Thirteen Years to Forge a Sword: How Patience and Perseverance Helped Humanity Conquer Tuberculosis

Internal TCM recognizes four incurable diseases: wind (stroke), consumption (痨), tympanites (abdominal bloating), and dysphagia. Of these, "consumption"—also called lung consumption, lao zhai, xu lao, xu sun—is what we today call tuberculosis. TB is a contagious, wasting disease caused by infection with Mycobacterium tuberculosis; in late stages patients often have low fever, emaciation, sputum, hemoptysis, night sweats, chest pain, and fatigue.

Tuberculosis is preventable and treatable today but was extremely difficult to cure in ancient times. Ancient Chinese physicians recognized its contagiousness, attributing its cause to "consumption worms" (痨虫) and understanding that these worms could pass between people; but given the conditions of the time, transmission was hard to block.

Although ancient TCM could not cure TB, it did try hard to find ways to relieve symptoms, and quite a few monographs were published on the subject, the most famous being Hu Shenrou's Shenlou Wu Shu and Wang Qishi's Liyuan Yuanjian. Some of the treatments in these works are still used today. The experience ancient TCM gained in treating consumption was also borrowed to treat other deficiency-wasting diseases, one of their contributions to later medicine.

Tuberculosis has caused humanity enormous suffering. The "human-blood steamed bun" in Lu Xun's fiction is the most extreme but completely ineffective folk remedy ancient Chinese people devised when they had no other way to treat TB.

TB troubled not only China but the whole world; until the early 20th century humanity had not conquered it. By then, immunology had developed enough to attract wide medical attention, and many scientists wondered whether a TB vaccine could block transmission.

But theory and practice are far apart. The earliest attempts by scientists mostly ended in failure. Some tried to kill TB bacilli and make an inactivated vaccine; some tried to extract protein components from the bacilli for a vaccine; others directly used small doses of live bacilli to stimulate experimental animals' immune systems. All failed.

This may relate to certain properties of the bacillus. Among pathogenic bacteria, Mycobacterium tuberculosis is unusual. Its division cycle is about 18–24 hours, far slower than common bacteria (most divide every 20–30 minutes). Its cell wall is thick, slowing nutrient absorption and blocking external damage to its interior. The tubercle bacillus is highly adaptable and can survive for long periods in low-oxygen, nutrient-poor environments. So developing a TB vaccine was very hard.

But there are always scientists undaunted by difficulty. Two at the French Pasteur Institute—Albert Calmette (1863–1933) and Camille Guérin (1872–1961)—were especially interested and could endure solitude and hardship, devoting themselves to this work for a decade.

In 1906, while walking on a farm, Calmette and Guérin were inspired by a corn farmer. The two scientists noticed the farm's corn stalks were very short and asked the owner why. The farmer said it was because the corn had been planted for over ten generations and the seed had degenerated, producing poor crops.

The farmer's words gave them the idea: if tubercle bacilli could be serially passaged, their virulence might likewise degenerate. So they decided to pass the bacilli from generation to generation to attenuate Mycobacterium tuberculosis.

But in fact someone had discovered this principle before Calmette and Guérin: Qing-dynasty Chinese physicians had used this method when inoculating people with smallpox seed.

During the Jiaqing reign of the Qing, the physician Zhu Yiliang wrote in his Zhongdou Xinfa: "The longer the seed is passed on, the more refined its medicinal power, and the more skillful the manual selection, the more the fiery poison is washed out and the pure essence alone remains; thus it is perfectly safe and harmless." Chinese variolators had already found that serial passage over many generations could reduce smallpox virulence and improve inoculation safety; only their experience never received scientific attention.

Later, the English country doctor Edward Jenner found that cowpox vaccination was safer and more effective against smallpox, so afterward European scientists considered making vaccines in cows.

Inspired, Calmette and Guérin tried serial passage in experimental animals to attenuate bovine tubercle bacillus, eventually producing a vaccine against tuberculosis.

With this strategy fixed, they spent thirteen long years passing the bacillus through 230 generations in animals before successfully developing the vaccine against Mycobacterium tuberculosis. In 1921, the French doctor Weill-Hallé first used this live-attenuated vaccine clinically. The first infant vaccinated had lost both parents to TB; the result was satisfactory.

The orphaned infant was being raised by his grandmother, herself a TB patient; without immunity, he would probably have been doomed too. After receiving Calmette and Guérin's vaccine, the child successfully developed antibodies. They then went through more than 300 clinical trials to verify the vaccine's safety.

In 1924, Calmette and Guérin announced their invention to the world. After World War II, the United States and Britain spent 16 years confirming that this vaccine safely and effectively prevented tuberculosis. From then on, it was widely used in TB prevention and control. As of April 2026, more than 4 billion people worldwide have received BCG.

To honor the two great scientists, the scientific community took the first syllables of their given names and named their vaccine BCG (Bacille Calmette-Guérin). Today, Chinese newborns must receive two vaccines: hepatitis B vaccine and BCG.

BCG gave humanity real hope of finally escaping "consumption." Though because BCG coverage is not universal there are still many TB patients worldwide, I believe that with time, as BCG is given universally to newborns, Mycobacterium tuberculosis will eventually vanish from humanity as smallpox did.

Today BCG is used not only to prevent and treat TB; scientists have found it also enhances macrophage activity and activates T lymphocytes, strengthening the tumor-suppressing effect of macrophages and T cells, and is used as adjuvant therapy for some tumors. BCG also helps prevent asthma relapse and childhood colds.

The process of developing BCG offers us many lessons. To achieve any breakthrough in the life sciences requires both talent and erudition and enormous effort.