Spaghetti and Peas: A short story by Geraldine Brooks
The infant lay curled like a nautilus, her vertebrae no bigger than a string of pearls. I ran my finger over the tiny bones, and inserted the needle—obscenely large against her small back.
She didn’t cry. Bad sign. I’d been braced for it: the usual high-pitched, cat-like keen that accompanies the administration of antibiotic directly into the spinal fluid. As distressing as it is to hear a baby scream, not hearing it is always worse. Means the infection’s winning.
Some infinitely gentle, infinitely suffering thing. Eliot? Yeats? Sic transit high school English. Probably Eliot. I think it must be Eliot.
Less than twelve hours. That’s all it took to transform a healthy baby into a critical case. The airborne bacteria had entered her body, swarmed and multiplied, overwhelming her immature immune system. I withdrew the syringe and instead of standing aside for the nurse, swabbed the injection site myself and placed the dressing as tenderly as I could.
Whatsoever you do to the least of them… Matthew, 25:40. Those Sunday school teachers in Canton, Ohio knew how to make the gospel stick. Ten years since I graduated from Ohio Wesleyan and entered med school in Rochester, New York. Five years since I started my internship in pediatrics at Children’s Hospital in Boston, and now I’m chief resident. Still feeling absolutely outraged at the prospect of losing another patient. Will I ever get used to it? Should I ever get used to it? No good thinking about that now. Janeway’s coming. Physician-in-chief. Grand Rounds. Take a deep breath. Present the case:
Female, six months old, admitted 1.06am, presenting with high fever, mother reported severe vomiting, apparent neck stiffness. Blood pressure—I read off the catastrophically low numbers that described thread-thin blood vessels inflamed and collapsing, her blood clotting, depriving tissues of oxygen. On examination, gangrene noted in extremities. Not visible on examination: the bloody, gelatinous pus already covering the surface of her brain, the membrane known as the dura mater—tough mother—but not tough enough to protect her from this onslaught. Spinal tap confirmed Haemophilus influenza type B, the infamous Hib, and this year, 1963, as it has every single year, it will make one in every 200 infants gravely, life-threateningly ill. Especially deadly for two- to six-month-old infants, as inherited maternal immunity typically wanes and breast-feeding ends. For these, the most vulnerable, for the least of them, no effective vaccine existed.
“Prognosis?” Charles Janeway demands.
I reel off the grim numbers: Five per cent chance of death, even with prompt treatment. Forty five percent chance of severe deficits, most commonly: deafness, brain damage.
Janeway nods. “This bacterium, Hib, is the most common cause of childhood bacterial meningitis in this country. It is devastating. And it is preventable. Maybe one of you young people –’’ he scanned our faces as we clustered around the bed—“Maybe someone here today will be the one who figures this out.”
Pipettes, test tubes, reagents. Put this with that. Watch it change color. Do it again. And again. And again. For twenty years.
That was the reality of trying to be the guy who figured it out. From that day on the ward at Boston Children’s, I bent my life to it. From residency, I went back to school, to Harvard as a post-doc in molecular genetics and bacteriology. They hired me as chief of Infectious Diseases at Harvard Medical School. I got a Guggenheim for further research in Geneva. Then in 1976, University of Rochester Medical Center named me Chair of the Department of Pediatrics and Chief of Pediatric Infectious Diseases.
In Boston I’d met Porter Anderson, the best bacteria juggler I’d ever seen in a lab. I managed to get him interested in Hib, and he came to Rochester to continue the work. Our early investigations led to a vaccine that worked on toddlers, but not on the most vulnerable, the infants. Then, in April, 1983, breakthrough: we knew we had the answer. The solution was elegant: we needed to create a conjugate vaccine, pairing polysaccharides and proteins. I wanted to describe it to my daughters, so I had to come up with something they could understand.
Spaghetti and peas. The Hib germ consists of a protein in the form of a sphere, like a pea. But on the surface of the bacterium are sugars—long, stringy polysaccharides, like slimy strands of spaghetti. In our lab, we’d grown the Hib germ in culture and then broken it down chemically into its components. Babies’ immature immune systems knew how to make antibodies that fought against the proteins—the peas—but they didn’t recognize the sugars—the strands of spaghetti, wound all around the protein, encapsulating it, hiding it from detection.
Porter’s work narrowed down to this: binding the sugar strands to a recognizable protein that the T-cells of the infant immune system could identify, capture and destroy. We tried diphtheria toxoid proteins, the same as in diphtheria vaccines and already proven effective in infants as young as two months.
I started to look for a company that could take this further: do the large- scale trials that assure safety and verify disease prevention, that had the clout and the know how to work with the FDA and the CDC. A big company that could champion the vaccine and bring it to the public.
“What do you mean, more like a public health initiative than a business proposition?”
The Big Pharma exec looks at me and I can’t read his expression. Is he embarrassed or disdainful? And in every well-appointed office I visit it’s the same story: “Promising science here, but not worth it to us to undertake costly clinical trials and battle through Federal regulations for a vaccine with a limited market (finite number of babies born each year) and high liability (anything to do with infants a legal minefield).”
Here’s what I think, though they won’t say it: vaccines are cheap and hospital-administered antibiotics are expensive. There’s more profit in a 10-day course of antibiotic injections to treat 20,000 annual cases than there is in a cheap vaccine to prevent them.
“But you’re a doctor and a scientist, not an entrepreneur.”
Joan sits with our five girls around her. I give her a wry grin. “And tenured department chairs generally don’t quit their jobs. It’s reckless, and I know I’m no businessman.” I open my gym bag to reveal the books I’d just scooped up from the library. Biographies of famous corporate CEOs, texts about Japanese business practices. “Management 101.” The girls smile. So does Joan. But I don’t want them to take this lightly. “We’ll have to take a second mortgage. There’s a big chance we could go bankrupt. The decision affects all of you.”
Andrea, my eldest, fixes me with her direct blue gaze. “You’ve always looked down on people who go into medicine to make money. You said you’re in it to help people.” Her sisters nod. They’ve all heard my dinner-table sermons. “You’ve always wanted to make this vaccine. We think you should go for it.”
Praxis Biologics (founders: David Hamilton Smith, Porter Anderson and our fellow researcher, Richard Insel) opened in a former girls’ school in 1983, where we turned the disused classrooms into labs. Some people said my hiring practices were unconventional. Maybe. I did hire a young woman who hadn’t finished college as Praxis’s director of clinical research. But I liked the way she thought, and that’s what matters. I could teach her the rest. To the young scientists, my pitch was direct: “You’ve done nice work, you’ve got grants, you can have a great career in basic science. But if you really want to have an impact, come work for me and develop vaccines to save babies.”
By 1985 we had FDA approval for a vaccine for babies two and older, but not for the most vulnerable, the younger infants, where the need was greatest. We took Praxis public in 1987, without waiting for the FDA. I had confidence, but confidence can’t cover payroll. The house was mortgaged many times over, and some weeks we went right to the brink. In 1988 clinical trials began in Finland. By the following year, our tiny company had more new vaccines in clinical trials than any other US corporation.
The brave parents of fifty-three thousand infants let us trial our experimental vaccine on their babies, at two months and six months, with a booster dose at 14 months. No child who received the complete dose became infected. In December 1988, the FDA approved the vaccine for use in children over 18 months, and finally, in 1990, for infants over two months old.
Somewhere along the line, Big Pharma changed its mind about our vaccine. There was a bidding war for Praxis between two giants, companies we code-named Red Wing and Blue Jay. In June 1989 we agreed to merge with American Cyanamid for a share price that valued the company at $238 million. I paid off the mortgage and bought a summerhouse on Martha’s Vineyard. Then I started to work on giving the rest of the money away.
A year after the FDA approved the vaccine for 2-month-olds, the CDC reported a 71% decrease in spinal meningitis in children less than 15 months. By 1997, there were 81 cases of invasive Hib disease reported in the US, down from 20,000 a decade earlier.
“I’ve found a lump.” I was in the shower when I found it; I can’t stop fingering it, there at the base of my neck. Lymph nodes. My wife looks up, questioning.
“What’s it mean?”
Diagnosis: melanoma. Treatments: anything, no matter how experimental. Object: to beat the cancer. If not, then to keep on doing the work of medical science. If it’s the last thing I do. If it’s the last thing I can do.
Tired now. Bald. Depleted. Metastatic brain tumors. Trying cell therapy.
Doctors make lousy patients. The other patients in the chemo suite listen to music, nap, hold hands with their partners. Not me. I ask too many questions, second guess, tell people how to do their jobs. I don’t mean to. Just habit. Sometimes, I forget I’m a cancer patient in New York and think I’m back on the wards, a pediatrician treating babies in Boston. Every big teaching hospital is the same. Same noises. I close my eyes and hear the wince of the gurneys—why can’t they ever oil those wheels? The syncopated beeping of monitors dopplering from dozens of bedsides. The hushed, anxious fragments of conversations. The self-important attendings, barking orders.
“Dr. David Smith? Sorry to disturb you…”
I open my eyes. ‘Yes nurse?”
“I’m not your nurse. I’m an intern here. I – I heard you and Dr. Anderson won the Lasker Award for your work on Hib. I just finished my pediatric rotation and the attending was saying how we might never see a case of bacterial meningitis now, unless we work in the developing world. “
“Are you thinking of going into pediatrics?”
“No. Oncology, actually. Gene therapy, maybe…cancer vaccines…”
I close my eyes again. Janeway’s coming. Grand Rounds. But this time, I’m the one who says it:
Maybe you will be the one who figures it out.
Endnote: David Hamilton Smith died February 23rd 1999. He was 67 years old. From funds realized from the sale of Praxis in 1989, Smith founded the Cedar Tree Foundation. Its grants fund scientific research, the Smith Fellowships for graduate field work in environmental sciences, and causes such as land preservation and science-based alternatives to the overuse of antibiotics and pesticides in agriculture.