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Authors: Paul McKellips

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When the first recipe failed, as evidenced by the fact the monkeys were still alive, Raines had to go back to the computer modeling and revise her assumptions.

She manipulated the genes in the tularemia and created a bio-hazard that had to be restrained within the cement walls of the BSL-4 facility. With formula in hand she produced the new strain in glass. The aerosolized delivery produced inhalation tularemia without breaking the strength of the bacteria. The pre-clinical animal trial was successful. All four rhesus monkeys were infected and symptomatic within three to five days, and dead with complications from pneumonia within a week. The vaccine did not preserve their immunity. The monkeys were not immune from the tularemia.

Raines then had to produce a new vaccine, one that would keep the next group of monkeys alive.

It took great skill for Raines to successfully produce a lethal strain of tularemia, but creating the new super vaccine would require innovation normally reserved for Nobel winners. Evolving and translating the procedures Raines was developing in her basic BSL-4 research laboratory into a process that could be scaled up in a manufacturing environment to make millions of doses would require as much luck as it would skill.

Success would require a scientist with dedication and a willingness to be patient. There would be failure and disappointment. No one was more patient or dedicated than Lieutenant Colonel Leslie Raines.

When the first four monkeys were rolled into her BSL-4, she knew they were in a death chamber. Raines went above and beyond the enrichment requirements that her staff gave the four rhesus monkeys and made sure they had extra treats to eat and toys to play with while they waited for a lethal dose of tularemia. If millions of people and animals were going to live, she knew that four monkeys had to die first.

When Raines got the great news that the rhesus monkeys had died, she suited up and went into the BSL-4 and quietly thanked the non-human primates and stroked their fur from the openings in the cages. Raines was an animal lover at heart, but her mind was full of science.

Sixteen more dead monkeys cut her to her soul. She hadn’t found the right vaccine formula yet. She hadn’t found the correct immune response mechanism. She killed those monkeys, and she felt horrible, personally responsible.

Losing the animals she was desperately trying to save gnawed at her relentlessly. She worked many nights until 0400 hours, slept on the couch and got back into the lab by 0600. She was moody, short and irritable. Nothing else mattered. She couldn’t even comprehend a tularemia bio-weapon killing millions of people.

She had to save the next four rhesus monkeys.

Maybe it’s the adjuvants
, she reasoned.

A small-molecule drug had a molecular weight of less than 1,000, whereas the virus-like particle Raines was using as the basis of her new vaccine was more than 10,000-fold greater in size. The dosage amount would be based on both weight and biological potency.

In the four failed vaccine tests that caused 16 dead rhesus monkeys, Raines took scrupulous notes. Every procedure, piece of equipment and data discovered was documented. Raines knew each process had to be described and characterized in great detail, including the nature and performance of the specific equipment used for every step of the process. The requirements created an essential rigidity to her approach which was necessarily unforgiving of an error in judgment. Any misstep along the way could result in a very time-consuming and expensive correction in the manufacturing process as soon as the vaccine product candidate left the Fort Detrick BSL-4 and landed in France at LyonBio.

In normal vaccine development, Raines and her team might have required five-to-nine years in repetitive pre-clinical trials. The FDA would demand the studies prior to moving the vaccine for rapid evaluation in human clinical trials.

But developing a vaccine for a bio-weapon was different than a vaccine intended for universal pediatric use. A bioterrorism threat was an emergency situation and testing for efficacy was not always as practical, and not always possible.

LyonBio was equipped to be the pilot plant for the Phase 1 human clinical trials that might not ever happen. Bulk preparation of the Phase 3 final vaccine for full-scale manufacturing was the most likely scenario.

But if Raines couldn’t save four rhesus monkeys, none of it would matter anyway.

Qazvin University of Medical Sciences

Ghods Hospital

Markazi Province, Iran

G
hods Hospital, built in 1991, was a fairly small, but modern regional hospital. Iranian doctors were well-trained, and the equipment in the hospitals was quite modern. Even though the Islamic Republic of Iran was estranged and isolated from the west, the universities, hospitals and businesses were anything but third world.

Markazi Province was Kazi’s favorite province in Iran. It was also his family name. Literally translated, Markazi meant central, as in the central province of Iran. With Azak as the capital city of the province, more than 1.3 million people called Markazi home.

Kazi fashioned himself as being middle of the road, in the center. He was born in Pakistan to Iranian immigrant parents, then raised in Iran by his ultra religious grandparents, and educated in the United States before his career took him to The Netherlands, Pakistan and back to Markazi Province in Iran.

Kazi’s parents were murdered in cold blood by Pakistani terrorists in 1981. They broke into the house in the middle of the night looking for food and money. He always assumed the thieves allowed him to live because he was only a 12-month old infant at the time. He couldn’t remember anything about his first year in Pakistan. He never heard his mother’s screams as the men slit her throat or the single gunshot that was fired into his father’s head.

His grandfather flew to Islamabad to collect him from the orphanage. Forty-eight hours after his parents were murdered he was living in Markazi Province with a grandfather he had never met.

Kazi’s grandfather was a highly educated man and worked as the Dean at the Arak University of Medical Sciences. AUMS did train some doctors, but their specialty was research, especially training doctors who were both clinicians and basic science researchers.

Kazi spent his formative years playing in his grandfather’s lab, mixing chemicals together and dissecting every dead animal he could get his hands on. Kazi was fascinated with the similarity and interconnectivity of organs, between both humans and animals.

Kazi’s grandfather, Qazvin, was also a religious zealot. He was a member of a secret and clandestine religious group which he co-founded with several others in 1953 called the Hojjatieh Society. They were an underground messianic sect which hoped to quicken the coming of the apocalypse in order to hasten the return of the Mahdi, the future redeemer of Islam who had been hidden through occultation since the 7th century.

Qazvin and the others wanted to bring back the Imam through violence rather than waiting piously for the Imam’s eventual return on his own schedule. But after the Iranian Revolution began, the Hojjatieh Society was banned and persecuted by Ayatollah Khomeini’s government. The Hojjatieh rejected both democratic and Islamic forms of government. They preferred to wait and be governed by the Islamic Messiah. Any form of government to the Hojjatieh was illegitimate or unnecessary at best. They were not interested in democratic reforms or totalitarian regimes. They wanted no government at all.

The Hojjatieh Society was important but unfulfilling to Kazi’s grandfather until he attended a mosque in Qom and heard an Imam who was a Twelver. By the end of that Friday’s holy day, Qazvin and his 14-year-old grandson Kazi were radical Twelvers. Kazi had centered every dream on the return of the Twelfth Imam, the Mahdi.

Kazi’s grandfather encouraged him to pursue college studies in the medical sciences. He applied to many universities in Europe and in the United States with his Pakistani passport and credentials. He was accepted to every university he applied to but one stood out: war eagle.

Kazi knew nothing about Auburn University, let alone the state of Alabama, but the name “war eagle” matched his own self image. He, too, was raised to be a war eagle and entered Auburn in the fall of 1998 as an 18 year old.

Kazi thrived for three full years and made hundreds of friends across the Auburn campus and throughout Alabama and neighboring Georgia. Everything changed for Kazi on September 11, 2001. In one swift instant he became a suspicious Middle Eastern man. The terrorist hijackers were Sunni. He was Shiite. Most of the 9/11 terrorists came from Saudi Arabia, but Kazi was from Pakistan and Iran. Eight months shy of graduating Auburn with a bachelors of science in microbiology with honors, Kazi was ostracized and discarded. He was as angry as a war eagle.

The job market in the United States for Middle Eastern men after 9/11 was very challenging. Kazi applied all over the world before finally getting a job at Brezden University Medical Center in The Netherlands where he worked as the microbiologist on a team that studied avian influenza. Though he was brilliant and perhaps one of the most gifted microbiologists in the world – thanks to his early years in Qazvin’s laboratory – Kazi couldn’t shake the anger.

His frequent trips back to Islamabad and Tehran allowed Kazi to meet people who were willing to pay for his significant expertise while he put his Brezden job in jeopardy by missing so many days of work. By the time he was terminated, Kazi was an international freelancer, a Shia Muslim Twelver with an angry past and a “war eagle” attitude.

In 2006, the executive branch of the Iranian government, as well as elements of the vaunted Revolutionary Guard, fell under heavy influence by a resurgent Hojjatieh Society. Kazi’s grandfather, Qazvin, became more valuable to the radical government the older and wiser he became. When the elderly Qazvin assumed an advisor’s role to the Iranian president, the university was named after him. By extension, Kazi became the nation’s “war eagle” who had the power to travel freely as an eagle among all nations.

Kazi and Qazvin looked through the charts of the 47 people from the Bourvari District of villages that had already been admitted to the 130 rooms of Ghods Hospital in Markazi. More than 400 other Persian-Armenians had filled the waiting rooms and were spread out in lines under tents and trees onto the hospital grounds and parking lot.

“Many of the children have ulcers, open sores on their hands, arms and faces,” Qazvin said as he reviewed the charts.

“They were infected by contact to the skin. Many of them played in the mist and followed the truck. The adults?” Kazi asked.

“Swollen glands in the throat, shortness of breath, cough, fever, and some with chest pain. We have one fatality, but probably from a heart attack,” Qazvin said.

Kazi stood up and paced back and forth in the administrator’s office while looking out through the glass walls at the Persian-Armenian patients who lined the corridors.

“Okay, grandfather…this is a very effective Phase One clinical trial. Let’s call in the BBC now and other Arabic media outlets. Start all of these patients on intravenous ciprofloxacin and then send them all home with a seven day supply of streptomycin. Make sure that you announce all of the precautions.”

“And you?” Qazvin asked his grandson.

“This exceeded my expectations. It proves we can produce an aerosol version without degrading the bacteria. I must head back to Damghan and make the corrections. Soon we will test the new strand in a Phase Two trial. God be with you, grandfather.”

Kazi kissed his grandfather and walked down the corridor, out the door past hundreds of panic-stricken and infected Persian-Armenians and their children – the same ones who had played innocently in the cool mist just three days before in the villages of Dehno, Khorzend, Farajabad, Bahmanabad and Sangesfid.

23

ISAF Headquarters

Kabul, Afghanistan

G
eneral Ferguson, US Navy Captain “Camp” Campbell and retired Special Agent Billy Finn were on a conference call with Lieutenant Colonel Leslie Raines back at Fort Detrick.

“Colonel, again my apologies for keeping you up so late,” General Ferguson said as he transitioned to her part of the call.

“No problem, sir, I’m getting ready to turn-off the lights and hit the couch right here in my office. All tucked in with the blanket my grandmother Lydia knitted for me,” Raines said as the energy in her voice started to fade. With fingers crossed and a voice less than hopeful, Raines announced that she had just launched her fifth preclinical test with the vaccine-resistant tularemia she had created. Each of the four new rhesus monkeys were injected with the fifth generation of the vaccine designed to trigger an immune response to the lethal inhalation tularemia Raines had developed. Within five days, they would all know if they had four more dead monkeys or if Raines had finally cracked the code.

Major Spann opened the door to Ferguson’s office unannounced and burst into the room. The general was immediately angry.

“Major!”

Spann was out of breath.

“Sir, BBC right now, tularemia outbreak in Iran.”

Spann fidgeted with the remote controls and finally got the TV on and tuned to the BBC as Raines kept the line open and listened from Maryland.

“Again, Iranian health authorities have announced a natural outbreak of tularemia. Tularemia is known by several societal names including rabbit fever, deer fly fever, Pahvant Valley plague, and Ohara’s fever. But today, more than 400 people living in the villages of Dehno, Khorzend, Farajabad, Bahmanabad and Sangesfid – mostly in the Markazi Province – call it torment. Authorities at Ghods Hospital are appealing for calm. This is not – I repeat – not a fatal condition if infected patients receive antibiotics immediately. Health officials are stressing that this is also a very preventable disease, and some vaccines may already exist. Tularemia bacterium is found in wild animals and can occur from undercooked meat and in infected drinking water supplies. The people in these villages should make sure their meats are thoroughly and sufficiently cooked and should boil their drinking water before consumption, at least until this outbreak is under control. Authorities stress that this is a sanitation issue, and no one should panic.

BOOK: Jericho 3
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