem of citrus greening.
1. Why is that viral gene in there?
When you insert a new gene (such as an herbicide resistance gene in Monsanto's Roundup Ready crops) into a plant, you also need to insert a piece of DNA called a promoter that tells the plant to turn the gene on. The scientists who created the GMOs chose to insert the promoter from the cauliflower mosaic virus (CaMV), as it is particularly good at this task and is very well studied. This promoter also happens to include part, but not the entirety, of gene VI from the virus.
* 2. Was it put there by accident or by purpose? * 2(a). If by accident, how, when, what happened? * 2(b). If by purpose, why, and by whom?
As stated above, the fragment of gene VI was placed into the GMOs on purpose. Because fragments of genes are generally inactive, the presence of the gene fragment is not expected to be problematic and showed no evidence of causing problems during the testing of the GMOs. Furthermore, because cauliflower mosaic virus is a naturally occurring virus, the full gene VI can be found in many non-GMO crops (for example, see this 2004 study).
3. How come the American scientists never detected this viral gene? * 3(a). Was it because of incompetence, or was it because the American scientists were not allowed to publish their finding, if they had found it before the Europeans?
These findings were not published before because we already knew that many GMOs contain a fragment of CaMV gene VI. In fact, in the Podevin and du Jardin study, the authors "found" the gene VI fragments by simply querying a database. A more substantial finding would have been if they found evidence that the gene VI fragments are actually made into functional protein (a prerequisite for the gene VI fragment to cause any deleterious effects), but this study did not investigate this issue. Rather, the study simply looked at what proteins might be produced in the worst case scenario and concluded that any possible proteins made from the gene VI fragments are unlikely to be human allergens or toxins. The authors speculate these possible proteins could be harmful to the plant itself, but because many of these GMOs are very productive plants that produce high yields in commercial settings, this possibility seems unlikely.
Sydney Brenner, who won the Nobel Prize in Physiology or Medicine for his work on programmed cell death, wrote a nice essay in the journal Science (subscription required) describing what he saw as a major paradigm shift in the 1950s and 60s that created modern molecular biology. Prior to the discovery of the structure of DNA by Watson and Crick, biologists had been focusing on how DNA and its associated proteins might be carrying out the functions of the cell. The discovery of the structure of DNA, however, fundamentally changed how researchers approached these questions by revealing that DNA is really just carrying information. Brenner writes:
"We can now see exactly what constituted the new paradigm in the life sciences: It was the introduction of the idea of information and its physical embodiment in DNA sequences of four different bases. Thus, although the components of DNA are simple chemicals, the complexity that can be generated by different sequences is enormous. In 1953, biochemists were preoccupied only with questions of matter and energy, but now they had to add information. In the study of protein synthesis, most biochemists were concerned with the source of energy for the synthesis of the peptide bond; a few wrote about the “patternization” problem. For molecular biologists, the problem was how one sequence of four nucleotides encoded another sequence of 20 amino acids."
Indeed, following this paradigm shift, Watson and others quickly worked out the question of how the information encoded in DNA gets read by the cell and their work now forms the central dogma of modern molecular biology. Therefore, Kuhn's concept of paradigm shifts does indeed apply to biology.
William Press and Freeman Dyson recently published a very interesting paper showing that the optimal IPD strategy depends on whether your opponent is mindlessly following a particular algorithm or is actually sentient. In particular, if you who can figure out your opponent's algorithm, you can then game the opponent's algorithm for your benefit. You may find reading the paper (http://www.pnas.org/content/109/26/10409) and the accompanying commentary by Stewart and Plotkin (http://www.pnas.org/content/109/26/10134) to be useful.
Seriously, flash/gif-based webcomics like Homestuck have been doing this for a while.
You've got it backwards. The cost of materials for sequencing is dropping to $1k, but the data analysis (stitching together all of the short DNA reads to assemble a full genome sequence) still costs well in excess of $1k. For example, a 2011 Chemical and Engineering News article suggests that the cost of the analysis was still ~$100k.
A molecule like this has already been made by Frasier Stoddart in 1994 (https://en.wikipedia.org/wiki/Olympiadane). The 1994 version, unlike the olympicene synthesized here, actually has interlocking rings versus rings that are simply juxtaposed.
The same group of researchers published a paper in 2009 in the journal Science using a technique called atomic force microscopy (AFM) rather than the scanning tunneling microscopy (STM) approached used here. This technique allowed them to resolve the atomic structure of pentacene, showing the classic ring structure as one might see drawn on a chalk board in their chemistry class. Combined with their means of imaging molecular orbitals by STM, these researchers have developed some really nice tools for studying molecules. Here's the citation for the AFM paper:
Gross et al. (2009) The Chemical Structure of a Molecule Resolved by Atomic Force Microscopy. Science, 325: 1110. doi:10.1126/science.1176210
Well, let's say these engineered worms escape into the environment. 1) the paper does not show whether the changes they made to the worm's genome are heritable, so the worm's offspring might not be able to incorporate the unnatural amino acids and the trait might go away after the escaped engineered worms die. Even if the trait is heritable, the paper suggests that the gene cassette they engineered into the worm gets lost from the genome over time, so after a few generations, the trait would likely be lost. 2) these worms do not have the ability to synthesize the unnatural amino acids on their own. They incorporate the unnatural amino acids into their proteins only when the researchers feed the worms large amounts of the unnatural amino acid. Without a source of unnatural amino acids, they are just slightly broken versions of a normal C. elegans worm.
Does this make you feel any better?
In the case of this study, the researchers are tricking the worm to incorporate an unnatural amino acid in the place of a stop codon (TAG to be specific). The researchers created an reporter gene that codes for a red fluorescent protein (mCherry) after a TAG stop codon. If the worm is not able to incorporate the unnatural amino acid, the cell will stop producing the protein once it encounters the TAG stop codon and not produce the red fluorescent part of the reporter gene. Successful incorporation of the unnatural amino acid, however, allows the cell to bypass the TAG stop codon and produce the red fluorescent part of the reporter gene. So, even though the unnatural amino acid is not directly producing the fluorescence, seeing the worms glowing red means that the worm's cells were able to incorporate the unnatural amino acid successfully.
You actually wouldn't need to even start with Vaccinia virus. In 2008, scientists at the J Craig Venter Institute synthesized and assembled the genome of an entire bacterium from scratch (Gibson et al. 2008. Complete Chemical Synthesis, Assembly, and Cloning of a Mycoplasma genitalium Genome. Science 319: 1215 - 1220. doi:10.1126/science.1151721) . The bacterial genome they synthesized was 580,000 base pairs compared to the 186,000 base pair size of the smallpox genome. Of course, commercial gene synthesis companies would never sell anyone any sequence resembling a smallpox sequence, but given enough resources, a government or even some well funded group could conceivably resurrect smallpox without needing a sample of the virus.
With new gene synthesis technologies (such as the ones used by Craig Venter to create his "synthetic" bacteria), one could fairly easily resurrect smallpox from DNA chemically synthesized in the lab along with some engineered cell lines. This was demonstrated with poliovirus nearly a decade ago (Cello, Paul, and Wimmer 2002 Chemical Synthesis of Poliovirus cDNA: Generation of Infectious Virus in the Absence of Natural Template Science 297: 1016. doi:10.1126/science.1072266). So, even eliminating every remaining sample of smallpox on Earth would not guarantee that the virus could not one day be resurrected as a bio-weapon.
Here's a small detail that the article leaves for the last paragraph:
“The next step will be to differentiate between different DNA samples and, ultimately, between individual bases within the DNA strand,” said study co-author Dr. Tim Albrecht. “I think we know the way forward, but it is a challenging project and we have to make many more incremental steps before our vision can be realized.”
In other words, they can zip DNA through this device quickly and measure some signal as the DNA passes through, but no one knows yet whether it is possible to extract accurate sequence information from the signal they get. Similar implementations (that admittedly have a less sensitive way of getting a signal from the different DNA bases) have so far failed to see significant enough differences between the DNA bases to be useful for sequencing. It's not clear that this method will work as advertised
It's typical of mathematicians. They construct a well posed problem and convincingly show that a solution exists, but make no effort at finding the actual solution to the problem.
There are existing techniques that give ~tens of nanometers resolution using fluorescence microscopy (discussed in a feature in Nature Methods ). Techniques such as PALM/FPALM/STORM (developed by Betzig, Hess, and Zhuang, independently) use photoswitchable fluorophores to image and localize single fluorescent molecules with high precision then reconstruct the image from these single molecule images. Another technique, STED (stimulated emission depletion, developed by Hell) uses stimulated emission to effectively shrink the size of the point spread function of a fluorescence microscope. Yet another technique, structured illumination microscopy (developed by Gustafsson), plays tricks with moiré patterns to extend the resolution of optical microscopy. All would, in theory, be applicable on Smith's array tomography samples.
On issue with superresolution fluorescence microscopy, however, is that the spatial resolution of an image is dependent on the density of antibodies bound to the sample. The Nyquist criterion defines how frequently one must sample the underlying structure (the neuron) in order to achieve a specific spatial resolution. In this case, each antibody that binds to the neuron is one sampling event. Therefore, achieving very high resolution requires binding more antibody to the sample than typical for standard immunohistochemistry. This can be difficult, especially in samples that are embeded in resin (as is required to get the 70 nm sections used in the array tomography method), as the embeding process can drastically reduce the antigenicity of the sample.