About

Experienced Research Professor with a demonstrated history of working in biomedical research in academia, government and industry. Skilled in Vaccines, Biotechnology, Technical Writing, CBRN, and Research and Development (R&D). Strong education professional with a Doctor of Philosophy (Ph.D.) focused in Biochemistry from University of California, Riverside and postgraduate training in immunochemistry from Scripps Clinic & Research Foundation.

Experience

• University of Utah School of Medicine

  • • Research Professor   ( Aug 2018 – Present  /  3 yrs 3 mos )

      1. • Research Professor - infectious diseases, Department of Pharmaceutics and Pharmaceutical Chemistry

• Department of Pharmaceutical Chemistry, University of Utah

  • • Adjunct Professor   ( Jan 2013 – Present  /  8 yrs 10 mos  /  Location :   Salt Lake City, UT )

      1. • Faculty appointment in the Department of Pharmaceutical Chemistry

• Galloway & Associates, LLC

  • • President and Founder   ( Jun 2010 – Present  /  11 yrs 5 mos  /  Location :   St George, UT )

      1. • Galloway & Associates, LLC is a certified veteran-owned small business with core expertise in the area of developing medical countermeasures (MCM) to biologic, chemical, radiation and nuclear (CBRN) threat agents and emerging infectious diseases. The firm provides strategic consulting services, project and proposal management, due diligence, merger and acquisition support, and access to subject matter expertise. Galloway & Associates’ mission is to provide a bridge enabling public, private, academic and non-governmental organizations to more efficiently partner in developing of MCM.  

         • We focus on clients with research and product development interests involving chemical and biological defense technologies as well as pharmaceutical products. The firm provides technical and strategic insight, access to emerging new technologies, and supports all aspects of advanced development. We understand and serve both the government customer as well as those developing products to meet CBRN and infectious disease MCM mission requirements. Our clients include small, medium and large innovative technology and product development companies, academic institutions, governmental defense and public health establishments. We have extensive experience in conceiving, developing and managing technologies and research programs within and between industrial, academic and governmental environments.  

         • Galloway & Associates supports governments and commercial clients in the following areas:

           1. • Assessment and evaluation of approaches and technologies for MCM development

              •  Development, demonstration and transition approaches and technologies for surveillance, detection, diagnosis, mitigation and defeat of WMD effects

         • Consultations address the following areas:

           1. • Surveillance

              • Diagnostics

              • Detection

              • Pre-treatments (emphasizing vaccines and antibodies)

              • Therapeutics

              • Related functions and technology platforms

• [Defense Threat Reduction Agency]   ( Total Duration :  6 yrs 3 mos  )

  • • Director, Joint Science & Technology Office  ( Nov 2006 – Jan 2010  /  3 yrs 3 mos )

      1. • Duties and Responsibilities/Accomplishments : Provided the intellectual leadership for planning and executing DoD CBD S&T efforts to meet chemical and biological national defense requirements. Coordinated Joint CBD Program S&T development with JCS-J8/Joint Requirements Office (JRO) for CBRN Defense and with Joint Program Executive Office (JPEO-CBD), under the oversight of the Assistant to the Secretary of Defense for Nuclear, Chemical and Biological Defense (ATSD(NCB)). Provided technical and analytical support to the ATSD(NCB). Provided scientific and technical program leadership, management, supervision, and direction to military and civilian scientists, engineers, and program managers engaged in a wide variety of science and technology programs and projects. Lead Agency actions on chemical and biological science and technology matters relating to congressional activities, interactions with senior government officials, representatives of foreign governments, industry and academia. Conducted technical and analytical assessments, executed projects and construct training tools related to CB counter-terrorism, domestic preparedness and force protection issues. Coordinated, integrated and directed all chemical and biological technology activities necessary to fulfill DTRA's combating WMD R&D and combat support agency roles. Direct management of 143 employees with an annual budget approximating $650M. Member of the Senior Executive Service.

    • Chief, Medical Division JSTO , ChemBio Defense Directorate   ( Jun 2005 – Nov 2006  /  1 yr 6 mos  /  Location :  Alexandria, VA )

      1. • Provided the intellectual leadership for planning, funding and executing DoD CBD medical S&T efforts to conduct research leading to the development of medical countermeasures against chemical and biological agents. Coordinated Joint CBD Program S&T medical requirements with JCS-J8/Joint Requirements Office (JRO) and with Joint Program Executive Office (JPEO-CBD). Provided scientific and technical program leadership, management, supervision, and direction to military and civilian scientists, engineers, and program managers engaged in a wide variety of medical science and technology programs and projects. Conducted technical and analytical assessments, and executed projects involving the development of vaccines, therapeutics and diagnostics of importance to the DoD chemical-biological defense program. Communicated with numerous government agencies, pharmaceutical industry and university representatives in the pursuit of biodefense research interests. Directly supervised 26 employees with an annual budget approximating $300M.

    • Program Manager JSTO, ChemBio Defense Directorate    ( Nov 2003 – Jun 2005  /  1 yr 8 mos  /  Location :   Alexandria, VA )

      1. • Provided the intellectual leadership for planning and executing DoD CBD S&T efforts leading to the development of vaccines and pretreatments against chemical and biological agents. Restructured the Vaccine Research Program. Coordinated Joint CBD Program S&T requirements with JCS-J8/Joint Requirements Office (JRO) and with Joint Program Executive Office (JPEO-CBD). Provided scientific and technical program leadership, management, supervision, and direction to military and civilian scientists, engineers, and program managers engaged in a wide variety of vaccine and pretreatment projects. Conducted technical and analytical assessments for project evaluation and funding; provided guidance for future research directions in vaccine and pretreatment research. Developed and implemented the annual program build for vaccines and coordinated the budget development process. Directly supervised 6 individuals with an annual budget approximating $40M.

• The Ohio State University

  • • Associate Professor of Microbiology   ( Sep 1984 – Jun 2007  /  22 yrs 10 mos  /  Location :   Columbus, OH )

      1. • full tenured academic appointment with associated research and teaching duties

         • Mentored 13 Ph.D. students to completion

         • Conducted research in microbial pathogenesis and toxins

• United States Navy

  • • CAPT, MSC USNR Ret   ( Jul 1980 – Jun 2006  /  26 yrs )

      1. • Active duty 1980 - 1984 Naval Medical Research Institute Bethesda, MD 

         • Naval Reserve 1984-2001

         • Active duty: 2001-2007 

         • 2001 - 2003 Deputy Director, Biodefense Research Directorate, Naval Medical Research Center, Rockville, MD

         • 2003-2007 DTRA [aka .. Defense Threat Reduction Agency] 

• United States Army

  • • Medical corpsman and medical laboratory technician   ( Feb 1969 – Dec 1971  /  2 yrs 11 mos  /  Location :   Ft. Monroe, VA )

      1. • Trained as medical corpsman and medical laboratory technician

         • Attained rank of E5

Education

• University of California, Riverside

• Doctor of Philosophy (Ph.D.)  /  Biochemistry  /  1973 – 1978

COLUMBUS, Ohio - Researchers here have shown that mice injected with fragments of DNA from anthrax bacteria can be immunized against the disease. In traditional vaccine approaches, researchers have used live, weakened or dead pathogens - or proteins produced by the organisms - to produce an immune response.

This new approach represents a new -- and perhaps, safer -- way to produce vaccines against highly contagious diseases.

This latest study, published in a recent issue of the journal Infection and Immunity, improves on earlier work that suggested that DNA-based vaccines might be effective. By using combinations of two gene products produced by the bacteria responsible for causing anthrax -Bacillus anthracis - the researchers were able to successfully immunize mice against the disease.

The work was headed by Darrell Galloway, associate professor of microbiology at Ohio State University, and colleagues at the National Institute of Dental and Craniofacial Research and the Biological Defense Research Directorate program at the Naval Medical Research Center in Silver Spring, MD.

Anthrax is a lethal disease if not detected shortly after exposure to bacterial spores. Antibiotics are effective in halting it if given soon after exposure before any symptoms develop. It is one of the leading potential agents discussed for use in biological terrorist attacks.

"The current work is a strong argument for the feasibility of using a DNA-based immunization strategy against anthrax."

Once anthrax spores are inhaled, they are pulled deep into the lungs where they usually are consumed by macrophages - white cells that scavenge the body for pathogens and other components that may lead to disease.

"Unfortunately," Galloway says, "the macrophages seem to be uniquely sensitive to this bacteria and are essentially targeted." Once inside the macrophages, the spores germinate producing bacterial cells that multiply until their numbers literally burst the cells, spreading infection. The bacterial cells produce and release toxin components that specifically attack additional macrophages, ultimately leading to death. This, in turn, releases massive amounts of cytokines - critical chemical components of the immune response that cause physiologic effects throughout the system.

"Ultimately, the destruction of the macrophages, and the dumping into the bloodstream of the large amounts of cytokines produced by these cells, causes the patient to go into shock which ultimately kills him," Galloway says.

His team focused on using the genes responsible for producing the bacterial toxin. These genes normally secrete three gene products - protective antigen (PA), lethal factor (LF) and edema factor (EF). The protective antigen combines with the lethal factor to form a molecule known as lethal toxin, which can invade the cell and claim credit for the fatal potential of anthrax.

"Without PA," Galloway said, "neither of the remaining two toxin components would be effective."

To construct their vaccine, the researchers assembled groups of mice and injected them three times at two-week intervals with plasmids - circular DNA molecules that are widely used for the cloning and expression of genes and their products - containing fragments of PA and LF.

Some mice received PA plasmids only, some LF plasmids only and some received a combination of both. A control group received plasmids lacking PA or LF genes. Two weeks after the last injection, researchers measured the groups' antibody response to both gene products. Mice receiving gene-laden plasmids developed strong immune responses to the gene product they were exposed to.

"Significantly," the researchers wrote, "titers (measures) of antibody to the LF antigen appeared to be about twice those of antibody to the PA. This suggests that the LF antigen induces a greater response."

The researchers also found that mice that had received both PA and LF had nearly twice the immune response of mice receiving either agent alone. This is extremely important for researchers striving to produce the most effective vaccine.

The groups of mice were then injected with five times the lethal dose of the anthrax bacterial toxin. All mice that had received the plasmid injections were immune while all animals in the control group died within several hours.

Galloway says that the results are important enough to suggest that an effective vaccine might be possible that focuses on using additional Bacillus anthracis antigens, including a mutated form of the lethal factor antigen. This point is important since earlier vaccine studies were focused on using the PA antigen alone.

"The LF antigen appears to be much more immunogenic and produces an immune response lasting much longer than the response to the PA antigen," he said.

The researchers believe their current work is a strong argument for the feasibility of using a "DNA-based immunization strategy against anthrax" and that any future vaccines should incorporate a mutated version of the LF antigen.

In a recent, as-yet unpublished study, the Ohio State University research team, in collaboration with scientists from Battelle, has demonstrated that the vaccine can protect against a significant aerosol challenge more than a year following the last inoculation.

• # Contact: Darrell Galloway, (614) 292-3761; Galloway.3@osu.edu. Written by Earle Holland, (614) 292-8384; Holland.8@osu.edu.

A new anthrax vaccine that uses pieces of the bacteria's DNA seems to work -- at least in mice, say researchers at Ohio State University.

The vaccine has successfully protected mice against anthrax, according to a recently published study in Infection and Immunity. And the study's lead author, Darrell Galloway, an associate professor of microbiology at Ohio State, says the researchers have had success with other animals as well. 

But despite all that, Galloway adds, don't look for the vaccine any time soon. The earliest human trials are still at least 18 months away.

Galloway's research comes amid heightened concern. Officials are scurrying to find more ways to counter the disease as increasing incidents of anthrax exposure are reported. The only approved vaccine, made by only one factory, is earmarked for the military and must be taken over many months.

Anxiety over anthrax has swept across the United States since a Florida photo editor died from it two weeks ago. A number of his co-workers were found to have spores on them; 31 people on Capitol Hill in Washington, D.C., have tested positive for exposure; two aides to network news anchors Tom Brokaw and Dan Rather and a U.S. postal worker have tested positive for skin anthrax,; and spores were found in the New York governor's Manhattan office complex. The finely powdered form of anthrax most have confronted appears to have been delivered through the mail.

Anthrax is caused by the bacteria Bacillus anthracis. Once the bacteria enter the bloodstream, it produces three toxins. When these toxins combine with each other, they can then enter human cells and cause the cells to die. Untreated, anthrax can be fatal.

Traditional vaccines use the actual pathogens or proteins produced by the disease and can be made in several ways: by crippling the disease organism so it can't cause the full-blown disease but it can trigger the body's immune system; by using only the part of the organism that causes an immune response; or by using a weakened or aged disease organism.

Unlike those vaccines, Galloway's research used fragments of DNA from anthrax toxins. This approach is also known as genetic immunization. The researchers focused on two of the toxins -- protective antigen (PA) and lethal factor (LF). 

They injected some mice with PA fragments, others with LF fragments, and still more with both. A control group received none. Each animal received three vaccines over a two-week period and then was exposed to five times the lethal dose of anthrax.

The mice in the control group died within hours of exposure, but all the vaccinated animals survived. Those who were co-immunized with both PA and LF showed the strongest immunity against the disease.

"If we co-immunized, we got a better response than if we immunized with either alone," Galloway says.

Galloway adds that a DNA-based vaccine offers definite advantages over traditional vaccines. DNA-based vaccines produce a stronger immune response. They are easier and less costly to produce. They require no cold storage, and they are very stable compounds with a long shelf life. And because DNA-based vaccines are so specifically targeted, there is less chance of side effects, he says.

Like the current anthrax vaccine, Galloway says the DNA-based vaccine would also probably require a series of shots. "I would envision that it will probably be a two- to three-dose situation," he says.

[Dr. Stephen Albert Johnston (born 1948)], director of the Center for Biomedical Inventions at the University of Texas Southwestern Medical Center in Dallas, worked on the original development of genetic vaccines and says this was a good test of the anthrax vaccine. The mice were, in fact, protected against the disease, he adds.

"Genetic vaccines are attractive to use against bio-threats because they are very easy to produce and rapidly scale up," he says.

Galloway thinks it could eventually be possible to immunize against three or four bio-threat agents in one vaccine. No DNA-based vaccines have yet been approved for use in humans, however.

SOURCES: Interviews with Darrell Galloway, Ph.D., associate professor of microbiology, Ohio State University, Columbus; [Dr. Stephen Albert Johnston (born 1948)], director, Center for Biomedical Inventions, University of Texas Southwestern Medical Center, Dallas; July 2001 Infection and Immunity

As anthrax exposures continue and the specter of smallpox has loomed on the horizon, many officials have begun discussing widespread vaccination against the two diseases in an effort to reduce public concern about terrorist threats.

But the vaccines now in use present a number of problems--ranging from lack of manufacturing capacity to side effects--that render large-scale vaccination programs problematic.

Medical researchers have been working on efforts to produce safer vaccines. But until now, drug companies have put relatively little money into what has been considered a low-margin, low-priority part of the business.

For both anthrax and smallpox, the side effects of the vaccines are serious enough that widespread vaccination could cause more damage than the diseases themselves unless the vaccines are used only after a major outbreak has begun.

Anthrax vaccination of soldiers has produced reports of severe side effects, such as bleeding and thyroid malfunction, and has been linked to six deaths.

Just what degree of risk there is from the vaccine, however, is unclear. Many medical authorities say it is safe, but some doctors have suggested it could be one of the causes of the mysterious Gulf War syndrome, which some troops sent to the Persian Gulf in the early 1990s have said they suffer from

Fear of the vaccine is perhaps greater than fear of anthrax. As many as 400 members of the U.S. military have been court-martialed or have resigned rather than submit to the vaccination because of the perceived risks. Some physicians share their misgivings.

“You won’t see me getting in line for the vaccine,” says [Meryl Jae Nass, MD (born 1951)], a longtime critic.

The vaccine is produced by only one manufacturer, BioPort Corp. of Lansing, Mich., and the technology is nearly 40 years old. Although the company is currently producing the vaccine, the Food and Drug Administration will not allow it to be shipped because of various deficiencies in quality control and manufacturing at the plant.

The vaccine is unusual in that it is not targeted at the bacterium itself, as are most vaccines, but at the toxin produced by the bacteria as they grow. That toxin produces the cellular damage that can lead to death from an anthrax infection.

The toxin has three major components: protective antigen, lethal factor and edema factor. When the toxin is released in the body, individual molecules of the protective antigen clump together on the surface of target cells to form a doughnut-shaped pore. This pore is then used by the other two components to enter the cell, where they are lethal.

The vaccine is designed to stimulate antibodies to the protective antigen, preventing it from attaching to cells. In theory, if the action of the toxin is blocked, then the immune system can eradicate the bacteria or they can be killed with antibiotics.

“We buy the individual some time to fight off the infection,” said microbiologist [Dr. Darrell Ray Galloway (born 1946)] of Ohio State University.

BioPort grows a strain of Bacillus anthracis that secretes only protective antigen. The bacterial culture is filtered--in a process much like making coffee in a filter pot--to collect the antigen along with any other materials that are secreted by the bacterium. The material that drips through the filter becomes the vaccine. It contains no bacteria, either dead or alive.

But the antigen does not stimulate a strong immune response. To get good immunity, six doses of the vaccine must be given at two-week intervals.

Critics fear that the other bacterial components collected along with the antigen may cause side effects, so research has focused on eliminating them.

“The interest is in more highly defined vaccines so one knows precisely what one is being immunized with,” Galloway said.

The Army has been working with the National Institutes of Health to use genetic engineering techniques to produce a pure antigen. Although both the military and the NIH have consistently refused to talk about their work, other experts say that human tests will begin early next year. That vaccine will also require multiple doses.

In his research, [Dr. Darrell Ray Galloway (born 1946)] also is targeting the toxin. But instead of using the antigen protein itself, he is injecting mice with the gene that causes the body to produce the protein. Researchers have been producing such DNA vaccines against a variety of diseases, and they are generally thought to produce a more powerful immune response and fewer side effects than standard protein vaccines.

He also uses the gene for the lethal factor in his vaccine. “We get a greater response with both than with one alone,” he said. Preliminary results in mice reported earlier this year indicate that the DNA vaccine can blunt anthrax infections, but Galloway must conduct many more tests, including vaccination of primates, before use of the vaccine in humans can be considered

The most optimistic estimate would be 18 to 24 months before clinical trials could begin, he said.

The smallpox vaccine produces a different set of problems. Like the anthrax vaccine, it employs old technology--dating back to experiments by Edward Jenner, the pioneer of vaccines, in 1796.

Smallpox is produced by a virus called variola, but researchers do not use it to produce the vaccine. Instead, they use a related virus called vaccinia, which produces a disease called cowpox.

The normally mild infection produced in humans by the live vaccinia provides very good protection against smallpox--so good that the disease has been eradicated from nature. Today, variola is known to exist only in one laboratory each in the United States and Russia, although U.S. officials suspect that Iraq and perhaps other nations may also possess some virus stocks.

“The risk of its being used as a weapon is not very high, but it’s there,” said [Dr. Donald Ainslie Henderson (born 1928)] of Johns Hopkins University, who ran the global smallpox eradication campaign. “And if you got an outbreak, it would be a terrible global catastrophe.”

Existing stocks of the smallpox vaccine were grown in calf cells, collected and freeze-dried more than 30 years ago.

The vaccines are believed to still be effective, but they are contaminated with proteins and other materials from the cow cells that may produce adverse reactions in some individuals.

New Rules From the FDA

The FDA no longer allows vaccines to be grown in animal cells. The new contracts for vaccine production recently signed with several companies require that vaccinia be grown in human cells. That process is straightforward and should not introduce difficulties, and manufacturers assume that the new vaccine will be as effective as the old one.

“There are no technical hurdles here,” said Lance Gordon, chief executive of vaccine manufacturer [VaxGen, Incorporated]. “Everything that has to be done to make a state-of-the-art smallpox vaccine is technology already in use.”

But critics caution that a smallpox vaccine grown in human cells has never been tested and that assumptions don’t always hold up.

Vaccinia, moreover, can itself produce problems ranging from open sores all over the body to death.

The death rate is estimated to be as high as 2 in a million cases, meaning that if the entire U.S. population were vaccinated, about 600 people would die of the vaccine.

Inadvertent contamination of the eye--caused perhaps by touching the vaccination site and then the eye--can produce severe problems, including blindness.

Vaccinia itself is infectious. That’s a valuable trait in a vaccination program because it provides protection to people who weren’t directly vaccinated.

But in a modern society with large numbers of people whose immune systems have been damaged, by HIV infections or as a result of drugs taken for organ transplants, that contagion could be a major problem that likely would lead to additional deaths.

All told, vaccinating all Americans against smallpox could cause 3,000 severe adverse reactions and a much larger number of lesser problems, according to [Dr. Thomas Patrick Monath (born 1940)], an executive at British vaccine manufacturer Acambis.

If a terrorist group actually launched a smallpox attack, however, “we don’t have any choice as a society” other than to use the vaccinia vaccine, said [Dr. Darrell Ray Galloway (born 1946)].

The U.S. population now is almost entirely unvaccinated--the effect of the vaccine largely wears off after about 20 years, so most people who received the vaccine as children are no longer immune. An unprotected outbreak of smallpox potentially could kill millions of people, experts say.

A small number of researchers have been exploring the possibility of using a different type of vaccine, a killed-virus vaccine, which would eliminate the danger to immunosuppressed individuals.

But development of such a vaccine, like that for anthrax, has been hindered by lack of a market, and any product is still at least a couple of years from human tests.

For that reason, officials have pushed for a major expansion of the current smallpox vaccine supply. Right now, the country has about 15 million doses, not nearly enough to contain a major outbreak.

The World Health Organization once had 200 million doses in storage in Switzerland, but the international body ran out of money to keep them, and they were destroyed after President Reagan reduced U.S. payments to the United Nations. ‘

[Vical Incorporated] and the Ohio State University announced that the U.S. National Institute of Allergy and Infectious Diseases (NIAID) will fund a one-year Small Business Technology Transfer Research (STTR) grant to collaborate on a preclinical research project to develop DNA vaccines against anthrax. 

[Vical Incorporated] will recognize the revenue from the grant as the work is performed. The grant does not change the company's forecast for a net loss of between $28 million and $32 million for 2002. 

Vical's patented naked DNA technology allows scientists to construct rings of genetic material, known as plasmids, that express one or more proteins once inside the body. The anthrax vaccine would use this proprietary technology to establish immune system defenses against the bacterial proteins produced by anthrax that combine to cause toxic effects. This approach may have significant safety and manufacturing advantages over traditional vaccines that use live, weakened, or dead pathogens to produce an immune response. 

Initial research on this type of anthrax vaccine was conducted in mice by [Dr. Darrell Ray Galloway (born 1946)] at Ohio State University and the U.S. Naval Medical Research Center. His research produced the initial finding indicating that a DNA vaccine could be developed that would protect against aerosolized or weaponized anthrax spores.

With the nation’s terror alert level raised to orange – or high – on Tuesday and evidence that al-Qaida may be planning another strike, fear of a biological terrorist threat is again running high.

Dr. Darrell Galloway, associate professor of microbiology and director of biological defense at the Naval Medical Research Center, has been researching the use of a DNA-based vaccine to immunize against anthrax or other pathogens – a vaccine which may prove safer and more effective than traditional vaccines.

“Anthrax is a toxin-mediated disease bacterium that, once it gets in the body, grows,” Galloway said. “It secretes three proteins as it grows and they can combine to produce toxins, causing the symptoms of anthrax,” Galloway said.  Anthrax is caused by the bacterium Bacillus anthracis.

“If we target the toxin proteins and neutralize them, we can prevent the physiological effects of anthrax,” Galloway said. In traditional vaccines the actual pathogens or proteins produced by the disease itself, or some byproduct of it, are used to immunize. The immune system responds by making antibodies to neutralize the toxin. This involves a lot of work, time and expense to inject or prepare a vaccine, Galloway said.

The DNA-based vaccine provides cells with the target proteins needed to develop an immunity.  “If we target the toxin proteins and neutralize them, we can prevent the physiological effects of anthrax,” Galloway said.

In traditional vaccines the actual pathogens or proteins produced by the disease itself, or some byproduct of it, are used to immunize. The immune system responds by making antibodies to neutralize the toxin. This involves a lot of work, time and expense to inject or prepare a vaccine, Galloway said.

“We inject genes and individual cells. They make the vaccine on their own within the body,” Galloway said. “There are no side effects from preservatives normally in a vaccine.”

The current vaccine has a large number of complications, requiring several booster immunizations.

With the DNA-based vaccine, recipients “don’t have to boost as many times – it’s easier and cheaper,” said Mike Boehm, professor of plant pathology, who is also in the same Naval Reserve unit as Galloway.

The research started in conjunction with the U.S. Navy and Ohio State.

ViCal Incorporated, based in San Diego, holds the patent on the DNA-based vaccine, and Galloway was interested in their expertise.

“My lab and the Navy demonstrated proof of principle vaccine, so we expanded the project with ViCal,” Galloway said.

ViCal will take vaccine to human clinical trial. These initial trials are divided into phases. Phase I is a safety study where a few individuals are immunized. Here they look for indications of safety. Studies are usually conducted on volunteers from colleges.

“Its going to take several years for al the studies to be done. It depends on how aggressively the study is pushed,” Galloway said. “It will probably be two to five years to complete the study to the FDA’s satisfaction.”

Pending the FDA’s approval, ViCal will then choose whether to market it.

“They could sell it to the military, foreign governments or even the public,” Galloway said. “It depends on cost effectiveness – how it compares to the current vaccine.”

While anthrax is the particular area studied in Galloway’s research, the vaccine can be used on other pathogens.

“DNA vaccines show a lot of promise – this new approach is also being used experimentally for HIV and tuberculosis,” said Andrew Phipps, research scientist at the Batelle Memorial Institute. Phipps specializes in biodefense research.

These advancements in technology are the most important issue.

“DNA-based immunization can be effective is the key point here,” Galloway said. “If we show it works here, we can show it can work elsewhere.”

Anthrax was a way to get more attention and money for the research.

“It’s a novel approach to a hot topic,” Boehm said.

NEW YORK – An Ohio State University professor is part of a team that developed a new protocol that the U.S. Navy now uses to detect biowarfare (BW) agents, such as anthrax, aboard its ships.

"Until mid-2002, the only equipment to detect biological agents that warships had were the sailors themselves," said Michael Boehm, an associate professor of plant pathology at Ohio State and a lieutenant commander in the U.S. Naval Reserve.

"The military was ill-prepared to deal with what might happen if a 37-cent letter filled with anthrax or smallpox was opened on a ship at sea."

Boehm was called to active duty shortly after September 11, 2001, to help the Navy develop an inclusive biowarfare agent detection program. In late 2001, he headed for the Naval Medical Research Center's Biological Defense Research Directorate (BDRD) in Silver Spring, Md. Boehm's active duty stint ended in February 2003, and he returned to Ohio State.

He and his colleagues at BDRD developed, implemented and trained Navy personnel in how to sample, test and respond to possible biowarfare attacks by agents such as anthrax and smallpox that, this past spring, the Navy adopted as a standard operating procedure for detecting the presence of BW agents. According to Boehm, the plan can be used anywhere there's a suspected BW incident.

Boehm shared his experience in designing the protocol on September 9 at the meeting of the American Chemical Society in New York City. Co-presenters, all with the Naval Medical Research Center's Biological Defense Research Directorate, included [Dr. Alfred Joseph Mateczun Jr. (born 1942)], [Dr. Darrell Ray Galloway (born 1946)],, Robert Bull, Joan Gebhardt, Timothy Stello and Richard Gotautas.

The researchers devised a three-tiered biowarfare agent detection system:

Level 1 – presumptive. Armed with portable hand-held assays, which look and function like home pregnancy test kits, trained personnel can determine within 15 minutes to an hour whether or not a suspected BW agent has infiltrated a ship. Developed in the early 1990s for use in Operation Desert Storm, such test kits give users quick results, but also have their limits, Boehm said.

"While these tests are a good, quick prescreen, the only definitive way to determine if the results of the hand-held test are truly accurate is to grow the organisms in a laboratory," he said.

Level 2 – confirmatory. Before the current testing system was in place, ship-bound Navy personnel had to wait 24 to 96 hours before getting a definitive answer on whether or not a suspected pathogen had infiltrated a ship, said Boehm. Suspicious samples were sent to land-based laboratories for testing. Under the new protocol, several warships have installed air filters connected to machines that run polymerase chain reaction (PCR) assays – tests that provide a genetic fingerprint of a biowarfare agent. These air filters "breathe" nearly 70 times the amount of air a sailor breathes.

"With PCR, we could find a single gene copy amid an ocean of pathogen in less than an hour," Boehm said. This kind of quick detection helps medical personnel know how to treat people who were exposed to the pathogen, ideally before those people have a chance to infect others.

Level 3 – definitive. The suspected specimen is sent to BDRD or another national laboratory, such as the Centers for Disease Control and Prevention or the U.S. Army's Medical Research Institute of Infectious Diseases for a full analysis.

"The problem with BW agents is that they come in a variety of forms, such as bacteria, toxins and viruses," Boehm said. "Several of the biggest threats – anthrax and plague – are bacteria and can be grown in a laboratory. But viruses like smallpox can only be grown in special conditions. Toxins can't be cultured."

While the three-tiered protocol was designed for seafaring ships, the same steps can be – and have been – taken to determine the presence of BW agents in buildings and other enclosed structures.

"BDRD used these three highly complementary approaches for detecting biowarfare agents to process more than 16,000 environmental samples collected from key points within Washington, D.C. during the anthrax outbreaks following September 11," Boehm said. Since then he and his colleagues also trained personnel from more than 30 Naval units to conduct confirmatory analyses.

The next step, Boehm said, is to develop a similar detection system for agriculture.

"The kind of system that we put in place for the Navy doesn't exist for training people to detect plant and animal pathogens," Boehm said.

• What do you view as your greatest challenge as the Director of the Chemical and Biological Technologies Directorate (DTRA-CB) and the Joint Science and Technology Office for Chemical & Biological Defense (JSTO)?

  • • A major challenge is to balance competing priorities in our Science and Technology (S&T) portfolio, which is as much art as science. It is important to maintain and enhance the right DoD core capabilities, yet it is also critical to build a future-looking program as we move forward. One of the most important “products” we produce is information and it is difficult to put a transition label on such an item. However, timely, accurate information is a very tangible commodity required by decision-makers in the event of any chem-bio situation. Technical knowledge in various aspects of chemical and biological agents is a critical aspect of the program and therefore our support of basic research is an important component of our overall program. Our investment in basic research also contributes to the recruiting and development of new scientific talent in the program. Staying ahead of various rapidly advancing technologies is a considerable challenge, yet fundamental to our ability to keep moving the program into the future. Recruiting and retaining new scientific talent into the program is one way to maintain our forward momentum in technology. Even as we balance the capabilities achieved by specific S&T products with the more global benefits of basic research, we must also be prepared to address unknown and/or emerging threats. As more technical capabilities become available to engineer biological agents, the threat to the warfighter increases. It is imperative that we stay ahead of that threat by developing capabilities that allow us to respond to and counter any unknown agent.

• Could you talk about the collaboration between your office and the other two elements of the CBDP triad, the Joint Program Executive Office (JPEO) for CB Defense and the Joint Requirements Office (JRO) for CBRN Defense? How do their priorities influence DTRACB portfolio management strategies?

  • • The JRO assists as an advocate for service and Combatant Commanders (COCOM) requirements within the overall Joint Staff process, and is responsible for the supporting analyses that establish the capabilities that we and the JPEO have to deliver. The JSTO and the JPEO work together as a technology pipeline that goes from the most basic science through applied and advanced research, all the way to final engineering development, test and evaluation, fielding, and total lifecycle sustainment. We both work to address the priority needs of the force, and within the mix of individual programs of record, MG Reeves, the JPEO, provides some further prioritization that helps the JSTO orient appropriately.

• The Chemical & Biological Defense Program (CBDP) provides funding through JSTO for nearly all of the efforts that are managed by DTRA-CB. Given this, how are you able to also support DTRA campaigns?

  • • The Agency’s Campaign 3 is about eliminating Weapons of Mass Destruction (WMD) as a threat, by rendering our military forces, equipment and facilities impervious or immune to the effects of WMD. The CBDP has a vision that is almost perfectly nested within the goals of Campaign 3, so that almost everything that we do in advancing the goals of the CBDP is consistent with advancing DTRA’s campaign. The agency gains tremendous leverage in this respect, but there are some aspects of Campaign 3 that are outside the domain of the CBDP.

• How do you reconcile the need to lean forward on newer projects like the Transformational Medical Technology Initiative (TMTI) with the need to support existing programs of record and fill current capability gaps?

  • • In addition to concerning ourselves with known threats, the types of agents traditionally associated with state offensive chemical or biological warfare programs, we also have to be concerned with emerging threats such as the potential for genetically modified biological agents. The Transformational Medical Technology Initiative will ultimately lead to the implementation of technologies to give the nation, the DoD, an integrated capability to respond quickly to the emergence or use of a never-before-seen pathogen, and develop treatments much more quickly than is now the case. The long range goal of TMTI is to provide an agile capability to respond to an unknown pathogen by providing both an advanced medical countermeasure development system and broad-spectrum medical therapeutic countermeasures. There is also important work to be done to enhance current capabilities, or to field new capabilities in the midterm, to provide our forces capabilities to protect against both known and potential threats.

• Many JSTO efforts focus on technology transition related to acquisition programs; sometimes, the product is simply knowledge that can be used to influence policy, doctrine or training. Do you see product-oriented and knowledge building efforts as having equal priority?

  • • The distribution of funding would suggest that transitioning technology is the primary focus. The knowledge base aspect, though, is quite important in helping us to gain a better understanding of what equipment capabilities ought to be, to enable decision-support tools, or to form the basis for further research directions.

• A number of other Federal entities are also addressing the threat of bioterrorism, chemical agent use, and toxic industrial chemicals to civilian targets. How do DTRA-CB projects benefit those efforts? What coordination takes place?

  • • I think that we have built very good relationships with the other federal agencies working in this area, most specifically the Department of Homeland Security and the Department of Health and Human Services. There are interactions at the political level, my level with my counterparts, and at the level of the actual technology managers. We often reciprocate with regard to participating in source selections, or reviews of portfolios. This helps us each to understand the needs and directions of the other, eliminate duplication, and, in fact, sometimes identify specific partnering opportunities.

• In the past, military technologies have also benefited civilian law enforcement and first responders. Are there efforts underway that you think could possibly benefit homeland defense and first responder communities?

  • • While most of our technology development is oriented to solve DoD requirements, you are correct to point out that there is a lot of potential overlap with areas of interest to the civilian sector. The outcome of our research programs frequently finds its way into applications in the civilian sector. Examples would include the detection technologies employed by the Department of Homeland Security and several vaccines (anthrax, plague, botulinum toxin) and therapeutics whose development has been supported through DoD programs. We also fund numerous projects in the academic and biotech sectors that contribute to the fundamental technical capability of the nation.

• What are your near-term and long-term goals?

  • • Near-term goals would include establishing more agile business practices with our performer base, including more efficient program management practices. To this end we have recently re-organized our structure in an effort to more efficiently cover a number of functions we feel are important to our overall mission. These include enhancing our ties with our international and interagency partners and establishing more effective partnerships with the DoD laboratories. This involves the implementation of our recently developed Strategic Plan which, among other goals, seeks to establish enduring capabilities within the DoD laboratories and other performers to provide S&T solutions for countering chem-bio threats. Among our goals is to enhance the recognition of DTRA as a leader (force) in the development of CB solutions and countermeasures. The development of CB countermeasures is truly a joint service venture involving many DoD institutions, as well as substantial federal and private sector involvement. As a joint agency, DTRA seeks to reflect and leverage the total scope of the effort across all these institutions and sectors.

On Tuesday evening, April 28, 2009, [Dr. Darrell Ray Galloway (born 1946)] was alone in his condo in Alexandria, Virginia, watching television and trying to unwind after work. His wife was in southern Utah, where they have a house, and where they hoped to retire soon. Galloway was a senior official at the Pentagon’s [Defense Threat Reduction Agency], and for days he had been going to meetings about a new strain of influenza from Mexico that was spreading fast. The strain, which combined genes from humans, swine, and birds, had become known as swine flu. Earlier that month, two children in Southern California had caught it. Then the virus swept through a high school in Queens; more than a hundred students with symptoms were sent home. The Obama Administration had declared a national public-health emergency. That night, Galloway watched news reports from Mexico City about overcrowded hospitals and closed schools; an estimated hundred and fifty people had died. He telephoned his eldest son and urged him not to make a planned trip to Mexico.

[Dr. Darrell Ray Galloway (born 1946)] is sixty-four years old. He is a short, athletic man with a welcoming but serious manner, like that of an amiable high-school baseball coach. The son of an intelligence officer, he was inspired to become a scientist by the launch of Sputnik and the space race that followed. In his spare time, he is an amateur astronomer, and he has built a small observatory in his back yard in Utah. He and a group of friends love to tinker with three old Soviet MIG fighter jets that they keep in a hangar nearby.

A former professor at Ohio State, Galloway is a microbiologist, and knew the grim history of influenza, a virus that often mutates faster than the body’s immune system can respond to it. The pandemic of 1918 infected a third of the world’s population and may have killed as many as fifty million people. In 2003, a strain of avian influenza emerged in Asia that was particularly lethal to humans, and the possibility that it could cause a human pandemic was a source of constant worry. But the virus did not spread between humans and remained confined largely to birds. Swine flu was a new, similarly threatening strain.

The [Defense Threat Reduction Agency] was created after the Cold War to protect the United States from weapons of mass destruction and to help other countries deal with the dangers of loose nuclear, chemical, and biological weapons. [Dr. Darrell Ray Galloway (born 1946)] was authorized by the military to work on a specific set of threatening diseases that were considered potential weapons in war or in terrorism, including anthrax, smallpox, tularemia, plague, and the Ebola and Marburg hemorrhagic fevers. Influenza, Galloway said, “was outside my lane.” But countering it would test the government’s ability to respond quickly to a biological threat. [NOTE - "when" was Galloway assigned to the DTRA? ..  According to Linkedin : 2001 - 2003 Deputy Director, Biodefense Research Directorate, Naval Medical Research Center, Rockville, MD /   2003-2007 DTRA ]  That night in April [of 2009], he resolved to do something about the looming pandemic.

The next morning, when [Dr. Darrell Ray Galloway (born 1946)] arrived at work, he summoned his staff and announced that they were to begin work immediately on creating a new antiviral drug to combat the swine flu. “I said, ‘What are we waiting for?’ ” Galloway recalled. “ ‘This is about as real as it is going to get.’ ”

A day later, at a meeting in the Pentagon, Galloway ran into stiff objections. Several officials said that it was a mistake for the military to get involved in the swine-flu outbreak. Galloway felt that the government was reacting too slowly to the spread of the pandemic. “I finally got fed up and blew my stack,” Galloway told me. “I said, ‘I didn’t come here to ask anybody’s permission to do this. I have done it.’ ” He got up and left, and the meeting broke up. Afterward, no one tried to stop him.

The Biological Weapons Convention of 1975 outlawed germ warfare. But in the nineteen-nineties two events unnerved the Pentagon. It was revealed that the Soviet Union had built a vast, illicit germ-warfare program, and that a Japanese cult, Aum Shinrikyo, had experimented with anthrax. The September 11th attacks increased the fear that terrorists could acquire dangerous pathogens; the anthrax letters in the weeks that followed raised the alarm. Former President George W. Bush, in his memoir, writes that, in October of 2001, while he was travelling in China, a White House pathogen detector went off, indicating the presence of deadly botulinum toxin. Vice-President Dick Cheney, his face pale, spoke with Bush in a video conference to inform him, saying, “The chances are we’ve all been exposed.” It turned out to be a false alarm, but, Bush writes, “at the time, the threats were urgent and real.”

Between 2001 and 2010, Congress approved fifty billion dollars to protect against biological threats. In addition, a special reserve fund of $5.6 billion, known as Project BioShield, was created in 2004 to help build a national stockpile. But after several years it became clear that money was not solving the problem. David Franz, the former commander of the United States Army Medical Research Institute of Infectious Diseases, told me, “We can’t afford it. We realize now how much it costs to make one vaccine for one pathogen. It is enormous, especially when you don’t know if you are ever going to need it.”

In 2006, the Pentagon ordered an unusual five-year research initiative to counter germs being used as weapons of war or terror, and assigned [Dr. Darrell Ray Galloway (born 1946)] to launch it. Instead of targeting pathogens one by one, an approach known as “one bug, one drug,” the initiative would seek to invent therapeutic drugs and vaccines that could counter multiple germs. They would also develop new processes that could be used to quickly create drugs and vaccines to fight previously unknown pathogens. Galloway and another official called it the Transformational Medical Technologies Initiative.

T.M.T.I. set extraordinary expectations for itself. An official description said that it would “spark another medical revolution,” similar to the mass production of penicillin in the Second World War, and declared that it might create new drugs and vaccines “within days.” As Galloway envisaged it, T.M.T.I. would start with basic research and go as far as possible toward developing a new drug or vaccine. No other single government agency was trying to do anything quite so ambitious.

[Dr. Darrell Ray Galloway (born 1946)] faced huge obstacles. The Defense Threat Reduction Agency had plenty of nuclear experts on its staff, but there were few people there with experience in microbiology or biotechnology. Critics argued that the program had overstated its capabilities. [Dr. Michael Thomas Osterholm (born 1953)], the director of the Center for Infectious Disease Research and Policy at the University of Minnesota, told me that T.M.T.I.’s plans to create drugs rapidly were the result of “wishful thinking,” and were “like trying a moon shot in ten minutes.” Bringing a new commercial drug or vaccine from laboratory to market in the United States can take ten to fifteen years and cost more than a billion dollars. The process of winning Food and Drug Administration approval, as the Pentagon has pledged to do with any drug or vaccine given to troops, involves preclinical testing in laboratory animals and three phases of clinical trials with human volunteers.

Nonetheless, Galloway pressed ahead. According to Patrick J. Scannon, the founder of a biotech firm called XOMA, who was an adviser to the military on biological issues during the Clinton and George W. Bush Administrations, “The Defense Department was creating a drug company.”

While [Dr. Darrell Ray Galloway (born 1946)] was setting up the program, concern about biological war and terror waned slightly. No weapons of mass destruction were found in Iraq, and although Al Qaeda had attempted to work with anthrax before September 11th, it had not got very far. There hadn’t been a terrorist attack using biological agents. But there were numerous dangerous outbreaks of naturally occurring infectious diseases around the world. Between late 2002 and mid-2003, a virus that causes severe acute respiratory syndrome, or sars, spread from southern China to twenty-eight countries and killed nearly eight hundred people. Then came avian influenza and swine flu, also known as 2009 H1N1.

There are two medical ways to deal with influenza: vaccines, which are given to healthy people before they are infected; and antiviral drugs, which can suppress the virus after infection, and give the body’s immune system time to regroup and recover. Galloway focussed on drugs because the existing antivirals had a limited impact. Tamiflu, one of the leading products, can shorten the duration of flu by only a day or two, and the swine-flu strain was already resistant to two other antivirals, developed in earlier years. It was possible that it would become resistant to Tamiflu as well.

[Dr. Darrell Ray Galloway (born 1946)] had assembled a technical staff for the T.M.T.I. program, and he had an early success with a drug to fight the Ebola and Marburg viruses. He saw swine flu as an opportunity to do more. “I wanted to prove that the program worked,” he told me. He also wanted to accomplish something tangible, if not strictly about war or terrorism. “How would it look if the government had a way to do this and we just sat on our hands?” he said. “If my job is to build a capability to respond to any unknown virus, how about this one?”

Another small team of scientists and medical experts within the Defense Department shared this sense of urgency. They had been trying for several years to modernize the way vaccines are made, and, during the pandemic, they decided to try to build a swine-flu vaccine using an entirely new method. Galloway was focussed on treatment; this group pursued prevention, under a program they called Blue Angel.

Vaccines are potentially the most powerful tool for preventing widespread illness and death from a virus. But they can be very difficult to create. Since the nineteen-fifties, there has been one F.D.A.-approved way to manufacture flu vaccines: inserting weak forms of the virus into chicken eggs. The egg-based vaccine depends on six discrete steps, and takes at least six months, or longer, to produce. The Centers for Disease Control and Prevention started preparations for a new vaccine in April, right after swine flu entered the United States. But a second wave of influenza would likely begin in four months, at the end of the summer.

The White House was concerned that the vaccine wouldn’t be ready in time for a pandemic. President Obama had just taken office, and aides worried about the prospect of a public-health disaster in his first year. Was there an alternative way to get a vaccine? The White House Homeland Security Council and the Office of Science and Technology Policy [ where  Rachel Elizabeth Levinson (born 1952) worked until 2005 ... the wife of Dr. Kincaid ] sent out a series of e-mail queries to government scientists in late April. One of them went to [Dr. Michael Vincent Callahan (born 1962)], a physician specializing in infectious diseases and rapid response who works at Massachusetts General Hospital and at the Defense Advanced Research Projects Agency, or darpa.

[Dr. Michael Vincent Callahan (born 1962)], who is forty-eight years old, thrives on practicing medicine under austere conditions in forbidding places. In earlier years, he served as an expedition doctor: climbing mountains and slogging through jungles with teams of explorers. One of his current projects is to help acclimate U.S. soldiers to the mountains of Afghanistan. “My thing is altitude and disasters,” he told me. When we met, he had just finished a night of hospital duty and was running on three hours of sleep. He repeatedly jabbed the button on a coffee machine, gulped down three cups of espresso, and chewed on candy-size tabs of an experimental nutraceutical that is supposed to bolster the immune system.

President Eisenhower established darpa in 1958, to undertake high-risk research in an attempt to find solutions to real problems. [Dr. Michael Vincent Callahan (born 1962)] and others at the agency quickly pulled together Blue Angel from a sheaf of futuristic programs they had been developing. Among them was PHD, an advanced blood test that could detect who would or would not become sick, days before symptoms arrived. Another, known as mimic, could model the human immune response in a test tube, creating a swift way to check the efficacy of vaccines. A third was save, a relatively inexpensive ventilator designed for the battlefield, which was the size of two large paperbacks and could be widely used by civilians in places such as school gyms if hospitals were overcrowded.

But the centerpiece of the program was an effort to modernize and speed up the production of vaccines. Instead of using chicken eggs, Callahan wanted to insert genetic code into specially grown tobacco plants. The code would cause the plants to generate viral proteins, and these could then be made into the active component of a vaccine. Tobacco is fast-growing and easy to manipulate genetically; in theory, once you have inserted the genetic code of the virus, the plants can quickly make pure and safe proteins in huge quantities. No one had yet made a vaccine for the public this way, nor had there been human clinical trials to determine if the vaccine could induce immunity in large numbers of people. But the Obama Administration was looking at all possibilities.

The White House contacted Callahan on April 28th. According to his records, officials requested a timeline with worst-case, medium, and optimistic projections for using the tobacco-plant method to manufacture hundreds of millions of doses of vaccine. Just then, Callahan was planning a “live-fire exercise,” an experiment in which he would use tobacco plants to try to make the active components of an avian-flu vaccine. He quickly substituted swine flu. The experiment was to be carried out by the Center for Molecular Biotechnology, in Newark, Delaware, a nonprofit branch of Fraunhofer U.S.A., a subsidiary of the large German applied-research and technology organization. Callahan sent a fragment of the swine-flu genetic code by e-mail to the executive director of the center. The center, using the tobacco plants, produced a purified protein in twenty-one days. This wasn’t a finished vaccine, but it suggested that the process of making one could be rapidly accelerated.

By contrast, it proved hard to grow the weakened strain of swine flu that could be placed in eggs. When it was finally shipped to the manufacturers, they found that the growth in the eggs wasn’t optimal for large-scale production. The manufacturers tweaked the strain, but not until the end of June were they ready to begin mass production.

On June 11th, the World Health Organization raised the alert level to six, meaning that a full-blown global pandemic had begun.

[Dr. Darrell Ray Galloway (born 1946)] kept an eye on Callahan’s work, but he stayed focussed on building a drug, not a vaccine. The first step was to acquire a full genetic blueprint of the swine-flu virus, and, to do this, he turned to [Dr. Walter Ian Lipkin (born 1952)], one of the leading detectives in the viral and bacterial world. A professor at Columbia University and the director of the Center for Infection and Immunity at the Mailman School of Public Health, Lipkin scrutinizes hundreds of pathogens every week, sifting the genetic codes for clues to their origins, behavior, structure, and identity.

Viruses are barely life forms. They infect a cell, hijack its machinery to replicate themselves, and then escape to infect new cells. The genes of the influenza virus are carried in RNA, or ribonucleic acid. Unlike many other viruses and organisms, the influenza virus does not correct genetic errors when it replicates, so it produces offspring that are not identical. The slightly different versions of the viral genome collectively resemble a swarm. To sequence the virus’s genes, Lipkin needed to scan as many versions as possible. Then he lined up the data to create a “consensus” snapshot of the swarm.

On April 30th, Lipkin and his staff acquired a specimen of the virus taken from the school outbreak in Queens. On May 1st, they began to sequence it. Every hour or so, they telephoned or e-mailed a progress report to [Dr. Paula Marie (Morgan) Imbro (born 1962)], a geneticist at the Tauri Group, in Alexandria, Virginia, who had been providing advice to Galloway’s T.M.T.I. program for more than a year. Lipkin’s staff sent [Dr. Paula Marie (Morgan) Imbro (born 1962)] the swine-flu sequence when it was finished. It looked like a piece of fine embroidery—tiny dots of green, blue, yellow, red, and purple. Lipkin had sequenced the virus in thirty-one hours.

[Dr. Darrell Ray Galloway (born 1946)] had solved the first major problem in developing his drug. To deal with the next, he chose [Dr. Patrick Lynn Iversen (born 1955)], a scientist at AVI BioPharma, a small biotech company in Corvallis, Oregon. They had worked together on the Ebola and Marburg viruses. On May 3rd, the swine-flu sequence arrived in Iversen’s e-mail in-box. The son of a national-park ranger, he is a hefty man, fifty-five years old, with a handlebar mustache and a gentle voice. He earned a Ph.D. in pharmacology at the University of Utah, and later became an assistant professor at the University of Nebraska. From his early days in science, Iversen was fascinated by the possibility that a chemical substance could target a precise location in genetic material, such as that of a virus or a tumor, and change its behavior.

Dr. Patrick Lynn Iversen (born 1955)]’s main research involved a technology known as “antisense,” which was first discovered in the nineteen-eighties. The process involved chemically synthesizing a short strand of DNA or RNA that could precisely interlock with a sequence found in a natural virus, like one Lego block attached to another. The natural strand was known as the sense strand, and the synthetic one as the “antisense” strand. If the antisense strand could attach tightly enough and in the right place, it would become a wrench in the gears of the genetic machinery, and stop the virus from replicating. The strand, in theory, could thus be turned into a powerful antiviral drug.

In the nineteen-eighties and nineties, Dr. Patrick Lynn Iversen (born 1955)] wrestled with the forbidding obstacles in antisense technology. One of the most difficult was to deliver the antisense strand to the right place at the right moment, after the virus had penetrated the cell, but before it had replicated and escaped to infect other cells. To accomplish this, the synthetic strand must be non-toxic, and it must not interfere with other genetic processes in the body. It must be potent enough to be effective and strong enough to resist rapid degradation. It must bind tightly to the invading virus. Each step in the process is complicated. Some of the early hopes for antisense technology were later dashed, and one scientific paper in the late nineties declared, “The technology remains in its infancy.” According to Cy Stein, of the Albert Einstein-Montefiore Cancer Center, in the Bronx, who also began working with antisense in the eighties, “The concept is the best idea since the hole in the toilet seat. But, in making this happen, there is one barrier after another that nature puts up to prevent you from doing what you want to do.”

In 1997, [Dr. Patrick Lynn Iversen (born 1955)] left Nebraska and joined AVI BioPharma, which had pioneered antisense chemistry. In his first years there, he tried to figure out how to use antisense to combat major diseases such as aids and cancer. But after September 11, 2001, he became preoccupied with viruses and terrorism. He had been planning to fly to New Jersey that day, but his flight was cancelled and the drive home from the airport took three hours. Along the way, he thought about the potential use of viruses: “I just thought, you know, flying a plane into a building—for a sort of low cost, you create a very high-cost event. If I were a terrorist, I would do a virus. This came to me as I was driving home, thinking, Things are a lot scarier if you could take a dog with some zoonotic virus and let him go in some neighborhood and the next thing you know people are tying up the whole medical system.”

[Dr. Patrick Lynn Iversen (born 1955)]’s new focus soon led him to obtain a patent on using antisense to target four major virus families. In some virus families, certain parts of genetic code appear the same across several species. These locations are known as “highly conserved regions,” meaning that they do not change from one strain of influenza virus to another. If he could target them, he thought, antisense technology could knock out different strains.

In 2002, the West Nile virus infected two dozen Humboldt penguins at the Milwaukee County Zoo, killing eleven. [Dr. Patrick Lynn Iversen (born 1955)] called Roberta Wallace, the senior staff veterinarian at the zoo, offering to synthesize an antisense compound against West Nile virus if she would give it to the remaining sick penguins. When Wallace agreed, he took the sequence of the virus from a database, designed the compound, and sent it to her in a vial. She injected it into three sick penguins. The birds survived the infection.

The success of the injection provided only anecdotal evidence that antisense could work, and Iversen was eager to find a more difficult challenge. On February 11, 2004, he made a presentation to the U.S. Army Medical Research Institute of Infectious Diseases, at Fort Detrick, Maryland, the Army’s premier laboratory for biodefense research. Hours later, a researcher at Fort Detrick accidentally stuck herself in the thumb with a needle while injecting mice with the Ebola virus. Ebola has gruesome symptoms that often cause the victim to bleed to death; there is no licensed vaccine or therapeutic drug to stop it.

While the terrified researcher was put in isolation, in a complex known as the Slammer, two cinder-block patient rooms that were hermetically sealed and filled with monitoring equipment, laboratory officials called [Dr. Patrick Lynn Iversen (born 1955)]. They wanted to know how rapidly he could synthesize an antisense compound against the Ebola virus. He quickly designed compounds based on the genetic sequence. Chemists worked for two days to synthesize it. In a telephone conference call, the F.D.A. gave emergency approval for use of the untested drug. The president of AVI BioPharma flew to the East Coast, carrying the vial. In the end, the researcher did not come down with Ebola, and she did not need Iversen’s drug. But the rapid response persuaded everyone involved, including Iversen and the Army laboratory, to launch a major new research effort into antisense and viruses.

One of the most enthusiastic participants was the researcher who had had the accident. She joined Iversen, and others in the lab, to create, test, and modify antisense compounds to counter viruses, including Ebola and Marburg. The first generation wasn’t potent enough; the second generation had problems with toxicity. With the third generation, the scientists had something to boast about. In 2006, they published the results of a trial in which seventy-five per cent of the monkeys given an antisense compound survived infection with the Ebola virus.

[Dr. Darrell Ray Galloway (born 1946)]'s programs had funded some of the Ebola and Marburg research, just as T.M.T.I. was getting started. He told me he knew that the antisense technology was working against those exotic viruses, and he felt confident that it would work against others. In the first hour after he launched the swine-flu effort, Galloway instructed his staff to call [Dr. Patrick Lynn Iversen (born 1955)] and invite him to join them. Iversen immediately agreed. On May 5th, the T.M.T.I. program, on Galloway’s orders, rushed a $4.1-million contract to AVI BioPharma. This kind of speed is almost unheard of in defense contracting. An accompanying memo from T.M.T.I. said it was possible that the experimental drug could be designed and found effective “in four to six weeks.” After that, “millions of doses” could be produced in time for the fall wave of swine flu. The memo warned that a pandemic could cripple military deployments, but it said nothing about the time required for testing by the F.D.A.

“This is where I get most of my negative thinking done.”

[Dr. Patrick Lynn Iversen (born 1955)] puzzled over the genetic sequence in the first days after he received it. He could not find the precise site he needed in order to attach the antisense compound. Lipkin had produced a richly detailed genetic blueprint, but the highly conserved region that Iversen needed was cloudy, as if covered with translucent tape.

Within days, [Dr. Paula Marie (Morgan) Imbro (born 1962)], the geneticist, had helped [Dr. Patrick Lynn Iversen (born 1955)] find a trove of swine-flu genetic sequences in a European database. They worked together on the phone—Iversen in Oregon and Imbro in Virginia—scrutinizing more than a thousand sequences each. Finally, Iversen recognized the precise place where he could attach his compound.

With the chemists, he attempted to create a synthetic compound that would latch on to the viral RNA in the right place, and stay there. On May 14th, he phoned the T.M.T.I. program: he and the chemists had succeeded. Afterward, [Dr. Patrick Lynn Iversen (born 1955)] held the substance in a small glass vial. It was fluffy and white. On closer examination, you could see that it was made up of spindly rods that seemed clean and pure.

[Dr. Randall Lawrence Kincaid (born 1951)], a biologist and entrepreneur who that week had become the scientific director of T.M.T.I., described Iversen’s work: “He distilled the background of influenza, the intricacies of the virus itself, and the types and strategies that would likely work or not work. I thought, Man, this is a guy who either has thought about this for a long time or is incredibly smart and in a few days came up with this. Either way, it is great.”

Engineering the compound did not mean that [Dr. Patrick Lynn Iversen (born 1955)] and [Dr. Darrell Ray Galloway (born 1946)] had found a workable drug. The next step was to test the substance in laboratory animals, starting with mice and moving on to ferrets, which are extremely susceptible to influenza infection and develop some of the symptoms seen in humans. After the blistering pace of events in May, the animal tests were delayed, week after week. There weren’t enough ferrets, and reams of paperwork were needed to obtain permissions from special committees, which sometimes meet only once a month.

In July, the influenza project faced a worrisome new crisis. In Argentina, the mortality rate among patients with swine flu began to soar. It was nine times as high as elsewhere. If the virus had mutated into a much more dangerous strain, it would make the egg-based vaccine useless, and it could also force [Dr. Patrick Lynn Iversen (born 1955)] to start over. Most people who had come down with swine flu in the spring had survived; a mutation could mean that the death rate would be much higher when the virus returned in full force in the fall. Several specimens from Argentina were rushed to Lipkin’s laboratory, at Columbia University, and the first analysis was carried out over the July 4th weekend. The researchers, entering the lab for dangerous pathogens, donned heavy protective suits. It turned out, however, that people in Argentina were being infected not only by the swine-flu virus but, at the same time, by streptococcus, a bacteria.

In August, [Dr. Patrick Lynn Iversen (born 1955)] got the laboratory-mice tests under way, but the first weeks were frustrating. The mice were set out in groups of ten and infected with a strain of influenza. Then one group was given the antisense compound, a second group Tamiflu, and a third a saline solution. Some mice in the early tests died unexpectedly because they were being given too much of the compound too fast. In the fourth round of tests, the scientists made the compound more concentrated but the doses less frequent, and the results looked promising. The treated animals had lower concentrations of virus and did not lose weight, as the animals usually do when they’re sick. “By the time we had finished with the mice, there was a high degree of optimism,” Kincaid told me.

Subsequent tests, in September, showed that infected ferrets that got Iversen’s compound had dramatically lower levels of swine flu than those who didn’t get it. The antisense compound also outperformed Tamiflu. “You know, ferrets sneeze, ferrets’ eyes get all runny, their noses get stuffy—they look like they’ve got the flu!” Iversen told me. “The first ferrets we treated were perfect. We had no sneezing, no runny nose, no stuff in the eyes, activity scores were perfect, and the sick guys were sick. So, you know, pretty cool.”

In Washington, on September 28th, [Dr. Randall Lawrence Kincaid (born 1951)] appeared before more than thirty government officials involved in the swine-flu crisis, from both civilian and military agencies. At this point, the second wave of the pandemic had arrived, but the conventional egg-based vaccine was still weeks away from delivery, and the Blue Angel tobacco-plant-based vaccine remained untested. A White House report warned that the pandemic could place “enormous stress” on the public-health system and cause between thirty and ninety thousand deaths in the United States in the coming months.

In a windowless Pentagon conference room, Kincaid spoke extemporaneously. He acknowledged that [Dr. Darrell Ray Galloway (born 1946)] and T.M.T.I. didn’t have a formal mandate to create a new antiviral drug, but “we saw an opportunity to see whether or not we could.” He described the good news from the four rounds of tests on mice. The exercise had shown “the potential for this capability to respond rapidly to an emerging threat,” Kincaid said, according to his notes. But he was taken aback at the first question: Can you make fifty million doses?

Kincaid insisted that it was just an exercise; the group was not ready to make fifty million doses. The officials pressed him about the remaining obstacles, and he told them that there were two main problems: how to give the drug to a large population, and how to get it approved by the F.D.A., which the group had not even consulted during the exercise. “People were energized,” Kincaid said. They saw the spindly white compound in [Dr. Patrick Lynn Iversen (born 1955)]’s vial as a real response to a deepening crisis.

The questions didn’t stop there. “We pushed it very hard,” said [Andrew Charles Weber (born 1960)], the assistant to the Secretary of Defense for Nuclear and Chemical and Biological Defense Programs. Weber, who took office in May of 2009, told me that, if needed, the new drug and the new vaccine would have been taken immediately into human clinical trials. “We realized in dealing with this declared national emergency that we needed a Plan B and a Plan C,” he said.

In the year after the pandemic began, swine flu infected between fifteen and thirty per cent of the population of the United States. But it was not as lethal as many officials had feared it would be. As a result, neither Galloway nor Callahan got the call to start mass production, and it is not known whether the antisense drug or the vaccine from tobacco plants would have proved safe and effective. Although the early results were promising, laboratory-animal studies often fail to predict how humans will react.

The work of both [Dr. Darrell Ray Galloway (born 1946)] and Callahan, however, resonated strongly in a debate about American preparedness that followed the pandemic. In January, 2010, President Obama, in his State of the Union address, promised “a new initiative that will give us the capacity to respond faster and more effectively to bioterrorism or an infectious disease.” For the next six months, officials met frequently to devise a strategy. The Department of Health and Human Services led the work, but the Defense Department was closely involved. When a new strategy was unveiled, in August, it called for many of the innovations and goals that Galloway had set for T.M.T.I. It also called on the government to support influenza vaccines that do not depend on chicken eggs. The Defense Department decided to make the T.M.T.I. a permanent program, with an annual budget of more than two hundred and fifty million dollars, and the Pentagon issued a formal order that emerging infectious diseases are a proper target for military research.

[Dr. Randall Lawrence Kincaid (born 1951)], the scientific director of T.M.T.I., told me that a major lesson was that a rapid response to a biological emergency must be accompanied by an equally rapid process for testing and approval. “There is no sense having brilliant, rapid science without it,” he said. The F.D.A.’s existing system of approval for new drugs, one of the most rigorous in the world, does not move quickly. Emergency fast-track procedures exist, but they are cumbersome. In the case of the most dangerous agents, such as Ebola, it is neither feasible nor ethical to run clinical trials on humans. Licensing for drugs and vaccines against these deadly agents must be based on testing in laboratory animals, despite the limitations of such work. If the country were engulfed by a deadly pandemic or bioterrorism attack, there would be questions of what risks to take, and whether people would be better off with or without a new drug or vaccine that had not been tested in humans.

The Obama Administration’s strategy calls for improving “regulatory science,” which means finding new methods and tools that can help the F.D.A. reach judgments more quickly. One idea is to look for indicators, known as biomarkers—such as protein levels in blood—that can allow you to make an early diagnosis or accurately predict a drug or vaccine’s effectiveness. Another proposal is to create F.D.A. “action teams” of experts and have them start working early with scientists who are developing a high-priority drug or vaccine.

At the end of 2009, [Dr. Darrell Ray Galloway (born 1946)] retired from the Defense Threat Reduction Agency, moved to Utah, and set up a small biodefense consulting company. [In December of 2010], AVI BioPharma submitted a formal request to the F.D.A. for approval to begin clinical trials of the antiviral. Meanwhile, there still is not a highly effective antiviral drug for dealing with swine flu. Over the past few months, a new wave of swine flu has hit Britain, sending more than seven hundred people to hospitals. Britain released 12.7 million doses of the pandemic vaccine for immediate use. Wide usage of the vaccine will stop the disease from spreading, but it isn’t going to do much for the people who are already sick. Their instructions are to stay hydrated and warm, and not to go to school or work. A similar outbreak occurred this winter in Cairo.

These outbreaks will probably be contained soon. But no one knows when the next deadly pathogen will show up and whether we’ll be able to respond rapidly to it. Patrick Scannon told me that [Dr. Darrell Ray Galloway (born 1946)] was right to act when he did. “Where could you hide if the flu turned rogue, and was Tamiflu-resistant?” he said. “The only thing left is to grab masking tape and a bottle of water, and lock the door. What is the responsible federal official going to do? Say, ‘Let’s not rush into this?’ What if you were wrong?”

In the event of another crisis, Galloway’s gamble may have pointed the way toward a rapid response. “What has been missing is an example,” Scannon said. “This was the first.” ♦