PHAGE 4

This was originally a website named PHAGE4.org in 2004 (now defunct).  The concept became a company (Leonardo Concepts Inc.) with one design, to stop the USSR Plague Bioweapon in the wake of 9/11. In 2004-5 the proposal was submitted to the NIH (NIAID) and research moved to the T4 lab at The Evergreen State College in Olympia, Washington, one of the premier labs in the world for studying the molecular genetics of bacteriophage. The idea was to make a novel phage drug, a medicine that could save people 24-48 hours after exposure to the infectious agent that was resistant to all known antibiotics. The first part of this site is material from the former website, the second part, an acceptance letter from the NIH. The third part is the outline of the research plan. The information here establishes the fact that the author was involved in biodefense, not making anything that could be misconstrued as harmful to human beings. The idea was to stop a pneumonic plague outbreak that could kill over 90% of the people exposed to it…in short, to be prepared for a national emergency. 



PHAGE 4 INFORMATION

I wish to thank all the scientists and fellow researchers who assisted in this bacteriophage project and to those friends and family who made it all possible.

 

OBJECTIVE
Choose one Soviet era biological weapon and prepare countermeasures to be used to protect the American population in the event of an attack by terrorists. The most likely out of 100 might be anthrax, plague, small pox, melioidosis, glanders, marburg, ebola, VEE, several others. (1)

It is the contention of this initiative that pneumonic plague is the agent most likely to be used by Al Qaeda. A brief look at history and the stated goals of Wahabism indicate why. Historical Pandemic that destroyed nations and civilizations were pneumonic in nature. Pneumonic Plague spreads rapidly like the flu and is nearly 100% fatal without treatment. (2)

The Plague of Justinian in the sixth century was the first recorded episode of Bubonic Plague. It depopulated much of the Mediterranean Basin and ended Roman Civilization. Christianity emerged to take it’s place in the power vacuum that followed. (3)

The Black Death began in Italy in 1340's and laid waste to a third of Europe. Before it was over Feudalism was broken, and disaffection with the church had led to the Renaissance and the birth of Science. In each case society was radically transformed, socially and politically. (4) (19)

Civilizations that lose 50% or more of their populations in a plague event suffer functional and psychological collapse. The societies are converted or taken over with relative ease.(5) The old society, the old belief systems are no longer of value if they cannot protect you. Historically after such an event new religions arise to replace old ones. Complex societies literally fall apart and reform into something different or split into more than one new entity be it tribe or state. (6)(16)

Nothing short of this level of mass casualties and shock will accomplish the goals the terrorists have set for themselves. The diabolical evil will that perpetrated 9/11 is perfectly capable of carrying out a far more destructive crime against humanity. Al Qaeda goals are the overthrow of Western Civilization and all other religions and the establishment of a world Caliphate. (7)

ANTIBIOTIC RESISTANCE
A main feature of weaponized pneumonic plague is antibiotic resistance. The Soviet plague bioweapon is resistant to 16 different kinds of antibiotics. Doxycycline, ciprofloxacin, and gentamicin presumably work but could be overcome fairly easily. (8) (9) (1) (11)

BACTERIOPHAGE THERAPY
Phage therapy is nearly as old as the science of microbiology. It is still used today in the former USSR to treat naturally occurring bacterial diseases we treat in the west using antibiotics. The best defense against weaponized plague that is resistant to antibiotics is bacteriophage. Felix D’ Herelle successfully treated bubonic plague victims using bacteriophage therapy. (18) (20) (17) (23)

HOW PHAGE WORKS
Phage attach to the plague bacillus, enters the cell and reproduces 200 copies of itself in 25 minutes. The phage ruptures (lyse) the cell and releases the copies that seek out more target bacteria in the blood stream. A small dose has a magnified effect. If each of the 200 daughter cells infects a plague bacillus there will be 40,000 new phage, then 8 million, then 1.6 billion at the end of the 4th cycle. (11)(12)(18) (24)

The Phage 4 Initiative seeks a legislative mandate for US biotech firm to produce phage specific to weaponized Yersinia pestis.

The process is to develop, test, evaluate, and produce a phage cocktail to be used only in the event of an attack on the US using a weaponized pneumonic plague. Namely the strains found in US labs and former USSR weapon stockpiles. The time line is 1-2 years from funding until delivery of 1,000,000 doses for the Strategic National Stockpile. This should be a back channel initiative operating quietly to produce biodefense medication. There is no pressure to make a commercially viable product. The stockpile is not for sale, it is not a commercial product that needs FDA approval. It is to be under DHS control, pre-positioned at regional hospitals, and used only in the event of a national emergency. 
Topoff One was an NSC war game simulating a pneumonic plague attack on Denver. It was stopped on day 4 with 4,000 ill and 2,000 dead. Plague had spread from Colorado into Europe and Asia. “It looked like an out of control epidemic...” The Phage Four Initiative is aimed at stopping an attack using antibiotic resistant pneumonic plague on a US population center, similar to the attack depicted in Topoff One. (13)

BIOSHIELD
Nearly a billion dollars is stalled because of the difficulty of bringing a commercial product to market. FDA approval costs 5-10 years and 200+ million dollars. Venture capital is dubious to invest huge sums when the government program isn’t really buying anything yet. Therefore very little is getting done despite the large amount of dedicated funds. Bureaucracies prefer tried and true methods like vaccine but it is impractical to vaccinate the entire country against dozens of agents. It is time for a fresh approach. (1) (14)

RELATIVE COSTS
SARS struck Canada and caused comparatively few deaths. The economic impact to Ontario alone was over one billion dollars. Extrapolating these impacts across the US after a successful attack killing hundreds of thousands or more leads to economic damage potentially in the trillions. The cost benefit ratio of developing phage against such an attack are on the order of a million to one. (15) 

THE FOUR GOALS
1. 1,000,000 doses of phage specific to Y. pestis
2. A test that in minutes can discern the sick from the worried well.
3. Technology transfer and set up for continuous phage production here in US.
4. Phage production to fight other antibiotic resistant bacterial agents. 

FUNDING (approximations)
1. Small and Slow: 100,000 doses of phage specific for Y. pestis. 
Three year time-line to delivery. Efficacy of approximately 2 years. ($500,000-$1,500,000)

2. Large and Fast: 1,000,000 doses of phage specific to Y. pestis, in US/USSR labs. 
Animal testing, limited human trials, technology transfers, production in US for future contingencies. 1-2 years ($2,500,000-$10,000,000) 

RECOMMENDATIONS
It is recommended that $2.5 million dollars be appropriated to a US biotech firm in order to finance the production of Y. pestis specific phage for the Strategic National Stockpile. Animal testing and limited human trials should be conducted to test the efficacy of the phage preparations. Test kits during an emergency will be indispensable. The time line of 1-2 years should be strictly adhered to and the products should be turned over to the Home Land Defense Agency to be distributed in the event of a national emergency. 

(1)   PBS: Plague War. Interviews. Kanatjan Alibekov.
(2) CDC, WHO
(3) The Decline and Fall of the Roman Empire. Edward Gibbon
(4) Rats, Lice and History. Hans Zinser
(5) The Conquest of New Spain. Bernal Diaz
(6)William McNeill. Plagues and Peoples.
(7) The New Yorker. The Revolt of Islam. 2001-11-19
(8) The Labyrinth of Biodefense. The PSR Quarterly, March 1991,Vol. 1, pg 24.
(9) Biohazard. Ken Alibek.
(10) The Biology of Viruses. Bruce A. Voyles. pg45.
(11) JAMA 2000;283:2281-90. (Acrobat Reader is required.)
(12) Science, June 22, 2001 pg2326
(13) Lessons From Topoff One. Thomas V. Inglesby. The Second Symposium on Bioterrorism. Nov. 28, 2000. (Acrobat Reader is required.)
(14) The Wall Street Journal, May 3, 2004. Anti-terror Drugs May Be Stalled Without Funds. (Link in PDF format. Acrobat Reader is required.)
(15) Ontario Ministry of Finance.
(16) The Black Death and the Transformation of the West. David Herlihy (1997)
(17) Nature, Aug. 22, 2002; Vol. 418 pg 884-889 COVER STORY
(18) 





DEPARTMENT OF HEALTH & HUMAN SERVICES                                        National Institutes of Health

NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

www.niaid.nih.gov

Date: August 10, 2004

Marshall Thomas

Leonardo Concepts, Inc.

16918 Cottonwood Way

Houston, TX 77059

Dear Marshall Thomas:

Your proposal entitled, “Pneumonic plague therapeutic” including the specific aim to evaluate bacteriophage as a treatment for Yesinia pestis infection in an aersol mouse model has been found to be responsive to the NIH Guide Notice: NOT-AI-04-044 (found at http://grants1.nih.gov/grants/guide/notice-files/NOT-AI-04-044.html) and you are hereby permitted to submit the full application letter for consideration. Be advised to follow all instructions for assembling a complete application (incomplete application will be returned without review). Comprehensive instructions can be found athttp://www2.niaid.nih.gov/biodefense/bioshield.htm.  Also remember to include a copy of this letter along with your application.

Please forward the signed original of the application, five (5) paper copies, and one (1) CD with a faithful PDF file copy to:

Edward Schroder, Ph.D.

Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6700-B Rockledge Drive, Room 2216
Bethesda, MD 20892-7616
Bethesda, MD 20817-7616 (for express/courier service)
Tel:             301-435-8537      
Fax: 301-402-2638

Your application should arrive at our offices on or before September 23, 2004.  If you have any questions or require further guidance in completing your application material, please do not hesitate to contact me for clarification.

Good luck with your application.

Sincerely,

Michael Kurilla, MD-PhD

DMID, NIAID, NIH, DHHS

RESEARCH PLAN

  1. Specific Aims

     The Phase II goal of this initiative is to test, and evaluate a drug therapy in small mammals that demonstrates efficacy against a category A pathogen and can be used successfully against antibiotic resistant biological weapons. Specifically, it is a drug that can successfully counter the large-scale use of an aerosolized pneumonic plague bioweapon against the civilian population, one that has been weaponized to be antibiotic resistant.

     The Strategic National Stockpile represents the repository of biodefense drugs for the United States to be used in the event of a national emergency.  Vaccine represents a proven means to guard against communicable disease but immunizing the entire country against dozens of biological agents is impractical because of the expense and the possible immunological effects.  Antibody therapy is also a proven treatment for some category A agents, but the rate of immunological complication is on the order of 10(4) versus 10(6) for vaccine.  What is more antibody proteins are often difficult to produce in very large quantities in an economical manner.  Both vaccine and antibody are readily available currently for U.S. armed forces as a means of prophylaxis and in response to attack using biological weapons on the battlefield.  Neither approach is currently available on the same scale for the civilian population.  If recent history is any guide it is the civilian population that will come under attack by biological weapons, probably in the not too distant future.  Antibiotic therapy has been wildly successful for the last 60 years against bacterial pathogen, though there is the specter of increasing antibiotic resistance, particularly in the hospital setting.  Antibiotic resistance is a primary feature of biological weapons developed during the Cold War and remains an issue of grave concern. (27) Developing new classes of antibiotics is a fabulously expensive endeavor and as a result there has been little commercial motivation to do so.  Antibiotic therapy is a mainstay of the SNS in the form of push packs that can be rushed to areas of disease outbreak in an emergency situation, however there is currently no contingency for defense against the use of biological weapons that exhibit antibiotic resistance.  The strategy of using bacteriophage therapy against antibiotic resistant strains of bacterial pathogens has been validated in previous studies. (2)(21)(34)  

     In Phase II aerosol pneumonic plague experiments will characterize empirically the efficacy of the bacteriophage drug in mice.  The experimental design will parallel that of previous in vivo tests of aerosol pneumonic plague against numerous different standard antibiotics recommended for the treatment of Y. pestis. (39) It is expected that the experiments will prove the ability of the bacteriophage drug to rescue mice 24 hours post challenge at the rate of 100%. This expectation is the measurable goal of success for Phase II trials and will constitute sufficient reason to proceed to Phase III.  A secondary goal is for the phage drug to prove even greater efficacy than the mean performance of the antibiotics at 48 hours post challenge.  The expectation that phage will show greater efficacy than the antibiotics has been borne out in previous studies with other pathogenic bacteria, and will constitute even greater evidence of the value of the phage model.  (34) The experimental design may be repeated with variations if the first study is deemed successful and valuable data can be gathered by varying parameters of the experiment.

     In 1942 when Luria performed the experiments on antibiotic resistance that were later to win him the Nobel Prize for medicine, he described the factor that has come upon the medical community with a vengeance in the last two decades. Luria, working with a brand new experimental class of drugs, antibiotics, proved that starting from a single organism, mutation was an inherent feature of microbial life forms.  The new drug was penicillin, not yet introduced for widespread use.  The new drug was shown to be ineffective against an organism that it had hardly ever been exposed to before.  The mechanism of plasmid DNA was as yet not known, but the effects were proven.  Man’s latest miracle drug was not able to extinguish a bacterium that had previously been shown to exhibit sensitivity.  Antibiotic resistance and the arms race between man made drugs and bacterium were already beginning to be lost, just as the first battle had begun. Bacteriophage have been locked in this battle for billions of years.  The mutual give and take of mutation and counter mutation have probably settled down into a steady state rotation that ends with the bacteria mutating against the lytic activity of the phage, but in the process loses its envelope or some other integral functional part that confers to it the ability to propagate wildly inside a host.  Phage and bacteria have always coevolved and always will.  This is the allure of phage for treating antibiotic resistance.  It is a battle that it has always won and always will win whether man chooses to participate or not. (9)  

     The ultimate goals in Phase III will be to prove the safety of the phage drug in human trials and to build a pilot plant to determine the technologies necessary to produce large amounts of phage for stockpiling, something not done since the 1930’s in the U.S.  The proof of concept of production capability will open the door to additions to the SNS.

 

B. Significance

     The category A pathogens that might be used as biological weapons represent a clear and present danger.  Out of all these pathogens, antibiotic resistant pneumonic plague is the biological warfare weapon that has the potential to be one of the most devastating.  In the war game Topoff One the scenario of an aerosol pneumonic plague attack on the city of Denver, Colorado was simulated.  The war game scenario was stopped after 4 days.  Approximately 4,000 ill and 2,000 dead were tallied with the epidemic mushrooming into a global crisis.  The borders of the state of Denver had been closed to no avail, with the disease spreading to Europe and Asia.  In the words of the war game director, “ It looked like an epidemic out of control...” (12) What had started as a domestic attack had ended in a potential pandemic, a worldwide outbreak of a communicable disease that, in the case of antibiotic resistance, would have proven nearly 100% fatal without treatment.  This scenario is the exact contingency, which the phage drug is intended to counter.  

     During the Cold War the former USSR began a biological warfare program specifically to target the U.S. civilian population centers in time of war.  One aspect of this monumental effort (30,000 people) was known as Project Bonfire. This program culminated in the creation of some of the most dangerous bioweapons ever devised, one of which was pneumonic plague that was resistant to virtually every known antibiotic. (27) Though the large stockpiles have probably been destroyed, the seed stock of this very expensive effort are no doubt still in existence.  The porosity and corruption of the Russian security apparatus in the wake of their economic and political collapse are still very much in evidence today. 

     Antibiotic resistance plasmids are naturally occurring across a wide spectrum of bacterial diseases and Y. pestis is no different.  In Madagascar a case of resistant plague was discovered in 1995, one that was resistant to multiple drugs, including all the drugs recommended for prophylaxis and therapy against plague. (5) The isolate carried the resistance genes in a plasmid and was able to conjugate to other Y. pestis isolates.   Without a response to antibiotic resistance in Y. pestis, be it natural or man made, the eventuality of a communicable disease outbreak of a kind not seen in over a century is a very real possibility.  Achieving the goals of this initiative will greatly enhance public health in this regard.  

     Historical Pandemic that destroyed nations and civilizations were pneumonic in nature.  Pneumonic Plague spreads rapidly and is nearly 100% fatal without treatment.  The Plague of Justinian in the sixth century depopulated much of the Mediterranean Basin and effectively ended Roman Civilization.  Christianity emerged as a political force to fill the power vacuum left in its wake.  The Black Death began in Italy in the 1340's and laid waste to a third of Europe.  Before it was over Feudalism was broken, and disaffection with the church led to the Renaissance and the birth of Science.  In each case society was radically transformed, socially and politically.  Civilizations that lose 50% or more of their populations in a plague event suffer functional and psychological collapse.  The societies are converted or taken over with relative ease.  The old society, the old belief systems are no longer of value if they cannot protect you.  Historically after such an event new religions arise to replace old ones.  Complex societies literally fall apart and reform into something different or split into more than one new entity be it tribe or state.  The impact of Yersinia pestis upon human history is perhaps greater than all other factors save geography and climate.  

     Phage therapy is nearly as old as the science of microbiology.  It is still used today in the Russia, Poland, and Georgia to treat naturally occurring bacterial diseases that we treat in the west using antibiotics, as well as the treatment of antibiotic resistant organisms.  Felix D’ Herelle successfully treated bubonic plague victims using bacteriophage therapy. (26) 

     Bacteriophage attach to the plague bacillus and enter the cell to reproduce 200 or more copies of itself in 25 minutes.  The phage lyse the cell wall and release the daughter cells that collide with more host bacteria in the blood stream.  A small dose has a magnified effect.  If each of the 200 daughter cells infects a plague bacillus there will be 40,000 new phage, then 8 million, then 1.6 billion at the end of the 4th cycle. (7) The phage are self limiting, if no host bacteria are available for reproduction they are cleared from the blood stream in approximately one week by the reticuloendothelial system, predominantly collected in the spleen.  The phage drug does not interact with eukaryotic cells, only those prokaryotic cells that are the narrow range of its host bacterial strain.  These phage are so specific in fact that their interactions with one host and lack of lytic activity in another function as the definition of where one strain ends and another begins.  

 C. Relevant Experience

     Dr. Stephen D. Prior will be the Principal Investigator project director for the proposed research project.  Dr. Richard M. Carlton will be acting as Co-Principal Investigator.  Dr. Biswajit Biswas will collaborate as a laboratory investigator. Dr. Hank Lockman will participate as a consultant.  Marshall Thomas will participate as the project leader and research assistant.  Their qualifications are listed below.

Principal Investigator

     Dr. Steven Pryor of Exponential Biotherapies, Inc. has served as the companies Chief Scientific Officer, Dr. Prior is the Research Director, National Security Health Policy Center and the Field Director of the Critical Incident Analysis Group. He advises the U.S. government on defense against bioterrorism and was formerly the President and CEO of Dynport, LLC.

Co-Principal Investigator  

     Dr. Richard M. Carlton of Exponential Therapies, Inc. is the Company’s President and a Director.  Dr. Carlton was previously the President of Clinical Trials Consulting, Inc., a firm that facilitated technology transfer and clinical trials for academia and industry.  In 1990, he founded the Center for Research in Anxiety Disorders, a clinical research site for new investigative drugs. 

Co-Investigator-Collaborator

     Dr. Biswajit Biswas of Exponential Biotherapies, Inc. is the Science Director of their laboratories and has worked intensively for the last nine years perfecting techniques for phage propagation and use in experimentation.  He is skilled in producing species that have efficacy against antibiotic resistant organisms and has published multiple papers on the subject working with his colleagues at EBI.

Consultant

     Dr. Hank A. Lockman of the Battelle Memorial Institute was hired specifically to run their program for testing aerosol pathogens in small mammals.  He was formerly a member of the faculty at Ohio State University.  The Battelle Memorial Institute began operation in 1929 and is the site of the longest running continual experimental facility in the U.S.  They have 16,000 employees and did $2.7 billion in scientific consulting last year.

Project Leader/Research Associate

     Marshall Thomas of Leonardo Concepts Inc. was a member of the Hanta Virus Team at Texas Tech University. Previously he was employed by McDonnell Douglas SSC (NASA) and has worked for the Lunar and Planetary Institute (USRA)   

D. Experimental Design and Methods     

     Bacteriophage that are capable of lysing bacteria in vitro have been successfully used to treat mice that were experimentally infected with, e.g., Bacillus cereus, Escherichia coli, and Salmonella typhimurium.  Phage therapy is an alternative to the use of antibiotics or vaccination and may augment both of the former modalities.  A virulent bacteriophage that lyses Y. pestis in vitro will be tested in mice.  Mice will be challenged with a lethal aerosol dose of Y. pestis and then treated with phage to determine if the phage are active in vivo, post exposure prophylaxis.

     Adult mice (50% male and 50% female) will be obtained from a USDA approved vendor and quarantined prior to the start of the study.  To determine the efficacy of the bacteriophage therapy, mice will be exposed to an aerosol containing virulent Yersinia pestis and then treated with phage that will be administered by intraperitoneal injection (IP).  Mice will be passed through an airlock into a class III-biosafety cabinet and loaded into a nose only exposure system.  As mice are placed into the exposure chamber, they will be provided with filtered fresh air until the exposures begin.  Aerosols will be produced from aqueous suspensions of Y. pestis in a 3-jet or 6-jet Collison nebulizer and delivered to the mice via a nose-only system.  The targeted aerosol challenge dose will be approximately 1 LD50.  A sample of the aerosol will be collected in an all-glass impinger for the duration of each exposure.  Impinger suspensions will be assayed to determine colony-forming units (CFU) per ml as per Battelle Standard Operating Procedure (SOP) Number MREF.X-054.  The volume of the test atmosphere sampled through impingers will be used to calculate the concentration of Y. pestis in the test atmosphere.  The mass-median aerodynamic diameters for Y. pestis aerosols may be determined with an Aerodynamic Particle Sizer spectrometer or, alternatively, by a cascade impactor.  Previously published values for mouse tidal volumes and minute ventilation will be used to determine the duration of the aerosol challenge.  All exhausts will be filtered through HEPA filters before exhausting into the class III-biosafety cabinet and then double HEPA-filtered again before exiting the building.  The mice will be decontaminated and removed form the class III cabinet as per Battelle SOP.  The mice in this study will be challenged over 4 days with approximately 50 phage treated and 20 untreated control mice challenged on each day.  Details on aerosol exposures are contained in Battelle SOP. 

     Mice will be treated b.i.d. with 10(9) or 10(11) plaque forming units (PFU) per mouse.  The first dose will be administered to groups of mice at 1, 6, 12, 24, and 48 hours after exposure, and subsequently at approximately 12 hour intervals after the first dose of phage (table 1, pg.14).  Phage will be administered IP and treatments will continue for 7 consecutive days following the first dose.  At 2 and 5 days after the initiation of phage therapy, 5 mice from each group will be exsanguinated for quantitative bacterial and phage titers of the blood.   The remainder of the mice will be observed for 14 days post challenge and then survivors will be euthanized.

     Previous tests involving aerosolized pneumonic plague tests and the post exposure prophylaxis of antibiotics have laid a good framework for comparisons to be drawn between phage and standard antibiotics.  The ability of phage to work against antibiotic resistant forms of Y. pestis is a factor that goes far beyond the simple comparisons that might be drawn relating to survivability of experimental animals.  With this in mind, it is only necessary for phage therapy to be equivalent to the mean performance of standard antibiotic treatment for Y. pestis to be judged a success.

     In one study of pneumonic plague against standard antibiotic treatment, Y. pestis strain CO92 was used with an LD50 at 2.3 x 10(4) CFU (Guyton’s formula). (39) Antibiotics of 20mg/kg were administered every 6 hours for 5 days, after waiting 24 and 42 hours respectively.  Ciprofloxacin at standard dosage proved most effective in prophylaxis and rescue of 100% of the mice at 24 hours and 60% rescue at 42 hours from 100 LD50.  After 48 hours only 25% were survivors. The factor of antibiotic resistance is difficult to apply without empirical results, but suffice it to say the outcome would have been much worse.  Should bacteriophage therapy rescue comparable numbers as antibiotics, and under similar study conditions than the best performing antibiotic, then the new drug must be viewed as an unqualified success.  In a separate study using baboons in place of mice one of the best performing antibiotics was streptomycin, which did not yield good results if the blood concentration of plague was greater than 4 x 10(4) per cm3. (42) The ability of bacteriophage to rescue plague victims at these blood specimen concentrations may be determined with some degree of certainty in the proposed experiment.  The specter of death by sepsis due to release of endotoxins and exotoxins may preclude rescue from this degree of infection.  The sensitivity of mice is considerably more to plague than human or baboon and there will have to be some statistical adjustment made to state such a finding with any degree of confidence.  Oral phage preparations may be desirable to treat cases of such high blood saturation by plague.  These questions lay the groundwork for future experiments to increase our understanding and expand our arsenal. 

 Phase III

     Phase II experimental studies of aerosol pneumonic plague challenge in mice will prove empirically that the phage drug works equally as well or better than standard antibiotic therapy against Y. pestis.  Finally in Phase III the human safety trials will validate the safety issue and the pilot plant project will investigate the technologies of materials handling and materials processing that a batch process for the new phage drug will entail.  

 

E. Human Subjects

No human subjects are involved in this aspect of the project.  An IND is scheduled for FDA review of human safety trials to be conducted in Phase III.

F. Vertebrate Animals

Vertebrate animals will be used in this study.  The animal standards documents will be supplied at the time of award or before. 

G. Consultants

Dr. Hank A. Lockman of the Battelle Memorial Institute will conduct the aerosol pneumonic plague experiments on mice. Dr. Lockman is a former member of the faculty at Ohio State University and was hired expressly by Battelle for his degree of expertise at aerosol pathogen testing in small mammals.  The Battelle Memorial Institute is the premier private entity for NBC testing and the only entity totally capable of performing these experiments outside of USAMRIID H. Contractual Arrangements

Exponential Biotherapies Inc., and Leonardo Concepts Inc., have entered into a contractual agreement concurrent with the STTR guidelines. 

Marshall Gregory Thomas

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WE APOLOGIZE for so many links and websites.
Diversification allows the mission to succeed, even if some pathways are blocked.  The author pledges transparent public accounting, and that all funds will go to victims of torture and abuse, and to reform our institutions so these crimes against humanity never happen again.  Marshall Gregory Thomas  

Plagarism: The book MONARCH: The New Phoenix Program contains footnotes and bibliography citations that give credit to the other authors.  It also contains the following attribution.  This work is a review of literature on the subject of war crimes pertaining to the use of microwave weapons against civilians. Contributing authors have been given credit through footnotes and in the bibliography. I wish to express my gratitude and appreciation for their invaluable contributions to understanding these ongoing crimes against humanity.  I wish to acknowledge the contributions of many authors, and particularly the heroic work of Michael Rupert, Jim Keith, Alex Constantine, John DeCamp, and Dr. Nick Begich. I have made every attempt as an editor of this compilation to cite sources and include them in my bibliography. Due to extreme circumstances I have made errors in this regard, and others, but the story put forth here is faithfully and truthfully rendered and begs further investigation. The purpose of this compilation of literature is to prod more capable investigators and legal authorities to take active parts in addressing these grave issues discussed herein. There has been no attempt to claim them as my own. I wish I had done a better job. I was under pressure to finish without an editor.  Errors were bound to occur and they have been acknowledged in blogs.  I'll correct other errors in a timely manner.  The nature of the creative process incorporates the work of others on some level.  Bach and Mozart incorporated gypsy music and the work of others.  Rap is based on sampling so the entire genre would not exist without using previous music.  Picasso said, "painters borrow, artists steal".  James Joyce said he was perfectly happy to go down in history as a cut and paste man.  Any historian or author might be accused of plagarism on some level because there are no completely new ideas.  Every popular movie borrows from a previous work. The reuse of themes and ideas is a constant in society.  Without the concept of fair use and the ability to borrow some part of previous creative works then an intellectually dynamic social is impossible.  We are attempting to stop the crime of the Century and are being accused of being guilty of a common eight grade transgression. Why is there no attempt to put into perspective the crime at hand versus the well menaing errors and omissions made in attempting to end this unspeakable horror.  Where is the sense of proportion and justice?


Error and Omissions:

The first edition of the book was completed without an editor and contains many spelling errors due to missing software spell check.  In addition there are errors such as the incorrect name for a tennis players who died under MKULTRA. Lt Col Michael Aquino is referred to as NSA General Aquino and his cult is The Temple of Set, not the Church of Set.  Some scientists names have been misspelled. These errors and omissions have been largely corrected in the second edition. The first edition has not been corrected due to the replacement cost. The errors are not crucial to the overall message. Authors have been given credit in footnotes and the bibliography. There have been some omissions but these will be corrected when brought to the editor's attention.  Errors in the films are due to lack of an editor. There are more than 200 short films and more than four full length documentary films in the public domain. The author has created new films that are corrected versions of the original films.  There will be references to errors in the films that have been corrected in the latest film version. This is due to time and money constraints and the need to publish books and films quickly. This haste was due to the gravity of the crimes and the emergency response dictated by a state of affairs that includes torture of women and children.  These small scale errors do not compromise the basic premise and factual basis of the charges of criminal activity by INSCOM and others.  Please do not allow spelling errors and errors of rank or the correct name of a satanic cult to stop the quest for justice. Perpetrators may be able to alter the content of books and films on the web. To simplify this complex case it has been reduced to four main facts to allow the case to be made in stark, simple terms, and make it harder for perpetrators to confuse the message. The FOUR FACTS prove to any logical, open minded person that there is a strong likelihood of criminal activity that demands investigation. Concentrate upon the message itself and the facts, and not upon the messenger.  Marshall Gregory Thomas  

Speech Two:

I don't claim to be any smarter or more important than anyone else.  If I'm different it's because of the path that this life has led me down.  I started searching for something that I couldn't really name when I was 25.  I bought a camera and went for long walks in the woods and began to identify with the natural world, nature worship you might say.  When I was 29 I quit my job with NASA and started teaching ESL.  I was gonna save the world, one child at a time.  I was very idealistic.  I moved into a Hispanic neighborhood and taught myself Spanish, with the help of my neighbors.  When I turned 33 I got sick, traveling in Central America on spring break.  I had surgery to remove a thyroid tumor and developed an autoimmune disease.  I went to my HMO and other doctors but they couldn't help me.  The school district fired me, I lost my savings, my insurance. I was sick and unable to work. The worst of the illness came and went like a roller coaster and was getting worse all the time.  After 18 months I felt like I was gonna die, but I didn't want to die in the big city, so I moved out into the country and lived on ten acres that belonged to a friend.  It was a shack in the woods with no running water, but I had escaped the big city.  A friend of mine later said that I had gone off alone like a dog to die, which kind of summed it up nicely.  I felt like I had a lot to give and wanted to join the team for the big win, wanted to be a part of society, but they had written me off.  For lack of a better term I guess they had just flushed me. My health was broken, my body had betrayed me, so I lived the life of the mind, writing books, or rather trying to. This state of affairs continued for several years until the relapses broke me.  The muscles of my neck and back contracted so badly I couldn't sleep for nearly 6 months.  I would pass out for 2 or 3 hours but never really rested or dreamed.  I don't really know how to describe the years of torment. Robbed of my physical body, and then gradually my mind, my very sanity.  For months I sat in a chair in the dark silence. Light and sound caused me physical pain.  My eyes were rolled up into my head.  My sense of time broke down and four hours seemed like 15 minutes.  When I held a glass in my hand the glass would either slip out of my hand, or accidently break in my hand.  I thought I was gonna wind up in a nursing home.  These last few years have been hard on a lot of people. They've lost their jobs, lost their homes, their families and their lives.  I know exactly how they feel.  I've been through much the same thing for the last 16 years.  I've gotten a PhD in suffering.  Out of desperation I went back to the doctor and got lucky and found someone who could help me.  After a few years I had recovered enough to walk a hundred yards without resting.  I decided to go back to school.  I was gonna save a million lives, change the world to make it worth the price I had paid to stay in this world.  I worked in the biology department and studied microbiology, and joined the Hanta Virus team.  After 9/11 I decided to make a medicine that would stop a biological weapon. The Soviet Plague bioweapon was resistant to antibiotics.  I came up with a solution and found business partners and formed a company, applied for an NIH grant under project Bioshield.  It was around that time that I learned that innocent people were being used as human guinea pigs to perfect the latest and greatest anti-personnel weapons coming out of the DOD weapons labs.  For years I've interviewed these people in person, like an epidemiologist, finding out their symptoms and what they have in common.  If I seem unemotional I'm sorry, it is because I have had to harden my heart to terrible human suffering that at times seemed without end.  My own government is waging an undeclared war on my own people.  I believe in people, I believe in their basic goodness.  Yet evil exists and works it's will in this world. I believe in my country and in it's ability to be a force for good in the world.  Lincoln called the US the last best hope of the human race.  If the human race ever needed hope, it needs it now, for now is perhaps the hour of it's greatest trial.  I guess I've been chosen, not because of superiority, but because of the path I've gone down.  I've been a curious mixture of a young pleasure seeker, atheist, an idealist, naturalist, scientist, a fool, and a failure.  I've been blessed with gifts, but I've paid for them.  Sitting Bull was a shaman of the Sioux people.  He prayed, fasted, and made sacrifices of his own flesh and blood.  He was given visions of the outcomes of battles, and visions of his own fate.  He paid for them.  Nothing in this life is free.  The demands of this moment are many and many shall be called.  The prize is potentially a new age of peace and freedom. The price of failure may be a fate worse than death itself.  I don't have all the answers, I don't call all the shots.  I don't blame you if you are skeptical, I would be too.  But if you ignore facts, then I do find fault. I only ask that you use your common sense.  The average man on the street is perfectly capable of deciding what is in his or her own best interest.  I am saying that the new weapons similar to those in public are being used on innocent people.  If the Russians used them on the US in 1956, and got away with it for years, then what chance do these people have.  I am claiming that criminal behavior committed all the way through the Cold War by the DOD on half a million people is still going on.  US citizens are being used as human guinea pigs in terminal experiments, experiments that end in death.  This is not new, it is a continuation of past behavior.  The figure of half a million people is the governments own figure.  The majority of the targets are political activists and whistleblowers. Historically these kinds of people have been under assault for many years.  This is a historical fact.  There are a few personalities in military intelligence who are borderline personalities, people who need to be investigated.  They are not crazy, but they are different.  One has a PhD in the science of death.  He is quite literally Dr. Death.  He has been in charge of developing the new weapons for the Army since 1980. These men have written about how to use the new weapons, advocated using them on civilians, expressed admiration for previous illegal DOD programs that were war crimes, and expressed interest in using weapons of torture to modify human behavior.  The alleged criminals helped move the classified weapons into the hands of law enforcement and vigilantes, and they've participated in a smoke screen cover up.  These facts are all out in the open, and there is much more, but this by itself should drive us to the logical conclusion.  Mark Twain said that history does not repeat itself, it rhymes.  I am describing the same old song with a different tune.  There is nothing new under the sun.  People will say there is no absolute proof.  The air tight proof is classified, hidden in Fort Mead, and no one is going to break in and steal it.  People will say that the victims are all crazy.  This is what they said about the other half million US citizens used as guinea pigs and target practice.  I am saying use the common sense that God gave you and stop listening to people who tell you not to believe your own eyes.  Critics are using a shoot the messenger strategy to smear me as a terrible human being.  Well of course they are, because they certainly can't use logic and reason to the refute the facts.  What better way to ignore the facts than to change the subject and make this about me. Let me make this very clear, this is not about me.  Human beings reduce things to one personality because it helps us put larger ideas in perspective.  The power is impressive and even seductive, but I am just an old transistor radio, I am not the music.  You are in love with the music.  Good, you should be, but I'm not the music, I am just another human being on this earth. I am laying my head on the chopping block and I fully expect to be destroyed.  I cannot be bought off, scared off, or controlled.  This power is not under their control and so they must destroy a thing to control it.  First I will be discredited as a public person, then destroyed financially, spiritually, and finally physically destroyed.  There is no avoiding it.  I am just another person on this earth and soon I will be gone.  Evil exists in this world, it is not imaginary.  Americans want to live in the world of Norman Rockwell because that is a safe place, but the world is in play and the fate of nations will be decided by the people, ordinary, everyday people.  This is our generations moment of truth.  Will we, the people of the world, confront the evil in our midst, will we overcome this fortress of evil that wages war on the innocent and seeks to determine our destiny.  Charismatic leaders by themselves will not get you to the mountain top.  Your fate can only be decided by you and people just like you who decide to act in unison.  I remember all the people killed by car bombs and suicide bombers, and how the victims bodies are always taken away, but the shoes remain.  The assassins have stolen their lives and their humanity.  They are rendered silent, except for the piles and piles of hundreds of shoes.  This program of torture and murder is largely unseen because the cause of death is often heart attack, cancer, or natural disease.  I intend to pressure my Congressional representative to stop this madness by telling them that I will speak for those who have been silenced. I will take a few minutes and a few dollars to mail them a single shoe in silent protest.  Speaking for those who are gone and cannot be replaced, in their place I will demand that the alleged criminals be detained, that their elite military intelligence brigade be disarmed, and that reforms take place to guarantee that this nightmare will never again threaten our freedom and the lives of the innocent.  It is a small gesture, but out of such small gestures may come a great wave of change. When the hour is struck, and it is time for a people to be free, and all people are united as one, then there is no force on earth that can stop our march to freedom. 

 

 

Please see the independent journalism on the following pages; videos 


that prove an arms race in speed of light weapons is taking place below the

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