Howard Lipton, MD, a researcher at Northwestern University in Illinois is attempting to transmit multiple sclerosis to nonhuman primates by taking cerebrospinal fluid and brain tissue from afflicted human patients and injecting it intracerebrally into chimpanzees and squirrel monkeys (1). Lipton has been awarded $411,975. His proposal indicates that the full cost of the research project will cost over $1.5 million before its completion in 2007.

This research will be conducted in collaboration with the New Iberia Research Center (NIRC) in Louisiana. Cerebrospinal fluid will be collected from human patients at Evanston Northwestern-Healthcare MS Outpatient Clinic in Illinois as part of a research protocol they have consented to take part in.

Use of infant chimpanzees

The project will use infant and baby chimpanzees, aged six months to one year. The research calls for three pairs, or a total of six chimpanzees. Although there is an official breeding moratorium on federally owned or supported chimpanzees since 1997, obtaining these young animals will not pose any problems, as described in the grant proposal:

NIRC has an established breeding program for 138 chimpanzees. There are currently 45 males and 93 females available and based on recent experience, six newborns should be ready for use on years 1-2 of the grant.

It is unclear how NIRC can promise new infant chimpanzees when there is an official breeding moratorium in place.

The justification for using infant chimpanzees and monkeys is that they are presumably more susceptible to infectious agents than older animals. The research proposal indicates that newborn chimpanzees would be most ideal; however, they would be less likely to withstand the rigorous procedure of intracerebral inoculation.

Frightening and painful

Under general anesthesia, the experiment calls for the chimpanzees and squirrel monkeys to be inoculated through the skull into the right frontal lobe of the brain with cerebrospinal fluid obtained from MS patients. Afterwards, they will be subjected to highly invasive tests every six months to observe for any signs of neurological disease.

The researchers will make use of cranial MRIs and cisternal taps, conducted under anesthesia, at six-month intervals.

A cisternal tap, or puncture, performed to extract cerebrospinal fluid for analysis, involves the insertion of a needle below the occipital bone (back of the skull). The needle is inserted close to the brain stem and is considered a dangerous procedure in humans (2). Yet Lipton’s grant proposal notes: “Cisternal punctures are easier, faster and safer to perform than lumbar punctures. Dr. Ratterree at Tulane Regional Primate Center routinely performs 20 to 30 cisternal taps on rhesus monkeys within several hours.”

For this study, the animals will be anesthetized prior to the cisternal tap (3). These procedures will also be performed on one other chimpanzee used as an experimental “control” (presumably also six months to one year old) for each year of the five year study.

Should any of the chimpanzees in the study develop neurological abnormalities, (including asymptomatic changes revealed by their cranial MRIs) they will then be subjected to open stereotaxic biopsy. All chimpanzees used in this study will remain in the nursery for two years and observed for the entire five years of the study for signs and symptoms of neurological disease.

From the abstract:

We propose to transmit MS to non-human primates by inoculating pairs of 0.5-1.0 year-old chimpanzees and squirrel monkeys intracerebrally (ic) with MS CSF mononuclear inflammatory cells (24 hr collection) and also with acute post-mortem plaques if optimum material becomes available. White matter lesions (serial cranial MRls), and CSF pleocytosis (serial cisternal taps) will detect subclinical disease in the animals. Stereotaxic biopsy will confirm the nature of developing lesions and enable serial brain-to-brain passage to demonstrate a replicating agent and its characterization.

It is not clear why Lipton believes he will be able to demonstrate an infectious agent is involved with multiple sclerosis when none has been demonstrated to date using chimpanzees and other animals. (4)

Last update: 1/3/06

Sources

(1) Information for this section was obtained from NIH Grant 5R01NS042890-03, received from NIH via FOIA, April 2005. “Identifying a viral cause of Multiple Sclerosis,” Northwestern University/Evanston Northwest Healthcare, IL. June 1, 2002 - May 31, 2007.

(2) Medline Plus, a service of the U.S.National Library of Medicine and NIH. Web retrieved on October 25, 2005 at http://www.nlm.nih.gov/medlineplus/ency/article/003428.htm

(3) NIH Grant 5R01NS042890-03, received from NIH via FOIA, April 2005. Page 27

(4) Information for this section was obtained from NIH Grant 5R01NS042890-03, received from NIH via FOIA, April 2005. “Identifying a viral cause of Multiple Sclerosis,” Northwestern University/Evanston Northwest Healthcare, IL. June 1, 2002 - May 31, 2007

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