诺贝尔医学奖论文剖析课件

Gajdusek获诺贝尔奖的研究思路 郭 雄 教授 西安交通大学医学院公共卫生系,诺贝尔奖论文剖析,The Nobel Prize in Physiology or Medicine 1976 for their discoveries concerning new mechanisms for the origin and dissemination of infectious diseases,Baruch S. Blumberg,D. Carleton Gajdusek,Daniel Carleton Gajdusek,1997,/wiki/List_of_Nobel_laureates,Daniel Carleton Gajdusek an American physician and medical researcher who was the co-recipient (with Baruch S. Blumberg) of the Nobel Prize in Physiology or Medicine in 1976 for work on Kuru, the first human prion disease demonstrated to be infectious.,/wiki/List_of_Nobel_laureates,Gajdusek had suggested the existence of “slow viruses,“ novel viruses that seemed to remain dormant for long periods of time before attacking the body. The concept of slow viruses emerged from Gajduseks studies of Kuru, a degenerative brain disease found among the Fore people of Papua New Guinea. The slow viruses were eventually implicated as the causative agents of other diseases, including Creutzfeldt-Jakob disease and mad-cow disease.,克雅氏病和疯牛病的 病原体,研究巴布亚新几内亚的一种 脑部退化疾病-库鲁病,慢病毒,侵袭机体,一个较长的不发病潜伏期,诺贝尔奖论文,非常规型病毒（朊病毒）与库鲁病的起源与消除,1.致亚急性海绵状脑病的非常规型病毒,2.常规型病毒通过缺陷性或非缺陷性复制引起慢性疾病,0.前言：研究背景-库鲁病-慢病毒感染-与人和动物,3.库鲁病,4.传染性海绵状脑病（克-雅病，皮质-纹状体-脊髓变性）,5.绵羊瘙痒病,6.亚急性海绵状脑病自然史推测：自然绵羊瘙痒病是克- 雅病，库鲁病和貂传染性脑病的假设起源,7.展望,诺贝尔奖论文,Daniel Carlton Gajdusek 丹尼尔卡里顿盖达塞克 1923 出生New York 1955 参与Kuru研究工作(33岁) 1976 获诺贝尔医学奖(53岁) for work on Kuru, the first human Prion disease Stanley B. Prusiner 1997年获诺贝尔医学奖主(55岁) 1942 美国中西部出生 1972 神经科住院医师 (30岁) 1982年发表于Science的论文 引起羊搔症的传染性新蛋白质粒子 Prion：一种不含核酸的传染性蛋白质或 少量核酸外围包有紧密的蛋白质外壳,目 录,一、研究背景与科学难点 二、论文研究思路的剖析 三、对科学研究工作的启示, 主要科学问题,新几内亚发生的一种严重危害人群健康的、呈地方性分布的疾病,病因？,发病机制？,有效控制措施？,？病,策略1？,策略2 ？,策略3 ？,-问题树-策略树,海绵状脑病( transmissible spongiform encephalopathies, TSE) , 是一组由传染性朊蛋白侵袭人类及多种动物中枢神经系统所致的致死性退行性脑病, 以病变区域广泛神经元缺失和神经胶质增生伴有明显空泡形成海绵状态为特征, 又称朊蛋白病。,概念 -朊蛋白病 （Prion diseases）,JOHNSON R T. Prion diseases . Lancet Neurol, 2005, 4 (10) : 635-642,海绵状脑病,Human diseases: 1. Kuru病或库鲁病 2. 克-雅病 (CJD) 3. Gerstmann Strussler 综合征 4. 致死性家族失眠症,Animal diseases: 1. 羊瘙痒病 2. 牛海绵脑病（疯牛病） 3. 大耳鹿慢性消耗病 4. 传染性雪貂白质脑病,Central Nervous System Failure,Long Incubation Period,No Cure,Death,海绵状脑病的特征,人类可传播性海绵样脑病,疾病名称 第一次报告时间 证明可传播时间 克-雅氏病（Creutzfeldt-Jakob病） 散发型 1921 1968 家族型 1924 变异型 1996 库鲁病（Kuru） 1955 1966 Gerstmann Strussler 综合征 1936 1981 致死性家族性失眠症 1986 1995,Kuru is a rare and fatal brain disorder that occurred at epidemic levels during the 1950s-60s among the Fore people in the highlands of New Guinea.,Kuru region in New Guinea,A map of Kuru prevalence in early fifties. Courtesy of Dr. D.C.Gajdusek, Paris, France,地方性分布,库鲁病（Kuru病,“Kuru”在该部落意 为“恐惧”或“寒颤”，故称该病为 库鲁病； 地方性分布，主要在发生New Guinea 的Fore部落区； 患者总数约3万；1957-1961年发生 1000例，以女性和未成年儿童居多； 成年男性为2% 死亡率高，19世纪50年代200例/年;病 死率达50-100%；,最初阶段：病人感到头疼和关节疼。 中期阶段：数周之后出现行走困难，并伴随着肢体颤抖。 晚期阶段：病人会丧失记忆。死前伴随大笑。 震颤、共济失调、脑退化痴呆,竭而死亡；丧失运动能力，言语含糊及无意识地狂笑，最后不省人事而死亡。,Carleton Gajdusek in Agakamatasa in 1978,A man with early stage Kuru. (a) His gait is broad-based and he is holding his walking stick. (b) The patient shows difficulty with fingernose testing. (c) Enlargement of panel (b), patient unable to touch the tip of myindex finger. (d ) The patient has difficulty with heelshin testing.,A woman with advanced Kuru. (a) For stability, the patient holds a steel rod implanted in the ground. She shows frontal lobe release signs, including (b) snout reflex, (c) hand grasp and (d ) foot grasp., 主要科学问题,新几内亚发生的一种严重危害人群健康的、呈地方性分布的疾病,病因？,发病机制？,有效控制措施？,？病,策略1？,策略2 ？,策略3 ？,-问题树-策略树,研究思路？,思路一、 A 基础研究-病毒学 B 病理学研究 C 实验动物研究 D 临床学研究 E 流行病学研究 F 环境因素调查 J 干预试验,思路二、 A 临床学研究 B 流行病学研究 C 环境因素调查 D 病理学研究 E 基础研究-病毒学 F 实验动物研究 J 干预试验,丹尼尔卡里顿盖达塞克 D.Carleton Gajdusek,1923年出生于美国 哈佛大学毕业 由于查明库鲁病病因而获得1976年诺贝尔医学奖 “如果你喜欢到未开化的地区去探险，那么，你有可能获诺贝尔奖。”,1943: from the University of Rochester (New York), where he studied Physics, Biology, Chemistry and Mathematics Yonkers, New York (20 Years old) 1946: obtained M.D. from Harvard University. postdoctoral research at Columbia, Caltech and Harvard a research virologist at the Walter Reed Army Medical Service Graduate School military service 1952-1953: a position at the Institut Pasteur in Tehran, offered by urgent opportunistic investigations of epidemiological problems in exotic and isolated populations“. (30 years old) 1954: as a visiting investigator at the Walter and Eliza Hall Institute of Medical Research in Melbourne, Australia.,1954: received the award in recognition of his study of the disease Kuru (a Fore word for “trembling”) 1956: Vincent Zigas, a district medical officer in the Fore Tribe region of New Guinea first introduced Gajdusek to Kuru. (34 years ) 1957: provided the first medical description of this unique neurological disorder, which was miscast in the popular press as the “laughing sickness” because some patients evinced risus sardonicus as a symptom. (35 years old) lived among the Fore, studied their language and culture and performed autopsies on Kuru victims.,1958: became head of laboratories for virological and neurological research at the National Institutes of Health (NIH) ,USA 1974：inducted to the National Academy of Sciences in the discipline of microbial biology. 1976: Notable awards: Nobel Prize in Physiology or Medicine (53 years old ),诺贝尔奖论文,T,非常规型病毒（朊病毒）与库鲁病的起源与消除,0,研究背景,诺贝尔奖论文,1,比较自然存在致海绵状脑病的病毒特征：致人类2种，致动物2种,致亚急性海绵状脑病的非常规型病毒,2,3,库鲁病,常规型病毒通过缺陷性或非缺陷性复制引起慢性疾病,4,5,传染性海绵状脑病（克-雅病，皮质-纹状体-脊髓变性）,绵羊瘙痒病,6,7,展望,亚急性海绵状脑病自然史推测：自然绵羊瘙痒病是克-雅病， 库鲁病和貂传染性脑病的假设起源,非常规型病毒（朊病毒）与库鲁病的起源与消除,1.致亚急性海绵状脑病的非常规型病毒,2.常规型病毒通过缺陷性或非缺陷性复制引起慢性疾病,0.前言：研究背景-库鲁病-慢病毒感染-与人和动物,3.库鲁病,4.传染性海绵状脑病（克-雅病，皮质-纹状体-脊髓变性）,5.绵羊瘙痒病,6.亚急性海绵状脑病自然史推测：自然绵羊瘙痒病是克- 雅病，库鲁病和貂传染性脑病的假设起源,7.展望,诺贝尔奖论文,研究思路？,思路一、 A 基础研究-病毒学 B 病理学研究 C 实验动物研究 D 临床学研究 E 流行病学研究 F 环境因素调查 J 干预试验,思路二、 A 临床学研究 B 流行病学研究 C 环境因素调查 D 病理学研究 E 基础研究-病毒学 F 实验动物研究 J 干预试验,目 录,一、研究背景与科学难点 二、论文研究思路的剖析 三、对科学研究工作的启示,创造性思维方法,丹尼尔卡里顿盖达塞克 D.Carleton Gajdusek,查明致库鲁病发生的“元凶”和控制措施的科学思维是什么？, 研究思路之一,病因？,发病机制？,控制措施？,？病,策略1,策略2,策略3 ？,-问题树-策略树,病理学,病毒 学,实验 动物,流行 病学,临床 学,环境 因素,预防 医学,研究思路之二,病因？,发病机制？,控制措施？,？病,策略1,策略2,策略3 ？,-问题树-策略树,病理学,病毒 学,实验 动物,流行 病学,临床 学,环境 因素,预防 医学,以1976年获得诺贝尔医学和生理学奖的论文内容为主； 检索该论文相关的文献59/162篇（1957-1976年/1957-2004年），按时间排序； 盖达塞克教授作为第一作者或作者之一。,研究思维的剖析,1957-1965 - 临床、流行病学和病理学,1957： ZIGAS, V.，GAJDUSEK, D. C. Kuru: Clinical study of a new syndrome resembling paralysis agitans in natives of the Eastern Highlands of Australian New Guinea. MED JOUR AUSTRALIA. 44 (21):745-754 GAJDUSEK, DC ZIGAS, V . Degenerative Disease Of The Central Nervous System In New-Guinea The Endemic Occurrence Of Kuru In The Native Population. New England Journal Of Medicine. 257(20): 974-978 1958: GAJDUSEK, DC, ZIGAS, V. Untersuchungen Uber Die Pathogenese Von Kuru. Klinische Wochenschrift. 36(10):445-459 1959: GAJDUSEK, DC，ZIGAS, V. KURU - CLINICAL, PATHOLOGICAL AND EPIDEMIOLOGICAL STUDY OF AN ACUTE PROGRESSIVE DEGENERATIVE DISEASE OF THE CENTRAL NERVOUS SYSTEM AMONG NATIVES OF THE EASTERN HIGHLANDS OF NEW-GUINEA. AMERICAN JOURNAL OF MEDICINE. 26(3): 442-469 KLATZO, I GAJDUSEK, DC. ZIGAS, V. Pathology Of Kuru. Laboratory Investigation. 8(4): 799- 781,1957-1965 - 临床、流行病学和病理学,1961: GAJDUSEK, DC, REID, LH. STUDIES ON KURU.4. KURU PATTERN IN MOKE, A REPRESENTATIVE FORE VILLAGE. AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 10( 4): 628-634 GAJDUSEK, DC, BAKER, J, ZIGAS, V. STUDIES ON KURU .3. PATTERNS OF KURU INCIDENCE - DEMOGRAPHIC AND GEOGRAPHIC EPIDEMIOLOGICAL ANALYSIS. AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 10(4): 599-609 GAJDUSEK, DC, ZIGAS, V. STUDIES ON KURU .1. ETHNOLOGIC SETTING OF KURU. AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 10(1):80-90 CURTAIN, CC, ZIGAS, V, GAJDUSEK, DC. STUDIES ON KURU .2. SERUM PROTEINS IN NATIVES FROM KURU REGION OF NEW GUINEA. AU SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 10(1):92-102 1962: SIMMONS, R T, GAJDUSEK, D C. Blood group genetical studies on Kuru-afflicted natives of the Eastern Highlands of New Guinea, and comparisons with unaffected neighboring tribes in Papua-New Guinea. Bibl Haematol. 13:255-259,1962: GAJDUSEK, DC. KURU - AN APPRAISAL OF 5 YEARS OF INVESTIGATION. EUGENICS QUARTERLY. 9(1): 69-70 1963: GAJDUSEK, D. CARLETON. Kuru. TRANS ROY SOC TROP MED AND HYG. 57 (3): 151-169 1964: NEUMANN, MA,GAJDUSEK, DC, ZIGAS, V. NEUROPATHOLOGIC FINDINGS IN EXOTIC NEUROLOGIC DISORDERS AMONG NATIVES OF HIGHLANDS OF NEW GUINEA. JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY. 23( 3):486-496 GAJDUSEK, DC, GIBBS, CJ. ATTEMPTS TO DEMONSTRATE TRANSMISSIBLE AGENT IN KURU AMYOTROPHIC LATERAL SCLEROSIS + OTHER SUB-ACUTE + CHRONIC NERVOUS SYSTEM DEGENERATIONS OF MAN. NATURE, 204(495): 257-267 1965: ALPERS, M, GAJDUSEK, CD. CHANGING PATTERNS OF KURU - EPIDEMIOLOGICAL CHANGES IN PERIOD OF INCREASING CONTACT OF FORE PEOPLE WITH WESTERN CIVILIZATION. AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE. 14( 5): 852-862,GAJDUSEK, DC .Physiology or Medicine 1976. 314,It contains more than 35,000 people living in 160 villages (census units) that have experienced kuru. All kuru-affected hamlets lie nestled among rain forest covered mountains from 1,000 to 2,500 m. above sea level.,In the Fore culture and linguistic group, among whom over 80 % of the cases occur, it had a yearly incidence rate and prevalence ratio of about 1 % of the population.,Figure 5. Kuru coincided with the height of the “epidemic”. 5a. Guru mortality rate in deaths per thousand population per annum in 1957-59 and 1961-1963. 5B. Male: female population ratio in each “tribal” group of the kuru region, 1958 and 1962.,Figure 4. River drainages of the kuru region with superimposed locations of the 160 villages in which kuru has ever occurred.,In 1957, it was found to affect all ages beyond infants and toddlers; it was common in male and female children and in adult females, but rare in adult males. This marked excess of deaths of adult females over males has led to a male-to-female ratio of over 3:1 in some villages, and of 2:1 for the whole South Fore group.,All died of their disease within 1 year after this photograph was taken.,Every patient required support from the others in order to stand without the aid of the sticks they had been asked to discard for the photograph.,Six women with Kuru so advanced that they require the use of one or two sticks for support, but still able to go to garden work on their own,The clinical course of Kuru is remarkably uniform with cerebellar symptomatology progressing to total incapacitation and death, usually within three to nine months. Two or more Fore children with advanced kuru in 1957 who sedentary for several months and were reaching the terminal stage of the disease.,1966-1969 - 实验动物学、病毒学、营养学,1966: BECK, E, GAJDUSEK, DC. VARIABLE SIZE OF SEPTAL NUCLEI IN MAN. NATURE, 210(5043):1338-1348 GAJDUSEK, DC GIBBS, CJ ALPERS, M. EXPERIMENTAL TRANSMISSION OF A KURU-LIKE SYNDROME TO CHIMPANZEES. NATURE, 209( 5025): 794-804 BECK, E, DANIEL, PM, ALPERS, M, GAJDUSEK, DC, GIBBS, CJ. EXPERIMENTAL KURU IN CHIMPANZEES - A PATHOLOGICAL REPORT. LANCET, 2(7472):1056 1967: KAKULAS, BA，LECOURS, AR，GAJDUSEK, DC. FURTHER OBSERVATIONS ON PATHOLOGY OF KURU - (A STUDY OF 2 CEREBRA IN SERIAL SECTION). JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY. 26(1):85-95ROGERS, NG, BASNIGHT, M, GIBBS, CJ, GAJDUSEK, DC. LATENT VIRUSES IN CHIMPANZEES WITH EXPERIMENTAL KURU.NATURE, 216( 5114):446 GAJDUSEK, DC. SLOW-VIRUS INFECTIONS OF NERVOUS SYSTEM. NEW ENGLAND JOURNAL OF MEDICINE. 276(7):392-402 GAJDUSEK, DC, GIBBS, CJ, ALPERS, M. TRANSMISSION AND PASSAGE OF EXPERIMENTAL KURU TO CHIMPANZEES. SCIENCE. 155(IS 3759):212-222 1968: GIBBS, CJ, GAJDUSEK, DC, ASHER, DM, ALPERS, MP, BECK, E, DANIEL, PM, MATTHEWS, WB. CREUTZFELDT-JAKOB DISEASE (SPONGIFORM ENCEPHALOPATHY) - TRANSMISSION TO CHIMPANZEE. SCIENCE. 161/IS 3839:388,1966-1969 - 实验动物学、病毒学、营养学,1968: Gajdusek, D C, Gibbs, C J. Slow, latent and temperate virus infections of the central nervous system. Res Publ Assoc Res Nerv Ment Dis, 44: 254-480 GAJDUSEK, DC, GIBBS, CJ, ASHER, DM, DAVID, E. TRANSMISSION OF EXPERIMENTAL KURU TO SPIDER MONKEY (ATELES GEOFFREYI). SCIENCE, 162( 3854): 693 1969: Beck, E, Daniel, P M, Alpers, M, Gajdusek, D C, Gibbs, C J. Neuropathological comparisons of experimental kuru in chimpanzees with human kuru. Int Arch Allergy Appl Immunol, 36( Suppl:553): 62-68 GAJDUSEK, DC, ROGERS, NG, BASNIGHT, M,GIBBS, CJ, ALPERS, M. TRANSMISSION EXPERIMENTS WITH KURU IN CHIMPANZEES AND ISOLATION OF LATENT VIRUSES FROM EXPLANTED TISSUES OF AFFECTED ANIMALS. ANNALS OF THE NEW YORK ACADEMY OF SCIENCES. 162(1): 529 Gibbs, C J, Gajdusek, D C, Alpers, M P. Attempts to transmit subacute and chronic neurological diseases to animals. Int Arch Allergy Appl Immunol, 36(Suppl:519): 52 LAMPERT, PW, EARLE, KM, GIBBS, CJ, GAJDUSEK, DC. EXPERIMENTAL KURU ENCEPHALOPATHY IN CHIMPANZEES AND SPIDER MONKEYS -ELECTRON MICROSCOPIC STUDIES. JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY. 28(3):353 Reid, L H, Gajdusek, D C. Nutrition in the Kuru region. II. A nutritional evaluation of traditional Fore diet in Moke village in 1957. Acta Trop, 26(4): 331-345,传染病? 家族性遗传病?,现场人群调查,病理学,流行 病学,临床 学,实验室 检查,无典型的病毒引起的传染病的炎症反应和免疫反应,患者无持续性发热；,脑脊液中无典型的传染病前期表现和淋巴细胞增多、蛋白质升高的异常现象；,病理改变又只限于神经系统, 表现为星形细胞增生和肥大, 神经元胞体、树突和轴突有进行性空泡变性, 表现为神经系统的变性改变，不支持是传染病。,病例:非病例血液遗传学调查,非典型传染病脑病,现场人群调查,病理学,流行 病学,临床 学,实验室 检查,无典型的病毒引起的传染病的炎症反应和免疫反应,不是典型传染病：,患者无持续性发热；,脑脊液中无典型的传染病前期表现和淋巴细胞增多、蛋白质升高的异常现象；,病理改变又只限于神经系统, 表现为星形细胞增生和肥大, 神经元胞体、树突和轴突有进行性空泡变性, 表现为神经系统的变性改变，不支持是传染病。,发现矛盾?,Gajdusek spent almost a year living with and studying the Fore, and collecting tissue samples from victims of Kuru in 1957.,When Gajdusek returned to the United States in 1958, he was able to carry out laboratory studies of Kuru at the National Institute of Neurological and Communicative Disorders and Stroke, where he eventually established the Laboratories of Slow, Latent, and Temperate Virus Infections and of Central Nervous System Studies.,The brain tissue obtained from victims of Kuru revealed many lesions and atrophy, but not the expected signs of infection. William Hadlow of the NIH Rocky Mountain laboratory pointed out the similarity between Kuru and a viral disease of sheep known as scrapie.,Ellis, Fay Jarosh, 2009,To test the possibility that Kuru was a viral disease, Gajdusek and his associate, Clarence J. Gibbs, inoculated chimpanzees with brain tissue from Kuru victims.,All cooking, including that of human flesh from diseased kinsmen, was done in pits with steam made by pouring water over the hot stones, or cooked in bamboo cylinders in the hot ashes. Infection with the kuru virus was most probably through the cuts and abrasions of the skin. or from nose-picking, rye rubbing, or mucosal injury.,Fore族特殊葬礼仪式- Family cook and ate deceased family members body tissue and brain. Fore部落土著有亲人死后用死者的脑涂抹于口周及眼周，并食用死者的身体组织和脑的不良风俗，而使该病广泛传播，尤其妇女及儿童。食物性传播,地区分布 (distribution of disease by place),1.国家间及国家内的分布 2.城乡分布 3.影响地区分布的因素 1)特殊风俗习惯和遗传特征。 2)自然地理因素。 3) 生物因素。 4) 社会经济环境。,2) 地方性 由当地的卫生习惯和卫生条件所造成的某病在某地区或人群中长期存在。 如：伤寒、痢疾及KURU病。,Figure 7. The overall incidence of kuru deaths in male and female patients by year since its discovery in 1957 through 1975.,干预效果：依据Gajdusek 研究，1968年停止食人葬俗后，库鲁病得到控制而逐渐消除，从而拯救了一个部落的人群。,1970-1972 - 流行病学、遗传和病理比较,1970: GAJDUSEK, DC, SORENSON, ER, MEYER, J. A COMPREHENSIVE CINEMA RECORD OF DISAPPERARING KURU. BRAIN, 93:65-69. GIBBS, CJ, GAJDUSEK, DC. ISOLATED AND MIGRATORY POPULATION GROUPS . HEALTH PROBLEMS AND EPIDEMIOLOGIC STUDIES .4. KURU . PATHOGENESIS AND CHARACTERIZATION OFVIRUS. AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 19(1):138-144. 1971: GAJDUSEK, DC. SLOW VIRUS DISEASES OF CENTRAL NERVOUS SYSTEM. AMERICAN JOURNAL OF CLINICAL PATHOLOGY, 56(3):320-337. GAJDUSEK, DC, GIBBS, CJ. TRANSMISSION OF 2 SUBACUTE SPONGIFORM ENCEPHALOPATHIES OF MAN (KURU AND CREUTZFELDT-JAKOB DISEASE) TO NEW WORLD MONKEYS. NATURE, 230(5296):588-597. Gibbs, C J, Gajdusek, D C. Transmission and characterization of the agents of spongiform virus encephalopathies: kuru, Creutzfeldt-Jakob disease, scrapie and mink encephalopathy. Res Publ Assoc Res Nerv Ment Dis, 49:383- 410. LAMPERT, P, HOOKS, J, GIBBS, CJ, GAJDUSEK, DC. ALTERED PLASMA MEMBRANES IN EXPERIMENTAL SCRAPIE. ACTA NEUROPATHOLOGICA, 19(2):81-86. 1972: Gajdusek, D C. Spongiform virus encephalopathies. J Clin Pathol Suppl (R Coll Pathol), 6:78- 83. GAJDUSEK, DC, GIBBS, CJ, ROGERS, NG, BASNIGHT, M, HOOKS, J. PERSISTENCE OF VIRUSES OF KURU AND CREUTZFELDT-JAKOB DISEASE IN TISSUE-CULTURES OF BRAIN CELLS. NATURE, 235(33):104-114.,1970-1972 - 动物模型、遗传和病理比较,1972: GAJDUSEK, DC, GIBBS, CJ. TRANSMISSION OF KURU FROM MAN TO RHESUS-MONKEY (MACACA-MULATTA) 81/2 YEARS AFTER INOCULATION. NATURE, 240(5380): 351-357. Gajdusek, D C, Alpers, M. Genetic studies in relation of kuru. I. Cultural, historical, and demographic background. Am J Hum Genet, 24(Suppl:1):38-45. Gibbs, C J, Gajdusek, D C. Isolation and characterization of the subacute spongiform virus encephalopathies of man: kuru and Creutzfeldt-Jakob disease. J Clin Pathol Suppl (R Coll Pathol), 6:84-96 Kitchin, F D, Bearn, A G, Alpers, M, Gajdusek, D C. Genetic studies in relation to kuru. 3. Distribution of the inherited serum group-specific protein (Ge) phenotypes in New Guineans: an association of kuru and the Gc Ab phenotype. Am J Hum Genet. 24(Suppl:72):85-84. AU LAMPERT, PW, GAJDUSEK, DC, GIBBS, CJ. SUBACUTE SPONGIFORM VIRUS ENCEPHALOPATHIES - SCRAPIE, KURU AND CREUTZFELDT-JAKOB DISEASE - A REVIEW. AMERICAN JOURNAL OF PATHOLOGY, 68(3):626-634. Plato, C C, Gajdusek, D C. Genetic studies in relation to kuru. IV. Dermatoglyphics of the Fore and Anga populations of the Eastern Highlands of New Guinea. Am J Hum Genet, 24(Suppl:86): 94-99. Simmons, R T, Graydon, J J, Gajdusek, D C, Alpers, M P, Hornabrook, R W. Genetic studies in relation to kuru. II. Blood-gro