Biosafety

BACKGROUND

Infectious diseases: Biosafety, as defined by the U.S. Centers for Disease Control and Prevention (CDC), describes safety measures applied to the handling of biologic materials or organisms with known potential to cause disease in humans. The CDC is a U.S. government agency focused on public health efforts to prevent and control infectious and chronic diseases. Exotic and deadly diseases must be studied under proper conditions to prevent infection and to find potential treatments optimally preventing future epidemics, and as a safeguard against practices such as bioterrorism. Bioterrorism is the use of disease-causing organisms as weapons.

Biosafety measures are important in protecting persons working with organisms that have the potential to cause harm. Biosafety within the lab environment is divided into four levels, with each increasing level involving higher risk of infection as well as being reflected in the greater precautions introduced at subsequent levels.

At Biosafety Level 1 (BSL-1), few precautions are required, as the involved risk is the lowest of the four biosafety levels. Biosafety Level 2 (BSL-2) is considered moderate risk; diseases such as hepatitis and mumps are studied at this level. Precautions are increased further at Biosafety Level 3 (BSL-3) in which deadly diseases, such as anthrax and West Nile virus, are studied. Diseases requiring BSL-3 often have a known cure or vaccine. Biosafety Level 4 (BSL-4) diseases are considered extremely hazardous and often have no known vaccine or cure. BSL 4 is required for work with dangerous and exotic organisms and diseases that pose a high individual risk of inhaled laboratory infections and life-threatening disease. Examples of diseases requiring BSL-4 precautions include the Ebola virus and other life-threatening hemorrhagic diseases. The CDC prints guidelines for working with agents at all biosafety levels.

Foods and products: Biosafety also may be more broadly defined as the safe transfer, handling, and use of any living modified organism resulting from biotechnology. Biotechnology refers to using living organisms or their products to make or modify a substance. For example, many foods grown within the United States have been genetically modified to produce or eliminate characteristics, depending on what is desired. Since 1994, the U.S. Food and Drug Administration (FDA) has approved more than 50 genetically engineered foods and determined they are as safe as conventionally produced varieties.

Since the 1990s, scientists have been able to change the genetic makeup of plants and animals that are used for human consumption. These food products are called genetically modified foods (GMFs), or genetically modified organisms (GMOs). GMFs are produced to enhance or improve the organisms' natural traits. Many foods in the United States, including corn, soybeans, and canola are genetically modified. In 2003, it was estimated that about 167 million acres in 18 countries were planted with genetically modified crops. Other genetically modified crops, such as rice with increased iron and vitamins, have been suggested to help reduce the amount of malnutrition in the world, especially in developing countries. Crops may also be genetically modified so they can withstand harsher temperatures than non-modified foods. As a result, these crops may help provide food to areas of the world where crops are difficult to grow. In addition to crops, animals have also been genetically engineered. For instance, researchers may genetically alter animals, including chickens and cows, to increase their productivity of meat, eggs, and milk.

In January 2000, more than 100 countries signed an agreement to regulate international trade of GMFs. The agreement covered issues such as the safe use, handling, and trade of any food or product that may have harmful effects on the environment or health.

In November 2008, Austrian researchers released findings that a genetically modified variety of corn lowered the fertility of female mice that consumed a genetically modified (GM) blend as compared to a group of rats fed only traditional corn. Although the researchers have denied that their findings are transferable to humans, Austrian feed companies have agreed not to sell the specific strain used in the study. Questions remain about the long-term effects that GMFs may have on humans. Since GMFs have been on the market for fewer than 20 years, long-term effects will need to be assessed in the years ahead.

Currently, GMFs that are sold inside the United States do not have to be labeled as genetically modified. This prevents consumers from making an informed decision about many of the foods they eat. In contrast, all of the European Union nations, as well as Australia, China, Japan, New Zealand, and several other countries, require the labeling of foods that are made with genetically modified ingredients. The only current way to ensure that a food product within the United States was not made with genetically modified components is if it is labeled as USDA Organic. One of the criteria for a product to be organic includes rejection of genetically modified organisms, including bioengineered animals and crops.

TECHNIQUE

Biosafety risk levels in the laboratory: The biosafety risk is categorized into four levels. All precautions and requirements from lower classified biosafety levels must be included in higher levels unless specifically addressed by the higher classification. For example, if the organism or agent studied fulfills requirements necessitating biosafety level 3 (BSL-3), all required precautions for biosafety levels 1 and 2 apply in addition to the BSL-3 precautions.

Biosafety level 1 (BSL-1) classification is assigned when working with microorganisms not known to cause disease or hazard. Precautions include a closed door to the workspace, signs labeled with any hazardous materials in use, a hand washing sink, and all open windows must have screens. Standard BSL-1 practices include the use of mechanical pipetting devices (specialized droppers) to transfer agents or organisms, required hand washing, and prohibition of smoking, eating, and drinking.

Biosafety Level 2 (BSL-2) classification is given to agents and organisms that may cause disease through ingestion, inhalation, or contact with mucus membranes. Mucus membranes are any of the membranes that line the moist parts of the body in contact with air, such as the mouth and nasal passages.

Any work that could cause infectious material to enter the air must be contained, usually within a biological safety cabinet, which removes potentially hazardous particles by using a high-efficiency particulate air (HEPA) filter. Most HEPA filters remove 99.97% of particulate matter larger than 0.3 microns in size, which includes all known bacteria.

Precautions for needles and sharp objects require that needles are not sheared, broken, recapped, bent, or manipulated prior to disposal in a biohazard-labeled sharps container. The door must remain closed and access to the lab is determined and monitored by the supervisor. Waste must be separated into bio-hazardous, chemical, radioactive, and general containment. Gloves are required. All infectious waste must be decontaminated with chemical treatment or steam sterilization (autoclaving). All work surfaces and any object that may have come into contact with any infectious agent must be decontaminated. An incident log must be maintained describing any event that has resulted in improper containment and/or release of bio-hazardous, chemical, or radioactive waste.

Biosafety Level 3 (BSL-3) is assigned when working with diseases and/or agents that are potentially lethal if inhaled and often are curable. These laboratories are usually located away from high-traffic areas, often within a containment building. BSL-3 facilities have a double-door entry and do not re-circulate air. All windows must be sealed and access must be restricted to entrance and exit through two self-closing doors. Because the infectious agents are transmittable by inhalation, air is designed to flow from areas of less contamination to those of higher contamination. At this biosafety level all activities need to support minimizing the creation of splashes and aerosols. All work is done within biological safety cabinets, and the room is sealed to isolate the hazardous substance as well as to avoid contamination. All supplemental guidelines from BSL-1 and BSL-2 apply to BSL-3. Lab personnel must be given medical surveillance and available immunizations for any agents potentially present in the lab.

Biosafety Level 4 (BSL-4) is assigned when working with dangerous and exotic organisms and diseases that pose a high individual risk of inhaled laboratory infections and life-threatening disease. BSL-4 laboratories exist either as a separate building or a clearly marked and isolated area within another building. All personnel must enter and exit through the shower and changing rooms. Full laboratory clothing must be worn at all times, including undergarments, pants, shirts, jumpsuits, shoes, and gloves, without exception. Laboratory clothing is left in the lab and treated as contaminated material, as personnel are required to take a decontamination shower prior to exiting the lab.

In addition to requirements listed for biosafety levels 1-3, BSL-4 classification dictates that entry into the facility must be limited by monitored and locked doors. There are two types of BSL-4 facilities: cabinet laboratories and suit laboratories. In cabinet laboratories, all work is done within a Class III biological safety cabinet. In suit labs, all personnel must wear positive pressure suits when inside the lab. Positive pressure refers to maintaining a higher pressure inside the suit or chamber than in the surrounding area outside of the suit or chamber. This is designed so that in the event of an accidental breakage air will flow out of the suit temporarily protecting the person from infection by inhalation or contact with the studied disease. The laboratory is effectively sealed from the outside environment and a double-door, pass-through autoclave is required for decontaminating all items leaving the lab, which must be contained with a durable and airtight seal. Windows need to be break-resistant in addition to being airtight. All exhaust air in BSL-4 suit labs and decontamination showers and chambers pass through two subsequent HEPA filters before discharge outside the unit, into an area that is not occupied. The decontamination of all forms of liquid wastes must be documented and applied to sinks, floor drains, chemical showers, and any autoclave chambers before discharge to a sanitation sewer.

BSL-4 labs in the United States: Although there are currently highly competitive efforts to produce more operational BSL-4 labs, presently there are five operating within the United States. Two are located in Atlanta, Georgia at the U.S. Centers for Disease Control and Prevention (CDC), and at Georgia State University. The National Institutes of Health (NIH) operates a BSL-4 lab in Bethesda, Maryland, and the Unites States military operates a BSL-4 lab in Frederick, Maryland. Southwest Research Institute in San Antonio, Texas is another operating BSL-4 lab.

Testing bioengineered foods: The U.S. Food and Drug Administration (FDA) completes efforts to ensure safety by publishing safety testing guidelines and creating a consultation process with industry with the help of scientific experts outside of the organization. FDA scientists advise companies on the tests needed to assess the safety of new foods. Companies then send the acquired safety and nutritional information to the FDA for scientific approval. The FDA consultation process is currently offered, although not required. However, even if a company does not complete the consultation process, they are legally required to produce safe products. Consumer advocates have pressed the FDA into making the consultation process a requirement, so far unsuccessfully. All currently approved genetically modified foods have been through the consultation process and all companies have cooperated, although not required to do so.

THEORY/EVIDENCE

Infectious diseases: Biosafety measures are important to protect persons working with organisms that have the potential to cause harm. Bioterrorism is the use of disease-causing organisms as weapons, and its threat is compounded by the existence and concentration of deadly diseases. Biosafety levels have been created not only to ensure the proper handling, transport, and health of all qualified personnel but also to protect against access by unauthorized individuals for bioterrorism or other harmful uses. Biosafety in the laboratory is practiced to safely contain biological threats during observation and study.

Biosafety, as defined by the U.S. Centers for Disease Control and Prevention (CDC), describes safety measures applied to the handling of biologic materials or organisms with a known potential to cause disease in humans. The CDC is a U.S. government agency focused on public health efforts to prevent and control infectious and chronic diseases. Exotic and deadly diseases must be studied under proper conditions to prevent infection and to find potential treatments optimally preventing future epidemics, and as a safeguard against practices such as bioterrorism.

Foods and products: In September 2001, traditional corn supplies were contaminated with genetically modified corn from the United States without the completion of an Advance Informed Agreement (AIA). Foreign genes were inserted and the transgenic (genetically modified) corn was mixed with traditional corn, leading to concern about the long-term impact on ecosystems and human health. Opponents of genetically modified foods (GMFs) also present that the companies are not required to give information or methods for detecting their modified varieties in the wild, thus making it very difficult to identify in the event of an unforeseen recall if a genetically modified product is found to cause harm in the future.

Concern about possible gene transfer between species of neighboring plants exists, as the characteristics in some modified species (e.g., herbicide tolerant, toxin-containing, insect-repelling) may exhibit unfavorable effects on surrounding organisms, because species of weeds or neighboring plants may gain these modified properties and disrupt environmental balance.

An argument against the use of genetically modified organisms is that artificially altering organisms' makeup may violate the organisms' intrinsic value. Intrinsic value is the quality and integrity of an object or organism naturally occurring, which is altered or removed by inserting or deleting DNA sequences. Some individuals believe that changing or interfering with the genetic makeup of a living organism is wrong.

Cartagena protocol: In January 2000, 130 countries signed an agreement to regulate international trade of genetically modified foods (GMFs) and more broadly all living modified organisms (LMOs). The agreement covered issues such as the safe use, handling, and trade of any food or product that may have harmful effects on the environment or health. The agreement allows member countries to restrict or ban the use of genetically modified or engineered organisms if the importing country determines there is a lack of consensus regarding the safety of that product.

The agreement requires that trading countries sign an AIA document specifying the importing country's intent to import a specific genetically modified organism. This document requires the explicit consent of the importing country, yet is criticized by some for not requiring more stringent inspection or verification of safety. Importation is not necessarily blocked if there is a lack of scientific knowledge about a product. Member countries in the Cartagena Protocol agreed to a period of four years wherein an exporting country would be held liable for any harm or damage arising from the importation of the genetically modified organism. Some point out that this does not protect or delegate responsibility in the event of any potential long-term health damages occurring beyond the four-year agreement.

The agreement states that exporters must label all GMFs so that importing countries may decide whether or not they want to purchase the products. Once a country purchases imported GMFs, that nation may decide whether or not to label the products. As of November 2008, the United States has not approved or agreed to the full terms in the Cartagena Protocol, yet must participate when exporting to a member country.

Currently, GMFs that are sold inside the United States do not have to be labeled as genetically modified. This prevents consumers from making an informed decision about many of the foods they eat. In contrast, all of the European Union nations, as well as Australia, China, Japan, New Zealand, and several other countries, require the labeling of foods that are made with genetically modified ingredients. The only current way to ensure that a food product within the United States was not made with genetically modified components is if it is labeled as U.S. Department of Agriculture (USDA) Organic. One of the criteria for a product to be labeled as USDA Organic includes not allowing genetically modified organisms, including bioengineered animals and crops, as the actual product or as an intermediary food source in the production of the product being sold.

HEALTH IMPACT/SAFETY

Infectious diseases: Biosafety in the laboratory is important to prevent sickness/death within the facility, as well as outside in the event of a breach in safety. The goal of biosafety is to increase safety. Diseases studied in Level 3 and 4 labs, by definition, may infect and even kill individuals through brief inhalation. Biosafety is important for everyone, but a lack or failure of biosafety is most likely to affect those most susceptible to infection, including those who may be working with the disease or agent and those in close proximity.

Foods and products: Preliminary evidence suggests that genetically modified foods (GMFs) may trigger allergic reactions. Researchers speculate that introducing a gene into a plant may create a new allergen, which may cause allergic reactions in sensitive people. Allergic reactions may also be triggered because modified foods contain genes from other organisms to which the consumer may be allergic. For instance, researchers decided against adding a gene from the Brazil nut to soybeans because it is possible that individuals who are allergic to Brazil nuts may have an allergic reaction to the modified soybeans.

It has also been suggested that GMFs may damage the body's organs. One animal study found that genetically modified sweet potatoes damaged the intestines of rats when compared to rats that received non-modified sweet potatoes.

The U.S. Food and Drug Administration (FDA) finds that all approved GMFs are as safe as their conventional counterparts.

FUTURE RESEARCH OR APPLICATIONS

Infectious diseases: The U.S. Centers for Disease Control and Prevention (CDC) has published a text entitled, Biosafety in Microbiological and Biomedical Laboratories (BMBL) 5th ed. This text details current standards for laboratory procedures. Future publications are expected to offer updated organism classifications, including emerging infectious diseases.

Changes in disease mutations and characteristics, politics, and terrorism climate will likely impact future guidelines' practices and procedures.

Plants and food: Genetically engineered plants face regulation by three government agencies: The U.S. Department of Agriculture (USDA), the U.S. Food and Drug Administration (FDA), and the U.S. Environmental Protection Agency (EPA). The USDA focuses on the safety related to the creation or production of genetically modified foods, while the FDA ensures that foods made from these materials are safe for humans and animals to eat. The EPA's scope of regulation involves ensuring that pesticides and/or chemicals introduced to growing plants are safe for human and animal consumption in addition to the environment. Although separate entities, the FDA, USDA, and EPA frequently cooperate with one another, as many products require review by all three agencies. The future may call for increased cooperation among the agencies, as approval for more products of varying safety is sought.

As more genetically modified food and products are engineered, more monitoring and regulation will be required. Research will be conducted not only with the goal of discovering new genetic manipulations but also to analyze and safely regulate existing products in both the short and long term. A genetically modified food or organism is essentially a new product potentially requiring post-market surveillance for safety. There is an emerging need for development of a low-cost and widely available method for genetic analysis for tracking crops. Recent and future research will further develop existing biotechnologies and nanotechnologies that have the ability to identify and monitor for the expression and presence of transgenes quickly and effectively in the field. Nanotechnologies are technologies arising from the engineering and creation of things from materials of less than 100 nanometers (one-billionth of a meter) in size.

Advances in manipulating recombinant deoxyribonucleic acid (DNA) and its analysis will have an impact on the ability to produce and test engineered food products. Recombinant DNA technology is the process of inserting or joining DNA from dissimilar sources.

Researchers are investigating ways in which to produce vaccines through genetically modify foods (GMFs). For instance, researchers are trying to develop bananas that produce human vaccines against infectious diseases, such as hepatitis B. Researchers are also working to develop vaccines in other plants, including tomatoes and potatoes. Scientists hope that these plants will be much easier to ship, store, and administer than traditional vaccines, which need to be refrigerated. Ensuring that other potentially dangerous hidden traits are not packaged along with the desired genetic changes will be of high importance for future researchers.

Researchers are also trying to produce genetically modified fish that mature more quickly than normal. The impact of the altered development period on protein formation and genetic complement may be of concern as well as the outcome of possible breeding with non-modified fish and the related safety.

Scientists are currently working to produce fruit and nut trees that grow their nuts years earlier than normal. Assessment of potential ecological impact is primarily a biosafety concern.

AUTHOR INFORMATION

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

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