How a Deadly Fire Gave Birth to Modern Medicine
On the evening of November 28, 1942, more than 1,000 revelers from the Boston College-Holy Cross football game jammed into the Cocoanut Grove, Boston's oldest nightclub. When a spark from faulty wiring accidently ignited an artificial palm tree, the packed nightspot, which was only designed to accommodate about 500 people, was quickly engulfed in flames. In the ensuing panic, hundreds of people were trapped inside, with most exit doors locked. Bodies piled up by the only open entrance, jamming the exits, and 490 people ultimately died in the worst fire in the country in forty years.
"People couldn't get out," says Dr. Kenneth Marshall, a retired plastic surgeon in Boston and president of the Cocoanut Grove Memorial Committee. "It was a tragedy of mammoth proportions."
Within a half an hour of the start of the blaze, the Red Cross mobilized more than five hundred volunteers in what one newspaper called a "Rehearsal for Possible Blitz." The mayor of Boston imposed martial law. More than 300 victims—many of whom subsequently died--were taken to Boston City Hospital in one hour, averaging one victim every eleven seconds, while Massachusetts General Hospital admitted 114 victims in two hours. In the hospitals, 220 victims clung precariously to life, in agonizing pain from massive burns, their bodies ravaged by infection.
The scene of the fire.
Boston Public Library
Tragic Losses Prompted Revolutionary Leaps
But there is a silver lining: this horrific disaster prompted dramatic changes in safety regulations to prevent another catastrophe of this magnitude and led to the development of medical techniques that eventually saved millions of lives. It transformed burn care treatment and the use of plasma on burn victims, but most importantly, it introduced to the public a new wonder drug that revolutionized medicine, midwifed the birth of the modern pharmaceutical industry, and nearly doubled life expectancy, from 48 years at the turn of the 20th century to 78 years in the post-World War II years.
The devastating grief of the survivors also led to the first published study of post-traumatic stress disorder by pioneering psychiatrist Alexandra Adler, daughter of famed Viennese psychoanalyst Alfred Adler, who was a student of Freud. Dr. Adler studied the anxiety and depression that followed this catastrophe, according to the New York Times, and "later applied her findings to the treatment World War II veterans."
Dr. Ken Marshall is intimately familiar with the lingering psychological trauma of enduring such a disaster. His mother, an Irish immigrant and a nurse in the surgical wards at Boston City Hospital, was on duty that cold Thanksgiving weekend night, and didn't come home for four days. "For years afterward, she'd wake up screaming in the middle of the night," recalls Dr. Marshall, who was four years old at the time. "Seeing all those bodies lined up in neat rows across the City Hospital's parking lot, still in their evening clothes. It was always on her mind and memories of the horrors plagued her for the rest of her life."
The sheer magnitude of casualties prompted overwhelmed physicians to try experimental new procedures that were later successfully used to treat thousands of battlefield casualties. Instead of cutting off blisters and using dyes and tannic acid to treat burned tissues, which can harden the skin, they applied gauze coated with petroleum jelly. Doctors also refined the formula for using plasma--the fluid portion of blood and a medical technology that was just four years old--to replenish bodily liquids that evaporated because of the loss of the protective covering of skin.
"Every war has given us a new medical advance. And penicillin was the great scientific advance of World War II."
"The initial insult with burns is a loss of fluids and patients can die of shock," says Dr. Ken Marshall. "The scientific progress that was made by the two institutions revolutionized fluid management and topical management of burn care forever."
Still, they could not halt the staph infections that kill most burn victims—which prompted the first civilian use of a miracle elixir that was being secretly developed in government-sponsored labs and that ultimately ushered in a new age in therapeutics. Military officials quickly realized this disaster could provide an excellent natural laboratory to test the effectiveness of this drug and see if it could be used to treat the acute traumas of combat in this unfortunate civilian approximation of battlefield conditions. At the time, the very existence of this wondrous medicine—penicillin—was a closely guarded military secret.
From Forgotten Lab Experiment to Wonder Drug
In 1928, Alexander Fleming discovered the curative powers of penicillin, which promised to eradicate infectious pathogens that killed millions every year. But the road to mass producing enough of the highly unstable mold was littered with seemingly unsurmountable obstacles and it remained a forgotten laboratory curiosity for over a decade. But Fleming never gave up and penicillin's eventual rescue from obscurity was a landmark in scientific history.
In 1940, a group at Oxford University, funded in part by the Rockefeller Foundation, isolated enough penicillin to test it on twenty-five mice, which had been infected with lethal doses of streptococci. Its therapeutic effects were miraculous—the untreated mice died within hours, while the treated ones played merrily in their cages, undisturbed. Subsequent tests on a handful of patients, who were brought back from the brink of death, confirmed that penicillin was indeed a wonder drug. But Britain was then being ravaged by the German Luftwaffe during the Blitz, and there were simply no resources to devote to penicillin during the Nazi onslaught.
In June of 1941, two of the Oxford researchers, Howard Florey and Ernst Chain, embarked on a clandestine mission to enlist American aid. Samples of the temperamental mold were stored in their coats. By October, the Roosevelt Administration had recruited four companies—Merck, Squibb, Pfizer and Lederle—to team up in a massive, top-secret development program. Merck, which had more experience with fermentation procedures, swiftly pulled away from the pack and every milligram they produced was zealously hoarded.
After the nightclub fire, the government ordered Merck to dispatch to Boston whatever supplies of penicillin that they could spare and to refine any crude penicillin broth brewing in Merck's fermentation vats. After working in round-the-clock relays over the course of three days, on the evening of December 1st, 1942, a refrigerated truck containing thirty-two liters of injectable penicillin left Merck's Rahway, New Jersey plant. It was accompanied by a convoy of police escorts through four states before arriving in the pre-dawn hours at Massachusetts General Hospital. Dozens of people were rescued from near-certain death in the first public demonstration of the powers of the antibiotic, and the existence of penicillin could no longer be kept secret from inquisitive reporters and an exultant public. The next day, the Boston Globe called it "priceless" and Time magazine dubbed it a "wonder drug."
Within fourteen months, penicillin production escalated exponentially, churning out enough to save the lives of thousands of soldiers, including many from the Normandy invasion. And in October 1945, just weeks after the Japanese surrender ended World War II, Alexander Fleming, Howard Florey and Ernst Chain were awarded the Nobel Prize in medicine. But penicillin didn't just save lives—it helped build some of the most innovative medical and scientific companies in history, including Merck, Pfizer, Glaxo and Sandoz.
"Every war has given us a new medical advance," concludes Marshall. "And penicillin was the great scientific advance of World War II."
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.”