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5. Developing Country Perspective: Microbial Research Commons Including Viruses
– Ashok Kolaskar
23

University of Pune, India

In recent years the BRIC countries (Brazil, Russia, India, and China) have been experiencing rapid industrial growth, and innovations have been occurring at a much higher rate than in many other countries. This trend is not limited to any one specific area but encompasses much wider spectrum of economic sectors. I am referring not just to research and development per se, but also to innovations at every level—in particular, the processes. This rate of innovation has ramifications for all aspects of science and society.

When we look at specifically India, we see companies like Biocon which are trying to develop more biologicals and getting into the largest applications as well as developing products that are important to improving the general health. A second example is the vaccines developed by the Serum Research Institute, which are administered to every third child in the world. There are companies involved in energy and, particularly, biorefining. These companies are learning to use not only the edible crops but also the non-edible crops such as castor bean. Appropriate microorganisms are critical for the process of biorefining whether it involves edible or nonedible biomaterials. A third area includes companies and industries that are looking at producing new types of biomaterials using microbes. So, the challenges are not very different from those in the United States or European countries.

There are also real differences, however. What we are seeing in these developing countries is a sudden increase in basic research as well as applied research, which is happening mainly with the support of government agencies. The private sector is not providing financial support to the same extent. For this reason, there is a need for microbial and genetic resources. Where are these resources going to come from? Right now, most of the resources are coming from the BRCs, including the American Type Culture Collection (ATCC).

India too has started in the recent past, creating similar resources. Microbial and other biological culture collections have been established in several universities and research institutions. As in the United States, we have lost some of these collections. Some of them were transferred as special collections. Ways to recirculate and reuse them have been established, but in a country like India these systems are still in the process of development. Lack of well established systems such as these is one of the main differences.

There are several culture collections in India. The Microbial Type Culture Collection (MTCC) at Chandigarh is the one that is recognized as part of the World Intellectual Property Organization, and it gets the deposits of cultures for patenting purposes. We now have laws similar to those in the United States as far as the patenting is concerned. The MTCC performs a role in India much like ATCC does in the United States.

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23 Presentation slides available at: http://sites.nationalacademies.org/xpedio/idcplg?IdcService=GET_FILE&dDocName=PGA_053663&RevisionSelectionMethod=Latest.



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5. Developing Country Perspective: Microbial Research Commons Including Viruses – Ashok Kolaskar23 University of Pune, India In recent years the BRIC countries (Brazil, Russia, India, and China) have been experiencing rapid industrial growth, and innovations have been occurring at a much higher rate than in many other countries. This trend is not limited to any one specific area but encompasses much wider spectrum of economic sectors. I am referring not just to research and development per se, but also to innovations at every level—in particular, the processes. This rate of innovation has ramifications for all aspects of science and society. When we look at specifically India, we see companies like Biocon which are trying to develop more biologicals and getting into the largest applications as well as developing products that are important to improving the general health. A second example is the vaccines developed by the Serum Research Institute, which are administered to every third child in the world. There are companies involved in energy and, particularly, biorefining. These companies are learning to use not only the edible crops but also the non-edible crops such as castor bean. Appropriate microorganisms are critical for the process of biorefining whether it involves edible or nonedible biomaterials. A third area includes companies and industries that are looking at producing new types of biomaterials using microbes. So, the challenges are not very different from those in the United States or European countries. There are also real differences, however. What we are seeing in these developing countries is a sudden increase in basic research as well as applied research, which is happening mainly with the support of government agencies. The private sector is not providing financial support to the same extent. For this reason, there is a need for microbial and genetic resources. Where are these resources going to come from? Right now, most of the resources are coming from the BRCs, including the American Type Culture Collection (ATCC). India too has started in the recent past, creating similar resources. Microbial and other biological culture collections have been established in several universities and research institutions. As in the United States, we have lost some of these collections. Some of them were transferred as special collections. Ways to recirculate and reuse them have been established, but in a country like India these systems are still in the process of development. Lack of well established systems such as these is one of the main differences. There are several culture collections in India. The Microbial Type Culture Collection (MTCC) at Chandigarh is the one that is recognized as part of the World Intellectual Property Organization, and it gets the deposits of cultures for patenting purposes. We now have laws similar to those in the United States as far as the patenting is concerned. The MTCC performs a role in India much like ATCC does in the United States. 23 Presentation slides available at: http://sites.nationalacademies.org/xpedio/idcplg?IdcService=GET_FILE&dDocName=PGA_053663&Rev isionSelectionMethod=Latest. 31

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There is also the National Collection of Industrial Microorganisms at Pune, and this is completely different from that in the United States. That is, there is a separate culture collection for those microbes that are industrially important and that can be used more for development or in a commercial fashion. We also have a separate culture collection for viruses, and we have a national facility for animal and tissue cell culture along the lines of the ATCC, although it has not grown to the same extent. In addition to these main collections at the national level, we have several specialized collections, and they do not get very much support from the national agencies. These are being done more at an institutional level or as specific projects. As long as those projects are ongoing, these culture collections will grow. For all of these culture collections, most of the information is available only in printed formats. Very few of them have their own websites where the full information is available. That makes getting information from these localized culture collections very difficult. These culture collections have also developed material transfer agreements (MTAs) —not quite to the level that we see at ATCC and similar collections, but they are following similar lines to those established by the ATCC. The result is a similar set of restrictions on distributing the cultures, with advantages and disadvantages that are similar to those with the ATCC. As seen in the United States and elsewhere, the majority of scientists generally try to get materials from these culture collections on an informal basis. As a consequence, it is difficult to be certain about the quality of the cultures used in performing scientific research. This lack of quality assurance makes it difficult to verify research results. Thailand has a similar network of culture collections. One part of the network, the Biotech Culture Collection, has nearly 3,430 cultures. The Department of Medical Sciences has its own separate collection, as does the Department of Agriculture and the Thailand Institute of Scientific and Technological Research. These distributed culture collections generally do not communicate with each other. This is the case not just in India, but in many countries. How good is that interaction in the United States, for instance? Human nature is the same everywhere, and scientists want to hold on to what they have, even though we keep saying that scientists like to publish. Yes, they do like to publish, but only the final results. Once scientists have developed those collections and materials, they want to hold on to them. There are a variety of issues facing culture collections in developing countries. In most of these culture collections the characterization is very minimal. Few culture collections are characterized at the DNA-fingerprinting level, and we do not know whether a given culture in the collection is the same as or different from some other culture. The data are not fully computerized, and information about the cultures is not easily available, as I have already mentioned. Moreover, in most culture collections there is duplication: The same cultures are available in different base collections, and.this leads to higher maintenance costs. The material transfer agreements are similar to those used by ATCC and by most repositories. There is no system in place to detect or prevent misuse of an MTA. An MTA may be signed, but we do not yet have a system to detect whether the MTA has been used or misused. Nor are there any good answers to the question of what needs to be done if the the MTA is misused. That aspect of the system is still very weak. Another major difference between the developed and developing countries is that, at least in India, very few scientists are conversant with taxonomic classifications. Even 32

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at the national culture collections, there is a paucity of skilled human resources. We keep boasting in India that we have a demographic advantage, and we do have a young population below the age of 25 years—nearly 550 million, out of 1.2 billion total population. If we train them properly, the members of this population segment can do wonders. However, there are several obstacles that come in the way of exploiting this population advantage; current state of training is not of acceptable level; remuneration is not attractive to bright youngsters; and finally the repetitive nature of the work does not offer intellectual stimulation. Inability to recruit new generation of taxonomists to replace the older retiring taxonomists is going to be a huge issue. Finally, concerns related to biosafety and national security are still not given due emphasis in developing nations compared to the developed countries. There are issues that go beyond the microbial commons. At the current time the desire to understand the functioning of an organism extends beyond the gene level. There is great interest in looking at metabolic pathways and figuring out how to describe them - what language should be used to describe the pathways - and how to describe the results obtained from analyzing the metabolic pathway information. It is important to deliberate about what sort of commons we will acquire for this purpose. We need to double what we have been doing last few years, try to collect the metabolic pathway information on all those microbes whose genomes are fully sequenced as well as study the data that are available in the public domain, and then curate them. Most of the metabolic pathway information that is available is not in the public domain and is not necessarily fully curated. Since labor costs in India are lower than in developed countries, our group at Pune University made use of that asset and tried to curate this information and build a metabolic pathway database. In a fashion similar to what the previous speaker described regarding brain research, we are trying to integrate all the relevant types of metabolic information into this database. This includes information on genes, enzymes, and various types of chemical and biochemical reactions in addition to information on the organisms themselves, and that is where we will need a proper commons. In addition, we have added the data acquisition and integration tools to see that all the data are entered in a systematic fashion. You can imagine the knowledge that can flow from such a resource—and this includes everything from visualization tools and structure predictions to the simulations of various structures and of the organism itself. We have indeed developed a visualization mechanism within the system for small molecules, the metabolites. It is also possible to develop models to look at large complexes. We would like to extend the analysis of the metabolic pathways to the level of patterns. However, the number of identified pathways is much smaller compared to the total number of pathways present. It is still a major challenge to identify all the pathways. Examining metabolic pathways is one of the major means to understand how the microbes are related to each other, rather than simply looking at their genomes and calculating the phylogenetic distances from each other based on the genome information. Indeed, the two approaches lead to two completely different trees representing the relationships among the microbes. This has a potential to change our whole understanding of the science. The study of metabolic pathway similarities amongst different organisms is also essential to engineer new pathways or new microbes with specific properties. Some pathways are absent in one particular bacteria versus other, so we can start looking at whether this is what differentiates one species from the other species. Most of 33

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the times we look at what the species have in common and not how they differ. If we use this molecular-level information and look at the differences that will probably tell us better how to even name them properly. We have given them names according to their macro properties, but we have not really taken micro-level details into account. Now that we are able to see the micro aspects, I think we should re-look at all of these things and decide how we should distribute, divide, and further classify them. One of the major issues in developing such a database is taxonomic classification, which has been done according to whatever is available from the National Center for Biotechnology Information. If this information has any errors, these errors will get translated into most of the secondary databases. In addition, there is no standard system to represent the metabolic pathways themselves, and we will have to develop that as well because, as we start looking at bringing in and integrating the information, we cannot go further unless we have certain standards. We create these standards mainly to coordinate activities and exchange information amongst different groups. Those who are specialists or who are working on a special project probably do not require these standards because they understand exactly what is being done. But when people come from different backgrounds and want to understand what is being said without any ambiguity, these standards become necessary. We must ask, however, how far to go with standardization. If we standardize too much, we may lose necessary flexibility. We have to bring in the systemization only to that level that is necessary for exchanging views, information, and in such a way that everyone can understand what is being done without any ambiguity. In many cases, the chemists have tried to put together some type of commons. We will have to see how well these can be integrated with the metabolic pathways database in development. The other issues that need to be considered for integrating the information generated by the chemists with metabolic pathways database are the accuracy of the data and also the accuracy of data entry. This is particularly so in the case of different isolates and different strains because there can be variations in chemical structures of metabolites and other pathway components even amongst the different isolates and of course different strains. Depending upon which commons we use, which tools we use, and the way we look at the microbes, we are going to describe the system in very different ways. We may require different words. We will, therefore, have to start asking the questions: What is the best way, how do we say it, and how can all these things be integrated into the system as we develop commons and semi-commons? Viruses are one set of organisms that will need to be examined because viruses are part of the microbial world. We tend to concentrate mostly on bacterial systems and do not include viruses at that level. However, since we have the full genome sequences of many viruses and their isolates, we can look at and identify them right at the protein level. We can look at which proteins are specific to a particular species and use that information as an identifier to classify and identify viruses. Our group at Pune University has developed a database of animal viruses. The database is entitled VirGen. In the process of developing this database, we found out that it is much better to identify the viruses first using the macro features and then confirm by using molecular properties. In order to do this, however, we need to develop many more appropriate tools and that is where the field of genomics and data mining of the viral genomes becomes very important. 34

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The genomic data must be structured in such a fashion that it is straightforward to get from family to the isolate level. With the full genomes of viruses being available, it is possible to examine and compare them. Fortunately, the International Committee on Taxonomy of Viruses (ICTV) has developed a universal taxonomic scheme for viruses, and one can make use of that. However, there is a long interval between the publication by a scientist and the assignment of standard nomenclature. Correlating the work published before and after the assignment of standard nomenclature could be an issue that needs to be addressed in developing the microbial commons. We included the whole genome phylogeny and the method to predict B-cell epitopes, based on that information in VirGen database. This sort of additional value- added information offers an example of how we can start integrating and creating information for the commons in ways that can be then used in other area of the microbial commons itself. As I mentioned, the ICTV classification information available in the published literature does not always match what is being published by the researcher. There is no standard method to describe viral isolates or the various strains. Electron micrographs and other image data are not readily available, which makes identification difficult and inaccurate. Only now are data in the form of images and, particularly, high-resolution graphic images being slowly added to the public-domain databases. There are other databases that have been created by various experts, but they are not publicly available. We need to include information from those databases as well, and, once that is done, there will be the new challenges of how to describe these databases in a consistent fashion and how to use them for extracting knowledge. Recombination occurs much faster in viruses than in bacteria and other microbes. Therefore, that will also need to be taken into account. Host and vector information will need to be described in standard language. At a minimum, immunological properties and therapeutic options will also need to be added to the databases. Having raised these various issues, it is fitting that I should also suggest some solutions. First, we will have to devise a means to build trust among developing nations that the developed nations are not looking to exploit their resources. Today, there is a huge gap in understanding and awareness between those in the developing nations and those in the developed world. Most of the scientists and culture collection people in developing countries feel that they wil be losing huge resources, financial and otherwise, if they make their collections available, even if their country’s administrators feel it should be done. This is where education is required. We need to show them that by sharing their materials and data, it will lead to a situation in which all will receive the benefits of that sharing and that it will be a win-win situation for both the developing nations and the developed nations. This is a critical issue that we will have to address in order to create the microbial commons and make it workable. Otherwise, the commons will not work, and only this small group will be talking about it. To really make it workable, we will have to communicate the value of cooperation to those in the developing nations. Networking and consortia among scientists can play a role, and the curators of culture collections as well as policy-makers from developed and developing countries need to understand the importance and get involved. Unfortunately, most of the time everyone is talking at cross purposes. This meeting is one of the few efforts to bring together all of the people who 35

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are interested in creating a microbial commons, and the policy makers are probably less well represented among the attendees than we might wish. Material transfer agreements should be standardized, and they must take into consideration national security and the biosafety issues. If we do not take these issues into account, those MTAs will not be accepted by most countries, including the United States. We will have to create awareness about open access and open educational resources. This is something that has been discussed in some detail in India. The National Knowledge Commission, which was established about three years ago by the current prime minister to look at what is necessary to transform India into a knowledge society, recommended that India move towards more open education resources and open access. The commission had seven members, and two advisors. Our role was to suggest methods to improve the total knowledge infrastructure, including access to and dissemination of knowledge. Instead of worrying about the philosophical definition of knowledge, we decided to look at the practical issues and try to work on those: How can we improve the creation of knowledge? How we can improve access to knowledge? How we can build the human resources to conceptualize the knowledge and knowledge network as well as the applications and services? We divided into groups to focus on and identify the areas related to each of these issues. We identified and consulted with various experts both formally and informally, and then we created background research and analysis groups, or working groups. After they deliberated, these working groups offered their findings and recommendations in a report, which was deliberated upon by the National Knowledge Commission. The final recommendations covered a variety of areas, including higher education research, how to improve the quality of Ph.D.’s, how to improve primary education, and how to improve the national knowledge network. The recommendations were given to the prime minister in the form of summaries, each about two to two-and-a-half pages long and containing about 10 to 12 specific recommendations. We kept them brief because we believed that the prime minister does not have more than 4 to 5 minutes to read this type of information. Many of the recommendations given to the prime minister have been now accepted by the government, and their implementation is in progress. One such action was the establishment of the National Science and Social Sciences Foundation, because we found that the scientists and social scientists in India do not work together. They have been kept in two different rooms, so to speak, and the wall has been very thick. So we decided to bring them together. The U.S. National Science Foundation has at least a small group working on the social sciences side, and it provides a certain amount of funds to the social sciences. In India, it does not work in the same fashion. The Department of Science and Technology works only on the scientific aspects. So we decided to create a new foundation to facilitate cooperation, and it is now being established. Similarly, we recommended the creation of a National Knowledge Network because improving access to all of the work we do is important. If the work is not accessible, then it is not going to serve anyone. So we are creating a gigabit network that will connect a large number of institutions within the country and will also connect to institutions in the United States. The funds to establish this network have been allotted both on the institutional side and on the Indian government side, and the connectivity is getting established. 36

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Five years ago we did an experiment to connect India and the United States at 660 megabits per second. Now, we are increasing the speed to one gigabit per second, and, probably, it will very soon be increased to 10 gigabits. The main point here is that the National Knowledge Commission suggested to the government that it should create open educational resources and open access systems, and now, as a consequence, all this work is getting funded. The government in India will provide significant funding for open access, just as it happened in the U.S. We have also started to provide open education resources, with courses developed with the various Indian Institutes of Technology and the Indian Institute of Science, the topmost institutes in the country. These courses have been made a public resource. In the context of the research commons, each country will have to establish policies to be followed concerning research papers published in the microbiology area. In India, we are just getting ready to do that, and this sort of symposium should help to push that effort further. Policy makers are being lobbied to make the outcomes of the government-funded research publicly available. A bill on open access has just been drafted and will be probably passed in the next parliament. Various steps are being taken to encourage scientists to publish in open access journals. The institutions are being given funding for that purpose in recognition of the fact that whenever open access is instituted, somebody has to pay for it. Individual scientists will not be able to pay. The Indian government is providing funds so that whenever a paper is accepted and published in an open access journal, the appropriate institution will get funding to be applied towards the costs of publishing; certain additional money will also be provided to these institutions. As a consequence, the institutions and the scientists will both have an incentive to publish in the open access journals. We also need to organize training programs by international experts to improve the quality of culture collections and the databases. In this way, I feel that we could really have much better interactions. Finally, we need to improve access to the specialized culture collections. These collections exist, but we need to improve access. Panel Discussion PARTICIPANT: I wanted to ask Stephen McCormack this question. You put up an interesting slide talking about perceived disincentives to sharing. I wanted to know if you were aware of any actual data on the degree to which there is any reality to that or how much of it is truly just a fear or an exaggerated perception as opposed to something that is been ground-truthed with real numbers. DR. McCORMACK: That is such a difficult number to come to up with and to be able to identify. I have given a lot of time and thought behind that to try and identify how a privately held collection or a privately held body of researcher data would be identified. I only know, from various experiences and in looking at things where the legality would come into play, that if it resulted in a product or it is used for research purposes and the proper license was not taken out, it could be a problem. This is really difficult information to get,so I cannot answer that definitively. 37

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PROF. WU: Relative to that, there is a very interesting opinion piece recently published in Nature Reviews Drug Discovery where three pharmaceutical companies—I think it was GSK, Merck, and Pfizer—together wrote about tearing down the firewall of data protection. They want to change the model from the proprietary nature of the data to the proprietary understanding of the data. They think that for all this potential data integration there is a need for them to do discovery with all the data. Instead of trying to generate all the data and keep that within the firewall, they prefer to have this public- private partnership to take the drug discovery to the next step. It is a very interesting opinion piece if you have not read it. PARTICIPANT: This question is also for Stephen McCormack. You mentioned that materials in the ATCC Special Collection that were deposited prior to 1980 were not subject to the Bayh-Dole provisions, and I was wondering if materials that were deposited prior to the Convention on Biological Diversity were also exempt from those requirements. DR. McCORMACK: I think you would have to ask the ATCC. I cannot make statements or representations for that organization. DR. SIMIONE: Since I work at the ATCC I will answer the question, but I am a little puzzled as to the pre-1980 distinction. The pre-1980 material is useful because it does not have bovine spongiform encephalopathy (BSE) implications, the prion “mad cow disease.” So it becomes useful for that, but from the Bayh-Dole standpoint—that one I cannot answer. I will be happy to try to find out. We have experts at ATCC who would be able to answer those questions. PARTICIPANT: I have an overview question for both Joan and Mark. I thought your presentations were really fabulous and interesting. I used to be a scientist, although not a biologist. My question to both of you, speaking with my law professor hat on, is: Where are the problems? What are the issues? It seems like you are working it out. What are the issues that somebody like me, speaking as a law professor, might want to be able to think about? Also, I had a comment on the point that Stephen McCormack made about how to define commercial use and when it is commercial use. I certainly would acknowledge that it is never going to be easy to define commercial use, but at least in my view, it is preferable generally to push these definitions downstream, and that is one of the nice things about a take-and-pay regime as opposed to the type of regime that would require you to determine whether the user is a commercial entity. When you can talk about activities at the point of use, it is advantageous from a legal point of view because there are always going to be fuzzy boundaries, but if you are at a point where the commercial potential is more concrete, there is more incentive for people to negotiate, to come to some sort of agreement and avoid a law suit. I wanted to know if you had a reaction to that. DR. McCORMACK: Yes, I think that that obviously is going to be the right approach. It is just in the creation of these proposed commons, right? If the understanding were that the take-and-pay regime would be the dominant one, and the repositories of these 38

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materials themselves were all held dominantly within such space, but with some partitioned in a semi-commons or in a completely privatized area, then, yes, I think that that would obviously be the right approach. PROF. REICHMAN: I would like to comment on the general discussion. Not being in your community officially, I have to say that I would rather see this discussion start at a much higher level. What I mean by that is, we are at a very interesting time in history when we have the capability to mash together huge amounts of information for the benefit of mankind. If we spend our time focusing first on how someone makes money, how you nibble around the edges of this commons, then we are not going to accelerate human understanding, we are not going to achieve the rate of progress that we have the potential to do. We will get bogged down in incrementalism. I think that the starting point for a reengagement and how one develops any kind of a science commons is to ask what the changes in thinking are in either the litigious community or in the sociology of science. We need to try to get people to share at the moment they know something new, and we need to invent within that framework a way that protects the potential opportunity to benefit in a fair way for the individuals who contribute, not knowing the value of what they are contributing at the time they contribute. So I would like to say we are doing this wrong, trying to build on what has been going on in the past, so let us start thinking about what are the real goals here, not making money. PROF. BENNETT: I have felt I am living in a parallel universe in that most of us scientists are more into the curiosity of the research than some of the other goals. That is why I told that little story about the money people, the power people, and the fame people. I also try to make the point that the genomics community and the other “omics” communities have had the chance to more or less start over. New kinds of information exchange have been developed that are so much better than some of the approaches that was developed early in the 20th century. We should be using the new capabilities as a model. I am more or less echoing what Mark has just said, but in a slightly different way. PARTICIPANT: Can I add a comment to that? First, I agree, but I would make one other supporting point, which is that in genomics in particular there has been an explosion of technological capability. This has made genome sequencing into a category of data that is now so easy to generate and is generated in such massive quantities that even if you tried to protect it or keep it behind a firewall, it is literally no longer practical to do that. Somebody with a new 454 or Illumina machine could simply reproduce everything you have done within half an hour tomorrow morning. So, getting to Mark’s point, I ask: Might you be able to separate data according to their nature, as in data that are easy to produce in such massive quantities versus those that must be processed in some more direct, intellectual sense to add value? PARTICIPANT: This project has such a broad charge. Why do we not add this as well? Ideally you would want to get rid of all transaction costs, but there are reasons that some stipulations should be put in place if everybody is going to be able to contribute and play, and there are a lot of reasons you want everyone to do that. And, yet, from what you said, and from what was quoted in the paper, if there is a barrier, the scientists are going to go 39

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around it and they will do as they like within their informal communities instead. So, are you thinking that the only situation that will really be acceptable is having no transaction costs, that there will not be any records where you have to refer back to the original source, or else people simply will not participate? How is that going to work out? PROF. BENNETT: You probably need a social scientist to answer a question like that, if you want any kind of answer at all, but I think there is a critical point where regulations become so burdensome and so expensive in time and energy that people start circumventing them. When I look at some of the documents that come out of certain international activities, they fail in that way. They really do, and at some level I think they are unnecessary. One of the most famous discoveries in the history of microbiology was penicillin, which came from a microbe. There was a time before penicillin was manufactured as a medicine, when people in Peoria were collecting penicillium strains, the fungus, from all over the world. What is wonderful about this story is that there were no barriers: The strain that finally was selected was from a cantaloupe in Peoria. It was not from some exotic place, and, yet, that process of discovery would not have gone on as easily as it did if there had been the kind of barriers there are now for accessing and using organisms. It would have been impossible. PARTICIPANT: I also wanted to pick up on what you were just saying about the way in which scientists are motivated by fame. Within the patent laws, there is what is referred to as the research exception. Maybe people do not always rely on it, but it is available as a way to allow the freedom to operate and do research. For data and materials, however, I do not know that we have something comparable, especially for those early stages of research when a private company might presume that everything is valuable or commercial, and it really does not know where the research is going to go. It just seems that in designing the commons, if there are some incentives and ways to get that early push of creativity going, then we know what the real values are likely to be. PARTICIPANT: I would like to ask the panel to address the education and training dimension of the commons. Maybe Joan Bennett and Ashok Kolaskar can address that. The question is: If you create a commons like this, there is an additional value in both directions for engaging the commons with the education and training process. For one thing, if you have a diverse community engaged in using the commons, and they have a diversity of expertise, then there is a tendency for the most sophisticated and well-funded members of the community to take greatest advantage of that and for the less well-known members of the community to be left behind and lose their funding. So, there is a major advantage in training all members of the community to take maximum advantage of the microbial commons, and, by doing that, you lower the fear barrier for those disadvantaged members of the community to contribute to the commons. This can be the case both within a particular country and also internationally, so there is a great value in making sure that all members of the community are well trained in using the commons. There is also a major benefit to the quality of the data and the resources in the commons to having a much larger number of trained eyeballs examining what is in there. It may be scientists from diverse countries around the world, or it may be 40

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undergraduates at diverse educational institutions throughout the United States or other countries. I was wondering if any of you would like to comment on that. PROF. BENNETT: Great idea. PARTICIPANT: First, I guess I am a little confused about your emphasis on commons. The commons is a vehicle to achieve something significant in the community. So training is something that needs to be done in order to create within the entirety of the communities that participate in microbial biology more very well-educated individuals who can work across disciplines, who understand enough about one subdomain of microbial biology, let us say, and enough about one or two other domains to be conversant and to advocate for the future of the programs that you hope to foster. The result would be the creation of a more evident, interactive environment. So, on the training side I would say the focus should be on finding a way to bring the brightest people who are attracted to aspects of your field to projects around this kind of an international effort. They need to be given enough resources for a long enough period that they can be trained and be creative and have an impact. We should make sure that they are trained in more than one discipline. PROF. WU: Yes, there has been a lot of discussion regarding the under-appreciation of data scientists, those people who are involved in maintaining the quality of the data and now managing the data. So we need to encourage both training and this kind of cultural change in terms of appreciating the value of people who are doing this kind of work. That would be a separate issue that needs to be addressed as well. PROF. KOLASKAR: I think there is an absolute need to provide training, especially with reference to the developing countries. The scientists who are doing high-quality research work will not necessarily participate in these types of activities. The gains are very few. Those who publish good, high-quality research papers get much better recognition than those who are working in the commons infrastructure activities. That is why training becomes very important—and not just for those who are involved in culture collections or in database creation. Those are definitely essential. But even for these scientists, the training is important, and that is why I feel that we will have to really give a very high priority to do this, and only then will we be able to develop better commons. PARTICIPANT: Let me make a concrete suggestion since the word "concrete" has been used. In the six or so years of trying to put together this international neuroinformatics facility, training has been a topic, and the international participants involved in trying to form something that would be practical there have wandered all over the map in terms of things that one could do. A blue ribbon review panel for OECD looked at this last May, and the conclusion was that one should do something very much like a Cold Spring Harbor course. The idea is that a limited amount of money engaged in something practical like that would result in the biggest impact. Perhaps one could create the equivalent in Europe of a Cold Spring Harbor course for two weeks and encourage the member nations to have a competition for their best potential trainee. The trainees would need to be multi-disciplinarily prepared persons, and the curriculum of the course should cover a broad enough spectrum so that all of the participants from the member nations went away feeling a broad sense of camaraderie. Perhaps within about a year or two 41

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years, a syllabus could be produced that could be used to train people in other countries through the standard curriculum and departmental type functions. That was a formula that we came up with. Then the idea was to go after EU funding and funding from various other sources to support that course. It was not easy to get everybody to agree to that sort of thing and I am not sure it will actually happen, but that is what we are trying to do. A similar sort of approach might be useful to you here. 42