Americans Fell for a Theranos-Style Scam 100 Years Ago. Will We Ever Learn?
The huckster understands what people want – an easy route to good health -- and figures out just how to provide it as long as no one asks too many questions.
"Americans are very much prone to this sort of thinking: Give me a pill or give me a magical bean that can make me lose weight!"
The keys to success: Hoopla, fancy technology, and gullibility. And oh yes, one more thing: a blood sample. Well, lots and lots of blood samples. Every testing fee counts.
Sound familiar? It could be the story of the preternaturally persuasive Elizabeth Holmes, the disgraced founder of Theranos who stands accused of perpetrating a massive blood-testing fraud. But this is a different story from a different time, one that dates back 100 years but sounds almost like it could unfold on the front page of The Wall Street Journal today.
The main difference: Back then, watchdogs thought they'd be able to vanquish fake medicine and scam science. Fat chance, it turned out. It seems like we're more likely to lose-weight-quick than make much of a dent into quackery and health fraud.
Why? Have we learned anything at all over the past century? As we sweep into a new decade, experts says we're not as advanced as we'd like to think. But the fight against fraud and fakery continues.
Quackery: As American As America Itself
In the 17th century, British healers of questionable reputation got a new name -- "quack," from the Dutch word "quacksalver," which originally referred to someone who treats others with home remedies but developed a new meaning along the lines of "charlatan." And these quacks got a new place to sell their wares: the American colonies.
By 1692, a Boston newspaper advertised a patent medicine that promised to cure "the Griping of the Guts, and the Wind Cholick" and – for good measure – "preventeth that woeful Distemper of the Dry Belly Ach." A couple centuries later, the most famous woman in the United States wasn't a first lady or feminist but a hawker of nostrums named Lydia Estes Pinkham whose "vegetable compound" promised to banish "female complaints." One advertisement suggested that the "sure cure" would have saved the life of a Connecticut clergyman whose wife killed him after suffering from feminine maladies for 16 years.
By the early 20th century, Americans were fascinated by electricity and radiation, and both healers and hucksters embraced the new high-tech era. Men with flagging libidos, for example, could irradiate their private parts with the radioactive Radiendocrinator or buy battery-powered electric belts equipped with dangling bits to supercharge their, um, dangling bits.
The Rise of the Radio Wave 'Cure'
Enter radionics, the (supposed) science of better health via radio waves. The idea was that "healthy people radiate healthy energy," and sickness could be reversed through diagnosis and re-tuning, write Dr. Lydia Kang and Nate Pedersen in their 2017 book "Quackery: A Brief History of the Worst Ways to Cure Everything."
Detecting illness and fixing it required machinery -- Dynamizers, Radioclasts and Oscillocasts – that could cost hundreds of dollars each. Thousands of physicians bought them. Fortunately, they could work remotely, for a fee. The worried-and-potentially-unwell just needed to send a blood sample and, of course, a personal check.
Sting operations revealed radionics to be bogus. A skeptic sent a blood sample to one radionics practitioner in Albuquerque who reported back with news of an infected fallopian tube. In fact, the blood sample came from a male guinea pig. As an American Medical Association leader reported, the guinea pig "had shown no female characteristics up to that time, and a postmortem examination yielded no evidence of ladylike attributes."
When Quackery Refused to Yield
The rise of bogus medical technology in the early 20th century spawned a watchdog industry as organizations like the American Medical Association swept into action, said medical historian Eric Boyle, author of 2012's "Quack Medicine: A History of Combating Health Fraud in Twentieth-Century America."
"When quackery was recognized as a major problem, the people who campaigned for its demise were confident that they could get rid of it," he said. "A lot of people believed that increased education, the truths of science, and laws designed to protect consumers would ultimately drive quackery from the marketplace. And then throughout the century, as modern medicine developed, and more effectively treated one disease after another, many observers remained confident in that prediction."
There's a bid to "flood the information highway with truth to turn the storm of fake promotional stuff into a trickle."
But fake medicine persisted as Americans continued their quest to get- healthy-quick… or get-rich-quick by promising to help others to get- healthy-quick. Even radionics refused to die. It's still around in various forms. And, as the Theranos scandal reveals, we're still hoping our blood can offer the keys to longevity and good health.
Why Do We Still Fall for Scams?
In our own era, the Theranos company rose to prominence when founder and CEO Elizabeth Holmes convinced journalists and investors that she'd found a way to cheaply test drops of blood for hundreds of conditions. Then it all fell apart, famously, when the world learned that the technology didn't work. The company has folded, and Holmes faces a federal trial on fraud charges this year.
"There were a lot of prominent, very smart people who bought into the myth of Elizabeth Holmes," a former employee told "60 Minutes," even though the blood tests never actually worked as advertised.
Shouldn't "prominent, very smart people" know better? "People are gullible," said Dr. Stephen Barrett, a psychiatrist and leading quack-buster who runs the QuackWatch website. But there's more to the story. According to him, we're uniquely vulnerable as individuals to bogus medicine.
Scam artists specifically pinpoint their target audiences, such as "smart people," desperate people and alienated people, he said.
Smart people, for example, might be overconfident about their ability to detect fraud and fall for bogus medicine. Alienated people may distrust the establishment, whether it's the medical field or government watchdogs, and be more receptive to alternative sources of information.
Dr. Barrett also points a finger at magical thinking, which comes in different forms. It could mean a New Age-style belief that our minds can control the world around us. Or, as professional quack-buster Alex Berezow said, it could refer to "our cultural obsession with quick fixes."
"Americans are very much prone to this sort of thinking: Give me a pill or give me a magical bean that can make me lose weight! But complex problems need complex solutions," said Berezow, a microbiologist who debunks junk science in his job as a spokesman for the American Council on Science & Health.
American mistrust of expertise makes matters worse, he said. "When I tell people they need to get vaccinated, I'm called a shill for the pharmaceutical industry," he said. "If I say dietary supplements generally don't work, I'm a shill for doctors who want to keep people sick."
What can ordinary citizens do to protect themselves from fake medicine? "You have to have a healthy skepticism of everything," Berezow said. "When you come across something new, is someone trying to take advantage of you? It's a horrible way to think about the world, but there's some truth to it."
"Like any chronic disease, we will have to live with it while we do our best to fight it."
The government and experts have their own roles to play via regulation and education, respectively. For all the criticism it gets, the Food & Drug Administration does serve as a bulwark against fakery in prescription medicine. And while celebrities like Gwyneth "Goop" Paltrow hawk countless questionable medical products on the Internet, scientists and physicians are fighting back by using social media as a tool to promote the truth. There's a bid to "flood the information highway with truth to turn the storm of fake promotional stuff into a trickle," said Dr. Randi Hutter Epstein, a writer in residence at Yale School of Medicine and author of 2018's "Aroused: The History of Hormones and How They Control Just About Everything."
What's next? Like death, taxes and Cher, charlatans are likely to always be with us. Boyle quoted the late William Jarvis, a pioneering quack-buster in the late 20th century who believed health fraud would never be eradicated: "Like any chronic disease, we will have to live with it while we do our best to fight it."
This month, Leaps.org had a chance to speak with Holden Thorp, Editor-in-Chief of the Science family of journals. We talked about the best ways to communicate science to the public, mistakes by public health officials during the pandemic, the lab leak theory, and bipartisanship for funding science research.
Before becoming editor of the Science journals, Thorp spent six years as provost of Washington University in St. Louis, where he is Rita Levi-Montalcini Distinguished University Professor and holds appointments in both chemistry and medicine. He joined Washington University after spending three decades at the University of North Carolina at Chapel Hill, where he served as the UNC's 10th chancellor from 2008 through 2013.
A North Carolina native, Thorp earned a doctorate in chemistry in 1989 at the California Institute of Technology and completed postdoctoral work at Yale University. He is a fellow of the National Academy of Inventors and the American Association for the Advancement of Science.
Read his full bio here.
This conversation was lightly edited by Leaps.org for style and format.
Matt Fuchs: You're a musician. It seems like many scientists are also musicians. Is there a link between the scientist brain and the musician brain?
Holden Thorp: I think [the overlap is] relatively common. I'm still a gigging bass player. I play in the pits for lots of college musicals. I think that it takes a certain discipline and requires you to learn a lot of rules about how music works, and then you try to be creative within that. That's similar to scientific research. So it makes sense. Music is something I've been able to sustain my whole life. I wouldn't be the same person if I let it go. When you're playing, especially for a musical, where the music is challenging, you can't let your mind wander. It’s like meditation.
MF: I bet it helps to do something totally different from your editing responsibilities. Maybe lets the subconscious take care of tough problems at work.
HT: Right.
MF: There's probably never been a greater need for clear and persuasive science communicators. Do we need more cross specialty training? For example, journalism schools prioritizing science training, and science programs that require more time learning how to communicate effectively?
HT: I think we need both. One of the challenges we've had with COVID has been, especially at the beginning, a lot of reporters who didn’t normally cover scientific topics got put on COVID—and ended up creating things that had to be cleaned up later. This isn't the last science-oriented crisis we're going to have. We've already got climate change, and we'll have another health crisis for sure. So it’d be good for journalism to be a little better prepared next time.
"Scientists are human beings who have ego and bravado and every other human weakness."
But on the other side, maybe it's even more important that scientists learn how to communicate and how likely it is that their findings will be politicized, twisted and miscommunicated. Because one thing that surprised me is how shocked a lot of scientists have been. Every scientific issue that reaches into public policy becomes politicized: climate change, evolution, stem cells.
Once one side decided to be cautious about the pandemic, you could be certain the other side was going to decide not to do that. That's not the fault of science. That’s just life in a political world. That, I think, caught people off guard. They weren't prepared to shape and process their messages in a way that accounted for that—and for the way that social media has intensified all of this.
MF: Early in the pandemic, there was a lack of clarity about public health recommendations, as you’d expect with a virus we hadn’t seen before. Should public officials and scientists have more humility in similar situations in the future? Public officials need to be authoritative for their guidance to be followed, so how do they lead a crisis response while displaying humility about what we don't know?
HS: I think scientists are people who like to have the answer. It's very tempting and common for scientists to kind of oversell what we know right now, while not doing as much as we should to remind people that science is a self-correcting process. And when we fail to do that – after we’ve collected more data and need to change how we're interpreting it – the people who want to undermine us have a perfect weapon to use against us. It's challenging. But I agree that scientists are human beings who have ego and bravado and every other human weakness.
For example, we wanted to tell everybody that we thought the vaccines would provide sterilizing immunity against infection. Well, we don't have too many other respiratory viruses where that's the case. And so it was more likely that we were going to have what we ended up with, which is that the vaccines were excellent in preventing severe disease and death. It would have been great if they provided sterilizing immunity and abruptly ended the pandemic a year ago. But it was overly optimistic to think that was going to be the case in retrospect.
MF: Both in terms of how science is communicated and received by the public, do we need to reform institutions or start new ones to instill the truth-seeking values that are so important to appreciating science?
HS: There are a whole bunch of different factors. I think the biggest one is that the social media algorithms reward their owners financially when they figure out how to keep people in their silos. Users are more likely to click on things that they agree with—and that promote conflict with people that they disagree with. That has caused an acceleration in hostilities that attend some of these disagreements.
But I think the other problem is that we haven’t found a way to explain things to people when it’s not a crisis. So, for example, a strong indicator of whether someone who might otherwise be vaccine hesitant decided to get their vaccine is if they understood how vaccines worked before the pandemic started. Because if you're trying to tell somebody that they're wrong if they don't get a vaccine, at the same time you're trying to explain how it works, that's a lot of explaining to do in a short period of time.
Lack of open-mindedness is a problem, but another issue is that we need more understanding of these issues baked into the culture already. That's partly due the fact that there hasn't been more reform in K through 12 and college teaching. And that scientists are very comfortable talking to each other, and not very comfortable talking to people who don't know all of our jargon and have to be persuaded to spend time listening to and thinking about what we're trying to tell them.
"We're almost to the point where clinging to the lab leak idea is close to being a fringe idea that almost doesn't need to be included in stories."
MF: You mentioned silos. There have been some interesting attempts in recent years to do “both sides journalism,” where websites like AllSides put different views on high profile issues side-by-side. Some people believe that's how the news should be reported. Should we let people see and decide for themselves which side is the most convincing?
HS: It depends if we're talking about science. On scientific issues, when they start, there's legitimate disagreement about among scientists. But eventually, things go back and forth, and people compete with each other and work their way to the answer. At some point, we reach more of a consensus.
For example, on climate change, I think it's gotten to the point now where it's irresponsible, if you're writing a story about climate change, to run a quote from somebody somewhere who's still—probably because of their political views—clinging to the idea that anthropogenic global warming is somehow not damaging the planet.
On things that aren't decided yet, that makes sense to run both. It's more a question of judgment of the journalists. I don't think the solution to it is put stark versions of each side, side-by-side and let people choose. The whole point of journalism is to inform people. If there's a consensus on something, that's part of what you're supposed to be informing them about.
MF: What about reporting on perspectives about the lab leak theory at various times during the pandemic?
HS: We’re the outlet that ran the letter that really restarted the whole debate. A bunch of well-known scientists said we should consider the lab leak theory more carefully. And in the aftermath of that, a bunch of those scientists who signed that letter concluded that the lab leak was very, very unlikely. Interestingly, publishing that letter actually drove us to more of a consensus. I would say now, we're almost to the point where clinging to the lab leak idea is close to being a fringe idea that almost doesn't need to be included in stories. But I would say there's been a lot of evolution on that over the last year since we ran that letter.
MF: Let's talk about bipartisanship in Congress. Research funding for the National Institutes of Health was championed for years by influential Republicans who supported science to advance health breakthroughs. Is that changing? Maybe especially with Sen. Roy Blunt retiring? Has bipartisanship on science funding been eroded by political battles during COVID?
HS: I'm optimistic that that won't be the case. Republican Congresses have usually been good for science funding. And that's because (former Sen.) Arlen Specter and Roy Blunt are two of the political figures who have pushed for science funding over the last couple decades. With Blunt retiring, we don't know who's going to step in for him. That's an interesting question. I hope there will be Republican champions for science funding.
MF: Is there too much conservatism baked into how we research new therapies and bring them to people who are sick, bench-to-bedside? I'm thinking of the criticisms that NIH or the FDA are overly bureaucratic. Are you hopeful about ARPA-H, President Biden’s proposed new agency for health innovation?
HS: I think the challenge hasn't been cracked by the federal government. Maybe DARPA has done this outside of health science, but within health science, the federal government has had limited success at funding things that can be applied quickly, while having overwhelming success at funding basic research that eventually becomes important in applications. Can they do it the other way around? They’ll need people running ARPA-H who are application first. It’s ambitious. The way it was done in Operation Warp Speed is all the money was just given to the companies. If the hypothesis on ARPA-H is for the federal government to actually do what Moderna and BioNTech did for the vaccine, themselves, that's a radical idea. It's going to require thinking very differently than the way they think about dispersing grants for basic research.
MF: You’ve written a number of bold op-eds as editor of the Science journals. Are there any op-eds you're especially proud of as voicing a view that was important but not necessarily popular?
HS: I was one of the first people to come out hard against President Trump['s handling of] the pandemic. Lots of my brothers and sisters came along afterwards. To the extent that I was able to catalyze that, I'm proud of doing it. In the last few weeks, I published a paper objecting to the splitting of the OSTP director from the science advisor and, especially, not awarding the top part of the job to Alondra Nelson, who is a distinguished scientist at black female. And instead, giving part of it to Francis Collins. He’s certainly the most important science policy figure of my lifetime, but somebody who’s been doing this now for decades. I just think we have to push as hard as we can to get a cadre of young people leading us in Washington who represent the future of the country. I think the Biden administration leaned on a lot of figures from the past. I’m pushing them hard to try to stop it.
MF: I want to circle back to the erosion of the public’s trust in experts. Most experts are specialists, and specialists operate in silos that don’t capture the complexity of scientific knowledge. Are some pushbacks to experts and concerns about the perils of specialization valid?
HS: You're on the right track there. What we need is more respect for the generalist. We can't help the fact that you have to be very specialized to do a lot of stuff. But what we need is more partnership between specialists and people who can cross fields, especially into communication and social sciences. That handoff is just not really there right now. It's hard to get a hardcore scientist to respect people who are interested in science, education and science communication, and to treat them as equals. The last two years showed that they're at least as important, if not more so.
MF: I’m grateful that you’re leading the way in this area, Holden. Thank you for sharing your thoughts and your work.
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.”