Primal patients; With the help of almost 4,000 baboons, doctors in this research colony outside of San Antonio are discovering treatments for AIDS, hepatitis C and other threats facing man
Fort Worth Star Telegram
July 7, 2002, Sunday FINAL EDITION
Carolyn Poirot; Star-Telegram Staff Writer
Hilde half shuts her large, dark eyes and lies back on the exam table. She is totally relaxed for her annual physical, not even flinching when blood is drawn from her extended left leg for a complete blood count, serum cholesterol measurements and electrolyte tests.
A strong, healthy female who has participated in hepatitis and HIV studies, Hilde lives in the "infectious village" at the Southwest Foundation for Biomedical Research, southwest of San Antonio. She is chronically infected with the viruses, but they have never made her sick.
Hilde is, after all, a chimp - one of 235 chimps who, along with 3,700 baboons and several hundred other monkeys, rabbits and opossums make up the largest biomedical research colony of nonhuman primates in the world. By contrast, the world's second-largest colony has just 225 baboons.
The research animals, bred and raised at the foundation's on-site Southwest National Primate Research Center, are credited with helping to achieve medical breakthroughs ranging from the development of high-frequency ventilators now used in all neonatal intensive-care units to the hepatitis B vaccine. Baboons are being used in studies to find vaccines against both AIDS and hepatitis C.
The animals have helped scientists find the gene that causes hypercholesterolemia and three genes associated with obesity in adult humans, as well as genes associated with smoking and alcoholism, diabetes, high cholesterol and an increased risk of developing blood clots.
Researchers say their work would be impossible without these primates.
"During the 20th century, virtually every major advance in medical knowledge and treatment has involved research using animal models," says Dr. Robert Shade, scientific director of the Southwest Foundation. "There is no other way for us to study the impact of lifestyle changes on disease susceptibility, and we need animals to help us take advantage of the Human Genome Project."
Indeed, with the mapping of the human genome and the possibility of fighting and preventing human disease by targeting specific genes linked with these diseases, these primates are more important to medicine than ever.
Why? Because genetically, they're a lot like us.
Primates like us
Chimps share 99 percent of their DNA with humans; monkeys, about 94 percent, says John VandeBerg, Ph.D., director of the primate research center. (Chimps are not monkeys; monkeys have tails.)
"Humans and chimps are much more similar to each other than chimps and monkeys," VandeBerg says. "You are much more closely related to chimps than monkeys are, much more."
Nancy Martin, the staff technician helping give Hilde her recent physical, has known the chimp since she was born at the primate center, May 28, 1986.
"She was a nursery baby. I helped feed her and change her diaper and play with her when she was really little. She's very frisky and very social," Martin says, patting the large animal's arm.
"Animals act most normal with the person who feeds them," says Pat Frost, the veterinarian conducting the examination. "Sometimes the animals tell us who they prefer. Sometimes they huff and make raspberries with their lips. Often they offer their wrists if they want you to take care of them. We let them choose."
Frost looks down Hilde's throat, inspects her tonsils, palpates her abdomen to check her liver and appendix, records her blood pressure and takes her temperature - normal at 98 degrees. Hilde weighs a little more than 50 kilos - about 110 pounds.
Chimps are seven times as strong as humans and very, very quick. They are sedated with a Valium-like drug for examinations and any hands-on treatments, says Tom Butler, DVM, chairman of the Department of Laboratory Animal Medicine at the foundation. He heads a team of seven veterinarians who care for the chimps, monkeys and other animals.
Because these primates are much like us, genetically and physically, they are susceptible to many of the same infectious diseases and biological problems as humans. Working with these animals, scientists are able to investigate complex diseases including AIDS, hepatitis, heart and lung disease, hypertension, obesity, high cholesterol, endometriosis and infertility.
Although the chimps' genetic code most closely mirrors our own, the animals are no longer being bred for research anywhere in the world because they are not vital to any large-scale projects currently planned, and it costs an estimated quarter of a million dollars for a chimpanzee's lifetime care. The center was the last to breed them; it stopped about six years ago and now gives fertile females Norplant implants.
Scientists say that baboons and other monkeys make better animal models to test treatments and are much less expensive. In fact, much of the work at the primate research center depends on more than 2,100 rather exclusive baboons in a pedigreed colony. Their genetic traits and family histories are recorded for six generations.
Baboon beginnings
Founded 60 years ago by Texas oilman Tom Slick as an independent, nonprofit biomedical research institution, Southwest Foundation was established on a 5,000-acre ranch covered with mesquite. A serendipitous discovery in the spring of 1956 launched what would become the foundation's best-known work: establishing the importance of diet and heredity in the development of coronary artery disease.
A scientist from the foundation was at Louisiana State University's School of Medicine studying atherosclerosis with an LSU pathologist when a colleague sent them the aorta of a 16-year-old female baboon who had died of natural causes at New Orleans' Audubon Park zoo.
They found that the baboon's aorta closely resembled the human aorta - and, more important, the baboon had developed atherosclerotic lesions remarkably similar to those they had seen in autopsies on people who died of coronary artery disease.
They knew immediately that baboons could teach them a lot about the development of human heart disease.
Two years later, the National Institutes of Health awarded the Southwest Foundation a grant to establish a colony of baboons for medical research, and the Texas Heart Association awarded the institution $10,000 a year, for five years, to construct large outdoor pens where the baboons could live in colonies. The primate center was born.
Today the research center sits on 397 acres (much of the land was sold off to develop facilities) and has expanded to a collection of 34 buildings, including laboratories, offices, an animal hospital with a neonatal intensive-care unit, a library, five large outdoor cage units and two 6-acre corrals.
VandeBerg, a specialist in biochemical genetics, was the driving force behind efforts to make the regional primate center an NIH-sanctioned center. The designation came two years ago, making this just one of eight NIH centers in the nation.
Already, the NIH has provided for the development of new housing, with roomy activity centers to replace older facilities. The national designation is also expected to attract new grants and contracts with scientists from across the country.
Baboon babies, human babies
It's early afternoon in the baboon nursery, and the tiny babies are awake from their naps and playing in groups of six to eight. Their playroom is equipped with Little Tykes toys and lots of fingertip towels, which the babies carry around for security blankets.
Unexpectedly, a baby baboon, clutching its blanket, comes wobbling out of a playroom door left ajar for visitors to get a better view.
Cindy Jo Brenner, one of several caretakers, quickly but gently scoops up the baby in her arms, cuddling and stroking it as she carries it back to its basinette.
She secures a banana treat to feed the baboon and reassures it while she talks. The baby is not accustomed to strangers, she explains, and may feel a little insecure.
Babies in the nursery are hand-fed by bottle in the arms of caretakers until they can eat on their own and graduate to a cage of surrogate moms and aged nannies who care for the little ones until they are ready to move to regular group cages. About 30 live in the nursery at any given time. Some have been removed from abusive mothers, some rescued from aggressive females who take them from their mothers but have no milk to feed them, and some are participating in infant studies. From birth to old age, they provide data for researchers.
Baby baboons, born here almost every day, have a special place of honor because they are essential to one of the foundation's most compelling success stories: the development of treatments that help premature human babies breathe.
The No. 1 complication of premature birth, respiratory-distress syndrome, was most often fatal in very premature human babies until about 20 years ago, when researchers here, using premature baboons, developed two treatments: The first is a synthetic surfactant, a chemical that coats the inside of the lungs to prevent them from collapsing. The second is a positive-pressure, high-frequency ventilator. It delivers very small bursts of air at an extremely rapid rate to prevent the lung damage often caused by long-term use of standard hospital respirators.
Both treatments were tested extensively on baboons in cooperation with neonatologists at Wilford Hall Medical Center at Lackland Air Force Base in San Antonio.
"A lot of these advances began with the recognition that premature baboons are identical to premature human babies in preemie lung disease," VandeBerg says.
For Chloe Elizabeth Clifton, born three months premature and weighing well under 2 pounds, the two treatments were a lifesaver. She was given a 50-50 chance of survival when she was born Oct. 14, 1994, at Harris Methodist Fort Worth. She would have had almost no chance without the pulmonary surfactant she was given immediately and might well have suffered lifelong lung damage without a high-frequency ventilator.
Today, Chloe is a healthy, happy second-grader, who will be 8 in October and is most proud of her recent straight-A report card. "She has no health problems. There is no clue that she was so premature," says her father, Gary Clifton. "She's kinda tall and lanky, but then, so am I."
The Fort Worth family advocates the research done at the Southwest Foundation. "[At first], we had no idea where these treatments were developed," says Melissa Clifton, Chloe's mother. "It's nice to connect them with work right here in Texas. We are very happy to help put a human face on the technical, scientific research."
More recently, Southwest Foundation researchers have been testing a therapy on baboons that may prove even better for babies whose lungs have not yet fully developed. The treatment, known as nasal CPAP (continuous positive airway pressure) blows air into the nose at constant pressure but does not involve intubation or mechanical ventilation.
"You can start feeding them by mouth less than eight hours after birth, and it eliminates the need to wean them off a ventilator," says K. Dee Carey, DVM, Ph.D., chairman of the Department of Physiology and Medicine at the Southwest Foundation.
"If they do stop breathing, you can rescue them with the ventilator. We've been keeping data on this for about a year and a half, and you can see the difference. They just do better. They develop faster," Carey says.
Life in the colony
Linda Brent, Ph.D., is an animal anthropologist and is responsible for environmental enrichment at the Texas foundation. She chooses toys, exercise equipment and special treats that will stimulate the animals and keep them from getting bored. She also walks around with a modified laptop computer strapped over her shoulders and watches the baboons, carefully recording what they do.
Brent is completing the third year of a five-year mother-baby study to help determine the genetic factors involved in postpartum depression and the development of maternal anxiety disorders.
"I do mom-and-baby studies - what makes a good mom, what factors may contribute to abuse and neglect," Brent says. "What I do is watch the animals, observe and collect data before and after they give birth."
She has found that stress behaviors - scratching and fidgeting - often increase to four times the normal average just after giving birth. Some of the new mothers pull their hair out.
"We observe how they look and act, and measure hormones in their urine, so it is totally noninvasive," says Brent, who developed the computer program used to analyze the data she collects.
"Baboons are real similar to people in a lot of ways," she says. "They have the same complications with birth, such as breech births and gestational diabetes. Sometimes they require C-sections. They go through menopause."
Some of the moms are really protective, and some let their babies run wild. The protective ones have a built-in leash. They hold their babies by their tails. Some are so protective they never let go the first three or four months.
Brent's research helps determine whether a particular type of mothering may run in families and have genetic links.
"At our facility, more than 90 percent of the baboons are kept outside in large cages or corrals, where they form social groups, so we are able to do research and they are able to lead a good life," Brent says.
About 700 baboons are housed in each of two 6-acre corrals filled with what looks like heavy-duty gym equipment in the form of telephone poles, concrete culverts and 55-gallon drums.
The baboons roam freely, breed naturally and play - jumping, climbing, swinging and chasing after one another. The corral is enclosed by 10-feet-high, variegated-steel siding, angled inward to provide shade somewhere in the corral at all hours of the day. In winter, hay is brought in to give the animals a warm place to bed down.
"We have housed as many as possible outdoors in groups, and they get along well," says Butler, chairman of Laboratory Animal Medicine, as he and a visitor watch the animals from the roof of a large cage on one end of a corral.
"One thing that keeps a monkey happy is to have another monkey with it - that and food. They will eat anything," Butler says."Anytime you have 6,000 animals, some of them are going to get sick, and there will always be some bites and scratches that need medical care. Sometimes they just get rambunctious and run into things and scrape their knees and elbows. We see some trauma from fighting and some from playing."
Butler and his veterinary staff oversee care of the animals and support researchers in designing experiments so they get the data they need.
Care of the animals is guided by two principles: first, that animals deserve high-quality care and state-of-the-art preventive medicine; and second, that high-quality scientific data can be derived only from animals that are treated humanely and provided with proper care.
"We know we have an unusual colony here, so we open it to any scientist who wants to come here for legitimate medical research," Butler says.
Growing old together
The emphasis at the primate center is on minimal or noninvasive testing - blood and urine tests, needle biopsies, MRIs, CAT scans and spinal taps - to get the samples researchers need. Because of this and because most of the drugs tested here have already been tested for toxicity, 100 percent of the chimpanzees and 90 percent of the baboons here are living well into old age.
Chimps live up to 35 years in the wild, but they live 40 to 60 years at the primate center because of the health and dental care they receive. Baboons have an average life span of 25 years in captivity. No one is certain how long they live in the wild because they have not been studied extensively in the wild, Shade says.
Many of the chimps and baboons are living long enough to develop some of the natural diseases of aging, including prostate and breast cancer, endometriosis, osteoporosis, high blood pressure and obesity.
"Most of our animals eventually die of old age," says Michelle Leland, DVM, a staff veterinarian who provides animal care and does research in the Department of Physiology and Medicine. "As they get older, they are really valuable because they begin developing arthritis and osteoporosis. When they die of old age, we save samples of their brain for researchers studying Alzheimer's and Parkinson's."
Efforts are made to keep the animals as comfortable and healthy as possible. Darla was a 23-year-old female baboon with diabetes and a very bad back. An X-ray taken March 18 shows severe osteoporosis with numerous mini-fractures all along her spine.
"When this X-ray showed how horrible her back was, we put her in with an older group and gave her steroids for pain. Then we found out she was diabetic so we started giving her insulin injections twice a day for three weeks, but the steroids were interfering with her diabetes meds, and she stopped eating," Leland recalls.
Darla was put in an individual cage, and her diet was supplemented with her favorite fruits and vegetables, but she still wasn't eating. "She was insulin-resistant, hurting and wouldn't eat. We provided the best of care to the end, but finally she was starving herself," Leland says. The only caring thing left to do was to euthanize her.
Plans call for building a semi-retirement village for aging chimps on the San Antonio campus in the next couple of years, and construction will begin near Shreveport, La., this year on "Chimp Haven," a sanctuary to provide lifetime care for hundreds of chimps no longer needed for biomedical research, entertainment or pets.
A best-kept secret revealed
Although it is well-respected in scientific circles, the primate center and its baboon colony isn't known by most people in Texas, including visitors to SeaWorld, who pass right by the Southwest Foundation.
Why has it been such a well-kept secret, and why are scientists here finally opening their work to public scrutiny? Animal-rights activists are a big part of the answer to both questions.
In October 1984, when the Star-Telegram learned that the baboon heart that kept "Baby Fae" alive for almost three weeks at Loma Linda University Medical Center in California came from San Antonio, the paper sought interviews and pictures but was denied admission to the Southwest Foundation.
Scientists said they were unwilling to open their research to criticism and attacks from animal-rights activists and figured the less visible they were, the better. They were too busy with the science to do the public relations necessary to justify their work. However, scientists are now concerned that activists' endeavors have increased to the point that they are endangering future cures.
Without animal research, there would be no blood transfusions, painkillers, antibiotics, insulin, vaccines, coronary bypass surgery or organ transplants, says the foundation's scientific director, Shade. There would be no treatments or vaccines against anthrax, canine parvovirus, feline leukemia, rabies and more than 200 other diseases that threaten the lives of millions of dogs, cats and other pets, and farm animals.
"The public has a lot of misinformation about animal research, partly because scientists have been afraid to speak up and defend the importance of our work," says Shade, whose own research links salt sensitivity and high blood pressure.
"There is a general misconception that animal research is unnecessary, that medical science can be studied using computer models and other synthetic methods.
"The truth is, if animal research were discontinued, scientific progress in medicine would come to a halt" Shade says.