Innovative low cost technologies for biomedical research and diagnosis in developing countries
http://www.100md.com
《英国医生杂志》
1 Sustainable Sciences Institute, San Francisco, CA, USA, 2 Division of Infectious Diseases, School of Public Health, University of California, Berkeley, CA, USA
Correspondence to: E Harris eharris@socrates.berkeley.edu
Introduction
Reagents as well as consumable supplies can be substituted by simpler variants. Academic and biotechnology laboratories in the United States and Europe are becoming increasingly dependent on kits that call for mysterious reagents from specialised vendors. Although this practice has greatly facilitated experiments, it has also taken away an important element of the scientific method, which is to understand each step of a process in order to comprehend the whole. Breaking down a technique into its component parts also allows more effective troubleshooting when things don't work as expected.
Laboratories in the developing world do, however, use some kits. Often, once a protocol has been established, scientists generate their own reagents from which they produce kits. In Nicaragua, for example, the national reference laboratory of the Ministry of Health adapted an enzyme linked immunosorbent assay (ELISA) kit for diagnosing dengue fever. By shortening incubation periods and generating their own reagents, they reduced the time required for diagnosis from 3 days to 4 hours.8 Finally, they produced and packaged their own kit, which is distributed and used in laboratories throughout the country. Direct comparisons showed that the kit performed better than others used in the region (A Balmaseda, personal communication). Conversely, commercial kits are often "dissected" and replaced with the individual reagents to make the process less costly.
Challenges
Fortunately, many technologies that started off as prohibitively expensive are now affordable and are being implemented in many laboratories throughout the world. Take the polymerase chain reaction. Whereas 15 years ago, it was costly and high tech, most research laboratories in developing countries now have access to this technology.7 Some laboratories produce their own enzymes and share equipment and resources. However, real-time polymerase chain reaction has now become the standard for many procedures., but the machines and probes required for this technique are still too expensive for most laboratories. Thus, scientists trying to publish results generated with lower cost technologies are at a disadvantage because many peer reviewers will accept only more sophisticated techniques.
Countries in developing areas of the world have vastly different levels of scientific proficiency and technological advancement. For instance, Brazil, Mexico, Argentina, Cuba, India, China, and Singapore are highly developed scientifically and are largely self sufficient in terms of training, reagents, and equipment. Smaller and poorer countries with little national investment in technology are more dependent on the developed world and are often more scientifically isolated.9 10
Organisations developing low cost technologies
Program for Appropriate Technology in Health (www.path.org)
Special Programme for Research and Training in Tropical Diseases (www.who.int/tdr/)
Bill and Melinda Gates Foundation (www.gatesfoundation.org)
Foundation for Innovative New Diagnostics (www.finddiagnostics.org)
Sustainable Sciences Institute (www.ssilink.org)
Yet, scientists everywhere feel the pressure to implement the newest technologies. For example, the current "buzz" about genomics, proteomics, and DNA chips creates an artificial need for their implementation in settings where they might not be appropriate. The technology is changing so fast that a major investment now can be obsolete in a few years. For smaller countries, a more reasonable strategy could be to outsource samples through collaborators until the technology stabilises. Resources can instead be invested in better computers, broadband access, and software to allow for efficient data analysis, bioinformatics, and data mining, as well as in classic technologies and standard equipment.
In some respects, the future looks promising for researchers, physicians, and patients in the developing world. New tools are being created with global applicability in mind—for example, the recent Grand Challenges in Global Health Initiative.11 Low cost technologies for genetic research are being adapted into generic tools appropriate for healthcare applications, such as diagnosis and monitoring treatment, and these will help shift medical practice from treatment to cost effective screening and intervention. Other applications include cost effective diagnosis of diseases in plants and animals using rapid and cheaper bioassay technologies. For instance, lab-on-a-chip technology promises instant diagnosis of bacterial or viral infections, resulting in more targeted treatments.12-14 These assays transfer the complexity of large scale laboratories on to minute computer chips and take advantage of volume manufacturing to reduce cost.
Conclusions
Avilés H, Belli A, Armijos R, Monroy FP, Harris E. PCR detection and identification of Leishmania parasites in clinical specimens in Ecuador: a comparison with classical diagnostic methods. J Parasitol 1999;85: 181-7.
Belli A, Rodriguez B, Avilés H, Harris E. Simplified PCR detection of New World Leishmania from clinical specimens. Am J Trop Med Hyg 1998;58: 102-9.
Harris E, Roberts TG, Smith L, Selle J, Kramer LD, Valle S, et al. Typing of dengue viruses in clinical specimens and mosquitoes by single-tube multiplex reverse transcriptase PCR. J Clin Microbiol 1998;36: 2634-29.
Huang TS, Liu YC, Lin HH, Huang WK, and Cheng DL. Comparison of the Roche amplicor Mycobacterium assay and Digene sharp signal system with in-house PCR and culture for detection of Mycobacterium tuberculosis in respiratory specimens. J Clin Microbiol 1996;34: 3092-6.
Miagostovich MP, Nogueira RM, dos Santos FB, Schatzmayr HG, Araujo ES, Vorndam V. Evaluation of an IgG enzyme-linked immunosorbent assay for dengue diagnosis. J Clin Virol 1999;14: 183-9.
Russomando G, Figueredo A, Almiron M, Sakamoto M, Morita K. Polymerase chain reaction-based detection of Trypanosoma cruzi DNA in serum. J Clin Microbiol 1992;30: 2864-8.
Harris E. A low-cost approach to PCR: appropriate transfer of biomolecular techniques. New York: Oxford University Press, 1998.
Balmaseda A, Guzman MG, Hammond S, Robleto G, Flores C, Tellez Y, et al. Diagnosis of dengue virus infection by detection of specific immunoglobulin M (IgM) and IgA antibodies in serum and saliva. Clin Diag Lab Immunol 2003;10: 317-22.
Coloma J, Harris E. Science in developing countries: Building partnerships for the future. Science's Next Wave 2002 Sep 27.
Harris E. Scientific capacity building in developing countries. EMBO Rep 2004;5: 7-11.
Grand Challenges in Global Health. www.grandchallengesgh.org. (accessed 14 Oct 2004).
Technology Networks. Lab-on-a chip.com. www.lab-on-a-chip.com/home (accessed 14 Oct 2004).
Oak Ridge National Laboratory. Incredible shrinking labs: chipping away at analytical costs. www.ornl.gov/info/ornlreview/meas_tech/shrink.htm (accessed 14 Oct 2004).
AZoNano. Lab-on-a-chip used to detect bacterial infection in the stomach. www.azonano.com/details.asp?ArticleID=933 (accessed 14 Oct 2004).(Josefina Coloma, program )
Correspondence to: E Harris eharris@socrates.berkeley.edu
Introduction
Reagents as well as consumable supplies can be substituted by simpler variants. Academic and biotechnology laboratories in the United States and Europe are becoming increasingly dependent on kits that call for mysterious reagents from specialised vendors. Although this practice has greatly facilitated experiments, it has also taken away an important element of the scientific method, which is to understand each step of a process in order to comprehend the whole. Breaking down a technique into its component parts also allows more effective troubleshooting when things don't work as expected.
Laboratories in the developing world do, however, use some kits. Often, once a protocol has been established, scientists generate their own reagents from which they produce kits. In Nicaragua, for example, the national reference laboratory of the Ministry of Health adapted an enzyme linked immunosorbent assay (ELISA) kit for diagnosing dengue fever. By shortening incubation periods and generating their own reagents, they reduced the time required for diagnosis from 3 days to 4 hours.8 Finally, they produced and packaged their own kit, which is distributed and used in laboratories throughout the country. Direct comparisons showed that the kit performed better than others used in the region (A Balmaseda, personal communication). Conversely, commercial kits are often "dissected" and replaced with the individual reagents to make the process less costly.
Challenges
Fortunately, many technologies that started off as prohibitively expensive are now affordable and are being implemented in many laboratories throughout the world. Take the polymerase chain reaction. Whereas 15 years ago, it was costly and high tech, most research laboratories in developing countries now have access to this technology.7 Some laboratories produce their own enzymes and share equipment and resources. However, real-time polymerase chain reaction has now become the standard for many procedures., but the machines and probes required for this technique are still too expensive for most laboratories. Thus, scientists trying to publish results generated with lower cost technologies are at a disadvantage because many peer reviewers will accept only more sophisticated techniques.
Countries in developing areas of the world have vastly different levels of scientific proficiency and technological advancement. For instance, Brazil, Mexico, Argentina, Cuba, India, China, and Singapore are highly developed scientifically and are largely self sufficient in terms of training, reagents, and equipment. Smaller and poorer countries with little national investment in technology are more dependent on the developed world and are often more scientifically isolated.9 10
Organisations developing low cost technologies
Program for Appropriate Technology in Health (www.path.org)
Special Programme for Research and Training in Tropical Diseases (www.who.int/tdr/)
Bill and Melinda Gates Foundation (www.gatesfoundation.org)
Foundation for Innovative New Diagnostics (www.finddiagnostics.org)
Sustainable Sciences Institute (www.ssilink.org)
Yet, scientists everywhere feel the pressure to implement the newest technologies. For example, the current "buzz" about genomics, proteomics, and DNA chips creates an artificial need for their implementation in settings where they might not be appropriate. The technology is changing so fast that a major investment now can be obsolete in a few years. For smaller countries, a more reasonable strategy could be to outsource samples through collaborators until the technology stabilises. Resources can instead be invested in better computers, broadband access, and software to allow for efficient data analysis, bioinformatics, and data mining, as well as in classic technologies and standard equipment.
In some respects, the future looks promising for researchers, physicians, and patients in the developing world. New tools are being created with global applicability in mind—for example, the recent Grand Challenges in Global Health Initiative.11 Low cost technologies for genetic research are being adapted into generic tools appropriate for healthcare applications, such as diagnosis and monitoring treatment, and these will help shift medical practice from treatment to cost effective screening and intervention. Other applications include cost effective diagnosis of diseases in plants and animals using rapid and cheaper bioassay technologies. For instance, lab-on-a-chip technology promises instant diagnosis of bacterial or viral infections, resulting in more targeted treatments.12-14 These assays transfer the complexity of large scale laboratories on to minute computer chips and take advantage of volume manufacturing to reduce cost.
Conclusions
Avilés H, Belli A, Armijos R, Monroy FP, Harris E. PCR detection and identification of Leishmania parasites in clinical specimens in Ecuador: a comparison with classical diagnostic methods. J Parasitol 1999;85: 181-7.
Belli A, Rodriguez B, Avilés H, Harris E. Simplified PCR detection of New World Leishmania from clinical specimens. Am J Trop Med Hyg 1998;58: 102-9.
Harris E, Roberts TG, Smith L, Selle J, Kramer LD, Valle S, et al. Typing of dengue viruses in clinical specimens and mosquitoes by single-tube multiplex reverse transcriptase PCR. J Clin Microbiol 1998;36: 2634-29.
Huang TS, Liu YC, Lin HH, Huang WK, and Cheng DL. Comparison of the Roche amplicor Mycobacterium assay and Digene sharp signal system with in-house PCR and culture for detection of Mycobacterium tuberculosis in respiratory specimens. J Clin Microbiol 1996;34: 3092-6.
Miagostovich MP, Nogueira RM, dos Santos FB, Schatzmayr HG, Araujo ES, Vorndam V. Evaluation of an IgG enzyme-linked immunosorbent assay for dengue diagnosis. J Clin Virol 1999;14: 183-9.
Russomando G, Figueredo A, Almiron M, Sakamoto M, Morita K. Polymerase chain reaction-based detection of Trypanosoma cruzi DNA in serum. J Clin Microbiol 1992;30: 2864-8.
Harris E. A low-cost approach to PCR: appropriate transfer of biomolecular techniques. New York: Oxford University Press, 1998.
Balmaseda A, Guzman MG, Hammond S, Robleto G, Flores C, Tellez Y, et al. Diagnosis of dengue virus infection by detection of specific immunoglobulin M (IgM) and IgA antibodies in serum and saliva. Clin Diag Lab Immunol 2003;10: 317-22.
Coloma J, Harris E. Science in developing countries: Building partnerships for the future. Science's Next Wave 2002 Sep 27.
Harris E. Scientific capacity building in developing countries. EMBO Rep 2004;5: 7-11.
Grand Challenges in Global Health. www.grandchallengesgh.org. (accessed 14 Oct 2004).
Technology Networks. Lab-on-a chip.com. www.lab-on-a-chip.com/home (accessed 14 Oct 2004).
Oak Ridge National Laboratory. Incredible shrinking labs: chipping away at analytical costs. www.ornl.gov/info/ornlreview/meas_tech/shrink.htm (accessed 14 Oct 2004).
AZoNano. Lab-on-a-chip used to detect bacterial infection in the stomach. www.azonano.com/details.asp?ArticleID=933 (accessed 14 Oct 2004).(Josefina Coloma, program )