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Indian Journal of Medical Microbiology, Vol. 29, No. 4, October-December, 2011, pp. 331-335 Review Article Ethics in biotechnology and biosecurity S Jameel Senior Scientist and Group Leader, Virology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi - mb110 067, India Date of Submission: 07-Dec-2010 Code Number: mb11084 PMID: 22120790 Abstract Great advances in technology produce unique challenges. Every technology also has a dual use, which needs to be understood and managed to extract maximum benefits for mankind and the development of civilization. The achievements of physicists in the mid-20th century resulted in the nuclear technology, which gave us the destructive power of the atomic bomb as also a source of energy. Towards the later part of the 20th century, information technology empowered us with fast, easy and cheap access to information, but also led to intrusions into our privacy. Today, biotechnology is yielding life- saving and life-enhancing advances at a fast pace. But, the same tools can also give rise to fiercely destructive forces. How do we construct a security regime for biology? What have we learnt from the management of earlier technological advances? How much information should be in the public domain? Should biology, or more broadly science, be regulated? Who should regulate it? These and many other ethical questions need to be addressed.Keywords: Biotechnology, biosecurity, dual use research, fink report Introduction Every major advance in science and technology has produced unique dual--use challenges. In the middle of the 20 th century, physicists unlocked the secrets of the atom, understood "nuclear fission" and the fundamental forces of nature. This led to the development of nuclear energy. It also led to the development of the atomic bomb, which unleashed horrors never witnessed earlier. In the late 20 th century, rapid developments in Electronics and Information Technology gave us computers, Internet and a host of unimaginable communication and entertainment devices. This ready access to information, however, has also led to intrusions on our privacy. Biotechnology is no different. The technology that has the ability to enhance public health and agriculture can also be used to create bioterror agents, which can unleash fiercely destructive forces. History is witness that man has used many technological advances for the purpose of waging war. While the Industrial Revolution gave us machines to increase our productivity, it also led to advances in mechanized combat. The wars of the 20 th century killed more people than all previous recorded conflicts. The 21 st century was still young when airplanes, earlier known only as machines for transporting people and materials, were used in an act of terror to bring down the World Trade Center in New York. Every iteration of technology appears to make the tools of destruction more accessible to the "rich" as well as the "determined". In a world with increasing disparity, injustice and hatred, the increasing availability of biological materials, electronics and computing power is likely to create an explosive mix. With our past experience of managing other dual use technologies, can we also secure biotechnology from abuse? This review will explore the issue of biosecurity in a biotechnology or life sciences environment. Examples of Dual Use Biotechnology In the late 1970s and the early 1980s, when the science and tools of genetic engineering were developing, there were many apprehensions about this new science. Detractors envisioned a scenario in which eugenics would alter natural selection in the human race and new species would be created. While that has proven far more difficult to do, simpler life forms have been ′created′. Let us look at some examples from the world of human viruses. In 2002, Eckard Wimmer and colleagues from the State University of New York (SUNY) in Stony Brook, reported the first chemical synthesis of a human pathogen - the poliovirus. [1] This was at a time when the disease poliomyelitis (or polio) was eliminated from most of the world by vaccination and just a handful of countries still showed human-to-human transmission of wild type poliovirus. The SUNY scientists ordered small bits of DNA (or oligonucleotides) from commercial suppliers and stitched those together into a DNA copy of the RNA genome of poliovirus using the polymerase chain reaction (PCR) technology. At that time, as at present, PCR was a popular technology for amplifying and detecting small amounts of nucleic acids in disease and forensic samples. The DNA copy was converted into the RNA genome of poliovirus by an in vitro transcription step and the RNA ′translated′ into viral proteins using a cell-free lysate system reported about a decade earlier. [2] The synthetic genome produced exactly the same proteins as RNA extracted from wild type poliovirus. Further, infectious virus was produced from both, which showed identical plaques on lawns of HeLa cells and neurovirulence in a transgenic mouse model. The synthetic virus was as infectious as the wild type virus. The authors commented - "If the ability to replicate is an attribute of life, then poliovirus is a chemical with a life cycle". The chemical formula of poliovirus was reported to be C 332,652 H 492,388 N 98,245 O 131,196 P 7501 S 2340 . This first chemical synthesis of a human pathogen raised many ethical questions. Could synthetic poliovirus be used as a bioweapon? The answer was probably not. Poliovirus is transmitted through food (not aerosols) and this is not a terribly efficient mode of transmission. Only 1 in 200 to 1000 persons exposed to poliovirus suffer paralysis and only a fraction of these succumb to the disease. Most importantly, extensive global polio vaccine campaigns have ensured that most of the world′s population has protective immunity against poliovirus. But consider a scenario about 25 years after the world is declared polio-free. Vaccination would have ceased (as with smallpox following its successful eradication) and children and young adults will carry no immunity against this pathogen. A synthetic poliovirus has the ability to create much damage to such a population. If poliovirus can be synthesized, how about far more dangerous human viruses such as the Ebola virus or the Smallpox virus? Both are highly infectious, are transmitted through aerosols and have high case of fatality rates. Further, the human population has no immunity to Ebola virus and has waning immunity to the Smallpox virus, vaccination against it having ceased in the mid-1970s. These viruses have genomes and life cycles that are far more complicated than poliovirus, so there appears to be no imminent danger at present of their chemical synthesis. But the future might be different. Did anyone anticipate two decades ago that poliovirus could be created de novo? The highly lethal 1918 pandemic strain of influenza virus has already been re-created from RNA fragments isolated from the lungs of a victim frozen in the Alaskan permafrost since that time. [3] Consider also the case of measles virus and a preventable vaccine against it. Measles is a big killer, especially among children under 5 years of age. Of the 1.4 million vaccine-preventable deaths reported in this group for the year 2002, about 38% or 532,000 deaths were attributed to measles. [4] A preventive vaccine against measles was licensed in the 1960s. It has an excellent safety record and proven efficacy to prevent disease, reduce mortality and interrupt transmission. Then why is it not being used as effectively? The vaccine delivery through injections appears to be a problem in resource-limited settings. The lack of adequately trained personnel and concerns over inadequate safe injection practices become critical during mass campaigns when millions of doses of vaccine have to be administered. A solution to this problem was found in aerosolization of the measles vaccine. In a process called "carbon-dioxide-assisted nebulization with a bubble dryer", the vaccine virus is mixed with supercritical CO 2 to produce microscopic bubbles and droplets, which are then dried to make an inhalable powder, and placed into a small plastic sack. [5] By taking one deep breath from the sack, a child can be effectively vaccinated. This is all good, but here is the dual use dilemma. Can the same technology be used to aerosolize bioterror agents such as anthrax? New Challenges and New Paradigms New pathogens pose new challenges, which require new paradigms for effective detection and control. Ever since its inception, biotechnology has vigorously addressed issues related to human and animal health. But the scenario is changing rapidly. To effectively combat new pathogens, we need a strategic capability to go from the first identification of the pathogen to millions of doses of an effective drug or vaccine within weeks and months. It currently takes 10 to 15 years to do this. The acquisition of such capabilities will require new concepts for screening microbial targets and drug candidates in chip-scale biomimetic systems. The need for years of animal testing prior to the initiation of human clinical trials must also be cut drastically. Some new technological tools are discussed below as examples of these approaches. Various groups are developing organ-on-a-chip systems to study infections of organs in a micro-scale device. The lung-on-a-chip microdevice takes a new approach to tissue engineering by placing two layers of living tissues - the lining of the lung′s air sacs and the blood vessels that surround them - across a porous flexible boundary. To determine how well the device replicates the natural responses of living lungs to stimuli, the researchers tested its response to inhaled living E. coli. Bacteria were introduced into the air channel on the lung side and white blood cells were flowed through the channel on the blood vessel side. The lung cells detected the bacteria and, through the porous membrane, activated the blood vessel cells, which in turn triggered an immune response that ultimately caused the white blood cells to move to the air chamber and destroy the bacteria. Nanoparticles introduced in the device were found to induce inflammation. [6] The Defense Advanced Research Projects Agency (DARPA) Biological Warfare Defense Program of the United States Army is developing an artificial human immune system-on-a-chip, which consists of human immune cells and micro-scale immune structures. This technology will facilitate rapid screening of candidate vaccines within weeks instead of years. [7] A novel microfluidics chip developed by researchers at Massachusetts General Hospital (MGH) will let doctors examine how white blood cells called neutrophils help the body cope with burns and other traumatic injuries. It may also shed light on why the immune system sometimes spirals out of control, resulting in dangerous inflammation. [8] Again, we come across the dual use dilemma. Can the same technologies that reduce the time taken for drug and vaccine development be used to fast track the development of a particularly potent toxin? To Publish or Not to Publish Scientists historically view new discoveries as increasing our understanding of the world we live in, and such information is largely directed towards common good. The discoveries are announced in publications, to be viewed, followed and improved upon by peers. This is how traditional scientific knowledge is known to advance. But bioethicist Arthur Caplan argues - "We have to get away from the ethos that knowledge is good, knowledge should be publicly available, that information will liberate us. Information will kill us in the techno-terrorist age". [9] A philosophical question facing the biologist is whether certain research constitutes "forbidden knowledge" that should either be banned or restricted on grounds of security. Such controversy first arose in 2001 when Australian scientists reported that insertion of a single immunomodulatory gene in the mousepox virus genome converted the benign virus into a highly lethal murine pathogen. [10] Critics argued that since bioweapons developers can use similar strategies to increase the lethality of human viruses, such information is dangerous and should be kept out of the public domain. The report a year later, of the chemical synthesis of poliovirus [1] raised similar concerns. German scientists reported in 2007 in the journal Cell, their success at altering the DNA of the bacterium Listeria, a human pathogen, to enable it to cause disease in mice, which are not its natural host. [mb11] . While this research provided a mouse model for Listeria, which would help in developing new vaccines and therapies, it can also have troubling implications. Can similar approaches be used for reverse engineering an animal pathogen into one that causes disease in humans? Should such research be published? Biosafety, Biosecurity and the Biologist How do we create a security regimen for biology? Biosafety deals with the broad concept of practicing biology in a safe environment. Biosecurity includes tools for keeping the work safer and protecting workers from exposure (harm). It also implies the prevention of deliberate use of pathogens and toxins. Both biosafety and biosecurity require that scientists continuously exercise their judgement and question themselves. Is the project safe? At what safety level should the proposed experiment be done? Are we taking all the right safety and security precautions? And it is important to back up that judgment with suitable training of personnel involved in the work. The Fink Report and Regulatory Systems The National Research Council of the United States National Academy of Sciences put together an expert group - Committee on Research Standards and Practices to Prevent the Destructive Application of Biotechnology - under the chairmanship of Prof. Gerald Fink of the Massachusetts Institute of Technology to deliberate on these issues. The Fink Report "Biotechnology in an Age of Terrorism", released in late 2003, concluded that some life sciences research, though perfectly legitimate, might be misused to threaten public health and national security. [12] It identified those experiments to be of concern, which would give the following attributes to a pathogen - increase its virulence, transmissibility or host range, make the pathogen resistant to existing vaccines or drugs, make it easier to convert into a weapon or enable it to evade existing diagnostic techniques. The Fink Report calls for a "bottoms-up" approach to address the problem of dual-use and biosecurity, and advocates self--governance by the life sciences community. The report urges the creation of a "comprehensive system, both nationally and internationally", and states that "only a system of international guidelines and review will ultimately minimize the potential for the misuse of biotechnology". Towards a more comprehensive biosecurity regime, it made seven recommendations to the US government.
In March 2004, the United States Department of Health and Human Services created an NSABB, which has the mandate to advise and guide on local and federal biosecurity oversight of all federally funded life sciences research. It was also tasked with developing, evaluating and modifying guidelines for biosecurity, communicate these to the scientific community and the public at large, develop programmes for education and training in biosecurity, and develop a code of conduct for life scientists that can be adopted by federal agencies and professional organizations. Currently, in the United States all academic institutions engaged in recombinant DNA research, which receive funds from the National Institutes of Health, must comply with federal oversight guidelines. These include the setup and registration of an Institutional Biosafety Committee, which is overseen by a Recombinant DNA Advisory Committee (RAC). The Biosecurity Regulatory Framework in India The biosecurity regulatory regimen in India stems from the Environment (Protection) Act, 1986 that laid down rules and procedures for the "manufacture, import, use, research and release of genetically engineered organisms and their products". The Department of Biotechnology (Ministry of Science and Technology) and the Ministry of Environment and Forests, with appropriate inputs from the Ministry of Agriculture and Ministry of Health and Family Welfare, implement this regulatory regime. For genetically engineered products in India, the regulatory regime operates through the coordination of four authorities - (1) Recombinant DNA Advisory Committee (RDAC), (2) Institutional Biosafety Committees (IBSC), (3) Review Committee on Genetic Manipulation (RCGM), and (4) Genetic Engineering Approval Committee (GEAC). All the Committees have representation of various stakeholders, which include scientists, policy makers and members of the public. The RDAC and RCGM report to the Department of Biotechnology; and the GEAC reports to the Ministry of Environment and Forests. The RDAC reviews national and international developments in biotechnology and advises the Government on policy. The IBSCs are mandated to be in place at all organizations and institutions involved in recombinant DNA work and form the first and most crucial part of the biosecurity regime by designing, reviewing and monitoring biosafety at the ground level. The RCGM provides biosafety clearance on the recommendation of the IBSCs. Finally, the GEAC reviews all the biosafety data and is the nodal body for providing clearance for clinical (medical and veterinary) and field (agricultural) trials of recombinant DNA products, and for the final release of these for licensure. The Government of India has initiated several policy changes through the new National Biotechnology Development Strategy, 2007. The most significant aspect of the new policy is the creation of a National Biotechnology Regulatory Authority (NBRA), which will replace the GEAC. A bill to establish the NBRA was drafted in 2008 and has undergone extensive public consultations, but is yet to be tabled in the Indian Parliament. The NBRA will have: (1) Risk Assessment Unit; (2) Regulatory Branches, one each for (a) Agriculture, Fisheries and Forestry, (b) Human and Animal Health, and (c) Industrial and Environmental Applications; and (3) several cross-sectorial offices to feed and advise the NBRA. The Dual Use Research of Concern (DURC) awareness is very low even among scientific circles in India.[13] To quote Prof. Kameshwar Rao of the Foundation for Biotechnology Awareness and Education, Bengaluru - "The identification and monitoring of DURC is presently dependent upon the level of awareness of the IBSCs, which is patchy. There is no concern and/or mechanism now in place for the funding agencies to identify projects with DURC implications or for the journal editorial system to identify them at the stage of peer review. The levels of awareness at the funding and publication stages certainly need to be addressed, keeping in view the international consensus that there should be no restrictions on the kind of research one undertakes or on international communication of advances in science, but intent on only the identification of the risk and means of mitigating it". [13] Epilogue How do we manage the risks of dual use research in life sciences without being overly restrictive to the scientific enterprise? National biosecurity measures are required but not sufficient because biotechnology is a global activity. Managing the risks will require policies that are implementable at the international level to ensure that only legitimate scientists can access deadly organisms and oversee potentially dangerous research. The global biosecurity network is a chain whose strength depends upon its weakest link. This therefore requires an effective and globally ratified system of controls and regulations. Till such a system is in place, effective national guidelines and self-regulation by scientists, an overwhelming majority of who are driven by the goodness of their work, will serve to keep dual use research under the umbrella of biosecurity. Disclaimer The opinions expressed in this article are the author′s own. They should not be taken as the official position of his employing organization. References
Copyright 2011 - Indian Journal of Medical Microbiology |
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