Reasonable Rascal
07-18-02, 01:40
POLIOVIRUS, CHEMICAL SYNTHESIS
******************************
Date: Sat 13 Jul 2002
Source: Science Online, Thu 11 Jul 2002 [edited]
<http://www.sciencemag.org/cgi/content/abstract/1072266>
Chemical Synthesis of Poliovirus cDNA: Generation of Infectious Virus
in the Absence of Natural Template
--------------------------------------------------
[Abstract of the paper by Jeronimo Cello, Aniko V. Paul and Eckard Wimmer of the Department of Molecular Genetics and Microbiology, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794-5222, USA.]
Full-length poliovirus cDNA was synthesized by assembling oligonucleotides of plus and minus strand polarity. The synthetic poliovirus cDNA was transcribed by RNA polymerase into viral RNA, which translated and replicated in a cell-free extract resulting in the _de novo_ synthesis of infectious poliovirus. Experiments in tissue culture using neutralizing antibodies and CD155 receptor-specific antibodies and neurovirulence tests in CD155 transgenic mice confirmed that the synthetic virus had biochemical and pathogenic characteristics of poliovirus. Our results show that it is possible to synthesize an infectious agent by in vitro chemical/biochemical means solely following instructions from a written sequence.
--
ProMED-mail
<promed@promedmail.org>
*****
[2]
Date: Fri 12 Jul 2002
From: Pablo Nart
Source: BBC News Online, Thu 11 Jul 2002 [edited]
<http://news.bbc.co.uk/hi/english/sci/tech/newsid_2122000/2122619.stm>
First synthetic virus created
-----------------------------
Scientists have assembled the first synthetic virus. Scientists are divided about whether a virus is alive. For those that think it is, then this synthetic artefact would constitute a simple form of life. Responding to criticisms that such research could lead to bioterrorists engineering new lethal viruses, the scientists behind the experiment said that only a few people had the knowledge to make it happen. To construct the virus, the researchers say they followed a recipe they downloaded from the internet and used gene sequences from a mail-order supplier. Having constructed the virus, which appears to be identical to its natural counterpart, the researchers, from the University of New York at Stony Brook, injected it into mice to demonstrate that it was active. The animals were paralyzed and then died.
"The reason we did it was to prove that it can be done and it now is a reality," said Dr Eckard Wimmer, leader of the biomedical research team and co-author of the study published in the journal Science [see above}. "This approach has been talked about, but people didn't take it seriously," said Dr Wimmer. "Now people have to take it seriously. Progress in biomedical research has its benefits and it has its down side. There is a danger inherent to progress in sciences. This is a new reality, a new consideration." According to researcher Jeronimo Cello, the poliovirus assembled in the laboratory is one of the simplest known viruses. "It was very easy to do," he said. The more dangerous smallpox virus would be complex and difficult to assemble, but Cello says, "it would probably in the future be possible". Dr Wimmer added: "The world had better be prepared."
Dr Wimmer said assembling poliovirus showed that eradicating a virus in the wild might not mean it was gone forever because biochemists could now reconstruct those viruses from blueprints. Dr C.J. Peters, Director for the Center for Biodefense at the University of Texas Medical Center at Galveston, said experts had known for years that it was theoretically possible to assemble a virus in the lab. Dr Peters said he was concerned that publicity about a synthesized virus might lead some people to believe "that there is nothing that can be done about bioterrorism - which is not the case". He added that it was possible that viruses like Ebola virus could be assembled in laboratories, but there were only a few people in the world with that skill.
Polio is on the brink of being eradicated worldwide and there are plans to stop inoculations against the disease after it disappears from nature. Dr Wimmer said that this policy should be reconsidered. Stopping vaccination could lead to a generation of people highly susceptible to polio, enhancing its appeal as a weapon. The World Health Organization is planning to stockpile vaccines against a return of polio and Dr Wimmer said that policy should be followed everywhere.
[By Dr David Whitehouse]
******
[3]
Date: Fri 12 Jul 2002
From: Cinde Fisher
Source: New York Times, Fri 12 2002 [edited]
<http://www.nytimes.com/2002/07/12/science/12POLI.html?todaysheadlines>
Scientists Create a Live Poliovirus
-----------------------------------
Scientists reported yesterday that they had constructed a virus from scratch for the first time, synthesizing a live poliovirus from chemicals and publicly available genetic information. The work, conducted by scientists at the State University of New York at Stony Brook, was financed by the Pentagon as part of a program to develop biowarfare countermeasures.
The scientists constructed the virus using its genome sequence, which is available on the Internet, as their blueprint and genetic material from one of the many companies that sell made-to-order DNA. Dr. Eckard Wimmer, Professor of Molecular Genetics and Microbiology at Stony Brook and leader of the project, said they made the virus to send a warning that terrorists might be able to make biological weapons without obtaining a natural virus. "You no longer need the real thing in order to make the virus and propagate
it," Dr. Wimmer said.
The work set off a debate over whether the same technique might be applied to other viruses. "Could someone make a highly pathogenic virus like Ebola virus?" asked Dr. Robert A. Lamb, a professor at Northwestern University and President of the American Society for Virology. "Could you in fact make that in a rogue laboratory that doesn't need more than two skilled workers? My feeling is you probably could."
The development could also mean that even after poliomyelitis is eradicated as a disease, as is expected in the next few years, vaccinations might still be needed to protect against use of synthetic polio as a bioweapon. "This just says we're going to have to sustain some immunization for the indefinite future," said Dr. D. A. Henderson, principal adviser on public health preparedness to the secretary of health and human services.
The work, published online yesterday by the journal Science [see above], could conceivably be classified as the first creation of life in a test tube. But most scientists say that viruses are not truly living because they cannot reproduce on their own.
The Defense Advanced Research Projects Agency said it had provided about $300 000 over the last 3 years for the work. "Understanding the process of viral DNA production is key to identifying new ways to kill viruses and understand how viruses could change and escape from vaccines," the agency said. Experts agree that the research, or the synthesis of any pathogen, does not violate the 1972 treaty banning germ weapons, which gives wide latitude to all kinds of defensive research.
Stephen S. Morse, Director of the Center for Public Health Preparedness at Columbia University and a former official of the defense agency, said there was nothing nefarious about the Pentagon sponsoring such research. "Hopefully, this will help people to be realistic about assessing future threats," he said.
Some scientists criticized the work. "I think it's inflammatory without scientific justification," said Dr. J. Craig Venter, who sequenced the human genome and is trying to synthesize micro-organisms for uses like cleaning the environment. "To purposely make a synthetic human pathogen is irresponsible." Dr. Steven Block, a Stanford University expert on the applications of biotechnology to biowarfare, called the work a stunt. He played down any threat caused by synthetic viruses. "This is not the route to new kinds of terrific genetically engineered bioterror," he said. Even if people were not vaccinated, Dr. Block said, polio would not make a good bioweapon because it was not as infectious and lethal as many other pathogens. In most cases, he said, it would be easier to obtain a natural virus than to build one from scratch. The one exception, he said, is smallpox, because the world's two known remaining stocks of the virus are closely guarded. Smallpox would be nearly impossible to synthesize from scratch using the same technique, he said.
Many viruses are simple, consisting of some genetic material, either DNA or RNA, surrounded by a coat of protein. The genetic material instructs the cells infected by the virus to produce more viruses. So if one could produce such a virus's DNA or RNA and put it in the proper cell, new viruses would be produced. Indeed, scientists have recreated viruses this way in the past. But they started with genetic material derived from a natural virus. What is new is that the genetic material was synthesized from scratch. However, given that the naturally derived genetic material worked, it was little surprise that the synthetic material worked, too, so this was a trivial advance, some scientists said.
The poliovirus genome is tiny, consisting of 7500 chemical units, or bases, of RNA. Still, even assembling a genome of 7500 units is tedious. The machines, which usually make DNA rather than RNA, can reliably make only 50 to 100 bases in a stretch. So the Stony Brook scientists ordered numerous 60-base stretches from a company that sells DNA by mail-order for as little as 40 cents a base. The stretches were then painstakingly strung together. The DNA was then converted into RNA using a commercially available enzyme. The next step would be to put the RNA into cells to churn out new viruses. But Dr. Wimmer put the RNA instead into a mixture of proteins taken from cells, a technique he developed in 1991. That allows him to claim that the virus was made without the use of any living cells. Making the polio took three years, though Dr. Wimmer said it could probably now be done in 6 months. His collaborators were Dr. Aniko V. Paul, another professor in his department, and Dr. Jeronimo Cello, a postdoctoral researcher. The new
virus, when injected into the brains of mice, gave them a paralytic disease equivalent to poliomyelitis. However, the synthesized virus was much weaker than the natural one. Dr. Wimmer said he thought that was because his team deliberately introduced mutations into it to distinguish it from the natural virus.
Dr. Wimmer said many other viruses, especially ones with small genomes like HIV and hepatitis C virus, could be made this way. But the smallpox virus has a genome almost 200 000 bases long, putting it out of reach of current synthesis technology. Moreover, smallpox relies on some of its own proteins for replication, so just making the genes would not be enough. Dr Block said, "You can't take smallpox DNA, inject it into a cell and expect to get smallpox out." Still, DNA synthesis technology is improving. Some experts say it will be possible to recreate smallpox someday, though it would most likely be done by making genetic changes to a related virus like cowpox, rather than synthesizing the entire genome from scratch.
The new work could intensify questions about whether biotechnology needed to be regulated, or whether the genome sequences of pathogens should be available on the Internet, as they are now. "I think that this advance will bring the question of gene sequences more to the forefront than it was before," said Dr. Raymond A. Zilinskas, a biowarfare expert at the Monterey Institute of International Studies. He is organizing a workshop next month to advise the Defense Department on whether certain research should not be published. The National Academy of Sciences has also formed a committee to look at this question. Dr. Joseph A. Walder, chief executive of Integrated DNA Technologies, the company that synthesized the polio DNA for Dr. Wimmer, said his company was now considering checking sequences ordered by
customers against a database of pathogens.
Last year there were 480 cases of polio in the world and the World Health Organization hopes to eradicate wild poliovirus by 2005, said Dr. R. Bruce Aylward, the official in charge of the project. Once that happens, he said, many countries want to stop vaccinating. Dr. Aylward said he did not think the threat of synthetic polio would deter many countries from ending vaccinations. He said polio would not make a good bioweapon because only 1 out of every 200 to 1000 people exposed to it suffers paralysis and only a
fraction of those die. But Dr. Wimmer said polio, as it has done in the past, could spread panic and that vaccines would have to be stockpiled if not routinely administered. "In 20 or 25 years," he said, "if a good percentage of the world is not immunized against polio virus, then the virus would be a terrible terrorist agent."
[By Andrew Pollack]
--
Cinde Fisher,
Honolulu,
Hawaii
[Two of several reports received by ProMED-mail are reproduced above, together with the abstract of the Science Online paper. These give a fairly balanced impression of the achievement of the Stony Brook group and the range of comments that it has provoked. Dr. Wimmer and colleagues have used the published sequence of the poliovirus genome and existing technology to synthesize a complete poliovirus virus genome from cDNA constructed from commercially available oligonucleotide components. The reconstituted RNA genome was the template for production of infectious poliovirus in a cell free system, which allows the Stony Brook group to claim that poliovirus had been synthesized _de novo_. In principle, this is something that has been possible for some years past given time, money and motivation. Nonetheless, the technical skill of the Stony Brook group should in no way be diminished.
Some of the comments on the implication of this results seem somewhat off the mark. The complete sequences of most types of vertebrate viruses have been determined and have been in the public domain for some time. It is too late to attempt to place some kind of embargo on the use of this information. It is also the case that infectious cDNA copies of many pathogenic RNA viruses are available and can be used for the genetic modification of many important pathogens. Usually the direction of effort is towards attenuating the virulence of pathogenic viruses, but the reverse is equally possible. To take poliovirus as an example: It is well established that the Sabin vaccine strains only differ by a relatively small number of nucleotides from virulent poliovirus. As long as stocks of live attenuated polioviruses exist, the genetic modification of vaccine virus is a technically simpler route to production of virulent virus than the synthesis of virulent poliovirus virus _de novo_. This technology is fairly routine in many laboratories. However, unfortunately most viral pathogens are far from extinction and it is a simpler matter to use existing pathogens rather than develop laboriously synthesized products. Even in the Stony Brook case the data suggest that the synthetically derived poliovirus was inferior to the natural variety. In my view the greater hazard in this field is the construction of hybrid viruses lacking specific antigens which could be used to attack and penetrate pre-immunized populations.
Fortunately the _de novo_ synthesis of large complex viruses such as variola virus is a long way off. Nonetheless, Dr. Wimmer rightly emphasizes that the chemical synthesis of novel or eradicated pathogens is a new reality which must be taken account of in future planning. However, an effective strategy is not immediately obvious to me. - Mod.CP]
******************************
Date: Sat 13 Jul 2002
Source: Science Online, Thu 11 Jul 2002 [edited]
<http://www.sciencemag.org/cgi/content/abstract/1072266>
Chemical Synthesis of Poliovirus cDNA: Generation of Infectious Virus
in the Absence of Natural Template
--------------------------------------------------
[Abstract of the paper by Jeronimo Cello, Aniko V. Paul and Eckard Wimmer of the Department of Molecular Genetics and Microbiology, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY 11794-5222, USA.]
Full-length poliovirus cDNA was synthesized by assembling oligonucleotides of plus and minus strand polarity. The synthetic poliovirus cDNA was transcribed by RNA polymerase into viral RNA, which translated and replicated in a cell-free extract resulting in the _de novo_ synthesis of infectious poliovirus. Experiments in tissue culture using neutralizing antibodies and CD155 receptor-specific antibodies and neurovirulence tests in CD155 transgenic mice confirmed that the synthetic virus had biochemical and pathogenic characteristics of poliovirus. Our results show that it is possible to synthesize an infectious agent by in vitro chemical/biochemical means solely following instructions from a written sequence.
--
ProMED-mail
<promed@promedmail.org>
*****
[2]
Date: Fri 12 Jul 2002
From: Pablo Nart
Source: BBC News Online, Thu 11 Jul 2002 [edited]
<http://news.bbc.co.uk/hi/english/sci/tech/newsid_2122000/2122619.stm>
First synthetic virus created
-----------------------------
Scientists have assembled the first synthetic virus. Scientists are divided about whether a virus is alive. For those that think it is, then this synthetic artefact would constitute a simple form of life. Responding to criticisms that such research could lead to bioterrorists engineering new lethal viruses, the scientists behind the experiment said that only a few people had the knowledge to make it happen. To construct the virus, the researchers say they followed a recipe they downloaded from the internet and used gene sequences from a mail-order supplier. Having constructed the virus, which appears to be identical to its natural counterpart, the researchers, from the University of New York at Stony Brook, injected it into mice to demonstrate that it was active. The animals were paralyzed and then died.
"The reason we did it was to prove that it can be done and it now is a reality," said Dr Eckard Wimmer, leader of the biomedical research team and co-author of the study published in the journal Science [see above}. "This approach has been talked about, but people didn't take it seriously," said Dr Wimmer. "Now people have to take it seriously. Progress in biomedical research has its benefits and it has its down side. There is a danger inherent to progress in sciences. This is a new reality, a new consideration." According to researcher Jeronimo Cello, the poliovirus assembled in the laboratory is one of the simplest known viruses. "It was very easy to do," he said. The more dangerous smallpox virus would be complex and difficult to assemble, but Cello says, "it would probably in the future be possible". Dr Wimmer added: "The world had better be prepared."
Dr Wimmer said assembling poliovirus showed that eradicating a virus in the wild might not mean it was gone forever because biochemists could now reconstruct those viruses from blueprints. Dr C.J. Peters, Director for the Center for Biodefense at the University of Texas Medical Center at Galveston, said experts had known for years that it was theoretically possible to assemble a virus in the lab. Dr Peters said he was concerned that publicity about a synthesized virus might lead some people to believe "that there is nothing that can be done about bioterrorism - which is not the case". He added that it was possible that viruses like Ebola virus could be assembled in laboratories, but there were only a few people in the world with that skill.
Polio is on the brink of being eradicated worldwide and there are plans to stop inoculations against the disease after it disappears from nature. Dr Wimmer said that this policy should be reconsidered. Stopping vaccination could lead to a generation of people highly susceptible to polio, enhancing its appeal as a weapon. The World Health Organization is planning to stockpile vaccines against a return of polio and Dr Wimmer said that policy should be followed everywhere.
[By Dr David Whitehouse]
******
[3]
Date: Fri 12 Jul 2002
From: Cinde Fisher
Source: New York Times, Fri 12 2002 [edited]
<http://www.nytimes.com/2002/07/12/science/12POLI.html?todaysheadlines>
Scientists Create a Live Poliovirus
-----------------------------------
Scientists reported yesterday that they had constructed a virus from scratch for the first time, synthesizing a live poliovirus from chemicals and publicly available genetic information. The work, conducted by scientists at the State University of New York at Stony Brook, was financed by the Pentagon as part of a program to develop biowarfare countermeasures.
The scientists constructed the virus using its genome sequence, which is available on the Internet, as their blueprint and genetic material from one of the many companies that sell made-to-order DNA. Dr. Eckard Wimmer, Professor of Molecular Genetics and Microbiology at Stony Brook and leader of the project, said they made the virus to send a warning that terrorists might be able to make biological weapons without obtaining a natural virus. "You no longer need the real thing in order to make the virus and propagate
it," Dr. Wimmer said.
The work set off a debate over whether the same technique might be applied to other viruses. "Could someone make a highly pathogenic virus like Ebola virus?" asked Dr. Robert A. Lamb, a professor at Northwestern University and President of the American Society for Virology. "Could you in fact make that in a rogue laboratory that doesn't need more than two skilled workers? My feeling is you probably could."
The development could also mean that even after poliomyelitis is eradicated as a disease, as is expected in the next few years, vaccinations might still be needed to protect against use of synthetic polio as a bioweapon. "This just says we're going to have to sustain some immunization for the indefinite future," said Dr. D. A. Henderson, principal adviser on public health preparedness to the secretary of health and human services.
The work, published online yesterday by the journal Science [see above], could conceivably be classified as the first creation of life in a test tube. But most scientists say that viruses are not truly living because they cannot reproduce on their own.
The Defense Advanced Research Projects Agency said it had provided about $300 000 over the last 3 years for the work. "Understanding the process of viral DNA production is key to identifying new ways to kill viruses and understand how viruses could change and escape from vaccines," the agency said. Experts agree that the research, or the synthesis of any pathogen, does not violate the 1972 treaty banning germ weapons, which gives wide latitude to all kinds of defensive research.
Stephen S. Morse, Director of the Center for Public Health Preparedness at Columbia University and a former official of the defense agency, said there was nothing nefarious about the Pentagon sponsoring such research. "Hopefully, this will help people to be realistic about assessing future threats," he said.
Some scientists criticized the work. "I think it's inflammatory without scientific justification," said Dr. J. Craig Venter, who sequenced the human genome and is trying to synthesize micro-organisms for uses like cleaning the environment. "To purposely make a synthetic human pathogen is irresponsible." Dr. Steven Block, a Stanford University expert on the applications of biotechnology to biowarfare, called the work a stunt. He played down any threat caused by synthetic viruses. "This is not the route to new kinds of terrific genetically engineered bioterror," he said. Even if people were not vaccinated, Dr. Block said, polio would not make a good bioweapon because it was not as infectious and lethal as many other pathogens. In most cases, he said, it would be easier to obtain a natural virus than to build one from scratch. The one exception, he said, is smallpox, because the world's two known remaining stocks of the virus are closely guarded. Smallpox would be nearly impossible to synthesize from scratch using the same technique, he said.
Many viruses are simple, consisting of some genetic material, either DNA or RNA, surrounded by a coat of protein. The genetic material instructs the cells infected by the virus to produce more viruses. So if one could produce such a virus's DNA or RNA and put it in the proper cell, new viruses would be produced. Indeed, scientists have recreated viruses this way in the past. But they started with genetic material derived from a natural virus. What is new is that the genetic material was synthesized from scratch. However, given that the naturally derived genetic material worked, it was little surprise that the synthetic material worked, too, so this was a trivial advance, some scientists said.
The poliovirus genome is tiny, consisting of 7500 chemical units, or bases, of RNA. Still, even assembling a genome of 7500 units is tedious. The machines, which usually make DNA rather than RNA, can reliably make only 50 to 100 bases in a stretch. So the Stony Brook scientists ordered numerous 60-base stretches from a company that sells DNA by mail-order for as little as 40 cents a base. The stretches were then painstakingly strung together. The DNA was then converted into RNA using a commercially available enzyme. The next step would be to put the RNA into cells to churn out new viruses. But Dr. Wimmer put the RNA instead into a mixture of proteins taken from cells, a technique he developed in 1991. That allows him to claim that the virus was made without the use of any living cells. Making the polio took three years, though Dr. Wimmer said it could probably now be done in 6 months. His collaborators were Dr. Aniko V. Paul, another professor in his department, and Dr. Jeronimo Cello, a postdoctoral researcher. The new
virus, when injected into the brains of mice, gave them a paralytic disease equivalent to poliomyelitis. However, the synthesized virus was much weaker than the natural one. Dr. Wimmer said he thought that was because his team deliberately introduced mutations into it to distinguish it from the natural virus.
Dr. Wimmer said many other viruses, especially ones with small genomes like HIV and hepatitis C virus, could be made this way. But the smallpox virus has a genome almost 200 000 bases long, putting it out of reach of current synthesis technology. Moreover, smallpox relies on some of its own proteins for replication, so just making the genes would not be enough. Dr Block said, "You can't take smallpox DNA, inject it into a cell and expect to get smallpox out." Still, DNA synthesis technology is improving. Some experts say it will be possible to recreate smallpox someday, though it would most likely be done by making genetic changes to a related virus like cowpox, rather than synthesizing the entire genome from scratch.
The new work could intensify questions about whether biotechnology needed to be regulated, or whether the genome sequences of pathogens should be available on the Internet, as they are now. "I think that this advance will bring the question of gene sequences more to the forefront than it was before," said Dr. Raymond A. Zilinskas, a biowarfare expert at the Monterey Institute of International Studies. He is organizing a workshop next month to advise the Defense Department on whether certain research should not be published. The National Academy of Sciences has also formed a committee to look at this question. Dr. Joseph A. Walder, chief executive of Integrated DNA Technologies, the company that synthesized the polio DNA for Dr. Wimmer, said his company was now considering checking sequences ordered by
customers against a database of pathogens.
Last year there were 480 cases of polio in the world and the World Health Organization hopes to eradicate wild poliovirus by 2005, said Dr. R. Bruce Aylward, the official in charge of the project. Once that happens, he said, many countries want to stop vaccinating. Dr. Aylward said he did not think the threat of synthetic polio would deter many countries from ending vaccinations. He said polio would not make a good bioweapon because only 1 out of every 200 to 1000 people exposed to it suffers paralysis and only a
fraction of those die. But Dr. Wimmer said polio, as it has done in the past, could spread panic and that vaccines would have to be stockpiled if not routinely administered. "In 20 or 25 years," he said, "if a good percentage of the world is not immunized against polio virus, then the virus would be a terrible terrorist agent."
[By Andrew Pollack]
--
Cinde Fisher,
Honolulu,
Hawaii
[Two of several reports received by ProMED-mail are reproduced above, together with the abstract of the Science Online paper. These give a fairly balanced impression of the achievement of the Stony Brook group and the range of comments that it has provoked. Dr. Wimmer and colleagues have used the published sequence of the poliovirus genome and existing technology to synthesize a complete poliovirus virus genome from cDNA constructed from commercially available oligonucleotide components. The reconstituted RNA genome was the template for production of infectious poliovirus in a cell free system, which allows the Stony Brook group to claim that poliovirus had been synthesized _de novo_. In principle, this is something that has been possible for some years past given time, money and motivation. Nonetheless, the technical skill of the Stony Brook group should in no way be diminished.
Some of the comments on the implication of this results seem somewhat off the mark. The complete sequences of most types of vertebrate viruses have been determined and have been in the public domain for some time. It is too late to attempt to place some kind of embargo on the use of this information. It is also the case that infectious cDNA copies of many pathogenic RNA viruses are available and can be used for the genetic modification of many important pathogens. Usually the direction of effort is towards attenuating the virulence of pathogenic viruses, but the reverse is equally possible. To take poliovirus as an example: It is well established that the Sabin vaccine strains only differ by a relatively small number of nucleotides from virulent poliovirus. As long as stocks of live attenuated polioviruses exist, the genetic modification of vaccine virus is a technically simpler route to production of virulent virus than the synthesis of virulent poliovirus virus _de novo_. This technology is fairly routine in many laboratories. However, unfortunately most viral pathogens are far from extinction and it is a simpler matter to use existing pathogens rather than develop laboriously synthesized products. Even in the Stony Brook case the data suggest that the synthetically derived poliovirus was inferior to the natural variety. In my view the greater hazard in this field is the construction of hybrid viruses lacking specific antigens which could be used to attack and penetrate pre-immunized populations.
Fortunately the _de novo_ synthesis of large complex viruses such as variola virus is a long way off. Nonetheless, Dr. Wimmer rightly emphasizes that the chemical synthesis of novel or eradicated pathogens is a new reality which must be taken account of in future planning. However, an effective strategy is not immediately obvious to me. - Mod.CP]