The Immune System: A Grand Unifying Theory for Biomedical Research
The germ theory of disease launched a revolution that transformed medicine. For the first time in history, disease was understood as an attack by microscopic organisms, organisms that were soon identified, characterized, and defeated.
Yet, we have not conquered disease. Cancer, heart disease, diabetes, stroke, and parasitic diseases are just some of the top causes of death in the world today. Research has helped us understand and treat these illnesses, but is there a unifying principle explaining them all? a common mechanism that could help us transform biomedical science once again?
Perhaps there is: the immune system.
Since 430 BC we have known of biological structures and processes that protect the body against disease; but even today we are just beginning to understand how deeply involved they are in our lives. The immune system’s cellular sentries weave an intricate early warning network through the body; its signaling molecules—the cytokines—trigger and modulate our response to infection, including inflammation; it is involved in even so humble a process as the clotting of blood in a wound. Today we are beginning to grasp how—from cancer to diabetes, from heart disease to malaria, from dementia to depression—the immune system is involved at a fundamental level, providing us with the framework to understand, and to better treat these wide-ranging ailments.
Cancer is often described as a "wound that never heals," referring to the chronic inflammatory state that creates a tumor-promoting environment. Indeed, cancer cells develop into a tumor by disabling and hijacking components of the immune system; immunosuppression and tumor-promoting inflammation are the two facets of cancer immunology. Both Type 1 and Type 2 diabetes are linked to the immune system; the former is an autoimmune condition in which the immune system attacks the insulin-producing cells in the pancreas, while the latter is linked to insulin resistance through high levels of cytokines produced during inflammation. Pro-inflammatory cytokines are also linked to heart disease, which is the leading cause of death in the developed world. The malaria parasite is an expert at manipulating our immune system, cloaking itself in molecules that reassure our immune sentinels that nothing is amiss, while wreaking havoc in our blood cells. Most intriguingly, we are now beginning to learn about the neuroimmune system, a dense network of biochemical signals synthesized in neurons, glial cells, and immune cells in our brains critical to the function of our central nervous system. Perhaps unsurprisingly, these markers of the neuroimmune system are disrupted in disorders such as depression, anxiety, stroke, Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Cytokine levels have been shown to vastly increase during depressive episodes, and—in people with bipolar disorder—to drop off in periods of remission. Even the stress of social rejection or isolation causes inflammation, leading to the fascinating idea that depression could be viewed as a physiological allergic reaction, rather than simply a psychological condition.
With this knowledge comes power: modulating the immune system to our advantage is a burgeoning field of research, particularly for cancer. Cancer immunotherapy heralds a turning point in treatment, with astonishingly rapid remissions achieved in some patients undergoing early stage clinical trials. New classes of drugs known as "checkpoint inhibitors" target specific immunological pathways, and we can reprogram "designer immune cells" to target cancer cells, changing the way that cancer is treated. Aspirin, a humble drug that reduces inflammation, may even be able to prevent some cancers; a tantalizing possibility that is currently being investigated in a large-scale clinical trial. Aspirin is already known to prevent heart attack and stroke in some people, also through its anti-inflammatory and anti-clotting effects. Fascinating studies imply that supplementing antidepressants with anti-inflammatory drugs can improve their efficacy. Vaccines for infectious diseases such as malaria and HIV are imminent, exploiting the power of the immune system to control and eradicate disease. It couldn’t happen at a better time; as antibiotics become increasingly ineffective due to widespread resistance, a problem classified by the World Health Organization as a "global threat," we will have to develop vaccines to fill that gap too. All of these fields are converging in ways we haven’t seen previously; oncologists, parasitologists, neurobiologists, and infectious disease specialists are all collaborating with immunologists.
It is an exciting time in biology and medicine. The new discoveries of the breadth and potential of our immune response merely hint at the revelations to come. These research findings will always capture the public’s attention, and always be newsworthy, because they represent the tantalizing hope that we can endure beyond disease, and prolong life. However, we must be careful, because the dismaying social success of sham medicine, with its "miracle cures" and "immune boosting diets," highlights how easily this message can be distorted. If we can drive research forward, while communicating it effectively, we may be on the cusp of another revolutionary period in biomedical science.
