Intermediate Physics for Medicine and Biology: Everything Is Tuberculosis

Everything Is Tuberculosis,
by John Green.

Recently I read the current bestseller Everything Is Tuberculosis: The History and Persistence of Our Deadliest Infection, by John Green. Tuberculosis is the deadliest infectious disease worldwide. According to Green,

Just in the last two centuries, tuberculosis [TB] caused over a billion human deaths. One estimate, from Frank Ryan’s Tuberculosis: The Greatest Story Never Told, maintains that TB has killed around one in seven people who’ve ever lived. Covid-19 displaced tuberculosis as the world’s deadliest infectious disease from 2020 through 2022, but in 2023, TB regained the status it has held for most of what we know of human history: Killing 1,250,000 people, TB once again became our deadliest infection. What’s different now from 1804 or 1904 is that tuberculosis is curable, and has been since the mid-1950s. We know how to live in a world without tuberculosis. But we choose not to live in that world…

Some of the symptoms of tuberculosis are difficulty breathing, coughing up blood, night sweats, and weight loss. It is a slowly progressing disease, which led to its now-archaic nickname “consumption.” Green writes

Some patients will recover without treatment. Some will survive for decades but with permanent disability, including lung problems, devastating fatigue, and painful bone deformities. But if left untreated, most people who develop active TB will eventually die of the disease.

In Chapter 1 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I stress the importance of understanding the sizes of things. Tuberculosis is caused by bacteria, which are each a couple microns long and about a half a micron wide. But the body reacts to these bacteria by surrounding them with white blood cells and T cells of the immune system, “creating a ball of calcifying tissue known as a tubercle.” Tubercles vary in size, from a few tenths of a millimeter to a centimeter. That’s too big to pass through capillaries in the bloodstream and too big to fit into a single alveolus in the lungs.

IPMB only mentions tuberculosis twice. Russ and I write

Spontaneous pneumothorax [air between the lung and the chest wall] can occur in any pulmonary disease that causes an alveolus (air sac) on the surface of the lung to rupture: most commonly emphysema, asthma, or tuberculosis….

Some pathologic conditions can be identified by the deposition of calcium salts. Such dystrophic (defective) calcification occurs in any form of tissue injury, particularly if there has been tissue necrosis (cell death). It is found in necrotizing tumors (particularly carcinomas), atherosclerotic blood vessels, areas of old abscess formation, tuberculous foci, and damaged heart valves, among others.

This history of tuberculosis as a disease is fascinating. Green writes that in eighteenth century Europe “the disease became not just the leading cause of human death, but overwhelmingly the leading cause of human death.” Oddly, it became romanticized. People like the poet John Keats and the pianist Frederic Chopin died of tuberculosis, and the illness came to be linked with creativity. It also became associated with female beauty, as the thin, wide-eyed, rosy-cheeked appearance of a woman with tuberculosis became fashionable. Later, the disease was stigmatized, being tied to race and a lack of moral virtue. When a person suffered from tuberculosis, they often went to a sanatorium for rest and treatment, and usually died there.

The German microbiologist Robert Koch isolated Mycobacterium tuberculosis in 1882. Koch was a rival of Frenchman Louis Pasteur, and both worked on treatments. I was surprised to learn that author Arthur Conan Doyle—famous for his Sherlock Holmes stories—also played a role in developing treatments for the disease. Tuberculosis remains latent in people until it’s activated by some other problem, such as malnutrition or an immune system disease like AIDS. Many infectious diseases attack children or the elderly, but TB is common in young adults. Physicist Richard Feynman’s 25-year-old wife Arline died of tuberculosis.

Green explains that

in the decades after the discovery of Koch’s bacillus, small improvements emerged. Better diagnostics meant the disease could be identified and treated earlier, especially once chest X-rays emerged as a diagnostic tool.

The main impact of medical physics on tuberculosis is the development of radiography. X-rays weren’t even discovered until 1895, a decade after Koch isolated the tuberculosis bacterium. They arrived just in time. The often-decaying bacteria at the center of a tubercle accumulates calcium. For low x-ray energies, when the photoelectric effect is the dominant mechanism determining how x-ray photons interact with tissue, the cross section for x-ray attenuation varies as the fourth power of the atomic number. Because calcium has a relatively high atomic number (Z = 20) compared to hydrogen, carbon, nitrogen, and oxygen (Z = 1, 6, 7, 8, respectively), and because lung tissue in general has a low attenuation because of the low-density of air, tubercles show up on a chest x-ray with a great deal of contrast.

The primary treatment for tuberculosis nowadays is antibiotics. The first one to be used for TB, streptomycin, was discovered in the 1940s. By the mid 1950s, several antibiotics made TB curable. I was born in 1960, just after the threat of tuberculosis subsided dramatically in the United States. I can still remember us kids getting those TB skin tests in our forearms, which we all had to have before entering school. But I don’t remember being very worried about TB as a child. The threat was over by then.

A vaccine exists for tuberculosis (the Bacillus Calmette–Guérin, or BCG, vaccine), but it’s mainly effective when given to children, and isn’t used widely in the United States, where tuberculosis is rare. In poorer countries, however, the vaccine saves millions of lives. Currently, mRNA vaccines are being developed against TB. This crucial advance is happening just as Robert F. Kennedy, Jr. is leading his crazy anti-science crusade against vaccines in general, and mRNA vaccines in particular. The vaccine alliance GAVI is hoping to introduce new vaccines for tuberculosis, and this effort will certainly be hurt by the United States defunding GAVI. The World Health Organization has an “end TB strategy” that, again, will be slowed by America’s withdraw from WHO and the dismantling of USAID. Green’s book was published in 2025, but I suspect it was written in 2024, before the Trump administration’s conspiracy-theory laden effort to oppose vaccines and deny vaccine science got underway.

Many of these world-wide efforts to eliminate TB depend on access to new drugs that can overcome drug-resistant TB. Unfortunately, such drugs are expensive, and are difficult to afford or even obtain in poorer countries.

In the final pages of Everything is Tuberculosis, Green writes eloquently

...TB [tuberculosis] in the twenty-first century is not really caused by a bacteria that we know how to kill. TB in the twenty-first century is really caused by those social determinants of health, which at their core are about human-built systems for extracting and allocating resources. The real cause of contemporary tuberculosis is, for lack of a better term, us...

We cannot address TB only with vaccines and medications. We cannot address it only with comprehensive STP [Search, Treat, Prevent] programs. We must also address the root cause of tuberculosis, which is injustice. In a world where everyone can eat, and access healthcare, and be treated humanely, tuberculosis has no chance. Ultimately, we are the cause.

We must also be the cure.

Green serves on the board of trustees for the global health non-profit Partners In Health. To anyone wanting to join the worldwide fight against tuberculosis, I suggest starting at https://www.pih.org.