doi:10.1038/nindia.2016.88 Published online 11 July 2016
The essence of biosafety is protecting the individual (research worker), environment and organism (research material). Past experiences of biosafety failures in many western countries have often resulted in big disasters and huge economic losses.
For example, in 2006, the incident involving the accidental transfer of live anthrax from the Centre for Disease Control’s Bioterrorism Rapid Response and Advanced Technology (BRAAT) laboratory to Lawrence Livermore National Laboratory put a number of research workers at risk. Similarly the 2007 outbreak of foot-and-mouth disease in the United Kingdom due to a leak of the virus from a site jointly operated by The Pirbright Institute and Merial resulted in huge economic loss and a temporary embargo in animal trade with the European Union.
In order to handle such diverse levels of threats, posed by various types of organisms, different biosafety containment levels are used. Experiments using organisms on laboratory animals must be carried out in Animal Biosafety Level (ABSL) facilities, where strict containment levels (ABSL I – IV) are followed; while experiments involving large or loose housed animals with designated high risk pathogens are handled in BSL-III Agriculture (BSL-III-Ag). While GMP/GLP clean rooms operate under positive pressure to exclude contaminants from entering the area, biosafe laboratories work under negative pressure to prevent escape of pathogens from inside to the environment.
Is biosafety much ado about nothing?
The primary argument posed to the proponents of biosafety is ‘how was biological research undertaken in earlier times?’ To add substance to this claim, many of the vaccines that are currently in use, were developed and tested prior to the biosafety era. For example, Louis Pasteur’s rabies vaccine was passaged in monkeys and rabbits a number of times, an experiment which was not performed as per today’s biosafety standards. However, this virus is still in use as a vaccine. The other argument is that very few laboratory accidents involving pathogenic organisms have been documented even in the recent times.
Although these arguments sound agreeable to some, in this era of technology and development they may not hold ground for a technically qualified person. Even during earlier times, natural biosafety measures were considered while identifying a site for a laboratory facility. For example, during 1893, the Indian Veterinary Research Institute was established away from populous regions at 7500 feet above sea level in the Kumaon hills. All the difficulties in the transportation of people and equipment to this isolated area were endured for the requirement of biosafety, at least to the extent of avoiding unintentional release or spread of organisms even if not in the context of protection of the research worker. The present biosafety concepts not only protect against the spread but also personnel and environment, which is highly justified.
The resources required for any biosafety laboratory involve establishment, validation and continuous maintenance. All these processes are cyclical and never-ending. However, it is not only the infrastructure or the equipment that facilitates biosafety; more important is the attitude of the working personnel, who strictly and scrupulously follow the laid-down procedures. If a three-minute shower is prescribed, the workers must strictly adhere to it. If they compromise this procedure for frivolous reasons, such as lack of hot water, not only do they put themselves at risk but also their co-workers and the environment.
Therefore, along with infrastructure a substantial amount of resource is required for training and awareness campaigns, especially in countries like India. In addition to the above resource requirements, two important constraints are felt at the ground level — uninterrupted power supply and optimal and continuous usage of the facility. Any biosafety laboratory must run 24 x 7, and any break-down results in breach of biosafety and requires revalidation of the entire facility. This puts great pressure on the research institutions in India, which do not have direct control over the electricity supply and have to rely on the state governments for this. Also, such power usage comes at a huge cost. In addition, most universities institutions engaged in biological research cannot afford to recruit full-fledged support engineers with expertise in running and maintaining such laboratories.
Although many institutions are able to succeed in obtaining grants for the initial establishment of biosafe laboratories by convincing the authorities of its needs, they fail to factor in the operational requirement for the subsequent years in terms of annual maintenance and validation. This has resulted in a situation where a number of biosafety laboratories have been established but are not fully operational.
The concept of establishment of several ABSL facilities and the likelihood of their continuous usage are largely unrealistic as animal experiments on target species are carried out only on potential promising lead molecules, after results of extensive research in laboratories and laboratory animals. In this context, it is felt that a few ABSL laboratories across the country may be established but their operation should be on a revenue-earning model. Additional factors, such as the purchase and transport of animals, feed, veterinary care, necropsy and disposal can be provided at a nominal cost, which in turn should be funded as a part of a proposed research grant.
However, at present no such mechanism exists in our country. Any institution running a BSL/ABSL laboratory is denied funding, for maintenance of the facility, when it approaches a research-funding agency. These laboratories are often suggested to generate their own revenue for this purpose, which is unrealistic.
Alternative approaches to biosafety requirement
Alternative approaches to assays requiring high biosafety containments are recently gaining momentum. Development of assays that can be performed at low BSL for the detection of high-risk pathogens can be helpful, especially in resource constrained regions like India.
One such approach is the use of pseudotypes for performing quantitative and qualitative serology of infectious diseases such as rabies and influenza. In this approach, the rabies/influenza viral envelope is engineered on a retroviral core containing a reporter gene (Mather et al., 2013). These surrogate viruses can be used in place of the actual rabies/influenza viruses in a serum neutralisation assay, thereby negating the need for biosafety containment. The Translational Research Platform for Veterinary Biologicals (TRPVB) has already initiated research into this approach with the support of Viral Pseudotype Unit, University of Kent and University of Westminster.
Regulatory guidelines for biosafety laboratories
Biotechnology research is regulated through institutional biosafety committees, review committee on genetic manipulation and genetic engineering advisory committee. However, no such agency is available to approve and validate biosafety laboratories in India, unlike that of GMP/GLP facilities, which are regulated by Drug Controller General of India. India's Department of Biotechnology has initiated some effort in this direction to develop mechanisms for validation and certification of biosafe laboratories.
Biosafety in the context of emergency preparedness
India needs to work on diseases that do not normally occur in the country but are considered a potential threat. Such research cannot be carried out at this moment extensively, due to the lack of BSL facilities. In turn, the emergency preparedness of the country is largely hampered.
However, such facilities exist throughout the developed nations. For example, the United Kingdom has established a state of the art laboratory for research on exotic diseases with fool proof biosafety procedures and containment at a cost of 1450 crore rupees (http://www.pirbright.ac.uk).
India should not be left behind in infrastructure generation and capacity building in the area of emergency preparedness. Furthermore, Indian biological research fraternity requires such facilities for their research to be globally accepted.
Trade related biosafety
Although OIE monitors disease occurrence globally, some countries do not report assiduously to such world agencies. Hence, there is a likelihood of disease incursions, when trade occurs between such countries by unreported but prevalent diseases. Under these circumstances, if nation-specific highly biosafe labs are available to handle and test for such pathogens, trade can occur between these countries without the fear of incursions of unreported diseases.
There also exists a dichotomy between scientific publications from a country and diseases reported, which lowers the credibility of the diseases reported from a country.
Biosafety and veterinary research: The path ahead
More than 70% of animal diseases are zoonotic. It is, therefore, essential that laboratory based research does not add to already existing genetic diversity of potentially dangerous organisms existing and circulating. Therefore, it is important that laboratory based research is performed strictly adhering to biosafety practices and regulations.
In this connection the following challenges need to be addressed: Creating widespread awareness on biosafety requirements, establishing and enforcing regulations on biological research, establishing all inclusive biosafety experimentation units, funding support to biosafety laboratories for annual maintenance, establishing licensing, validation and technical audit modalities for BSLs, uninterrupted power supply to these laboratories.
To sum up, the answer to the question raised in the title is an emphatic 'no'. However, consideration should be given during establishment of such facilities for their operational and utilisation needs.