Feel freezing cold all the time? Can’t seem to warm up? We explain why some of us feel colder than others, even when the heating is on full blast. With so many of us working from home, deciding when to turn on the central heating is a now a crucial part of the day. You get to 10am and you start to wonder why you’re still freezing… and if it’s too early to switch the dial on.
I’m freezing pretty much all the time, winter or not. I can’t feel my fingers in spring and I still need a jacket during July’s heatwave evenings. I won’t even begin to tell you how many layers I wear when I go skiing. Yet, my housemate can walk down the street in shorts in December, and others sweat the second they put a coat on.So why do some people just seem to feel the cold more than others – and what does it mean?
Finding out what is ‘normal’ when it comes to our temperature is pretty tricky though, explains Dr Clare Eglin from the Extreme Environments Laboratory in the Health and Exercise Science department at the University of Portsmouth. While our core temperature should ideally not change, “our perception of whether we find somewhere warm or cool is very individual and usually down to our skin temperature,” Dr Eglin says.
“This is what gives our body feedback, and lots of things can affect that from the clothes that we are wearing to the activities we are doing – and also the wind and dampness of the environment.” However, there are genetic and personal factors that can mean that two people, wearing the same thing, in the same environment feel different temperatures.
Why do some people feel colder than others?
Everyone’s body has a slightly different reaction to cold and some people feel cold more often than others, which is known as cold intolerance.
There are many factors that contribute to this, including:
Overall body size can impact how cold you feel, as smaller people have less cells in their body that produce heat
People with higher levels of body fat and/or muscle mass have more insulation and a higher resting metabolic rate so burn energy faster
Being active not only warms the body immediately but can have a long-term effect on temperature regulation
Older people also tend to have a slower resting metabolic rate, so may feel the cold more
These factors do mean that gender is a big divider, as women are generally smaller than men and carry less muscle mass. We’ve all fought over the thermostat in the office (or central heating while at home) but the fact is that “the temperature deemed comfortable for most people is meant to be about 21 degrees. Actually, that’s ideal for a man in a suit, but women generally do better with a higher temperature,” says Dr Eglin.
Interestingly, we feel this disparity internally too. “Estrogen and progesterone, which change throughout the menstrual cycle, affect how quickly our blood vessels constrict to the cold. So depending what part of the menstrual cycle you’re in, you might find your hands and feet get colder, affecting your overall temperature perception,” says Dr Eglin.
Plus, your temperature perception can change throughout the day. “For instance, at six o’clock in the morning your core temperature is at its lowest, and from midday to mid-afternoon, it’s at its highest,” she adds.
Why do my hands feel cold?
Don’t panic if, like me, you have hands like ice cubes on a summer’s day. “It is a very typical thing, particularly for women, as our hands are really good for regulation,” says Dr Eglin. Our hands have a large surface area but a small volume and are filled with lots of blood vessels very close to the surface of the skin. “They’re very good for losing heat and so therefore, when you’re slightly cool, the blood flow shuts down,” she says.
While “peripheral temperature is generally nothing to worry about”, it can be a sign of Raynaud’s syndrome, an extreme response to cold or stress where arteries narrow to the point that fingers and toes turn white or blue and feel cold and numb – but circulation returns to normal when warm again.
Is it bad to be cold all the time?
Generally, being cold is simply down to our body type, and as long as we take precautions it’s not a bad thing. But if constant coldness is mixed with other symptoms it could be a sign of something more serious. For example, coldness paired with tiredness or dizziness could be a symptom of an iron or B12 deficiency, or even anaemia.
Constantly being cold coupled with hair loss, a change in your digestive system and weight gain could also be a sign of a low thyroid – when the gland stops producing enough thyroxine (a hormone which regulates your metabolism).
Ultimately, your body is pretty good at regulating itself, so trust what it’s telling you. “Our behaviour is the most important thing when it comes to keeping warm. I think quite often we underestimate the weather in the UK. You always hear people say ‘It’s not that bad, it’s not like we’re in the Arctic!’, but with the windchill and dampness it can be very cold. We don’t pay enough attention to that,” says Dr Eglin. So, bundle up when you’re feeling the chill.
Chloe Gray is the senior writer for stylist.co.uk’s fitness brand Strong Women. When she’s not writing or lifting weights, she’s most likely found practicing handstands, sipping a gin and tonic or eating peanut butter straight out of the jar (not all at the same time).
A new study from the University of California San Diego School of Medicine has found that 'de novo mutations' in a father's sperm can predict the risk of autism in a child (file image)
Mutations in a father’s sperm could predict the risk of a child being diagnosed with autism, a new study suggests. The genetic flaws, known as ‘de novo mutations’, can appear in a child’s DNA through problems with sperm production.
Researchers found that 15 percent of men with autistic children had these disease-causing mutations in their sperm.The team, from the University of California San Diego School of Medicine, says the findings could lead to test in which fathers have their sperm screened to determine their future children’s risk of the developmental disorder.
Autism spectrum disorder (ASD) is a developmental disorder in which sufferers have a hard time communicating and with behavior.It encompasses several conditions – including autism and Asperger’s syndrome – and symptoms can range from mild to severe.
Children are usually diagnosed by age two after they exhibit signs such as reduced eye contact, not responding to their name and performing repetitive movements.According to the Centers for Disease Control and Prevention, about one in 59 children has ASD.
Boys are much more likely – up to four times – to have the condition than girls. Despite decades of research, the causes of ASD remain a mystery. Both genetics and environmental factors are believed to play a role. However, recent studies have suggested that de novo mutations may be the cause of between 10 and 30 percent of ASD cases.
These mutations occur for the first time in a family member as the result of a mutation in the sperm or egg of a parent. For the study, published in the journal Nature Medicine, the team looked at the sperm of eight fathers who had children already diagnosed with ASD.
The sperm was analyzed for mosaicism, a condition in which a person has genetically different sets of cells within their body. ‘While medical textbooks teach us that every cell in the body has an identical copy of DNA, this is fundamentally not correct,’ said first author Dr Martin Breuss, an assistant project scientist at UC San Diego Health Sciences.
‘Mutations occur every time a cell divides, so no two cells in the body are genetically identical.’ Mosaicism occurs in an unborn baby’s early developmental stages after an error in cell division. ‘[It] can cause cancer or can be silent in the body. If a mutation occurs early in development, then it will be shared by many cells within the body,’ said Dr Breuss.
‘But if a mutation happens just in sperm, then it can show up in a future child but not cause any disease in the father.’Disease-causing mutations were found in about 15 percent of the fathers’ sperm cells, the researchers said.
‘My laboratory has a long-standing interest in understanding the origins of pediatric brain disease, and how mutations contributes to disease in a child,’ said co-senior study author Dr Joseph Gleeson, a professor of neuroscience at UC San Diego School of Medicine.
‘We previously showed that mosaicism in a child can lead to diseases like epilepsy. Here, we show that mosaicism in one of parents is at least as important when thinking about genetic counseling.’
The researchers say their findings could be developed into a clinical test that fathers could undergo to test the risk of recurrence in future children or for men who haven’t had children yet but want to know the risk.
A wedding in Oklahoma leads to 15 vaccinated guests becoming infected with the coronavirus. Raucous Fourth of July celebrations disperse the virus from Provincetown, Mass., to dozens of places across the country, sometimes carried by fully vaccinated celebrants.
As the Delta variant surges across the nation, reports of infections in vaccinated people have become increasingly frequent — including, most recently, among at least six Texas Democrats, a White House aide and an aide to Speaker Nancy Pelosi.
The highly contagious variant, combined with a lagging vaccination campaign and the near absence of preventive restrictions, is fueling a rapid rise in cases in all states, and hospitalizations in nearly all of them. It now accounts for about 83 percent of infections diagnosed in the United States.
But as worrying as the trend may seem, breakthrough infections — those occurring in vaccinated people — are still relatively uncommon, experts said, and those that cause serious illness, hospitalization or death even more so. More than 97 percent of people hospitalized for Covid-19 are unvaccinated.
“The takeaway message remains, if you’re vaccinated, you are protected,” said Dr. Celine Gounder, an infectious disease specialist at Bellevue Hospital Center in New York. “You are not going to end up with severe disease, hospitalization or death.”
Reports of breakthrough infections should not be taken to mean that the vaccines do not work, Dr. Anthony S. Fauci, the Biden administration’s top pandemic adviser, said on Thursday at a news briefing.
“By no means does that mean that you’re dealing with an unsuccessful vaccine,” he said. “The success of the vaccine is based on the prevention of illness.”
Still, vaccinated people can come down with infections, overwhelmingly asymptomatic or mild. That may come as a surprise to many vaccinated Americans, who often assume that they are completely shielded from the virus. And breakthrough infections raise the possibility, as yet unresolved, that vaccinated people may spread the virus to others.
Given the upwelling of virus across much of the country, some scientists say it is time for vaccinated people to consider wearing masks indoors and in crowded spaces like shopping malls or concert halls — a recommendation that goes beyond current guidelines from the Centers for Disease Control and Prevention, which recommends masking only for unvaccinated people.
The agency does not plan to change its guidelines unless there is a significant change in the science, said a federal official speaking on condition of anonymity because he was not authorized to speak on the matter.
The agency’s guidance already gives local leaders latitude to adjust their policies based on rates of transmission in their communities, he added. Citing the rise of the Delta variant, health officials in several California jurisdictions are already urging a return to indoor masking; Los Angeles County is requiring it.
“Seatbelts reduce risk, but we still need to drive carefully,” said Dr. Scott Dryden-Peterson, an infectious disease physician and epidemiologist at Brigham & Women’s Hospital in Boston. “We’re still trying to figure out what is ‘drive carefully’ in the Delta era, and what we should be doing.”
The uncertainty about Delta results in part from how it differs from previous versions of the coronavirus. Although its mode of transmission is the same — it is inhaled, usually in indoor spaces — Delta is thought to be about twice as contagious as the original virus.
Significantly, early evidence also suggests that people infected with the Delta variant may carry roughly a thousandfold more virus than those infected with the original virus. While that does not seem to mean that they get sicker, it does probably mean that they are more contagious and for longer.
Dose also matters: A vaccinated person exposed to a low dose of the coronavirus may never become infected, or not noticeably so. A vaccinated person exposed to extremely high viral loads of the Delta variant is more likely to find his or her immune defenses overwhelmed.
The problem grows worse as community transmission rates rise, because exposures in dose and number will increase. Vaccination rates in the country have stalled, with less than half of Americans fully immunized, giving the virus plenty of room to spread.
Unvaccinated people “are not, for the most part, taking precautions, and that’s what’s driving it for everybody,” said Dr. Eric J. Rubin, the editor in chief of the New England Journal of Medicine. “We’re all susceptible to whatever anyone’s behavior is in this epidemic.”
Dr. Gounder likened the amount of protection offered by the vaccines to a golf umbrella that keeps people dry in a rainstorm. “But if you’re out in a hurricane, you’re still going to get wet,” she said. “That’s kind of the situation that the Delta variant has created, where there’s still a lot of community spread.”
For the average vaccinated person, a breakthrough infection is likely to be inconsequential, causing few to no symptoms. But there is concern among scientists that a few vaccinated people who become infected may go on to develop long Covid, a poorly understood constellation of symptoms that persists after the active infection is resolved.
Much has been made of Delta’s ability to sidestep immune defenses. In fact, all of the existing vaccines seem able to prevent serious illness and death from the variant. In laboratory studies, Delta actually has proved to be a milder threat than Beta, the variant first identified in South Africa.
Whether a vaccinated person ever becomes infected may depend on how high antibodies spiked after vaccination, how potent those antibodies are against the variant, and whether the level of antibodies in the person’s blood has waned since immunization.
In any case, immune defenses primed by the vaccines should recognize the virus soon after infection and destroy it before significant damage occurs.
“That is what explains why people do get infected and why people don’t get seriously ill,” said Michel C. Nussenzweig, an immunologist at Rockefeller University in New York. “It’s nearly unavoidable, unless you’re going to give people very frequent boosters.”
Understand the State of Vaccine Mandates in the U.S.
There is limited evidence beyond anecdotal reports to indicate whether breakthrough infections with the Delta variant are more common or more likely to fan out to other people. The C.D.C. has recorded about 5,500 hospitalizations and deaths in vaccinated people, but it is not tracking milder breakthrough infections.
Additional data is emerging from the Covid-19 Sports and Society Workgroup, a coalition of professional sports leagues that is working closely with the C.D.C. Sports teams in the group are testing more than 10,000 people at least daily and sequencing all infections, according to Dr. Robby Sikka, a physician who worked with the N.B.A.’s Minnesota Timberwolves.
Breakthrough infections in the leagues seem to be more common with the Delta variant than with Alpha, the variant first identified in Britain, he said. As would be predicted, the vaccines cut down the severity and duration of illness significantly, with players returning less than two weeks after becoming infected, compared with nearly three weeks earlier in the pandemic.
But while they are infected, the players carry very high amounts of virus for seven to 10 days, compared with two or three days in those infected with Alpha, Dr. Sikka said. Infected players are required to quarantine, so the project has not been able to track whether they spread the virus to others — but it’s likely that they would, he added.
“If they’re put just willy-nilly back into society, I think you’re going to have spread from vaccinated individuals,” he added. “They don’t even recognize they have Covid because they think they’re vaccinated.”
Elyse Freitas was shocked to discover that 15 vaccinated people became infected at her wedding. Dr. Freitas, 34, a biologist at the University of Oklahoma, said she had been very cautious throughout the pandemic, and had already postponed her wedding once. But after much deliberation, she celebrated the wedding indoors on July 10.
Based on the symptoms, Dr. Freitas believes that the initial infection was at a bachelorette party two days before the wedding, when a dozen vaccinated people went unmasked to bars in downtown Oklahoma City; seven of them later tested positive. Eventually, 17 guests at the wedding became infected, nearly all with mild symptoms.
“In hindsight, I should have paid more attention to the vaccination rates in Oklahoma and the emergence of the Delta variant and adjusted my plans accordingly,” she said.
An outbreak in Provincetown, Mass., illustrates how quickly a cluster can grow, given the right conditions. During its famed Fourth of July celebrations, the small town hosted more than 60,000 unmasked revelers, dancing and mingling in crowded bars and house parties.
The crowds this year were much larger than usual, said Adam Hunt, 55, an advertising executive who has lived in Provincetown part time for about 20 years. But the bars and clubs didn’t open until they were allowed to, Mr. Hunt noted: “We thought we were doing the right thing. We thought we were OK.”
Mr. Hunt did not become infected with the virus, but several of his vaccinated friends who had flown in from places as far as Hawaii and Alabama tested positive after their return. In all, the cluster has grown to at least 256 cases — including 66 visitors from other states — about two-thirds in vaccinated people.
“I did not expect that people who were vaccinated would be becoming positive at the rate that they were,” said Steve Katsurinis, chair of the Provincetown Board of Health. Provincetown has moved swiftly to contain the outbreak, reinstating a mask advisory and stepping up testing. It is conducting 250 tests a day, compared with about eight a day before July 1, Mr. Katsurinis said.
Health officials should also help the public understand that vaccines are doing what they are supposed to — preventing people from getting seriously ill, said Kristen Panthagani, a geneticist at Baylor College of Medicine who runs a blog explaining complex scientific concepts.
“Vaccine efficacy isn’t 100 percent — it never is,” she said. “We shouldn’t expect Covid vaccines to be perfect, either. That’s too high an expectation.”
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.
