The Geography of Immunology

A Brief History of Bovine Immunology in Texas

by John S. Emrich and Charles Richter
March/April 2018, pages 62–65

Away from the large metropolitan areas of Texas, grazing herds of cattle have been such a fixture that their visage has been an emblem of the 28th state for the past century. Since the mid-19th century, cattle ranching has been more than a way of life; it is an economic engine, producing beef, milk, and leather. As the cattle industry has made up a significant segment of the state’s economy for a century and a half, Texas has also been a leader in bovine immunological research. With IMMUNOLOGY 2018™ in Austin, Texas, we take a look at this research through four important historical advances, beginning with “Texas fever,” a disease specific to the state that almost permanently ruined the industry, and concluding with a modern breakthrough in AIDS research using bovine models.

Texas cattle industry

In the 16th century, early Spanish explorers first brought cattle to the area that is now Texas. Some of the livestock that were meant to sustain both the expeditions and permanent missions escaped and formed the basis for enormous wild herds that became Texas Longhorns. Until 1780, the market for beef from Texas was very limited because of Spanish restrictions on trade with French colonies. The United States annexed Texas in 1845, but it was not until the end of the Civil War that the age of the great cattle drives began with the Chisholm Trail, leading to the markets in Kansas. That legendary era only lasted approximately 20 years until the proliferation of barbed wire and the expansion of the railroad made the drives difficult and unnecessary. Today, Texas still leads the nation in cattle production, with over 12 million head at the beginning of 2018.

Because cattle ranching has always been vulnerable to disease, the understanding of how to prevent and cure infections has saved the industry on multiple occasions. Veterinary researchers and immunologists have been instrumental in investigating the causes of cattle diseases and developing methods to combat them.

Theobald Smith and Texas fever (bovine babesiosis)

Before the Civil War, southern cattle were often considered “scrawny” or lean compared with those in the north. Once the cattle drives from Texas to the north began, the reason for this became clear, as northern cows started to fall ill after mingling with southern herds. Symptoms for affected cows included increased basal temperature, pulse, and respiration; loss of appetite; and in some cases, hemoglobinuria for a duration of eight to 10 days. Mortality rates for northern cattle were as high as 90%, giving rise to legitimate fear of what soon became known as Texas fever.

States quickly outlawed Texas cattle drives across their borders and instituted quarantines against the Texas herds, jeopardizing the entire industry if a solution could not be found.

Through years of observation, ranchers had long believed that ticks played an important role in the transmission of Texas fever. Their homegrown theory, however, was dismissed for decades by researchers at the U.S. Department of Agriculture (USDA) as lacking “the slightest foundation.” The first researcher to give the tick theory serious credence was Theobald Smith (AAI ’20), working on behalf of the USDA Bureau of Animal Industry. In 1889, Smith developed a simple experiment to test the tick vector theory of Texas fever transmission.

First, he set up pens with healthy northern cattle, introduced tick-laden southern cows, and observed the northern cattle for signs of illness. Within four months, three quarters of the northern cattle had died of Texas fever. Smith then painstakingly removed all of the ticks from the southern cows and moved them to a tick-free pen with fresh northern cattle, and again observed the northerners for signs of illness. This time they were all asymptomatic.

The ranchers’ theory was vindicated, and Smith had proven, for the first time, that ticks could act as a disease vector. Smith published his findings in 1893, and the same year, the Texas state legislature established the Livestock Sanitary Commission [renamed the Texas Animal Health Commission (TAHC) in 1959] to fight Texas fever.

Smith continued his work on Texas fever and, in experiments over the next four years, he isolated and identified the pathogen that the ticks were carrying. He named this protozoan Pyrosoma bigeminum, but the genus is now known as Babesia, and either Babesia bovis or Babesia bigemina can cause the disease. In addition, he identified mechanisms of immunity to the disease among northern and southern cattle populations. This research suggested that vaccines could be possible, but Smith also developed a practice that was immediately effective: dipping cattle in chemical baths containing an arsenical solution to kill any attached ticks. A cow with no ticks cannot transmit Texas fever to other cows. Because cattle fever ticks are host specific, simply removing cattle from an area will cause the ticks there to starve. This strategy, combined with federally mandated dipping, reduced the tick population enough that most cattle quarantines could be lifted by 1916. Although cattle fever ticks were considered eradicated in the United States by the 1960s, acaricide-resistant ticks from Mexico are currently re-emerging in South Texas.


Once Texas fever was under control, another persistent problem began to vex the cattle industry: bovine brucellosis—a highly contagious disease that can decimate a herd through spontaneous abortions and decreased milk production; cause weight loss, loss of young, and infertility; and spread lameness throughout American cattle herds. By the mid-1930s, it was estimated that the majority of herds had infection rates of 13–16%. In addition, humans can also contract brucellosis from infected cattle.

Called “undulant fever” in humans for the waves of temperature variation, cases of brucellosis in the United States went from only 46 in 1926 to 1,787 in 1934. People most often caught brucellosis by drinking raw milk, a problem that Karl F. Meyer (AAI ’22, president 1940–41) largely solved by 1931 by promoting diagnostic tests and pasteurization. In Texas, however, livestock workers were the primary victims through their close contact with infected cattle. Bovine brucellosis proved difficult to combat effectively: in the 1930s and 1940s, arsenical and mercurial drugs were tried, as well as therapeutic vaccines, but they produced very limited success. Dozens of articles on aspects of Brucella appeared in The Journal of Immunology at this time. Although Texas began a calf-vaccination program in 1959, compliance rates remained low as the vaccine sensitized the calves to the standard serum agglutination test. In 1980, the TAHC instituted new standards developed by the USDA, and just 10 years ago, Texas was finally declared free of bovine brucellosis.


The soil of the southwestern Texas plains is not fertile ground for many crops, but it does produce one unwanted harvest: anthrax spores. In the 1950s and ’60s, bone-meal production, a process in which bones of cattle that had died from anthrax were ground and spread in the low-acid soil of pastures as a feed component, unwittingly seeded the soil with the spores, creating a new and extended problem for the cattle industry.

Unlike the bacteria that cause Texas fever and brucellosis, Bacillus anthracis is a remarkably tenacious organism, able to survive for decades in spore form. Typically, the spores are buried at a safe depth, but a wet spring—followed by a dry summer—sets the stage for their emergence after the drought breaks. As there is no way to eradicate B. anthracis from the environment, the disease must be managed through vaccination or culling.

Robert Koch identified the bacterium in 1876, and Louis Pasteur subsequently developed an anthrax vaccine in 1881. In 1935, Max Sterne isolated an avirulent strain of B. anthracis and produced an effective, attenuated vaccine with it that is still in use today. Most cattle, however, will not be exposed to anthrax spores, so the culling of infected animals has been a more economical option. One of the first AAI members in Texas, Kenneth L. Burdon (AAI ’36), founding chair of microbiology at Baylor College of Medicine, spent much of his career researching spore-producing bacteria and developed methods of differentiating B. anthracis from other species in the genus. Accurate diagnosis in both human and cow from only clinical signs is very difficult, so Burdon’s criteria have been important in effectively identifying infection.

Human immunology and HIV

Texas cattle have recently proven to be allies in human immunology research, including the fight against HIV. In 2013, as part of a widespread team of researchers, Waithaka Mwangi (AAI ’02) and Michael Criscitiello (AAI ’01) at the Texas A&M University College of Veterinary Medicine & Biomedical Sciences, found that bovine antibodies possess unique structures of exceptionally long complementaritydetermining regions (CDRs) that form “stalk” and “knob” domains. The knob on the long CDR H3 turned out to be almost completely responsible for binding to viruses, leading researchers to wonder whether any of the structures they target exist on human pathogens.

They did not have to wonder long. A new study, also involving Mwangi and Criscitiello, has now elicited broadly neutralizing antibodies (bNAbs) in cows. These antibodies, which are capable of neutralizing multiple HIV strains, can be produced in cows much faster than is currently possible in human experimentation. The cows at A&M received immunizations with a protein that antigenically mimics the HIV envelope glycoprotein, rapidly eliciting broad and potent serum antibody responses. Ten to twenty percent of people with HIV also produce bNAbs, but typically only after two years of infection and not at a rate sufficient to produce therapeutics. The cow study showed 96% neutralization breadth in only 381 days.

Cows may have evolved the ability to produce bNAbs so quickly as a result of their complex digestive tracts: the resident bacteria necessary to break down tough grasses pose an infection risk if they escape the gut, so a versatile mechanism to produce antibodies would be beneficial to them. The antibodies that the cows produce have promise to work in humans—“with a few tweaks,” according to Criscitiello. This study may also have potential as a model for production of antibodies for other human diseases.

Although the cattle industry in Texas today is almost unrecognizable from its 19th-century roots, many of the challenges of keeping cows healthy remain the same. At many institutions across the state, immunologists continue to perform important research that expands knowledge of both bovine and human immunity.



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