Biological weapons constitute an increasingly important ethical and political issue for science and technology. This entry examines that issue by defining biological weapons (BWs), reviewing the history of their use, considering efforts to deal with future threats, and analyzing the ethical and political aspects of BWs.
Biological warfare is the intentional use of disease-causing microorganisms or other entities that can replicate themselves—such as viruses, infectious nucleic acids, and prions—against humans, animals, or plants for hostile purposes. It also may involve the use of toxins, which are poisonous substances produced by living organisms, including microorganisms (such as botulinum toxin), plants (for example, ricin derived from castor beans), and animals (snake venom, for instance). The synthetically manufactured counterparts of those toxins are considered BWs when they are used for purposes of warfare.
Although biological agents have the potential to cause mass casualties, the numbers are often more a matter of scare mongering than real: when it is claimed, for example, that a pound of botulinum toxin can kill six billion people, which is not a real possibility. It nevertheless remains the case that one-quarter of all deaths worldwide and about 50 percent of all deaths in developing countries are attributed to infectious diseases. Although human beings have developed several physiological defenses against disease and in certain cases have acquired immunity through evolution, these natural defenses may be minimal in societies weakened by war or by famine, drought, stress, or other natural disasters.
Early Biological Warfare
Biological warfare may be as old as civilization. In the earliest forms it involved drawing enemy troops into disease-ridden areas on the basis of an etiological belief that epidemics were caused by inhaling air infected by particular telluric emissions. Animal and plant toxins also were used commonly in many societies to poison arrows and other kinetic weapons. In later times disease was spread by means of pollution of the environment (for example, dropping human or animal carcasses into wells or catapulting them into besieged cities), the use of kinetic weapons that were dipped into decaying corpses, and the distribution of objects contaminated by people with highly infectious illnesses such as smallpox.
However, it was not until the end of the nineteenth century that the propagation of disease and thus the effectiveness of such actions began to be understood. By 1914 microbiology had advanced considerably: Major bacterial disease-causing organisms had been isolated and cultivated; the existence of viral diseases had been discovered, although the pathogens were not yet well understood; and parasitic diseases were being studied. There was also an improved understanding of disease transmission, and that understanding contributed to better prophylaxis, prevention, and countermeasures. Not surprisingly, those insights and new techniques soon were applied for hostile purposes. World War I witnessed the first acts of sabotage (against animals) with cultivated disease-causing organisms.
During the 1920s and 1930s the fear of biological warfare increased significantly in parallel with scientific progress and as a consequence of experiences with the Spanish flu epidemic in 1918. In World War II only Japan actually used biological agents, employing them during military operations in China. Nazi Germany and the Allies did not produce an operational offensive BW before the end of the war apart from a limited British retaliatory capability to infect German cattle with anthrax.
The Cold War and Afterward
After World War II the Soviet Union and the United States, and to a lesser extent the United Kingdom, were the principal states continuing research, development, and production of offensive BWs. The United States formally halted its program in 1969 and then destroyed its existing BW stockpiles. An internal review had demonstrated the military utility of biological warfare, but the United States concluded that a BW capability would not contribute significantly to its existing security posture. The announcement of the termination of the offensive BW program was accompanied by the argument that BWs were of low military significance, which other countries were happy to adopt. To many diplomats a moral imperative became the driving force to achieve an international treaty, and the unilateral U.S. gesture thus helped pave the way for the 1972 Biological and Toxin Weapons Convention (BTWC). The Soviet Union, however, did not reciprocate and even accelerated its BW program despite being one of the three corepositories of the BTWC, along with the United Kingdom and the United States. The program survived the 1991 breakup of the Soviet Union essentially intact, and despite assurances by the Russian leadership, there remain considerable doubts about whether Russia has terminated all prohibited BW activities.
BW proliferation became a major worry in the late 1980s in part as a consequence of the use of chemical weapons in the Iran–Iraq war. The concerns were heightened significantly in the 1990s when the United Nations Special Commission on Iraq (UNSCOM), which was set up after the liberation of Kuwait in 1991, revealed the advanced and extensive nature of Iraq's BW programs. As the invasion of Iraq by American-led coalition forces in March 2003 illustrated, the mere assumption of the presence of BW can be highly destabilizing to international security. Countries such as China, Egypt, India, Iran, Iraq, Israel, North Korea, Pakistan, Russia, South Korea, and Taiwan are mentioned in connection with BW proliferation, but there is considerable uncertainty about whether those programs are offensive or defensive and about their level of sophistication.
Biological weapons involve dual-use technologies and processes that can be employed for both legitimate and prohibited activities. The ambiguities that result from the dual-use potential of those technologies are increased by the facts that (1) the active ingredient of the weapon (that is, the biological agent) is central to the making of the offensive weapon as well as to the development of some key means to protect against or manage the consequences of exposure to the biological agent (such as vaccines and medication) and (2) the final stage of the armament dynamic during which the applied technologies have no purpose other than weaponization may not become apparent until the biological agent is placed in a delivery system. As a consequence, the judgment of the true nature of certain activities comes down to a judgment of intent, and a country that has an antagonistic relationship with the state making the intelligence assessment is at greater risk of being called a proliferator than is one that has a friendly relationship. The perceived intent of a state is a major subjective component in the threat assessment.
Terrorism with pathogens became a primary concern in the 1990s after it was learned that the Japanese religious cult Aum Shinrikyo, which had conducted two deadly attacks with the nerve agent sarin in 1994 and 1995, also had unsuccessfully released BWs. Although another religious cult, the Rajneesh, had infected some 750 people with salmonella in an attempt to influence local elections in Oregon in the United States in 1984, the threat was not taken seriously until 2001, when an unknown perpetrator killed five people and infected seventeen more with anthrax spores delivered in letters. The fact that those attacks occurred in the wake of the terrorist strikes against the United States on September 11, 2001, heightened threat awareness around the world.
Future Threats and Ways to Deal with Them
The principal tool against biological warfare is the BTWC. The convention was the first disarmament treaty: It ordered the total destruction of all BW stockpiles, and it contains a comprehensive ban on the development, production, and possession of BWs. The core prohibition of the BTWC is based on the so-called General Purpose Criterion (GPC), which prohibits not specific objects as such (for instance, pathogens) but rather the objectives to which they may be applied (hostile purposes). The main advantage of the GPC is that its application is not limited to technologies that existed at the time of the conclusion of the treaty negotiation but to all innovations. This has proved critical in the light of the rapid advances in biology and biotechnology at the end of the twentieth century and the beginning of the twenty-first. As a result of the GPC the parties to the BTWC have been able to reaffirm the prohibition in the light of those technological developments at the periodic review conferences of the convention. However, the treaty lacks meaningful tools to verify and enforce compliance. Since its entry into force in 1975 there have been several allegations and some confirmed cases of material breaches, but the inability to deal with them under the treaty provisions has contributed to the perception of its weakness.
The BTWC also is being challenged by rapid developments in biotechnology and genetic engineering despite the availability of the GPC. Although these developments hold out the promise of improving the quality of life, much of the knowledge can be employed for hostile purposes by improving the stability and virulence of existing warfare agents or even by creating new agents based only on some components of an organism. The dual-use potential of many products, processes, and knowledge implies that any strengthened BTWC regime would require inspection rights in relevant scientific institutions and biotechnology companies. Many establishments are extremely reluctant to grant international inspectors access to their facilities for fear of losing propriety information.
As a consequence, efforts to strengthen the BTWC by means of a supplementary legally binding protocol have failed. The stalled multilateral negotiation process has shifted attention to a range of initiatives to be undertaken by individual states that are parties to the BTWC, including enhanced export controls, encouragement to establish ethical standards and professional codes of conduct, and the enactment of national legislation criminalizing activities contrary to the objectives and purpose of the BTWC by natural and legal persons and corporations.
Moral and Ethical Standards
The argument often is made that investments in technologies that contribute to the design and production of armaments are unethical because they ultimately contribute to the destruction of humans or consume resources that otherwise could have contributed to the improvement of humankind. Because of widespread moral aversion to biological warfare, involvement in BW development and production programs is condemned by many people.
The question of moral judgment is, however, complicated. First, work in the field of biology can be conducted without any link to the military establishment but still contribute to the development of biological weapons. Second, many activities are directed toward enhancing defence and protection against and the detection of biological warfare agents as well as toward the improvement of prophylaxis and the development of new pharmaceuticals. However, improvement in defence necessarily implies an understanding of the offensive characteristics of existing biological warfare agents as well as those of new pathogens, including genetically modified variants. The distinction between offensive and defensive research and development is difficult to make. In fact, the source of the complications with respect to moral judgment is the dual-use potential of most of the technologies involved.
Some scientists, researchers, and technicians, whether as individuals or as members of professional groups, have objected to participation in BW-relevant programs. However, international conventions do not always provide unambiguous moral guidance. International law governs behavior among states, not the conduct of individuals. In a narrow sense all state activities that fall outside the scope of an international prohibition are legal, contributing to a continuing tension between morality and legality.
This becomes clear in the justification of so-called biochemical nonlethal weapons despite the fact that both the BTWC and the Chemical Weapons Convention (CWC) prohibit any weapon that uses toxicity or infectivity whether or not its primary effect is incapacitating or lethal. Several states continue to pursue such weapon programs and justify them on humanitarian grounds. However, the use of a fentanyl derivative by Russian forces in the Moscow theater siege in October 2002 demonstrated that the margin between incapacitation and killing is very narrow. Fentanyl and its derivatives are obtained from opium-producing plants, and thus fentanyl is a biochemical toxicant that is covered by both disarmament treaties. Several U.S. agencies are actively pursuing several nonlethal technologies based on biochemical action. Since the 1920s the United States has systematically objected to the inclusion of harassing and incapacitating agents in the prohibitions against chemical and biological warfare.
Finally, the belief in the value neutrality of scientific activities and technology—the denial that the introduction of new insights or technologies has societal ramifications—held by many scientists constitutes a considerable obstacle to having discussions of ethical and moral issues. Especially if the potential negative societal effects are obvious and cannot be denied, the neutrality of science will be proclaimed (this does not happen if the societal benefits are clear). Indeed, many scientists feel actively discouraged to take part in ethical discussions and accept social responsibility for their work, convinced that research should be guided by its own thrust, independent from and indifferent to the outside political and social world. This view is sustained by early specialization and the lack of sufficient overlap and interaction between disciplines in teaching programs. Also, many scientists and professionals in the fields of biology and biotechnology are unaware of the existence of the BTWC.
In the early twenty-first century the BTWC, as well as the CWC with regard to toxins, is the main legal instrument to prevent biological warfare. However, an international treaty is subject to continuing pressures as a consequence of changes in the international security environment and technological developments that have a direct bearing on the objectives and purpose of the agreement.
Although the BTWC has a broad scope, the document governs only state behavior. Many developments relevant to the BTWC take place on substate (universities, research laboratories, and companies as well as terrorism) and transnational levels (transnational corporations and international organizations as well as terrorism). The responsibilities of these actors in supporting the goals of the BTWC is great but not well recognized. The impact of the convention on their economic activities is also great because certain transactions may be prohibited and certain goals are forbidden.
Both the research and industry sectors in the field of biology have a large stake in the successful implementation of the convention because otherwise their reputation could be tarnished. The introduction of ethical codes of conduct with respect to issues involving biological warfare in educational curricula and industry practices not only reinforces the treaty regime of the BTWC but also protects the economic interests of the research establishments and companies involved. To assess the moral or ethical aspects of their activities scientists and professionals must be aware not only of international rules and norms but also of how those rules and norms evolve.
JEAN PASCAL ZANDERS
Alibek, Kenneth, with Stephen Handelman. (1999). Biohazard. London: Hutchinson.
British Medical Association. (1999). Biotechnology, Weapons and Humanity. Amsterdam: Harwood Academic Publishers.
Dando, Malcolm R. (2001). The New Biological Weapons: Threat, Proliferation, and Control. Boulder, CO: Lynne Rienner.
Geissler, Erhard, and John Ellis van Courtland Moon, eds. (1999). Biological and Toxin Weapons: Research, Development and Use from the Middle Ages to 1945. SIPRI Chemical & Biological Warfare Studies no. 18. Oxford: Oxford University Press.
Lederberg, Joshua, ed. (1999). Biological Weapons. Cambridge, MA: MIT Press.
Roffey, Roger. (2004). "Biological Weapons and Potential Indicators of Offensive Biological Weapon Activities." In SIPRI Yearbook 2004: Armaments, Disarmament and International Security. Oxford: Oxford University Press.
Sims, Nicholas A. (2001). The Evolution of Biological Disarmament. SIPRI Chemical & Biological Warfare Studies, no. 19. Oxford: Oxford University Press.
Stockholm International Peace Research Institute. (1970–1975). The Problem of Chemical and Biological Warfare, 6 volumes. Stockholm: Almqvist & Wiksell.
Wright, Susan, ed. (1990). Preventing a Biological Arms Race. Cambridge, MA: MIT Press.
Zanders, Jean Pascal, ed. (2002). "Ethics and Reason in Chemical and Biological Weapons Research." Minerva 40(1): 1–91.
Zilinskas, Raymond A., ed. (2000). Biological Warfare: Modern Offense and Defense. Boulder, CO: Lynne Rienner.
American Society for Microbiology. "American Society for Microbiology Cautions That Scientific Publication Restraints May Have Negative Impact on Public Health and Safety." Available from http://www.asm.org/media/index.asp?bid=2813.
"Biological Weapons and Codes of Conduct." Available from http://www.ex.ac.uk/codesofconduct/Chronology/index.htm. Of particular interest are the sections "BW Codes" and "Conducting Research during the War on Terrorism: Balancing Openness and Security."
Biological Weapons, Genetic Identification
Biological Weapons, Genetic Identification
Biological weapons are weapons whose payload consists of microorganisms that can cause infections, or the toxic components of the microorganisms. Examples of microorganisms include viruses (e.g., smallpox, Ebola, influenza), bacteria (e.g., Bacillus anthracis, Clostridium botulinum, Yersinia pestis ) and protozoa. The most prominent example of a toxic component is the variety of toxins produced and released from bacteria (e.g. neurotoxins produced by Clostridium ).
Genetic technologies can be useful in the detection of biological weapons. Of particular note is the polymerase chain reaction, or PCR, which uses select enzymes to make copies of genetic material. Within a working day, a target sequence of genetic material can be amplified to numbers that are detectable by laboratory tests such as gel electrophoresis. If the target sequence of nucleotides is unique to the microorganism (e.g., a gene encoding a toxin), then PCR can be used to detect a specific microorganism from among the other organisms present in the sample.
Hand-held PCR detectors that have been used by United Nations inspectors in Iraq during their weapons inspections efforts of 2002–2003 purportedly can detect a single living Bacillus anthracis bacterium (the agent of anthrax) in an average kitchen-sized room.
The sequence of components that comprise the genetic material (genome) of a microorganism can also be deduced using techniques such as electrophoresis. Once a sequence is known, it can be compared to the many bacterial, viral, protozoal, and other microbial sequences in databases, in order to determine if the deduced sequence resembles a catalogued sequence. In this way, the nature and identity of biological weapons can be determined.
Genetic engineering has also made possible the splicing of the genetic determinants for a lethal agent from one microorganism or other life form into another microbe. For example, the former Soviet Union experimented with the instillation of the gene responsible for the production of cobra toxin into normally harmless bacteria that reside in the intestinal tract.
While recent events in the United States and in other countries, in particular Iraq, have brought biological weapons into prominence, the military use of biological weapons is centuries old. The bloated bodies of disease victims were routinely dumped into wells to poison the drinking water, or were even catapulted over the walls of fortified cities that were under siege.
More recently, biological warfare was an accepted part of the military campaigns of governments around the world. During World War I, for example, Germany actively explored the weaponization of Bacillus anthracis and Burkholderia mallei. The latter causes Glanders disease in cattle. Its' use was intended to cripple the agriculture base of the enemy.
During World War II, Britain also intended to cripple German agriculture by airdropping discs (or cakes) of anthrax. Indeed, five million anthrax cakes were ultimately produced, although they were not used. Also during this war, German and Japanese prisoners were used as guinea pigs in the testing of microbial weapons, including hepatitis A, Plasmodia species, Rickettsia, Neisseria meningitis, Bacillus anthracis, Shigella species, and Yersinia pestis. The U.S. had an active biological weapons program during World War II, and extending even into the 1960s. This program was finally terminated in 1968 by the order of then president Richard Nixon.
The production of biological weapons can be accomplished with relatively unsophisticated microbiological technology and by a typically trained microbiologist. Furthermore, the equipment necessary to accomplish weaponization (i.e., incubators, autoclaves, fermenters, centrifuges, refrigerators, and lyophilizers) can be housed in only a few thousand square feet. Thus, biological weapons manufacture is not difficult to conceal.
Furthermore, while biological weapons can be deployed in traditional weaponry (i.e., rockets), the weapons can also be literally carried in someone's pocket to the target site. This can make the deployment of biological weapons virtually impossible to stop, unless the carrier passes near an instrument designed to detect the biological agent.
Microorganisms are very light and so can be dispersed easily in air currents. This is especially true for bacterial spores, which, when dried, are powdery in texture. Furthermore, because exposure to only a few spores can be sufficient to cause disease (e.g., the inhalation form of anthrax, which is caused by spores of Bacillus anthracis ), the biological weapon can be easily delivered to the target. The anthrax-containing letters that were mailed in the United States in the latter part of 2001 attest to the ease of delivery.
Bacillus anthracis and Clostridium botulinum are two prominent examples of spore-forming bacteria that have been used as bioweapons. Spore forming bacteria normally grow and reproduce as "vegetative" cells. But, in harsh environmental conditions that threaten the survival of the bacteria, the microbes have evolved the ability to transform into an almost dormant form known as a spore. The spore is surrounded by a resilient coat that allows it to persist for decades, perhaps even centuries. When conditions again become favorable for growth and reproduction, the spore resuscitates into the vegetative form. Thus, if spore biological weapons do not kill immediately, the residual spores can persist to cause illness many years later.
The microbial agents used as biological weapons are typically highly infectious. The direct exposure of even a small number of people to the weapon can quickly lead to a large number of illnesses or casualties. Bacteria such as Clostridium botulinum and various species of Salmonella readily cause contamination, either by their growth in food or by the production of potent toxins. Such food-borne microbial threats are also considered to be biological weapons. Indeed, in the aftermath of the U.S. anthrax attacks in 2001, the vulnerability to sabotage of the food production and supply systems in many countries has become evident.
Ironically, the features that make biological weapons attractive to those who wage war or terrorism, namely their ease of dispersal, particularly via air, and their infectivity, has also proved to be a stumbling block to their use. A shift in the prevailing wind can carry the lethal payload back to those who deployed it, similar to the chemical warfare casualties that occurred during World War I. For example, the open air testing of anthrax on Gruinard Island off of the coast of Scotland in 1941 made the island inhabitable for decades afterwards. In a second example, as part of the U.S. Army's "Operation Sea Spray" in 1951–1952, balloons filled with Serratia marcescens were exploded over San Francisco, to evaluate the effectiveness of aerial biological warfare on a major urban center. The organism, which up until then was thought to be innocuous, allegedly produced an increase of pneumonias and urinary tract infections in the citizens of the city. As a final example, an accidental release of anthrax spores from a bioweapons facility in 1979 killed 66 people and sickened over 70 who were 4 kilometers downwind, in the city of Sverdlovsk, in the former Soviet Union. Sheep and cattle up to 50 kilometers downwind became ill.
█ FURTHER READING:
Cirincione, Joseph, Jon B. Wolfsthal, Miriam Rajkuman, and Jessica T. Mathews. Deadly Arsenals: Tracking Weapons of Mass Destruction. Washington, D.C.: Carnegie Endowment for International Peace, 2002.
Lavoy, Peter R., Scott D. Sagan, and James J. Wirtz. Planning the Unthinkable: How New Powers Will Use Nuclear, Biological, and Chemical Weapons. Cornell University Press, 2001.
Infectious Disease, Threats to Security
Biological weapons are organisms or their by-products used to deliberately spread disease. They include bacteria, viruses, rickettsiae , protozoa , fungi , and their toxins. The effects of biological warfare agents are diverse, but they generally incapacitate or kill their victims, or destroy crops or livestock.
Biological weapons have been used for centuries. The Tartar army catapulted plague-ridden corpses over city walls in the 1346 siege of Kaffa. All major participants in World War II developed biological weapons, however Japan, which dropped bubonic plague–infested debris on Chinese cities, was the only country known to have used them. In 1969 the United States abandoned research and production of biological weapons. Within three years, remaining U.S. stockpiles were destroyed. In 1975, 118 countries signed the Biological Weapons Convention that outlawed the development, possession, and stockpiling of biological weapons.
Biological weapons are often called "the poor man's weapon of mass destruction" because they are cheap and easy to produce. The production processes used to make biological weapons are similar to those used to develop medicines or make yogurt. Since facilities, equipment, and supplies resemble those for biotechnical and medical research, they can be hidden within legitimate facilities, making it difficult to track development of biological weapons. Compared to chemical or nuclear weapons, biological weapons are easily handled and effective in small amounts.
Exposure to most biological weapons occurs by inhaling an aerosolized agent. The most difficult part of producing the weapon is getting the agent into a small, stable form for dispersal. Agents can be dispersed as part of a conventional warhead or sprayed from a plane or a small canister. Attacks are nearly impossible to detect in early stages and may not become known until symptoms of disease appear. Defense against biological weapons may include protective clothing and masks, vaccinations, and antibiotic or antiviral therapy. Quick identification of biological agents is essential to save lives and maintain military effectiveness.
There are more than sixty potential biological warfare agents. Two of the most common are anthrax and botulism. The anthrax bacteria, Bacillus anthracis, commonly cause disease in cattle, horses, and sheep. In humans, cutaneous anthrax, which causes skin ulcers, accounts for about 95 percent of U.S. cases, with little mortality. However, inhalation of anthrax spores destroys lung and intestinal membranes, causing severe respiratory distress, shock, and death in about five days. Although antibiotics can be used, the mortality rate for inhaled anthrax is nearly 100 percent after symptoms appear. Anthrax is easy to cultivate and forms highly resistant spores that can remain active and potentially lethal for at least forty years.
Botulism is caused by Clostridium botulinum neurotoxin. Inhaling a very small amount of this bacterial toxin blocks electrical signal transmission in the nervous system and causes progressive muscular paralysis. Paralysis of respiratory muscles leads to asphyxiation and death. Tracheostomy and use of a ventilator reduce mortality, but recovery may take months of intensive nursing care.
Advances in biotechnology may produce biological weapons that are even more toxic, fast acting, and resilient. Genetic engineering may produce new organisms or toxins designed to target specific populations. Cloning techniques may allow for mass production.
see also Nervous Systems; Neuron; Poisons
Biological Weapons. Special Edition of the Journal of the American Medical Association 278, no. 5 (1997).
Solomon, Brian, ed. Chemical and Biological Warfare. New York: H. W. Wilson Company, 1999.
Biological Weapons, Genetic Identification
Biological Weapons, Genetic Identification
The ability to use microorganisms and their components as weapons has been a reality for decades. Individual countries and organizations such as the United Nations have mounted efforts to detect the use and presence of microbial weapons. A recent example is the effort by United Nations and United States inspectors to detect evidence of microbial weapons in Iraq in the aftermath of the two Gulf Wars.
Initiatives like the aforementioned represent the use of forensic science . Traditional forensic investigations relied on the use of techniques that required the growth of the target microorganism. This approach has limitations. For example, the growth conditions selected might not be suitable to permit the growth of the target microbe. Furthermore, the laboratory facilities required, especially for the culture of highly infectious organisms, may not be widely available.
The use of genetic techniques of identification represents a promising forensic approach. Genetic technologies can be useful in the detection of biological weapons. Of particular note is the polymerase chain reaction , or PCR , which uses select enzymes to make copies of genetic material. Within a working day, a target sequence of genetic material can be amplified to numbers that are detectable by laboratory tests such as gel electrophoresis . If the target sequence of nucleotides is unique to the microorganism (e.g., a gene encoding a toxin), then PCR can be used to detect a specific microorganism from among the other organisms present in the sample.
Hand-held PCR detectors that have been used by United Nations inspectors in Iraq during their weapons inspections efforts of 2002–2003 purportedly can detect a single living Bacillus anthracis bacterium (the agent of anthrax ) in an average kitchen-sized room.
The sequence of components that comprise the genetic material (genome) of a microorganism can also be deduced using techniques such as electrophoresis. Once a sequence is known, it can be compared to the many bacterial, viral, protozoan, and other microbial sequences in databases in order to determine if the deduced sequence resembles a catalogued sequence.
see also Anthrax, investigation of the 2001 murders; Biosensor technologies; Chemical and biological detection technologies; Nucleic Acid Analyzer (HANAA); PCR (polymerase chain reaction); RFLP (restriction fragment length polymorphism); STR (short tandem repeat) analysis; Toxins.