The Beautiful Cure summary

Do you know what the most studied topic in human biology is? Nope – it’s not depression, digestion, or sleep. It’s the incredibly complex response of the body to a minor injury like a cut.

Anyone can tell you the basic things that happen to your body after it’s scratched or scraped. Your skin breaks, you bleed, the area turns red, and, eventually, it scabs over. 

This all sounds very simple. But there’s an enormously complex system of cells, tissues, proteins, and hormones all working together to make it happen. That’s your immune system, and it actually wasn’t well understood until recently. 

Fortunately, many scientists throughout history have been utterly fascinated by the human immune system. In these blinks, we’ll get acquainted with some of those scientists and their discoveries. Then we’ll take a closer look at some of the immune system’s complexities, including the surprising factors that can change how it functions.

Along the way, you’ll discover

• what it means for an immune cell to be immature;
• why your body sometimes attacks itself; and
• the best time to use an inhaler. 

In hindsight, it seems obvious. But in 1989, Charles Janeway was the first person to argue that the body can’t just react to every unknown substance that enters it. He realized that a second signal is necessary in order to kick off an immune reaction. 

Janeway agreed with his predecessors that the immune system must respond to things that haven’t been in the body before. But he also argued that this response must be limited to germs. Otherwise, our immune systems would be constantly overreacting.

Janeway’s research was right about the overarching structure of the immune system: it involves innate and adaptive immunity, which work together to form immune responses.

The key message here is: Our innate immune systems are programmed to deal with specific threats.

Janeway primarily argued for the existence of pattern-recognition receptors – or just receptors, as they’re known today. These are fixed shapes on the surface of T and B cells that interlock specifically with germs or infected cells. In other words, they’re designed to help our bodies fight illness. 

Janeway’s theory was one step toward a more holistic understanding of the immune system. Another piece of the puzzle was provided by an unlikely critter: the fruit fly. 

Scientist Jules Hoffman examined fruit flies whose toll genes, which develop in the embryo, were inactive. His experiments showed that flies are completely dependent on the toll gene in order to clear fungal infections. And the truly exciting part? Humans turned out to have a similar gene – ten of them, in fact! 

But how exactly did toll genes work? One more scientist, Bruce Beutler, completed that puzzle.

On September 5, 1998, Beutler discovered that the toll gene called TLR4 encodes for a pattern-recognition receptor. This gives immune cells with this particular receptor the innate ability to lock on to a specific type of bacteria called LPS. When the cell locks on to LPS bacteria, this signals to the body that there may be something in it that requires an immune response.

After Beutler’s discovery, other scientists were able to determine which kind of germ each receptor can lock on to. TLR5 and TLR10, for example, specifically lock on to molecules found in parasites. 

The innate immune system can thus recognize particular types of germs or threats – and has specific cells optimized to deal with them. But what connects the innate and adaptive immune systems? We’ll look at that in the next blink.

In the 1970s, Canadian immunologist Ralph Steinman was grappling with an important yet baffling question: How, exactly, do immune reactions start?

At the time, scientists had already discovered that immune reactions couldn’t be started in a cell culture dish without some T and B cells from the spleen. But Steinman wondered what in that spleen material was so critical to kickstarting an immune reaction.

So Steinman decided to get up close and personal with one of those cell culture dishes. And he found something no one else had: stuck to the glass were spiky cells with spindly, tree-like projections sticking out of them. He decided to call them dendritic cells. 

The key message here is: Dendritic cells are alarms that can alert the human body when something’s wrong.

Over a 10-year period, students in Steinman’s lab discovered that dendritic cells taken from skin were much worse at stimulating an immune reaction than ones from the spleen. But when the dendritic cells from skin were grown in a cell culture dish for a few days, they became potent. What did this mean?

Well, it turned out that dendritic cells basically exist in two states – “on” and “off.” 

Immature dendritic cells are considered “off” because they have little ability to trigger an immune reaction. But they can capture germs, bacteria, and dead cells. Meanwhile, mature dendritic cells are considered “on” because they can trigger an immune reaction – and switch other immune cells “on” as well. 

Putting it all together, immature dendritic cells patrol our organs and tissues – especially those that come into contact with the germ-filled outside world. They detect germs, then capture and destroy them. 

Once a dendritic cell has captured a germ, it switches into a mature state and travels into the spleen or the lymph nodes. Then, the mature cell “shows” other cells the germ fragments it’s collected. In order  for the T cells to respond to the threat, however, the dendrite needs to have co-stimulatory proteins on its surface. These are only present at high levels in dendritic cells that have come into contact with germs. If there’s no co-stimulatory protein, T cells will become tolerant, and they won’t be able to cause immune reactions at all. 

Dendritic cells serve as an alarm system for the immune system. The next type of cell we’ll be looking at is its communications department.

Have you ever had two colds at once? It might be impossible for you to say for sure, but the answer is probably not. Even as far back as the nineteenth century, scientists were aware that being infected with two different viruses at the same time is very uncommon. But why is that?

Back in the 1950s, two scientists, Jean Lindenmann and Alick Isaacs, set out to find the answer. What they found – a new type of cell called cytokines – changed medical science forever.

The key message here is: Cytokines help the body coordinate the right immune response.

Lindenmann and Isaacs’ discovery started with an experiment. In it, they infected bits of membrane from fertilized chicken eggs with a mixture of flu virus and red blood cells. 

The two scientists found something exciting. The red blood cells that had been coated with the virus and then washed off the egg membrane were able to stop another, separate viral infection. At this point, the two men weren’t considering that an entirely new substance could be responsible for this. Instead, they reasoned that perhaps some fully intact virus could have detached from the red blood cells and thereby blocked a second infection.

To test this, they painstakingly separated any possible virus from the liquid in their test tubes and from the red blood cells. What they found was that the liquid itself was able to stop viral infections.

This was baffling, because it meant there was some substance or particle in the liquid doing the work. What exactly the substance was remained a mystery; Lindemann decided to name it interferon.

Eventually, scientists determined that interferon was a soluble protein, and that the human body has over a hundred proteins just like it. Collectively, they’re called cytokines. 

Each cytokine has a unique purpose. Some help to switch the body’s systems on or off. But their common function is to serve as communication between cells and tissues, helping our bodies form just the right immune response.

The best part? Cytokines have enormous potential to be used in medication.

One type of cytokine – actually, the very same interferon that Lindenmann and Isaacs discovered – now forms part of the treatment for hepatitis B and C. Other cytokines can be used to kill cancer cells, particularly melanoma and advanced kidney cancer. 

We’ve just heard all about cytokines. Now it’s time to learn about their alter ego, the anti-cytokine.

Rheumatoid arthritis is an autoimmune disease that affects roughly 1 in 100 people in every country. It causes immune cells to accumulate in the joints and destroy cartilage and bone; the resulting pain and stiffness can be debilitating. 

Fortunately, we now have powerful medication to treat this painful condition. But that medication may never have come about without the work of one scientist, Sir Marc Feldmann. Feldmann’s discovery of anti-cytokines sparked an industry that now provides pain relief to millions of people.

The key message here is: Anti-cytokines stop destructive immune responses and could help cure autoimmune diseases. 

After choosing to study rheumatoid arthritis in particular, Feldmann teamed up with a clinician, Sir Ravinder Maini, to try to tackle the disease. 

First, they isolated cells and fluid from patients’ joints. They soon found that one particular cytokine was especially abundant: tumor necrosis factor, or TNF for short. TNF has the ability to kill diseases, but it’s also quite toxic to the human body. Feldmann and Maini wondered what would happen if they blocked TNF’s activity in patients’ joints. 

To block TNF, the two scientists needed an anti-cytokine. Anti-cytokines can come in the form of antibodies, which are Y-shaped soluble proteins that can neutralize germs. The average person has around 10 billion differently shaped antibodies. But Feldmann and Maini needed one that could specifically latch on to and destroy TNF, essentially acting as an anti-cytokine. 

Fortunately, scientist Jan Vilcek had already created the necessary anti-TNF antibody. The first patient with rheumatoid arthritis was treated with the antibody on April 28, 1992, and other patients soon followed. The results were astonishing. Patients said they felt better immediately after receiving the antibody infusion. And after two weeks, the reduction in swelling and tenderness in their joints was significant. One person could even play golf again!

Thanks to this anti-cytokine alone, millions of people with rheumatoid arthritis are able to live without wheelchairs. And they’re not the only ones who have benefited. TNF-blocking anti-cytokines can also treat Crohn’s disease and colitis, which are caused by inflammation in the digestive system. In the future, the discovery of TNF could affect all kinds of illnesses, from the common cold to diabetes to cancer.

So far, we’ve established that the immune system is extremely complex and multilayered. And it only gets more so! The next few blinks will look at some factors that can alter the immune system’s functioning.

In 1948, biochemist Edward Kendall obtained a substance he called adrenal compound E from pharmaceutical company Merck. He gave the compound to his partner, physician Philip Hench, who administered it to a patient with debilitating rheumatoid arthritis. Two days after receiving the vaccination, the patient could walk again. It seemed like a miracle.

Nowadays, compound E is known as cortisone. Eventually, scientists discovered that cortisone was not only effective in treating rheumatoid arthritis, but could also reduce skin irritations when used in a cream.

But how does it work, exactly? Well, as the name suggests, it’s based on the hormone cortisol, which is secreted by our adrenal glands. Essentially, cortisol levels rise when we’re stressed, to prepare our bodies to respond quickly to potential threats. But cortisol also suppresses our immune systems. 

The key message here is: Our immune systems need stress hormones, but too much can be destructive.

Cortisol taught us that stress – something we think of as occurring in our minds – also has effects on our bodies. 

Evidence shows that people who are stressed for long periods have a harder time fighting viral infections and take longer to heal when they are injured. They also respond worse to vaccination. And one study even determined that men diagnosed with HIV were two to three times more likely to develop AIDS if they had higher levels of stress or less social support. 

It’s clear that stress greatly affects the immune system. Of course, this poses a question: How can we counteract stress? 

Several studies have tested the potential stress-relieving effects of everything from laughter to tai chi. In one study, patients with diabetes watched comedy films with hospital staff. These patients experienced increased immune system activity. However, this could have been due to the social camaraderie of the situation rather than the laughter. 

Or take mindfulness, a technique that aims to get practitioners to focus on the present moment. An analysis of 20 trials found that mindfulness practice could lower some markers of inflammation and increase numbers of particular T cells in patients with HIV. 

On the other hand, some trials concluded that mindfulness had no effect on cytokine and antibody levels. So it’s not yet clear whether mindfulness can decrease stress and aid our immune systems. For now, the best we can say is that it may help.

We know that planetary motions affect countless aspects of life on Earth, from the tides to the seasons. But the planets – more specifically, the cycles of day and night – affect us on an even more acute level. Statistics tell us, for example, that car accidents happen most often at 3:00 a.m. 

Our immune systems, too, work differently depending on the time of day. Studies have shown that mice infected with salmonella at 10:00 a.m. – just about bedtime for mice – have a strong immune response. Being infected at 10:00 p.m., however – right when the mice are waking up – leads to a weaker immune response. It turns out that the same pattern is true for humans.

The key message here is: Our immune systems function differently at certain times of day – and at certain points in our lives. 

Human immune systems are strongest during our natural rest time – night – and weakest during the day. One reason for this is that our bodies keep cortisol, the hormone that suppresses our immune system, at low levels during the night. 

While we aren’t exactly sure why this occurs, we’re definitely aware of the consequences. For example, a strong but unwanted nighttime immune response can worsen symptoms of gout, an inflammation of the joints. 

Fortunately, we can also use the time of day to our immune systems’ advantage. Inhaled steroids given to asthma patients, for instance, are four times more effective when taken once a day between 3:00 p.m. and 5:30 p.m.

And it’s not just the time of day that greatly affects our immune function. It’s the time we’re at in our lives, too.

As we age, our bodies begin producing fewer immune cells, and those cells take longer to detect and respond to signs of disease. However, the blood of elderly people actually shows more signs of an active immune response than younger people’s blood. This indicates inflammation, which means the immune system is less able to tell the difference between germs and its own healthy cells. 

Fortunately, there’s good news. Vaccines can actually be tailored to the particular characteristics of elderly immune systems. Flaggelin, for example, is a germ molecule that the immune system can easily detect. Elderly mice and elderly humans both respond better to a flu vaccine that includes flaggelin than one that doesn’t.

We often think of autoimmune diseases in isolation. Rheumatoid arthritis, for example, doesn’t really seem to have much to do with diabetes, which in turn doesn’t seem to have much to do with HIV. But in fact, that’s not quite true. Actually, autoimmune diseases may have a common underlying cause. 

The work of Shimon Sakaguchi, a Japanese scientist, led to a revolution in the understanding of autoimmunity. But Sakaguchi’s work stemmed from that of two other Japanese scientists, Yasuaki Nishizuka and Teruyo Sakakura. These two were working to determine whether hormones played any role in the development of cancer.

As part of their research, Nishizuka and Sakakura removed the hormone-producing thymus gland from mice. After the thymus gland was removed, the mice’s ovaries completely self-destructed! It was an autoimmune reaction in the extreme. But could autoimmune reactions be stopped after they’d started? And if so, how?

The key message here is: Low levels of regulatory T cells could cause all kinds of autoimmune diseases.

Sakaguchi used Nishizuka and Sakakura’s experiment as a jumping-off point to see if he could stop an autoimmune disease in mice. So he simply gave the mice with the disease a vaccination of immune cells from a healthy mouse. This stopped the autoimmune disease in its tracks. 

Sakaguchi’s experiment showed that a healthy mouse would have some immune cells that could attack both germs and the body itself. Other immune cells, however, specifically stop autoimmune reactions. The latter type of cell came to be known as regulatory T cells, and it turned out that low levels of them could underlie many types of autoimmune disease.

We all have regulatory T cells, and the ones in the gut are perhaps the hardest-working. These cells have to maintain an extraordinarily difficult balance between good bacteria – the ones that help us digest various molecules – and bad, disease-causing bacteria. 

So how can we help the regulatory T cells in our guts? Well, having a high-fiber diet full of fruits, vegetables, and cereal grains is one way. This type of diet can reduce blood pressure, lower the risk of colon cancer, and also stimulate the production of regulatory T cells. This helps protect us against autoimmune disease.

There’s no doubt that regulatory T cells will be part of the revolution in the study of autoimmune diseases. But such a revolution has already begun in the treatment of cancer. 

Sharon Belvin was diagnosed with stage IV melanoma at the age of 22. The skin cancer had already spread into her lungs, and doctors gave her only a 50 percent chance of surviving the next six months. Treatments like chemotherapy hadn’t worked, so, as a last-ditch effort, she signed up for an experimental clinical trial for a new medication.

After three months and four injections, the tumor in Belvin’s left lung had shrunk by 60 percent. A few more months passed, and the tumor had completely disappeared. Sharon was in remission from cancer.

Sharon’s treatment had been developed by Jim Allison, whose discovery led to a revolution in cancer medicine. Its success is directly due to curiosity-driven research into how our immune systems work as a whole. 

The key message here is: Harnessing our immune systems’ power could help us beat all kinds of devastating diseases.

Allison began by considering the way that immune responses end. After T cells first detect a threat, they multiply. Then, once the threat has been dealt with, the immune response gets switched off and the body returns to its normal state. However, with cancer, the immune response is switched off too early, which gives the cancer cells free rein to continue multiplying.

Allison’s idea was to switch off the immune system’s own “switch off” signal. That way, the body could continue fighting the cancer for as long as needed.

Recall that proteins on the surface of dendritic cells send a warning signal to receptor proteins on T cells. What Allison did was identify a second mysterious receptor on the surface of T cells, called CTLA-4. In both Allison’s lab and another, scientists determined that blocking it with an antibody actually increased the reaction of T cells against a threat. 

Could blocking this receptor treat tumors? Allison decided to find out.

Patients treated with the CTLA-4-blocking antibody had their tumors expand at first because they were being flooded by immune cells. But then, they steadily decreased in size over time. This approach, known as immune checkpoint therapy, is now a mainstream method of fighting cancer.

Allison’s is just one example of a treatment that harnesses the innate power of the human immune system. Since it was first developed, scientists have discovered over 20 other receptors that switch off specific types of immune cell. Taking the brakes off may help fight not only cancer, but also chronic infections like HIV.

The research is still young, but we may very well be on the eve of a revolution in immunology. Whatever the outcome, there’s no denying that our immune systems are immensely powerful – and harnessing that power could improve the lives of countless people.