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 under my fingers. When I found the place, I inserted the needle — obscenely large against her tiny back — and slowly depressed the plunger, delivering a massive dose of antibiotic directly into her spinal fluid.

Some infinitely gentle, infinitely suffering thing. Eliot? Yeats? Sic transit freshman English. Probably Eliot. I think it must be Eliot.

She didn’t cry. Bad sign. I’d been braced for the usual high-pitched, cat-like keen that accompanies this excruciating procedure. As distressing as it is to hear a baby scream, not hearing it is always worse. Means the infection’s winning. In less than 12 hours, a massive invasion of bacteria had swarmed her tiny body, 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. That, I can remember. 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 tiny 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 1:06 am, 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, blood coagulating unregulated, clots forming, the blood-deprived tissues dying. 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 in 1963, still the cause of some 20,000 meningitis cases in the United States a year. Especially deadly for infants between the ages of six months, when inherited maternal immunity typically wanes, and two years, when the child’s own immune system has developed sufficiently to respond to existing vaccines. But for the babies in between, the most vulnerable, for the least of them, no effective vaccine existed.

“Prognosis?” Charles Janeway demanded.

I reeled off the grim numbers: Five percent chance of death. Forty-five percent chance of severe deficits, most commonly: deafness, brain damage.

Janeway nodded. “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.”

*

I spent the next 20 years trying to be that person. From my residency I went on to Harvard as a postdoc in molecular genetics and bacteriology, then became chief of infectious diseases at Harvard Medical School, and got a Guggenheim for research in Geneva. In 1976 I was named chair of the department of pediatrics and chief of pediatric infectious diseases at University of Rochester Medical Center.

At Harvard I’d met bacteriologist 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 experiments led to a vaccine that worked on toddlers, but not the most vulnerable infants. In April 1983, we knew we had the answer. The solution was elegant, involving polysaccharides and proteins, but 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 to the peas — the proteins — but not to the sugars — the spaghetti, which wound all around the protein, encapsulating it so that it evaded recognition. The focus of our work has been to bind the sugar strands to a recognizable protein that the T cells of the immune system could identify, capture, and destroy. We used diphtheria toxoid proteins, same as in diphtheria vaccines, and already proven effective in infants as young as two months. The vaccine was effective in animal trials. Porter and I tried it out on ourselves. But to bring it to market, I thought we’d need Big Pharma to take it over. A company that could do the large-scale trials that assure safety and verify disease prevention, that had the clout and the knowhow to work with the FDA and the CDC. A big company that could bring it to the public.

*

“What do you mean, more like a public health initiative?”

The Big Pharma exec looks at me, and I can’t read his expression. Is he embarrassed or disdainful? 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 antibiotics are expensive. There’s more profit in a long course of antibiotics 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. I know I’m no businessman.” I opened my gym bag to reveal the book I’d just scooped up from the library. Biographies of famous corporate CEOs, texts about Japanese business practices. “Management 101.” The girls smiled. So did Joan. But I didn’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.”

“You’ve always looked down on people who go into medicine to make money,” said Andrea, the eldest. “You said you’re in it to help people.” She looked around the room at her sisters. “We think you should go for it.”

*

Praxis Biologics (founders: David Hamilton Smith, Porter Anderson, and our fellow researcher, Richard Insel) opened its lab in a former girls’ school in 1983. They said my hiring practices were unconventional. Maybe. I did hire a young woman who hadn’t finished college as Praxis’ director of clinical research. But I liked the way she thinks, and that’s what matters. I can teach the rest. To the young researchers, my pitch was pretty 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.”

We took Praxis public in 1987, without FDA approval for the HibTITER vaccine. I had confidence, but confidence can’t cover payroll. The house has been mortgaged many times over, and my board had just about had it. They wanted me out. They want to sell the company. But if they do that, we’ll lose control of the process. The vaccine might never be released. In January 1988, they forced me to resign as CEO and president. It took me two months to round up enough support and enough voting shares. Then I sacked the board.

I was back as CEO when clinical trials began in Finland. Fifty three thousand infants received the vaccine at two 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 four years later for two-month-olds. The number of cases in the United States has decreased 98 percent, to less than a hundred a year.

*

“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?”

“Nothing good.”

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.

But today I’m too tired even to be a nuisance. I close my eyes and listen to the familiar sounds of a big teaching hospital wash over me. The wince of the gurneys — why can’t they ever oil those wheels? The syncopated beeping of monitors. The hushed, anxious fragments of conversations.

“Dr. David Smith? Sorry to disturb you …”

I open my eyes. “Yes, nurse? Time for vitals?”

“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 the HibTITER. I just finished my pediatric rotation, and the attending was saying how we might never see a case of spinal meningitis now, unless we work in the developing world.”

“Are you thinking of going into pediatrics?”

“No. Oncology, actually. Gene therapy, maybe …”

I close my eyes again. I can hear Janeway, as if it were yesterday. Grand Rounds on the ward, speaking over the body of that limp little baby girl:

Maybe one of you young people here today will be the one who figures this out.

Endnote: David Hamilton Smith died Feb. 23, 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. His donations and support were critical in the preservation of Polly Hill Arboretum.

*

This story was originally posted on  The Art of Saving a Life website. Vaccines are one of the greatest advances in human history. They have saved millions of lives, and led to better health and opportunity for children and families everywhere. The stories behind this success and the future promise of immunization, must be told.

They are stories of risk and bravery, the passion and dedication of scientists, the love of parents, and the determination of health workers.

“The Art of Saving a Life” is a collection of these stories, as told by more than 30 world-renowned photographers, painters, sculptors, writers, filmmakers, and musicians in a project funded by the Gates Foundation. In “Spaghetti and Peas,” Geraldine Brooks writes an intimate portrait of Dr. David H. Smith told in flashbacks. Dr. Smith co-invented the vaccine against Hib, a bacterium that can lead to pneumonia and meningitis, and historically caused about 370,000 child deaths every year in poor countries.

Geraldine takes us into Dr. Smith’s mind as he is being treated for cancer, when he thinks back on his life and the key moments of discovery and perseverance that resulted in the extraordinary Hib vaccine. 

About the phot0graph: GMB Akash shows how health workers go the distance ,to try and reach every Bangladeshi child. By boat on remote waterways and by foot through sandy pathways, Akash follows health workers as they bring vaccines to some of the most remote areas of Bangladesh. Akash spent many days in the field, lovingly capturing almost every aspect of the country’s successful vaccination program. In his photos, young mothers cross flood zones with their babies in their arms to reach the health clinic; an elderly man transports vaccines to a remote island by boat; and pregnant women receive antenatal care, including tetanus vaccine. He also captures young children ill in hospital with pneumonia, for which Bangladesh will soon introduce a vaccine.

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