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Kindle Notes & Highlights
by
Matt Richtel
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March 13 - March 28, 2020
Enbrel. It was aimed at treating rheumatoid arthritis. What was so widely anticipated about Enbrel, made by a Seattle company called the Immunex Corporation, was that it was designed specifically to limit the effects of an overreactive immune system without undermining the entirety of the system.
four major factors of day-to-day life that impact autoimmunity and immunity broadly, in the lives of Linda and Merredith, Bob, Jason, and you and me. These four factors are sleep, stress, the gut, and hygiene.
What does an immune system do when it’s not properly trained? It overreacts. It becomes aggrieved by things like dust mites or pollen. It develops what we called allergies, chronic immune system attacks—inflammation—in a way that is counterproductive, irritating, even dangerous. There has been a rise in autoimmunity too.
At least half of the cells in our body are bacterial, not human. One hundred trillion bacterial cells, and they are mostly in our gut. In the individual, they are called a microbiota, and the collection of them, and the breadth of their genetic building blocks, is called the microbiome.
Each of us develops a working relationship with our environment.
The microbiota in the gut of an infant who is delivered vaginally differs from the microbiota of an infant delivered by cesarean section.
“The bacterial population that develops in the initial stages is to a significant extent determined by the specific bacteria to which a baby happens to be exposed.”
The incredible cooperation between human and microbe has led to a new terminology to describe us. We are superorganisms.
But what specifically does the microbiome help with? Digestion, nutrition, obesity—broadly,
microbiome plays a key role in dampening the immune system, in addition to helping it to attack foreign invaders.
The hygiene hypothesis stated that our environment has become so clean that it has left our immune system insufficiently trained.
For most of human history, stress meant imminent threat, and imminent threat meant the body needed to be alert, fully functional, even a bit superpowered. This is where the hormone cortisol comes in. It is secreted by the adrenal gland.
In times of stress, the release of cortisol comes slightly after the release of one of two other key hormones, norepinephrine and epinephrine.
I mentioned the sympathetic response, the flight-or-fight response, above. It has a powerful impact on heart rate, blood pressure, the flow of digestive juices, and other core involuntary functions.
So sleep sets off and intensifies an adrenaline-fueled dampening of the immune system.
“What happens today is that many people are living with imaginary bears at every step of their lives—something in the news or around the bend is going to get them.” What followed was what he called a “norepinephrine high.”
the connection between the immune system and the adrenal system may be so intimate that it’s difficult to separate the two.
moment of one of the twentieth century’s major scientific moments—when CD80 and CD86 met their mates.
“They get a signal. They kill themselves. If it didn’t work, people would get diabetes, multiple sclerosis, lupus,”
The term for one of the key cell types stimulating regeneration of our tissue is fibroblast—highly versatile and hearty cells that proliferate and migrate to the site. These cells are drawn by signals sent by macrophages.
“Tumor production is possible overhealing,”
“Tumors are wounds that do not heal.”
Werner explained to me that a cell that turns cancerous needs to undergo at least five to ten different genetic changes.
mutated cell that is likely to survive and become cancer has chanced upon the ability to send signals to immune cells with the instruction: Don’t attack me; protect me and nurture me.
the likelihood of getting cancer depends in large part on how often a person experiences injury or certain types of injury. This is just math. More injury means more cell division and, simply, more opportunity for dangerous mutation to occur.
The risks grow with each puff. Similarly, sun exposure, absent sunscreen, presents another opportunity for a wound and an inflammatory response, which, combined with mutations directly induced by UV irradiation, enhance the risk of the development of skin cancer, including the particularly dangerous melanoma.
James Allison had discovered we could modulate the immune system by playing with CTLA-4. That’s the molecule on T cells that helped dampen or kill an immune system response.
The PD stands for programmed death, which I’ve briefly described already. It is a molecule on a T cell that causes the immune system to self-destruct—in effect, to commit suicide.
Lonberg was helping give birth to a new class of drug called monoclonal antibody therapeutics.
monoclonal antibodies are exact copies of antibodies. Antibodies are essential pieces of the immune system. They sniff out and bind to antigens on other cells, including bad actors.
He pictures a T cell, roaming the body, and it has powerful cannons on its surface. The job of this artillery is to take out dangerous organisms. But the surface of the T cell also has many antennae. The antennae receive signals from other parts of the immune system authorizing the T cell to fire or, as often as not, telling it not to fire. The cancer had succeeded in connecting to an important antenna, or maybe several, that had hit pause on the cannon. So Lonberg and his cohorts wondered if they could use an antibody to block that antenna from getting a signal.
Remember cytokines? They are proteins that send signals to the immune system, creating a powerful, virtually instantaneous telecommunications network,
Food and Drug Administration approved for use in people with melanoma, that deadly skin cancer, the drug called Yervoy I mentioned a few pages earlier, made by Bristol-Myers.
“a novel type of cancer drug that works by unleashing the body’s own immune system to fight tumors.”
beefed up his microbiome with a yogurt diet—“we try to protect them and regrow the good bacteria in their gut.”
8, 1990, was a sunny day with a lenticular cloud over the Alaskan peak of Denali, then officially known as Mount McKinley. Dr. Brunvand
a potent new danger rose on the list of mortal causes: neurodegeneration. Alzheimer’s, Parkinson’s, sometimes Lou Gehrig’s disease, in which the motor function of the brain disintegrates.
When a child is conceived, one of the first organs to form is the yolk sac. It eventually becomes round and grows to an average of 6 millimeters. It is a sort of food filter, with nutrition coming from the mother through the yolk sac and into the tiny forming life.
As the brain develops and neurons mature and die, the microglia consume the refuse. Does this sound familiar? It should. It is like the work of monocytes. It is phagocytosis.
our brains wind up over the years with a lot of detritus—garbage—that needs to be eaten up. That spurs the microglia to eat synapses. The janitor starts doing its job, but then the janitor goes nuts and starts eating everything in sight.
what people share in common or prey on what divides them. The lesson of the immune system is that the better able we are to find common ground, the more allies and weapons we have to contend with a greater, common foe.
