Kyoto Univ. Ethics and Safety No. 55
February 8, 2019

Secretary General Katsuo Nishiyama
Association requesting Kyoto University to verify the doctorate degree granting of Manchuria 731 unit
military officer

Makoto Noda
Kyoto University Vice President (Research Ethics and Safety Promotion Officer)

Investigation results on misconduct in research activities in dissertation (Notification)

 

Regarding the above marking, regarding that is, the verification of the thesis requested by you, we will treat the request as a report on misconduct in research activities at the Liaison Campaign Promotion Headquarters Liaison Meeting on 18th September, we conducted a investigation. The preliminary investigation has been completed, so we will inform you of the results as follows.

 

If there is any objection to the contents of this notification, you can file a dispute through this administrative staff to this position within seven days from the date of receiving this notification.

 

 

 

Target article: Experimental study on "plague" vector ability of "Cainocephalus canis Curtis"

 

Result: Formal investigation is not conducted

 

Reason: Because the following results were obtained by the verification of "the impossibility to grasp the headache of the affected monkey” and “one of monkeys with plague (attached 10 Cainocephalus canis Curtis) continued over 39 for 5 days” that were addressed by you as the rational basis for research fraud,.

 

 

 

(1) About headache of the affected monkey

 

               It is not easy to appropriately scientifically evaluate whether monkeys who do not speak words feel headache. However, since the nerve conduction path that conveys pain sensation is well preserved from rodents to primates including humans, it is neurophysiologically reasonable to think that monkeys have a headache as well as humans. Meanwhile, even now the method of assessing headache in animal models is considered an important issue.

               Many animal model studies are conducted using rodents such as mice and rats. There, as "headache-like behavior", there are cases of hyperalgesia (reduction of the threshold value of defense reaction against contact with the affected part), decrease in activity amount, grooming behavior of the face by hindlimbs, facial expressions of the pain (exclusion of tests, inflation of nose ), Anxiety-like or grazing behaviors are mentioned (Refs 1 and 2). On the other hand, if limited to migraine, it is considered that in a wide range of cerebral cortex observed by electrophysiological electroencephalogram measurement in an animal model, cortical spreading depression (CSD) has been increasingly used as a more objective indicator. But the infectious headache was judged by the above observation of behavior and the alleviation of the behavior by the therapeutic agents because the physiological indicators could not be used. Although it is certainly not possible to find a literature describing a headache model targeting primates, method of determining the animal headache occurring by the observation of behavior, whether incomplete, are still used with a certain validity.

             Although it is not described in the experiment concerning the target dissertation at the time how the author judged the monkey's "headache”, it can be inferred that it was judged that a headache is occurring by some behavior index it can.

              Taken together, it is impossible to conclude that the target article is "not targeted to monkeys" based on the fact that monkey headache can not be evaluated.

(References)
1. Erdener SE et al. (2014) Modelling headache and migraine and its pharmacological manipulation. Br J Pharmacol. 171: 4575 · 4594
2. Chou T - M, Chenn S - P, (2018) Animal models of chronic migraine. Current Pain and Headache Reports, 22: 44.

 

(2) About the body temperature of monkeys

               About that despite the fact that the body temperature of monkeys varies from species to species and the fluctuation range in daytime is large, there is no taxonomic description of the monkeys used in the experiment in the target article and "one monkey (attached 10 Cainocephalus canis Curtis)  continued over 39 for 5 days”, investigating Tetsuo Tatsumi's dissertation "The Study on the Daily Variation of Physiology and Behavior Indicators and the Habitual Acclimation in Experimental Monkeys"(Degree Award Number: No. Z12200, Degree awarded date: March 15, 1995) on which the requesting person is based, it was the result of body temperature measurement in active situation about the daytime hyperthermia of the three kinds of monkeys freely active. The body temperature was measured intraperitoneally in Tsai and in subcutaneous tissues in the back of the neck in rhesus monkeys. The intraperitoneal body temperature was about 0.75 ℃ high in rhesus monkeys compared with subcutaneous body temperature demonstrated in a recent paper (Ref. 3),  in addition, Mr. Tatsumi also comments that there was a difference in body temperature due to the difference in measurement site in the thesis dissertation. Mr. Tatsumi further advanced the study on the body temperature of monkey and observed that the body temperature of 38 ℃ continued similarly when the rhesus monkey was held by the monkey chair during the day, but at the same time the heart rate raised, furthermore, fine body movements were sustained and furthermore, in the blood test, as the rise of creatine kinase, GOT, GPT, LDH were seen, he judged that the result observed showed the rhesus monkey was under the situation that it is held in considerable excitation / stress state. Mr. Tastumi further advanced the research and reported the observed results of various parameters including bodily temperature gradually stabilized by habituation when continuing the holding to the monkey chair. Specifically, if kept holding for 8 hours every day for 5 days, after 9 days of free activities, and repeating the 5 day holding, repeat holding keeps a stable body temperature of 37 ° C after repetitive holding. At the same time, heart rate and body movement also declined, stabilization of creatine kinase, GOT, GPT was obtained. To summarize the experimental results on monkey's body temperature in Mr. Tatsumi's thesis, the monkey's body temperature is low at night and has high circadian rhythm during the day, but the high body temperature during the day is dependent on the activity situation of the monkey. If you are quiet in the room, you can understand that it is a stable body temperature around 37 ℃ although it is higher than nighttime body temperature. On the other hand, with regard to the human body temperature, it varies from 36 to 37 ° C. As it is also in the quoted paper by Mr. Tatsumi (reference 4), the temperature difference between nighttime hypothermia and daytime high body temperature is 0.8 ° C. It has been reported that it has a circadian rhythm. To summarize the above, it can be said that humans and monkeys also have a circadian rhythm of body temperature, depending on the monkey's body temperature measurement condition, monkey's daytime body temperature fluctuation may be similar to human body temperature fluctuation.

              On the other hand, regarding the body temperature of the monkey in the environment of the infection experiment, for example, in the following reference paper 5, the average temperature is 36.5 ° C. (fluctuating at 35.3-37.7 ° C.) although there is a difference in day and night. It is stated that it increased to 38.9 ℃ when infected with HIV virus.

              Therefore, it can be said that body temperature can rise to 39 ° C or more by infection in monkeys, it is unknown what kind of method, when and how the body temperature was measured by the special experiment using the monkey, it can not be concluded that the experiment object (human monkey) is not a monkey as it is impossible to "keep body temperature above 39 ℃ over 5 days".

 (References)
3. Michael A. Taffe (2011). A Comparison of intraperitoneal and Subcutaneous Temperature in Freely Moving Rhesus Macaques. Physiology and Behavior 103 (5), pp. 440 · 444
4. Ashoff J and Wever R. (I 976). Human circadian rhythms: a multioscillatory system. Federation Proc. 35: 2326-2332.
5. Horn TFW et al. (1998) Early physiological abnormalities after simian immunodeficiency virus infection. Proc Natl Acad Sci USA, 95: 15072-15077.

(3) Conclusion

              Research activity misconduct in this case is "Is the monkey of the experimental animal used in the section “ The special experiment” in the thesis actually was not a human?".

              It is illegal to base the speculation on the environment in which the research was carried out in the examination of research fraud and it is necessary to prove that the research result obviously deviates from the rationality of science. Therefore, based on the above "3. Investigation Result", it can not be said that there is such a scientific rational reason that it can clearly deny that an animal used in "VII special experiment" in this thesis is a monkey and it can not be concluded that it is fake / tampering of the experiment report.

              Therefore, in addition to the absence of scientific rational reasons that require this investigation on the grounds of suspected fabrication in the request form, hearing with the author is also impossible, and it is impossible to scientifically verify the target dissertation. It is impossible to continue the investigation because there is no experiment notebook or raw data and we will not conduct this investigation. 

(Translated by the secretary general, Association requesting Kyoto University to verify the doctorate degree granting of Manchuria 731 unit military officer)