Zweig Fund Celebrates Its Twentieth Year

For two decades, the Zweig Fund has made possible research to improve the health, welfare, and performance of racehorses.

In 1979, its first year, $220,000 was allocated for research on equine leukocyte (white blood cells) antigens, pneumonia, and enteritis in neonates and very young horses; respiratory illnesses at a specific track; the links between growth rate and performance in thoroughbreds; an improved equine influenza vaccine; selenium and vitamin E deficiency problems in horses; and equine reproduction.

We showed that the diaphragm is, indeed, an important and active muscle in exercise and that it probably does not normally fatigue despite the development of severe arterial hypoxemia and hypercapnia, says Ainsworth. Her diaphragm work has made it possible to evaluate diaphragm function in the horse for the first time and to study under what circumstances the diaphragm fatigues.

Now, 20 years, more than 200 research projects, and $7 million later, the Zweig Fund celebrates its twentieth anniversary with a long list of significant accomplishments.

"Zweig-funded research has generated considerable productivity in every domain of the major equine research fields," says Robert Gilbert BVSc, MMedVet, Dipl ACT, associate dean for clinical programs and professional service at Cornell.

"Zweig projects not only have contributed in significant ways to scientific progress but also have directly influenced practice in veterinary medicine and equine husbandry," he adds. "Moreover, Zweig research has triggered whole new lines of research activity funded under other sponsorships."

Here are just a few highlights.

Cardiopulmonary Research

Richard Hackett, center, assisted by Vincent Soderholm and Lisa Thorson, has designed special equipment to better understand the role of respiration in performance and disease.

Work on cardiopulmonary function has focused on better understanding how respiration limits athletic performance in horses-from evaluating diaphragm function and fatigue and the causes, effects, and treatment of lung edema (water in the lungs) to better understanding the causes of exercise-induced pulmonary hemorrhage (bleeding) and the basic mechanics of respiration.

Drs. Richard Hackett DVM, MS, Dipl ACVS, and Norm Ducharme DVM, MSc, Dipl ACVS, for example, have used Zweig funds over the past decade to look at the function of the larynx and palate during exercise to better understand diseases such as intermittent soft palate displacement and laryngeal hemiplegia (roaring), as well as other aspects of respiratory flow mechanisms. Using a face mask with an ultrasonic flowmeter in conjunction with the indoor treadmill, the researchers can take precise respiratory flow measurements during inspiration and expiration while horses are at rest and galloping high speed.

Hackett and Ducharme have developed a grading system for laryngeal function that is used to assess yearlings before sale, as well as to predict whether the horses are at risk of roaring once they begin strenuous work. It is also used by veterinarians to screen horses before laryngeal surgery, thereby often avoiding unnecessary "tie-back" surgery because of abnormalities that were evident at rest but were then shown to be insignificant during exercise. The system is now commonly used throughout the country.

Reproduction

Barry Ball's studies of sperm behavior during fertilization have resulted in more successful breeding practices.

Just as in humans, conception and pregnancy in horses are intricate and complicated processes. For years, equine reproductive specialists have pondered why some mares have difficulty getting pregnant or lose their fetuses and why some stallions are more fertile than others.

Zweig funding has been used for a host of studies related to reproduction, including projects on evaluating potential fertility of breeding stallions; the role of hormones in a mare's fertility cycle, in conception, and in early pregnancy; gamete (egg and sperm) physiology; changes that sperm undergo upon entering the female; factors contributing to foal loss; and embryonic development.

As a result, Cornell's equine reproductive specialists now have an enhanced understanding, for example, of how sperm survive in the mare's reproductive tract. Dr. Barry Ball DVM, PhD, determined how sperm first undergo critical changes after entering a female's oviduct and the vital role that calcium plays as a trigger for changing sperm as it prepares for fertilization. This knowledge has led to more rational management of breeding stallions, to the use of frozen or chilled semen, and to methods of artificial insemination with extremely low numbers of sperm.

Using a model he developed, Dr. Ball also uncovered how an embryo triggers essential biochemical signals and structural changes that allow the mare to recognize the pregnancy and produce hormones and other changes to support it.

Orthopedics

Alan Nixon is a pioneer in developing gene therapy approaches to repair damaged cartilage.

Like all athletes, racehorses suffer from a host of bone and joint problems. The Zweig Fund, therefore, has supported diverse projects that have looked at muscle morphology and rehabilitation, gait analysis, tests for diagnosing osteoarthritis, surgical procedures to repair bowed tendons, and ways to repair cartilage defects and prevent arthritis.

For almost a decade, for example, Dr. Alan Nixon BVSc, MS, Dipl ACVS, an equine orthopedist, has systematically worked out procedures to restore healthy cartilage that has been damaged by knee and fetlock chips, infection, ostreochondritis dissecans disease (OCD), or overuse. Specifically, he has developed methods to harvest immature cartilage cells (chondrocytes) from foals, culture them, stimulate them, and construct an implant that can resurface damaged joints and promote cartilage growth.

The implants have been so successful that they are now used on a regular basis to repair cartilage disease in the stifle, shoulder, fetlock, and knee of the horse. These techniques are now also being used in knee injuries in people, partly as a result of these Zweig studies, Nixon says.

Infectious and Genetic Disease

Dorothy Holmes, left, developed influenza vaccines that can be sprayed directly into a horse's nose. Here she and Cindy Lamb swab a horse's pharynx for virus samples.

Numerous diseases continue to plague horses, cutting their racing careers short and causing their owners serious economic losses. Zweig-funded research has supported work on developing or improving vaccines for equine influenza, strangles, and Lyme disease. Other projects sought to understand the causes and/or treatments for equine protozoal myeloencephalitis, equine degenerative myeloencephalitis, equine arteritis virus, Potomac Horse Fever, Equine Motor Neuron Disease, and Equine rhabdomyolysis-commonly known as tying up or Monday Morning Disease.

Dorothy Holmes DVM, PhD, for example, was funded for almost ten years during which time she successfully developed an equine influenza vaccine that was superior to those that were commercially available. Instead of being delivered by injection, Holmes' vaccine can be sprayed into a horse's nose. And it provides protection against the flu for at least ten months, much longer than other vaccines.

Holmes successfully developed two vaccines because horses are susceptible to two types of influenza viruses. Another outstanding advantage to Holmes' vaccines is that they cause no side effects. The older, injected vaccines often caused swelling, muscle soreness, appetite loss, and dullness. And since owners were encouraged to vaccinate their horses a week before a competition or other large gatherings of horses, many owners wouldn't use the vaccine for fear that their horse would be temporarily compromised. Unlike other vaccines, Holmes' vaccine is also temperature-sensitive, growing only in the cooler upper respiratory tracts, and therefore incapable of producing illness in the lungs.

Basic Research

Douglas Antczak oversees the development of linkage maps, Cornell's contribution to the international effort to map the horse genome.

Without basic research from which to build higher levels of knowledge, vaccines, implants, and higher pregnancy rates would not be possible. Recognizing the importance of basic research, the Zweig fund has supported a wide range of projects, including immunogenetic studies of the horse; investigations of basic nutritional questions regarding calcium, vitamin E, and the effects of carbohydrate diets; and efforts to better understand the gene map of horses.

Douglas Antczak VMD, PhD, director of the James A. Baker Institute for Animal Health, has used Zweig funds over the years to support Cornell's contribution to the mapping of genes in horses.

Although mapping the human genome is far ahead of comparable efforts in horses, the patterns of gene order on human chromosomes tend to be wonderfully close to those of the horse.

"That means that much of the progress that has been made in mapping human genes can be-and is being-applied to horses, allowing researchers to forge ahead at an unprecedented rate," Antczak explains.

Cornell's role in this international undertaking, supported in large part by Zweig Fund monies, is to contribute to the development of a linkage map for the horse. The linkage map pinpoints particular regions on a chromosome that carry genes for specific traits, such as running speed or susceptibility to disease.

Although the Horse Genome Project was launched just a few years ago, researchers already have developed genetic tests to identify severe combined immunodeficiency disease (SCID), hyperkalemic periodic paralysis (HYPP), and lethal white disease so breeders can prevent potentially troublesome stallion-mare pairings. Soon, scientists hope to be able to determine the genetic contributions to conditions such as heaves (chronic obstructive pulmonary disease) or wobbles (a defect in cervical vertebral formation); influence breeding programs; and aid in diagnosing, treating, and preventing a spectrum of genetically based diseases.