Race for a Remedy
Retired from the track, thoroughbred First Flight served as a "factory" to produce botulism antitoxin
- By Carolyn H. Crowley
- Smithsonian magazine, December 2000, Subscribe
(Page 5 of 5)
By Carolyn H. Crowley
Among the more than 100,000 items in the Smithsonian's medical collections are a horse's halter and a vial of botulinum antitoxin derived from horse's blood. Botulinum toxin is the most powerful and deadly of all natural poisons — gram for gram more lethal than nerve agents.
The halter and vial of antitoxin came from First Flight, a 1,200-pound thoroughbred that holds a record of service to this country few humans or animals can rival.
After being injected by U.S. Army researchers with inactivated toxins to stimulate his immune system, First Flight became, in 1990, the world's only known source of antitoxin against all known types of the neurotoxin that causes botulism — a paralyzing, and potentially fatal, disease. For at least one young family, the existence of that antitoxin turned a terrifying ordeal into a story with a happy ending.
On December 29, 1997, Tracy Baird gave birth by cesarean section to a third daughter, Tessler. Three days later, Tracy and her husband, William, took their baby home.
Within 14 hours, Tessler had trouble breathing. "Panic was on her face," Tracy says. "I thought she was choking." The Bairds rushed Tessler to a nearby hospital.
"She was throwing herself up in the air, jerking her shoulders up to expand her lungs. I thought she was having a seizure," Tracy says. "But she was having trouble getting oxygen." Doctors placed her on a mechanical ventilator, and transferred her to Children's Hospital in Columbus, Ohio.
One hour later, her fingers barely stirred. "Her pupils weren't moving. She was paralyzed," Tracy remembers.
Initially, the doctors ruled out infant botulism as a diagnosis, because they knew of no cases in children less than a week old. The neurologist remarked that the child had the appearance of being brain dead, and warned the Bairds that if a brain scan confirmed that, they might want to consider taking her off the ventilator. But the test showed that Tessler was normal.
The doctors began to suspect infant botulism, and sent the Bairds to get a stool sample from Tessler's last diaper. The anxious parents and the doctors waited as the Ohio Department of Health examined the sample for toxins. Finally, after a few days had passed, word came back that Tessler, indeed, had infant botulism.
Infant botulism — unlike its adult counterparts — occurs when a baby ingests botulinum spores, as ubiquitous as the dust on which they may travel. Because of competing bacteria that mature humans usually have in their intestines, these bacterial spores are killed or pass through the system before they're able to produce toxin in adults. When adults get botulism, it is from a toxin created by bacteria outside the body, found in food, for instance, that is not cooked well enough to kill the bacteria, and then sealed, allowing these anaerobic microbes to create neurotoxin.
But infants can become ill by ingesting the spores themselves, which create toxin in the oxygen-free environment of the child's intestines. Botulinum bacterial spores travel widely, and can be found in a variety of sources, including foods such as honey.
Infant botulism is rare, but the mortality rate is high if severe cases are not diagnosed and treated quickly. It strikes as many as 100 babies a year in the United States, most younger than 6 months.
There have been more than 1,700 confirmed cases in nearly 50 states since its recognition as a distinct disease in 1976. Parents may notice infrequent bowel movements, listlessness, lethargy, poor feeding, and drooling from the mouth because of an inability to swallow, as babies, essentially, become "floppy." The progression of weakness eventually necessitates hospital admission. The toxin can cause paralysis and loss of muscle tone in the respiratory tract, resulting in asphyxiation and possibly death.
Before Tessler was definitively diagnosed, her doctors had contacted infant botulism experts at the California Department of Health Services who were developing a new human-derived botulinum antitoxin for infants. There are seven known types of botulinum toxin, types A through G, each of which must be treated with antitoxin derived from different antibodies. The California researchers' antitoxin was for types A and B, which accounted for all but three of more than 1,500 infant botulism cases reported to that point. But the toxin found in Tessler's sample, it turned out, was type F, a rare form. There was no suitable antitoxin available. None, that is, except for the antitoxin derived from First Flight's blood.
The Army had stored First Flight's antitoxin, the only one for all seven botulinum toxin types. But, up to then, only 59 adults — no children — had received the equine-derived botulinum antitoxin. So the Bairds now faced a dilemma: try the antitoxin on their daughter or wait the many months it would take, while she was on the ventilator, for the poison to work its way out of her body.
"A doctor suggested injecting me," Tracy Baird recalls. "He said if Mom has a reaction — she may stop breathing — the baby likely will too. Other doctors said the shot wouldn't help Tess because, at that point, she'd been sick for more than a week." The Bairds chose the antitoxin injections, with a fearful Tracy getting the first one, just enough to test for adverse reactions. Everyone waited an hour for reactions, but none came.
The Army's doses were for adults, and little Tess weighed only seven pounds. As Tracy was doing all right, doctors decided to administer almost one-half the adult dose intravenously to Tessler. Within four hours there was some movement in her hands and toes. Twelve hours after the first dose, she received a second one and gradually began to improve. Within a week, Tessler Baird was breathing on her own again, and was fully mobile. She spent three weeks recovering in the hospital.
Three years later, the only signs of her disease are scars on her chest from feeding tubes. "She's absolutely perfect," Tracy says and smiles. "A normal, ornery child."
"It's unbelievable to me that the Department of Defense — with its bombs, airplanes and guns — also manages these medical research and treatment programs," Tracy says. "Thankfully, we were able to use its treatment. The military saved my daughter's life."
The horse that helped save Tessler began his medical career in 1978 when he was 10 years old. Already retired from racing, First Flight had served as a ceremonial caisson horse for funeral and military processions at Arlington National Cemetery. But, skittish in crowds, he is said to have bolted with a general's coffin during a somber funeral. Needless to say, he was retired again. Soon thereafter, he was selected for a then-new botulinum antitoxin program.
"If a horse ever knew his value to the medical world, it was First Flight. He was a fractious, hot-blooded, pumped-up, macho horse," says George Lewis, who worked with First Flight for many years. Now retired, Lewis was a colonel in the U.S. Army Veterinary Corps when he worked with First Flight at the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) at Fort Detrick, Maryland. Its mission is to develop medical countermeasures — vaccines, drugs and diagnostics — to protect American military personnel from biological warfare agents and endemic infectious diseases.
First Flight was not vicious or dangerous but had a mind of his own, says Lt. Col. Terry Besch, another veterinarian who worked with the horse for years.
"Woe to the technician who didn't have a way with horses," she says. First Flight would "lightly nip. A loud 'Hey!' and quick snap on the lead line by an experienced person" and First Flight cooperated again. He then stood nicely to be groomed or have his blood withdrawn and "gratefully accepted a pat and a carrot, then he was off to the fields to boss around the other horses," Besch says. He was almost always the dominant horse in the pasture, "proud and full of himself as if he knew he had some importance."
Using delicate and dangerous techniques, a research team under Lewis' direction produced small quantities of each of the seven toxin types and slightly changed them so that they would not be toxic to First Flight. Instead they would cause him to respond by producing antibodies that would neutralize botulinum toxin. Lewis injected these new products, called toxoids, into First Flight. Then, once the horse had developed antibodies, the actual toxin — in carefully titrated amounts — would be injected to further boost antibody production. It was this procedure that frightened and worried Lewis: if he miscalculated, the injections could kill the horse.
Time after time, as he approached First Flight, syringe in hand, Lewis prayed, "God, I hope I got it all right."
"I was attached to the horse and the project, and to the importance of what we were doing," Lewis continues. "We'd double- and triple-checked everything, but still I had doubts, concerns and fears. I knew there were 10 to 100 times the amount of antibody in him than was needed to neutralize the toxin" that he was about to inject into First Flight. Still, he spent a number of uneasy nights sleeping in the barn with the big, dark bay gelding, checking him every few hours for signs of botulism poisoning.
First Flight wasn't always a compliant patient. Lewis remembers one crisp fall day in a big field at Fort Detrick. "With fire in his eyes, he almost killed me."
First Flight had had enough of the discomfort from people sticking needles into him. The horse tolerated injections and bleedings on a regular basis, without tranquilizers. But on this day, First Flight fought medical research. He swung around quickly as Lewis swabbed his hip for yet another injection and double-kicked his rear legs.
A hoof whisked by each of Lewis' ears. "I stepped back, let him — and me — calm down and then immunized him," Lewis remembers.
In 1980 First Flight was transferred to the University of Minnesota Medical School, which had developed the best technology in the country for processing equine immunoglobulin. Under contract to the Army, researchers there collected some 1,600 liters of blood from First Flight over the course of the next decade — storing the hyperimmune plasma and returning the red blood cells, in saline, to the horse's circulatory system. In 1990, as trouble escalated in the Persian Gulf, the Army asked the Minnesota researchers to use the stored plasma to produce large quantities of botulinum antitoxin. The serum from First Flight thus became the sole source of the "heptavalent" botulinum antitoxin shipped in 1991 to Saudi Arabia to treat soldiers and civilians, a precaution in case Iraqi President Saddam Hussein unleashed biological weapons during the Gulf War.
The United States suspected Iraq had a significant stockpile of biological weapons, which are almost impossible to detect during research and production. Biological warfare research facilities can be concealed in the guise of legitimate biotechnical or medical laboratories. In the end, it was found that Saddam Hussein had produced and stockpiled massive quantities of biological weapons — including botulinum toxin — but apparently did not use them. In case he had, First Flight's antibodies stood ready to help. And, in Tessler's case and others worldwide, they actually did.
First Flight died alone at age 31 of natural causes on May 17, 1999, in his paddock's long grass at Fort Detrick's Large Animal Research Facility. In "human years," he was over 90 years old. He was cremated and his ashes were buried at Fort Detrick near a small marker dedicated to his service to medical research.
By Carolyn H. Crowley
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