Research

Research

Transmissible Spongiform Encephalopathies (TSEs)

Infecting chimpanzees with this fatal class of diseases has no justification since their causes and progression are well documented in humans.

About TSEs

Transmissible spongiform encephalopathies (TSEs) are a class of fatal neurodegenerative diseases caused by an infectious agent which has to date been identified as an abnormal proteinaceous particle termed a “prion.” TSEs can be hereditary, occur spontaneously, or can be transmitted through direct inoculation of infectious tissue. (1)

TSEs have the characteristic symptoms of progressive neurodegeneration that include lack of muscular coordination, tremors, increasing mental confusion, and progressive muscular weakness that ultimately overcomes the entire body. The disease is always fatal, typically in a matter of months once the onset of symptoms appears. (2)

Although there is some variation in how the different TSEs manifest themselves, all result in symptoms of progressive neurological deterioration that is caused by the development of “spongy” holes in the brain, resulting in the characteristic spongiform appearance of brain tissue when examined upon autopsy.

Both human and animal victims

TSEs are observed in humans and animals. In humans, though rare, the disease appears in several forms that include: Creutzfeldt-Jakob disease (CJD), fatal familial insomnia, Gerstmann-Straussler-Scheinker (GSS) disease, variant Creutzfeldt-Jakob disease (vCJD), and kuru, a form of the disease once attributed to cannibalism and now unobserved. (3)

CJD, the most common form of human TSE, occurs in approximately only one person per million. Sporadic non-inherited CJD accounts for 85-90% of all cases. The hereditary form accounts for approximately 5-10% of cases. (4)

In 1996, a new category of CJD emerged in the U.K., termed variant CJD (vCJD), which has been linked to ingestion of beef from cattle afflicted with bovine spongiform encephalopathy (BSE). Since 1996 a small number of cases of vCJD have appeared in France, Italy, Canada, Ireland and the U.S. (5)

In animals, TSE manifests as scrapie in sheep, BSE (also known as mad cow disease), and chronic wasting disease of North American deer, elk and mink.

Use of chimpanzees in TSE research

In the 1960s, Carleton Gajdusek, an American doctor, injected three chimpanzees with brain tissue from victims who died of kuru. All three chimpanzees used in that first experiment became seriously ill and died from a kuru-like disease.

Gajdusek and Clarence Joseph Gibbs, a virologist, established the Laboratory of Slow, Latent and Temperate Virus Infections in 1961, an early division of NIH. Untold numbers of animals, including more than 1,000 nonhuman primates, many of which were chimpanzees, were infected with lethal TSEs such as CJD, GSS and scrapie. (6)

A timeline of sufferings

1961: Gibbs and Gajdusek establish the Laboratory of Slow, Latent and Temperate Virus Infections as part of NIH’s Laboratory of Central Nervous System Studies. (7)

1965: Gibbs and Gajdusek experimentally transmit kuru to chimpanzees (8)

1967: Gibbs and Gajdusek experimentally transmit CJD to a chimpanzee (9)

1981: Gibbs, Gajdusek and CL Masters publish that Gerstmann-Straussler-Scheinker (GSS) can be transmitted to chimpanzees (10)

1981: Gibbs, Gajdusek, and others demonstrate that TSEs are not maternally transmissible by administering several TSE agents (kuru, CJD, scrapie) to both monkeys and chimpanzees. 10 babies are born to affected mothers but none of them develop clinical disease. (11)

Infecting chimpanzees with TSEs continued as demonstrated by a 1994 experiment in which Gibbs and Gajdusek transmitted CJD to a chimpanzee from contaminated electrodes.

These same electrodes had caused two human patients to become ill with CJD after they were unintentionally infected during a neurosurgery procedure, even though the electrodes had been sterilized using conventional methods. The electrodes, it was later discovered, had been used two years earlier on a patient known to have died of CJD.

In the 1994 experiment on a chimpanzee, the same electrodes were sterilized again and implanted into the chimpanzee’s cortex. Eighteen months later the chimpanzee became ill with CJD. The redundancy of this experiment is readily apparent since it had already been demonstrated, albeit unintentionally, that standard methods of sterilization would not destroy the CJD agent of infection, even with the lapse of two years. (12)

What happens to chimpanzees when infected with TSEs

From what we know based on decades of TSE experiments on chimpanzees, their response is nearly identical to humans. Infected chimpanzees suffer from the full range of neurodegenerative symptoms that affect humans, including inevitable death.

Like humans, there is a significant incubation period, averaging two to three years, between infection and the manifestation of the disease. (13) The symptoms begin gradually with impaired coordination, slight confusion, behavioral changes, and weakness of extremities.

Once manifested, they progress rapidly and aggressively so that the victim suffers from involuntary movements, such as jerks and tremors, mental confusion, delirium, blindness, and paralysis. Death ensues in a few weeks to possibly a few months.

From a Freedom of Information Act (FOIA) request submitted by NEAVS for information on recent TSE research at the New Iberia Research Center in Louisiana, a protocol advises that the infected primates (chimpanzees included) should be monitored for signs of withdrawal, aggression, tremors, muscle spasms, muscular incoordination, limb neglect, disorientation, and paralysis.

The protocol also specifies feeding afflicted animals with a prepared liquid diet which they refer to as “Kuru Diet” made up of vanilla wafers, hot water, baby food, SMA infant formula, oral electrolyte solution, and when non-tube fed, monkey biscuits. (14)

A photo caption from an article about infected chimpanzees states:

The chimpanzee showed tremor, incoordination, myoclonic [spasmodic] jerking, fasciculation [twitching], right-sided neglect of limbs, and confusion (as manifested by inattention, listlessness, lethargy, and irritability). (15)

Overview of recent and current TSE research on chimpanzees

Due to difficulties with obtaining complete information about publicly funded animal research in the U.S., it is not possible to calculate the exact numbers of chimpanzees who have been infected with prion disease.

The 1997 report issued by NIH on chimpanzee use in research indicated that there are “57 known infectious exposures to kuru, Creutzfeldt-Jakob, and malaria.” (16) This does not specify, however, the numbers for each category of disease, or whether the categories overlap.

Information received by NEAVS through the Freedom of Information Act indicates that 57 chimpanzees were used for TSE research from 1998 to 2003 at New Iberia Research Center. (17) This number may or may not be in addition to the earlier number reported by NIH in 1997.

According to the experimental protocol received from FOIA requests, blood and blood products derived from human patients with spongiform encephalopathies will be tested in animals. Scientists will then examine what effect leucodepletion [removal of white blood cells] has on the ability of the infected blood and blood products to transmit infection.

As stated in the protocol: “This must first be done at New Iberia Research Center in chimpanzees using human leukocytes.” The protocol also states that they will test “susceptibility of chimpanzees fed head meat and brain/spinal cord from cattle with BSE.”

The above protocol is reflected by this grant for New Iberia Research Center: (18)

Researcher:

Thomas J. Rowell

Grant No.

3N01NS092302-003

Project:

Slow, Latent and Temperate Virus Infections

Institution:

New Iberia Research Center/University of Louisiana

Project runs:

October 31, 1998 - October 31, 2003

Funding:

$3,110,453 for the entire 5 years (19)

The abstract indicates that the goal of the study is to infect nonhuman primates with TSEs to provide a bank of infected tissue for study.

Up until shortly before his death in 2001, Clarence Gibbs was still infecting chimpanzees and other nonhuman primates with TSEs as indicated by this NIH grant. (20)

Researcher:

Clarence J. Gibbs

Grant No.

1Z01NS002950-04, -05

Project:

Transmissible Spongiform Encephalopathies

Institution:

NIH/National Institute of Neurological Disorders and Stroke

Project runs:

2000, 2001

Funding:

Unavailable

In a 1997 book on the history of spongiform encephalopathy research, author Richard Rhodes claims that Clarence Gibbs expressed dismay over using chimpanzees in TSE experiments and claimed he was unable to continue doing so. It is difficult to know what to make of his statement in light of this research protocol apparently under his direction in 2001.


Sources

(1) E-medicine: Prion Related Diseases. Web retrieved on October 7, 2005 at http://www.emedicine.com/neuro/topic662.htm

(2) Ibid.

(3) Ibid.

(4) World Health Organization (2002). Bovine spongiform encephalopathy. Fact Sheet No. 113; http://www.who.int/mediacentre/factsheets/fs113/en/

(5) Ibid.

(6) Brown P, Gibbs CJ Jr, et al. 1994 Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease. Ann Neurol. May;35(5):513-29.

(7) CJD Voice, “In Memory of Dr. Gibbs,” web retrieved on May 19, 2005 at http://members.aol.com/larmstr853/cjdvoice/drgibbs.htm

(8) Gajdusek DC, Gibbs CJ, Alpers M.1966 Experimental transmission of a Kuru-like syndrome to chimpanzees. Nature. Feb 19;209(25):794-6.

(9) Gibbs CJ Jr, Gajdusek DC, et al. 1968. Creutzfeldt-Jakob disease (spongiform encephalopathy): transmission to the chimpanzee. Science. 1968 Jul 26;161(839):388-9

(10) Masters CL, Gajdusek DC, Gibbs CJ 1981 Creutzfeldt-Jakob disease virus isolations from the Gerstmann-Straussler syndrome with an analysis of the various forms of amyloid plaque deposition in the virus-induced spongiform encephalopathies. Brain Sep;104(3):559-88.

(11) Amyx HL, Gibbs CJ Jr, Gajdusek DC, Greer WE. 1981 Absence of vertical transmission of subacute spongiform viral encephalopathies in experimental primates. Proc Soc Exp Biol Med. Apr;166(4):469-71.

(12) Gibbs CJ et al 1994. Transmission of Creutzfeldt-Jakob disease to a chimpanzee by electrodes contaminated during neurosurgery. J Neurol Neurosurg Psychiatry. 1994 Jun;57(6):757-8.

(13) Asher DM, Gibbs CJ Jr, Sulima MP, et al. 1993. Transmission of human spongiform encephalopathies to experimental animals: comparison of the chimpanzee and squirrel monkey. Dev Biol Stand. 80:9-13.

(14) NIH Grant N01-NS-9-2303, “Study of slow, latent and temperate virus infections of the nervous system caused by conventional and unconventional viruses,” University of Southwestern Louisiana, October 31, 1998 - October 31, 2003. Attachment IA, Statement of Work - LCNSS, pp. 6-8.

(15) Gibbs, C.J. and Asher D.M., “Subacute Spongiform Unconventional Virus Encephalopathies,” in Baron, S. (ed.) 1996. Medical Microbiology, The University of Texas Medical Branch at Galveston, 4th ed. Section 2: Virology. Web retrieved on May 17, 2005 at http://gsbs.utmb.edu/microbook/ch071.htm

(16) National Resource Council, Institute for Laboratory Animal Research, 1997 “Chimpanzees in Research: strategies for their ethical care, management, and use” National Academy Press. (Note b, Table 2.1)

(17) NIH Grant N01-NS-9-2303, Received from FOIA. “Study of slow, latent and temperate virus infections of the nervous system caused by conventional and unconventional viruses,” University of Southwestern Louisiana, October 31, 1998 - October 31, 2003.

(18) Computer Retrieval of Information on Scientific Projects. Online database at http://crisp.cit.nih.gov/

(19) NIH Grant N01-NS-9-2303, Received from FOIA. “Study of slow, latent and temperate virus infections of the nervous system caused by conventional and unconventional viruses,” University of Southwestern Louisiana, October 31, 1998 - October 31, 2003.

(20) Rhodes, Richard. Deadly Feasts: Tracking the Secrets of a Terrifying New Plague. Simon & Schuster, 1997. Rhodes, p 85.

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