Long before September 11, 2001, we already had a licensed vaccine against anthrax to give to soldiers and lab workers before exposure. In 2000 the highest-ranking physician in the DoD wanted an additional way to vaccinate against anthrax after an attack on the battlefield, so this was a novel indication for the anthrax vaccine. It could only be done with an FDA-approved investigational new drug (IND) protocol and after documenting the informed consent of anyone who received the vaccine. This request rolled downhill to us at USAMRIID.
USAMRIID immediately put together a team led by one of our physicians who was an anthrax vaccine expert. After eighteen months and twenty-nine revisions, the protocol was ready to submit to the FDA for final approval in late 2001.
Then the anthrax letter attack struck.
This was no longer a paperwork exercise. In the heat of the anthrax crisis, the CDC, as the national public-health response authority, had no mechanism to vaccinate civilian victims after they had been exposed. Why not just give them antibiotics to prevent disease? That works for most people exposed, but unfortunately Queen Anthrax is sneaky. She hibernates inside lymph nodes in the chest, waiting for the chance to reemerge and strike weeks or months later, even in those previously treated with antibiotics.
We know about anthrax’s method of hiding from monkey studies. One of USAMRIID’s anthrax scientists exposed forty monkeys to anthrax spores and treated them afterward for thirty days with antibiotics. Monkeys survived while on treatment, but after the antibiotics were stopped, five monkeys still died of anthrax—even fifty-eight days after infection.1 Another study from the 1950s showed living spores hiding in the chest ninety-eight days out from infection. Something triggers the spores to awaken, germinate, grow, reproduce, secrete their toxins, cause disease, and kill. Antibiotics may delay things, but once they are stopped, Queen Anthrax exploits the vulnerable window to exact her toll. In 1979 after an accidental release of anthrax from a biological weapon plant in the Soviet town of Sverdlovsk, some people became sick even forty-two days later.
Like playing Russian roulette, the revolver chamber spins, but we can’t predict which unlucky victim will take the bullet. In USAMRIID’s monkey study, only monkeys that received vaccine plus antibiotics all survived anthrax after the antibiotics were stopped. So it makes sense to give the vaccine along with antibiotics after an attack to those at highest risk. This gives them a fighting chance to build up a second line of defense with their immune system to knock out the awakening Queen Anthrax.
Because USAMRIID had already carried the new anthrax vaccine protocol all the way to the FDA, in the heat of the anthrax letter crisis, it was simple for USAMRIID, whose purview covered primarily the military, to hand it off to the CDC as a “boilerplate” for quick adaptation for civilians. Within days the CDC had a revised protocol and approval to give the vaccine as an IND to those at risk.
But after the 9/11 attacks, anthrax was not the only perceived threat. The new senior physician in the DoD, Dr. William Winkenwerder Jr., handed us another “tasker”: develop protocols for the DoD’s other unique bioweapons vaccines and treatments to be ready for military forces at war. The request split the threat agents into two tiers, with Tier 1 as the highest priority. Tier 1 seemed reasonable to me, focusing on three top threats: anthrax, smallpox, and botulinum toxins, but some of the products were not licensed and would require us to develop FDA-approved protocols.2
As the anthrax vaccine protocol experience showed, drafting any single protocol requires significant time and effort. Personnel in my Medical Division had practical experience giving one-of-a-kind vaccines against those threat agents to protect lab workers across the country, so we started a working group and plunged in feet first, along with our regulatory and virology colleagues. We held our first meeting on September 22, 2001—only eleven days after the 9/11 attacks.
I wanted the protocols to be nimble, easy to administer, and simple for a soldier to comprehend. I hoped to streamline them to two-page consent forms, with twenty-page protocols. In the heat of a battle or a bioweapon attack, no one can afford to get bogged down in paperwork.
I should have known better. After all the required regulatory language was added and after multiple levels of review, these documents ballooned to fifteen-plus-page consent forms and eighty-plus-page protocols. The botulinum antitoxin protocol grew to the size of a phone book, over two hundred pages long! It took nine months to launch our first protocol to the FDA, despite the urgency after 9/11.
We were now well into 2002. As we neared completion of the Tier 1 protocols, the White House started posturing for war with Iraq, so we felt pressured to get cracking on the Tier 2 protocols, which included vaccines against second-line threat agents: Q fever, tularemia, and three encephalitis viruses.3
Whoever had put together the Tier 2 list of vaccines had just looked on a menu of products in our stockpile and picked them, but the person clearly had no understanding of the diseases or the products. Although the idea of protecting the forces against these diseases had merit, many of the products were not appropriate for giving to soldiers en route to the battlefield. None were licensed. All were INDs.
Q fever and tularemia were already treatable with antibiotics. The Q fever vaccine required a skin test before giving the vaccine, or soldiers risked severe local reactions, so you couldn’t just line people up and inject them all with the vaccine and forget about it. The tularemia vaccine was on temporary hold with the FDA awaiting new data from us. The VEE virus vaccine sidelined some people for a couple of days with fever, making them feel as if they had been run over by a truck. Around 5 percent felt as if they had the disease that the vaccine was supposed to prevent. The eastern and western equine encephalitis virus vaccines required multiple boosters. We really needed licensed vaccines, but none existed for the diseases in question.
This is nuts, I thought. I just couldn’t envision vaccinating hundreds or thousands of military forces with any of these IND vaccines as they lined up to board and later jump out of airplanes. All recipients would have to be educated about the vaccines and their side effects and voluntarily accept the risk of getting them. Our working group decided to push back against Tier 2.
By this time I felt comfortable in my role as Medical Division chief, and I wasn’t afraid to speak up. Our leaders at Fort Detrick listened.
So on April 17, 2002, I drove down to the Pentagon as the voice of the Contingency Protocol Working Group to bring our concerns to Dr. Winkenwerder and Dr. Anna Johnson-Winegar, the deputy assistant secretary of defense for chemical-biological defense.
I felt nervous. These were the highest-ranking DoD leaders I had ever briefed. All three military surgeons general reported to Dr. Winkenwerder, and Dr. Johnson-Winegar had significant power over USAMRIID. I would be representing USAMRIID on behalf of the USAMRIID commander and the commanding general at Fort Detrick, so I appreciated the confidence they had in me, and I didn’t want to let them down. The commanding general would also attend the briefing, which ratcheted up the pressure.
We sat around Dr. Winkenwerder’s conference table, with Dr. Winkenwerder at the head, Dr. Johnson-Winegar to his right, and me in the “briefing spot” to his left.
A colleague summarized the status of the Tier 1 protocols. I was up next.
We flipped through printed PowerPoint slides as I conveyed our concerns and the significant challenges of vaccinating large numbers of military personnel with the Tier 2 IND products. I felt pressured to rush, as I tried to explain the differences when working with investigational vaccines versus licensed ones, because Dr. Winkenwerder kept saying, “Got it,” to move me along. I was concerned he didn’t really get it, though.
At the end of the briefing, I emphasized that we still had the capability to vaccinate small military or special forces units, if needed, because we already had vaccine protocols ready for our lab workers or other “at risk” personnel.
When I finished talking, a hushed silence fell over the room as I waited for a response. Like a dog waiting to be kicked, I stared down at the last paper slide on the table, afraid to look up to read the feedback on the faces of others around me. I believed I had an equal chance of being applauded or thrown out of the room.
Dr. Johnson-Winegar broke the silence. “I agree,” she said.
I could have hugged her!
After some more discussion between her, Dr. Winkenwerder, and my commanding general, Dr. Winkenwerder agreed with my recommendations. The Tier 2 vaccine protocols were pulled off the table. I felt a one-hundred-pound weight lift off my shoulders.
As I gathered my papers, I felt triumphant. I had helped stop a useless exercise, and at the same time protected my personnel and still offered an option to protect the soldiers at highest risk.
A couple of days later, our commanding general sent a note to confirm that the protocols were indeed off the table.
My elation was short-lived, though. By this time, I had gotten used to getting hit with a new disaster right when things started to go well. It seemed to go with the job.
I just didn’t think it would come so soon . . . or from within.