SAB NewsInsights from The Science Advisory Board's "Oligonucleotides" studyPosted 9/7/2006 Each member of The Science Advisory Board who participated in this study was invited to comment on the following: Do you believe that suppliers should screen custom oligo orders for potential biosecurity threats (e.g., DNA for a bacterial gene that produces a deadly toxin)? Why or why not? If yes, how should any screening be conducted so that scientists with honorable intentions are not mistaken for bioterrorists? For instance, should suppliers just decline suspicious orders or should they report such orders to a domestic or international agency like the US Department of Homeland Security or Interpol? The following are a sample of the qualitative insights included in the report. The responses, which have been edited for grammar and clarity, appear below along with each respondent's first name, job position and geographic location. "Absolutely not. Asking suppliers to report such activity changes the relationship between the supplier and customer. Other mechanisms to detect such activities should be in place, but not reside with the supplier." Crystal, Lab Director/Supervisor/Coordinator, North America Absolutely not. There is no way screening could be conducted so that scientists with honorable intentions are not mistaken for bioterrorists. Take the Thomas Butler case for example. The intentions of this scientist were determined by the authorities without regard for the science. Dileep, Staff Scientist, North America "Absolutely not. This would put an extra burden on the provider, which would ultimately translate into additional time and/or cost for the consumer. The task would invariably affect researchers with 'honorable intentions' and could potentially put a heavy burden for the average consumer to purchase custom oligos (documentation, verification, etc). One can also expect that scientists with less than honorable intentions would likely be able to circumvent such regulations (e.g., shorter, more 'generic' oligos, etc.), thus making such a watchdog step not very value added. In all cases, ""suspicious"" orders (whether from questionable sources, or those using ""unusual or peculiar)." Danise, Staff Scientist, North America "Absolutely! One could easily construct the minimum sequence needed for the ""active site"" of the Ebola outer membrane protein from oligos. This could then be integrated into the genome of less dangerous viruses. Studies have been done that show the less dangerous viruses then cause hemorrhaging! The fragment is only 200 a.a. if I remember correctly. The suspicious orders should be passed to Interpol because the capacity of a US department to work internationally is lower." Jim, Graduate Student/Research Assistant, North America "According to the law in Japan, here, that should be YES. First, all of the oligo supply should be for research only that would be the rule for scientists. For this means, if someone ( or a scientist?) orders any oligo with biotoxin threats, the supplier has the right to check his aim and confirm with the organization the researcher is from." Yuha, Staff Scientist, Asia "Although I believe the potential for making a biotoxin from scratch in a ""home"" lab is unlikely and more a scare tactic which blinds us from more likely possible threats, the ease at which this could be implemented should be fairly easy. I do think the funding should come from the DHS and not from the companies themselves." Patrick, Staff Scientist, North America "Although it may be desirable for suppliers to screen custom oligo orders for potential biosecurity threats, I don't think that it would effectively decrease the risk of bioterrorism. A nefarious terrorist intending to design a bioweapon would most likely not use a commercial (traceable) supplier for oligos, or would design the weapon so that it would not be easily detected from the oligo sequences (e.g., the harmful gene would be cloned and amplified by unrelated flanking oligos). If a supplier were to receive a ""suspect"" order, it would not serve any security purpose to just decline the order: the rejected order would then be sent to another supplier, which might or might not screen and flag the order. On the other hand, reporting such orders to a monitoring/surveillance agency might not have the ability to distinguish legitimate research uses from criminal intentions, unless there is other data indicating that the customer has suddenly changed from a well-established pattern of orders or displayed some other unusual activities. Unfortunately, suppliers might face a lose-lose proposition. Failing to report a suspect order that leads to a bioterrorist attack might lead to negligence or liability lawsuits, while overzealous unfounded reporting might lead to defamation claims." Karen, Principal Investigator, North America "Are you asking us to solve world's problems in a couple of lines of text? To make it clear for you: The issue of bioterrorists does not have its source in the science itself and, therefore, it is not science's ""job"" to deal with it. Every scientist knows that problems have to be solved at their roots. Ask your favorite politician if you look to solve these issues." Dubravko, Post Doctoral Fellow, Europe "As for certain chemical substances, oligo ordering can be monitored. If such delicate oligos are ordered, a short summary of the project should be provided and this laboratory should be reported to the appropriate national security agency." Luc, Staff Scientist, North America At first I do not believe that no honorable scientist or lab will employ or tolerate anyone in their lab doing suspicious experiments. Suppliers might screen orders of unknown and new labs and/or labs from foreign countries with doubts of trustworthiness. In case of suspicious orders they may ask for a justification or permit which such labs may apply for at the domestic agency controlling weapon trading. Roland, Staff Scientist, Europe "Because of the highly competitive nature of Pharmaceutical work, we do not want anyone to know what early-stage molecular targets we are working on. If oligo synthesis companies started screening oligos, many companies would be forced to do their synthesis in-house, and the oligo synthesis industry would probably suffer financially." Katherine, Staff Scientist, North America "Big Brother is watching YOU! No thank you, stop this! I believe, that a guy who really wants to do ""naughty things"" has other ways to get its oligos made. Screening will just add extra costs and take more time to the production. And imagine: a company finds ""oligos to amplify a cholera toxin""... actually, I could be working on this toxin, and need them. Imagine the trouble to get those ...oligos after they have found that the allow amplifying the toxins; more letters, more phone talks, government agencies bothering around ... No thank you not for me. Stop the terrorist mania; they get the materials anyway through ""personal machines"", on a late Saturday evening ... and no way to control this, and much safer for them." Marcel, Staff Scientist, Europe Big brother should stay out of research and focus on real threats. Screening oligo orders for potential biosecurity threats is ludicrous and will ultimately not provide any real security. Bruce, Principal Investigator, North America "Biosecurity threats are already dealt with through university committees such as recombinant DNA review boards. If the oligo companies are careful about who they sell oligos to, then I don't think they need to screen oligos for biosecurity threats. I'm not sure how these issues are handled in industry, although I think that the biosecurity rules are federal and would cover industries. It seems that if oligo companies had to do such screenings, they would have to have a group to report the problem to (so that the oligo companies would not have to take on the investigation or enforcement). Would that be Homeland Security? This seems like an extra burden for the oligo companies to take on." Katherine, Principal Investigator, North America "Biosecurity twaddle! No, No, No. The scientific community should in no way encourage the maximum security state to spread its coercive tentacles further into society." David, Staff Scientist, Europe "Definitely not. A screening procedure would be inefficient, a bureaucratic burden to the serious scientists and a waste of time and money. There are too many unsolved, and may be even unsolvable questions. There is no way to tell if an oligo will be used for honorable research or for bioterrorist activities. Even if a procedure would permit to identify terror oligos with a high probability with an ""acceptable"" rate false positives, whatever this limit may be, any terrorist could either synthesize his own oligos or find someone else to do it. Since there are too many ways, methods, companies and oligo synthesizers in labs in the world, who could manage to control each of them, and who would be responsible for financing this undertaking? How could even an international agency in countries with uncooperative governments or organizations manage to control each lab with the capacity to synthesize oligos? Who would be held liable for hindering research, research careers and financial losses that complying companies." Peter, Post Doctoral Fellow, Europe "DNA synthesis businesses should not take the roll of policeman or security agents. Besides, the availability of instrumentation and reagents for DNA synthesis is so wide spread that it would be a fruitless exercise. It is too easy to get around any type of surveillance." Ivan, Graduate Student/Research Assistant, North America "Drugs and chemicals are regularly kept watch upon for misuse, oligos are no different. I would have no problem knowing that my orders are being recorded in a database to screen potential threats. All honorable work can be easily explained, as transparency is a hallmark of scientific research. It is the manufacturers right to collect this data, and the government's right to ask to see such a database." Alan, Graduate Student/Research Assistant, North America "For security reasons, it is reasonable to set new rules that will require the oligo providers to run systematic controls on the product they deliver to their clients. A simple approach would be to query each oligo sequence against a database of pathogens in order to identify any instances where one oligo matches a pathogen gene sequence. If such instances are detected, the oligo vendor would be responsible to contact any Federal Agency to request a background check on the client and a clearance for delivering the oligo." Manuel, Principal Investigator, North America "Gee, What a question! Do you honestly think that anybody with illegal intentions is going to order from a commercial supplier? And even if, what would you screen for? Desktop synthesis is much easier and very accessible to most labs." Michael, Post Doctoral Fellow, Europe Given the current international events I believe that companies should screen oligo orders for potential biosecurity threats. In the modern political and technological environment I believe that labs dealing with these genes or organisms are tightly regulated and should have no problem proving their legitimate purchase of such products. And if the companies are unable to acquire such validation than yes I do believe it is their responsibility to not sell these products. It is no different then chemical suppliers selling bomb making material. Stephanie, Graduate Student/Research Assistant, North America How is it proposed to distinguish between state sponsored bioterrorism and individual bioterrorists? Austin, Principal Investigator, North America "I am not in favor of suppliers filtering such requests. Any such research going on in a laboratory will definitely be taken care of by the higher authorities of the respective institutes. Moreover such screening will affect the work by unnecessary interference. At the most, suppliers may collect a declaration from the PI in this regard." Vikas, Post Doctoral Fellow, North America "I am not sure it is good idea to screen custom oligos for potential biosecurity because of the following simple reasons. 1. First off all it is an expensive undertaking. 2. If a terrorist group is planning (even thinking) such an attack, I don't think they will be coming to a commercial supplier for the synthesis. Since the table top oligo synthesizer is cheap they will purchase the instrument. Considering the above reasons I don't think it is good idea." Madaiah, Lab Director/Supervisor/Coordinator, North America "I am very uncomfortable with the thought of a commercial company deciding whether or not a scientist is a threat and worth turning them over to government harassment. I suppose a company could run every oligo through a quick blast search, to see if it made anything they considered objectionable. If a positive hit is found, then the company could refuse to provide the oligo and tell the researcher why. However, I don't see any reason that commercial companies (oligo companies, phone companies, etc.) should be spying for the US government." Margaret, Principal Investigator, North America "I believe oligo houses should make oligos - period. Oligo houses should not be comparing sequences of ordered oligos to anything. I used to direct an in-house core DNA synthesis facility. If someone wants to make oligos for a dishonorable purpose, there are plenty of other ways to get oligos than to purchase them from an oligo supplier. If someone has enough knowledge to construct a recombinant organism that produces a toxin at levels sufficient to be a concern, then they certainly have enough intelligence to make their own oligos for the same purpose." Bob, Lab Director/Supervisor/Coordinator, North America "I believe this 'potential biosecurity threat' is a red-herring personally. However, to ensure the over-zealousness of our present governments and their headline grabbing sound bites, maybe oligos SHOULD be screened against known pathogens. But rather than automatically declining orders or reporting to some quasi-militaristic paranoid arm of the government, maybe a bit of common-sense should be exercised, such as examining the postal address of oligo orders and some discrete enquiries?" Jason, Staff Scientist, Europe "I believe, if a supplier feels suspicious about their client they can ask some security agency to conduct a quick security check of the client/institute. But this should have a time frame (maximum 3 weeks from date of order), because if security check takes too long then it would hamper honorable research and for science time is very important." Aditi, Post Doctoral Fellow, North America I can't say that I've ever thought about it. I don't think that it would be an effective way of preventing bioterrorism when a person could easily buy an oligonucleotide synthesizer and make the oligo. I think such screening would not be likely to catch a major threat. Jennifer, Principal Investigator, North America I do believe that the cost of the table desk oligo synthesizers offer an easy way of producing needed oligos for those who are not going to put in public domain their work results. Krzysztof, Graduate Student/Research Assistant, Europe I do feel that there should be some sort of check but without becoming completely paranoid because I am sure that bioterorist can purchase machines to synthesize their own oligos. So it is a little too much to start suspecting all scientist of wrong doing. Lets not get paranoid! Francoise, Post Doctoral Fellow, Europe "I do have mixed feelings here. On the one hand, because I am involved in counterterrorism R&D I strongly believe some potential threats should be looked at. On the other, progress in science should not be hampered too much. So, limited, fast, screening at the supply side without any price and delivery consequences would be OK." Maarten, Lab Director/Supervisor/Coordinator, Europe "I do not believe that the responsibility lies with the suppliers of oligos to screen for potential threats, any more than I believe they have the capability to effectively perform such screens without incurring a prohibitive cost. I believe that it is up to security agencies to monitor suspected organizations, and know when they are purchasing synthetic oligos and act accordingly. If a suspected group is making purchases, it would then be possible to collect information on their past purchases and try to identify whether or not there actually is a significant threat." David, Graduate Student/Research Assistant, North America "I do not believe the synthesizers should screen. If someone wants to make oligos for such purposes, they will find another way." Raymond, Lab Director/Supervisor/Coordinator, North America "I do not know. But it has become so easy to produce oligos ""at home"" and how do you control such synthesis?" Marta, Graduate Student/Research Assistant, Europe I do not think that suppliers should screen custom oligo orders. There has to be some freedom left in science and there is too much paranoia associated with potential biosecurity threats. Past experiences have taught us that once there is one screening mechanism in place others soon follow. Perhaps governments should screen themselves first. Paul, Principal Investigator, Europe I do not think the suppliers has the right or the responsibility to check each order of their customers. Because that can also lead to spying on competitive labs. If someone wants do any illegal activities with a gene then buying a synthesizer and synthesizing your own oligo is not a problem anyway. And commercial suppliers may not check and control the academic research. Asli, Post Doctoral Fellow, Europe I do think that oligo suppliers should be able to screen orders for such threats. Orders that are flagged should be reported to appropriate agencies. The suppliers should not decline an order based on this screen. I do think that it should be the responsibility of the agency to provide the method of screening (software) and the sequences for which to screen. Allowing the supplier to select the method and sequences could jeopardize the confidentiality of the customer. It would be best if the supplier does not even know if there are flagged sequences. The screening software should just send the information to the agency. Peter, Staff Scientist, North America I don't believe that suppliers should screen oligo orders for potential security threats. The suppliers job should be limited to provide quality products at the best price. Let law enforcement officers identify and deal with potential threats whichever way be deemed appropriate. Dipankar, Staff Scientist, North America "I don't see any potential dark side of commercial gene synthesis since DNA represents no threat but is an intermediate tool to make protein, the final and effective product. However, protein synthesis could be the real threat if there is no control by the biotech who produces it." Franck, Principal Investigator, North America "I don't think screening any regular DNA order is very practical or sensible. Any individual or firm with intentions of bioterrorists will have funds, talent, space and access to such synthesis facility on their own. So I believe, more screenings will just slow down the pace of regular scientists. And in a far-fetched way the only people to benefit from this will be the companies who sell oligo-synthesizers! And referral of so many ""not actually suspicious cases"" to Interpol will divert them from real issues." Alfica, Post Doctoral Fellow, North America "I don't think screening of custom oligos, every time, is warranted. It is too costly and too time consuming for distributors to screen for threats of every order. Targeted screening may be warranted, though it must be done in a regulated manner." John, Staff Scientist, North America "I don't think suppliers should screen oligo orders for the above purpose because, so far, we, the community of scientists have shown great responsibility when ordering these oligos. We have our own screening mechanisms in the academia, hospital, etc. If we start to involve ""official"" agencies in a basic process for a laboratory, such as ordering oligos, the drawbacks for research will outnumber the advantages." Elena, Post Doctoral Fellow, Europe "I don't think that suppliers should be required to screen oligos for potential biosecurity threats for 2 main reasons. First, the costs and time-consumption of extensive screening will be passed down to the end-user and negatively effect the majority of consumers, the people who aren't a threat in the first place. Second, if dishonorable people want to clone toxic genes or perform other biosecurity threats, they will figure out a way to do so, regardless of screening on the part of the oligo companies. I do not think that screening will deter them, they will find away around it (like make their own oligos for example)." Caroline, Post Doctoral Fellow, North America "I don't think the order should be denied but it should be justified by both the end-user and the end-user's confirmed supervisor. Sometimes a toxic gene product is used to determine if tissue-specific gene targeting has been successful in transgenics, so refusing an order may interrupt legitimate research." Katherine, Staff Scientist, North America "I have personally had custom oligos made to PCR and clone a portion of a bacterial toxin that could not be transported in its entirety (this was pre-9/11). It was the only way to subclone this gene. The goal of the research was to generate a chimeric toxin for structure activity relationship studies. Had the oligo suppliers been watchdogs then I'm sure I would had have a long justification period that would only serve to slow the pace of research. I don't believe that it is the job of suppliers to regulate the scientific and bioterrorist communities. Even if they did, there are always ways around them. Do we then regulate the sale of oligo synthesizers and related chemicals. Where do we draw the line?" Timothy, Principal Investigator, North America "I have read about the issue, and this might be necessary, but not for trusted customers. But, in principle this is not a valuable idea." Konstantin, Graduate Student/Research Assistant, Europe I haven't thought about this before. William, Graduate Student/Research Assistant, North America "I strongly support the freedom of research and thus am against a screen for potential biosecurity threats. This screen would not help to avoid misuse as people with ""dangerous"" intention won't officially buy oligos through a supplier rather they synthesize them themselves. Restrictions enhance the fantasy and creativity to escape them!" Marie-Theres, Professor/Teacher, Europe "I think it is an infringement of our scientific privacy (i.e., what we are trying to research) to screen these DNA sequences for anything. While most are fairly specific, one could easily be mistaken for some oddball virus and a scientist would have to spend a lot of his/her research time defending these. Don't screen the DNA, screen the customers. I think it is pretty clear who is ordering oligos and for what purpose (i.e., from a company or academic lab) without doing full blown screen of the actual DNA sequence." Deborah, Principal Investigator, North America "I think it is getting too complicated to screen oligo orders. Very often oligos are so short that the sequence information you get is not going to tell much about the genes cloned. There is just going to be more hassle than benefit for this type of things. By far the majority of scientists are not trying to kill other people. There is enough control already over the research conducted, at least in the European and I think also in the North American research." Elina, Post Doctoral Fellow, Europe "I think it is stupid to screen custom oligos for potential biosecurity threats. I'm a strong believer of the fact that not all risks can be prevented (in general). The more you try to prevent things like this, the more it will happen in the end. I think that all things that have been done to prevent terrorism so far, have increased the chance of terrorist attacks rather then decreased." Wilco, Post Doctoral Fellow, Europe "I think it would be very difficult to screen for such DNA sequences without adding extra cost or time to the synthesis. In addition, someone could order pieces which they would later construct into something larger which may not be easily recognizable as small oligos. Frankly, I think someone with bad intentions would probably have their own synthesizer." Lynn, Staff Scientist, North America "I think screening should be used, and the suspicious orders should be subject to further verification and registration." Jeff, Post Doctoral Fellow, North America I think that a customer that orders such oligos should be kept in a database for future reference. I think all good intentioned scientists will be happy to comply with being flagged if they order such oligos in the name of homeland security. Alex, Staff Scientist, North America I think that a security screening would be too much. However considering the many false entries in GENBANK a supplier might decline the synthesis of an oligo just because an uncommon multiple cloning site is used which is by chance included in a bioterror entry. Thorsten, Post Doctoral Fellow, Europe I think that all DNA is subject to use controls and could be handled by the DHS or other agency as a regulatory body to allow for proper authorization of certain biohazard threats. It always could be a possibility however remote that we can anticipate for. Steve, Staff Scientist, North America "I think that as long as the purchase order comes from an institution (university/company) and there is an appropriate paperwork in place, such screening may not be necessary. If the order comes from individuals for instance then the order needs more scrutiny as to what gene is being synthesized, etc." Enal, Lab Director/Supervisor/Coordinator, North America "I think that it is a very good idea to screen oligo for potential treats, however it is difficult to see the intention of a bioterrorist just from a gene. It is possible to use as a bioweapon a gene that is not from a bacteria that is infectious but rather from a normal cell that defends an organism. Also some toxins are used as therapy at low doses in some cases (for example botulinum of botox which can paralyze muscles but also used in cosmetic application). An alternative would be to rely on the client to write a brief aim of the experiment and this should carry the signature of a PI from a recognized university. The company should have any suspicious sequence checked by a committee and if the sequence is proved to be suspicious then a full investigation should take place to determine who is at the origin of this order. The original lab should be asked to give a more detailed description of the aim of the study. Only then the order should be cancelled and the incident reported. Of course I envision a lot of bureaucratic work and many mistakes along the way. Personally I would think that those with bioterrorist intentions would not work from within US at least not at the incipient study as most countries involved in leading these activities have the potential of synthesizing oligos without the danger of being found and the research ended at this stage." Rosalind, Post Doctoral Fellow, North America "I think that it will not help much to screen oligos. You need a considerable amount of knowledge, a pretty well equipped lab or space and some pretty good safety measurements in place to be able to produce these toxins without exposing yourself to lethal amounts. People who have this knowledge and determination are probably not going to use a commercial supplier for their oligos. If it is possible to use a quick database search connected to the oligo ordering process that flags suspicious orders, why not. They can report anything suspicious to Homeland security/Interpol." David, Post Doctoral Fellow, North America "I think that this kind of screening is very hard to conduct with any real efficiency due to the complexity of the material (that is DNA/RNA) and how the same things could be used legally and illegally. However, I think that making sure the companies/institutions are real and that the scientists and addresses are real would be the first screening process. Similarly as when you buy dangerous chemicals, purchase of dangerous (synthesized) genes/viral/bacterial strains should be flagged/licensed." Thorarinn, Staff Scientist, Europe "I think they should not decline suspicious orders, but information about produced oligos should be screened for potential biosecurity threats by domestic or international anti-terrorist agencies." Alexei, Lab Director/Supervisor/Coordinator, Europe "I think this question is irrelevant as there are plenty of automated oligo synthesizers, which are NOT under any screening." Jan, Graduate Student/Research Assistant, Europe "I would imagine that any terrorist with the ability to use such oligos would also be able to synthesize them him/herself using a bench-top synthesizer and a few bottles of phosphoramidites. I doubt that they would use a commercial facility. Screenings would do little to deter bioterrorist uses, and would merely allow the manufacturers and authorities to claim that they are at the forefront of the war on bioterror, when in reality their actions are little more than posturing." Jeremy, Professor/Teacher, North America "I would say most of the oligos synthesized are small and so to make out what gene it is targeted to is faint and would be difficult to find out accurately. Moreover having 3 codons and 6 possible amino acid sequence make the job further complicated. So one can hardly tell anything very accurately about the research going on from the basis of oligos that one uses. I know one of my friends is doing research on one kind of toxin (it is not fetal to humans but causes pain), how do you distinguish those orders from other biosecurity threats? I would say suppliers should not screen and it is hardly possible from the possibility of one oligo among million others. Until now, policing agencies have done a very good job about bioterorists and let the professionals do their job." Ashish, Graduate Student/Research Assistant, Asia "I would say yes, there should be a dark list of labs where bioterrorist are identified. However, this list should be elaborated and supplied by an international security agency. The names in this list should not be supplied with oligos and other products that could endanger others welfare." Ana, Post Doctoral Fellow, Europe "If I was a terrorist and had money to build a whatever biological weapon, I would hire scientists and buy equipment to be independent of ""outsiders"" potentially dangerous for my intentions, thus I would be as secretive as possible. If I was a terrorist and as silly as they usually are, I would use ""natural"" biological weapons as, e.g., anthrax, thus trying a ""low-tech-approach"" and not try to build a complicated synthetic thing. Thus: it is not a good idea to screen for such ""potential terrorist-molecules"" as they will not buy such a stuff publicly and if they do the chance not to find them is very good. Moreover, this screening system will be (besides being ineffective) very expensive: who pays?" Marco, Principal Investigator, Europe If someone turns to the dark side and is determined to synthesize evil oligos then there isn't much we can do to stop them. Screening isn't going to help. Lets all look at the causes of terrorism rather than the symptoms. Jason, Graduate Student/Research Assistant, Europe "If the research facility ordering the oligo is not published in the area pertaining to the biosecurity threat related oligo, the facility should be reported to a government agency for further questioning." John, Graduate Student/Research Assistant, North America "If we start there, what's next? A ban on reagents for scientists who perform stem cell research?" Jen, Staff Scientist, North America "I'm not at all sure how this would be feasible. Would the supplier be responsible for entering all sequences into some giant database? If so, how close a match would be considered a ""threat""? Many might partially match just by random chance. This would clearly add a great deal to the cost and the turnaround time for each oligo. As all research projects need to complete biohazard data to begin with, this assumes that scientists using the oligos are lying! I think this would be a morass. The only precaution I might suggest is if the supplier gets an order from a customer who is not affiliated with any known company or research institution, perhaps greater screening of those orders might be justified." Gail, Principal Investigator, North America "I'm not sure of the utility of a screening program. Maybe could only create problems to honest scientists, while bioterrorists could have enough money to be able of producing oligos by their own." Silvia, Staff Scientist, Europe "Interesting point, which I haven't put much thought into it until now. Although that would probably increase quite significantly the amount of work involved for the supplier (thus increasing end product price), perhaps some genes should be 'under surveillance'. The supplier should most probably contact the proper authorities instead of acting on his own, like declining specific orders, unless there is collaboration between suppliers and government offices and suspicious activities were being tracked. Say a scientist persistently tries to achieve the DNA for a deadly toxin, supplier after supplier. The suppliers would deny the orders until proof of legitimacy of research is provided (some agreement between suppliers and companies regarding intellectual property would probably be in place). In the meantime, the proper authorities would have been warned and would be following the case, doing also their own research/background check on the subject and company. Not saying a lot of false alarms would not happen, but it is like in the airport. I WANT them to stop me and check my luggage and shoes and I account for the extra time when I travel. I wish they could stop every single person and do their job. It is a hassle and it takes a lot of extra time to get in a plane. However, we are making it harder for people with ill intentions to get their way, even if some of us will have to deal with a little extra annoyance just to go to Disney World with our families. Relax and enjoy the trip. Safer is better." Luciana, Principal Investigator, North America "It is not the role for a corporation to police the scientific community. If certain suppliers were to start screening oligos, then buyers would be likely to purchase their oligos elsewhere out of principles alone, or from another country where these rules do not apply, if they were to seek harmful products. Those who mean harm will always find a way around the rules and the honorable scientists would suffer. Also, the issue would arise where to draw the line as a ""deadly"" sequence. What organisms would be included in the list and who would decide this? Restricting research on these matters would most likely happen progress. Would this mean reporting on researchers working on HIV, as this is a deadly pathogen after all?" Barry, Principal Investigator, North America "It is possible that scientists are honorably studying a biosecurity threat in order to find treatments against it. Declining the orders would make it difficult to the research. If such steps would be taken, then some sort of code/authority would need to be given to labs doing this research so that they could be authorized to make the necessary purchases." Laura, Principal Investigator, North America "It may be wise to screen in order to ensure authorization for research using 'dangerous sequences' has been secured from the sponsoring research institution that is also in charge of ensuring oversight from appropriate 3rd parties. This way, the research institution and researcher bear responsibility and are under the proper review. This would be much different than automatic reporting of 'dangerous sequences' to a government agency often very ill-informed and equipped to evaluate the request." Nathan, Staff Scientist, North America "It should not be the role of suppliers to police the types of oligonucleotides they synthesize. That would render them liable in case of misuse, when they have no way of setting up a system that would be foolproof to do that police work. If you don't hold them liable, then that solves the problem of distinguishing between ""good"" and ""bad"" use, which is only reasonable after the use in any case. Such surveillance would not only be full of holes but slow down the entire pipeline. Overall, my belief is that if someone is intent on committing a crime, they will find a loophole easily in a system that apportions responsibility to usage surveillance to the suppliers of any sort of components. Reports of ""suspicious"" orders will cause paperwork that will keep policing agencies from doing their real jobs, involved with infiltration of networks and watching over people's behavior." Heather, Principal Investigator, Europe It would be an enormous task for the supplier to check each and every oligo for its potential to be used as biosecurity threat. Krishan, Post Doctoral Fellow, North America It would be fair to do a screen of custom oligos and any suspicious orders should be questioned by asking the orderer to provide information about why a suspect oligo is being produced. Only after that has been conducted should attention be directed to Homeland Security if the answers are still suspicious. James, Principal Investigator, North America "It would be hard to screen orders for that. If there were sequences the company had an pairwise comparison algorithm for, they could screen orders for certain specific things. I suppose these orders could be flagged and looked at in more detail. Initially, it would be very difficult to determine which toxins to screen for and to set up a system to screen for them. However, I think it would be in the best interest of the company to do so. If someone ordered sequences and produced a toxin which was used in a malicious fashion, I think there would be serious repercussions for that company. Biomedical technology companies seem to operate sort of under the radar of the general public. If something like this were to happen, I think a lot more people would have opinions on what sort of molecular products should be available commercially. The media could certainly sensationalize something like that and cause regulations to be put in place on many products and services that we scientists take for granted because for the large part they are harmless. The other side to this question, is what does the company do if they find someone has ordered sequences for a gene which could produce a toxin. I am sure that the bulk of their orders are from academic researchers and other biomedical technology companies. It would be very difficult to determine which requests are from a genuine company or institution and which ones are just a falsified purchase order. I think a great many man hours could be spent trying to track down purchase orders. There would be no way to screen based on name, location, purchase order vs. credit card, etc. I imagine the only way a company would be able to screen for these things and for anything productive to come of the screen (without us having to pay more per basepair to cover the extra overhead) is if the flagged orders were examined by someone else. But that gets into the whole ""homeland security"" business. A very complex question." Beverly, Staff Scientist, North America "It would seem to be perfectly reasonable to screen oligo orders against some list of highly dangerous genes. However, this could only pick up a small percentage of the actually dangerous genes. It might be very easy to elude any scrutiny either by changing codon usage, or replacing some amino acids with others." Keith, Lab Director/Supervisor/Coordinator, North America "My god, I have absolutely never ever though about this. I live in Europe, and there is no problem with this, really. Sorry to say, but this is an American problem that hopefully will not spread to Europe, like so many other things. If we are supposed to screen on everything there is, how on earth are we going to conduct research? One thing is quite clear for me: I'll definitely not cross any border with a vial in my suitcase (use UPS instead), much less when entering the US. It is enough that my olive oil was screened last time! There is ABSOLUTELY NO question for me that the supplier should NOT have to inform Interpol and MUCH LESS the Department of Homeland Security (NOT MY HOMELAND I may add). It is enough that Europe still forwards names of passenger lists! Man, I am so mad right now and I hope you get a bunch of angry European emails on this." Verena, Post Doctoral Fellow, Europe "No I do not believe that suppliers should be responsible for ""policing"" orders. Would this not impart liability on them if they fail to identify a suspicious order?" Christopher, Staff Scientist, North America "No I do not think that oligo orders should be screened for possible hazardous materials. If terrorists want to use biological weapons it would not be affordable to synthesize necessary amounts in this way. And if terrorists need those oligos to refine their process of generating a hazardous toxin they could not be easily distinguish from normal scientists. There is always a certain risk that terrorists might think of new ways to threaten our security, but to be 100% secure also means to abandon our freedom. If terrorists should ever be able to make us control everything and everyone then they have truly won!" Timo, Graduate Student/Research Assistant, Europe "No screening must be conducted. If, for any reason, a company starts screening oligo orders and report the results to governmental or other agencies, I would immediately stop purchasing from them and select a new supplier. If that meant ordering from a company abroad, than that would be what I'd do. I do not accept interference with science on ill-defined and usually not justified grounds." Frank, Principal Investigator, Europe No screening should occur. Usually people order through their companies/institutes which are known. Basically when you want to operate as an institute or company you need certain certifications to make sure that work is performed within the regulations and only combined with these certifications you are allowed to work with custom oligos. Alan, Graduate Student/Research Assistant, Europe No they should not screen! Stefan, Lab Director/Supervisor/Coordinator, Europe "No, at least not from academic institutions where freedom of research should be maintained." Zen, Post Doctoral Fellow, Europe "No, because anyone capable of amplifying genes with any potential biosecurity threat are also capable of making their own oligos, or getting around any screening procedures the companies would implement anyway - their screening procedures would then just waste time and cause conflict with legitimate research and possible do more harm than good to the research community at large. At worst, if screening is implemented (and assuming it worked well without a lot of 'false positive' error rates) and they detect a potential threat, they should query the investigator first for an explanation or have the investigator's institute sign a letter of assurance that the oligos are for legitimate scientific research in the investigator's field." David, Principal Investigator, North America "No, because this could likely result in far more false alarms than useful tips. Chasing so many wild geese is a poor use of resources especially since the history of bioterrorism strongly indicates that the genetic engineering of threat agents is very unlikely. Most terrorist cells have it as their goal to achieve rapid results. Thus those that would even consider biological agents are far more likely to try to obtain and grow a known pathogen rather than try to engineer one. The potential threat of bioterrorism is vastly overstated by the media and some government officials. Conventional explosives and/or the release of toxic industrial chemicals are a far greater risk." Phillip, Principal Investigator, North America "No, I am not sure how that would be done. One could always buy their own synthesizer and make any oligo they wanted." Chris, Principal Investigator, North America "No, I do not think that custom oligo orders should be screened for potential biosecurity threats. If there is any screening that should be done, it should be at the individual level (customer), not the product being ordered. There is little chance that screening by DNA sequence information would yield any reliable hits. Furthermore, there is a good chance that hits will come up that identify a threat where none exist, thus imposing unnecessary stress on scientists." Ivan, Staff Scientist, North America "No, I do not think that the orders should be screened." Vladimir, Principal Investigator, Europe "No, I do not think the suppliers should screen custom oligo orders for potential biosecurity threats. The government should set up the regulations on the orders for the custom oligos that could cause potential biosecurity threats. The order should get approved by the institution or company Biosafety office before sent to the suppliers." Weiying, Staff Scientist, North America "No, I don't think so. Many bacterial toxins and other ""dangerous"" genes are studied not for bioterrorists purposes, but also for medical research. And who from suppliers will decide whose research is safe and whose is dangerous, who need that oligos for medical research and who for other dangerous activities?" Pavel, Post Doctoral Fellow, Europe "No, I really don't think so. This will not stop any ""bioterrorist"" to synthesize their oligos if they really want to. But if the companies want to implement this procedure they should only do so if this will not increase the oligos price and not delay the delivery. " Diana, Post Doctoral Fellow, North America "No, I think it is unnecessary to screen for potential biosecurity threats! However, although screening could be conducted on oligos ordered from known rogue nations, unfortunately, no matter where you are, there will always be ""respectable"" scientists going over to the dark side!" Mauritz, Post Doctoral Fellow, Africa "No, I think the scale of the potential threat does not justify regular screening. Such procedures would siphon money, energy and personnel from the regular customer service facilities. Also, oligos are available from other not supervised countries." Ildiko, Principal Investigator, Europe "No, if research is not free to operate anymore, I stop in this line of field." Hugo, Staff Scientist, Europe "No, if they really want to get these oligos, they can easily get them from other sources as well." Yibin, Lab Director/Supervisor/Coordinator, North America "No, it doesn't really help since they have their own sources, and will likely use their own sources." Betty, Lab Director/Supervisor/Coordinator, North America "No, it is the right of scientist to do the research he would like to do. The government only need control the result, not the process." Xiang, Staff Scientist, North America "No, it should not be necessary. The founding principles of scientific practices is good ethics. If someone wants to violate those principles they can do it irrespective of this screen." Amrita, Post Doctoral Fellow, North America "No, it takes more than just a PCR product to produce something dangerous. And then it still needs to be efficiently weaponised. Newspapers do like to publish a good story though." Valerie, Post Doctoral Fellow, Europe "No, it would be impossible to tell legitimate researchers from terrorists. Where the request comes from would show more than what was requested." John, Staff Scientist, North America "No, it's none of their business." Jamie, Principal Investigator, North America "No, research should be independent and free and not controlled by the government. The government or company already controls the research by the grant attributions. They cut the budget of research fields they don't appreciate (e.g., effects of the OGM on health). Bioterrorist are terrorists. I don't think they will use the company services for their activities." Catherine, Post Doctoral Fellow, Europe "No, since people with terroristic intentions will always find a supplier who does not screen sequences and if some companies screen then other companies that do not screen will have a certain advantage on the market." Christoph, Principal Investigator, Europe "No, suppliers should not be held responsible for the end uses of their products. I would pay up to $1.00 more per oligo if a company did decide to apply a security screening layer to their oligo synthesis. Any company that has this screening could decline to synthesis an order unless a grant number (NIH grant or other granting agency) was supplied. Many granting agencies have the peer reviews and other check in place to screen honorable intentions have bioterrorists. The reporting of this activity should be co-coordinated through the Defense of the Homeland security agency." Ann, Staff Scientist, North America "No, suppliers should not screen custom oligo orders for biosecurity threats. This potentially impinges on trade secrets, patent issues and patient/genetic privacy issues for both academic and private sector researchers. Furthermore, the application of potential toxins (both in protein or encoded DNA) already has to be done with institutional approval at the research setting. This type of research institutional oversight can help satisfy issues of privacy." Edward, Principal Investigator, North America "No, suppliers should not screen for potential biosecurity threats. Customers ordering custom oligonucleotides should have already be vetted to be authorized to order and receive these prior to ordering specific oligos." Philip, Post Doctoral Fellow, Europe "No, there is no need to screen individual oligos for screening the bioterrorism. Instead just keeping the record of ordering agency by the company should be appropriate. Suppose if any organization orders any oligos, that should be their responsibility not the oligo suppliers. But if order is from an individual or from an organization which is not authorized these order must be screened for security." Pratibha, Post Doctoral Fellow, North America "No, there is not much information you could gain in that action and reporting could create embarrassment to the denouncing company." Joao, Post Doctoral Fellow, Europe "No, this goes beyond 'security conscious' well into the realm of paranoia. The States might be able to implement that domestically but what about all the other countries?" Leonard, Principal Investigator, North America "No, this is too much effort for very limited value. Very difficult to determine what 'security risks' are. What seems ok today might be exploited in some way tomorrow." John, Professor/Teacher, North America "No, we have too much control points already at too many different places." Nikolaus, Principal Investigator, Europe No. Louis, Staff Scientist, North America No. Safar, Graduate Student/Research Assistant, Asia No. Paul, Staff Scientist, North America No. Nathalie, Graduate Student/Research Assistant, Europe No. Dongyu, Staff Scientist, North America No. Milan, Professor/Teacher, Europe No. Guy, Staff Scientist, Europe No. Peng, Graduate Student/Research Assistant, Asia No. Seung-Hyo, Post Doctoral Fellow, North America No. Robert, Principal Investigator, North America No. All of us have burned feet from walking on the road of good intentions! Anyone with bioterroist leanings can simply purchase an oligo synthesizer and not worry about having a 3rd party snoop into their sequences! Allison, Laboratory Technician, North America "No. Any serious bioterrorist organization should have its own oligosynthesizer. If not, it will have its oligos made commercially by a company outside the US or even Europe not bound by such regulations. If screening were to occur, most government agencies are not able to correctly interpret the information received, leading to many false positive (hounding innocent researchers) and false negative (simply missing the implications) trails." Martin, Physician, Central/South America "No. As long as they make sure they are ordering from a customer account and not some ordinary Joe on the street, that should be sufficient." Michael, Staff Scientist, North America "No. At first I thought yes, but with today's technology you can practically synthesize these oligos in your kitchen. There isn't a way to control this and besides, you'd have to be crazy to order a biological weapon from a commercial source. Then again, terrorism has always been illogical." Alicia, Staff Scientist, North America "No. First of all, how would you define so-called ""potential biosecurity threat""? Causing cancer? Relating to human diseases? There will be no limitation in this kind of classification. The whole idea of screening potential biosecurity threats is just a ridiculous concept and another money-wasting topic." Yin, Graduate Student/Research Assistant, North America "No. First, the clients trusted the suppliers for not gaining research intention and possibly associated intellectual property from the oligo sequence information. Secondly, the bioterrorists can always find ways to make the products if they wish." Lei, Staff Scientist, North America "No. For if the supplier cannot be held responsible for the use, then nor should the oligo supplier!" Nagavalli S., Post Doctoral Fellow, Europe "No. How do we know that the bio-supplier knows how to best determine who might be a terrorist or just a well-intentioned scientist. Lord, I don't want my reputation to be based on what some employee at a tech company thinks!" Sarah, Post Doctoral Fellow, North America No. I think that this sounds rather paranoid to me. gerard, Post Doctoral Fellow, Europe No. I think this is nonsense. Howard, Professor/Teacher, North America No. I'm not sure how the supplier of oligos is going to be able to know the intents and purposes of every purchaser. Joyce, Staff Scientist, North America "No. It would delay ""honest"" research and compromise confidentiality of research while doing very little to control bioterrorism. If yes, they should just be reported to a domestic agency which is aware of the kind of research that is being conducted at those institutions (through the funding agencies and the bioethics committee of each institution)." Oswaldo, Staff Scientist, Europe "No. Oligo sequences should not be screened for biosecurity threats because the vast majority of uses for ""suspicious"" oligos will be legitimate scientific investigations. Declining ""suspicious"" orders would unduly retard free and creative inquiry. The only way screening could be effectively implemented would be to establish and fund a dedicated investigative office to whom reports could be made. I do not have faith that current agencies would efficiently and effectively sort through potential threats in a timely fashion. Obviously, any such reporting/investigation system would be expensive and would be easily by-passed by anyone with in-house synthesis capabilities." Thomas, Principal Investigator, North America "No. Suppliers should not be paying attention to the sequences that they are synthesizing. This is proprietary information and it is not the suppliers responsibility to screen for threats. Currently in the biosecurity industry, we already have too many regulations that are interfering with progress." Amy, Principal Investigator, North America No. The amount of oligonucleotides that would have to be synthesized to make a large scale or even small scale poisoning of a population is so large that it would never be outsourced to a company. This is just shear paranoia. R. Scott, Staff Scientist, Europe "No. The signal to noise is too high to warrant this sort of program. The odds that a given order are to be used in a nefarious way are too small, as are the odds that such a use would actually be harmful. In other words, it would be a waste of time and effort." Jonathan, Department Head, North America "No. There is too much hysteria about this and, anyway, if terrorists want primers they can get a machine themselves." Iain, Principal Investigator, Europe No. This is beyond the scope of a manufacturer. James, Principal Investigator, North America No. This is far fetched bordering on paranoid. Paul, Principal Investigator, North America "No. This is not an effective way to control biosecurity threat. The synthesis of oligos can be done in many average laboratories. Furthermore, the commercial companies are not going to be able to discriminate genuine use versus use such as this question indicates." Ramaswamy, Professor/Teacher, North America "No. This would get into the area of privacy due to ""big brother"" monitoring-like activity." Haeri, Lab Director/Supervisor/Coordinator, North America "No. We do not and should not live in a country where big brother watches our every move. As scientists we should be treated with the respect and trust that we deserve and be allowed to make our own judgments on what type of research we do. And besides all that highly dangerous organisms have very close homology to other harmless organisms at the genetic level so such a degree of monitoring would be impractical and point the finger at too many honest, law abiding scientists." Gillian, Post Doctoral Fellow, Europe Not necessary. USA suffers from terrorism. We do not. Jun, Staff Scientist, Australasia/Pacific "Not practical in the real-world for two reasons: 1. True, one can develop complex algorithms to determine biosecurity threats, but the mathematics will still depend on incorrect human assumptions that only certain microbes pose problems. For example, the biodisruption of an industry, such as the milk and cheese industries, may not stem from the government's bioagent list, but can come from a common microbe. [The milk and cheese industries could be disrupted/destroyed with Staphylococcus aureus, as it is not on the governments list as a bioagents. The microbe already is a common source of milk and milk product contaminations. In addition, 10% to 40% of people infected with this bacterium are asymptomatic carriers (i,ii,iii,iv)]. Fear or economic problems stemming from a microbe are real. So too is the cost of non-vaccinees traveling overseas and coming back with a virus or bacteria. The death rate may be zero, but disrupting an industry or treating the sick does make an economic impact statement. 2. In addition, one can synthesize ones own genes/DNA fragments to produce whatever one desires. So why go through a commercial supplier? Consequently, the idea of a supplier screening custom oligo orders for potential biosecurity threats may seem good on paper (i.e., an academic answer), but in the real world it is useless and not practical. i. Noble WC, ed. (1981) Microbiology of human skin. 2nd edition. London, United Kingdom: Lloyd-Luke Ltd. ii. Alterkruse SF, Timbo BB, Mowbray JC, Bean NH, Potter ME (1998) Cheese-associated outbreaks of human illness in the United States, 1973 to 1992: sanitary manufacturing practices protect consumers. J Food 61: 1405-1407. iii. Bone FJ, Bogle D, Morgan-Jones SJ (1989) Staphylococcal food poisoning from sheep's milk cheese. Epidemiol Infect 103: 249-258. iv. Johnson EA, Nelson JH, Johnson M (1990) Microbiological safety of cheese made from heat-treated milk. Part II. Microbiology. J Food Prot 53: 519-540." Richard, Lab Director/Supervisor/Coordinator, Europe Not really. I don't think people doing those things make it so obvious. Ramars, Post Doctoral Fellow, North America "Not that I'm a proponent, but there are several answers to the dark side's pursuit of oligos for biohazard synthesis. The instrumentation, technology and reagents to custom create one's own oligos are readily available for purchase. Furthermore, any savvy molecular biologist could undermine a company's attempts to screen custom ordered oligos, much like hackers undermine anti-virus security and firewalls. Moreover, these potential ""screens"" would require funding to accomplish and those costs would necessarily be absorbed by the common end-user. I suspect that if this were the case, we as end-users would look for alternative (i.e., less expensive) sources for our custom oligo needs." David, Principal Investigator, North America "Oh Big Brother, Where Art Thou! People! Let's all take a break from FoxNews to get away from the politically-led paranoia, and get back to the real world! Here is a dose of reality...ready, take a deep breadth, because it comes. Should someone want to make a bioweapon using oligos, s/he would probably not be ordering domestically, and furthermore, would probably have access to a private oligo synthesizer on which to do it! And of course, that synthesizer would probably be in a mobile bioweapons factory (or so it's been purported)! But should a company find an order so bizarre, then yes, contact the Dept. of Homeland Security...because they have been so good about solving domestic bioterrorism (hmmm, what ever happened regarding those anthrax mailers?). And if anything, DHS should probably be investigating and overseeing private companies to ensure they are not in the business of making bioweapons, and that is both domestically and via off-shore subsidiaries (talking to you, Haliburton!). To summarize, Big Brother, don't waste anymore of my tax-dollars on bogus ""security threats"" that merely provide convenient excuses for your prying eyes." Anthony, Staff Scientist, North America "Ok to screen, but people should be aware that the orders will be screened and invited to let the company know in advance that they are ordering sensitive material and provide checkable proof of credentials." Sue, Principal Investigator, Europe "Please let's not get the government involved before some verification is made of a potential malicious intent. I don't think that suppliers should just decline suspicious orders either, because there is bound to be some company that supplies the investigator, and if there is malicious intent, such provision could be deadly for us all. My suggestion is that the supplier contact someone in authority at the investigator's institution. Presumably, this person could either provide verification that the oligo is needed for legitimate reasons or if not, the responsible person at the institution could alert local authorities (and then possibly federal officials) of a potential threat." Wendy, Principal Investigator, North America "Policing is not and should not be the suppliers' job. Moreover, this will not be of any help because bioterrorists can find other means of getting the oligos they need." Mrinal, Principal Investigator, North America Price. Yanlin, Staff Scientist, North America Pure nonsense. If someone is that advanced terrorist they can certainly synthesize their own oligos. Anna, Principal Investigator, Europe "Researchers using toxins are known to their institutions, and their institutions pay the bills. Analyzing sequences would be quick, but redundant, unless the purchaser is not from an identifiable institution, or out of the country." Ralph, Principal Investigator, North America "Screening a short 20mer may show homology to number of genes, including genes from pathogenic organisms. If the primers were only specific for a gene encoding a deadly toxin, then perhaps the suppliers should query. Again this probably depends on the source of the order - academia, industry or private. The likelihood of a bioterrorist using a commercial supplier may be small - if you want this to be unknown, then they may just buy their own primer synthesizer." Donna, Post Doctoral Fellow, Europe Screening custom oligo sequences for possible threat should not be an issue. You can buy a bench top synthesizer or find other ways to gain any sequence you want. Nicholas, Post Doctoral Fellow, Europe "Screening of oligos does not make sense. Most DNA sequences of potential biosecurity threats are unknown. What if someone primes in regulatory regions for amplification of promoter/terminator and gene of interest? We would have to much regulation. Science with bacteria or viruses would become to difficult. If someone is planning to design new bioweapons, these people are presumably able to synthesize their goes. Should we monitor the use of microbial media, should we restrict sequence information too?" Michael, Principal Investigator, Europe "Screening oligos for terrorists now? Things have really gotten out of hand. You can't buy Sudafed/Nyquil/etc anymore since those can be used to make drugs, and if you buy more that one bag of fertilizer, it gets reported to homeland security as a possible bomb threat. An international phone call? Better monitor that. What's next? Give it up, people. Either we can live under an oppressive Soviet-style regime, in which the government ""protects"" us by spying on everything we do, or we can simply accept that there are some reasonable risks we take to enjoy life, liberty, and the pursuit of happiness." Mark, Staff Scientist, North America "Screening procedures should be established. However, screening of all DNA sequences synthesized by every supplier is probably impractical while maintaining anything like the efficiency and throughput of synthesis demanded by the genuine customer. Screening could more simply be done at the level of the customer, e.g., is the order coming from an established academic or commercial research institute. Recent stories in the press of DNA samples being mailed to personal addresses without any checks highlight a simple way that security could be dramatically improved without serious adverse effect on either the supplier or customer." Graeme, Principal Investigator, Europe Screening should be conducted and suspicious orders should be reported to an agency. I do not believe the oligo company ought to police what is or isn't made. Mike, Lab Director/Supervisor/Coordinator, North America "Screening should take place. The level of control should be at the receiving institution, similar in accountability to that currently in place for the purchase of radionuclides." John, Principal Investigator, North America Screening would be a good idea with follow up reporting to a relevant agency. It should be easy enough to verify a scientist credentials. For once this would ensure that we are actively in the business of prevention of bioterrorist attacks instead of complaining after the event. Kathryn, Principal Investigator, Europe "Screening would be a good idea, nobody should be naive about these issues. For the same reason, we can also no just go and buy any toxin from the pharmacy without providing any justification. Orders of this kind should be questioned briefly, true researchers will be able to give reasonable answers concerning their motivations! But be aware that some of us use e.g., diphtheria toxin to select against non-homologous recombination in ES cells." Thomas, Lab Director/Supervisor/Coordinator, Europe "Should be screened and followed up. We have safety committees on campus that have to check and sign off of all recombinant studies, this sort of request would be scrutinized. You can see legitimate uses though." Anne, Professor/Teacher, North America Should not screen. Ed, Professor/Teacher, North America Such a screen would be difficult to design and completely useless. Do you really think that bioterrorists would not find other ways to reach their means? Christina, Post Doctoral Fellow, Europe "Such screening makes no sense, since if a production of biological weapons is an intend, the organization planning this production can purchase a synthesizer and make synthesis of oligos by themselves. All suspects obtained in such a screening will be normal scientists." Alexei, Lab Director/Supervisor/Coordinator, Europe Such screening may cause more sense of insecurity between scientists and oligo suppliers than a general sense of insecurity caused by bioterrorism. Edita, Quality Assurance/Quality Control, Europe Such screening would be a waste of everyone's time and money. Anyone doing something suspicious would probably be making their own oligos. Frances, Principal Investigator, North America "Such scrutiny already exists for certain precursor chemicals and I have no objection to this. However, any such intervention in the field of oligos would be completely ineffective. It only takes one synthesis to produce a gene which can be propagated ad infinitum biologically, one ""rogue"" with a synthesizer could supply the entire global terrorist community. In addition, the (US) authorities would undoubtedly place the burden of scrutiny on the suppliers thus increasing the costs of legitimate research." Dave, Principal Investigator, Europe Such sequences should be registered in a drugs record book at the ordering institute comparable with narcotics record books. Gilbert, Principal Investigator, Europe Suppliers should be ethically bound to provide the best possible products with any disclaimers and/or requirements for safe handling of products. Any products can be misused and the issue of biosecurity threats is complex. Reputable and ethical scientists should have complete documentation to account for all bacterial gene and other potentially hazardous biologicals used in scientific discovery. Sandra, Lab Director/Supervisor/Coordinator, North America "Suppliers should do all they can to make sure the products they make are used for peaceful or peacekeeping purposes. They should screen and report any suspicious orders to authorities. Having said this, clearly there are ways for terrorists to get around any of these measures." Byron, Principal Investigator, North America "Suppliers should not be the authority to screen oligo orders . It is not their duty, responsibility or authority on matters of biosecurity. Any person or illicit organization interested in products of potential biosecurity will have better methods and resources for this purpose." Shankar, Staff Scientist, North America "Suppliers should screen custom oligo for potential biosecurity. However, it may not so easy and practical to do. It may interfere with research by adding bureaucratic and administrative filters that certainly won't facilitate scientific work. In that case, suppliers shouldn't decline suspicious orders and shouldn't report to a domestic or international agency. The first step to do is to have a database of the scientific groups that need that kind of oligonuceotides to work. Suppliers will have to have a database of their users. In case of a suspicious order they should contact authorities of the institution (laboratory head, department head) from which they are receiving that particular order before filling a report to a domestic or international agency." Andres, Graduate Student/Research Assistant, North America Suppliers should screen custom oligo orders for potential biosecurity threats. Suspicious orders should be declined as well as reported to domestic and/or international agencies. Tahira, Post Doctoral Fellow, North America The company should at least blust their oligos for the potential toxicity. For me it is hard to imagine how the terrorists can use RNA oligos in terroristic attacks. Usually for research amount of custom oligos is really small. Companies who get a big order of toxic oligos should inform the security service because it would be more likely not for research. Iryna, Principal Investigator, Europe "The only screens that are necessary are for potential bioterrorist threats that do not exist outside the laboratory (e.g., small pox). Most of potential bioterrorist threats that I know of are caused by infectious agents that can be obtained in nature, and can be obtained from culturing organisms that can be readily found outside the laboratory. Any screen that is used must respect academic and research integrity. A researcher at a reputable institution should have access to the research tools and techniques that are available. The burden of proof that a customer is a potential bioterrorist must rest with the government, and there must be overwhelming and irrefutable evidence that the suspect is a bioterrorist beyond any reasonable shadow of doubt." Robert, Professor/Teacher, North America "The responsibility of making certain sequence oligos lays wholly on the lab, that ordered it. By themselves, most if not all DNA oligos are not hazardous as they are. To make a biosecurity threatening product (viral, bacterial gene, etc.) out of the purchased oligos so far takes long time and substantial effort and definitely requires other components (e.g., viral packing system) to get delivered in the cells. Thus, combination of some specific primer orders with other e.g., viral component production may be actually suspicious. Overall there should be no threat related to bioterrorism with synthetic oligos as they are, they are merely not sufficient to produce e.g., active viruses. However some control of what is being orderd may makes sense, especially with a relation to the particular labs which place the orders (say if some lab works with Y. pestis and is certified to do such, which is a complicated procedure by itself requiring background checks etc., such lab probably does not comprise any bioterrorism threat)." Alexander, Post Doctoral Fellow, North America "The sale and purchase of deadly toxins is currently tracked, so it is only logical that the precursors to these toxins also be tracked. Assuming that this tracking did not cause pre-emptive action on those purchasing them, there would be no harm in government involvement here. This should only be used for investigative purposes once a biological incident/attack occurred." Vincent, Staff Scientist, North America The screening should already be in place so that people who might be engaged in terrorist activity should not be working in high risk areas. I do not think it should fall on the supplier to vet orders. Thelma, Lab Director/Supervisor/Coordinator, Europe "The vast majority of research conducted at academic and industrial sites is tightly controlled already. An academic lab will be working on projects funded through charities and government agencies and as such these programs have already been scrutinized and approved by authorities. Industrial settings will not undertake research that will be detrimental to their long term survival. In this respect I would feel that screening of oligo orders is un-necessary and intrusive on research. I would expect that if this was to occur researchers would be worried that there may be a possible infringement of their own intellectual property positions/publication opportunities in that other researchers may be able to deduce elements of sensitive research programs being conducted in rival laboratories if the information on oligos being ordered was ever leaked. I feel that many locations may revert to in-house synthesis rather than face yet more questions over research that has already been approved. You can never ensure no one will abuse the system, those wishing to clone genetic material for malevolent use will most likely not use a commercial supplier anyway. They would use a stand alone machine and be less traceable. As we have seen simple laboratories for making crude weapons have been found in houses around the world. These people are inventive and adaptable. They do not need the high-tech and highly regulated environment of an academic or industrial lab to operate. Authorities should concentrate on finding the individuals with the skills to conduct and the ad hoc laboratories they set-up. Let academics have the freedom they deserve to conduct legitimate research. It is in this free environment that discovery is most rapid and how we can benefit humanity as a whole most effectively. Benefits to all people will help undermine those who wish to destroy. We live in a free society, lets keep it that way!" Jonathan, Post Doctoral Fellow, Europe "There are a lot of scientists working with toxins that are not bioterrorists and I believe that it would be near impossible to determine who was ordering oligos for dishonorable purposes. The majority of scientists that order oligos are doing productive and legitimate purposes. I suspect that most bioterrorists have enough money to purchase their own machines and can acquire unsavory fellows to do their dirty work. Therefore, I do not believe that suppliers should spend millions of dollars to screen orders for potential biosecurity threats. Not only would it not be very effective but that additional cost would be passed on to the customers." Patricia, Principal Investigator, North America "There are limitations already in place for who may order materials. Companies are responsible for identifying suspicious orders, they should not be selling oligos to individuals, only to institutions. Government scrutiny of scientific research activities borders upon infringement of human rights and is unacceptable. The paranoia will hamper research and slow down progress." James, Professor/Teacher, North America "There is no reason to worry about genes. A gene is not harmful. In fact, full genomes are freely available at GenBank. No problem at all." Gabriel, Principal Investigator, Europe "There should be a screening process in place. The policing should be done by the government and the research community as a whole working hand in hand. The government alone should not determine what is a biosecurity threat and scientists alone need the trust of the government and society as well as the scientific community as a whole for ethical guidance and support. There are many reasons why studying what may be considered risky science is of great value to our world as a whole. It may reveal major ways to fight disease and even fight potential terrorists threats like germ warfare. However, it is only through open involvement of the public, the scientific community and the government that this progress can be made." Jani, Professor/Teacher, North America "There's a 'dark side' to ANY technology, just look at the death toll from driving cars!! I worry that the 'dark side' is the fear-mongering that goes on by critics and more insidiously, 'the government' when the *potential* 'dark side' is used as a tool to scare the populace into more regulation or more invasions. I do NOT think that screening should be conducted. It's too easy to game the system anyhow, why wouldn't someone just make there own if need be?" Ivo, Staff Scientist, North America "They can screen oligos and get back to the person's supervisor/institution and ask for approval. A lot of scientists in the US are foreigners and I can guarantee that if this were reported to DHS/Interpol, then it would make their stay and travel to the US more complicated (as if it's not already complicated) than normal. Reasonable checks and balances are always needed but the keywords are ""reasonable"" and ""logical""." Bindi, Principal Investigator, North America "They should not supply them. Scientists working in these fields could apply for prior clearance and show the documentation to the company. In cases of violations, it will be better to report to the institution rather than Homeland Security, which does not understand how science works." Ho-Leung, Post Doctoral Fellow, North America "They should screen, and people should have to have a permit to receive gene fragments from possibly dangerous organisms. However, the permit should be quick and easy, based on simply proving you are a legitimate researcher (e.g., funded by real grants, established company). Anyone who is not easily able to prove legitimacy would have to jump through more hoops (e.g., people who work for a 3-person, privately funded company would have to go through a security check). The gene screening would have to be subtle, since genes could be hidden as pieces in other, benign genes. Plus, the ORFs would have to be analyzed to determine if the DNA sequence was just altered, and protein homology considered so someone cannot just change a few residues to mask a pathogenic protein." Jonathan, Lab Director/Supervisor/Coordinator, North America They shouldn't screen them. Nobody screens knives as they are supposed to be used for eating only. Toni, Staff Scientist, Europe "This is ridiculous to ask or expect oligo suppliers screening customer orders for potential bioterrorism. Since oligo synthesizer is available to anyone and anywhere, you think the bioterrorist will use commercial service ""to cut their running cost""? They can synthesis oligo by themselves!" Robert, Professor/Teacher, North America "This really depends on the nature of the research. Yes if you are doing toxin research. No if you are doing anti-cancer research like mine, on transcription factors. Should you report to Homeland Security? Your grant may require it, if yes, then you must. If your findings are significant (i.e., a potential threat exists) then you should." Beverly, Professor/Teacher, North America This will complicate oligo orders and I do not think that it brings more safety. Noureddine, Principal Investigator, Europe "Time: if suppliers were to screen each order, same-day delivery would be nigh high impossible. And time is one of the factors I look for in a supplier. Also, should the oligo be of some patent-pending gene/DNA sequence, the supplier would be infringing privacy and intellectual property rights. Presumably the suppliers would have to keep records if there is a screening process, hence more work for suppliers, cost increases for consumers. Possibly, private companies, research institutes etc could set up some kind of account with suppliers, such that, unless the account number is provided, the supplier has the right to decline. This prevents private buyers from having a garage-laboratory, yet gives scientists some convenience." Beatrice, Graduate Student/Research Assistant, Australasia/Pacific "To quote Benjamin Franklin, ""The man who trades freedom for security does not deserve nor will he ever receive either."" If orders for oligos come from legitimate sources, then there really shouldn't be any need for oversight. Once the government starts deciding what is or isn't appropriate for research, progress is halted. Look at the stem cell debate for example. I can see that if John Q. Public orders two oligos for anthrax to be delivered to his apartment in Queens that this might look suspicious and perhaps should be checked out. But the worry is that the government will start policing everything legitimate scientists are trying to accomplish. I think it would be a step towards the end of intellectual freedom." Rebecca, Principal Investigator, North America To screen each and every order of oligos will be unpractical and in some cases that will affect the secrecy in research. The best way would be to offer oligo orders license to one or more authorized persons in an institution. Dinesh, Post Doctoral Fellow, Europe "Unfortunately, in this day and age it seems necessary to screen orders for potential misuse. If you have to wait to buy a gun, then I think it is just as reasonable for orders of suspicious content (i.e., pathogenic gene) to be screened for authentic research intentions." Tony, Staff Scientist, North America Why bother screening oligos? What's to stop someone from simply buying a DNA synthesizer and making the oligos themselves? You can buy DNA synthesizers on Ebay! George, Professor/Teacher, North America "Why not. We live in a different world now. I don't work in a lab that is doing bacterial research so they would probably have a different opinion. I don't think orders should be declined. If the government is that suspicious all the information to contact these labs should be available to tract where the primers go. Primers are very specialized product mailing them to a basement some where would be weird. I think everything is computerized now so keeping tract to identify particular primers would be possible. Is it the companies responsibility if they are so inclined. The government should supply the information they want. Would I stop ordering from a company that is letting the government screen my order, no. As long as the information stayed confidential. Would I stop ordering from a company that did not send me my order without indicating why or asking because they thought it was inappropriate, yes." Tom, Laboratory Technician, North America "Wow! That is an interesting question and the proverbial slippery slope. My company has engaged in biodefense research in the past under government grants and I don't believe we ever pondered this before. I don't think this should happen but in today's climate and with this particularly paranoid government (Bush, etc.) I don't doubt that it is occurring. I believe if someone really wanted to avoid detection they would simply synthesize there own oligos and not order them. When I order an oligo I expect confidentiality on the part of the supplier as I work for a biotech company. The second I doubt that confidentiality I will make sure we get our own synthesizer (in fact all my previous employers had them and didn't use outside suppliers)." Eric, Staff Scientist, North America Yes and no. I think that you could automatically do a search of the oligo through a database but realistically if a person is going to order something like that they could make it themselves. Angela, Laboratory Technician, North America "Yes because in the industry we are more and more tight in terms of Health and Safety, which I think it is important." Marc, Production/Manufacturing, Europe Yes I agree with the option that the suppliers should screen the oligos and then confirm the order albeit with proper directions and specifications known to the scientist. Prashanth, Graduate Student/Research Assistant, Europe Yes I believe that. Right now anyone with a little molecular biology knowledge and some kits could produce anything. I think that suppliers just need to conduct a search on published papers by the orderer and if they detect any problem inform to the competent authorities. Enrique, Principal Investigator, Europe Yes I think that suppliers should screen for potential threatening products. All suppliers know what institutions and departments their customers are from and therefore could have access to a list of labs licensed to work on potential threat organisms. If the scientist ordering the suspicious oligos is not on the list then the supplier should first contact the institution where they work and then if suspicions are not allayed then contact a domestic authority. Jennifer, Graduate Student/Research Assistant, Europe "Yes the orders should be screened, but since some research will require the purchase of potentially 'dangerous' sequences there must be some system in place that allows researchers to declare their intentions in an official way; perhaps additional documentation authorized by someone senior in the institution could be submitted alongside the order? This could be supplied either at the time the order is placed, or if the order is unexpectedly flagged as dangerous then the suppliers should contact the purchaser and request clarification of the purpose of the oligos." Maxine, Post Doctoral Fellow, Europe "Yes, because terrorists will stop at nothing to destroy Western Civilization." Louis, Lead Medical Writer, North America "Yes, definitely suppliers should verify the origin of the order. Not many labs have reasons to work on deadly toxin." Michael, Principal Investigator, North America "Yes, for ordering these kinds of oligos it should be necessary to have a special form from an international agency or the government which allows the customer to buy these oligos for safe research." Gudrun, Staff Scientist, Europe "Yes, I believe that scientists planning to do research on extremely pathogenic organisms should register with the government. The risk of not doing so is too great in this day and age." Vincent, Lab Director/Supervisor/Coordinator, North America "Yes, I do believe that oligo orders should be screened for biosecurity threats. This is a responsibility for every human being to do everything possible to discourage harm to others. However, governments should help in developing databases available to vendors with oligo sequences that may have 'dark potential'." Pradip, Staff Scientist, North America "Yes, I think a basic screen should be applied and then documentation of the funding source should be requested for sensitive products. If the funding can not be documented then a report should be made to appropriate agencies to ensure that the project is not against world wide interests. I don't think they should just decline the order because the project may in fact be benign and already approved by scientific review." Deborah, Laboratory Technician, North America "Yes, I think that screening should be conducted. However, I feel that if screening is done it should be performed on a universal, across the board (i.e., national) scale by all companies who offer such services. Moreover, signatures on some type of screening-agreement form should be made a requirement for all purchases of this nature. And, most importantly, the sequences of interest and the types of methods used to detect them should be standardized before such an approach is implemented." Janice, Principal Investigator, North America "Yes, I would believe that suppliers should screen, because it is this threat is always possible. but the disadvantage will be they will take more time for product delivery and subsequently will loose customers. So definitely some international and domestic agencies should be started and should work exclusively for the concerned purpose, and should deliver the results to the suppliers within a day. Then we can avoid the threat and suppliers also can keep their customers with trust." Gulrej, Graduate Student/Research Assistant, Asia "Yes, in case of suspicion, explanation should be offered." Borut, Department Head, Europe "Yes, in today's context it is imminent to screen custom oligo orders for biosecurity threats. Suppliers should keep a track of the orders that their customers place and if they smell anything suspicious they should immediately report the matter to the concerned authorities rather than just declining the order. Just declining suspicious orders may not help in preventing bioterrorism as these can place an order on an another supplier and may eventually get the product they wanted. In case of a regular or a reputed customer, the supplier can contact the customer and check the need for the customized order before processing the order." A.K., Staff Scientist, Asia "Yes, screening on custom order should be done by routine to prevent possible terroristic threat. Any suspect order should be reported to a domestic or international agency for investigation." Nadia, Professor/Teacher, Europe "Yes, screening should occur and provision of an institutional biosafety protocol number would assure compliance with regulation similar to ordering animals on an IACUC protocol." Peter, Professor/Teacher, North America "Yes, Simple BLAST search would determine the sequence. This should than be reported to the right agency especially when it is not going through an known academic or commercial company." Ignatius, Professor/Teacher, North America "Yes, there is otherwise very little ability for the national security forces to check up on something like this, it is already entirely too easy for potential terrorists to clone and mass produce bacterial toxins, so it would be good to have an extra level of control in place." Donny, Post Doctoral Fellow, North America "Yes, to potentially prevent attacks or disrupt threats. Alert authorities when orders come in that pertain to biosecurity." Alice, Professor/Teacher, North America "Yes, to reduce possible risks. I think, that it should be reported to the police or another agency to react against possible terroristic activities." Wolfgang, Post Doctoral Fellow, Europe Yes. Christopher, Lab Director/Supervisor/Coordinator, North America Yes. Vasan, Quality Assurance/Quality Control, Asia "Yes. Bioterrorism has become a major threat in the modern world. As the technology is freely available, there is a great risk of misuse. Anthrax is one example! It is the responsibility of the scientific community as well as the service providers to arrest the exploitation of cutting edge technologies for antisocial activities. I strongly suggest the implementation of proper screening of orders for custom oligo orders. It should be made mandatory to give complete details of the organization, affiliation of the scientist and a declaration along with the order." Dipak, Graduate Student/Research Assistant, Asia Yes. It keeps the supplier clean if any bioterrorism threat is present. A declaration on the part of the scientist should be useful for not being mistaken for a bioterrorist. Tomal, Staff Scientist, Asia "Yes. It seems likely that scientists would be able to know in advance of submitting orders whether any concerns might be attributable to their orders. If this is accurate, it seems like such scientists could easily seek prior approval from a vendor seeking either exceptions or pre-approvals or provide scientific justifications for specific oligos. I would also defer to the opinion of the US Department of Homeland security to seek their advice on how the vendor should proceed. From my perspective, I would not have a problem any way one would handle this as all of our projects would not likely fall under such suspicion or raise such concerns. Regardless, I can see how clients might be worried if they submitted orders that were delayed or rejected." Robert, Professor/Teacher, North America Yes. Large scale orders to particular institutes or universities that exceed the average order rate for other universities from any country can be looked-up as suspicious. Scientists making such orders can be asked to give detailed justifications of their research and their work can be judged for potential biohazard by an unbiased independent panel before international security agencies are notified. R., Post Doctoral Fellow, North America "Yes. Pre-registration and security clearance established before ordering. Otherwise, report to authority." Yongjian, Staff Scientist, North America Yes. Selected publication will point to scientist field of interest and by that will rule out any mistakes. Supplier should decline such order and if the scientist insist on purchasing. They should report such orders to a domestic or international agency or at least add a question for the purpose of the study. Atzmon, Lab Director/Supervisor/Coordinator, North America Yes. Suppliers should decline suspicious orders and report such orders to a domestic or international agency like the US Department of Homeland Security or Interpol. There should be a list of PI's working on specific biosecurity threats and they would get the green light. Others would need screening. Jennifer, Graduate Student/Research Assistant, North America Yes. The supplier should have to contact the office of sponsored programs of the University to determine if the scientists has approval by an internal review board. George, Professor/Teacher, North America "Yes. This is a complicated area that needs input from customers, suppliers, infectious disease researchers, and appropriate government representatives. I believe that we can develop some guidelines that would detect real or significant threats that must be passed on to appropriate authorities. These types of issues are not new as companies like Boeing have to also monitor and report possible violations or threats to security as they are a major supplier of equipment that can cause serious damage if in the wrong hands." Nicholas, Lab Director/Supervisor/Coordinator, North America Yes. This poses a clear mechanism for dispersal of a deadly weapon. This should be monitored by Homeland Security or Interpol. Beverly, Principal Investigator, North America |
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