The Antibody Initiative Responding to Rabies

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Vaccines and antibiotics have made the symptoms of many infectious diseases unfamiliar to Americans. That has not been the case for rabies. A viral disease that infects the nervous system, rabies is transmitted through saliva, as well as brain and nervous system tissue. Both the horrific symptoms of the disease, and its transmission via the bite of an infected animal, have rendered rabies a particularly feared and fabled disease.

At first, an infected victim might experience malaise and a slight tingling at the site of the bite wound. But, soon the virus infects the brain, eventually causing hallucinations, severe agitation, strange or violent behavior, and hydrophobia – the fear of and inability to drink water, coupled with extreme thirst. The manifestation of these later symptoms generally forecasts certain death, as it is then too late for successful treatment.

The museum’s collections contain objects illustrating the fear rabies has evoked. They also contain objects exemplifying the various attempts to cure or mitigate the disease prior to the discovery of antibody-based treatments and vaccines. For example, some believed that a madstone, a special rock or concretion, was able to draw out the “poison” of rabies if quickly pressed against a bite wound. Pharmacists also sold botanical extracts to treat rabies symptoms. The 1896 National Dispensatory advised using a tincture of Datura stramonium (sometimes called jimsonweed or devil’s trumpet) to treat the hydrophobia associated with rabies infection. None of these remedies could prevent death by rabies.

 

Madstone
apothecary bottle that once contained Datura stramonium

Two attempts at mitigating the suffering of rabies: on the left, a madstone; on the right, an apothecary bottle that once contained Datura stramonium

Working in France, Louis Pasteur and Emile Roux developed the first rabies vaccine in 1885. Soon thereafter, four New Jersey boys became national celebrities when they were sent to France and successfully treated for suspected rabies infection. Rabies, which had previously been a death sentence, was now potentially treatable.

Pasteur with the people he cured of rabies infection

Lantern slide from the New York City Health Department showing Pasteur "with a group of children he saved from rabies"

Since Pasteur’s pioneering work, the struggle to find a safe and effective vaccine against rabies has taken almost 100 years, and the search continues for a more practical and cheaper vaccine. Pasteur’s vaccine used dried nerve tissue from rabies-infected rabbits to trigger a patient’s own immune response. For the first time, victims had hope of survival. However, live or incompletely deactivated virus within the vaccine would sometimes actually cause rabies infection. Moreover, the source of the vaccine, nerve tissue, could trigger serious allergic reactions, including auto-immune encephalomyelitis.

The Semple method improved on Pasteur’s vaccine by using phenol to more reliably deactivate the virus in the vaccine, but the use of nerve tissue in the vaccine retained its inherently dangerous side effects. In 1958, Lilly introduced a vaccine that replaced nerve tissue with virus grown in duck embryos. The duck embryo vaccine was safer – but it was not as effective.

INSERT
a Lilly duck embryo vaccine from ca 1960

Two vaccines from the museum’s collection: on the left, a Semple Method vaccine from ca 1948; on the right, a Lilly duck embryo vaccine from ca 1960.

Currently, improved cell culture techniques have enabled the production of extremely safe and effective rabies vaccines. Unfortunately, the high cost of these newer vaccines has meant that some poorer countries continue to rely on the Semple method of rabies treatment. Thus, scientists are working to develop cheaper rabies vaccines. One approach uses recombinant technology to insert a benign rabies gene into the world’s oldest vaccine – the vaccinia virus – which was used to eradicate smallpox.

Despite the lifesaving potential of the rabies vaccine, the treatment is of no use if those who need it do not have access to it. The museum’s collections contain objects documenting early 20th-century efforts to bring the rabies vaccine to all citizens, even those living far from clinics. For example, the H. K. Mulford Rabies Vaccine Outfit was sold as a mail-order kit available to doctors throughout the country. The kit contained directions and equipment for administering the 21 day course of daily doses of vaccine. To ensure the freshness and effectiveness of the vaccine, only the first three doses were included in the kit; the remaining doses were supplied via five subsequent Special Delivery shipments. The lengthy vaccine treatment was not a pleasant process, but it was a far better option than facing death by rabies.

Mulford's Rabies Vaccine
Mulford's Rabies Vaccine

Mulford Rabies Vaccine Outfit, ca 1921

Advertisement for the Humane Coyote Getter

Original advertising and directions for the “Humane Coyote Getter” – a device for trappers.

In the U.S., wild animal populations, such as fox, bats, and raccoons, are the most common carriers of the rabies virus. Scientists and veterinarians have worked together to develop vaccines and vaccine-delivery methods for wild animal populations. The museum’s collections include examples of this innovative research.

During the 1960s, investigators at the Centers for Disease Control and Prevention (CDC) attempted to develop a device that would allow animals to “self-vaccinate.” The scientists modified earlier devices used by trappers and ranchers so that they would vaccinate, rather than kill, the foxes, coyotes, or raccoons that happened upon them.

One such early device was the “Humane Coyote Getter,” a spring-loaded tube gun weaponized with a shell of poisonous cyanide. Trappers set the device by partially burying it, then covering it with bait – a piece of scented wool. When a coyote bit at the wool, the device shot a stream of cyanide into the coyote’s mouth. CDC researchers sought to refashion the “Getter” into a more humane device: they rigged it with shells of an oral rabies vaccine, rather than cyanide. Unfortunately, testing showed that the altered device sometimes wounded the animal’s mouth. Further, the oral vaccine failed to create an acceptable level of immunity to rabies. Thus, both the vaccine and the device were deemed failures.

Coyote Getter
Cutaway Diagram of the Coyote Getter

Left: A Coyote Getter from the museum’s collection. This specimen was donated to the museum by a veterinarian who worked on the CDC project investigating devices for self-vaccination of wildlife. Right: a cut-away diagram of the Coyote Getter modified to shoot vaccine, courtesy of Scientific American, June 1992, Vol. 266, No.6.

Another device tested by the CDC was the Vac-Trap. Researchers started with a common trap design: animals would spring the trap by stepping on a metal pressure plate. They modified it so that animals stepping on the trigger plate would be jabbed with a syringe full of vaccine. During testing, the device proved far more viable than the Coyote Getter, as it did not harm the targeted animals, and it produced protective antibody levels in vaccinated animals. However, the device’s limitations proved insurmountable. It was expensive, the swinging vaccine syringe often missed its target, and – most worrisome – a Vac-Trap could be activated by and inject any animal that stepped on its trigger plate, including a human.

Both the Humane Coyote Getter and the Vac-Trap illustrate that the struggle against rabies has been two-fold: first, to devise safe and effective vaccines and therapies; secondly, to develop effective methods to deliver those vaccines to vulnerable populations, whether human or animal.

A Vac-Trap from the museum’s collection
An illustration of the Vac-Trap in action, courtesy of Scientific American, June 1992, Vol. 266, No.6.

Left: A Vac-Trap from the museum’s collection. Right: An illustration of the Vac-Trap in action, courtesy of Scientific American, June 1992, Vol. 266, No.6.

The virus that causes rabies can be spread simply by handling an infected animal, even without a bite occurring. Thus, even though rabies is far more common among wild animals, the disease is most often transmitted to humans via domesticated animals, usually dogs and cats. The museum’s collection of anti-rabies treatments is a testament to this close relationship between humans, dogs and cats, and rabies. The collection is rich in vaccines for veterinary use, some suitable only for cats or only for dogs. A metal tag, proof that a pet’s rabies vaccination was completed and registered, is sometimes included in the package along with each dose of the vaccine.

Rabies Vaccine and Tag
Rabies Vaccine

Rabies Vaccines

Efforts to stem human cases of rabies have been very successful in the United States, due to the combined effectiveness of the rabies vaccine and of regulations requiring pet vaccination. Despite this success, the CDC reports that each year 40,000 people in the U.S. must be treated for possible rabies infection because they were bitten by animals with unknown vaccination status. Treatments for rabies must be administered before or very soon after infection. Once the major symptoms of rabies begin, even current treatments have almost no hope of saving a victim’s life.

Despite the reliability of the vaccine, rabies is still a very real threat in some areas of the world. According to the CDC, every year more than 50,000 people die from rabies because they lack access to vaccines and because animal populations in urban areas are not routinely vaccinated.