Study Shows “Living Drug” Can Provide a Lasting Cure for Cancer
Doug Olson was 49 when he was diagnosed with chronic lymphocytic leukemia, a blood cancer that strikes 21,000 Americans annually. Although the disease kills most patients within a decade, Olson’s case progressed more slowly, and courses of mild chemotherapy kept him healthy for 13 years. Then, when he was 62, the medication stopped working. The cancer had mutated, his doctor explained, becoming resistant to standard remedies. Harsher forms of chemo might buy him a few months, but their side effects would be debilitating. It was time to consider the treatment of last resort: a bone-marrow transplant.
Olson, a scientist who developed blood-testing instruments, knew the odds. There was only a 50 percent chance that a transplant would cure him. There was a 20 percent chance that the agonizing procedure—which involves destroying the patient’s marrow with chemo and radiation, then infusing his blood with donated stem cells—would kill him. If he survived, he would face the danger of graft-versus-host disease, in which the donor’s cells attack the recipient’s tissues. To prevent it, he would have to take immunosuppressant drugs, increasing the risk of infections. He could end up with pneumonia if one of his three grandchildren caught a sniffle. “I was being pushed into a corner,” Olson recalls, “with very little room to move.”
Soon afterward, however, his doctor revealed a possible escape route. He and some colleagues at the University of Pennsylvania’s Abramson Cancer Center were starting a clinical trial, he said, and Olson—still mostly symptom-free—might be a good candidate. The experimental treatment, known as CAR-T therapy, would use genetic engineering to turn his T lymphocytes (immune cells that guard against viruses and other pathogens) into a weapon against cancer.
In September 2010, technicians took some of Olson’s T cells to a laboratory, where they were programmed with new molecular marching orders and coaxed to multiply into an army of millions. When they were ready, a nurse inserted a catheter into his neck. At the turn of a valve, his soldiers returned home, ready to do battle.
“I felt like I’d won the lottery,” Olson says. But he was only the second person in the world to receive this “living drug,” as the University of Pennsylvania investigators called it. No one knew how long his remission would last.
Three weeks later, Olson was slammed with a 102-degree fever, nausea, and chills. The treatment had triggered two dangerous complications: cytokine release syndrome, in which immune chemicals inflame the patient’s tissues, and tumor lysis syndrome, in which toxins from dying cancer cells overwhelm the kidneys. But the crisis passed quickly, and the CAR-T cells fought on. A month after the infusion, the doctor delivered astounding news: “We can’t find any cancer in your body.”
“I felt like I’d won the lottery,” Olson says. But he was only the second person in the world to receive this “living drug,” as the University of Pennsylvania investigators called it. No one knew how long his remission would last.
An Unexpected Cure
In February 2022, the same cancer researchers reported a remarkable milestone: the trial’s first two patients had survived for more than a decade. Although Olson’s predecessor—a retired corrections officer named Bill Ludwig—died of COVID-19 complications in early 2021, both men had remained cancer-free. And the modified immune cells continued to patrol their territory, ready to kill suspected tumor cells the moment they arose.
“We can now conclude that CAR-T cells can actually cure patients with leukemia,” University of Pennsylvania immunologist Carl June, who spearheaded the development of the technique, told reporters. “We thought the cells would be gone in a month or two. The fact that they’ve survived 10 years is a major surprise.”
Even before the announcement, it was clear that CAR-T therapy could win a lasting reprieve for many patients with cancers that were once a death sentence. Since the Food and Drug Administration approved June’s version (marketed as Kymriah) in 2017, the agency has greenlighted five more such treatments for various types of leukemia, lymphoma, and myeloma. “Every single day, I take care of patients who would previously have been told they had no options,” says Rayne Rouce, a pediatric hematologist/oncologist at Texas Children’s Cancer Center. “Now we not only have a treatment option for those patients, but one that could potentially be the last therapy for their cancer that they’ll ever have to receive.”
Immunologist Carl June, middle, spearheaded development of the CAR-T therapy that gave patients Bill Ludwig, left, and Doug Olson, right, a lengthy reprieve on their terminal cancer diagnoses.
Penn Medicine
Yet the CAR-T approach doesn’t help everyone. So far, it has only shown success for blood cancers—and for those, the overall remission rate is 30 to 40 percent. “When it works, it works extraordinarily well,” says Olson’s former doctor, David Porter, director of Penn’s blood and bone marrow transplant program. “It’s important to know why it works, but it’s equally important to know why it doesn’t—and how we can fix that.”
The team’s study, published in the journal Nature, offers a wealth of data on what worked for these two patients. It may also hold clues for how to make the therapy effective for more people.
Building a Better T Cell
Carl June didn’t set out to cure cancer, but his serendipitous career path—and a personal tragedy—helped him achieve insights that had eluded other researchers. In 1971, hoping to avoid combat in Vietnam, he applied to the U.S. Naval Academy in Annapolis, Maryland. June showed a knack for biology, so the Navy sent him on to Baylor College of Medicine. He fell in love with immunology during a fellowship researching malaria vaccines in Switzerland. Later, the Navy deployed him to the Fred Hutchinson Cancer Research Center in Seattle to study bone marrow transplantation.
There, June became part of the first research team to learn how to culture T cells efficiently in a lab. After moving on to the National Naval Medical Center in the ’80s, he used that knowledge to combat the newly emerging AIDS epidemic. HIV, the virus that causes the disease, invades T cells and eventually destroys them. June and his post-doc Bruce Levine developed a method to restore patients’ depleted cell populations, using tiny magnetic beads to deliver growth-stimulating proteins. Infused into the body, the new T cells effectively boosted immune function.
In 1999, after leaving the Navy, June joined the University of Pennsylvania. His wife, who’d been diagnosed with ovarian cancer, died two years later, leaving three young children. “I had not known what it was like to be on the other side of the bed,” he recalls. Watching her suffer through grueling but futile chemotherapy, followed by an unsuccessful bone-marrow transplant, he resolved to focus on finding better cancer treatments. He started with leukemia—a family of diseases in which mutant white blood cells proliferate in the marrow.
Cancer is highly skilled at slipping through the immune system’s defenses. T cells, for example, detect pathogens by latching onto them with receptors designed to recognize foreign proteins. Leukemia cells evade detection, in part, by masquerading as normal white blood cells—that is, as part of the immune system itself.
June planned to use a viral vector no one had tried before: HIV.
To June, chimeric antigen receptor (CAR) T cells looked like a promising tool for unmasking and destroying the impostors. Developed in the early ’90s, these cells could be programmed to identify a target protein, and to kill any pathogen that displayed it. To do the programming, you spliced together snippets of DNA and inserted them into a disabled virus. Next, you removed some of the patient’s T cells and infected them with the virus, which genetically hijacked its new hosts—instructing them to find and slay the patient’s particular type of cancer cells. When the T cells multiplied, their descendants carried the new genetic code. You then infused those modified cells into the patient, where they went to war against their designated enemy.
Or that’s what happened in theory. Many scientists had tried to develop therapies using CAR-T cells, but none had succeeded. Although the technique worked in lab animals, the cells either died out or lost their potency in humans.
But June had the advantage of his years nurturing T cells for AIDS patients, as well as the technology he’d developed with Levine (who’d followed him to Penn with other team members). He also planned to use a viral vector no one had tried before: HIV, which had evolved to thrive in human T cells and could be altered to avoid causing disease. By the summer of 2010, he was ready to test CAR-T therapy against chronic lymphocytic leukemia (CLL), the most common form of the disease in adults.
Three patients signed up for the trial, including Doug Olson and Bill Ludwig. A portion of each man’s T cells were reprogrammed to detect a protein found only on B lymphocytes, the type of white blood cells affected by CLL. Their genetic instructions ordered them to destroy any cell carrying the protein, known as CD19, and to multiply whenever they encountered one. This meant the patients would forfeit all their B cells, not just cancerous ones—but regular injections of gamma globulins (a cocktail of antibodies) would make up for the loss.
After being infused with the CAR-T cells, all three men suffered high fevers and potentially life-threatening inflammation, but all pulled through without lasting damage. The third patient experienced a partial remission and survived for eight months. Olson and Ludwig were cured.
Learning What Works
Since those first infusions, researchers have developed reliable ways to prevent or treat the side effects of CAR-T therapy, greatly reducing its risks. They’ve also been experimenting with combination therapies—pairing CAR-T with chemo, cancer vaccines, and immunotherapy drugs called checkpoint inhibitors—to improve its success rate. But CAR-T cells are still ineffective for at least 60 percent of blood cancer patients. And they remain in the experimental stage for solid tumors (including pancreatic cancer, mesothelioma, and glioblastoma), whose greater complexity make them harder to attack.
The new Nature study offers clues that could fuel further advances. The Penn team “profiled these cells at a level where we can almost say, ‘These are the characteristics that a T cell would need to survive 10 years,’” says Rouce, the physician at Texas Children’s Cancer Center.
One surprising finding involves how CAR-T cells change in the body over time. At first, those that Olson and Ludwig received showed the hallmarks of “killer” T-cells (also known as CD8 cells)—highly active lymphocytes bent on exterminating every tumor cell in sight. After several months, however, the population shifted toward “helper” T-cells (or CD4s), which aid in forming long-term immune memory but are normally incapable of direct aggression. Over the years, the numbers swung back and forth, until only helper cells remained. Those cells showed markers suggesting they were too exhausted to function—but in the lab, they were able not only to recognize but to destroy cancer cells.
June and his team suspect that those tired-looking helper cells had enough oomph to kill off any B cells Olson and Ludwig made, keeping the pair’s cancers permanently at bay. If so, that could prompt new approaches to selecting cells for CAR-T therapy. Maybe starting with a mix of cell types—not only CD8s, but CD4s and other varieties—would work better than using CD8s alone. Or perhaps inducing changes in cell populations at different times would help.
Another potential avenue for improvement is starting with healthier cells. Evidence from this and other trials hints that patients whose T cells are more robust to begin with respond better when their cells are used in CAR-T therapy. The Penn team recently completed a clinical trial in which CLL patients were treated with ibrutinib—a drug that enhances T-cell function—before their CAR-T cells were manufactured. The response rate, says David Porter, was “very high,” with most patients remaining cancer-free a year after being infused with the souped-up cells.
Such approaches, he adds, are essential to achieving the next phase in CAR-T therapy: “Getting it to work not just in more people, but in everybody.”
Doug Olson enjoys nature - and having a future.
Penn Medicine
To grasp what that could mean, it helps to talk with Doug Olson, who’s now 75. In the years since his infusion, he has watched his four children forge careers, and his grandkids reach their teens. He has built a business and enjoyed the rewards of semi-retirement. He’s done volunteer and advocacy work for cancer patients, run half-marathons, sailed the Caribbean, and ridden his bike along the sun-dappled roads of Silicon Valley, his current home.
And in his spare moments, he has just sat there feeling grateful. “You don’t really appreciate the effect of having a lethal disease until it’s not there anymore,” he says. “The world looks different when you have a future.”
This article was first published on Leaps.org on March 24, 2022.
Imagine eating a slice of cake for breakfast. It's deliciously indulgent, but instead of your blood sugar spiking, your body processes all that sweetness as a healthy high-protein meal. It may sound like sci-fi, but this scenario is not necessarily far off.
"People with diabetes could especially benefit because sweet proteins don't trigger a need for insulin."
The Lowdown
An award-winning agtech startup called Amai is developing "sweet proteins," based on the molecular structure of naturally occuring exotic fruits. These new sugar substitutes could potentially replace artificial sweeteners and help people who are trying to curb their sugar intake. People with diabetes could especially benefit because sweet proteins don't trigger a need for insulin.
While there is a sweet protein currently on the market today called thaumatin, it's expensive, has a short shelf life, and is lacking in the taste department. But Amai's proteins taste 70 to 100 percent identical to the sweet ones found in nature. Once their molecular structure is designed through a sophisticated computing platform, they are made through fermentation, which is akin to brewing beer. These non-GMO proteins are over 10,000 times sweeter than sugar, which means much less needs to be produced and used.
Diseases like diabetes and heart disease, which are often linked to sugar overconsumption, have been on a major upswing over the last few decades, especially in the United States. According to the CDC, 100 million adults in the United States are now living with diabetes or prediabetes, which if not treated, often leads to type 2 diabetes within five years. By 2030, scientists predict cases of diabetes in the U.S. will increase by 54 percent. If sugar proteins like the type Amai is creating become widely available, these numbers could begin to decrease.
Next Up
Amai's sweet proteins are still in the research and development stage, but the Israeli startup is raising significant funding that should help expedite the process. They're also substantially upping their production ability by expanding their facilities.
Will consumers be comfortable ingesting a lab-designed food product?
And in March, the USDA and FDA announced plans to regulate cell-cultured foods, the category in which these sugar proteins would fall, so Amai researchers are hopeful they'll have an easier path to approval once their product is market ready.
Open Questions
All this progress may sound promising, but Amai still has a long way to go before the reality of healthy cake becomes tangible. Some questions to consider: Will consumers be comfortable ingesting a lab-designed food product? Will it taste enough like real sugar?
And if some products and brands begin to adopt it, will it ever overtake the real thing in popularity and make a dent in diseases like diabetes and obesity? Only time, more research, and a lot more money will tell, but in the meantime, feel free to daydream about eating entire pints of ice cream without needing to hit the gym.
One of the World’s Most Famous Neuroscientists Wants You to Embrace Meditation and Spirituality
Neuroscientist, philosopher, and bestselling author Sam Harris is famous for many reasons, among them his vocal criticism of religion, his scientific approach to moral questions, and his willingness to tackle controversial topics on his popular podcast.
"Until you have some capacity to be mindful, you have no choice but to be lost in every next thought that arises."
He is also a passionate advocate of mindfulness meditation, having spent formative time as a young adult learning from teachers in India and Tibet before returning to the West.
Now his new app called Waking Up aims to teach the principles of meditation to anyone who is willing to slow down, turn away from everyday distractions, and pay attention to their own mind. Harris recently chatted with leapsmag about the science of mindfulness, the surprising way he discovered it, and the fundamental—but under-appreciated—reason to do it. This conversation has been lightly edited and condensed.
One of the biggest struggles that so many people face today is how to stay present in the moment. Is this the default state for human beings, or is this a more recent phenomenon brought on by our collective addiction to screens?
Sam: No, it certainly predates our technology. This is something that yogis have been talking about and struggling with for thousands of years. Just imagine you're on a beach on vacation where you vowed not to pick up your smart phone for 24 hours. You haven't looked at a screen, you're just enjoying the sound of the waves and the sunset, or trying to. What you're competing with there is this incessant white noise of discursive thinking. And that's something that follows you everywhere. It's something that people tend to only become truly sensitive to once they try to learn to meditate.
You've mentioned in one of your lessons that the more you train in mindful meditation, the more freedom you will have. What do you mean?
Sam: Well, until you have some capacity to be mindful, you have no choice but to be lost in every next thought that arises. You can't notice thought as thought, it just feels like you. So therefore, you're hostage to whatever the emotional or behavioral consequences of those thoughts are. If they're angry thoughts, you're angry. If they're desire thoughts, you're filled with desire. There is very little understanding in Western psychology around an alternative to that. And it's only by importing mindfulness into our thinking that we have begun to dimly see an alternative.
You've said that even if there were no demonstrable health benefits, it would still be valuable to meditate. Why?
Sam: Yeah, people are putting a lot of weight on the demonstrated health and efficiency benefits of mindfulness. I don't doubt that they exist, I think some of the research attesting to them is pretty thin, but it just may in fact be the case that meditation improves your immune system, and staves off dementia, or the thinning of the cortex as we age and many other benefits.
"What was Jesus talking about? Well, he certainly seemed to be talking about a state of mind that I first discovered on MDMA."
[But] it trivializes the real power of the practice. The power of the practice is to discover something fundamental about the nature of consciousness that can liberate you from psychological suffering in each moment that you can be aware of it. And that's a fairly esoteric goal and concern, it's an ancient one. It is something more than a narrow focus on physical health or even the ordinary expectations of well-being.
Yet many scientists in the West and intellectuals, like Richard Dawkins, are skeptical of it. Would you support a double-blind placebo-controlled study of meditation or does that miss the deeper point?
Sam: No, I see value in studying it any way we can. It's a little hard to pick a control condition that really makes sense. But yeah, that's research that I'm actually collaborating in now. There's a team just beginning a study of my app and we're having to pick a control condition. You can't do a true double-blind placebo control because meditation is not a pill, it's a practice. You know what you're being told to do. And if you're being told that you're in the control condition, you might be told to just keep a journal, say, of everything that happened to you yesterday.
One way to look at it is just to take people who haven't done any significant practice and to have them start and compare them to themselves over time using each person as his own control. But there are limitations with that as well. So, it's a little hard to study, but it's certainly not impossible.
And again, the purpose of meditation is not merely to reduce stress or to improve a person's health. And there are certain aspects to it which don't in any linear way reduce stress. You can have stressful experiences as you begin to learn to be mindful. You become more aware of your own neuroses certainly in the beginning, and you become more aware of your capacity to be petty and deceptive and self-deceptive. There are unflattering things to be realized about the character of your own mind. And the question is, "Is there a benefit ultimately to realizing those things?" I think there clearly is.
I'm curious about your background. You left Stanford to practice meditation after an experience with the drug MDMA. How did that lead you to meditation?
Sam: The experience there was that I had a feeling -- what I would consider unconditional love -- for the first time. Whether I ever had the concept of unconditional love in my head at that point, I don't know, I was 18 and not at all religious. But it was an experience that certainly made sense of the kind of language you find in many spiritual traditions, not just what it's like to be fully actualized by those, by, let's say, Christian values. Like, what was Jesus talking about? Well, he certainly seemed to be talking about a state of mind that I first discovered on MDMA. So that led me to religious literature, spiritual or new age literature, and Eastern philosophy.
Looking to make sense of this and put into a larger context that wasn't just synonymous with taking drugs, it was a sketching a path of practice and growth that could lead further across this landscape of mind, which I just had no idea existed. I basically thought you have whatever mind you have, and the prospect of having a radically different experience of consciousness, that would just be a fool's errand, and anyone who claimed to have such an experience would probably be lying.
As you probably know, there's a resurgence of research in psychedelics now, which again I also fully support, and I've had many useful experiences since that first one, on LSD and psilocybin. I don't tend to take those drugs now; it's been many years since I've done anything significant in that area, but the utility is that they work for everyone, more or less, which is to say that they prove beyond any doubt to everyone that it's possible to have a very different experience of consciousness moment to moment. Now, you can have scary experiences on some of these drugs, and I don't recommend them for everybody, but the one thing you can't have is the experience of boredom. [chuckle]
Very true. Going back to your experiences, you've done silent meditation for 18 hours a day with monks abroad. Do you think that kind of immersive commitment is an ideal goal, or is there a point where too much meditation is counter-productive to a full life?
Sam: I think all of those possibilities are true, depending on the person. There are people who can't figure out how to live a satisfying life in the world, and they retreat as a way of trying to untie the knot of their unhappiness directly through practice.
But the flip side is also true, that in order to really learn this skill deeply, most people need some kind of full immersion experience, at least at some point, to break through to a level of familiarity with it that would be very hard to get for most people practicing for 10 minutes a day, or an hour a day. But ultimately, I think it is a matter of practicing for short periods, frequently, more than it's a matter of long hours in one's daily life. If you could practice for one minute, 100 times a day, that would be an extraordinarily positive way to punctuate your habitual distraction. And I think probably better than 100 minutes all in one go first thing in the morning.
"It's amazing to me to walk into a classroom where you see 15 or 20 six-year-olds sitting in silence for 10 or 15 minutes."
What's your daily meditation practice like today? How does it fit into your routine?
Sam: It's super variable. There are days where I don't find any time to practice formally, there are days where it's very brief, and there are days where I'll set aside a half hour. I have young kids who I don't feel like leaving to go on retreat just yet, but I'm sure retreat will be a part of my future as well. It's definitely useful to just drop everything and give yourself permission to not think about anything for a certain period. And you're left with this extraordinarily vivid confrontation with your default state, which is your thoughts are incessantly appearing and capturing your attention and deluding you.
Every time you're lost in thought, you're very likely telling yourself a story for the 15th time that you don't even have the decency to find boring, right? Just imagine what it would sound like if you could broadcast your thoughts on a loud speaker, it would be mortifying. These are desperately boring, repetitive rehearsals of past conversations and anxieties about the future and meaningless judgments and observations. And in each moment that we don't notice a thought as a thought, we are deluded about what has happened. It's created this feeling of self that is a misconstrual of what consciousness is actually like, and it's created in most cases a kind of emotional emergency, which is our lives and all of the things we're worrying about. But our worry adds absolutely nothing to our capacity to deal with the problems when they actually arise.
Right. You mentioned you're a parent of a young kid, and so am I. Is there anything we as parents can do to encourage a mindfulness habit when our kids are young?
Sam: Actually, we just added meditations for kids in the app. My wife, Annaka, teaches meditation to kids as young as five in school. And they can absolutely learn to be mindful, even at that age. And it's amazing to me to walk into a classroom where you see 15 or 20 six-year-olds sitting in silence for 10 or 15 minutes, it's just amazing. And that's not what happens on the first day, but after five or six classes that is what happens. For a six-year-old to become aware of their emotional life in a clear way and to recognize that he was sad, or angry…that's a kind of super power. And it becomes a basis of any further capacity to regulate emotion and behavior.
It can be something that they're explicitly taught early and it can be something that they get modeled by us. They can know that we practice. You can just sit with your kid when your kid is playing. Just a few minutes goes a long way. You model this behavior and punctuate your own distraction for a short period of time, and it can be incredibly positive.
Lastly, a bonus question that is definitely tongue-in-cheek. Who would win in a fight, you or Ben Affleck?
Sam: That's funny. That question was almost resolved in the green room after that encounter. That was an unpleasant meeting…I spend some amount of time training in the martial arts. This is one area where knowledge does count for a lot, but I don't think we'll have to resolve that uncertainty any time soon. We're both getting old.
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.