Introduction

An award-winning investigative journalist's horrifying true crime story of America's deadliest drug contamination outbreak and the greed and deception that fueled it.

Two pharmacists sit in a Boston courtroom accused of murder. The weapon: the fungus Exserohilum rostratum. The death count: 100 and rising. Kill Shot is the story of their hubris and fraud, discovered by a team of medical detectives who raced against the clock to hunt the killers and the fungal meningitis they'd unleashed.

"Bloodthirsty" is how doctors described the fungal microbe that contaminated thousands of drug vials produced by the New England Compounding Center (NECC). Though NECC chief Barry Cadden called his company the "Ferrari of Compounders," it was a slapdash operation of unqualified staff, mold-ridden lab surfaces, and hastily made medications that were injected into approximately 14,000 people. Once inside some of its human hosts, the fungus traveled through the tough tissue around the spine and wormed upward to the "deep brain," our control center for balance, breath, and the vital motor functions of life.

Now, investigative journalist Jason Dearen turns a spotlight on this tragedy—the victims, the heroes, and the perpetrators—and the legal loopholes that allowed it to occur. Kill Shot forces a powerful but unchecked industry out of the shadows.

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Excerpt

October 2012

ALBANY, KENTUCKY

The gravedigger arrived just after sundown, the night already full of the trills of crickets and katydids. He headed to the top of the cemetery’s hill and pushed his shovel into the earth quietly, chunk- ing out the grass and weeds on top before hitting soil. He was careful not to attract the attention of the residents of the small homes adjoining the site or of those in cars traveling along North Cross Street, the town’s nearby thoroughfare.

The deceased was a judge, Eddie Lovelace, and his funeral a few weeks earlier had lasted hours, with what seemed like the en- tire 2,000-person town in attendance. State troopers, farmers in bibbed overalls and boots, even a man the judge had sent to jail twice came to pay their respects.

Two weeks before his death, the judge had still been presiding over criminal cases in the Colonial-style courthouse a few blocks from his house. The seventy-eight-year-old still walked three miles every morning—the same route down to the Talbott Funeral Home, then over to the Clinton County Hospital. Eleven days before his funeral he had collapsed after stepping off his porch to retrieve the Lexington Herald-Leader from the mailbox. He had staggered to his feet and made it back to his kitchen, paper in hand, calling to his wife, Joyce, and waking her up. She immediately noticed that his face looked different. “My legs just aren’t working,” he’d said. She hurried to call her daughter, Karen, a nurse who lived down the street.

The next day, as Lovelace lay in a hospital room at Vanderbilt University Medical Center, a neurologist confirmed that he’d had an atypical stroke, in an unusual part of the brain.

The judge died a week after arriving at Vanderbilt. The cause of death was listed as unknown, and he was buried a few blocks from his small house on Lovelace Street, which had been named in his honor.

Less than a month later, the gravedigger scooped out a couple of feet of dirt before his blade reached the top of Lovelace’s cement vault. The weight of the earth above it had already created a tight seal, but a few swings from a sledgehammer cracked the vault

open, interrupting the quiet.

The next morning, a hearse drove three hours north to Louisville, where the body was unloaded and taken into a low-slung mortuary building. The exhumed corpse was eased onto a stainless-steel table. The judge was still dressed in his robes, a gavel in his right hand. A key to the front door of his house was in his pocket, where he al- ways kept it.

The medical examiner cut open the remains and studied each major organ. Multiple areas of the judge’s brain showed evidence of hemorrhaging. As the pathologist reached the top of the spine, he noticed a growth covering the base of the brain stem—a micro- organism, a translucent jellylike mold.

This was unheard of: a deadly mold blooming in the central nervous system of an otherwise healthy person. The medical examiner scraped out a sample and placed it in a sterile container for the lab. After the judge’s swift death, his family and community had bur- ied him and started grieving. That was before they learned of the

U.S. government’s murder investigation. The expanding list of casualties. The injections. The source.

The judge had been buried before many others, but now his body and the microbe that had colonized his brain were evidence.

___

Two months earlier

SMYRNA, TENNESSEE

Thomas Rybinski stood on his boat and looked out over the sparkling lake, the humidity enveloping him like a soggy blanket. It was a Saturday in August 2012, and he and his wife, Collette, had met two other couples for a weekend boating trip. The weather was ideal: light winds, the water surface glassy. The engine hummed as Rybinski piloted the bass boat into their favorite cove, where they anchored and grilled dinner. It was the perfect antidote to a day that had started strangely.

Rybinski had been unsteady since breakfast. From dawn to dusk, the fifty-five-year-old father of three was usually a blur of action. But when he had swung his legs out of bed that morning, he could move only gingerly, and he felt chills and nausea. His head hurt, and as he drank his morning cup of coffee he rubbed his hand over his head to try and quiet the banging inside. He thought it was probably a sinus headache. Still, Captain Tom, as his friends referred to him, kept his boating date. Out on the water he’d started

to feel better, but the headache still bothered him; the next day they cut their trip short and went home.

On Monday, Rybinski felt well enough to work. For thirty-five years he’d been at General Motors, most recently as an auto de- signer. He was popular at GM and still youthful in middle age, although after long rides on his Harley his lower back flared up because of a bulging disk. Rybinski did not like to miss work—he loved cars, loved talking about them—and he got steroid injections that made the pain tolerable for months at a time.

By the end of the week Rybinski’s mind was foggy and he walked with a slump. He told Collette, “I feel like the inside of my head is going to explode.” Collette thought he might have the flu.

On August 26, about a week after the boating trip, he went to Vanderbilt University Medical Center, a dense collection of Lego-like buildings in the heart of Nashville. His symptoms were consistent with meningitis, an infection some physicians describe as a swollen cen- tral nervous system. It’s marked by inflammation of the meninges, the membranes that protect the spinal cord and brain stem. But Rybinski was not at high risk for meningitis. He had not been around a large group of people who could transfer bacteria, nor had he recently had surgery. His doctor looked elsewhere for an expla- nation. Rybinski had gone hiking in Colorado about a month ear- lier; perhaps a tick bite had introduced a pathogen? He was tested for Rocky Mountain spotted fever, a tick-borne bacterial disease with symptoms similar to meningitis. Such a diagnosis, while seri- ous, was also possibly good news: most serious bacterial infections can be treated with antibacterial drugs. Still, Rybinski’s doctors could not be sure until they tested his spinal fluid.

They checked him in to the hospital and gave him antibiotics and drugs to reduce the swelling. To everyone’s relief, Rybinski regained his sharpness. After five days, they installed a catheter in his arm so he could administer the medications to himself, and he went home.

A few days later the headaches were back. Since being discharged, Rybinski had had a couple of good days, when he seemed like his old self. But he was declining quickly, and Collette had seen enough. She called in to work, grabbed his medications, and drove them to the closest emergency room to avoid the heavily trafficked twenty- four-mile trip to Vanderbilt. By the time they arrived, he was speak- ing gibberish. The doctor ordered an ambulance to take him back to Vanderbilt. There, in intensive care, Rybinski moved in and out of consciousness. One of the times he came to, he could not re- member their wedding. It broke Collette’s heart.

Vanderbilt University Medical Center

Dr. April Pettit walked down the hushed, fluorescent-lit hallway in Vanderbilt’s critical care unit, the beeping of machines and the murmur of nurses greeting her as she started her shift. Just a year earlier, she had finished her fellowship and been hired by Vanderbilt as an attending physician. The thirty-four-year-old Pettit had a degree in public health and expertise in infectious disease. But she had little experience with cases of meningitis like the one in the patient she’d just inherited. She scanned his paperwork. Thomas Rybinski was a man in his fifties who had been healthy except for the back pain he felt when he rode his motorcycle. He was deteriorating quickly from meningitis of an unknown origin. To complicate matters, he could speak but was not making sense, so she had to rely on his medical records and his previous interviews with her colleagues for clues.

Pettit studied Rybinski’s medical history and charts. Her first task was to build a differential diagnosis, a list of possible causes of his meningitis and stroke, ranked from the most likely to the least. From there, she would move from the top of the list to the bottom, methodically ruling out potential causes one at a time. Bacterial meningitis was still the odds-on favorite, but he had not responded to antibiotics, and they had started him on an antifungal, too, just in case. There were other meningitis-causing microbes she needed to cross off the list, like viruses. So far all the labs were coming back negative, including a battery of tests of Rybinski’s spinal fluid. She was still waiting for the results of a fungal culture, even though fungal meningitis had almost never been diagnosed in previously healthy people like Rybinski. Fungi usually have no clear pathway to a human spinal column. In fact, the lab at Vanderbilt had not grown a fungus in a spinal fluid sample for nearly thirty years. But Rybinski was short on time. At the very least, a negative culture would allow Pettit to cross fungus off her differential diagnosis.

Across the street, inside a sterile room the size of a walk-in refrigerator, the lab tech had put three samples of Rybinski’s spinal fluid into separate vials. One held a sugary solution called Sabouraud agar, another used a form of mucus, and another was a crimson concoction of blood and brain matter. (The tech had performed these cultures for decades, but that last one still grossed her out.) Typically, if the fluid stays clear after a week or two, it’s considered free of microbes. But some fungi could take weeks to show up, and hospital officials decided to monitor the culture until the process had run its course. While this was sound medical practice, it was also a problem: Rybinski’s condition continued to worsen.

Six days after Rybinski was readmitted, his face was drooping on the right side, a sign of an intensifying stroke. A CT scan of his head revealed excess fluid around the brain. The doctors also found blocked oxygen-providing arteries in the back of his head.

In Rybinski’s scans, reproduced later in The New England Journal of Medicine, the ghostly image of his brain is clearly wrong: tidy folds of tissue are interrupted by what looks like an off-white cluster in the center. Even to a layperson, it is obvious that this mass should not be there. Notes attached to the scan identified the anomaly as a pool of blood that collected near where the brain and spine meet. Similarly, the arteries that fed his brain were weakened by aneurysms, which had burst and bled into surrounding areas. These were the obvious ravages of an invasive species adapting to an unfamiliar ecosystem: Rybinski’s central nervous system. There it had grown and multiplied, interrupting the flow of blood to his brain. This caused a stroke. What the images did not explain was exactly what was causing this or why. The next day, in a refrigerator behind a door marked biohazard, one of Rybinski’s cultures started changing. Where there had been clear spinal fluid, there was now a fuzzy mound of blue-green—the microbe up close. The technician was shocked. She needed to report the results immediately.

Unbeknownst to Pettit, another St. Thomas clinic patient had been admitted into Vanderbilt’s ICU, just down the hall from Rybinski: Judge Eddie Lovelace. Because the judge’s stroke so swiftly took away his ability to communicate, his doctors didn’t know about his headaches, nausea, or the other signs of meningitis. They had no reason to order a spinal tap or test for a microbial invader.

Day 1, September 18, 2012: One case

TENNESSEE DEPARTMENT OF HEALTH, NASHVILLE

Pettit’s email set off alarm bells in Dr. Marion Kainer’s head.

“We have a case of a 55yo immunocompetent man with Aspergillus fumigatus meningitis,” Pettit wrote, using the scientific name for the common fungal species identified by Vanderbilt’s lab. “He had been receiving lumbar epidural steroid injections at an outside facility which is the only explanation we can find to explain this. He also has an L4–L5 1cm epidural abscess which supports this theory. I wanted to inform you of this in case you feel that an investigation is warranted.”

Kainer, one of the state’s chief medical detectives, called Pettit immediately. “Tell me everything from the beginning,” she said. The Tennessee Department of Health operates within a net- work of state and federal agencies that employ epidemiologists like Kainer—doctors responsible for tracking and finding the cause of disease outbreaks. In the case of a sexually transmitted disease like HIV, public health officials study how it has been transmitted and to whom, and then find ways to reduce exposure and death. The stakes are always high when Kainer launches an investigation. Each day that passes without answers means illness can spread.

A native Australian who speaks with a caffeinated intensity, Kainer had studied brain science before she refocused on epidemiology, motivated by a devastating epidemic at a hospital in Melbourne that killed one of her patients. The cause was a drug-resistant infection plaguing hospitals worldwide called methicillin-resistant Staphylococcus aureus, or MRSA. An especially robust bacterium with a thick cell wall, MRSA can fend off the antibacterial agents used in cleaning products, making it hard to eradicate. As a clinician, Kainer knew how to research diseases and prescribe treatments. The loss of her patient to MRSA had rocked her confidence. When it came to investigating the cause of a disease—epidemiology—Australia in the early 1990s was far behind the United States.

She applied to the Epidemic Intelligence Service (EIS) at the U.S. Centers for Disease Control and Prevention (CDC) in Atlanta. The two-year program is a disease detective’s West Point. The agency plays a part in fighting everything from annual flu outbreaks to Ebola. Since finishing her training at the CDC, Kainer had made a name for herself as an aggressive investigator.

Now Tom Rybinski’s file was in front of her. It was only one person, not even a cluster of cases, but the disease was rare and unexplained. Three days later, Kainer got a call back from the clinic manager. There had been no construction and no mold problems at the St. Thomas clinic, either. But there was troubling news: two other patients had called in reporting dizziness, a stiff neck, and other meningitis-like symptoms.

The U.S. Centers for Disease Control and Prevention, Atlanta

Dr. Benjamin Park had already seen a lot in his decade at the CDC—patients blinded by fungal infections due to tainted contact lens solution, children dying from the flu, and dozens of nurses sickened during the global outbreak of the coronavirus SARS- CoV. Each case represented a vexing life-threatening puzzle, and Park had become a seasoned investigator.

A slender and boyish man who was just turning forty, he had the calm manner of someone who’d witnessed his share of death up close. His office overlooked the CDC’s campus, a labyrinthine collection of modern buildings with green-tinted windows, connected by underground tunnels. CDC scientists develop everything from

antidotes for chemical weapons like anthrax to experimental treatments for rare infections that appear without warning. This agency is the brain of the nation’s response to disease epidemics.

It was a quiet Thursday when Kainer’s email popped into his inbox. Tennessee was requesting help from the CDC, and Kainer wanted to know if they had heard of any fungal meningitis cases in the United States. Park had not, but a brain-altering fungus could be a serious public health concern. At the moment, Kainer had only one confirmed fungal meningitis patient, Rybinski, but a couple of others had cropped up at the same clinic. These new cases had arrived at St. Thomas Hospital— which was affiliated with the neurosurgical clinic—with signs of meningitis. Kainer already recognized that the situation warranted a more aggressive investigation, and Park agreed.

On the same day that Eddie Lovelace’s granddaughter sang at his funeral at Albany First Baptist, Kainer sent out a health alert in Tennessee for all clinics and hospitals to report any patients who had meningitis-like symptoms following an epidural injection. Since the alert went out, her phone had been ringing nonstop. Within hours, she’d received reports of four more possible cases from doctors in Nashville. Two of the cases had experienced stroke in the same part of the brain as Rybinski and had deteriorated quickly.

Confirming these new cases would be tricky. The patients were all having cerebrospinal fluid removed for a fungal culture, but the results could take weeks, and they did not have the luxury of time. If this was the same disease that Rybinski had, these patients could die in the weeks before a culture turned positive.

This was an ominous sign. If the number of cases spiked quickly, a time lag in diagnoses would be a problem for doctors in Tennessee who wanted to start to preventatively prescribe antifungal medications before a positive lab result.

While Rybinski had tested positive for a fungus, none of the handful of other spinal fluid samples had yielded anything similar. Also, nothing as yet had been found at the clinic to account for a mold outbreak.

As Park worked methodically on the investigation, he also felt a growing dread; there were signs that this case might worsen, fast. They’d already ruled out their most promising hypothesis. The first patients had all been treated by only one person, Dr. John Culclasure. But the seventh to come forward had been injected by another St. Thomas doctor. If these cases were connected, this new variable would rule out a problem specific to Culclasure’s procedure. There was some good news, relatively speaking. All of the patients were still affiliated with just one place, the St. Thomas pain clinic. Whatever was happening, it appeared that the answers might lie inside the pain clinic’s walls.

Kainer was looking at seven suspected fungal meningitis cases from the St. Thomas clinic, which had voluntarily closed down and sequestered all of its medical supplies. But only one spinal fluid culture had come back positive. She could not wait for more test results. Kainer needed records for everyone who had been treated there in the past few months: their ages, their allergies, the dates and number of injections they’d received. The information would help her calculate which patients were most at risk and where any new infections could occur. But the clinic’s computers were incompatible with the state’s and the patient files would not download. Kainer improvised, sending her staffers in person to manually transcribe each chart. The handwritten data was faxed across town to the health department office, where another employee began build- ing a database.

As her staff collected patient data, Kainer began to pursue the infection’s source. At the top of her list was a facility that had made steroids for the back-pain injections. The New England Compounding Center.

___

Four months earlier

FRAMINGHAM, MASSACHUSETTS

Barry Cadden leaned forward in his chair, angling for a view of his small audience over a stack of papers. A dozen members of his sales force had gathered in the conference room, notepads at the ready. “All right. Welcome, everybody. So as we know, we’re being filmed today. No goofy questions like the last time, right?” he said. It was May 2012, and this was the third sales training video Cadden had shot in recent days. In the prior session, some sales representatives had asked questions about legally sensitive subjects that he wanted to avoid.

Cadden’s receding hairline and downcast eyes gave him a look of tired resignation. But his hands sliced energetically through the air as he spoke. “We’re pioneers,” he said, explaining to those in the room the company’s decade-long role as, he believed, Good Samaritan in the national drug market. The United States had regularly faced supply shortages of many common medications—70 in 2006 had grown to 210 by 2011. There were many reasons for the shortfalls, not the least of which was that Big Pharma, brand-name companies like GlaxoSmithKline, Pfizer Inc., Johnson & Johnson, or Bristol-Myers Squibb, sometimes abandoned manufacturing certain drugs after they lost their lucrative patent protections. Also, drug manufacturers relied increasingly on a global supply chain that was prone to disruption. Some 80 percent of the raw materials in the pharmaceuticals sold in the U.S. are imported from Europe, India, or China, and if a foreign company had a problem—armed conflicts, political upheaval, trade disputes, animal diseases, contamination during transport—the U.S. market felt it. Amid these supply interruptions, hospital pharmacists were under intense pressure to keep important drugs on the shelf, but many medications were made in-house without preservatives and had a short shelf life. This made in-house compounding an expensive balancing act. How could a hospital make enough drugs to meet patient demand, but not so much that they would spoil on the pharmacy shelf and have to be discarded? During these frequent breakdowns in the supply chain, the steroids, antibiotics, and eye-numbing agents used in common surgeries were impossible to source, but still needed.

While Big Pharma decided what medications to make, big-box retailers like Walmart took over the pharmacy market in many communities, driving corner drugstores out of business. But Walmart and many other large retail pharmacies did not compound many drugs, creating an opportunity for down-on-their-luck pharmacists. In stepped more nimble operations like the New England Com- pounding Center.

Federal law allowed compounding pharmacies to customize medicines for special-needs patients. If a child needed a lower dose of a commercially available drug, like a painkiller, or someone was allergic to a binding agent in their synthetic thyroid hormones, the patient’s doctor wrote a prescription and a compounding pharmacist made it from “active pharmaceutical ingredients” (APIs), the chemical constituents of drugs, and excipients like fillers or bulking agents. For hundreds of years, this kind of work was a normal part of an apothecary/pharmacist’s duties, and the practice was thus exempted from many federal drug safety regulations passed in the early twentieth century. By the 1980s, as mass-manufactured drugs under the purview of the U.S. Food and Drug Administration be- came dominant, the practice of compounding became a niche part of the business. Then, by the start of the 2000s, drug shortages made compounding a necessity once more.

It was a hero’s narrative, and Cadden delivered it with a sincere confidence.

When Cadden’s brothers-in-law, Gregory and Douglas Conigliaro, cofounded NECC in 1998, it was a family business, making small quantities of custom medications that no one else did. Be- cause Douglas, an anesthesiologist, owned a pain-management practice in Florida, his ownership of NECC presented a legal conflict of interest. His siblings stepped in, and his wife, Carla, held a majority of the ownership in her name.

Douglas and Greg’s sister, Lisa Conigliaro Cadden, and her husband, Barry, ran the day-to-day operations and held about a third of the company’s shares. Even the company’s location was a family affair. A sign in the parking lot advertised Conigliaro Block, Nationwide Foam, Inc., and Conigliaro Industries—all owned by Greg Conigliaro. Anyone arriving at the generic business park situated between a swamp and a pond in a neighborhood of plain clapboard houses would likely miss the pharmaceutical laboratory sandwiched between the concrete-block maker and a recycling center, their attention drawn instead to the hills of old mattresses and discarded furniture in the parking lot. Across the street, a sports pub that opened at 11:30 a.m. was a popular spot for employees.

In its first years, NECC had earned a few million dollars filling modest orders mostly to strip-mall pain clinics and doctors’ offices, which could not afford to employ pharmacists to compound sterile drugs in-house. Federal law permitted compounding pharmacies to legally ship a percentage of their wares without a prescription— usually 5 percent, depending on the state—to other states for so- called office use, a small quantity that doctors could stock as an emergency supply. NECC had been relying on the office use ex- emption to compound an increasing quantity of popular medicines like the corticosteroid betamethasone, the heart-stopping cardioplegia drugs used by cardiac surgeons, and hundreds more without prescriptions. No one tracked exactly how many drugs NECC made or where they were shipping them; state and federal drug safety of-ficials relied on compounding pharmacists like Cadden to honestly self-report. The practice was already lucrative, and Cadden saw room for exponential growth.

His first priority was building a sales force filled with what he called “killers”—sales reps like him who would go after hospital pharmacies aggressively.

When the demand for compounding began to increase in the nineties, Congress and the FDA scrambled to catch up. In 1997, Congress passed the Food and Drug Administration Modernization Act (FDAMA). Section 503A still exempted small-time low- risk compounding from standard drug approval requirements. It focused instead on the more egregious practices of large-volume compounding businesses. Pharmacies could no longer solicit doc- tor prescriptions, nor could they make drugs that were identical to a commercially available product, unless it was on the FDA’s drug shortage list. A compounded medication had to be customized in some way. And pharmacies could neither market nor advertise their products. Doctors had to reach out to compounders when a patient needed a prescription, not vice versa. Under the FDAMA, if a compounding pharmacy did any of these things the FDA could shut them down, after a long process of warnings.

A group of compounding pharmacies sued, and in 2002 the Supreme Court weighed in on a key issue in the case. With a 5–4 split decision in Thompson v. Western States Medical Center, the ruling paved the way for compounding pharmacies to continue to market and advertise drugs. The ruling paralyzed the FDA’s years- long efforts.

The agency was hamstrung.

Still facing the camera, Cadden stopped speaking abruptly, leaned back, and grinned. He had learned that one of the most powerful tools in sales is fear. When it came to doctors, that might be the fear of making mistakes in mixing complicated medicines. The fear of killing someone. The fear of malpractice lawsuits. “This is how we help them. You give them more hours back. And the big dirty word is the liability issue,” he said, his arms drawing circles, hands splayed like starfish.

Sending out drugs without patient prescriptions is illegal, and Cadden knew it. But the Massachusetts Board of Registration in Pharmacy was a chronically underfunded operation with only three investigators covering more than eleven hundred pharmacies. (Dozens of other states were in a similar boat.) It was responsible for overseeing forty-seven larger compounding pharmacies similar to NECC. Not one of Massachusetts’s three pharmacy inspectors was trained or qualified to inspect sterile rooms. And the FDA inspectors who were had to be invited in by the state board. “We’re like a pimple on a flea’s behind in pharmacies,” he said, getting laughs. In the privacy of his conference room, he mimicked a scene from NECC’s last state inspection. “They don’t even know what they’re looking at. They have no clue. They go around, like, ‘Barry, this place looks great!’” he said with a snicker. “I give ’em a cup of coffee and out the door. That’s what it is like!”

NECC revenues had spiked from $5 million in 2004, before the U.S. Pharmacopeia changed its safety standards, to $13.1 million in 2007, the year they changed. In 2011, the company took in $27.4 million, and as Cadden spoke in 2012, it was on track to earn nearly $50 million. NECC’s drugs were cheaper than the brand names— they could pass on the savings of not having to comply with federal CGMPs—and were readily available. They would receive regular orders from 8,500 hospitals and their surgical clinics.

It was Cadden’s job to keep it all on track. He and his wife, Lisa, had recently built a $1.4 million, thirteen-room mansion and owned three other properties, including a waterfront weekend house in Rhode Island, held a $1.5 million trust, as well as luxury cars. The Conigliaros were also getting rich.

Cadden paused again. He’d been talking for a while and still had not explained how the “clean rooms” one floor below were going to handle the deluge of orders he expected them to bring in. Cadden had carefully separated the two parts of his business. The lab was behind a door that required a key card to enter, and the reps were never to communicate directly with the pharmacists. This gave them plausible deniability; they could not question Cadden’s commitment to quality if they did not see evidence contradicting it. If a salesperson needed the lab to rush an order out or to change some- thing, they had to go through Ronzio or Cadden’s other consigliere, Sharon Carter, a stern, crisply dressed woman who oversaw order processing. Only the people who worked inside the clean room knew what was happening there. All anyone else needed to believe in faithfully and to communicate forcefully was one word: quality.

“The most important thing we do every day in the lab is produce quality—and understand that we do it. Understand that you should use that as part of your sales approach. Absolutely understand that we’re not selling jelly beans. These are, you know, sterile products.”

But achieving quality, sterility, is not easy. The colossal brand-name manufacturers like GlaxoSmithKline and Pfizer that make sterile drugs under FDA oversight are required to record each tiny step; when errors pop up, there is a diary of what went wrong. The system is onerous because it is designed to force profit-minded companies to protect the public health. Drugs made in these regulated factories often vary in strength and preparation. The FDA defines what minute levels of variance are considered safe, for ex- ample, between brand-name and generic drugs. It is an exacting process—one that compounding pharmacies like NECC are not required to follow.

Cadden’s predilection to skirt safeguards had piqued the federal government’s interest a decade earlier. In March 2002, the FDA suspected that a contaminated batch of the company’s steroids had killed a man, William Koch, and sickened at least five other people with “meningitis-like symptoms.” After a physician reported the problem to the FDA, inspectors visited NECC to evaluate Cadden’s manufacturing processes. The FDA would file their concerns— which included letting a batch of steroids sit out for days with nothing but a piece of tinfoil covering the beaker—with the state board. The inspections also found that NECC kept no records. Cadden couldn’t verify if his drugs met USP safety standards, and there was no way for NECC to respond to complaints or adverse events. One inspector noted in a report that Cadden was helpful on the first day, but after he spoke to a lawyer, everything changed: “From that point on it was essentially ‘talk to my lawyer.’” The incident was settled quietly.

Later that year, Cadden made a batch of methylprednisolone acetate steroid that sickened at least two more people with meningitis-like symptoms, and the FDA returned for another round of inspections. This time the inspectors were more forceful, recommending to the Massachusetts oversight board that NECC be “prohibited from manufacturing until they can demonstrate ability to make product reproducibly [sic] and dependably.” In response, Cadden wrote letters promising to make changes to his processes. He hired another pharmacist, bought equipment, and expanded the lab. The state launched a committee to update its regulations for com- pounding pharmacies, a recognition that the industry had grown beyond its control. The state appointed Cadden to serve on the committee.

In 2004, the Massachusetts board received a complaint from a surgical center in Rapid City, South Dakota, that NECC was sell- ing drugs without legal prescriptions. The board investigated and sent NECC an advisory letter. The same day, it also looked into two other complaints about the company from pharmacists in Wisconsin and Iowa. Again, Cadden promised to clean up his act and the inquiries faded away.

Cadden did not mention any of these smudges on his record to his sales reps, of course. Instead, he encouraged them to counter any skepticism about NECC from doctors or hospital pharmacists by name-dropping: “Know in your area who our big clients are. The big names. I mean, use that stuff. Drop those names out there. They love that stuff.” Indeed, the reps saw some well-known names on the roster, chief among them Massachusetts General Hospital in Boston. Association with the world-famous institution enhanced NECC’s credibility. What Cadden didn’t mention was that, after years of striking out with Mass General, NECC had finally landed the account with a tried-and-true tactic: payoffs. NECC and Ameridose started paying a pharmacy staffer, Claudio Pontoriero, $5,000 a month. In exchange, he steered orders for a variety of drugs NECC’s way, bringing in cash and cachet. The deal went unnoticed for five years, and earned Pontoriero more than $355,000.

Cadden’s tone turned somber. He put his palms together as if in prayer. Hospitals had to trust that the reps were telling them the truth about the efforts NECC made to keep its drugs safe, and the reps had to trust Cadden. “We live and die with this place. I know if we don’t produce quality this whole thing goes up in smoke . . . I know that,” he said. The room was silent.

The most important factors, he continued, were all of the things that the sales team and clients never saw, like environmental monitoring for contaminants. NECC would indeed hire an employee to test the sterile rooms’ air, work surfaces, and floors. She had no training in the discipline, but it allowed Cadden to boast in marketing materials about the company’s commitment to safety.

Listening to Cadden felt like drinking from a fire hose, one sales rep at the seminar would say later. A pharmacy tech described a riveting display of self-confidence bordering on arrogance. But he had given them the practical and psychological tools they needed to sell to hospitals and surgery centers around the nation. NECC was competing with hundreds of other compounders, and even some hospitals’ own pharmacies. But the competition was not as fast as NECC, Cadden said. If they used the script, they would be successful. “If you relay all the information that you should, as best you can, they’re going to think about that. And that’s a big part of your job—to relay that information to them. Okay? Go down that checklist.”

NECC was making tens of millions of dollars annually. He now had dozens of employees, and the fax machines that he called “ATMs” were in constant whir and clank. Cadden saw the potential for a great deal more.

___

Day 8, September 25, 2012: 1 confirmed case, 8 suspected

VIRGINIA DIVISION OF CONSOLIDATED LABORATORY SERVICES, RICHMOND

As doctors and public health investigators scrambled to respond to what was happening in Tennessee, a package arrived in Beverly Jones’s mycology lab inside a public health laboratory building in Richmond. She slipped on her safety glasses and removed the biological sample.

For nearly two decades Jones had served as Virginia’s “one- man mycology lab,” as her bosses called her jokingly. She was the guru of fungi. When people got sick from a fungus or mold, the samples ended up here. The background noise in her laboratory was the low

hum of a refrigerator housing a rainbow of vials: dextrose, potato flakes, and other agars, culture media that could coax a fungus into growing big enough to study.

After fifteen years working in a diagnostic bacteriology lab, in 1994 Jones had been assigned to mycology—the she hadn’t studied in grad school at Virginia State University. She did not take the news of her assignment well. She’d Mycology was quiet compared to more high-profile bacterial viral pathogens, like the flu, West Nile, and MRSA.

But Jones eventually came around. She’d been chosen for the mycology laboratory because worked hard and her bosses thought she’d relish the challenge. Fungal diseases were puzzles, and Jones developed a passion solving them. She worked alone in her tiny

lab most days, was tough at first, but then became a perk of the job.

That day, the sample Jones received came from the cerebrospinal fluid of a forty-seven- year-old man named Doug Wingate. He was a patient in Roanoke who’d been stricken with debilitating strokes after falling ill with a indefinable form of meningitis—although

Jones did not know these details. She had been given only the sample ID number and the task of determining its species. All she knew was that another lab had tried, unsuccessfully, to culture it already.

After two days, Jones saw nothing helpful in her petri dish. She tried different foods to promote growth: potato flake agar, brain-heart infusion, Sabouraud dextrose agar. She also tried something she had learned in one of her early mycology classes. Sometimes,

as she put it, immersing the fungus in nutrient- deficient water, starving it, made the fungus “angry” as it fought for survival. Jones chuckled whenever she described this technique to colleagues. She set about making the fungus angry.

Day 8: Centers for Disease Control and Prevention, Atlanta

Dr. Ben Park huddled before a speakerphone in his office, eyes droopy behind his glasses after hours of conference calls. Across from him, Dr. Rachel Smith, who had joined CDC’s Epidemic Intelligence Service a little more than a year earlier, jotted notes. Occasionally he glanced out the bank of windows looking over the agency’s grassy campus. It was midday and they had already been on a seemingly never-ending rotation of conference calls, the mundane yet crucial busywork of any epidemiological investigator.

They dialed into a call where Cadden and Greg Conigliaro waited. Kainer, the Tennessee epidemiologist, was on the call, along with four members of the Massachusetts pharmacy board that oversaw NECC and the state’s public health agency. Cadden’s voice crackled greetings over the speaker. The mood was serious but amicable.

So far the investigation had been like walking through a darkened room looking for a tiny object. Since Rybinski’s illness came to light, Tennessee’s suspected meningitis case count was rising steadily, plus a few more St. Thomas pain clinic patients complain- ing of headaches and nausea. To rule out possible causes, the investigators had to trace the supply chain for every single item used in each procedure: syringes, anesthetics, surgical dye, the trays that held the medical instruments and vials.

As the first patient, the index case, Rybinski had provided an early clue—the fungus Aspergillus fumigatus that bloomed in a vial with the sample of his spinal fluid. Spinal fluid from subsequent patients, however, was not matching his profile; initial tests showed no

Aspergillus. It had been a week since Rybinski’s diagnosis, but none of the other suspected cases had tested positive for a fungus. But if it was not Aspergillus-caused meningitis, what was it?

___

Day 11, September 27, 2012: Centers for Disease Control and Prevention, Atlanta

Drs. Park and Smith at the CDC were on the phone with a hospital and epidemiologists at North Carolina’s Department of Health and Human Services. An anesthesiologist told them that a spinal tap on a patient named Elwina Shaw had produced cloudy spinal fluid. She also had symptoms consistent with fungal meningitis, and had suffered a stroke overnight. Park and Rachel perked up. Elwina’s stroke was characteristically similar to Rybinski’s. The anesthesiologist happened to also be a partner at the clinic where Elwina had received her injections and con- firmed that she’d been given methylpred. The doctor did not think Elwina had long to live. And it wasn’t just the steroids that were suspect. The clinic had used the same iodine solution as an antiseptic and the same anesthetic as the Tennessee cases.

The CDC had requested brain tissue and cerebrospinal samples for any new cases so they could see if it was a fungus matching the one in Rybinski’s body. Rybinksi would be moved into hospice care and die within days. If Elwina’s family consented to an autopsy, samples from her body could be flown to Atlanta quickly.

The request for an autopsy reached Elwina Shaw before she died. Her other daughter, Anna Allred, worked as a hospital chaplain, and had been against the idea. She saw it as intrusive and disrespectful. Elwina sat up in her hospital bed and told everyone except Anna to leave. “You and I have to talk, and then we have to pray,” she said. Anna had participated in many deathbed conversations, but this was her mother. Anna had an aversion to autopsies after a particularly difficult visit to a morgue during her chaplain training.

“You have to accept that this needs to be done,” Elwina told her gently. If her body could provide clues that might save other lives, they should not stand in the way. Anna delivered Elwina’s wishes to her family. They signed the papers.

Elwina’s samples, along with Rybinksi’s and a few others, were delivered to the lab of an esteemed CDC pathologist, Dr. Sherif Zaki.

Unlike Jones’s small lab in Virginia, Zaki’s lab was state-of-the-art, its hallways decorated with framed photographs of some of the pernicious microbes he had battled over the years. In 1992, Zaki was involved in the discovery of the hantavirus, which caused severe pulmonary infections and initially had a mortality rate of 50 to 60 percent. After 9/11, he had also worked on the

anthrax attacks.

The samples of brain and spinal tissue arrived fixed in a solution called formalin and embedded in a wax block. Scientists cut slices off the block to examine under a microscope. They added blue and red stains that identify bacteria, as well as something called Grocott’s methenamine silver, or GMS, stain, which identifies fungi. Rybinski’s sample immediately turned a deep red. He had had an aneurysm, a kind of ballooning, in the arteries of his brain. Zaki noted a fungus and recognized it as Aspergillus.

Zaki moved on to Elwina. The blood vessels of her brain tissue were also inflamed. Something was different than Rybinski’s sample. In fact, the fungus from her sample did not look similar at all—it was elongated, with sectioned-off chambers and scars on the ends where its reproductive spores detached. Describing the microbe’s unusual branch-like structure, Zaki noted in his report that there were “rare fungal” structures. He could not identify it by sight. The CDC would sequence its DNA along with samples collected from other patients and try to find a match.

Day 10: Richmond

There it was. The water agar Beverly Jones used days earlier had indeed made the mold angry.

She held her dish up for a better look. The half inch of mold that had grown was not blue-green like Aspergillus. Mycologists use terms like woolly, suede-like, cotton-like, or glabrous (smooth or leathery). This fungus was soft like suede. The sample was placed onto a slide using two long knitting-needle-like tools from beneath her worktable. She inserted the tips into a tube with a torch flame to sterilize the ends, slipped on white sleeves and gloves over her lab coat, and placed the petri dish into a ventilated sterile work- bench called a hood. She used her needles to tear the mold into smaller pieces and stuck a chunk on a slide. She added blue dye, then squashed the sample below a second slide. At her microscope, she took a closer look.

At first Jones saw only a bird’s nest of black hairlike strands. This told her nothing. She turned the slide over. Boom. There was something ghostly and glowing in the blue dye. She zoomed in. It looked like a translucent pea pod or a see-through worm. Inside the worm-like body were separate chambers, and at the end of it were scars, where the fungus’s reproductive spores had detached as it multiplied in her dish.

She’d seen this fungus before, in samples from patients in Virginia with sinus infections. While the CDC pursued DNA identification, Jones and her colleagues had recognized it almost immediately. Jones had more details about the mold in an old mycology book she kept on a shelf in her small lab. This fungus ate grass and corn voraciously. It was not a well-known human pathogen. There was no literature showing that it had ever caused meningitis, let alone strokes.

The CDC had just sent out its Epi-X alert, and Virginia’s health officials suspected the samples she was studying had come from a patient—Doug Wingate—with a profile similar to the ones in Tennessee. In public health, it didn’t get any bigger than a CDC investigation. They also said that one patient had tested positive for a common mold, Aspergillus fumigatus. Jones called in her supervisor, asking her to look through the microscope and confirm Jones’s finding. “This ain’t no Aspergillus,” the supervisor said with a chuckle. Jones nodded in agreement.

___

Day 17, October 4, 2012: 5 dead, 35 cases

CENTERS FOR DISEASE CONTROL AND PREVENTION, ATLANTA

Dr. Park spoke slowly into the phone. Cadden and NECC had sent a list of the clinics that had received the company’s steroids. More than 17,000 vials had been distributed in more than two dozen states. He now recognized how widely NECC’s drugs had been distributed, and he had the FDA’s confirmation of contamination. He felt unsettled. This was unlike anything he or the CDC had ever dealt with, and there were still a lot of unknowns. The CDC estimated that 13,534 patients had been exposed. The number of dead and sick was rising by the day. The still-evolving case definition being used to identify at-risk patients included symptoms of meningitis in people who’d also received an injection of NECC’s methylpred. Did the mold in the vials match the fungus inside the patients? Also, they had still not confirmed the species of fungus. There was a 40 to 50 percent mortality rate in the patients they knew about. Yet Park thought there was still a small chance they were about to name the wrong culprit. Listening in were a gaggle of reporters, from The Tennessean and The New York Times to the Associated Press. Park started with a. brief description of what had been happening in Tennessee, and how the testing of patients’ spinal fluid had been negative until a fungus was discovered in one sample.

Symptoms, including the strokes, were manifesting one to four weeks after injection. Park told reporters that he believed what they had seen so far was likely to intensify. NECC had faxed recall notices for the three lots of steroids, but the drugs were distributed so widely that there was no guarantee word would reach doctors and nurses. The drugs had been distributed throughout nearly half of the country. Park read out the names of the states: California, Connecticut, Florida, Georgia, Idaho, Illinois, Indiana, Maryland, Michigan, Minnesota, North Carolina, New Hampshire, New Jersey, Nevada, New York, Ohio, Pennsylvania, Rhode Island, South Carolina, Tennessee, Virginia, Texas, and West Virginia.

What was once a cluster of cases was now an outbreak. The media in the affected twenty-three states started alerting the public. The CDC opened up its Emergency Operations Center, which is used only during pressing public health threats, most recently a year be- fore, after the earthquake and tsunami in Japan that inundated a nuclear plant and caused a meltdown. The control center’s monitors flickered on, with neon-colored maps tracking the state-by-state spread of known cases. Fifty staff members flooded in initially, and would grow to hundreds, all CDC employees reassigned from their normal posts. They made their way down call lists of potential victims. Vats of coffee were wheeled in.

The effort would be the largest direct-patient outreach in the CDC’s history to that point, dovetailing with the efforts of state health departments in Michigan, Indiana, Tennessee, Virginia, Florida, New York, and the other affected states, where health care workers, law enforcement officers, and volunteers raced to dial each patient.

Albany, Kentucky

The call took Joyce Lovelace by surprise. The woman from the out- patient clinic where Judge Lovelace had been treated for back pain the previous summer wanted to know how he was doing. They had a patient with an unusual disease and were doing a routine follow- up. “Well, he passed away,” Joyce said, confused. The caller offered condolences before hanging up.

A few days later, Joyce mentioned the call to her daughter, Karen. Her mother’s story rang a bell. Karen had seen a report about the alert from the Tennessee state health department and had reached out to her father’s doctor to inquire about his shots. As her mother relayed the message from the clinic, the details struck Karen as similar to the state alert—headache, nausea, and strokes in patients who’d received a steroid injection. Her father had been buried with “unknown cause” on his death certificate. This meant that Eddie’s family could not collect his life insurance, which did not cover death by old age or illness, just an accidental or untimely demise. None of them believed the healthy judge had died so suddenly without cause, but they seemed to have no recourse.

Joyce decided that her husband’s body be exhumed.

___

Day 31, October 18, 2012: 20 dead, 257 cases

NASHVILLE

Dr. Marion Kainer had barely slept in weeks and was surviving on coffee, adrenaline, and fear. When she did catch a few hours of sleep, it was often on a couch in her office. About a month had passed since she had reported the first case, Tom Rybinski’s, to the CDC. It was late on October 18, and her birthday. She stayed up going over mathematical models of patient data that her staff had been collecting since late September. She was close, finally, to answering a question that could help doctors put up a better fight against a disease with an initial 40 to 50 percent mortality rate: Were patients at a higher risk of infection depending on which of the three batches of NECC’s methylprednisolone acetate they received? If doctors had this “attack rate” for each lot that was distributed, they could prioritize treatment for the patients injected with the most dangerous lot.

Since the outbreak’s first hours, Kainer had worked toward gathering the raw data she needed to calculate the attack rates. She’d sent her staff to the St. Thomas clinic and others, where they’d faxed each patient’s information in to headquarters. They had collected hundreds of profiles this way, painstakingly building their database. But most clinics had not noted which lot a given patient had received, so Kainer’s team had to compare the date of the shot with inventory records. About a thousand people in Tennessee had received the contaminated drugs, and the patient database was now substantial enough for a meaningful epidemiological analysis.

The CDC and state health departments were close to notifying 99 percent of the nearly 14,000 people at risk, but they weren’t able to provide them with many answers, and antifungal medications were still hard to come by. Now the team finally had the raw numbers they needed. It turned out that, for the Tennessee cases at least, the attack rate was significantly higher in patients from the June lot, followed by August, and then May.

Within days, the CDC released guidelines for clinicians to prioritize antifungal treatments for the people injected with the June and August lots.

Day 43, October 30, 2012: 28 dead, 363 cases

CENTERS FOR DISEASE CONTROL AND PREVENTION, ATLANTA

The index case in Tennessee, Tom Rybinski’s, had identified the pathogen as the fungus Aspergillus fumigatus, but no subsequent patient had tested positive for it. The CDC’s investigators needed to confirm the fungal species before they could finalize their own treatment guidelines, which were still evolving.

Weeks earlier, Beverly Jones in Virginia had identified a mold in the samples that was not known to cause meningitis. Once Dr. Mary Brandt, Dr. Park’s boss at the CDC, got the photos, she agreed; this was not Aspergillus.

Meanwhile, the CDC’s labs were inundated with dry-ice-packed boxes filled with vials of cerebrospinal fluid. The goal was to isolate the fungal DNA and run it through a genetic database to find a match. But first they needed a tool that could reach into a sample and amplify just the bit of genetic material they wanted to study. Working with one, or even just a few, strands of fragile DNA is difficult. But Brandt’s lab would make copies of the fungus’s genetic code via a polymerase chain reaction, which works like a microscopic photocopy machine, spitting out millions of copies of DNA in about two hours.

A pattern became clear. Sample after sample revealed the genetic bar code of a fungus rarely implicated in human disease. The limited scientific literature that did exist said it was a plant pathogen that ate grasses and corn. There were no known meningitis cases caused by this microbe in previously healthy patients.

Dozens of samples later, they could confirm what many had suspected from the start. They had spent weeks looking for the wrong killer. Rybinski’s positive test for Aspergillus fumigatus had indeed been a red herring.

The true culprit was a rare fungus, Exserohilum rostratum, that was known in the scientific literature as a voracious eater of corn. This was unprecedented. view abbreviated excerpt only...

Discussion Questions

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3. Do you feel more or less confident in the oversight of drugs in our country after reading Kill Shot?
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6. If you didn't know this was a work of non-fiction, do you think you would have believed this to be true?

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