Wendy Baltzer

In 2008, Chewy (see Cut to the Bone) was one of almost 6,000 dogs and cats referred by veterinarians across the Pacific Northwest to OSU’s small-animal clinic and hospital, a leading institution not only in minimally invasive surgery but also in therapeutic laser research and treatments for cancer, cardiovascular disease and other illnesses.

After his surgery, Chewy participated in a double-blind study (meaning that nobody knows which patients are getting the therapy and which are getting a placebo) conducted by his surgeon Wendy Baltzer. She is administering low-level laser treatments to 12 subjects to test whether the technique speeds healing after surgery. Another recent study led her to invent a new method of Achilles tendon repair using a muscle flap as described in the March 2009 issue of Journal of Veterinary Surgery. And with a seed grant from the American Kennel Club Canine Health Foundation, she is currently looking into hormonal links to the growing incidence among dogs of cruciate ligament ruptures like the one that hobbled Chewy.

Baltzer’s career demonstrates the three-pronged mission of a land grant university. That’s because teaching, research and outreach are tightly bound into every aspect of her practice. It’s this tripartite opportunity — to mentor aspiring veterinarians, to investigate novel treatments and to heal cherished pets — that keeps Baltzer in academia when she could earn significantly more in private practice. She sums up her commitment this way: “You can’t help but love coming to work.”

Lucky recovered from cancer to qualify for national competition. (Photo: Rod Krahmer)

All three dogs came to Oregon State University’s animal hospital when they got sick. And all the dogs got well, thanks to powerful new tools and innovative treatments at OSU’s College of Veterinary Medicine.

Those new tools and treatments may someday lead to healing humans, too.

“There are ties between human and animal health, just as there is a bond between people and their pets,” says Dr. Stuart Helfand, a veterinarian at OSU.

Helfand is studying new ways to treat dogs who have cancer. In the operating room where OSU’s veterinarians perform surgery on dogs like Holly, Lucky and Mogli, the doctors often use a state-of-the-art operating microscope — a special instrument that magnifies body parts so they can see more clearly when they operate. To find the exact size and location of the cancer, they also use a high-speed CT scanner — a type of X-ray machine that takes 3-D pictures of bones and organs to detect injury or disease.

“We have the best CT scanner in veterinary medicine,” says Helfand. “It allows us to do things we never dreamed of.”

In the hallway outside the laboratory where Dr. Helfand does his research, there are snapshots of the dogs he has treated. Mogli looks like he’s winking, but he actually has just one eye. To help Mogli get well, the doctors had to remove his diseased eye. But this dog with the friendly face and glossy black coat doesn’t seem to mind too much. He still loves to chase squirrels and wag his tail. That’s why Dr. Helfand calls this display of snapshots the “Wall of Heroes.” These animals are heroes, he says, because they are bravely helping doctors learn more about healing sick pets — and sick people, too.

Illustration by Amy Charron

That’s why oncology research at Oregon State University’s College of Veterinary Medicine is attracting the attention of researchers at medical schools, including Oregon Health & Science University.

“Canine cancer often mimics human cancer,” says Stuart Helfand, who came to OSU in 2005 to begin the college’s oncology program. “But I’m a big believer in looking at cancer holistically; it’s not about humans on one side and dogs on another. It’s about studying and treating cancer. And there are ties between human and animal health, just as there is a bond between people and their pets.”

If OSU’s animal health clinic is the public face for the College of Veterinary Medicine, its research laboratories are the legs. Here is where Helfand and his colleagues study how cancer works in dogs and cats and what treatments may kill, or at least slow down, deadly cancer cells. Helfand’s interest in cancer research began in immunotherapy, which seeks to boost the immune system to fight cancer. Through this portal, his interests have expanded in a number of research directions.

Drs. Stuart Helfand, right, and Bernard Seguin are developing new cancer treatments in the OSU College of Veterinary Medicine. (Photo: Karl Maasdam)

“I was trained as a clinician but came to realize that there were many questions we could not answer in the clinic alone,” he says. “This attracted me to research in the laboratory with an eye toward learning things that could be brought back to our patients in the clinic, so-called translational research.”

A particularly aggressive form of cancer in dogs, known as hemangiosarcoma, drew Helfand’s attention because it has resisted attempts to find a cure. In cell cultures, it can be used to investigate angiogenesis, the process through which growing tumors develop a blood supply. Helfand is also studying proteins that act as chemical messengers, telling cells to reproduce and regulating other cellular activities. One type, an enzyme known as tyrosine kinase, serves as an “on” or “off” switch and also plays a role in human cancers.

“This field has expanded rapidly, and our laboratory is focused on learning how to exploit abnormal tyrosine kinases in several cancers that affect dogs and cats,” Helfand adds. “Through these efforts, we are hopeful we can improve care for animals while helping to establish these tumors as models for human cancer and contributing to improvements in human health.” Results from Helfand’s research have now begun to find their way into his clinical oncology practice.

Dogs are an attractive model for human cancers for two reasons: genetics and a shorter lifespan. People often live 75 years or more and may not develop cancer until late in life. Dogs, on the other hand, go through generations much more quickly and have distinct breeds with unique genetics, making them ideal for looking at the mechanisms leading to cancer. Why, for example, does bone cancer in humans affect teenagers at a disproportionate rate, and in dogs, primarily strike large breeds like Rottweilers, Saint Bernards, Irish wolfhounds and Great Danes?

A Surgeon’s Best Friend

Bernard Séguin, a small-animal surgeon with the college, discovered just how difficult it can be to have a pet stricken with cancer when his Rottweiler mix, George, developed bone cancer. He operated on the dog himself and helped extend his life several more months before the tumor made a fatal return. “Large-breed dogs are at great risk for bone cancers,” says Séguin, a native of Montreal who came to OSU from the University of California-Davis. “We aren’t quite sure why. Teenage humans also are at greater risk, and medical doctors want to know why. So we are working together.”

 

Saving Orion

Unlike humans, whose hair falls out during chemotherapy, dogs don’t lose their fur. I didn’t learn that when I was training to be an oncologist. I know it now because my dog has cancer.

Séguin is teaming with Dr. Charles Keller, an OHSU pediatric oncologist, on a joint study of bone cancer they hope will help both dogs and humans. And in the surgical suite, sometimes under extraordinary circumstances, Séguin is applying what Helfand and others are learning in the laboratory.

Last year, Holly, a greyhound, was referred to the OSU clinic with a tumor in her humerus bone. The tumor was in an unusual location, in the middle of the bone, rather than at the tip, which is much more common. The usual course of action for such tumors is to amputate the leg, because the surgery is so invasive and the tumor can spread. But as OSU researchers learn more about cancer, they are looking at other protocols.

In the first operation of its kind anywhere, Séguin and his colleagues removed the diaphysis, or the long shaft of the humerus, and replaced it with a section of Holly’s ulna, then performed microvascular surgery to connect tiny blood vessels, giving blood to the new bone structure instantaneously. “We are able to push the envelope here in part because we have the technological capability,” Séguin says. “We have the best CT scanner in veterinary medicine that allows us to do things we never dreamed of, and we have an operating microscope that few teaching hospitals have. We can match equipment with most vet colleges in the country.”

Regional Resource

Helfand has a vision of creating a regional cancer program at the college that would serve as a clinical resource for Northwest veterinarians, and that, as a leading research facility, would collaborate with medical researchers. What is missing, he says, is a building, endowed faculty positions and a linear accelerator for providing radiation treatment. Radiation therapy, he says, has both curative and palliative benefits for animals.

“When you remove a tumor surgically, the challenge is to get all the cancer tissue out,” Helfand says. “To be safe, you often remove some of the surrounding tissue. But soft tissue sarcomas frequently occur on the legs, where there isn’t a lot of soft tissue, which is why amputations frequently are the course of action. Radiation could help reduce amputations as well as reduce the animals’pain.

“It’s all about increasing the quality of life for the animals,” he adds.

When Helfand leaves the clinic floor en route to his research laboratory, he frequently walks by what he calls his “Wall of Heroes,” photos of animals treated for cancer at OSU. Most are dogs; some recovered from their disease, others did not. Each of them, he says, has a story.

“We had one dog, brought in by a gentleman who told us: ‘This is my son’s dog. My son just died, andthis is our last link to him. You must save him,’” Helfand explains. “That was emotional. In most cases, our lifespan exceeds that of our pets, and when you get a pet, you need to accept that you will experience heartbreak.

“Sometimes,” he adds, “it works out the other way.”

At the other end of the spectrum from heartache is hope, and the OSU oncology program is creating that for a growing number of visitors. Research advances, diagnostic and surgical skill and sophisticated technology are making the term “cancer” slightly less frightening.

Just ask Lucky. The 1-year-old golden retriever was training for hunting competitions when she developed a large aggressive tumor along her spine. It looked like her life would be cut short. In 2007, her owner, Rod Krahmer of Salem, brought Lucky to OSU where Helfand and Séguin collaborated on a treatment of chemotherapy and surgery.

“I am happy to report,” Krahmer wrote in a recent email to Helfand and Séguin, “that all is great four years post-op!!! There has been little effect from the surgery. She lost some range of motion when turning her head (neck) to the right, but compensates with no problems. Lucky has achieved her Master Hunter title and will be working towards an invitation to the Master National Hunt Test (the Super Bowl of retriever games) in Maryland this year!”

“That,” says Séguin, “is what we live for.

I know it now because my dog has cancer.

Despite being treated for cancer, 9-year-old Orion is still brimming with joyful, enthusiastic energy. "He's blissfully unaware of his diagnosis," says owner Dr. Jody Kujovich of Portland. (Photo courtesy of Jody Kujovich)

My 9-year-old golden retriever Orion, who is undergoing a pioneering cancer treatment at Oregon State University’s College of Veterinary Medicine, still wears his luxuriant fur coat of amber flecked with gray. His oncologist, Dr. Stuart Helfand, is designing a treatment unique to Orion’s particular cancer by growing the dog’s own cells in a laboratory and using them to test the effectiveness of various therapies. Orion may be the first canine with cancer ever to receive this type of “personalized medicine.”

“Mayo Clinic for Dogs”

Before he got sick, Orion often jogged with me. Several days after one of our regular runs, I found him collapsed on the living-room floor. We rushed him to our hometown vet, Dr. Robert Franklin. After hearing a muffled thumping through his stethoscope and then taking an ultrasound of Orion’s heart, Dr. Franklin told us that Orion had cardiac tamponade, a life-threatening accumulation of fluid inside the sac that encloses the heart. When fluid accumulates, the sac acts like a balloon. The pressure builds up, compressing the heart. Eventually, it can no longer pump blood, as in Orion’s case.

Dr. Franklin placed a needle into Orion’s chest and drained a liter of fluid, a risky but life-saving procedure. Orion’s heart resumed beating vigorously, and within minutes he was back on all fours, heading straight for the door.

Orion, it turned out, has hemangiosarcoma, a devastating cancer that arises from the lining of blood vessels. Because of their vascular location, the tumor cells are perfectly poised to spread easily and extensively throughout the body. Capricious tumor cells are swept into the bloodstream and carried to distant locations, in Orion’s case forming a large tumor inside his heart. His prognosis was particularly poor because of the size and location of the tumor, which would continue leaking fluid around his heart.

Orion (Photo courtesy of Jody Kujovich)

Knowing the cherished place Orion holds in our family, Dr. Franklin advised us to take him to OSU. In less than an hour, we had an appointment for the next day. Even with my connections as a physician, I would be hard-pressed to arrange appointments for an internist, cardiologist, oncologist, and surgeon along with a few diagnostic procedures, all in the space of a single afternoon on less than 24 hours’ notice.

My husband and I, along with our two children and our 12-year-old golden, Woof, accompanied Orion to the Lois Bates Acheson Veterinary Teaching Hospital. What we found was an unparalleled, state-of-the-art facility equipped with high-tech instruments and staffed by an impressive, multidisciplinary team of board-certified specialists. “OSU is like the Mayo Clinic for dogs,” I’ve been telling my friends ever since.

After examining Orion, OSU surgeon Dr. Milan Milovancev said, “I might be able to remove the tumor from his heart.” He described a high-risk procedure for a patient of any species. It would not cure Orion, but it would solve his most urgent problem. He might not survive the surgery, but without it, he would not survive at all. This was our reasoning as we made our heart-wrenching decision and departure from the hospital, leaving Orion behind looking at us with confused but trusting eyes.

Pate and Biscuits

The following morning, Dr. Milovancev skillfully and successfully removed the tumor from Orion’s heart. With a boost from a blood transfusion, Orion sailed through this remarkable surgery. Recognizing the importance of family, his doctors invited us to visit the next day. With unpleasant mental images of the intensive care units (ICUs) I’m all too familiar with, I was surprised when my daughter and I were ushered out to a lush lawn beside the hospital. A frail and surgically shaved Orion appeared, flanked by two of his doctors. He walked tentatively but with a definite tail wag when he saw us.

The four of us lounged in the grass, hand-feeding Orion doggy pate served up on his favorite biscuit as exotic aromas from the nearby large-animal facility wafted by. Dr. Krystal Claybrook, the oncology intern, described Orion as periodically restless and anxious in his ICU cage. “He calms down after I climb in with him and pet him for a while,” she added, as if this were a routine physician practice. Perhaps it is in this place where everyone emanates kindness. She reminds me of the power of personal touch, and I am grateful for her willingness to provide it to Orion. (It served, too, as a refresher course on bedside manner.)

“You can pick him up in the morning,” the student announced as we prepared to leave. I stared at her in disbelief. Could Orion really be discharged 48 hours after major heart surgery? “He’ll do better at home,” the student explained. And he did. Within a week, he was already eying the squirrels.

Smart Drugs

Despite the successful surgery, Orion’s squirrel-chasing days are limited. Hemangiosarcoma is a virtual death sentence for dogs, and Orion’s cancer has already spread. Surgery followed by chemotherapy can prolong life, but only by months. It is typically treated with doxorubicin, an old chemotherapy drug with no new tricks.

Enter Stuart Helfand, professor of veterinary oncology at OSU, who has devoted most of his professional life to fighting canine hemangiosarcoma. This man brings so much energy to the battle, you get the feeling he just might eventually win. Dr. Helfand has identified an Achilles heel of these cancer cells and is looking for a lethal therapeutic arrow.

Normal healthy cells contain intricate networks of tightly regulated pathways that carry the messages which control how fast cells grow and divide. The signaling pathways inside a single cell are more complex than a modern computer microprocessor integrated circuit. Tyrosine kinases are the gatekeepers that regulate the flow of signals and trigger activation of the cell. In cancer cells, this circuitry is “turned on” permanently, resulting in uncontrolled tumor growth and spreading.

Tyrosine kinase inhibitors, or “TKIs,” are a new class of “smart drugs” targeted at the cancer-causing defect. Like modern military weapons, they are designed with precision guidance. Because they are aimed directly at the deranged circuits, they kill cancer cells while sparing their healthy counterparts. In contrast to conventional chemotherapy, which kills all dividing cells indiscriminately, TKIs are selectively lethal with less collateral damage. The difference between drugs like doxorubicin and TKIs is like the difference between a carpet-bombing and a satellite guided missile that uses stealth to take out a target with surgical precision.

Bench to Bedside

Dr. Brian Druker, now director of the Knight Cancer Center at Oregon Health & Science University, developed the first TKI, imatinib (Gleevec). By targeting the defective tyrosine kinase driving the uncontrolled proliferation of leukemic cells, imatinib has revolutionized the treatment of chronic myelogenous leukemia (CML)

Fast-forward 10 years through the development of new and more potent TKIs. Dr. Helfand’s lab has shown that these drugs are active against canine hemangiosarcoma cells, which are also driven by malfunctioning tyrosine kinase-controlled circuitry. Several of these drugs are now available for veterinary use. Unfortunately, the most promising TKI, dasatinib, is not.

“I feel a moral obligation to try to do a better job for each new hemangiosarcoma patient I see,” Dr. Helfand says. As a test of his conviction, he proposes treating Orion with dasatinib, showering me with research data identifying this as the most effective TKI. The evidence is compelling, and he makes a strong case for translational research, the fashionable term used when research results are fast-tracked from the bench to the beside for use in patients. Dr. Helfand took a generous chunk of Orion’s tumor at the time of surgery and cultivated his tumor cells (now named “OR-HSA”) in his lab for further investigation. “Orion’s cells are now growing with unbounded fury,” he announces, information I digest with mixed emotions as I envision similar reckless behavior inside Orion’s body.

Over the next week, he tests Orion’s tumor cells against four different TKI’s and confirms they are exquisitely sensitive to dasatinib. Researchers call this individualized selection of therapy “personalized medicine,” and Orion may be the first canine patient to receive it. This novel strategy not only targets a drug selectively to the specific cancer-causing defect, but also delivers the right therapy to the right patient most likely to benefit.

However, there are a few practical considerations: Dasatinib has never been used as a treatment for dogs. Since it is approved for people, I could prescribe it, to the tune of about $6,000 for a one-month supply — a prohibitive cost for most families without pet insurance. There is also no published information defining a safe and effective canine dose. In Orion’s case, translational research and personalized medicine carry substantial risks.

Ironically, I was an oncology fellow working in Dr. Druker’s lab when imatinib was initially tested on animal and human tumor cells. It was exhilarating to watch this drug make the giant leap from the lab to the first clinical trial in patients with CML. I now find myself on the cutting edge of veterinary oncology asking Dr. Druker’s advice on a source and dose of an imatinib offspring. We call this a “curbside,” a term that probably has different connotations for Orion. It’s “doctor speak” for an informal consultation or picking of a colleague’s brain, in this case an internationally recognized expert who is willing to advise me about my dog.

Pills in Meatballs

Time is of the essence. Appeals to the manufacturer for “compassionate use” (free drugs) are fraught with bureaucratic delays, especially a request for a dog. Fortunately, Dr. Druker has other inspired ideas and over the next several days, his sympathetic colleagues uncover several sources of the drug. A few hours after Orion’s story is posted on a CML patient discussion website, a woman in Minnesota offers to donate a stash of unneeded drugs in her closet. She finds time to package them up between trips to another state where she is also in a clinical trial of a new TKI.  The next day a veterinarian in Florida offers to send her partner’s leftover drugs. A self-described stargazer who “just loves that big bright guy and his dog in the sky,” she finds cosmic satisfaction in donating drugs to his astronomical namesake. Meanwhile, my OHSU colleagues also find some local dasatinib leftovers to tide us over. A pharmacist friend cuts the pills into guesstimated doggy-size doses and hand-delivers them to an unsuspecting Orion. Within three days, I have drugs in hand and an ample supply on the way.

“I’m amazed how things are coming together for Orion,” remarks Dr. Helfand when I tell him about the bounty. Scrounging up free drugs was a coup, but giving them to Orion is another story.   “I have no idea what dose to give a canine patient,” he admits. Research dogs are often used to determine the doses that cause toxicity during drug development. Obtaining this information from the pharmaceutical company, however, is harder than procuring national security secrets from the CIA. As a clinical investigator, Dr. Druker has privileged access but discovers that dog data are disappointingly sparse.

Dr. Helfand opts for the low-dose conservative approach, “because we need to crawl before we can run.” In the end, giving him dasatinib is a leap of faith for all of us. Orion makes canine medical history as he unceremoniously wolfs down half of a donated pill in a Purina One meatball.

Determining an effective but tolerable dose remains a challenge. Doses and side effects are usually established by a series of clinical trials over several years, an investigational luxury not afforded many dogs. Despite his impressive research track record, Dr. Helfand will tell you his job “is always about quality of life,” and he means it. We exchange a flurry of emails and phone calls while we try a variety of remedies for the drug’s assault on Orion’s gut. He is on call for Orion 24/7, ready to discuss everything from the quality of his poop to the quantity of his pep. True to his word, he remains as committed to maintaining the quality of Orion’s life as he is to prolonging it. En route from Corvallis to the airport, Dr. Helfand cheerfully makes a detour from I-5 to hand off a bag of a new medicine to add to his anti-nausea arsenal. A compassionate doggy drug deal goes down in a Starbucks parking lot.

Chemo Cocktail

Orion also receives doxorubicin, a drug that is delivered directly into a vein. Dasatinib may weaken his tumor cells, making them more vulnerable to the next doxorubicin carpet bombing. Dr. Helfand’s work suggests this combination chemotherapy cocktail might achieve an overall greater tumor cell kill.

So once every three weeks Orion returns to the teaching hospital for an intravenous blast of old-fashioned chemotherapy. He snoozes during the drive, but wakes up when we exit from I-5, probably already smelling the alcohol-and-disinfectant odor of the hospital. He knows exactly where we’re going, yet trots willingly from the car toward the hospital. “Orion’s here!” calls out the receptionist before we’re even through the front door. In my hospital, hollering a cancer patient’s name in the front lobby would violate a multitude of HIPPA (Health Information & Privacy Protection Act) regulations. Here, it’s just plain friendly, and Orion’s tail wags with the rhythm of a metronome when he hears his name.

Now a seasoned patient, he’s a willing examinee for a team of students and vets at various levels, tolerating indignities as egregious as a rectal thermometer. He enjoys being hoisted up on the slippery stainless-steel examining table for an ultrasound about as much as I enjoy root canals. But he knows that no one can resist a golden and everyone treats him kindly. Goldens, if nothing else, are opportunists, and he enjoys the extra attention even more than the cookies.

So much to do, so little time. Even on chemo day, Orion is still the dog who thinks cats were created for the single purpose of high-speed chases. He races off in hot pursuit of the neighbor’s cat and returns looking triumphant, having re-established his rank and authority in the neighborhood.  This is “quality of life,” Orion style.

Medical Crosstalk

Dasatinib is not a magic bullet, but pioneering its use in a dog with hemangiosarcoma is a step forward in controlling this lethal cancer. Orion’s personal battle has sparked an innovative collaboration among researchers in veterinary and human medicine. A flask of his frozen tumor cells was shipped to the Druker lab early on in his course. Dr. Jeffrey Tyner, an investigator there, tested Orion’s cells against a large panel of TKIs still in early phases of research and development. Although these drugs are not realistic treatment options for Orion, they might be for a dog or person down the road.

Orion’s case illustrates the crosstalk between veterinary and human medicine and the physician-scientists who deliver it. He is the hub of a collaboration united around a crucial common goal: to win the battle against cancer by translating laboratory research into patient care. His crusade is also an unprecedented example of the blending of scientific investigation with unselfish acts of compassion from unexpected sources. The dedication of his oncologist and devoted long-time vet, ongoing support from his enlarging constellation of friends, and the love of his family articulate around him in a rich flow of energy as he takes tough medicine.

Of course, Orion is unaware of this behemoth effort on his behalf and his legacy already in place. His cells may be immortalized, even if he cannot be, perhaps providing the material for groundbreaking discoveries in cancer research. Trotting through the neighborhood still sporting his surgical buzz cut, he is a magnet for curious dog lovers. Orion has taught the neighborhood children that cancer is not contagious — and that you can fight it, live with it and joyfully chase tennis balls during the battle. He has taught my children how to give unconditional love as well as how to receive it, and reminded our family to adhere to Horace’s adage carpe diem.

We don’t know how long Orion will be with us, but he is now, and that is a gift beyond measure. So far, it has been an amazing run with an extraordinary dog.

Jody Kujovich is a hematologist/oncologist at Oregon Health & Science University. Her writing ranges from scholarly articles on her area of specialization, hemostasis (blood clotting), to lunchbox poetry for her children.

Update: On July 4, Orion died after his condition worsened over the weekend. “Even though you know this will come, it is still a shock to go through it. He was such a fighter,” Ken Strothcamp and Judy Kujovich said in an email to Terra.

nvestigating the link between human and animal health is a critical focus for Cyril Clarke, dean of OSU’s College of Veterinary Medicine, as he leads the college in a new era of veterinary research. (Photo: Karl Maasdam)

Veterinarians, as everyone knows, care for dogs, cats and livestock. Less well-known is their role in safeguarding human health.

“It’s important to point out the strengths and critical assets that veterinarians bring to public health,” observes Cyril Clarke, Lois Bates Acheson Dean of Veterinary Medicine.

Clarke ticks off the key intersections of animal-human health one by one. First, the vast majority of emerging infectious diseases worldwide — swine flu, avian flu, HIV-AIDs and Ebola, to name a few — have animal origins. Next, 80 percent of pathogens that pose a national-security threat — infectious agents like anthrax, for instance — are transferred to humans from animals. And food-borne illnesses such as salmonellosis and E-coli infection, which sicken thousands of Americans each year, typically are traced to livestock.

“Veterinarians really are the guardians of a safe food supply,” says Clarke, who grew up in South Africa and began eyeing a veterinary career during summers at his grandparents’ farm near Kruger National Park. “They are responsible for investigating the causes of diseases linked to contaminated foods and for maintaining a healthy food supply.”

Too, animal studies can reveal the causes of and cures for human illnesses. Researchers have developed well over 400 animal models of human disease, Clarke says. Studies with mice, for instance, have resulted in new understandings of tumor progression in lung cancer, as well as suggesting new diagnostic methods and therapies. Golden retrievers, which can carry spontaneous mutations in the dystrophin gene that causes a condition similar to Duchenne’s muscular dystrophy, have shed light on this lethal childhood disease.

Clarke’s own research program at Oklahoma State University, in fact, was funded in part by the National Institutes of Health and other agencies that support human health studies. That’s because his investigations of microbial pathogens in bovine respiratory disease — studies spurred by his initial professional interest in agriculture and livestock — illuminated principles of immune response and antimicrobial resistance that have applications in human health.

It is at this nexus of human-animal health where Clarke and his OSU colleagues in the human health sciences are laying the groundwork for a signature program that they hope will gain recognition nationally and internationally — what he calls an “area of critical mass and excellence.” Clarke is working closely with fellow deans Tammy Bray (College of Health and Human Sciences) and Wayne Kradjan (College of Pharmacy) to design a multidisciplinary research and graduate program that will blend together and build upon OSU’s strengths in the health sciences. Under the university’s realignment plan, the three colleges are being folded into an overarching Division of Health Sciences.

“As we look to the future, the College of Vet Med will have a much larger research program — one that is overlaid and undergirded by an inter-departmental, cross-disciplinary graduate program in comparative (cross-species) health sciences,” says Clarke. “We will also be enhancing our opportunities for outreach so that we can extend new knowledge to our stakeholders and constituents.”

To support the College of Veterinary Medicine at OSU, contact the Oregon State University Foundation.

In OSU's Lois Bates Acheson Veterinary Teaching Hospital, veterinary surgeon Wendy Baltzer repairs a ligament injury for an aging Chow mix using state-of-the-art arthroscopic instruments. (Photo: Jill Bartlett)

The surgical suite in OSU’s small animal clinic bristles with crisp efficiency. A masked med tech wearing scrubs of sea-foam green unpacks sterile instruments from stainless-steel carts, treading lightly on puffy blue booties. Above the operating table, a state-of-the-art Stryker scope hangs like a giant jointed bug with shiny hooded eyes. The scene suggests an episode of “ER” – until the patient is wheeled in.

Patient No. 504-775 is a medium-sized, black-and-white canine, flat on his back, a pincushion of IV needles and plastic tubes. His head hangs limply, ears in a reverse flop. Three legs splay wildly, the fourth shaved bare and suspended vertically. Chewy! My graying old Chow mix, his injured leg naked and pink, looks unbearably vulnerable. My heart constricts with love.

I’m sitting just outside the Chang Surgical Suite, nearly pressing my nose to the viewing window while the team expertly preps my dog for arthroscopic surgery. The lump in my throat doesn’t stop me from smiling at the incongruity of it all: The mongrel I rescued from the pound 13 years ago for $35 is undergoing a $3,000 treatment at the Lois Bates Acheson Veterinary Teaching Hospital, whose $300,000 scope would be the envy of many human hospitals. The sight of my overweight mutt sprouting IV tubes, his vital signs blipping across a video screen as a nurse swabs disinfectant on his leg, is both poignant and droll.

While Chewy’s pedigree is not pure, his zest for life is. Unbridled exuberance is often his undoing. He has been bested by a porcupine (100 quills in the snout), humiliated by a pair of Rottweilers (a nasty bite on the flank), and scolded by me (too many times to count) for gleefully chasing my cat whenever he thinks he can get away with it. In December, he tore his knee running after a deer on our wooded hillside, yelping and sinking to the ground in pain. In doing so, he joined the 1 million other American dogs that go under the scalpel each year with a rupture of the cranial cruciate ligament, a tough, fibrous tissue that holds the leg bones in place. The annual cost to pet owners: $1.3 billion, according to a 2005 article in the Journal of the American Veterinary Medical Association.

That’s where Wendy Baltzer comes in. As one of a handful of Oregon doctors specializing in canine knee repairs, the assistant professor in OSU’s College of Veterinary Medicine performs eight to 10 cruciate ligament surgeries a month. Sixty-pound Chewy, who was referred to OSU by his regular vet in Corvallis, is a mid-sized patient for Baltzer, who has operated on miniatures weighing barely 2 pounds all the way up to mastiffs and Great Pyrenees tipping the scale at 230. “No other species has such a wide size disparity as the dog,” she says. “But on the inside, they’re all the same.”

Seeing Within

Veterinary students Elizabeth James (left) from Roseburg, Oregon, and Sara Neilson of Salt Lake City, Utah, prep Chewy for his surgery. (Photo: Jill Bartlett)

Even to a casual observer, Baltzer’s command of the scene is clear. The 40-year-old surgeon, noticeably pregnant under her scrubs, strides into the operating theater with a calm certitude gained from 15 years of teaching, research and clinical practice, the past three at OSU. Growing up on a California ranch where animals were as integral to her world as oxygen, she also happened to live next-door to a veterinarian. Add to that her love of science, and a career caring for domestic species was almost preordained.

On this December morning as Chewy lies unconscious, she confers with her team (a resident, an intern, two fourth-year students, an anesthesiologist, a nurse anesthetist and a surgery technician) and then examines the instruments gleaming on a cloth of periwinkle blue: the to-be-expected needles, syringes and scalpels alongside more industrial-type tools – screws, hammers, chisels, drills. I try to push away the thought that they look uncomfortably like medieval torture devices.

Baltzer is about to perform a two-part procedure while the students observe and sometimes assist: arthroscopic removal of Chewy’s torn tissue followed by a “tibia plateau-leveling osteotomy” to alter the angle at which his two large leg bones – the tibia and femur – meet at the knee. (See illustrations in Terra UpClose sidebar)

This technique, invented by late Eugene veterinarian Barclay Slocum, makes the ropelike cruciate unnecessary. Trying to fix the ligament with tissue from a cadaver, as doctors typically do in humans, means months of downtime.

“It takes a year for them to recover,” Baltzer explains. “With humans, you can control their activity a lot more closely. But for 
my patients, I need something that’s a lot more stable much more quickly. With this technique, there’s much less chance of failure.”

As Chewy lies supine and inert, a breathing tube protruding between his teeth, Baltzer cuts two tiny incisions (she calls them “portals”) in his knee. Through one portal she inserts the scope – a fiberoptic camera about the size of a breath mint – which is linked to a television monitor. Through the other she guides a tiny instrument called a shaver. Then, watching the magnified image of Chewy’s torn tissue on the overhead screen – a glowing kaleidoscope in shades of scarlet, pink and magenta – she manipulates the tools with her small, gloved hands, adeptly cutting away the ragged remnants of the painful rupture that had forced Chewy to totter around on three legs. The shaver sucks up the frayed tissue as it cuts.

“Learning to triangulate – to figure out where you are inside the joint while watching the monitor – is kind of like playing video games,” says Baltzer, who teaches courses in principles of surgery, small-animal surgery and small-animal medicine. “It takes two or three years to master.”

Cadavers and Spleens

Chewy received a "tibia plateau-leveling osteotomy" after tearing his cruciate ligament. The technique changes the biomechanics of the animal's leg. (Photo: Jill Bartlett)

Baltzer honed the delicate art of arthroscopic surgery as a resident at Texas A&M University. “To be a surgeon, you have to be kinesthetic,” she says. “When I was a third-year vet student practicing surgery on a cadaver dog, I was the first person in the class to get the spleen out. I loved it! My professor came to me and said, ‘You should do surgery.’”

In those days, minimally invasive surgery was an emerging field. Not until last year did it become coursework required by the American College of Veterinary Surgeons.

The scope Baltzer is using on Chewy, which international medical equipment manufacturer Stryker provided to the teaching hospital for about half-price, makes OSU uniquely positioned in the state. “As far as I know,” Baltzer says, “we’re the only referral practice in Oregon that does arthroscopy on all knees. Because we’re a teaching institution, we try to do everything state-of-the-art. It’s more time-consuming than traditional surgery, and it’s less profitable because of the equipment cost. But research has shown that arthroscopy has a much quicker healing period. The patient is walking on the leg a lot sooner, and they’re much more comfortable postoperatively.”

After the damaged ligament and meniscus (a pillow-like disc that cushions the joint) are gone, Baltzer opens the leg for Step Two of the procedure. I had been lulled by the relatively bloodless arthroscopy, so I’m jolted by how fast the wads of gauze being packed around Chewy’s exposed bone are soaked in blood. I wince at the electric drill’s high-pitched whirrrrr as the doctor slices into the bone. Trying to quiet my nerves, I take note of Chewy’s chest rising and falling, rising and falling. I scrutinize the anesthesiologist, whose eyes are fixed on the rainbow of electronic signals flowing rhythmically across a computer screen to monitor blood pressure, heart rate and oxygen levels. Everything’s OK. I will myself to take a deep breath.

The last step before closing the incision is to affix a stainless steel plate over the cut bone. Drilling holes in bone isn’t all that different, Baltzer asserts, from drilling into wood for the carpentry projects she does at home with her husband, Craig Ruaux, an assistant professor in internal medicine at OSU. Using a depth gauge, she judges which size of surgical-grade screws are needed to secure Chewy’s new leg plate.

Tail End

Writer and dog owner Lee Sherman takes notes outside the Chang Surgical Suite as the surgical team removes Chewy's torn tissue arthroscopically. (Photo: Jill Bartlett)

When the last bit of hardware is in place, the surgeon catches my eye through the viewing window. “Wait there,” she mouths. A minute later, she rounds the corner and walks down the hall toward me, shaking loose her hair from the blue bonnet.

“It went great,” she assures me. “Now there’s nothing left but the suturing. Chewy will be fine – he just won’t be able to run around 
like a maniac.”

As she heads out to do rounds with students assigned to clinical rotation, I look back at the OR where the resident is closing the skin over the plate glinting in Chewy’s leg. The suite’s crisp sterility has been marred by wastebaskets overflowing with stained towels and bloody gauze. I think about how far Chewy’s leg has carried him, the hundreds of miles of beach sand, forest trail, park lawn and city sidewalk we’ve trekked together, his nose scenting the way.

With his meniscus gone he’ll get arthritis eventually, Baltzer says. And his days of table scraps are over: Per doctor’s orders, he’ll come home to a strict diet. Losing his excess weight will help prevent a rupture 
on his other knee.

This plain dog – who a friend once noted is “always smiling” – has been given another chance to romp and snuffle and snuggle and grin. As for me, I’ve been granted more time with the four-legged pal of unknown lineage who can melt my heart with a simple wag of his tail.

To support the OSU College of Veterinary Medicine, contact the OSU Foundation

As drug-resistant strains of TB spread around the world, Luiz Bermudez works urgently on new treatments. (Photo: Karl Maasdam)

M. tuberculosis is a tenacious germ.

Armored in a thick, waxy wall impervious to water, the bacterium can lie dormant in the lungs for decades, waiting for a weakness in its human host. When airborne on a cough or a laugh, it can infect a new victim in a simple breath of air. With a flip of a gene, it can dodge healing drugs by mobilizing legions of mutant clones.

Once considered a disease of the past (the last of Oregon’s sanitariums were closed in the 1970s), TB is making a comeback. Around the world, more than 8 million people are infected yearly, and 2 million die. Piggybacking on the epidemic of HIV/AIDS, the opportunistic TB pathogen is more dangerous than ever. Some 12,000 strains, each bearing a distinct “genetic fingerprint,” have turned up in hospitals, prisons, refugee camps and clinics.

In OSU’s biohazard lab, thousands of these strains are undergoing experiments that could give the world its first new TB therapy in four decades. Luiz Bermudez, M.D., is leading an investigation into the anti-TB properties of a drug commonly used to treat malaria. The two-year project is funded by a nearly $1 million grant from the Bill and Melinda Gates Foundation, a major partner in a worldwide race to defeat M. tuberculosis.

Some strains have developed fierce resistance to the powerful drugs rifampin and isoniazid, the “backbone of modern anti-TB chemotherapy,” explains Bermudez, a professor in the College of Veterinary Medicine. Until recently, scientists believed this potent cocktail had virtually wiped out the killer disease. But new drug-resistant strains have emerged. “Now it is very common for a healthy person to acquire drug-resistant bacteria directly,” Bermudez warns. “In terms of public health, that is a nightmare.”

The Centers for Disease Control (CDC) has designated some strains as “extensively drug resistant” (XDR) – that is, they survive just about anything doctors throw at them. In the U.S., 17 cases of XDR-TB have been reported.

With drug-resistant TB raging in hotspots such as Russia and Argentina, the Gates Foundation and others (including billionaire philanthropist George Soros, the World Health Organization and the World Bank) have mounted an aggressive 21st-century battle against the resurgent germ.

Of Germs and Genomes

Bermudez studies a family of infectious pathogens called mycobacteria, of which M. tuberculosis is one. Hansen’s disease, or leprosy, is another. A third is M. avium, which attacks humans whose defenses are compromised by conditions such as HIV-AIDS.

Bermudez and his colleagues – pharmacy professor Mark Zabriskie and several post-doctoral assistants – work with the rod-shaped microorganisms inside OSU’s Biosafety Level-3 laboratory. (Level 3 is designated by the CDC for airborne pathogens, including anthrax, West Nile virus, typhus and yellow fever.) The Gates-funded study focuses on Mefloquine, a drug that has proven extremely lethal to M. avium, both in test tubes and in animals. But there’s a downside: Mefloquine causes neurological side-effects – from depression to paranoia – in 15 percent of patients.

In a recent breakthrough, Bermudez was able to isolate the most active compound in Mefloquine. It turned out to have a dual benefit. “The compound that is most effective against mycobacteria is the least toxic of the compounds,” Bermudez says.

The agent has also proven effective against M. tuberculosis in test tubes. The researcher’s goal now is to pinpoint the “essential target” on the DNA of resistant TB mutants. That is, he’s looking for the key metabolic gene the germ needs to survive. Once he finds it, scientists can develop new drugs that attack TB in new ways. “Most antibiotics shut down bacteria by inhibiting protein synthesis,” Bermudez says. “For Mefloquine, we don’t yet know what the mechanism is. But it appears to do more than just inhibit the mycobacteria – it kills it.”

In a world where everyone is only a plane ride from everyone else and M. tuberculosis can be transmitted in a cough, a sneeze, even a hymn sung with gusto in church, the stakes couldn’t be higher.

By identifying how a deadly strain of bacteria causes Johne's disease in cattle, Luiz Bermudez and Marta Alonso-Hearn, hope to provide the basis for new treatments and shed light on human illness.

Little matters more to dairy farmers than the purity of their product and the health of their animals. So when Warren “Buzz” Gibson, co-owner and herd manager at the Lochmead Dairy in Junction City, Oregon, heard six years ago that an incurable cattle disease called Johne’s (pronounced “yo-knees”) could threaten his reputation for quality, he had all of his cows tested and continues to monitor annually, despite never having had a positive test.

Across the Oregon Coast Range at the Tillamook Creamery Association, Mark Wustenberg works with farmers to test for Johne’s and manage their herds to reduce other disease risks. “Our goal is to make sure this disease does not adversely affect our milk supply,” says the association’s vice president for dairy services.

Statewide, more than 50,000 cows in 200 of Oregon’s 350 herds are tested annually for the disease, according to the Oregon Department of Agriculture. Of herds tested in Oregon, Johne’s appears to be present in 60 to 70 percent at a low level (1 to 2 percent) of infection, says ODA field veterinarian Bruce Mueller. While other cattle diseases such as brucellosis have waned, the Johne’s threat has stimulated a national research and education campaign funded by the U.S. Department of Agriculture (USDA) at universities across the country, including OSU.

Gibson, Wustenberg and their peers have good reason to be vigilant. The cause of Johne’s — a bacterium known as Mycobacterium avium paratuberculosis (or MAP) — can survive for years in soil without losing its ability to infect. The organism lives in manure left by infected animals in pastures and barn stalls. When it reaches a newborn calf, it spreads slowly through the animal’s system with no apparent ill effects. But within two to five years, growing intestinal distress leads to diarrhea, weight loss and reduced milk production. By the time symptoms appear, death is imminent.

The MAP bacterium infects dairy herds worldwide and has been estimated to cost the U.S. industry $200 million annually in lost milk revenues alone. The financial impact soars to $1.5 billion when reduced milk production, decreased feed efficiency and expenses for replacement cattle are taken into account.

Moreover, a possible association between Johne’s in cattle and Crohn’s disease in people raises human health concerns. For now, studies to determine whether the same organism causes both diseases have reached differing conclusions. According to the Johne’s Information Center at the University of Wisconsin, no cases of Crohn’s have been linked to milk consumption.

Before he came to OSU in 2002, microbiologist Luiz Bermudez studied the Johne’s pathogen in wild and domesticated animals. Because of its importance to the animal agriculture industry, he now leads a research team that has discovered new details about how the organism goes about its dirty work in cattle. While a vaccine and other treatments can now reduce the severity of the disease, what Bermudez and his colleagues are learning could lead to more effective medications.

Understanding the tricks that MAP uses to evade an animal’s immune system could also improve treatment for other infectious diseases. That’s because as a class of microorganisms, Mycobacteria are responsible for scourges such as tuberculosis, leprosy, chronic lung problems and secondary infections in AIDS patients. Some Mycobacteria are common in soil and water. Others live harmlessly in humans until stress compromises our immune systems, giving the microbes an opening to multiply and cause further harm.

Most Deadly Infection

Conventional wisdom about Johne’s holds that transmission most commonly occurs through the consumption of manure-contaminated grass and hay. However, in 2006 Bermudez and his colleagues reported in the journal Infection and Immunity that it may be through another route — when a newborn calf first sucks at its mother’s udder — that the most deadly infection occurs. They compared the infectious ability of MAP cells grown in milk to those grown in a standard laboratory broth. The result: Those milk-raised cells were more than 10 times as effective in entering a model animal cell. “This is the most infectious form of the microorganism that the calf can get,” says Bermudez.

That report followed a series of papers describing the ability of Mycobacteria to invade host cells and to thrive inside those cells without being destroyed by the host’s immune system. Now, unconfirmed results of further research suggest that the OSU team has identified a mechanism that could prove to be the organism’s Achilles heel: the genes and proteins involved in binding the pathogen to a host cell and getting it inside the cell. Like a Trojan horse, once inside cell walls, MAP subverts the cell’s own machinery, eventually killing it and releasing a new wave of infection (see sidebar illustration). The new work was conducted by a team including lead author Marta Alonso-Hearn, Lia Danelishvili and Lisbeth Meunier-Goddick at OSU and Dilip Patel, a former OSU scientist now at the University of Tennessee, Knoxville.

“The bacteria are not supposed to get inside those cells,” says Bermudez. “For the first time, we have shown that the bacterium has a mechanism that interacts with the host cell and makes the host cell ingest it. This is a very sophisticated mechanism.”

Until a more effective vaccine or a less costly treatment is found, however, monitoring and prevention through good sanitary practices are still a farmer’s best protection, adds Bermudez. He serves on the scientific advisory board of a national research initiative known as the Joint Integrated Johne’s Disease Program at the University of Minnesota, a collaboration of 21 universities funded by the USDA.

For Buzz Gibson, testing for Johne’s amounts to good insurance. Annually, he insists that his veterinarian take blood and fecal samples from 35 to 40 cows and send them to the ODA Animal Health Lab in Salem for analysis. “I want to be ready. I don’t want to wake up one morning and see a headline linking Johne’s and Crohn’s,” he says.

The Lochmead dairy milks 580 Holsteins daily, supplying the company’s 44 Dari Mart stores from Cottage Grove to Corvallis. The herd is now one of four in Oregon — in addition to those owned by Dean and Patti Tohl in Tillamook, Jack Perrin in Woodburn and OSU in Corvallis — to receive the state’s highest level of certification for those that have tested negative for Johne’s.

A specialist in reproduction (the technical term is “theriogenology”), the OSU professor felt a kinship with animals as soon as he was old enough to explore the fields and woodlands around his suburban Pennsylvania home. The frogs, snakes and baby birds often tucked in little Chucky’s pockets earned him the nickname Nature Boy. “I never wanted to be a baseball player or a fireman or the president,” Estill says. “I never wanted to be anything but a vet. I didn’t have a Plan B.”

At Colorado State University, where he did his undergraduate work in zoology, his mentor and hero was Dr. Robert Pierson who, he says, was the “penultimate teacher.” Pierson let his young protégé ride along as he made his Saturday rounds to feedlots and dairies. “His truck,” Estill says, “was like a mobile classroom.”

Estill went on to earn his VMD at University of Pennsylania. (University of Pennsylvania awards the VMD, Veterinariae Medicinae Doctoris, while all other North American colleges of veterinary medicine award the DVM, Doctor of Veterinary Medicine.) Following an internship in food-animal medicine and surgery at the University of Georgia and 10 years in a private, mixed-animal practice in North Carolina, he received a Ph.D. at North Carolina State University and then joined the faculty at Mississippi State University. He came to OSU in 2002, where he teaches theriogenology, large-animal medicine, and animal handling and care, in addition to Rural Veterinary Practice I. He also oversees cattle reproductive medicine and nutrition for the university’s research herds, and conducts studies geared toward improving the health and fertility of livestock.

In the 30 years since earning the title of “doctor,” Estill has delivered hundreds of calves, most under emergency conditions. At large dairies, where three or four newborns come along every day, farmers are adept at routine deliveries. “I don’t get called,” he says, “unless there’s a problem.”

“My parents gave me my first cow when I was eight,” she says. Eventually, young Dana had a herd of 35 beef cattle, which she raised on the family farm in Klamath Falls. Tuition for her undergraduate education in animal science and agricultural business management was thereby assured.

But it wasn’t until she had spent seven years as a veterinary technician that Hoyt decided to return to school to earn her DVM. Now 34, she aspires to a practice in small-animal medicine, specializing in cancer care. It was her late Rottweiler, Astro, who spurred her interest in veterinary oncology. “He got lymphoma,” she says. “The chemotherapy he received extended his life by two years before we had to put him down.”

Hoyt — whose working style is a straight-ahead efficiency punctuated with well-timed wisecracks — softens visibly when she talks about her own menagerie: a cattle dog named Joe, a “mutt dog” named Greg, and a feline duo dubbed Billy and Dharma. The objectivity she brings to her work enters into her personal pet relationships not at all. In a burst of affectionate hyperbole, she insists: “Joe is the cutest dog in the world.”

The journey that brought 25-year-old Ueda to this farm in rural Oregon began 2,500 miles away on the island of Hawaii. She grew up in Waimea near the sprawling Parker Ranch, where 30,000 cattle graze across 175,000 sun-bathed acres. As a little girl, she often clambered onto the white wooden fences bordering the ranch to watch the veterinarians at work. “Ever since I was six or seven,” Ueda reports, “I’ve wanted to be a vet.”

She doesn’t envision a career wading through manure in drafty barns, however. She wants to work with laboratory animals in an academic research setting, probably a medical school, where she would monitor the health of such creatures as rats, mice, rabbits and monkeys and ensure proper treatment under federal regulations.

Even though her professional goal is a sterile workplace glinting with stainless steel, on this winter morning she gamely wraps a tool belt around her waist, loads it up with syringes and blood-collection tubes, and tramps through the dimly lit barn with her team. As she gives vaccinations, takes blood and milk samples, and treats abscesses, the cows’ steamy breath billows in the frigid air — which, at 35 degrees Fahrenheit, is a sharp reminder of how far from home Ueda has come.

Even with gee-whiz technologies like portable ultrasound, Estill says, “the arm is still the fastest and cheapest” way to gauge pregnancy in cows.

Crane’s ease and confidence as she tends the giant bovines belies her age of 27. That’s because she was born to the profession — literally. As she explains with a slight shrug, “It’s genetic.” She was still wearing preschool-sized Oshkosh overalls when she started accompanying her veterinarian father on his rounds on Prince Edward Island off the coast of Nova Scotia. One of her earliest memories is sitting on her dad’s medical case at age five, watching him treat a uterine prolapse. “It was very dramatic looking-like a big, pink balloon,” she says. “I remember my dad swearing for the first time.”

After completing her DVM at the University of Prince Edward Island’s Atlantic Veterinary College in 2002, she came to OSU for her two-year residency. Having done her master’s thesis on the topic, “ovarian cysts in dairy cows,” Crane is clearly headed down the path her father set her on, back when her rubber boots were many sizes smaller than they are today.

Down on the Farm

As OSU’s mobile veterinary clinic travels from farm to farm in Benton County, small-talk is all about large animals and their care. Professor Charles Estill, resident vet Bronwyn Crane, and fourth-year students Jaime Ueda and Dana Hoyt trade stories of midnight emergencies during on-call rotations — of a difficult birth that ended in euthanasia, of a horse struck by a car in the fog.

Read more…

Slideshow: Accompany veterinary medicine students on their rounds at the Van Beek Dairy.

Jaime Ueda braces herself against the 1,500-pound tranquillized cow as it shifts nervously from side to side. She hesitates, looking from the cantaloupe-sized swelling on the Holstein’s chest to the seven-inch knife she grips in her hand. “Are you kidding?” says the 4-foot-11, 100-pound veterinary student. “Ohmygod.” And then, taking a deep breath, she drives the knife into the abscess, sending a spray of white fluid across the hospital pen at the Van Beek Dairy.

“You did it!” Professor Charles Estill says, proudly. “You didn’t wimp out!”

Lancing abscesses is just one of the practical skills Estill passes on to the fourth-year students enrolled in Rural Veterinary Practice I, a required course in OSU’s College of Veterinary Medicine. Even students planning to practice on canaries or ferrets need experience working on farm animals, Estill says. That’s because biological agents such as anthrax and plague, and infectious diseases like avian flu and hog cholera, originate among livestock. A bioterrorist attack or a deadly pandemic would require veterinarians to step into the breach — to be, in Estill’s words, the “first line of defense.” In such a crisis, even a suburban cat-and-dog doctor could be recruited to work with infected herds or flocks. “Their license qualifies them to work on all species — every living, breathing thing on this planet, except people,” notes the 55-year-old specialist in bovine reproduction.

So on this chilly November morning Ueda, who aspires to a clean, white-coated career with lab animals, finds herself traveling the back roads of Benton County clad in canvas coveralls and rubber Muck boots. Unmindful of the passing landscape — of the leafless oaks etched in fog and the frost lingering beside the road — the 25-year-old from Oahu and fellow student Dana Hoyt, a 34-year-old Oregonian from Klamath Falls, chat about trans-tracheal washes and sheep scald, primary uterine inertia and dystocia as they ride along with Estill and resident vet Bronwyn Crane, 27, a native of Canada’s Prince Edward Island.

The “farm-visit” program, launched in 1981, serves a dozen commercial farms and hundreds of what Estill terms “backyard pets and hobby animals” such as llamas, alpacas, pigs and goats within a 30-mile radius of Corvallis. He and his students do pregnancy checks, disease surveillance and routine vaccinations for dairy cows, beef cattle and horses on a weekly or monthly basis. With referrals from local vets, they also handle emergencies and difficult cases throughout Oregon and, occasionally, in Washington and Northern California. The farm-visit teams conduct research, too, collecting specimens for studies on nutrition, reproduction and disease among the herds.

Today, their Ford F350XL mobile clinic — stocked with antibiotics and diagnostic compounds, syringes, blood-collection tubes capped in a rainbow of colors, portable ultrasound and X-ray machines, and boxes and boxes of latex gloves — stops first at the OSU Research Dairy. Over the past four decades, scientific breeding of dairy cows through genetic selection at OSU has doubled annual per-cow milk production, from 10,000 pounds in the 1960s to 20,000 pounds today. A healthy animal can pump out 100 pounds of milk every 24 hours.

In an industry that depends on slim profit margins for economic viability, any drop-off causes concern. So when one of OSU’s research cows suddenly started coming up short at milking time, Estill got a phone call.

The university’s high-tech milking barn hums with the rhythmic swish-swish of vacuum pumps as a New Zealander nicknamed “Kiwi” works a row of plump udders with practiced efficiency. The milk is measured as it streams through a jumble of transparent tubes, the quantity recorded instantly on electronic panels. The glowing numbers confirm the problem: The recalcitrant cow has given only 21.5 pounds so far that day — less than half that of her barn mates.

“Her name is No. 710,” Estill tells the students as he leads them to the “loafing barn” with the just-milked cow in tow. “OK, ladies, check her out. There’s room for lots of stethoscopes.”

The three women press their stainless-steel instruments against the Holstein’s white-and-black hide. Lifting her tail, they insert their digital thermometer and draw blood from her “tail vein.” After getting normal readings on heartbeat and body temperature, they perform “simultaneous percussion and auscultation” (thumping and listening) and “palpation” (feeling around inside the reproductive and intestinal tracts). No hint of disease. Tests for udder infection and ketosis again turn up nothing. Cow No. 710, they decide, is suffering from indigestion (no small problem for an animal that processes 50 pounds of feed a day).

“Lots of gas,” Crane concludes. Back at the lab, the blood sample shows low magnesium — a common finding associated with bowel trouble in cows. The Rx? Oral Epsom salts.

Not every vet-med mystery is so easily solved. Sometimes it takes extensive lab tests or even a full-blown study. In the winter of 2003-2004, many Willamette Valley dairies saw a decline in birth rates among their herds. After analyzing the animals’ feed — a mix that typically includes alfalfa, corn, grasses such as fescue and ryegrass, cottonseed and soybean meal, beet pulp, barley, canola and a “mineral pack” — Estill and fellow OSU researchers discovered an unknown compound, which they traced to mold. They’re now searching for ways to prevent harmful mold growth through silage inoculants, as well as proper harvesting and storage of hay and silage.

With support from the Agriculture Funding Consortium, Estill and a team of Canadian researchers are also investigating the effects on dairy-herd fertility of omega-3 fatty acids in flaxseed. He conducts field tests at the Van Beek Dairy in the hamlet of Bellfountain, where the mobile clinic travels every Monday. Today, the farm’s 1,350-head herd has Estill, Ueda, Hoyt and Crane up to their armpits in work. After vaccinating five-month-old calves for brucellosis, and then tagging and tattooing the animals’ ears to meet federal regulations, they each slip a shoulder-length Ag-Tek Poly-Sleeve onto their arm. Working methodically from barn to barn, they take turns reaching deep inside dozens of pregnant (or possibly pregnant) cows to gauge the growth of the fetuses. Standing on her toes, Ueda leans in and then calls out: “Oh! This is very cool! I can feel the tip of the fetus.” Estill tells her that sometimes, the unborn calf will suck on the examining vet’s finger.

At the end of the day, as they head for the muck hose and the warm truck, the team pauses beside a heifer in labor. Two tiny hooves have emerged, portending a new member of the Van Beek herd. When Estill talks about this part of his profession, he sheds some of the clinical matter-of-factness he typically exhibits. “Who could walk by an animal giving birth and not stop to watch?” he asks. “Who wouldn’t be awed by the wonder of the whole process?”

These students are enrolled in Rural Veterinary Practice I, required of all 80 OSU vet-med students — an enrollment that is currently 90 percent female. Hoyt is native to Oregon. The other two women are islanders, but their islands lie on opposite sides of the world — one in the balmy Pacific, the other in the Gulf of St. Lawrence off the chilly North Atlantic.

Here are their stories.

Born with a Stethoscope in Her Hand

Trading Muck Boots for a Clean, White Lab Coat

Going to College on the Black Angus Plan

Namesake for a Generation of Holsteins