The Death Predictor: A Helpful New Tool or an Ethical Morass?
A senior in hospice care.
Whenever Eric Karl Oermann has to tell a patient about a terrible prognosis, their first question is always: "how long do I have?" Oermann would like to offer a precise answer, to provide some certainty and help guide treatment. But although he's one of the country's foremost experts in medical artificial intelligence, Oermann is still dependent on a computer algorithm that's often wrong.
Doctors are notoriously terrible at guessing how long their patients will live.
Artificial intelligence, now often called deep learning or neural networks, has radically transformed language and image processing. It's allowed computers to play chess better than the world's grand masters and outwit the best Jeopardy players. But it still can't precisely tell a doctor how long a patient has left – or how to help that person live longer.
Someday, researchers predict, computers will be able to watch a video of a patient to determine their health status. Doctors will no longer have to spend hours inputting data into medical records. And computers will do a better job than specialists at identifying tiny tumors, impending crises, and, yes, figuring out how long the patient has to live. Oermann, a neurosurgeon at Mount Sinai, says all that technology will allow doctors to spend more time doing what they do best: talking with their patients. "I want to see more deep learning and computers in a clinical setting," he says, "so there can be more human interaction." But those days are still at least three to five years off, Oermann and other researchers say.
Doctors are notoriously terrible at guessing how long their patients will live, says Nigam Shah, an associate professor at Stanford University and assistant director of the school's Center for Biomedical Informatics Research. Doctors don't want to believe that their patient – whom they've come to like – will die. "Doctors over-estimate survival many-fold," Shah says. "How do you go into work, in say, oncology, and not be delusionally optimistic? You have to be."
But patients near the end of life will get better treatment – and even live longer – if they are overseen by hospice or palliative care, research shows. So, instead of relying on human bias to select those whose lives are nearing their end, Shah and his colleagues showed that they could use a deep learning algorithm based on medical records to flag incoming patients with a life expectancy of three months to a year. They use that data to indicate who might need palliative care. Then, the palliative care team can reach out to treating physicians proactively, instead of relying on their referrals or taking the time to read extensive medical charts.
But, although the system works well, Shah isn't yet sure if such indicators actually get the appropriate patients into palliative care. He's recently partnered with a palliative care doctor to run a gold-standard clinical trial to test whether patients who are flagged by this algorithm are indeed a better match for palliative care.
"What is effective from a health system perspective might not be effective from a treating physician's perspective and might not be effective from the patient's perspective," Shah notes. "I don't have a good way to guess everybody's reaction without actually studying it." Whether palliative care is appropriate, for instance, depends on more than just the patient's health status. "If the patient's not ready, the family's not ready and the doctor's not ready, then you're just banging your head against the wall," Shah says. "Given limited capacity, it's a waste of resources" to put that person in palliative care.
The algorithm isn't perfect, but "on balance, it leads to better decisions more often."
Alexander Smith and Sei Lee, both palliative care doctors, work together at the University of California, San Francisco, to develop predictions for patients who come to the hospital with a complicated prognosis or a history of decline. Their algorithm, they say, helps decide if this patient's problems – which might include diabetes, heart disease, a slow-growing cancer, and memory issues – make them eligible for hospice. The algorithm isn't perfect, they both agree, but "on balance, it leads to better decisions more often," Smith says.
Bethany Percha, an assistant professor at Mount Sinai, says that an algorithm may tell doctors that their patient is trending downward, but it doesn't do anything to change that trajectory. "Even if you can predict something, what can you do about it?" Algorithms may be able to offer treatment suggestions – but not what specific actions will alter a patient's future, says Percha, also the chief technology officer of Precise Health Enterprise, a product development group within Mount Sinai. And the algorithms remain challenging to develop. Electronic medical records may be great at her hospital, but if the patient dies at a different one, her system won't know. If she wants to be certain a patient has died, she has to merge social security records of death with her system's medical records – a time-consuming and cumbersome process.
An algorithm that learns from biased data will be biased, Shah says. Patients who are poor or African American historically have had worse health outcomes. If researchers train an algorithm on data that includes those biases, they get baked into the algorithms, which can then lead to a self-fulfilling prophesy. Smith and Lee say they've taken race out of their algorithms to avoid this bias.
Age is even trickier. There's no question that someone's risk of illness and death goes up with age. But an 85-year-old who breaks a hip running a marathon should probably be treated very differently than an 85-year-old who breaks a hip trying to get out of a chair in a dementia care unit. That's why the doctor can never be taken out of the equation, Shah says. Human judgment will always be required in medical care and an algorithm should never be followed blindly, he says.
Experts say that the flaws in artificial intelligence algorithms shouldn't prevent people from using them – carefully.
Researchers are also concerned that their algorithms will be used to ration care, or that insurance companies will use their data to justify a rate increase. If an algorithm predicts a patient is going to end up back in the hospital soon, "who's benefitting from knowing a patient is going to be readmitted? Probably the insurance company," Percha says.
Still, Percha and others say, the flaws in artificial intelligence algorithms shouldn't prevent people from using them – carefully. "These are new and exciting tools that have a lot of potential uses. We need to be conscious about how to use them going forward, but it doesn't mean we shouldn't go down this road," she says. "I think the potential benefits outweigh the risks, especially because we've barely scratched the surface of what big data can do right now."
How sharing, hearing, and remembering positive stories can help shape our brains for the better
Across cultures and through millennia, human beings have always told stories. Whether it’s a group of boy scouts around a campfire sharing ghost stories or the paleolithic Cro-Magnons etching pictures of bison on cave walls, researchers believe that storytelling has been universal to human beings since the development of language.
But storytelling was more than just a way for our ancestors to pass the time. Researchers believe that storytelling served an important evolutionary purpose, helping humans learn empathy, share important information (such as where predators were or what berries were safe to eat), as well as strengthen social bonds. Quite literally, storytelling has made it possible for the human race to survive.
Today, neuroscientists are discovering that storytelling is just as important now as it was millions of years ago. Particularly in sharing positive stories, humans can more easily form relational bonds, develop a more flexible perspective, and actually grow new brain circuitry that helps us survive. Here’s how.
How sharing stories positively impacts the brain
When human beings share stories, it increases the levels of certain neurochemicals in the brain, neuroscientists have found. In a 2021 study published in Proceedings of the National Academy of Sciences (PNAS), Swedish researchers found that simply hearing a story could make hospitalized children feel better, compared to other hospitalized children who played a riddle game for the same amount of time. In their research, children in the intensive care unit who heard stories for just 30 minutes had higher levels of oxytocin, a hormone that promotes positive feelings and is linked to relaxation, trust, social connectedness, and overall psychological stability. Furthermore, the same children showed lower levels of cortisol, a hormone associated with stress. Afterward, the group of children who heard stories tended to describe their hospital experiences more positively, and even reported lower levels of pain.
Annie Brewster, MD, knows the positive effect of storytelling from personal experience. An assistant professor at Harvard Medical School and the author of The Healing Power of Storytelling: Using Personal Narrative to Navigate Illness, Trauma, and Loss, Brewster started sharing her personal experience with chronic illness after being diagnosed with multiple sclerosis in 2001. In doing so, Brewster says it has enabled her to accept her diagnosis and integrate it into her identity. Brewster believes so much in the power of hearing and sharing stories that in 2013 she founded Health Story Collaborative, a forum for others to share their mental and physical health challenges.“I wanted to hear stories of people who had found ways to move forward in positive ways, in spite of health challenges,” Brewster said. In doing so, Brewster believes people with chronic conditions can “move closer to self-acceptance and self-love.”
While hearing and sharing positive stories has been shown to increase oxytocin and other “feel good” chemicals, simply remembering a positive story has an effect on our brains as well. Mark Hoelterhoff, PhD, a lecturer in clinical psychology at the University of Edinburgh, recalling and “savoring” a positive story, thought, or feedback “begins to create new brain circuitry—a new neural network that’s geared toward looking for the positive,” he says. Over time, other research shows, savoring positive stories or thoughts can literally change the shape of your brain, hard-wiring someone to see things in a more positive light.How stories can change your behavior
In 2009, Paul Zak, PhD, a neuroscientist and professor at Claremont Graduate University, set out to measure how storytelling can actually change human behavior for the better. In his study, Zak wanted to measure the behavioral effects of oxytocin, and did this by showing test subjects two short video clips designed to elicit an emotional response.
In the first video they showed the study participants, a father spoke to the camera about his two-year-old son, Ben, who had been diagnosed with terminal brain cancer. The father told the audience that he struggled to connect with and enjoy Ben, as Ben had only a few months left to live. In the end, the father finds the strength to stay emotionally connected to his son until he dies.
The second video clip, however, was much less emotional. In that clip, the same father and son are shown spending the day at the zoo. Ben is only suggested to have cancer (he is bald from chemotherapy and referred to as a ‘miracle’, but the cancer isn’t mentioned directly). The second story lacked the dramatic narrative arc of the first video.
Zak’s team took blood before and after the participants watched one of the two videos and found that the first story increased the viewers’ cortisol and oxytocin, suggesting that they felt distress over the boy’s diagnosis and empathy toward the boy and his father. The second narrative, however, didn’t increase oxytocin or cortisol at all.
But Zak took the experiment a step further. After the movie clips, his team gave the study participants a chance to share money with a stranger in the lab. The participants who had an increase in cortisol and oxytocin were more likely to donate money generously. The participants who had increased cortisol and oxytocin were also more likely to donate money to a charity that works with children who are ill. Zak also found that the amount of oxytocin that was released was correlated with how much money people felt comfortable giving—in other words, the more oxytocin that was released, the more generous they felt, and the more money they donated.
How storytelling strengthens our bond with others
Sharing, hearing, and remembering stories can be a powerful tool for social change–not only in the way it changes our brain and our behavior, but also because it can positively affect our relationships with other people
Emotional stimulation from telling stories, writes Zak, is the foundation for empathy, and empathy strengthens our relationships with other people. “By knowing someone’s story—where they come from, what they do, and who you might know in common—relationships with strangers are formed.”
But why are these relationships important for humanity? Because human beings can use storytelling to build empathy and form relationships, it enables them to “engage in the kinds of large-scale cooperation that builds massive bridges and sends humans into space,” says Zak.
Storytelling, Zak found, and the oxytocin release that follows, also makes people more sensitive to social cues. This sensitivity not only motivates us to form relationships, but also to engage with other people and offer help, particularly if the other person seems to need help.
But as Zak found in his experiments, the type of storytelling matters when it comes to affecting relationships. Where Zak found that storytelling with a dramatic arc helps release oxytocin and cortisol, enabling people to feel more empathic and generous, other researchers have found that sharing happy stories allows for greater closeness between individuals and speakers. A group of Chinese researchers found that, compared to emotionally-neutral stories, happy stories were more “emotionally contagious.” Test subjects who heard happy stories had greater activation in certain areas of their brains, experienced more significant, positive changes in their mood, and felt a greater sense of closeness between themselves and the speaker.
“This finding suggests that when individuals are happy, they become less self-focused and then feel more intimate with others,” the authors of the study wrote. “Therefore, sharing happiness could strengthen interpersonal bonding.” The researchers went on to say that this could lead to developing better social networks, receiving more social support, and leading more successful social lives.
Since the start of the COVID pandemic, social isolation, loneliness, and resulting mental health issues have only gotten worse. In light of this, it’s safe to say that hearing, sharing, and remembering stories isn’t just something we can do for entertainment. Storytelling has always been central to the human experience, and now more than ever it’s become something crucial for our survival.
Want to know how you can reap the benefits of hearing happy stories? Keep an eye out for Upworthy’s first book, GOOD PEOPLE: Stories from the Best of Humanity, published by National Geographic/Disney, available on September 3, 2024. GOOD PEOPLE is a much-needed trove of life-affirming stories told straight from the heart. Handpicked from Upworthy’s community, these 101 stories speak to the breadth, depth, and beauty of the human experience, reminding us we have a lot more in common than we realize.
A new type of cancer therapy is shrinking deadly brain tumors with just one treatment
MRI scans after a new kind of immunotherapy for brain cancer show remarkable progress in one patient just days after the first treatment.
Few cancers are deadlier than glioblastomas—aggressive and lethal tumors that originate in the brain or spinal cord. Five years after diagnosis, less than five percent of glioblastoma patients are still alive—and more often, glioblastoma patients live just 14 months on average after receiving a diagnosis.
But an ongoing clinical trial at Mass General Cancer Center is giving new hope to glioblastoma patients and their families. The trial, called INCIPIENT, is meant to evaluate the effects of a special type of immune cell, called CAR-T cells, on patients with recurrent glioblastoma.
How CAR-T cell therapy works
CAR-T cell therapy is a type of cancer treatment called immunotherapy, where doctors modify a patient’s own immune system specifically to find and destroy cancer cells. In CAR-T cell therapy, doctors extract the patient’s T-cells, which are immune system cells that help fight off disease—particularly cancer. These T-cells are harvested from the patient and then genetically modified in a lab to produce proteins on their surface called chimeric antigen receptors (thus becoming CAR-T cells), which makes them able to bind to a specific protein on the patient’s cancer cells. Once modified, these CAR-T cells are grown in the lab for several weeks so that they can multiply into an army of millions. When enough cells have been grown, these super-charged T-cells are infused back into the patient where they can then seek out cancer cells, bind to them, and destroy them. CAR-T cell therapies have been approved by the US Food and Drug Administration (FDA) to treat certain types of lymphomas and leukemias, as well as multiple myeloma, but haven’t been approved to treat glioblastomas—yet.
CAR-T cell therapies don’t always work against solid tumors, such as glioblastomas. Because solid tumors contain different kinds of cancer cells, some cells can evade the immune system’s detection even after CAR-T cell therapy, according to a press release from Massachusetts General Hospital. For the INCIPIENT trial, researchers modified the CAR-T cells even further in hopes of making them more effective against solid tumors. These second-generation CAR-T cells (called CARv3-TEAM-E T cells) contain special antibodies that attack EFGR, a protein expressed in the majority of glioblastoma tumors. Unlike other CAR-T cell therapies, these particular CAR-T cells were designed to be directly injected into the patient’s brain.
The INCIPIENT trial results
The INCIPIENT trial involved three patients who were enrolled in the study between March and July 2023. All three patients—a 72-year-old man, a 74-year-old man, and a 57-year-old woman—were treated with chemo and radiation and enrolled in the trial with CAR-T cells after their glioblastoma tumors came back.
The results, which were published earlier this year in the New England Journal of Medicine (NEJM), were called “rapid” and “dramatic” by doctors involved in the trial. After just a single infusion of the CAR-T cells, each patient experienced a significant reduction in their tumor sizes. Just two days after receiving the infusion, the glioblastoma tumor of the 72-year-old man decreased by nearly twenty percent. Just two months later the tumor had shrunk by an astonishing 60 percent, and the change was maintained for more than six months. The most dramatic result was in the 57-year-old female patient, whose tumor shrank nearly completely after just one infusion of the CAR-T cells.
The results of the INCIPIENT trial were unexpected and astonishing—but unfortunately, they were also temporary. For all three patients, the tumors eventually began to grow back regardless of the CAR-T cell infusions. According to the press release from MGH, the medical team is now considering treating each patient with multiple infusions or prefacing each treatment with chemotherapy to prolong the response.
While there is still “more to do,” says co-author of the study neuro-oncologist Dr. Elizabeth Gerstner, the results are still promising. If nothing else, these second-generation CAR-T cell infusions may someday be able to give patients more time than traditional treatments would allow.
“These results are exciting but they are also just the beginning,” says Dr. Marcela Maus, a doctor and professor of medicine at Mass General who was involved in the clinical trial. “They tell us that we are on the right track in pursuing a therapy that has the potential to change the outlook for this intractable disease.”