Empathy is a teachable skill. Based on repeated practice, synaptic plasticity is key to teaching empathy.
What we do or do not practice will shape the neuroarchitecture of our brains as we respond to things in our environment.
Parents can scaffold difficult social concepts by breaking situations into small chunks and providing tools to make learning easier.
I perched on the edge of an undersized plastic chair across from my daughter’s teacher at our first elementary parent/teacher conference of the year. “Your daughter listens well and is so well behaved, but her reading level is not exactly where it needs to be, and she’s having trouble with some math skills. But she is very sweet and kind, and that’s so important too—you can’t teach those things, but don’t worry, we can teach her the math and reading.
It’s the Oreo cookie approach to giving parents bad news—They sneak the negative in as white filling surrounded by thin wafers of good. But as a neuroscientist, I was stunned by the complete inaccuracy of the last statement.Of course, you can teach those things. You can teach empathy, teach kindness, and respect. These are not innate talents or solely genetic gifts. They are teachable skills.
We understand how learning works for things like 2+2=4 pretty well. Teachers typically use active participation and frequent practice spaced out over a period of time to teach classroom content. But there aren’t special neuroscience rules to help learn empathy, creativity, or countless other life skills–they follow the exact brain mechanisms as learning math facts.
There are spines on the edges of neurons that mediate synaptic connections between neurons and govern how we learn. In kids, the spines are super dynamic. They appear or retract based on experience and how frequently they are used. If you keep using a pathway, the spines are more likely to stick around. This results in the reshaping of synapses and long-term learning.
That school conference was a moment of profound insight into the bare-bones social skills my daughter was (not) learning at school, and it explained a lot about why her perfect classroom presence was completely train-wrecked when she got home from school.
I knew the social landscape of this classroom was terrible. A girl in my daughter’s class plays a game called “bus,” where the other girls line up to take rides on her back at recess. The girl is the bus, and she carries passengers around. It looks benign to the teachers who stand and monitor play at recess. But in this game, the girl charges for rides. Usually, the fare is an imaginary five cents, but my daughter gets charged $100 to take her ride every time. Why? Because the girl said, my 20th percentile weight daughter is just too heavy.
I knew complaints were flowing in about the class social situation—It wasn’t just the “bus” game. Another parent, fed up with her daughter being picked on, made T-shirts that said the girl was a bully and tried to pass them out at school. This is the real reason I was at the parent/teacher conference. Yet, when I brought it up, I quickly detected a relatively new teacher overwhelmed with classroom dynamics who was grateful for an “easy,” compliant kid. I saw a classroom in which my daughter was figuring out how to react to bad social situations on her own and failing.
It’s here that parents need to think carefully about the qualities we want our children to possess and then consistently and purposefully create opportunities for our kids to practice those skills. Deliberate parenting will make children who live deliberate lives. In my daughter’s classroom, I could see that math was being practiced—there were even memorized arithmetic songs.
But they were not teaching kindness, conflict resolution, or even problem solving, which are the things I prioritize as a parent—the building blocks of empathy. The school is not just relying on parents to teach empathy at home. They are actually assuming that kids either come in with these skills, or they don’t get them. If, in turn, parents think kids are getting social skills at school, then all our kids drop through a crevice.
My daughter saw two choices with the bully in her class: Confront her or tell on her. Unable to do either, she felt completely stuck when the girl price gouged her on the playground. With repeated practice, she is learning to stand there and internalize it.
Those are not the synapses I want firing in her, so I taught my daughter how to practice empathy. It’s not just the queen bee who needs to be taught empathy. Cognitive empathy is a powerful skill, and it’s the underdog that needs powerful skills.
First, I asked my daughter to explain the girl’s actions as if she were her best friend. “I guess she feels like she doesn’t want to be alone on the playground, so she’s in charge, and if she’s in charge, she can decide which friends to have.”
Next, my daughter became a detective, looking for body language to find motivation and predict patterns in the girl’s behavior. Even at age seven, becoming a social sleuth enabled her to understand the situation better. This gave her back a measure of personal control, and eventually, the power to speak up for herself, instead of standing there, glued to the asphalt, feeling terrible.
Then, we learned conflict resolution skills the same way as math, using active participation and frequent practice spaced out over time. I became the girl, and in our living room, I rudely charged my daughter $100 a ride until her reactions to it were second nature.
We came up with a system so she could be heard in these situations: STAFF:
Say how you feel.
Tell them it’s not okay.
Ask for what you want to have happened.
Find a friend.
She wasn’t frozen—she knew what to say, and it rolled off her tongue. There was a scaffolding to cling to. We used these social skill pathways repeatedly—on our terms—until spines had formed between newly used neurons, the pathways were solidified, and learning had happened.
Since neuronal connections that have been used are more likely to fire the next time, it’s second nature for her now. If we expect our children to be socially independent and to do it well, they need tools to do it with.
Neuroscience tells us that practice defines us as people, that the pathways we choose define our nature. Activity influences the brain’s architecture, and this neural plasticity is constantly occurring, even when they are still watching TV, eating dinner, or choosing which birthday present to open first. These spines are actively growing and shrinking, and the experiences are actually turning on and off genes that support this process.
Eventually, the neuronal pathways we use most become more likely to fire as our “default” setting. In essence, we practice being ourselves until we become who we are. Viewed through this lens, every moment is a critical period to teach critical skills important to us—skills like creativity, self-control, social awareness, and compassion.
Several proven social learning curricula target empathy, social learning, and conflict resolution skills in the classroom that have gotten great results that last for years, including roots of empathy (K-8), positive action (K-12), and responsive classroom (K-5). Still, you don’t have to wait for the teachers to do it. The window for explosive synaptic formation doesn’t close when children hit elementary school or even high school.
Social connections are being formed even more so in tween and high school kids, continuing into adulthood. Your child’s critical period for development is now. There’s no bad age to start working on these skills, and there’s no one correct way to do it, as long as you’re consistently practicing and folding it into your everyday life.
Find a way that works for your family, and if you’re consciously empathetic in spirit, then it will seep into your child.
By: Erin Clabough, Ph.D.
Erin is a neurobiologist, author, mother, and professor interested in understanding neurodevelopment in children.
Part of Dennis Plenker’s daily job is growing cancer. And a variety of different ones, too. Depending on the day and the project, different tumors may burgeon in the petri dishes stocked in the Cold Spring Harbor Laboratory where Plenker works as a research investigator. They might be aggressive breast cancers.
They might be glioblastomas, one of the deadliest brain tumors that rob patients of their ability to speak or read as they crowd out normal cells. Or they might be pancreatic cancers, the fast and vicious slayers that can overtake a healthy person within weeks or even days.
These tiny tumor chunks are transparent and bland—they look like little droplets of hair gel that accidentally plopped into a plastic dish and took hold. But their unassuming appearance is deceptive. If they were still in the human bodies they came from, they would be sucking up nutrients, rapidly growing and dodging the immune system defenses.
But in Plenker’s hands—or rather in the CSHL’s unique facility—these notorious killers don’t kill anyone. Instead, scientists let them grow to devise the most potent ways to kill them. These tumor chunks are called organoids. They are three-dimensional assemblages of malignant growths used to study cancer behavior and vulnerability to chemotherapy and the so-called “targeted drugs”—the next generation therapies.
Scientists used to study tumors at a single-cell level, but because tumors grow as cell clusters in the body, it proved to be inefficient. The three-dimensional structures make a difference. For example, chemo might destroy the tumor’s outer cell layer, but the inner ones can develop resistance, so where single cells may die, a 3D mass will bounce back. Organoids can provide a window into these little-known mechanisms of drug resistance.
They can reveal how normal tissues turn malignant and where the cellular machinery goes off-track to allow that to happen. As their name suggests, organoids are scientists’ windows into organs, whether healthy or stricken with disease. You need to know your enemy to beat it, Plenker says, and cancer organoids offer that opportunity.
Taken from patients currently undergoing cancer treatments, these tumor chunks will reveal their weaknesses so scientists can find the cancers’ Achilles’ heel and devise personalized treatments. “Organoids are essentially patients in a dish,” Plenker says. Only unlike real patients, the organoids can be subjected to all sorts of harsh experiments to zero in on the precise chemo cocktails that destroy them in the best possible way.
And they will likely provide a more realistic scenario than drug tests in mice or rats, as animal models aren’t perfect proxies for humans.
These notorious killers don’t kill anyone. Instead, scientists devise the most potent ways to kill them.
The way that cancer proliferates in the body is hard to reproduce in the lab. Stem-cell research made it possible. After scientists spent a decade understanding how various cells multiply and differentiate into other cell types based on molecular cues and nourishment, they were able to make cells grow and fuse into tissues.
To stick together like bricks in a nicely laid wall, cells need a biological scaffold that scientists call an extracellular matrix or ECM, which in the body is made from collagen and other materials. Today, the same collagen scaffolds can be mimicked with a gooey substance called Matrigel—and then seeded with specific cells, which take root and begin to multiply.
Some tissue types were easy to grow—Columbia University scientists grew viable bones as early as 2010.1 Others, like kidney cells, were trickier. They would grow into immature tissues incapable of performing their job of cleaning and filtering blood. It took scientists time to realize that these cells wanted more than scaffolding and food—they needed to “feel at home,” or be in their natural habitat. Kidney cells needed the feeling of liquid being washed over them, the Harvard University group found, when they first managed to grow functioning kidney tissue in 2018.2
Cancers have their own growth requirements. In the body, they manage to co-opt the organism’s resources, but keeping them happy in a dish means catering to their dietary preferences. Different cancers need different types of molecular chow—growth factors, hormones, oxygen and pH levels, and other nutrients. Pancreatic adenocarcinoma thrives in low-oxygen conditions with poor nutrients.3 Glioblastomas feed on fatty acids.4 These nutrients are delivered to organoids via a specific solution called growth medium, which the lab personnel regularly doles out into the dishes.
Plenker is charged with keeping this murderous menagerie alive and well. He is the one who designs the cancers’ dietary menu, a specific protocol for each type. And while his official title is facility manager and research investigator who works closely with David Tuveson, director of the CSHL’s Cancer Center, he is essentially a cancer custodian, a curator of a unique collection that aims to change the paradigm of cancer treatment.
Plenker’s research area is pancreatic cancer—one of the most notorious killers known. Often diagnosed late and resistant to treatment, it is essentially a death sentence—only 8 to 10 percent of patients remain alive five years after diagnosis. The chemo drugs used to treat it haven’t changed in 40 years, Plenker says. In the past decade, physicians tried combining multiple drugs together with relative success. Identifying winning combos can save lives, or at least prolong them—and that’s what the organoids will help clinicians do better.
In a groundbreaking clinical trial called PASS-01 (for Pancreatic Adenocarcinoma Signature Stratification for Treatment), Plenker’s team collaborates with other American and Canadian colleagues to identify the most effective chemo cocktails and to understand the individual patients’ tumor behaviors, which would lead to more personalized treatments.5
Scientists know the same cancer types behave differently in different patients. Typically, all malignancies have the so-called “driver mutation”— the cancer’s main trigger caused by a mutated gene. But tumors also often have “passenger mutations” that happen in nearby genes. These additional mutated genes can generate various proteins, which may interfere with treatment.
Or not. Scientists call these mutated gene combinations tumor mutational signatures, which can vary from one patient to the next. With some cancers, doctors already know what mutations signatures they may have, but with pancreatic cancer they don’t have good tale-telling signs, or biomarkers. “There aren’t many biomarkers to help clinicians decide which chemo may be better for which patient,” explains oncologist Grainne O’Kane, who treats pancreatic cancer patients at the Princess Margaret Hospital in Toronto, Canada.
That’s the reason O’Kane participates in the PASS-01 trial—it will give doctors a better view into the exact specifics of their patients’ malignancies. As they take their patients’ biopsies, they are sending little cancer snippets to the CSHL to be grown into organoids, which will be subjected to chemo cocktails of various combinations to design more personalized regiments for them.
The hospital treats all patients with the so-called standard of care chemotherapy, which is more of a one-size-fits-all approach. Some patients will respond to it but others won’t, so the goal is to define the second line of chemo defense in a more personalized fashion. “That’s where the biopsies we send to Tuveson’s lab might be useful,” O’Kane says. “They can help us find something to benefit patients after the first line of chemo stopped working.”
Organoids are patients in a dish. Unlike real patients, organoids can be subjected to experiments.
Scientists can try all kinds of combos on the tumorous organoids, which they can’t do in living people. “You can treat 100 organoids with 100 different compounds and see which one works, or which compound does a good job and which ones don’t work at all,” Plenker says. That would also allow scientists to define the precise amount of chemo, so doctors wouldn’t have to over-treat patients with harsh drugs that create sickening side effects. Ultimately, organoids should take a lot of guesswork out of the process.
With about 150 patients’ adenocarcinomas already collected, the team hopes to come up with some answers. O’Kane says her team already has three patients for which they were able to design the more personalized second line of defense chemo, based on what their organoids revealed. They haven’t yet tried it, because the trial has only started recently, but this would be the next step.
“Being able to piece all this information together in real time as patients are moving through their therapies can really improve the outcomes,” O’Kane says. And while they may not be able to save all of those who graciously donated their biopsy snippets to science, it will help build better treatments in the future. “Even if we won’t be able to help these specific patients we’re hoping to use this info in the future clinical trials,” O’Kane says.
Organoids can also help understand how cancer develops. This is particularly true for breast cancers, says Camilla dos Santos, associate professor and a member of the CSHL Cancer Center. She studies the inner life of human mammary glands, more commonly referred to as breasts, and is also part of the cancer custodian crew. The hormonal changes that women go through during pregnancy subsequently modify breast cancer risk, sometimes lowering it and sometimes increasing—a complex interplay of the body’s chemicals.
“We know that women who get pregnant for the first time before they turn 25 years old, have a 30 percent decrease in breast cancer incidents later in life,” dos Santos says. “When they turn 60 or 70, 30 percent of them will not develop cancer.” On the contrary, those who are pregnant past 38 have a 30 to 50 percent increase in developing aggressive breast cancer types. Clearly, some molecular switches are involved, but they are very hard to study within the body. That’s where organoids can provide a window into the surreptitious process.
Using breast organoids, scientists can model the complex life of mammary glands at various stages of a woman’s life. And while most women wouldn’t want their breasts poked and pierced when they are pregnant or breastfeeding, many donate their tissues after breast reduction surgery or prophylactic mastectomy due to high-risk mutations like the BRCA gene.
That’s where organoids shine because scientists can not only grow them, but also give them the pregnancy hormonal cues, which will make cells generate milk, stop lactating, or do it again—and study the complex cellular interactions that take place in real life.
There’s a lot to study. At birth, mammary glands are similar in both genders—just little patches of the mammary epithelium tissue. But when puberty hits, the female glands fill up with the so-called mammary tree—a system of ducts for future milk production, which fully “blooms” in pregnancy.
“When a woman becomes pregnant, the duct tree expands, growing two types of cells—luminal and myoepithelial ones,” explains Zuzana Koledova, assistant professor of Masaryk University in Czech Republic who also uses organoids in her work. When the baby is born, the luminal cells, which line the inside of the ducts, produce the proteins that comprise milk.
The myoepithelial cells reside outside the ducts and work as muscles that squeeze the ducts to push milk out. Dos Santos likens this pregnancy mammary gland growth to the changes of the seasons. The images of sprouting ducts look like blossoming trees in the spring while later they shrivel like plants do in the fall.
The body governs these processes via the molecular machinery of hormones, which stimulate breast cells growth during pregnancy, and later cause them to die out. The two pregnancy-related hormones, prolactin and oxytocin, are responsible for milk production. Prolactin induces the luminal cells to make milk while oxytocin makes the myoepithelial cells contract. Once the baby is weaned, the levels of these hormones drop, causing cells to shrink back to their non-pregnant state.
With organoids scientists can observe these cellular dynamics at work. Koledova’s team had watched breast organoids secrete milk based on biological cues. They even recorded movies of cells pumping tiny milk droplets in the dish they were growing in. Using tiny snippets of donated breast tissue, the team grew the organoids inside the Matrigel matrix in the growth media and then added the two pregnancy hormones into the mix, explains Jakub Sumbal, a mammary gland researcher in Koledova’s group.
As they began to secret proteins that compose milk, the organoids, which looked like little domes inside the dish, changed from translucent to opaque. “At first, you can see through them, but then as they produce these proteins, they kind of darken,” Sumbal says. “And you can see them pushing out these little droplets.”
Cancer patients would no longer have to undergo chemotherapy by trial and error.
Dos Santos’s team, who also did similar work, outlined molecular changes that follow such dish-based hormonal cues in their recent study.6 In response to hormonal messages, cells produce proteins, which they display on their surfaces, like status symbols. During pregnancy the burgeoning cells prepping for milk production display the “proteins flags” that make them look important, attracting nourishment. When it’s time to die, they commit a cellular suicide.
They signal to the bypassing macrophages—immune system cleanup crew—to devour them. “They essentially say ‘come eat me!’ to the macrophages,” dos Santos says. “Because I’m no longer needed.”
The ability to mimic these processes in a dish, allows scientists to study the molecular switches that trigger breast cancer development—or minimize it. Scientists know that cancerous cells can hide from the immune system and even co-opt it into protecting themselves. They do it by displaying their own “do not eat me” protein flags on the surface and avoid destruction.
“Sometimes cancer cells can recruit specific types of immune cells to protect them,” dos Santos says. “They can not only say ‘do not eat me,’ but say ‘come hang out with me’ to the macrophages, and the macrophages will send suppressive signals to the B-cells or T-cells, the body defenders.” It is as if the cancer requests protection—a crew of guardians around it to defend against other cells that would otherwise wipe it out.
Scientists can’t telescope into the body to peek at these interactions, but they now can watch these stealth battles unfolding in a dish. “Right now we are looking at the proteins that are secreted by the organoids—the proteins that go on the surface of the organoids’ cells and what they would communicate to the immune system,” dos Santos says.
“Even when there’s no immune system surrounding them, they would still be doing that.” There’s a way to mimic the immune system, too. Scientists can add B-cells, T-cells, macrophages, and other players into the growth medium and watch the full-blown cellular warfare in action. “That’s the next step in our research,” dos Santos says.
Understanding what hormonal fluxes trigger breast cancer, and how it recruits other cells for safekeeping, can give scientists ideas for pharmaceutical intervention. “We can find drugs that pharmacologically turn off the switches that trigger cancer or interrupt its signaling for protection,” dos Santos says. “That opens novel ways to treat people.”
Can organoid research lead to a new standard of care for cancer patients? That’s the ultimate goal, researchers say. That’s why Plenker works at keeping his collection of cancer glops alive and well and thriving—he calls it a living biobank. And he keeps a stash in the cryogenic freezer, too.
He is also developing protocols that would allow commercial companies to grow organoids the same way chemical industries make reagents or mice suppliers grow rodents for research. A benefit of organoid experiments is they don’t involve animals at all.
Hospitals may one day start growing organoids from their patients’ biopsies to design and test personalized chemo cocktails for them. Once science crosses over to that reality, the entire treatment paradigm will change. Cancer patients won’t have to undergo chemotherapy by trial and error.
Instead their cancer organoids will be subjected to this process—knocked out by a gamut of drug combinations to find the winning one to use in the actual treatment. Plenker notes that once enough data is gathered about the tumors’ mutational signatures, scientists may create a database of tumor “mugshots” matching them to the chemo cocktails that beat them best.
And then just sequencing a biopsy sample would immediately inform oncologists what drug combo the patient needs. “We may be about 10 years away from that,” Plenker says, but for now there’s a lot more research to do. And a lot more cancers to grow.
Lina Zeldovich grew up in a family of Russian scientists, listening to bedtime stories about volcanoes, black holes, and intrepid explorers. She has written for The New York Times, Scientific American, Reader’s Digest, and Audubon Magazine, among other publications, and won four awards for covering the science of poop. Her book, The Other Dark Matter: The Science and Business of Turning Waste into Wealth, will be released in October 2021 by Chicago University Press. You can find her at LinaZeldovich.com and @LinaZeldovich.
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. While these symptoms may indicate cancer, they can also have other causes. Over 100 types of cancers affect humans.
These factors act, at least partly, by changing the genes of a cell. Typically, many genetic changes are required before cancer develops. Approximately 5–10% of cancers are due to inherited genetic defects. Cancer can be detected by certain signs and symptoms or screening tests. It is then typically further investigated by medical imaging and confirmed by biopsy.
Most cancers are initially recognized either because of the appearance of signs or symptoms or through screening. Neither of these leads to a definitive diagnosis, which requires the examination of a tissue sample by a pathologist. People with suspected cancer are investigated with medical tests. These commonly include blood tests, X-rays, (contrast) CT scans and endoscopy.
The tissue diagnosis from the biopsy indicates the type of cell that is proliferating, its histological grade, genetic abnormalities and other features. Together, this information is useful to evaluate the prognosis and to choose the best treatment.
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We came up with a system so she could be heard in these situations: STAFF:
