Michael Callahan
Dr. Michael Callahan is an American infectious diseases scientist. He is a staff physician at the Massachusetts General Hospital (MGH) and a clinical subject matter expert for international clinical trials for the Assistant Secretary of Public Health Preparedness (ASPR) of the United States Department of Health and Human Services (HHS).1)
He also maintains appointments at Harvard Medical School and King Chulalongkom Medical University in Bangkok, and consults for the National Academies of Sciences, Engineering and Medicine, National Security Council (NSC), Biological Sciences Experts Group (BSEG), the Office of Net Assessment (ONA), National Institute of Allergy and Infectious Diseases (NIAID), Mitre, the American Society of Microbiology, Infectious Diseases Society of America (IDSA), and the American Society of Tropical Medicine and Hygiene.
Callahan serves as President of Cellular Therapies at United Therapeutics Corporation.
History
Education
Callahan received his M.S. in International Public Health and his M.D. from the University of Alabama School of Medicine, where he was the 19th Tinsley Harrison Scholar and received three academic and research awards in his graduate and medical training.2)
Career
In 2002, Callahan was appointed clinical director for Cooperative Threat Reduction programs at six former Soviet Union biological weapons institutes (including State Research Center of Virology and Biotechnology VECTOR, State Research Center for Applied Microbiology, Scientific Research Institute of Microbiology and Research Center of Molecular Diagnostics & Therapy), which included redirecting of unanticipated dual use and gain-of-function programs.
DARPA
Callahan was recruited in 2004 by the Defense Advanced Research Projects Agency (DARPA) to run their $260M Accelerated Manufacture of Pharmaceuticals program dealing with pandemics and microbial resistance.3) He ran the program from 2005-2012.
While at DARPA, he launched the Accelerated Manufacture of Pharmaceuticals (AMP) program, for which he received the 2010 DARPA Achievement Award, and which generated emergency use good manufacturing practice pH1N1 vaccines, and Nicotinia-expressed monoclonals such as ZMapp. Also while at DARPA, he launched Prophecy, an international physician “early alert” network which delivers 24/7 emergency consultation, reagents and therapeutics for catastrophic infectious disease outbreaks.
Zika
Callahan acted as CEO and co-founder of the Zika Foundation.4) 5)
In March 2014, Callahan co-authored a paper describing development of medical countermeasures to the Zika virus alongside Robert Malone and Jill Glasspool-Malone, and others.6)
He published a followup study in August 2016 titled Zika Fetal Neuropathogenesis: Etiology of a Viral Syndrome, again with the Malones.7)
He participated as a speaker at the Second Symposium on Gain-of-Function Research on March 10-11, 2016.8)
Rescue Medicine
In 1988, Michael Callahan started his first company called Rescue Medicine. Rescue Medicine has been supporting federal government and U.S. corporations operating in remote international environments for over 25 years. Founded in 1988, and staffed with disaster response physicians, medics, search and rescue technicians and pilots from the U.S. Office of Foreign Disaster Assistance, we have grown from a global emergency medical evacuation provider to the U.S. government’s primary on-site care provider for expatriates in high-risk environments.
In that time, the Rescue Medicine team has expanded from one aircraft, 3 flight crews and 39 responders to a global medical intelligence and expatriate medical practice with admission privileges to dozens of foreign hospitals. Over the last two decades we have become a global leader in disaster medicine research, with a special focus on the care and management of mass-casualty infections and poisonings. Together the U.S-based academic physicians, deployment teams and in-country U.S.-board certified physicians provide the most comprehensive and up to date situational awareness of emerging health crisis to federal agencies and private organization operating in dangerous and austere regions of the globe.9)
COVID Pandemic Policy Influence
DARPA’s Ventilator Guy in Wuhan - Michael Callahan, the Department of Defense’s virus intelligence expert in Wuhan, was key to the initial panic and ventilator guidance that killed thousands of Covid patients in spring 2020. Substack - Michael P Senger Nov 11, 2022
Aside from former Deputy National Security Advisor Matt Pottinger, another lesser-known national security figure who was key to the earliest days of the United States’ response to Covid-19 is Michael Callahan, longtime manager for the Defense Advanced Research Projects Agency (DARPA), and the United States government’s only confirmed point of contact regarding the earliest days of the Wuhan lockdown in January 2020.
Unlike more public-facing figures such as Anthony Fauci, Callahan isn’t often discussed in major media outlets. But stories of Callahan’s crucial role are available just beneath the surface, from outlets including Rolling Stone and National Geographic. His preferred media contact, Brendan Borrell, wrote a book centered around his exploits in the response to Covid.
Callahan had been one of the US government’s leading biowarfare experts since the early 2000s, when he was dispatched to the former Soviet Union for several years “to form alliances with scientists at some of the most secretive bioweapons laboratories in Russia and the former Soviet states.” This entailed the “reconfiguration of former biological weapons production facilities” in order “to fight disease rather than weaponize it,” primarily for purposes of vaccine production.
By way of background, the early 2000s were part of a brief lull in which America’s relations with former communist countries were uniquely dovish, with western officials seriously underestimating the strength of old ties and loyalties within the former Soviet Union especially.
Around that same time, Callahan worked in China during the original outbreak of SARS in 2003, a feat he shared with Matt Pottinger and—supposedly—with former White House Coronavirus Response Coordinator Deborah Birx.
Callahan had also supported gain-of-function research at the Wuhan Institute of Virology, and he spoke on gain-of-function research alongside Chinese CDC Director George Gao. Gao later appeared at both the Event 201 simulation of a coronavirus pandemic weeks before the initial outbreak of Covid as well as the subsequent simulation of the first-ever global outbreak of monkeypox, the facts of which came true soon after in the exact week predicted in the simulation. 10)
SUBCOMMITTEE ON PREVENTION OF NUCLEAR AND BIOLOGICAL ATTACK
ENGINEERING BIO-TERROR AGENTS - LESSONS FROM THE OFFENSIVE U.S. AND RUSSIAN BIOLOGICAL WEAPONS PROGRAMS HEARING before the SUBCOMMITTEE ON PREVENTION OF NUCLEAR AND BIOLOGICAL ATTACK of the COMMITTEE ON HOMELAND SECURITY HOUSE OF REPRESENTATIVES - 195th Congress JULY 13, 2005 11)
Prevention, however, must remain our top priority. This country cannot afford to falter to the third mission of response whereby we find ourselves picking up the pieces after terrorists have succeeded; at that point it is simply too late.
In April 2004, President Bush issued his biodefense directive in the form of HSPD-10. Essential to this first-ever mentioned national biodefense strategy are four pillars, of which the first is threat awareness. This pillar firmly grounded in the notion that through the building of a strong intelligent capability to identify and characterize the biothreat, as well as understanding of our new scientific trends may be exploited by terrorists to develop biological weapons is paramount to our success.
ENGINEERING BIO-TERROR AGENTS LESSONS FROM THE OFFENSIVE U.S. AND RUSSIAN BIOLOGICAL WEAPONS PROGRAMS
WITNESSES
- Panel I
- Dr. Kenneth Alibek, Executive Director, Center for Biodefense, George Mason University
- Oral Statement…………………………………………. 6
- Prepared Statement……………………………………… 8
- Dr. Roger Brent, Director and President, Molecular Sciences Institute
- Oral Statement…………………………………………. 11
- Prepared Statement……………………………………… 13
- Dr. Michael V. Callahan, Director, Biodefense & Mass Casualty Care, CIMIT Massachusetts General HospitalOral Statement…………………………………………. 15
- Prepared Statement……………………………………… 18
STATEMENT OF DR. MICHAEL V. CALLAHAN, DIRECTOR, BIODEFENSE & MASS CASUALTY CARE, CIMIT/MASSACHUSETTS GENERAL
Dr. Callahan… Thank you, Mr. Chairman, committee members.Like my predecessors, I can forego much of the testimony with regard to the gravity of the threat, and focus with more precision on some of the evolutions of the convening of technology intent in the nooks and crannies of the planet where these features and these factors co-exist.
I will speak specifically with regard to three applications. My first is, as a clinical infectious disease doctor who works in the developing countries of the world in management of the diseases caused by these agents, specifically lassa fever, hemorrhoragic fever, Marlburg, Ebola, epidemics from the past, cutaneous anthrax in northern Nigeria and other places. These are listed in the testimony.
My second contribution will shore up a lot of what Dr. Alibek has said. I work extensively in the former Soviet Union; I spend 30 percent of my time there. I spend that exclusively at the bench top with former weapon scientists in 14 institutes tempering priorities to the Department of State's biological bioindustry initiative.
A key point here that I would like to stress is that this program, unlike any of the others, has used the biodefense market and the biotechnology market of western nations to create a market pull, to bring these former weapon scientists to participate in part of the solution. And for this reason we have had excellent access to these institutes. These former weapons scientists, many of them aging, and many of them with their children here in the United States receiving higher education, call upon us across international cell lines to tell us that there has been a laboratory accident, to tell us they have a sick loved one in a Russian or former Soviet Union hospital. So as a physician, we attend to them.
As advocates and collaborators, we try to help them in their education. And our statistics are quite good. Out of 177 currently engaged programs spanning 14 institutes, I will tell you that the timeline for radical medical countermeasures to the agents of bioterrorism number 11 percent. 11 percent of our total portfolio in the Harvard system, and using the best of our academic and biotechnology resources here in the United States, has new answers coming out of the former Soviet Union program. It is that which they prepared, they also mitigated against. They had to consider blow back. They will perceive that there was an offensive use capability by other nations that were targeting them as well.
So they have been thinking about unknown threat agents being lodged at them for some time, and this is a paradigm shift in the way they have developed their own science.
The third and last application, which I will minimize for the purposes of this testimony, is that the Department of Homeland Security is embarking on a huge effort to bring subject matter expertise and intelligence community members together to chart a path. We are having great difficulties with this because of arbitration and because of some of the conflicts, and the fact that, quite frankly, our expertise is not read in.
I would like to contrast, as we go along the remaining time, with the sharp distinctions with nuclear weapons. The chairman and several others have already talked about these, but I would like to crystallize these for you because it is quite policy relevant.
First and foremost, you need to understand that there are seven critical ingredients to the manufacture of biological weapons. I would like to go through them with just a couple comments in each and try to help to develop good questioning off of those.
The first of these ingredients is access to agents. There is a lot of attention being spent at the locks or freezers in the former Soviet Union, this is important. It is what the Defense Threat Reduction Agency's priority goal is, and BII and Department of State is doing that as well; it is not necessary, though. I work in all of these countries and see these diseases as a routine evolution of human ecology, and I have several of the supporting materials that are in your folder that will talk about that in some detail.
We have over 200 laboratories in Subsaharan Africa from where we have documented anthrax and plague from humans. And these are laboratories which have the capability to isolate, to purify and to amplify to these agents from all the background infectious organisms. I will also note that many of these labs are occurring in fundamental Islamic communities or are far outside the scrutiny of western nations. They are, quite literally, at the end of the path.
Number two is that, in addition to the agents which are easy to get and found in every country of concern to the United States, is that there is a critical choke point, an actionable choke point with regard to the reagents. There are several reagents that are very helpful at amplifying these agents from their background. Several reagents. It might be an antibody, it might be a plasma that could be used for the construct of a genetic organism, or with the advent evolving technologies, it might be a small scale fermenter, an ager roller bottle system, or an agent which helps to produce a high, dry powder which has high loft efficiency. Reagents is a critical actionable place to focus on.
Expertise. Here I return our attention back to the former Soviet Union program because it epitomizes this to some degree. Expertise migrates much better than the technologies do. And the experts from all the programs, and quite frankly, in ill-intentioned, nefarious-minded, moderately-trained microbiologists out of the European program cold return to these western nations and reconvene all the necessary ingredients of this technology and infrastructure to do covert manufacture. I will note also that the reason why this is so holoendemic in developing countries in the world is because the veterinary communities produce their own pharmaceuticals locally. They need anthrax to make an anthrax vaccine that is used in northern Nigeria to treat the local economy, which is on the hoof. So there is an economic force driving the technologies of these developing and small-scale weapons as well.
Technology also contributes in a meaningful way to the reconvening–remodeling really–of old-style, traditional biological weapons, such as those that were found in the U.S. program prior to its dissolution in the early 1970s. You can take an old agent, an anthrax spore preparation, and you can modernize it, and this increases its magnitude and its ponderal impact, its impact upon the human populations. This is depicted in my third handout, which talks about, at one magnitude, reduction in the number of spores that you need based on the incorporation of modern immunologic principles and the use of a single new technology which became available in 2002.
Beyond expertise and technology, I will end quickly with some of the small points. One is budget. In our laboratory modeling exercises of small-scale biological weapons, we can produce 14 million lethal doses of anthrax as a model agent for a reagent cost of 36 pounds British Sterling.
That is the reagent cost, that is not salaries. And this is done. It is not a theoretical laboratory modeling exercise, it has been done with the surrogates. It was mapped very carefully. It has an Excel spreadsheet that goes with it, and a list of reagents and inventories.
It is also important to note that the people who participated in that exercise used all open source information, they used the U.S. Patent Office and they used out of print microbiology textbooks. It is a scary incredible thing, and it is not just theoretical, it has already been capitalized both in laboratory modeling and in actual experience. I refer you back to the intelligence community's information on the American anthrax attack in 2001, which we won't discuss here.
So after the budget, finishing up, production capability. I will just remind you–and this reflects the first point about the holoendemic nature of these laboratories is that you need a covert production capability. With the modern technologies, these laboratories are downsized. The laboratory model that was used to produce that anthrax biological weapon was 200 square feet, had a capital infrastructure cost of about $220,000, and the graduate students were not salaried, so there were some cost benefits in there as well.
What is so often overlooked in our homeland security threat analysis programs is that skilled research capital, even terrorist capital, needs to be preserved. So another choke point is to focus critically on the protection of terrorists while they are producing these agents. While biological containment, the laboratory equipment that you have that protects your workers from being infected can be improvised not at the highest level that is needed for aerosolized agents that are highly dangerous pathogens.
So here we look for the hypervaccined individual, and we look for things such as consistent antibiotic immuno suppression, which has been used in other programs as well.
My summation is short because it is made easy by colleagues here. The traditional weapons exist; they are very possible, they are very plausible, they have been modelled extensively by our European partners. The agents, the technologies are all preexisting. And one of the tragic benefits is that as we develop benefits in modern health care and modern technology, which serve us well, they have a dark side, they have a down side. And it is these same technologies which have dramatically increased the efficacy and the efficiency of killing of these threat agents.I will stop there, and I look forward to your questions.
[The statement of Dr. Callahan follows-]
Prepared Statement of Dr. Michael V. Callahan
Mr. Chairman, distinguished Members, it is an honor to appear before you to present information on the threat of traditional and next-generation biological weapons. My perspective is derived from experiences as a tropical medicine physician who studies and treats the diseases caused by these agents, from experiences working with former biological weapon scientists in Russia, and threat assessment activities on behalf of the Department of Homeland Security's National Bioterrorism Analysis and Countermeasures Center (NBACC).
I am a staff physician in the Division of Infectious Diseases at Massachusetts General Hospital in Boston, Massachusetts, and the Director of Biological Threat Defense at the Center for Integration of Medicine and Innovative Technology[[ (CIMIT). [[CIMITis a multi-institution, non-profit research organization funded by the U.S. Government to identify near-term solutions for critical military and civilian medical problems.
Since January 2002, I have also worked with the U.S. Department of State, in particular with the Bio-Industry Initiative (BII), a program which uses the U.S. biotechnology market and academic collaborations to redirect former Soviet biological weapons scientists to peaceful, sustainable medical research. Prior to this position I was on faculty at the Center for International Health at Boston University where I served as clinical investigator for tropical medicine research projects in sub-Saharan Africa. I currently maintain tropical disease research activities in five developing countries, which is pertinent to the discussion below.
Since the October 2001 anthrax attack, I have worked with biological terrorism working groups from the National Academy of Science, the Department of Defense, and the Department of Homeland Security. My focus areas are risk analysis of small scale biological weapon production, and consequence management following mass-casualty infections and poisonings.
This subcommittee has asked that I provide some perspective on the threat of engineered biological weapons. As there is considerable debate about several aspects of biological weapons, I have attempted to support this testimony with photographs from the field and from laboratory modeling activities.
I will emphasize here that I am not an expert on the former U.S. biological weapons program that was disbanded in 1971. I also understand that Dr. Alibek will provide testimony on the Soviet biological weapons program under Biopreparat. My reference to the FSU (Former Soviet Union) program will therefore, be restricted to information gained from ongoing research collaborations with ex-biological weapons scientists from 10 Russian institutes. It should be emphasized that my experiences helping BII to develop drug and vaccine commercialization opportunities for former weapons scientists have resulted in access to several institutions previously closed to westerners (Figure 1).
Further transparency is gained, perhaps ironically, by relationships forged from my medical care of former weapons scientists and their family members, and on occasion, emergency medical consultation to infections resulting from laboratory accidents*. Finally, it is probably relevant that my experiences conducting clinical research in remote African and Asian locales have sensitized me to some of the challenges a terrorist lab would encounter when attempting to make a biological weapon in an austere environment (Figure 2). === What is our current understanding of engineered biological weapons? === Most experts agree that biological weapons are the original weapons of mass destruction. Throughout history, the overwhelming majority of biological weapons were used in a crude form. For example the first recorded use of biological agents was in 1346 when the Tartars catapulted plague-ridden corpses into the city of Kafka.**
In more recent history, a branch of the Japanese army, Unit 731, reportedly dropped plague-infected fleas in ceramic bomblets over cities in China in WWII, which likely accounts for unusual changes in the epidemiology of this disease in several regions. Prior to the genomic revolution of the last two decades, laboratories in several countries worked with variable success to stabilize infectious microorganisms and toxins so that they could be stored and deployed with greater efficiency and predictability.
The advent of molecular biology, advances in our understanding of infectious diseases and immune regulation, and advances in micro-particle engineering and micro-encapsulation have all resulted in technologies that can be used to either advance the properties of biological weapons or as countermeasures to protect against them.
Past military interest in biological weapons was driven by the realization that a comparatively small investment is required to make a tactical weapon capable of killing a large number of enemies. In rare cases, military weapons programs considered biological weapons as part of strategic campaigns. The interest in using biological toxins and infectious microorganisms as weapons was also driven by characteristics of the agents themselves.
For example, in contrast with other munitions such as nuclear, chemical and conventional high explosives, only biological weapons are self-replicating. Moreover, these agents can be scaled-up from seed stock to a full stockpile on short notice and with considerably less engineering, manufacturing, capital investment and production signature than would be produced by nuclear or chemical weapons. A related characteristic is that biological weapons can be covertly transported as either minute quantities or in a form that leaves no signature, thus allowing the agents to cross international borders and be produced behind enemy lines.
Military strategists also noted that only biological weapons could be successfully deployed without detection, a desirable characteristic if attribution is to be avoided. By the time clinical symptoms would appear, those that deployed the weapon would be many hours or days distant. Most ominously, and in stark contrast to chemical and nuclear weapons,contagious biological weapons such as killer influenza and smallpox, have the unique capacity to cause casualties far beyond the immediate impact zone.
Biological Weapons and Terrorism
Many of the characteristics that make biological weapons attractive to past military programs also make them desirable to the terrorist. Fortunately, the convening of biological weapon capability and terrorist intent has not as yet resulted in a mass-casualty incident.
Unfortunately, several disquieting observations of the October 2001 anthrax attack using the U.S. mail system merit emphasis. First, the attack illustrated that advanced expertise had readily been exploited by a bioterrorist; the preparation in the Daschle letter contained extraordinarily high concentrations of purified endospores.
Second, the spore preparation was coated with an incipient which helped retard electrostatic attraction, thus increasing aerosolization of the agent. Third, the choice of the near-ubiquitous Ames strain, combined with the absence of forensic details in either the agent or the letters, indicate that the terrorist is scientifically informed, wary of detection and extremely dangerous.
I use this well-publicized case to demonstrate that from the perspective of the terrorist, biological weapons are likely to be the optimal choice for inducing terror. As a practical point, the terrorist is likely to be attracted to any means which causes maximal disruption, terror and loss of confidence while using the minimal amount of skilled personnel, specialized resources and financial investment. For example, the skills required for bioweapon manufacture may be derived from manufacturing practices that use similar technologies such as the fermentative and agricultural sciences, vaccine manufacture, potable water treatment and environmental microbiology. In this regard, bioweapons offer specific advantages for covert manufactureby the terrorist-
- 1. The agent may be produced using equipment designed for other
- peaceful purposes (so called `dual use').
- 2. Production requires minimal space and time, a characteristic
- that is increasing with modern technology.
- 3. Unlike any other weapon, infectious microorganisms are self-
- perpetuating, and therefore may be propagated among the
- terrorist groups or cells.
- 4. Several agents can cause casualties beyond those originally
- infected.
- 5. When human assets need to be preserved, these weapons allow the
- perpetrator to escape detection.
From the perspective of the threat analyst, there are 7 overlapping conditions that need to be present for a terrorist group to produce an effective biological weapon. Failure to meet any of the following conditions can thwart an attempt at weapons production. These conditions are consolidated from consensus opinion of different U.S. Government working groups, by CIMIT's modeling activities and from field experiences working with over one hundred laboratories in Southeast Asia and sub-Saharan Africa (reference Figure 1: a clinical infectious disease laboratory in rural northern Nigeria. The laboratory technician and I are holding up red blood cell agar plates containing the non-hemolytic Bacillus anthracis which was isolated from the skin lesion on a local goat herdsman. In this region, estimates of 15-40 cases of cutaneous anthrax are observed annually)- the seven conditions for biological weapon production are-
1. Access to agent- this condition requires that the terrorist has the ability to isolate or procure the microorganism or biological toxin. Note that many threat agents are endemic in Neotropical regions of the globe, including all countries of concern to the U.S. Naturally-occurring infections resulting from these microorganisms are routinely encountered in domestic animals, as is the local expertise required to recognize these infections. Procurement can involve coercion, misrepresentation of intent, or illegal purchase from a former weapons program or strain collection.
2. Reagents- this condition includes availability of factors required for successful biological isolation and amplification. Examples include specialized or improvised culture media, sporulation-inducers, and incipients to stabilize the agent or to improve purity.
3. Expertise- technical know-how can be derived from other disciplines. In modeling studies stated knowledge gaps to weapons manufacture may be overcome using internet based literature and patent reviews, use of out of print texts, and identification of solutions from parallel scientific or manufacturing disciplines.
4. Support technology: this category includes laboratory assets such as roller bottles, agar trays, fermentors, lyophilizers, egg incubators, cold storage capability, animal testing capability and biochemical test kits. The recent commercialization of an unnamed technology has dramatically simplified the challenges to manufacture of one bioweapon by allowing a less refined preparation to be used.
5. Budget- in both resource rich and austere economies, the financial cost of procurement, laboratory consumables, animals and maintenance of laboratory operations is significant. In modeling studies, the anticipated budget required to complete all manufacture tasks posed a greater challenge to a minimally resourced terrorist group than did other tasks.
6. Covert production- modeling for small scale anthrax suggests that a small appropriately-equipped laboratory with a footprint of 250 ft2 would meet the production needs of a small scale spore weapon. Although many agents can be purified and engineered in simple microbiology laboratories (which are found worldwide), large scale production, coating and stabilization would require a purpose-designated facility.
7. Laboratory Safety: skilled technicians require protection, however the procurement of specialized safety equipment is closely monitored. For this reason safety capability may be improvised, or lab workers may be hyper-vaccinated and maintained on antimicrobial prophylaxis to permit lower levels of containment to be used.
What can the Former Soviet Union Weapons Program teach us about Engineered biological weapons and bioterrorism? Recent terrorist attacks in Russia have prompted government actions to protect against terrorism. However, an ethnically diverse population, poor border controls, regional corruption, and the continued conflict in Chechnya have all produced conditions that could still result in a biological weapons attack by terrorists. According to one Russian government official, ``In no other place do the microbes, the expertise, the infrastructure co-exist in such close proximity with terrorist groups and chaotic times'' (name omitted). In the last 2 yrs the concern about terrorism has prompted new levels of disclosure and cooperation between the Russian Federation and the United States.
In the last 2 years there have been 4 conferences in Moscow and St Petersburg where prevention and response to bioterrorism was a major topic. These conferences are important for a second reason in that they provide a forum whereby the FSU scientists present previously unknown countermeasures or vaccine strategies which were used to protect production workers or government personnel from the USSR agents. Some recently described technologies, such as non-specific immune enhancers immune modulators have little precedence in Western biodefense and are exciting new additions to the BII's Advanced Vaccine and Drug Development program.
Traditional weapons programs
Traditional biological weapon manufacture is best illustrated by the former U.S., British and Soviet era production methods. In the Soviet era program, simple methodologies such as microbial fermentation were conducted on a grander scale. In two former production institutes (Stepnogorsk and Berdsk) fermentors used to produce weapon strains were many thousands of liters in volume, over two stories in height and under continuous stringent environmental control.
In these programs the kill efficiencies of the weapons were increased by maximizing the number of viable microorganisms in the final munition rather than focusing on engineering of the organisms which came later). SRCAM scientists recount that in the case of anthrax, attention was focused on increasing fermentation and spore production efficiency, and spore recovery using a number of methods such as foam flotation. Other expertise was directed at improved methods of milling to produce progressively smaller clusters of spores, a condition for successful delivery and sequestration in the terminal alveoli of the lung. By report, there were occasional production misadventures where fermentation runs were contaminated by other bacteria or anti-bacterial phages which destroyed the entire production run.
In the years since the end of the Russian program, our scientific understanding of microbial metabolism and the improved efficiency of automated small scale fermentors have increased the amount of vegetative bacteria that can be produced with minimal resources. Parallel sciences, such as biological insecticides which use bacterial spores afor peaceful purposes, have provided clues to maximize yield in a small laboratory. Perhaps most disturbing is the growing availability of small scale, autonomous operating fermentation systems which reduce the need for skilled technicians and a complex support infrastructure (e.g. Bioflo IV Fermentor, New Brunswick, Inc). These systems are becoming more common in agricultural regions of Africa.
When considered as a whole, traditional weapons technologies with alterations rather than genetic engineering are the most likely to be employed by a moderately resourced, moderately skilled terrorist group. There are many open sources and skilled personnel who can provide guidance to help assemble the critical components necessary for weapons development. Potentially, a former weapons scientist from Stepnogorsk could travel to country in the Middle East and reconvene a weapons capability from available veterinary, agricultural and clinical microbiology resources. For Middle Eastern countries, the easiest solution would be to isolate a virulent epizoonotic pathogen from a local infected animal. These scientists need not bring anything with them but their expertise.
To summarize, efforts to prevent traditional biological weapon production should include efforts to prevent migration of skilled personnel to hostile groups. Additional measures for prevention of weapons development include tight scrutiny of international collaborations and tracking the importation of small scale bacterial growth systems and close human and animal surveillance efforts to detect infections resulting from deficits in the safety of a weapons laboratory.
Next-generation Biological Weapons
Next-generation biological weapons are those that benefit from new technologies, those made from previously unknown infectious agents or biological toxins, and those where a traditional agent is dramatically altered by the addition of a high-tech capability. One concept that is central to discussions of enhanced virulencebiological weapons is that the same open source methodologies that advance our ability to improve upon human health may also be commandeered for nefarious purposes. Asecond point is that traditional biological weapons such as those produced in military weapons programs can be modernized to achieve new levels of lethality. The following case is used to illustrate this point.
In the former U.S. weapons program, estimates were made about the number of anthrax spores required for an LD50 (dose required to kill 50% of a population) and LD90 (dose required to kill 90% of a population). Extrapolations from these estimates indicate that between 8,000-10,000 spores would be required for infection. These estimates are likely accurate for the anthrax strains used in the pre-1971 program. Unfortunately, in recent years there have been dramatic advances in the modeling of airflow in the human lung which in turn has driven the field of aerosolized drug and vaccine delivery. In the last 8 years, particle physicists and pulmonary scientists have worked together to improve the efficiency with which drugs reach the alveoli of the lung, which is also the preferred target for the aerosolized anthrax spore. A parallel advancement has occurred in the field of immunology where new organic coatings have been invented which dramatically increase the uptake of particles by the specialized cells in the alveoli.
Unfortunately these cells are also responsible for providing the anthrax bacillus with a protected beachhead for replication. The result is that two unrelated technologies, a method for generating small drug and vaccine aerosols, and the development of specialized coating, are responsible for dramatically reducing the number of spores required to produce a successful infection. (Figure 3 depicts the methods used to produce a coated anti-floculated spore as well as the calculated reduction in spore concentration required for infecting 80,000 people in a large city. Select steps and information omitted for this testimony)
Genetic engineering has also played a role in altering the capability of biological weapons. Toward the end of the Soviet biological weapons program an effort had been made to make several agents resistant to antibiotics. Much of this work was done using techniques considered inefficient by today's standards. Biological weapon analysts with expertise in molecular biology believe that drug resistant biological weapons are a moderate probability event that could have disastrous consequences. The reasons for this are based in the current health care impact of antibiotic-resistant microorganisms, which are arising as a consequence of indiscriminate antibiotic use. What is not clear is how likely it is that a biological weapons scientist could make a threat agent that is both highly resistant and highly virulent. Such balanced capability would require that the organism be continuously tested against animals to maintain virulence. Thus in this case, the requirements needed to engineer-in genes for antibiotic resistance might also require an attendant investment to insure that the agent remained highly pathogenic.
Next generation biological weapons may also be engineered using negative selection techniques. In this case antigens to which the patient's immune response is directed are removed from the biological weapon. In worse case scenarios, the terrorist might eliminate the antigen on a bacteria, virus or toxin that was used as the basis for a government vaccine. If the patient was exposed to one of these antigen-negative biological weapons, they would be immunologically naive resulting in more severe infection and/or death. These types of agents are known as vaccine-evading biological weapons. Unfortunately, the concept that such agents could be developed is dramatically illustrated by the need for new vaccines to protect against circulating strains of influenza A/H3N2.
Next-generation biological weapons also include the engineering-in of properties that influence the ability of the body to mount an immune response. In recent years, there have been several publications which have demonstrated this concept to biodefense scientists and potentially, to any terrorist with internet access. One of the most disquieting publication in 2002 described a method for defeating vaccine-protected animals by inserting a gene which down-regulated the immune system resulting in overwhelming infection and depth (reference provided upon request). Another publication which will appear in an international journal this September describes a methodology which single-handedly solves two separate challenges facing a biological terrorist- how to move virulence genes from one agent to another, and how to store a biological weapon without depending on freezers and liquid nitrogen (reference provided upon request).
One of the most ominous of engineering feats that could be used by biological weapon scientists is to induce host tropism into the agent, whereby the agent is altered to favor infection of a specific human genotype. This seemingly far-fetched concept is already demonstrated by certain tropical parasite infections that cause more significant infections and sequelae in certain ethnic groups.
The efforts of the biological terrorist to produce a new threat agent can also be assisted by natural events. This scenario is best illustrated by current experience with avian influenza in Southeast Asia. Since 1998, the pathogenicity of this bird virus has increased as has its ability to infect the upper respiratory systems of pigs and humans. The result is that infected patients are exposed to a novel, highly pathogenic respiratory virus to which their immune system is completely naive. The danger of this event is exacerbated by the fact that influenza, unlike anthrax, can be transmitted from person to person.
I will summarize this written testimony by reaffirming the concept that the dark science of biological weapon design and manufacture parallels that of the health sciences and the cross mixed disciplines of modern technology. Potential advances in biological weapon lethality will in part be the byproduct of peaceful scientific progress. So, until the time when there are no more terrorists, the U.S. Government and the American people will depend on the scientific leaders of their field to identify any potential dark side aspect to every achievement
Again, I appreciate the opportunity to present this information before the Committee. I shall be happy to answer your questions and to provide additional documentation supporting the material presented.
Available via the World Wide Web- U.S. GOVERNMENT PRINTING OFFICE WASHINGTON - 2006 http://www.gpoaccess.gov/congress/index.html12)