Correspondence

Creutzfeldt-Jakob Disease Infectivity of Growth Hormone Derived from Human Pituitary Glands

N Engl J Med 1993; 328:358-359February 4, 1993

Article

To the Editor:

As part of a comprehensive evaluation of the risk of Creutzfeldt-Jakob disease in recipients of native human growth hormone (GH), we inoculated nonhuman primates with samples of all 76 lots of GH retained on file at the National Hormone and Pituitary Program distribution center in September 19851. A total of 1 ml from each lot was inoculated by intracerebral, intravenous, and intramuscular routes into three squirrel monkeys, and 25 of the same lots were pooled in different combinations and inoculated into chimpanzees. The protocol called for these animals to be observed for a minimum of five years.

Recently, after an incubation period of more than 5.5 years, one of the three squirrel monkeys inoculated with a lot of GH distributed between 1965 and 1968 was found to have clinical signs of progressive neurologic disease, which was verified histologically as Creutzfeldt-Jakob disease; the remaining two animals inoculated with this lot remain well. Although several animals inoculated with other lots have died of intercurrent diseases, none had neurologic signs, and their brains were histologically normal and free of PrP amyloid (the protein that accumulates in the spongiform encephalopathies). All the animals inoculated with other lots of GH remain well at this time.

In spite of the fact that, so far, only a single animal has become ill after an unusually long incubation period, after intracerebral inoculation, it is highly unlikely that this transmission resulted from any source other than the inoculum itself. We have recorded several similar instances of long-delayed transmissions to only one of several animals inoculated with brain tissue from patients with spongiform encephalopathy. More important, during more than 30 years of transmission experiments in primates, we have not observed a single instance of spongiform encephalopathy in animals inoculated with tissues affected by dozens of different neurologic diseases and caged with animals that died of Creutzfeldt-Jakob disease or kuru.

This experimental transmission thus validates the presumption that Creutzfeldt-Jakob disease in recipients of GH2 was caused by the inclusion of infected glands in batches of cadaveric pituitary glands used for the extraction of GH. Whether such glands were obtained inadvertently from persons who died of Creutzfeldt-Jakob disease or unavoidably from persons who died of other diseases while silently incubating the agent of Creutzfeldt-Jakob disease will never be known. It is interesting that only one of the seven patients with Creutzfeldt-Jakob disease who received GH prepared and distributed under the National Hormone and Pituitary Program could have been exposed to this particular lot of GH; however, the experimental transmission of disease after a prolonged incubation period to only one of three animals inoculated with 1 of 76 lots accords perfectly with epidemiologic observations that imply a rare, random, and low level of contamination of the distributed lots3-5.

Clarence J. Gibbs, Jr., Ph.D.
David M. Asher, M.D.
Paul W. Brown, M.D.
Judith E. Fradkin, M.D.
D. Carleton Gajdusek, M.D.
National Institutes of Health, Bethesda, MD 20892

5 References

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   Brown P, Gajdusek DC, Gibbs CJ Jr, Asher DM. Potential epidemic of Creutzfeldt-Jakob disease from human growth hormone therapy. N Engl J Med 1985;313:728-731
   Full Text | Web of Science | Medline

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   Gibbs CJ Jr, Joy A, Heffner R, et al. Clinical and pathological features and laboratory confirmation of Creutzfeldt-Jakob disease in a recipient of pituitary-derived human growth hormone. N Engl J Med 1985;313:734-738
   Full Text | Web of Science | Medline

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   Brown P. Virus sterility for human growth hormone. Lancet 1985;2:729-730
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   Fradkin JE, Schonberger LB, Mills JL, et al. Creutzfeldt-Jakob disease in pituitary growth hormone recipients in the United States. JAMA 1991;265:880-884
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   Brown P, Preece MA, Will RG. “Friendly fire” in medicine: hormones, homografts, and Creutzfeldt-Jakob disease. Lancet 1992;340:24-27
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Citing Articles (4)

Citing Articles

1. 1

   Adriano Aguzzi. 2010. Prions of Humans and Animals. .
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2. 2

   D. M. Asher. (2008) Kuru: memories of the NIH years. Philosophical Transactions of the Royal Society B: Biological Sciences 363:1510, 3618-3625
   CrossRef

3. 3

   Jean-Philipe Deslys, Jacques Grassi, Emmanuel Comoy. 2003. .
   CrossRef

4. 4

   A. AGUZZI, C. WEISSMANN. (1998) Prion diseases. Haemophilia 4:4, 619-627
   CrossRef