Trends in United States biological materials oversight and Institutional Biosafety Committees.

Author:Jenkins, Chris
 
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Introduction

Since 1975 when the Asilomar Conference convened over recombinant DNA technology and led to the creation of the National Institutes of Health (NIH) Guidelines for Research Involving Recombinant DNA Molecules (recently changed to Guidelines for Research Involving Recombinant and Synthetic Nucleic Acid Molecules), advances in biotechnology and recombinant DNA (rDNA) have necessitated oversight and safety reviews of life sciences research with biological materials through Institutional Biosafety Committee (IBC) oversight in the United States (Berg, Baltimore et al. 1975, Jackson October 1972). Over time from the Guidelines initial implementation, it has become accepted by the scientific and biosafety communities that additional monitoring of non-rDNA biohazards by IBCs should occur (Talbot, King et al. 1981, Dutton and Hochheimer 1982, O'Reilly, Shipp et al. 2012).

In contrast to the detailed NIH requirements for oversight of federally funded research that involves human subjects, animals, and even recombinant DNA, no uniform standard exists for oversight over additional forms of biological materials used in research as there are for animals, radioactive materials, or human subjects. Since the current regulatory environment does not prescribe a one-size-fits-all solution for the regulation of all biohazards, each institution must craft its own mechanism knowing that there are layers of biohazard oversight beyond those prescribed in the regulatory environment (Harris, 2005). This flexibility presents institutions with a myriad of options and little guidance on how to oversee biohazards beyond those prescribed in the NIH Guidelines.

This research hypothesizes United States life sciences regulation for research involving biological materials fails to provide adequate biosafety and biosecurity oversight, and IBCs charged to oversee research with biological materials require additional regulatory guidance in order to protect people, product, and the environment. The expected outcomes will highlight regulatory limitations and statute gaps with biohazards in research, propose policy changes, and provide the regulated community current 1BC practices and example methodologies for Institutional Biosafety Committees and institutions to adopt to enhance biosecurity and compliance with biological materials.

History of Recombinant DNA Technology and Oversight

Recombinant DNA (rDNA) technology is a relatively recent phenomenon. During a 1968 Senate Subcommittee hearing on a Joint Resolution to establish a new health science commission, Dr. Arthur Kornberg directed the subcommittee's attention toward the rapidly progressing field of molecular biology (Vettel, 1968). Dr. Kornberg noted important developments were near fruition and that the potential social impact of these advances could be far-reaching (Vettel, 2006). Dr. Kornberg was referring to discoveries which would provide the technical framework for the specialty commonly known as genetic engineering (Vettel, 1968). New techniques developing in this field would enable a researcher to recombine DNA, the hereditary material of the cell, in a very precise manner (Vettel, 1968). The rDNA introduced could provide a cell with the ability to manufacture products (for example, insulin) which were previously not part of the cell's make-up (Johnson, 2011).

In 1973, a group of scientists attended the Gordon Conference Session chaired by Drs. Maxine Singer and Dieter Sol to discuss the possibility of public health risks associated with genetic engineering (Singer and Soil, 1973). The concern was based upon the conjecture that the new techniques could accidently produce a recombinant molecule with hazardous characteristics (Heilman, 1973). It was speculated that an inadvertent modification of DNA in a previously harmless organism might enhance the organism's capability of producing a highly infectious disease (Singer and Soil, 1973). After extensive deliberation, the session's participants voted in favor of sending a letter to the National Academy of Sciences (NAS) suggesting that the academy consider the risks associated with genetic engineering and "recommend specific actions or guidelines" (Berg, Baltimore et al., 1974). In response to the Gordon Conference letter, NAS appointed a panel of experts to study the risk question (Johnson). The risk question was to be addressed at a conference near Asilomar State Beach in California (Paul Berg, 1975).

Asilomar Conference.

Prior to the Asilomar Conference in February, 1975, a call was issued by leading basic research scientists for a voluntary moratorium on life sciences research using rDNA technology in July, 1974 (Berg and Singer, 1995). For the moratorium, scientists agreed new rDNA technology created the potential for novel approaches in medicine, agriculture and industry, but also could result in unforeseen and damaging effects to human health and the environment. The moratorium would only be lifted after a conference was held to evaluate and regulate the risks associated with rDNA technology (Berg, Baltimore et al. 1974).

The conference, held at the Asilomar Conference Center in Monterey, California included scientists, lawyers, media, and U.S. government representatives. The primary goal of the meeting was whether to lift the moratorium, and if so, under which prescribed conditions rDNA research could be conducted in a safe and prudent manner. While little data beyond Berg's experiment existed at the time, despite opposition, the Conference ended with the understanding rDNA research should proceed but under strict guidelines (Berg, Baltimore et al., 1975). Such guidelines were collected and drafted into the 1976 Federal Register as the NIH Guidelines for Research Involving Recombinant DNA Molecules (NIH Guidelines, 1976), and were revised multiple times immediately after and in the subsequent years, most recently in March 2013, with a slight modification of the title to become the Niff Guidelines for Research Involving Recombinant and Synthetic Nucleic Acids (National Institutes of Health, 2013). The rationale for prompt action by scientists and the government from 1973 to 1976 was to protect laboratory personnel, the general public, and the environment from unintended or intended harm rDNA research with replicating organisms could potentially cause (Berg and Singer, 1995). In order to facilitate local protection with rDNA, the concept of the Institutional Biosafety Committee (IBC) was formed as a requirement for local review of biological materials for institutions upon receipt of federal funding in the NIH Guidelines. This Committee was and is today a community represented group of scientific peers with oversight at each individual entity, on research with rDNA molecules at each institution (National Institutes of Health 2013).

Definition and Applications of Recombinant DNA Technology.

An overview of rDNA and rDNA technology is provided followed by background on the evolution of the IBC. The NIH Guidelines define rDNA as "molecules that are constructed outside living cells by joining natural or synthetic DNA segments to DNA molecules that can replicate in a living cell, or molecules that result from the replication of those described above" (National Institutes of Health, 2013). Recently, changes to the NIH Guidelines now specify rDNA to also include synthetic nucleic acid research, due to advances in synthetic biology, and for the purposes of this document, research involving recombinant and synthetic nucleic acids will be referred to as rsNA (National Institutes of Health, 2013).

Recombinant and synthetic nucleic acids as a technology can be used because all organisms share the same chemical structure, with the only difference being the actual sequence of nucleotides (Lodish, 2000). Thus, when DNA from a foreign source is introduced into host sequences that can drive DNA replication and introduced into a host organism, the foreign DNA is replicated along with the host DNA (Brown, 2010). Consequently, the biological functions, and therefore applications and uses of rsNA are theoretically nearly limitless (Brown, 2010).

The most common application of rsNA is in basic life sciences research, where it is important to most current work in the biological and biomedical sciences (Brown, 2010). Recombinant DNA is used to identify, map and sequence genes, and to determine their function (Boyle, 2008). Recombinant DNA probes are employed in analyzing gene expression within individual cells, and throughout the tissues of whole organisms (Boyle, 2008). Recombinant proteins are widely used as reagents in laboratory experiments and to generate antibody probes for examining protein synthesis within cells and organisms (Alberts, 2008). While promising, rsNA is not without potential risk when manipulating the components of genetic heredity (Werkmeister and Ramshaw, 2012).

Risks of Recombinant DNA and Biological Materials

The history and use of recombinant DNA in biological organisms has a history of controversy, and no one understood the controversy more than Dr. Donald Frederickson. (Frederickson, 2000). Dr. Frederickson was the Director of the Niff in the mid-1970s and oversaw the rDNA technology controversy from start to finish with the issuance of the NIH Guidelines. While the possibilities and potential of rDNA seemed endless, researchers involved in rDNA experiments feared that they might produce unpredictable occupational and environmental hazards. For example, one risk was by increasing the virulence of viruses or the resistance of bacteria to treatment with antibiotics. The fear that gene splicing could produce epidemic pathogens was heightened by the fact that biologists were using microorganisms in their recombinant DNA research that have human hosts, most notably the bacterium E. coli.

The task to develop the principles formulated at Asilomar into a detailed set of technical guidelines on containment...

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