generation ago, biological weapons were called germ-warfare weapons. Biological weapons are very different from chemical weapons. A chemical weapon is a poison that kills upon contact with the skin. Bioweapons are microorganisms, bacteria or viruses that invade the body, multiply inside it, and destroy it. Bioweapons can be used as strategic weapons. That is, they are incredibly powerful and dangerous.

    They can kill huge numbers of people if they are used properly, and their effects are not limited to one place or a small target. Chemical weapons, on the other hand, can be used only tactically. It is virtually impossible to put enough of a chemical in the air in a high enough concentration to wipe out a large number of people over a large territory. And chemicals are not alive and can not spread through an infectious process.

    There are two basic types of biological weapons, those that are contagious and those that are not. Anthrax is not contagious: people don't spread it among themselves; you cannot catch anthrax from someone who is dying of it. Smallpox is contagious. It spreads rapidly, magnifying itself, causing mortality and chaos on a large scale.

    The most powerful bioweapons are dry powders formed of tiny particles, biodusts, which are designed to lodge in the human lung. The particles are amber or pink. They have a strong tendency to fly apart from one another, so that if you throw them in the air they disperse like a crowd, leaving a stadium. As they disperse, they become invisible to the human eye, normally within five seconds after the release. You can't see a bioweapon, you can't smell it, you can't taste it, and you don't know it was there until days later, when you start to cough and bleed, and by that time you may be spreading it around.

    The particles of a bioweapon are exceedingly small, about one to five microns in diameter. You could imagine the size this way: around fifty to a hundred bio-particles lined up in a row would span the thickness of a human air. The particles are light and fluffy, and don't fall to earth. You can imagine motes of dust dancing in a shaft of sunlight. Dust motes are mostly bits of hair and fuzz. They are much larger than weaponized bio-particles. If a dust mote were as thick as a log, then a weaponized bio-particle would resemble a child's marble.

    The tiny size of a weaponized bio-particle allows it to be sucked into the deepest sacs of the lung, where it sticks to the membrane, and enters the bloodstream, and begins to replicate. A bioweapon can kill you with just one particle in the lung. If the weapon is contagious in human-to-human transmission, you will kill a lot of other people too. So much death emergent from one particle!

    Given the right weather conditions, a bioweapon will drift in the air for up to a hundred miles. A hundred kilograms of anthrax spores would, in optimal atmospheric conditions, kill up to three million people in any of the densely populated metropolitan areas of the United States.

    Sunlight kills a bioweapon. Bacteria and viruses are generally vulnerable to sunlight. That is, a bioweapon biodegrades in sunlight. It has a "half-life", like nuclear radiation. This is known as the decay time of the bioweapon. Anthrax has a long decay time-it has a tough spore. Tularemia has a decay time of only a few minutes in sunlight. Therefore, tularemia should always be released at night. Ultraviolet light kills them quickly. Heavy rain or snow, wind currents, and humidity impede their effectiveness.

   While there are many number of organisms that bioterrorists could use as weapons, and we will analyze several of them in this study, smallpox and anthrax are the big two that are capable of causing disease and death sufficient to cripple a city, even a country.

   There are some that maintain that discussing the subject will cause needless alarm. There are some that maintain that denouncing the potential capability of Cuba in the development of bioweapons is not prudent. But existing defenses against these weapons are dangerously inadequate, and when, not if, biological terror strikes, as I am convinced it will, public ignorance will only heighten the disaster.

    In 1972, the United States signed the Convention on the Prohibition of the Development, Production, and Stockpiling of Biological and Toxins Weapons and on Their Destruction, commonly known as the Biological Weapons Convention. Soviet diplomats helped to write much of the language of the treaty, and the Soviet Union became one of the three depository states for the treaty. The other two were the United States and Great Britain. It was believed that the resources of the intelligence community and the vigilance and concern of the scientific community would serve to sound the alert to any violations of the treaty.

   But the belief turned out to be only in the years following the treaty. For there was no way to verify whether or not violations were taking place, and the truth is that much progress was made in the development and engineering of bioweapons in various countries around the world. This was not noticed for a long time. It was an invisible history.

   It is therefore critical that the international community continue to pursue the establishment of adequate verification measures that will increase the transparency of research programs in Cuba and elsewhere.

BIOWEAPONS: TERRORISM'S NEXT WAVE  
 

    Terrorists and outlaw countries are extending the world's fields of battle from physical space to bioweapons and cyberspace, the latter to be analyzed also in this study. They are known as high-tech weapons. The United States government has proposed $1.5 billion to prepare the nation against attacks via computers or viruses.

    A high-level U.S. government commission concluded on July, 1999, that the United States is ill prepared to combat the growing threat of biological weapons proliferation. The Committee was headed by former director of the Central Intelligence Agency John Deutch. The problem is made very complex by the growth of technology that can be used both commercially and in weapons.

   Most counter-terrorism experts view biological weapons as posing the greatest threat. A 1998 CIA publication notes that biological weapons have an advantage over chemical or nuclear weapons in that there are no reliable detection devices currently available nor are there any recognizable signals of the human senses. The report also points out that such a terrorist attack might be mistakenly attributed to natural causes.

   The U.S intelligence suspects 14 nations of having biological weapons programs-including Cuba-and some countries designated as sponsoring terrorism are suspected of either having a program or being able to start one using civilian bio-technology assets.

    A bacteriological weapon is grown in a fermenter tank, and it gives off a yeasty smell, somewhat like beer, or sometimes a meaty smell, like a meat broth. Virus weapons are not grown in fermenter tanks, because a virus does not cause fermentation when it grows. A virus converts a population of living cells into more viruses. What happens is called amplification of the virus. The machine that amplifies a virus is called a bioreactor.

    A bioreactor is a rather small tank with a complicated interior. The tank contains a warm liquid bath that is saturated with living cells. Nothing ferments inside the tank, and no gases are left off, so there is no odor. The cells are infected with a virus that is replicating. The cells leak virus particles, and the bioreactor becomes charged with them.

    A virus particle is a tiny nugget of protein that surrounds a core of genetic material, which consists of strands of DNA or RNA, ribbon-like molecules. These molecules carry the master software code that directs the activities of life. Viruses use their own software code to take over a cell and direct the cell's own machinery to make more virus particles, until the cell explodes and releases hundreds or thousands of copies of the virus.

   The ease of deployment of such weapons is of particular concern. In one scenario constructed for the Pentagon, 20 pounds of anthrax sprayed from a truck driven down New York City's Broadway would result in up to 1.8 million deaths.

    Under the White House proposal, 120 of the nation's largest cities would receive training in some of the unique aspects of response to terrorist events involving biological agents. They would also receive equipment sets required to continue the training and access to information and assistance related to biological materials.

    A lone terrorist creates a designer microbe deadly enough to annihilate Miami-Dade County. After it's unleashed into the air, the virus will jump, silently, from person to person, infecting thousands of unknowing victims. Air travelers will spread the microbe across the nation-and other nations- and millions will die within weeks. It hasn't happened yet, but it could, public-health experts advise. How do we successfully contain and combat the emerging threat of bioterrorism?

   Bioterrorism presents unique challenges. The effects of chemical warfare are often obvious immediately after an attack, allowing public-health officials time to mobilize and clean up the area within hours or days. But a biological attack might not be evident until weeks after the initial infection. And by then, the silent microbes could have spread to thousands, killings most in their wake.

   Well-trained physicians might not recognize the signs of infection by a bioweapon in a patient, especially if it is a mixed combination. Physicians should be warned that the effects of a bioweapon on the human body may be very different from natural disease caused by the same organism.

   To prepare, federal agencies have scrambled to set up new counter-terrorism strike forces. Behind all this is the very real fear that the world has entered a new stage in terrorism. Even crude weapons can easily cause mass disruption. The attack could range from the poisoning of an individual to sophisticated mass murder.

   For example, ricin is a lethal toxin extracted from the castor bean plant. This toxin was used by Soviet agents, using an umbrella-gun, to murder a Bulgarian in London, in 1978. Product tamperers, too, are increasingly turning to biological agents. There are E. coli, cholera, salmonella, HIV. The greater challenge without any doubt will come from those with broader grievances, from terrorists steeped in political hatred.

   Bioweapons are divided, in general, into strategic and operational types. Strategic biological agents are mostly lethal, such as small pox, anthrax, and plague. Operational agents are mostly incapacitating, such as tularemia, glanders, Venezuelan equine encephalomyelitis (VEE), dengue, yellow fever. Both types, however, cause extensive disruption, huge numbers of casualties.

    Release of small pox into the general population would be one of the most serious threats to mankind, said Dr. D.A. Henderson, director of the new Johns Hopkins Center for Civilian Bio-Defense Studies. Unfortunately, today that is a very real scenario. Some of the reasons bioterrorists prefer smallpox is its high fatality rates-it kills some 35 percent of its victims- and its long incubation periods-up to 14 days. While the victims do not experience symptoms during these two weeks, they can infect others. The smallpox virus is known as Variola major.

    About two weeks after infection, a victim may develop high fever, malaise, headache and backache. A rash then develops, spreading all over the body. There is no treatment and it is easily spread from person to person, Dr. Henderson said.  No one in the United States has been vaccinated during the past 25 years.  Even those immunized before that time are unlikely to still be protected. Smallpox is very contagious. One case of smallpox can give rise to twenty new cases. Each of those cases can start twenty more.

    Intelligence reports and other evidence have led the Centers for Disease Control and Prevention-CDC- officials to conclude that North Korea, and "other potential adversaries" may have harvested smallpox for use in weapons, threatening to revive a plague for which vaccines are no longer produced.

    CDC in Atlanta has placed smallpox at the top of their list of potential biological agents of mass destruction. U. S. intelligence officials cite Russian intelligence reports that concluded North Korea and other former Soviet client countries- which might include Cuba- were conducting research into using smallpox in weapons.

    CDC has begun to review its policy on the virus. Currently, agency officials said, U.S. inoculation stores would be sufficient to protect a mere 5 million to 7 million people. The idea of producing new stores of the vaccine is under consideration.

   The resurgence of concern about smallpox began with a Russian intelligence report ordered by former intelligence Chief Yevgeny Primakov, now Russia's Prime Minister. The 1993 report, "A New Challenge After the Cold war: proliferation of Weapons of Mass Destruction," stated that some countries were doing research into smallpox as a biological weapon.

   Every country with a large biological industry, which had a history of relations with the enormous Soviet biological weapon program, has the potential to produce smallpox virus, and other classical biological agents, such as anthrax, plague, and yellow fever. Cuba, with a long history of research on yellow fever and other tropical diseases, certainly has the capacity to produce such agents.

   Unlike small pox, anthrax is not spread from person to person, as previously mentioned, but it is just as deadly. Given appropriate weather conditions, 50 kilograms of anthrax released from an aircraft along a 2 kilometer line could create a lethal cloud of anthrax spores that would extend beyond 20 kilometers downwind.

   The aerosol cloud would be colorless, odorless, and invisible. They would infect people indoors as those on the street. An analysis by the Office of Technology Assessment of the U.S. Congress estimated that 150,000 to 3 million deaths could occur following the release of 100 kilograms of aerosolized anthrax over Washington D.C.

   Again, a long incubation period is a potential problem. Exposure to an aerosol of anthrax spores could cause symptoms as soon as two days after exposure. However, illness could also develop as late as eight weeks later.  Further, early symptoms of anthrax resemble a flu. Hence, persons are therefore often misdiagnosed. Untreated, 90 percent of people die, most within three days. Antibiotics can significantly reduce the risk of death, but only if given within the first few days of symptoms.

   Biological warfare experts are convinced that certain countries have developed, through genetic engineering, forms of anthrax that can overcome the vaccine now in existence. Any country with a modern microbiology laboratory-Cuba, for example- could perform the required manipulations to enhance the lethality of anthrax and create several strains of it. Anthrax is a biological weapon of choice because the bacillus forms a sturdy, long-lasting spore.

   The No. 1 threat that needs attention is the continued disintegration of Russia as a civil society. The first defector to emerge from the Soviet Union was Vladimir Pasechnik, a microbiologist from Biopreparat, who arrived in Great Britain in 1989. Pasechnik frightened British intelligence, and later C.I.A., when he told them that his work as director of the Institute of Ultrapure Biopreparations, in Leningrad, had involved offensive-biowarfare research into Yersinia pestis.

   Yersinia pestis is a pestilential microbe that causes plague, or Black Death, an airborne contagious bacterial organism, that wiped out a third of the population of Europe around 1348. The Soviet Union had developed a genetically engineered strain of plague that was resistant to antibiotics.

   Black Death can travel through the air in a cough from person to person, and a strain of multi-drug-resistant. Black Death might be able to amplify itself through a human population in ever-widening chains of infection. Other threats come from China, North Korea, Iran, and Cuba.

   We may not realize until too late that we have become the victims of a biological attack. A small amount of Marburg, Ebola, smallpox, released in an airport, subway, crowded shopping or stadium, could produce hundred of thousands of victims. The time required before symptoms are observed in a biological attack, according to First Responders Chem-Bio Handbook: A Practical Manual for First responders, 1998, is dependent upon the actual agent used. Refer too to Senator Bill Frist’s manual, 2002, on this subject.

    Casualties can present in minutes, hours, days, and even weeks after an attack. It is easier to make a biological weapon than to create an effective system of biological defense. It is easier to develop a biological weapon than to create a vaccine. At least eighty different types of bacteria, viruses, fungi can be weaponized.

    No one can seem to agree on the best approach to bio-defense. In a simulated attack staged in New York City in 1998, nearly all of the members of an emergency unit dispatched to the scene would have died because they were insufficiently protected. In September 1998, Clinton and Yeltsin agreed on a program of accelerated negotiations to strengthen the Biological Weapons Convention.

   An ad hoc group of countries have met several times since 1998 to develop guidelines for mandatory inspections in countries suspected of developing biological weapons. Other measures discussed include requiring countries to open their biological facilities to regular visits from international inspectors and setting up a unit to investigate suspicious outbreaks of disease.

   There is no technical solution to the problem of biological weapons. It needs an ethical, human, and moral solution if it is going to happen at all. Terrorism is the uncontrolled part of the problem. It is not what kind of sophisticated delivery system a country might have. The best delivery system for bioweapons would be a suitcase left in a crowded urban location. A vial of freeze-dried powder takes up less space than a pack of cigarettes.

    In 1992, the Institute of Oceanographic Studies of Cuba, and the Academy of Science conducted an intriguing experiment. It consisted in throwing to the ocean, from different points in Cuba's north coast, sealed bottles with a small note inside. The note requested from those who found them to reply to the address indicated. The note claimed it was a study of ocean contamination.

    Obviously, the real objective was to find the best delivery place in the coast to reach U.S. in an effective way. The results found that the north central coast of Cuba was the best site. This could be another form of delivery. Bioweapons are terrorism's next wave.

    As mentioned above, at least eighty different types of bacteria, viruses, fungi, and toxins, can be weaponized. We will describe next the most important lethal agents.

    Marburg and Ebola viruses both cause severe hemorrhagic fevers. Marburg virus was first recognized in laboratory workers in Marburg, Germany, and Belgrade, Yugoslavia, in 1967. These workers had been exposed to tissues and blood from African green monkeys imported from Uganda.

    There were 25 primary cases and six secondary cases in the outbreak. Ebola virus first emerged in two major disease outbreaks which occurred almost simultaneously in Zaire and Sudan in 1976. Over 500 cases were reported, with mortality rate of 80 percent.

    Marburg and both subtypes of Ebola (Ebola-Zaire and Ebola-Sudan) viruses are members of a new family of negative-stranded RNA viruses, the Filoviridae. The filoviruses are similar in morphology, density, and electrophoresis profile. Originally classified as rhabdoviruses, they appear to be more closely related to paramyviruses on the basis of recent genome sequence data.

   Filovirus particles are morphologically similar to rhabdovirus particles but longer. By electron microscopy, virions are plemorphic, appearing as long filamentous, sometimes branched forms, or   "U" shaped, "b" shaped, or circular forms.

   Clinical symptoms are similar with Marburg and Ebola virus infection. Following incubation periods of 4-16 days, onset is sudden, marked by fever, chills, headache, anorexia and myalgia.  These signs are followed by nausea, vomiting, sore throat, abdominal pain, and diarrhea.

   Pharyngeal and conjunctival infections are usual. Most cases develop severe hemorrhagic manifestations. Bleeding is often from multiple sites. Death occurs between days 7 and 16, usually from shock with or without severe blood loss. The most striking lesions are found in liver, spleen and kidney. Transmission occurs by contaminated blood samples, sexual contact, and more important, respiratory spread of infection.

    Experimental work on Marburg and Ebola viruses has been greatly impeded in the past by the high pathogenicity of these agents. New DNA technology will help to understand better the molecular structure of these viruses. Marburg virus has been successfully weaponized, and there is no known vaccine for it.

    Ebola virus was more difficult to weaponize. However, by 1991 it was believed several countries had been able to develop an Ebola weapon. Cuba is one of these countries. There is not known vaccine against Ebola either.
 

Tularemia

   Tularemia is caused by the bacteria Francisella tularensis. It can enter the human body through the skin, mouth, eyes, or nose. As a bioweapon, the bacteria would be delivered as a cloud to the target population, making entry through the airways into the lungs the most common route, although ingestion and entry through skin wounds is also possible.

    The disease may appear as ulcer or lesion at the place of entry and then progress to the lymph nodes and through the blood to other organs, including the lungs if the lungs are not already infested. The fatality rate is about 15 percent if not treated.

   Tularemia can remain alive for weeks in water and soil. It is highly infectious in that a very small number of bacteria can cause disease. After 2-10 days, symptoms, such as fever, chills, fatigue, chest discomfort, dry cough, weight loss would appear. Pneumonia may also be present.

   Once a person is exposed to tularemia, antibiotics can be given effectively whether or not symptoms have appeared. Streptomycin is the drug of choice. Vaccine is available. Human to human spread of the disease is rare. It could be used to overwhelm medical resources in a large city, leaving hospitals unable to cope with a flood of patients in need of constant treatment.

Anthrax

   Anthrax is, as mentioned before, in conjunction with smallpox, the biological weapon most likely to be encountered.  It is highly lethal; easy to produce in large quantities; relatively easy to develop as a weapon; easily spread in the air over a large area; easily stored; dangerous for a long time. All of these factors contribute to suspect that Cuba produces and store anthrax.

   Anthrax is caused by the bacteria Bacillus Anthracis. Anthrax has been recognized as an illness for centuries. Anthrax still occurs in countries where animals are not vaccinated, mainly in Africa and Asia. It does occur infrequently in many other countries, including the United States.

   When anthrax is used as a biological weapon, people become infected by breathing anthrax spores that are released into the air. Symptoms of inhalation anthrax can begin as early as 24 hours after breathing the spores. Initial symptoms include: fever, cough, weakness, and usually progress to breathing problems, shock, and death.

   It is expected that anthrax spores will be disseminated by air, causing inhalation anthrax. Because atmospheric stability is important to efficient spread, and because sunlight, as previously mentioned, is highly toxic to biological agents, they are most likely to be delivered at night.

    Particles from 1 to 5 microns in size are most efficient in causing infection, and can be present in clinically significant quantities more than 20 km. downwind. The inhaled infectious dose in man is quite high, estimated to be larger than 3,000 particles. The addition of detergents, irritants, or immuno-supressives to the aerosol may decrease the infective dose needed by up to 10-fold.

   Inhalation anthrax, also known as Woolsorter's disease, is a biphasic illness. The first phase occurs when the spores are carried to the mediastinal lymph nodes by pulmonary macrophages and cause a suppurative infection with edema and hemorrhage. This phase is characterized by nonspecific flu-like symptoms; mild fever, malaise, fatigue, myalgia, nonproductive cough, and at times a sensation of chest oppression or pressure. Rhonchi may be heard with a stethoscope.

    This phase can last for several days, or for as little as 24 hours in heavy infections, and can be followed by an asymptomatic period. The disease is treatable in this stage, but blood cultures are probably negative.

    The second phase develops suddenly with the development of severe shortness of breath and cyanosis. Hypotension and shock can occur. Stridor may be present due to enlargement of the lymph nodes near the trachea. The second acute phase typically lasts less than 24 hours. Usually ends in death despite therapy, due to the high number of toxin-producing organisms present by this stage in the illness.

    The standard therapy for inhalation anthrax is intravenous penicillin G by continuous infusion, 50 mg/kg in the first hour, followed by 200 mg/kg over the following 24 hours. In a biological warfare situation, it is recommended that vancomycin be a part of the regimen, in a dose of 500 mg every 6 hours.

   As soon as in vitro susceptibility data are available, therapy should be adjusted to include effective drugs. However, since most probably in a biological warfare situation, communications and support services will degenerate to a point of complete chaos, in vitro data would not be available.

   Recent tests with anthrax raise fears that U.S. vaccine can be defeated. The concern stems from recent evidence that Russia may have mixed together several strains of anthrax, presumably to enhance the lethality of its germ weapon. There is evidence also that Russian scientists have produced strains of anthrax genetically engineered to produce new toxins.

   The vaccine works by disabling a component of anthrax known as protective antigen, which helps the microbe's two toxins penetrate the cells they are attacking. Anthrax is one of the most effective and lethal bioweapons in existence.

Smallpox

   Smallpox is caused by a virus. The virus spread when an uninfected person comes in direct contact with a sick person and breathes in the virus. After two weeks, the incubation period of the smallpox virus, the infected person develops high fever, muscle aches and pains.

    After about three days of fever the person breaks out in a rash all over the body. At first it looks like red spots, and the spots gradually become blisters about the size of a pencil eraser. After about five days of rash, the fluid in the clear blisters turns to pus. The more pus spots that a person has, the more likely the person will die.

   There are two main types of smallpox virus: variola major, which kills about 25% of the people infected, and variola minor, which kills about 5%.of its victims. In 1965, the world Health Organization began a world-wide effort to eradicate smallpox. Studies by epidemiologists showed that the disease could be stopped from spreading if the people who came in contact with infected persons were all vaccinated.

   The disease was completely eradicated from the earth by 1977. Today, the smallpox virus exists only in two freezers, one in Moscow, Russia, and the other in Atlanta, Georgia, United States.

    There is evidence that certain countries may have harvested smallpox for use in weapons, threatening to revive a plague for which vaccines are no longer produced. Ironically, the danger smallpox would pose to a targeted population stems in part from the success medical science has enjoyed in battling the virus.

    Smallpox is unlike anthrax in that it is highly contagious but can be handled with impunity by those who are immunized against it. Yet with smallpox no longer recognized as a threat to human health, inoculations in the United States and most other countries have all but stopped. Military translation: the world's population is extremely vulnerable.

    The Pentagon has a program under way to develop a new vaccine, but its testing and development is projected to take until 2003. New intelligence assessment on countries doing research and development on the smallpox virus-Russia, North Korea, Iran, Cuba- could end up accelerating the Pentagon's program.

    Actual vaccine requires periodic boosters and wears out after ten years, though revaccination is required after three years in case of infection. Outside of the lab, variola virus thrives only in the human body.

    A virus's effectiveness as a weapon can be measured by its mortality rate, which reflects the number of people to contract the disease after exposure. Smallpox kills between 35 to 55% of unvaccinated persons, but its morbidity rate ranges from 70 to 90 percent. Those who do not die, can be permanently blinded. Others will bear scars as long as they live.

    Smallpox, unlike anthrax, requires no concentration process. It is, like anthrax, one of the most effective and lethal bioweapons in existence.

Botulinum Toxin (Bot Tox)

   It is the most toxic substance in the world. C. botulinum can be isolated from its natural habitat, the soil. It grows rapidly on common bacterial media. The conditions for achieving optimum toxin production have been well researched in Cuba. Cuba has the capacity to produce several grams in one day.

    Box tox is relatively stable, and can be stored in crystalline form. It can be absorbed through the mucous membranes, so aerosol dispersal is a likely way to be used. It can also be added to a municipal water or food supplies. Box tox is tasteless and odorless. Depending on the dosage, symptoms appear between 2 to 14 days. The symptoms include double vision, difficulty in swallowing and speaking, vomiting, and eventually respiratory failure.

    The protein is a neurotoxin and once the symptoms appear, the damage is irreversible. The only treatment involves passive antibody shots against the strains. The known disadvantages are that box tox is unstable in the air if exposed to sunlight and dry conditions. Box tox can also be destroyed by brief boiling.

Ricin

   Ricin is a protein toxin extracted from the castor bean plant. Ricin kills by destroying an important component of the protein synthesizing machinery of cells, the ribosome. It works as a slow poison, eventually causing a total body collapse as necessary proteins are not replaced. Ricin can be used to specifically target an enemy. An agent could be specific enough to use this procedure to target a single individual for assassination. There are not effective treatments once the ricin has produced clinical symptoms.

   Genetic engineering is a vital area on the development of bioweapons, and one area where Cuba has had surprising achievements.

   Genetic engineering refers to a set of technologies that artificially move functional genes across species boundaries to produce novel organisms. The techniques involve highly sophisticated manipulations of genetic material and other biological important chemicals. Genes are special chemicals that work as sets of blueprints to determine an organism's traits. Moving genes from one organism to another moves those traits.

   Through genetic engineering, genes can be moved across natural boundaries. The resultant organisms can have new combinations of genes-and therefore combinations of traits-that are not found in nature and, indeed, not possible through natural mechanisms. Such a technology is radically different from traditional plant and animal breeding.

   Basically, genetic engineering means that the DNA material of any source, living or dead cell, can be isolated, identified, altered, and introduced into the chromosome, (DNA), within any living cell. Most of the work involves isolation and identification of genes- the components within DNA which contain all the information for the synthesis of everything in every living cell.

   The information in a gene is a code. This information is relayed by a messenger. This intermediate messenger is called messenger RNA (mRNA). There is an enzyme which reads the DNA and makes this special kind of RNA from it. This mRNA then travels to the special machinery inside the cell, called a ribosome, and there the message is translated. The translation of mRNA leads to the synthesis of a protein.

Genetic engineering allows one to actually change the sequence of the DNA to allow a human gene, for example, to be expressed by bacterial enzymes and ribosomes. Thus, if one can get this gene into the chromosome of a bacterium (even though the gene encodes information for a human protein) or, if one alters certain of the gene regions to make these regions compatible for bacterial enzyme interaction, the result is important.

    Then this human gene will be expressed in a bacterium, and a human protein can be made in this way. The bacterium usually used for introduction of foreign genes is a very special laboratory strain of Escherchia coli, or E coli. Genetic engineering is wonderful and powerful. But, there is great potential for misuse.

    Genetic engineering can be used to modernize existing biological weapons and to develop genetically altered pathogens, resistant to antibiotics and vaccines. The main purposes when genetic engineering is used to alter the genetic makeup of disease-producing bacteria are: to find the right mechanism for transporting genes into the DNA of another microorganism; to achieve the transfer without reducing the bacteria's virulence.

    Genetic engineering can produce new kind of weapons based on chemical substances produced naturally by the human body. They could damage the nervous system, the heart, and produce death. For example, peptides are strings of amino acids which perform various functions in our bodies. One important group of peptides is called regulatory peptides, and is activated during times of stress, anger, love, fear, or to fight disease. Some regulatory peptides affect the central nervous system, and produce heart attacks.

   Peptides are regulators of the activity of other molecules, like proteins. Thus, there are peptides with hormonal activity, others with antibiotic activity. Genetic engineering has found a way to duplicate in the lab the genes for certain regulatory peptides, with known toxic properties.

   One of these, when present in large quantities, is capable of damaging the myelin sheaths protecting the thousands of nerve fibers that transmit electric signals from the brain and spinal cord to the rest of the body. Genetic engineering synthesizes the genes that code for the production of myelin toxin, reproduce them artificially in the lab, and insert them into bacterial cells. A toxin weapon is created.

   Certain countries, Cuba, for example, could be using their genetic engineering facilities to improve biological weapons. Their production can then be concealed in the biotechnology or pharmaceutical industry. Genetic engineering has then, as its main objective, to improve industrial production scale-up techniques; microbial production rates; yields of viable microorganisms; virulence; and resistance of microorganisms to antibiotics.

   Genetic engineering is also used to maximize viability of an agent during dissemination and increased survivability of biological aerosols, and to enhance the ability of microorganisms to degrade the target's natural defenses.

   To detect biological warfare agents is a very serious business, critical to our national security. Continuing research and field trials are made to come up with reliable sensors and instruments to detect these biological agents.

 
   One of the methods consists on collecting and preparing air samples, and then feeding them through diagnostic tests, looking for the bioagents by using highly specific molecular interactions. These devices are designed to determine the type and concentration of the agent within minutes.

   There are not yet, portable, fully automated, remote sensing systems that can detect a variety of known and novel biological agents. Biological weapons include bacteria, viruses, and toxins. Existing detection systems are fairly large, and not terribly accurate. They require humans to operate them. Most of them can detect the existence of a bioagent, but can not identify the specific agent.

Present Detectors

    The detectors now under development fall into three broad classes:

• Biochemical systems which detect a DNA sequence or protein
• Biological tissue-based systems, in which a bioagent through or biotoxin affects live mammalian cells
• Chemical mass spectrometry systems, which break down a sample into its component amino acids.

Mobility

    Present technology permits that complete departments that manufacture bioweapons be mounted on special trailers and be moved around a country. This fact makes even more difficult to detect production of bioweapons.

   A biotechnology center that produces bioweapons can not be detected from the air very easily. It could be confused with a pharmaceutical or biotechnology normal plant or center. A biotechnology center that produces bioweapons can not be detected by a simple short tour of the facilities, or by a group meeting with the personnel at the Center.

   However, what can be detected from such a visit is the state of the art, the facilities, and the trained personnel that work in the Center. It can also be known what kind of biomaterials, such as vaccines, synthezitation of protein, recombination of enzymes, peptides, proteins, homogenization processes, hydrolysis, filtration, dehydration, etc.

   Certainly, any biotechnology industry capable of performing such processes and products, is capable, and can, produce bioweapons.

   It can be detected by:
 

• Human intelligence. Defectors, or other scientists, engineers that somehow have knowledge of what is going on in the pertinent center and have the ethics and the decency to reveal their findings

• In site inspection of the Centers, with specialized scientists and engineers, with high tech equipment, in a task that can last for months.

1. These numbers depend on the agent and test conditions. These numbers are expressed as orders of magnitude
2. Times are expressed as orders of magnitude
3. Some methods require an extensive database of threat agents
4. With the exception of mass spectrometry, these can all be made more parallel by adding channels or arraying cells
5. Toxins contain no DNA

CUBA: THE BEGINNING

      In 1982, Dr. Ernesto Bravo, from the Medical School, Universidad de La Habana, a biochemist, visited Boston University. Dr. Lynn Margulis, then at Boston University, introduced Dr. Harlyn O. Halvorson to Dr. Bravo. Dr. Bravo's real mission was to develop interactions between Cuban and United States scientists. Soon, in summer 1983, Dr. Margulis and Dr. Halvorson visited Cuba. Shortly thereafter they created an organization called North American/Cuban Scientific Exchange, known by NACSEX.

    NACSEX organized visits of scientists to Cuba to exchange ideas and information. About 80 individuals were part of this program which continued in the 1980's and still is going on. These first visits led to a series of training programs. Primarily, new molecular biology technology from the United States was brought to the attention of active young Cuban scientists. Courses were given in La Habana. Advice was provided to a growing program. The Cuban medical and engineering community built a basic infrastructure in a very short period of time.

   In 1985, NACSEX conducted the Second International Seminar on Biotechnology and Interferon in Cuba. Dr. Silva Rodriguez, a well known Cuban scientist, spent then 3 months at University of Massachusetts, Amherst, learning new technology related to biotechnology and genetic engineering from Dr. Robert Zimmerman, a prominent United States scientist.

   At this time also, during a visit of Castro to the Soviet Union, in February 1981, Castro visited a laboratory where E. coli bacteria had been genetically altered to produce interferon. Castro's interest resulted in obtaining the help of Brezhnev, and immediately a strain of E. coli was sent to Cuba, along with the equipment and working technology.

   General Vladimir Lebedinsky, from the Soviet Union, visited Cuba in 1982, at Castro's personal invitation, with a team of military scientists. They assisted then the young Cuban scientists who were engaged in the creation of what can be considered today one of the most sophisticated genetic engineering labs in the world-capable of the kind of advanced bioweapons research done in Russia, Iraq, and North Korea.

    Cuba's biotechnology sector has come a long way since 1981. It is the world's second-largest producer, by volume, of Alpha interferon. Cuba is also the only country, besides highly developed nations, producing a range of human and recombinant interferon on an industrial scale.

    Cuba's research centers have also produced monoclonal antibodies, as well as chemically synthesized gene fragments and breakthroughs in virological research. One center, the most important one, the Center for Genetic Engineering and Biotechnology, CIGB, handles the research on proteins, hormones, vaccines DNA probes, modification of enzymes, biomass, and cell genetics.

    The biotechnology program has focused on the following areas:

·        development of genetic engineering

·        origination of vaccines, biological preparations

·        development of biotechnology for immunochemical applications

·        production of monoclonal antibodies

·        research with fetus

·        medical microbiology and tropical medicine

·        production of in vitro cultures

·        manipulation of embryos

   Cuba has had long practice in the art of deceiving outsiders, not to mention its own people. There is an official version for the general public and the outside world, one official version for the scientific community, and yet another secret series of activities known only to a small group of elite scientists and military personnel working on these centers.

    Despite the country's achievements in research and development, it has made limited progress in selling its products worldwide. At a 1993 trade fair, Foreign Trade Minister Ricardo Cabrisas reported that medical products had accounted for 10% of the value of exports in 1992. But more

than half of that figure corresponded to sales of a meningitis vaccine to Brazil.

    A considerable proportion of the rest was sales of interferon to China. It is estimated that, since 1991, Castro has spent over $3,500 million dollars in the development of this sector. In 1998, according to Cuba's official figures, the government spent $95 million dollars in modernizing the facilities.

   A report submitted by the U.S. Office of Technological Assessment to hearings at the Senate identified seventeen countries believed to possess biological weapons- Libya, North Korea, South Korea,Taiwan, Syria, Israel, Iran, China, Egypt, Vietnam, Laos, Cuba, Bulgaria, India, South Africa, and Russia.

Center for Genetic Engineering and Biotechnology

   The most important institution in Cuba's biotechnology industry is the Center for Genetic Engineering and Biotechnology, CIGB. It was established in La Habana, in 1986, at a cost of $150 million dollars. Located west of La Habana, 31 Ave, between 158 and 190 Streets, Cubanacan.

    The CIGB has the most modern and efficient technology for bioscientific research as well as facilities for manufacturing and continuous work flow. It has a total area of 60,000 square meters. The Center has state-of-the-art equipment, second only to the United States in the Americas.

     At the center work outstanding scientists and engineers dedicated to genetic research, virology, cloning, with the capacity to develop bioweapons, such as anthrax, smallpox, Ebola, and others.

    The main CIGB buildings cover an area of 43,200 square meters and contain specialized labs for both general purposes and dedicated research. The CIGB has a biotherium, barrier zones or white rooms, which allow research with sensitive and lethal agents. The CIGB's modern and efficient technological equipment includes mass spectrometers, infrared and ultraviolet, electron and scanning microscopes, gamma counters, DNA synthesizers. Also, and very important, downstream fermenters, drying and milling machines, centrifuges, which can, therefore guarantee research and development of bioweapons, such as bacteria and virus agents.

    In the CIGB work more than 700 highly skilled researchers, scientists, and engineers. Russians scientists cooperated with the CIGB several times, including, according to certain intelligence sources, assisting in the development of altered strains of bacteria. Major General Yury Kalinin, chief of the Main Directorate, and Deputy Minister of Russia, was invited to Cuba in 1990 to discuss the creation of a new biotechnology plant ostensibly devoted to single-cell protein.

     To facilitate the development of biological agents without suspicion, the CIGB has efficient, flexible, and dynamic organizations. It is structured into several large sub-directions made up, in turn, by a number of divisions with specifically oriented work lines.

    The main ones are: research and development in diseases in humans; development of new vaccines by genetic engineering; recombination of enzymes; analysis, design and modeling of peptides and proteins.

    The process of weaponizing anthrax, for example, can be done easily at these facilities. A few grains of freeze- dried bacteria are kept in a stoppered vial. Then, a small amount of a nutrient medium is put into the vial. A mother culture is created. With tiny pipettes, a scientist draws the mixture out of the vial and transfers a small amount into several slightly larger bottles. The bottles are left to incubate in a thermostatic oven for two days. So far, this process is very similar to the one to make a vaccine.

    A seed stock in a standard vial will swell to billions of microorganisms after 48 hours, but it will take weeks to of brewing to produce the quantities required for weaponization. Once the culture emerges from the oven, it is siphoned off into large flasks. The flasks are taken into a special room where they are connected to air-bubbling machines, which turn the liquid into a light froth. The bacteria can grow now more efficiently.

    Each new generation of bacteria is transferred into larger vessels, until is vacuum pressure into fermenters. These fermenters incubate the substance for two days. The bacteria continue to multiply until scientists decide they have reached maximum concentration. At this point, they process it through a centrifuge to be concentrated as much as thirty times further.

    Fermenters, and centrifuges, are equipment very similar to the ones used in the dairy industry, in the sugar industry, and liquor industries. These are industries where Cuba has had experience for years. Therefore, the equipment is now manufactured in Cuba. Even at this stage, there is not a weapon. The pathogen has to be mixed with special additives to stabilize it over a long period.  A scientist works with recipes. The raw ingredients are similar, but quantities and combinations of nutrient media, heat, and time vary. If something fails, the scientist has to start all over again.

    Smallpox, as mentioned before, requires no concentration. Also, it is a virus, not bacteria. Tissue cells are obtained from animals or humans. The tissue has to be kept alive outside its natural habitat in cell lines and stored at precise temperatures. Cells can be taken from the

kidneys of green monkeys or from the lungs of human embryos.

    The nutrient media needed to cultivate tissue cultures are different from those used to grow bacteria. A special complex of amino acids, vitamins, salts, and sera, distilled with de-ionized water, is crucial to the process that promote tissue cells and ultimately viruses to grow. The CIGB, in conjunction with other Cuban biological centers and institutes, like the Finlay Institute, or the Biocen, are quite capable of weaponizing such agents.

    Commercially, the CIGB has developed a number of preparations, such as:

·        Heberbiovac HB, a hepatitis B recombinant vaccine, the production of which has now been switched to a new purpose-built plant

·        Heberkinasa, a recombinant streptokinase. Applied by intravenous or intra-coronary injection, it rapidly dissolves life-threatening blood clots. This product is one of 50 types of enzymes obtained in Cuba

·        Hebermin, a healing and antiseptic cream containing human recombinant epidermal growth factor.

·        Hebertrans, which contains human transfer factor obtained from human leukocytes. It is used to treat herpectic infections

   The CIGB also has a computer network created in 1991 to provide computer communications, database access, information services and data processing to the Cuban scientific research community.

View of CIGB

Biocen

   The National Bio-preparations center, Biocen, located in Bejucal, south of Habana province, at Carretera de Beltran km 1 1/2 is engaged in industrial scale production of human vaccines. Also, culture media, nutritive bases and a wide range of genetic engineering products, developed at the CIGB and the Finlay Institute. It was created in 1992, at a cost of $15 million dollars.

    Biocen's culture media plant has an annual 40 tons capacity. It is equipped to carry out homogenization, hydrolisis, dehydration, milling, sifting, filtration, and several other processes required not only for the biotech and pharmaceutical industries, but for bacteria and virus weaponization. A new department that manufactures recombinant products went into operation in 1993. The complex also includes a plant producing immunological reagents and two vivaria labs.

    Innovative techniques have been developed at Biocen for obtaining culture media, substituting the traditional expensive nutritive bases, like meat, casein. They have developed 14 alternative protein sources. The development is vital for the creation of bioweapons.

   Among Biocen's special products are allergenic extracts, dust mites, insects, atmospheric fungi. A prominent Cuban scientist, Dr. Mario Estrada has done extensive research on fish-transgenesis with the assistance of the CIGB. Most of the more lethal toxins are developed from fish and marine research.

    Biocen follows the organization and functions of the Soviet Union, now Russia, mos important center, Biopreparat. Biocen can be considered the brains of the weapons program, and secrecy is vital. It supplies the scientific and engineering expertise for the projects commissioned by the military.

   Staff members do not know what colleagues in other parts of the organization are doing. Yet, even the most furtive networks are made of human beings. However, gossip, rivalry, desertion, allows information of secret activities to be known.

    The Carlos J. Finlay Medical Research Institute is commercially best known for the development of the world's first effective vaccine against both meningitis B and C. It is located in Ave. 27, No. 19805, La Lisa, Habana. The Institute occupies an area of 23,000 square meters, divided into three areas: fermentation, purification, and "clean rooms".  Over 950 persons work at the Institute. Of these, 60% are engineers and scientists.

   The Institute has done extensive work in the research and development of new vaccines. Among them are vaccines against Leptospirosis, Hepatitis, Cholera, and Meningitis. The Plant III area is well prepared for the production of bioweapons.

   The main areas of research and production of the Institute are related to bacteria and viruses. The Institute has been as important as the CIGB in the research and production of bioweapons. Commercially, it has worked on research and production of vaccines.

   The Institute was founded in 1937 by Dr. Flori, a very well known Cuban scientist. The center's research area is in microbiology.  The Institute has the necessary state-of the-art equipment for research and development of bioweapons related to tropical bacteria and viruses.

   Lately, the Institute has done extensive work on the strains of viruses and cells related to parainfluenza 3, adenovirus 3, measles, and influenza type A.  Hep2 two cell line was grown in minimum essential medium, MEM, containing 10% fetal calf serum, 1% glutamine, 100 U/ml

penicillin and 100 mg/ml streptomycin sulfate.

    Clinical specimens were processed using nasopharyngeal exudates of children who had been admitted to the William Soler Pediatric Hospital, in La Habana. An extensive scientific process was followed to evaluate the ability of the RNA-PCR method.

   The Institute has also conducted extensive research on yellow fever. Yellow fever is a viral disease that has caused large epidemics in the world. Infection causes a wide spectrum of disease, from mild symptoms to severe illness and death. The yellow in the name is explained by the jaundice that affects some patients. The disease is caused by the yellow fever virus, which belongs to the flavivirus group.

   The virus remains silent in the body during an incubation period of three to six days. There are two disease phases. Those patients who enter into the second phase or toxic phase develop jaundice, bleeding, kidney function deteriorates. Half of the patients in the toxic phase die within 10 days.

    A weaponized yellow fever virus produces a strong strain of what is known as urban yellow fever. There is no specific treatment for yellow fever. Prevention is through vaccination. There are other tropical disease that could be used as bioweapons, such as: malaria, dracunculiasis, filariasis, leishmaniasis, dengue, dengue hemorrhagic fever.

   Dengue is caused by the Dengue viruses. The disease is tropical in origin. There is no specific treatment available. Intravenous fluids and oxygen therapy are often used for patients who experience shock during their illness. Dengue is characterized by the rapid development of fever, intense headache, joint and muscle pain, and a rash.

   The hemorrhagic form of dengue fever is more severe and associated with loss of appetite, vomiting, and high fever. Untreated hemorrhagic dengue results in death in up to 30 percent of cases.

   The Institute is probably the best in the world in research and development related to tropical diseases. The Institute is funded in many activities by UNESCO, OMS, and the French government.

CIM  
   

   The Center for Molecular Immunology is a 15,000 square meter, two floor facility., built at a cost of $20 million dollars. Over 250 employees work at the Center, of which, 200 are scientists and engineers. The ground floor includes development, pharmacology, and toxicology. The auxiliary technical services, and secret research and development are on the second floor. Hollow fiber, fermenters, and "cleaning in place" units are installed on this floor.

   Their main research activities are on antibodies-hybridoma, molecular biology, cellular immunology.  CIM has laboratories equipped for cell culture, immunochemistry, and radiochemistry. Their work on the immune system is related to the development of stronger strains of virus and bacteria. The Center has all the pertinent equipment to produce

bio-weapons.

    There was a slippery interrelation between Soviet support to scientific programs to Cuba and Cuba's ability to develop biological weapons. For many years, the Soviet Union organized courses in genetic engineering and molecular biology for Cuban scientists. Scientists from the United States also organized courses, seminars, and other similar activities in Cuba since 1981. Many prominent European scientists have also cooperated in the development of Cuba's biotechnological industry in the last 20 years.

    There has been a constant exchange of scientific information, visiting scientists, technology transfer from the Soviet Union and the United States to Cuba. The Soviet Union sold industrial fermentation equipment vessels to Cuba. The models were the ones used to develop and manufacture bacterial biological weapons.

    Cuba also acquired equipment from other European countries under the excuse that the equipment was intended to grow single-cell protein for cattle feed. However, even exhaust filtration equipment capable of achieving 99.99 percent air purity was sold to Cuba. This level is used only in weapons labs.

    Cuba has also acquired the technology and the capacity to manufacture their own equipment. Some of the equipment required is very similar to equipment related to diary production, sugar cane processing, and liquor manufacturing, areas where Cuba has had great experience.

    There is a definitive and important relation with Iran in the field of biotechnology. Luis Herrera, one of the founders of the CIGB and the biotechnology program in Cuba is directing the Iran/Cuba activities. Refer to Chapter  XIII for further details on Cuba/Iran cooperation.

    Some analysts maintain that evidence of biological warfare research is not proof that viable weapons are being produced. However, even the most primitive biological weapons lab can produce enough of an agent to cripple a major city. Certainly, Cuba's facilities are recognized as outstanding.

    Viruses and bacteria can be obtained from more than two thousand microbe banks around the world. The international scientific community depends on this network for medical research and for exchange of information vital to the fight against disease. There are very few restrictions on the cross-border trade in pathogens.

    In the past twenty years Cuba has been working in the research and development of biotechnological products. Research has proven that viruses and toxins can be genetically altered to heighten their lethality, paving the way for the development of pathogens capable of overcoming existing vaccines.

    The arsenal of Cuba could include weapons based on tularemia, anthrax, epidemic typhus, smallpox, dengue fever, Marburg, Ebola. It could also extend to neurological agents, based on chemical substances produced naturally in the human body. It is easier to make a biological weapon than to create an effective system of biological defense.

    The United States plan to stockpile and develop vaccines against known agents is the most comprehensive of its kind in the world. Vaccines work by inducing the creation of antibodies that fight specific diseases. It is not medically advisable to combine too many different courses of vaccination. There are currently no known vaccines for brucellosis, glanders, and melioidosis, or for many viral diseases, such as Ebola and Marburg.

    Vaccines provide excellent protection against specific diseases, but the characteristics that makes them so effective is also the source of their limitations. Smallpox antibodies offer no protection against plague. Combined vaccines are possible, but most of these go straight to the metabolism of specific organisms. An all purpose antidote simply does not exist.

   Countries with the capacity and technology to produce sophisticated vaccines can certainly produce bioweapons. Cuba's biotechnology efforts have been very successful in the creation of vaccines.

    In 1957, European scientists identified the first cytokine, named interferon, which form a bridge between specific and nonspecific immune systems. They are produced in response to viruses and bacteria, or to a general stimulus in the blood. Interferon took years to isolate, but in 1979 an American produced interferon alpha artificially, called antiviral penicillin, a sophisticated biotechnological achievement. Cuba is a large producer of interferon.

    Cuba's biotechnological capacity places it in group four of the World Health Organization's five national categories. To reach group five, which contains the seven top industrial economies, Cuba must produce at least 20 percent of the 260 basic materials. It regularly produces 17 percent of these and certainly has the scientific ability to produce the others with biotech methods.

Priority access to research and development funding, 160 distinct research units and over 10,000 researchers give the Cuban scientific establishment an edge over their counterparts even, in some Western countries.

    Research is ongoing in medicine, genetic engineering, biotechnology, industrial applications, and bioweapons. Development of hardware and software for the research effort has been also a priority.

    The range of products, and research and development areas, include: monoclonal antibodies, vaccines against hepatitis B and bacterial meningitis, a neural growth factor, a range of interferon, enzymes, streptokinase, culture media with 14 alternative protein sources, several reagents, transgenetic fish, interferon beta, proteolytic peptides, lipopolysaccharide peptides, LBP-derived synthetic peptides, human Papillomavirus 16, MT-4 cells, and many others.

    Certainly, a country with such capacity can produce bioweapons. There is really no technical solution to the problem of bioweapons in Cuba. It would need an ethical, human, and moral solution, which is obviously impossible while the government is in the hands of a sociopath. Ordinary intelligence and surveillance techniques cannot prove the existence of a biological warfare program.

    Even the highest resolution satellite imagery can't distinguish between a large pharmaceutical plant or center and a weapons complex. The only conclusive evidence comes from first hand information. A site inspection of Cuba's facilities, by an objective international team must be requested.