History of tuberculosis
The history of tuberculosis encompasses the origins, evolution, and spread of tuberculosis throughout human history, as well as the development of medical understanding, treatments, and control methods for this ancient disease.
Tuberculosis is an infectious disease caused by bacteria of the Mycobacterium tuberculosis complex. Throughout history, tuberculosis has been known by differing names, including consumption, phthisis, and the White Plague. Paleopathological evidence finds tuberculosis in humans since at least the Neolithic, with molecular studies suggesting a much earlier emergence and co-evolution with humans.
Phylogenetic analyses indicate that the TB originated in Africa and evolved alongside human populations for tens of thousands of years. The disease spread globally through human migrations, adapting to different human populations and eventually developing into several distinct lineages with varying geographic distributions. While TB has affected humanity for millennia, it became particularly prevalent during industrialization when urban overcrowding aided transmission. The medical understanding of tuberculosis transformed in the 19th century with Robert Koch's 1882 identification of Mycobacterium tuberculosis as the causative bacterium, followed by the development of vaccines and antibiotic treatments in the mid-20th century.
Origins
The modern understanding of the evolutionary origins of Mycobacterium tuberculosis has been revolutionized by recent genomic and phylogenetic research. Current evidence suggests that tuberculosis is an ancient human disease that co-evolved with human populations for tens of thousands of years, rather than a recent acquisition from domesticated animals during the Neolithic as previously believed. There has also been a claim of evidence of lesions characteristic of tuberculosis in a 500,000-year-old Homo erectus fossil, although this finding is controversial.Phylogenetic evidence
Comprehensive phylogenetic analyses of the Mycobacterium tuberculosis complex demonstrate an African origin for the pathogen. Whole-genome sequencing of modern TB strains reveals that the bacteria emerged in Africa and followed human migration out of Africa. Research analyzing 259 global TB clinical strains suggests that tuberculosis arose roughly 70,000 years ago, expanding in two major waves: first around 67,000 years ago during human migration to South Asia, and again around 46,000 years ago during migrations to the Near East, Europe, and Asia.Within TB, researchers have identified multiple lineages associated with different geographical regions. These include Lineage 1, Lineages 2-4, Lineages 5-6, Lineage 7, Lineage 8, and Lineage 9. Animal-adapted lineages, including M. bovis which infects cattle, evolved from human strains rather than the reverse, contradicting earlier theories about TB's origins.
The discovery of M. tuberculosis Lineage 8 strains in East Africa, which retain genetic features seen in more ancestral mycobacteria but absent in other TB lineages, provides evidence for the ancient African origin of tuberculosis.
Paleopathological evidence
The oldest confirmed paleopathological evidence of human tuberculosis dates to the Pre-Pottery Neolithic in the Near East. Key early cases include remains from Dja'de el Mughara and Tell Aswad in Syria, Ain Ghazal in Jordan, and Atlit Yam in Israel, where molecular analyses confirmed the presence of TB DNA. In Europe, the earliest confirmed cases come from the Early Neolithic Linear Pottery culture sites in Germany.A controversial finding reported in 2014 based on DNA from 1,000-year-old skeletons in Peru suggested that tuberculosis might have been transmitted to humans from seals, possibly originating only 6,000 years ago. However, subsequent research has challenged this interpretation. The Peruvian samples showed evidence of a TB strain related to M. pinnipedii, but this represents a localized zoonotic transfer specific to pre-colonial South America rather than the origin of human tuberculosis. These seal-derived strains infected coastal populations and spread inland but were eventually replaced by European strains of M. tuberculosis brought in by colonists. This finding represents an example of animal-to-human transmission, but does not contradict the evidence for much earlier human tuberculosis in Africa and Eurasia.
The limited paleopathological evidence from the Upper Paleolithic despite its importance in TB evolution represents a paradox.This may be explained by the low population density of Paleolithic hunter-gatherers, which would have limited TB transmission and skeletal signs, or by limitations in identifying ancient tuberculosis.
Early evolution
Genomic research indicate that the emergence and spread of tuberculosis were not linked to animal domestication during the Neolithic, but rather to human population dynamics. The Neolithic demographic transition aided tuberculosis transmission and allowed it to become more widespread, but long before this, the pathogen had already become adapted to humans.The co-evolution between TB and humans is evidenced by the adaptation of different tuberculosis lineages to different human populations, reflecting geographical patterns of human migration and settlement. Genetic studies also show evidence of selection pressure exerted by tuberculosis on human populations, such as the changing frequency of TB susceptibility variants like TYK2 P1104A in Europeans over the past 2,000 years.
Although relatively little is known about its frequency before the 19th century, its incidence is thought to have peaked between the end of the 18th century and the end of the 19th century. Over time, the various cultures of the world gave the illness different names: phthisis, consumptio, yaksma, and chaky oncay, each of which make reference to the "drying" or "consuming" effect of the illness, cachexia.
In the 19th century, TB's high mortality rate among young and middle-aged adults and the surge of Romanticism, which stressed feeling over reason, caused many to refer to the disease as the "romantic disease".
Early civilization
In 2008, evidence for tuberculosis infection was discovered in human remains from the Neolithic era dating from 9,000 years ago, in Atlit Yam, a settlement in the eastern Mediterranean. This finding was confirmed by morphological and molecular methods; to date it is the oldest evidence of tuberculosis infection in humans.Evidence of the infection in humans was also found in a cemetery near Heidelberg, in the Neolithic bone remains that show evidence of the type of angulation often seen with spinal tuberculosis. Signs of the disease have also been found in Egyptian mummies dated between 3000 and 2400 BC. The most convincing case was found in the mummy of priest Nesperehen, discovered by Grebart in 1881, which featured evidence of spinal tuberculosis with the characteristic psoas abscesses. Similar features were discovered on other mummies like that of the priest Philoc and throughout the cemeteries of Thebes. It appears likely that Akhenaten and his wife Nefertiti both died from tuberculosis, and evidence indicates that hospitals for tuberculosis existed in Egypt as early as 1500 BC.
The Ebers papyrus, an important Egyptian medical treatise from around 1550 BC, describes a pulmonary consumption associated with the cervical lymph nodes. The Old Testament mentions a consumptive illness that would affect the Jewish people if they stray from God.
Ancient India
The first references to tuberculosis in non-European civilization is found in the Vedas. The oldest of them calls the disease yaksma. The Atharvaveda called it balasa. It is in the Atharvaveda that the first description of scrofula was given. The Sushruta Samhita, compiled during the period ca. 200 BCE - 500 CE, recommended that the disease be treated with breast milk, various meats, alcohol and rest. The Yajurveda advised affected individuals to move to higher altitudes.Ancient China
The Classical Chinese word lào 癆 "consumption; tuberculosis" was the common name in traditional Chinese medicine and fèijiéhé 肺結核 "pulmonary tuberculosis" is the modern medical term. Lao is compounded in names like xulao 虛癆 with "empty; void", láobìng 癆病 with "sickness", láozhài 癆瘵 with " sickness", and feilao 肺癆 with "lungs". Zhang and Unschuld explain that the medical term xulao 虛癆 "depletion exhaustion" includes infectious and consumptive pathologies, such as laozhai 癆瘵 "exhaustion with consumption" or laozhaichong 癆瘵蟲 "exhaustion consumption bugs/worms". They retrospectively identify feilao 肺癆 "lung exhaustion" and infectious feilao chuanshi 肺癆傳尸 "lung exhaustion by corpse transmission as "consumption/tuberculosis". Describing foreign loanwords in early medical terminology, Zhang and Unschuld note the phonetic similarity between Chinese feixiao 肺消 "lung consumption" and ancient Greek phthisis "pulmonary tuberculosis".The Huangdi Neijing classic Chinese medical text, traditionally attributed to the mythical Yellow Emperor, describes a disease believed to be tuberculosis, called xulao bing, characterized by persistent cough, abnormal appearance, fever, a weak and fast pulse, chest obstructions, and shortness of breath.
The Huangdi Neijing describes an incurable disease called huaifu 壞府 "bad palace", which commentators interpret as tuberculous. "As for a string which is cut, its sound is hoarse. As for wood which has become old, its leaves are shed. As for a disease which is in the depth , the sound it is hiccup. When a man has these three , this is called 'destroyed palace'. Toxic drugs do not bring a cure; short needles cannot seize . Wang Bing's commentary explains that fu 府 "palace" stands for xiong 胸 "chest", and huai "destroy" implies "injure the palace and seize the disease". The Huangdi Neijing compiler Yang Shangshan notes, "The proposed here very much resembles tuberculosis... Hence states: poisonous drugs bring no cure; it cannot be seized with short needles."
The Shennong Bencaojing pharmacopeia, attributed to the legendary inventor of agriculture Shennong "Divine Farmer", also refers to tuberculosis
The Zhouhou beiji fang 肘后备急方 "Handbook of Prescriptions for Emergencies", attributed to the Daoist scholar Ge Hong, uses the name of shizhu 尸疰 "corpse disease; tuberculosis" and describes the symptoms and contagion:
Song dynasty Daoist priest-doctors first recorded that tuberculosis, called shīzhài 尸瘵 "disease which changes a living being into a corpse", was caused by a specific parasite or pathogen, centuries earlier than their contemporaries in other countries. The Duanchu shizhai pin 斷除尸瘵品 "On the Extermination of the Corpse Disease" is the 23rd chapter in Daoist collection Wushang xuanyuan santian Yutang dafa 無上玄元三天玉堂大法 "Great Rites of the Jade Hall of the Three Heavens of the Supreme Mysterious Origins". The text has a preface dated 1126, written by the Song dynasty Zhengyi Dao master Lu Shizhong 路時中, who founded the Yutang dafa 玉堂大法 tradition, but internal evidence reveals that the text could not have been written before 1158.
This passage refers to the cause of TB in ancient medical terminology of jiuchong 九蟲 "Nine Worms" and gu 蠱 "supernatural agents causing disease", and qi. The Nine Worms generically meant "bodily parasites; intestinal worms" and were associated with the sanshi 三尸 "Three Corpses" or sanchong 三蟲 "Three Worms", which were believed to be biospiritual parasites that live in the human body and seek to hasten their host's death.
Daoist medical texts give different lists and descriptions of the Nine Worms. The Boji fang 博濟方 "Prescriptions for Universal Dispensation", collected by Wang Gun王袞, calls the supposed TB pathogen laochong 癆蟲 "tuberculosis worms".
This Duanchu shizhai pin chapter explains that the present Nine Worms does not refer to the intestinal weichong 胃蟲 "stomach worms", huichong 蛔蟲 "coiling worm; roundworm", or cun baichong 寸白蟲 "inch-long white worm; nematode", and says the supposed six TB worms are "six kinds" of parasites, but the next chapter says they are "six stages/generations" of reproduction. Daoist priests allegedly cured tuberculosis through drugs, acupuncture, and burning fulu "supernatural talismans/charms". Burning magic talismans would cause the TB patient to cough, which was considered an effective treatment.
In addition, Daoist healers would burn talismans in order to fumigate the clothes and belongings of the deceased, and would warn the tuberculosis patient's family to throw away everything into a changliu shui 長流水 "everflowing stream". According to Liu Ts'un-yan, "This proves that the priests of the time actually wanted to destroy all the belongings of the deceased, using charms as a camouflage."