In a typical experiment, Chinese prisoners were tied to stakes at staggered distances from a shrapnel bomb. The bomb was detonated and scientists then walked among them, carefully noting the nature and extent of the prisoners’ injuries and how long it took them to die. Other prisoners were shot with flamethrowers for similar purposes, or starved, frozen, or poisoned. Some, for unfathomable reasons, were dissected while still conscious. Most of the victims were captured Chinese soldiers, but Unit 731 also experimented on selected Allied prisoners of war to make sure that toxins and nerve agents had the same effects on Westerners as on Asians. When pregnant women or young children were needed for experiments, they were randomly snatched from the streets of Harbin. Nobody knows how many people died in Unit 731, but one estimate has put the number as high as 250,000.
The outcome of all this was that Japan and Germany finished the war well ahead of the rest of the world in understanding microbiology, nutrition, frostbite, weapons injuries, and above all the effects of nerve gases, toxins, and infectious diseases. Although many Germans were captured and tried for these war crimes, the Japanese almost entirely escaped punishment. Most were granted immunity from prosecution in return for sharing what they had learned with their American captors. Shiro Ishii, the physician who had conceived and run Unit 731, was extensively debriefed and then allowed to return to civilian life.
The existence of Unit 731 was a well-guarded secret, by Japanese and American officials alike, and would have remained unknown to the wider world forever except that in 1984 a student from Keio University in Tokyo came across a box of incriminating documents in a secondhand bookshop and brought them to the attention of others. By this time, it was far too late to bring to justice Shiro Ishii. He had died in 1959, peacefully in his sleep, at the age of sixty-seven after nearly a decade and a half of untroubled postwar life.
* The insensitivity in Nazi Germany could be breathtaking. In 1941, a psychiatric hospital at Hadamar, near Limburg, celebrated the putting to death of its ten thousandth cognitively deficient person with an official celebration with speeches and beer for the staff.
12 THE IMMUNE SYSTEM
The immune system is the most interesting organ in the body.
—MICHAEL KINCH
I
THE IMMUNE SYSTEM is big and kind of messy and all over the place. It includes a lot of things that we don’t usually think of in the context of immunity, like earwax, skin, and tears. Any invader that gets past these outer defenses—and comparatively few do—will quickly run into swarms of “proper” immune cells, which come pouring out of lymph nodes, bone marrow, the spleen, the thymus, and other corners of the body. There is a lot of chemistry involved. If you want to understand the immune system, you need to understand antibodies, lymphocytes, cytokines, chemokines, histamine, neutrophils, B cells, T cells, NK cells, macrophages, phagocytes, granulocytes, basophils, interferons, prostaglandins, pluripotent hematopoietic stem cells, and a great deal more—and I mean a great deal more.
Some of these overlap and some do multiple jobs. Interleukin-1, for instance, not only attacks pathogens but also plays a role in sleep, which may go some way to explaining why we are so often drowsy when unwell. By one calculation, we have some three hundred different types of immune cells at work within us, but Daniel Davis, professor of immunology at the University of Manchester in England, thinks the number is essentially incalculable. “A dendritic cell in the skin will be quite different from one in a lymph node, say, and so it all gets quite muddled to define specific types,” he says.
On top of all that, every person’s immune system is unique, making immune systems harder to generalize, harder to understand, and harder to treat when they go wrong. Moreover, the immune system doesn’t just deal with germs. It has to respond to toxins, drugs, cancers, foreign objects, and even your own state of mind. If you are stressed or exhausted, you are much more likely to suffer an infection, for instance. Because protecting us from invasion is such a limitless challenge, the immune system sometimes makes mistakes and launches an attack on innocent cells. Given the number of inspections immune cells make day after day, the error rate is really low. It is a great irony nonetheless that a very high proportion of the suffering we do is inflicted on us by our own defenses in the form of autoimmune diseases like multiple sclerosis, lupus, rheumatoid arthritis, Crohn’s disease, and many unappealing others. Altogether about 5 percent of us suffer from some form of autoimmune disease—a very high proportion for such an uncomfortable range of afflictions—and the numbers are growing faster than our abilities to treat them effectively.
“You could look at it and conclude that it’s crazy that the immune system attacks itself,” says Davis. “Alternatively, once you start to think about all that the immune system has to do, it’s surprising that it doesn’t happen all the time. Your immune system is constantly bombarded by things it has never seen before, things that may have only just come into existence—like new flu viruses, which are constantly mutating into new forms. So your immune system has to be able to identify and fight off a more or less infinite number of things.”
Davis is a big but gentle man in his forties with a booming laugh and the happy air of someone who has found his niche in life. He studied physics at Manchester and Strathclyde Universities in Britain, but then moved to Harvard in the mid-1990s and decided that biology was where his real interests lay. By chance he ended up in the immunology lab at Harvard and became gripped by the elegant complexity of the immune system and the challenge of trying to unravel it all.
Despite the intricacy at the molecular level, all parts of the immune system contribute to a single task: to identify anything that is in the body that shouldn’t be there and, if necessary, kill it. But the process is far from straightforward. A lot of things inside you are harmless or even beneficial, and it would be foolhardy or a waste of energy and resources to kill them. So the immune system has to be a bit like security people at airports watching stuff on a conveyor belt and only challenging those things that have nefarious intent.
At the heart of the system are five types of white blood cells: lymphocytes, monocytes, basophils, neutrophils, and eosinophils. They are all important, but lymphocytes are the ones that excite immunologists most. David Bainbridge calls lymphocytes “just about the cleverest little cells in the whole body” because of their ability to recognize almost any kind of unwanted invader and mobilize a swift and targeted response.
Lymphocytes are of two principal types: B cells and T cells. The B in B cells comes, a little oddly, from “bursa of Fabricius,” an appendix-like organ in birds where B cells were first seen.*1 Humans and other mammals don’t have a bursa of Fabricius. Our B cells are made in the bone marrow, but it is entirely coincidental that that starts with a b, too. T cells are more faithful to their source. Though created in the bone marrow, they emerge from the thymus, a small organ in the chest just above the heart and between the lungs. For a very long time, the role of the thymus in the body was a complete mystery because it seemed to be just full of dead immune cells—“the place where cells went to die,” as Davis put it in his superlative book The Compatibility Gene. In 1961, Jacques Miller, a young Franco Australian research scientist working in London, unraveled a mystery. What Miller established was that the thymus is a nursery for T cells. T cells are a kind of elite corps in the immune system, and the dead cells found in the thymus were lymphocytes that had failed to pass muster because they were either not very good at identifying and attacking foreign invaders or because they were too eager to attack the body’s own healthy cells. They had, in short, failed to make the cut. It was an immensely significant discovery. As the medical journal The Lancet observed, it made Miller “the last person to identify the function of a human organ.” Many people have wondered why he has never been honored with a Nobel Prize.