New Blood Test Can Detect Lymphoma Cells Before a Tumor Grows Back
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
When David M. Kurtz was doing his clinical fellowship at Stanford University Medical Center in 2009, specializing in lymphoma treatments, he found himself grappling with a question no one could answer. A typical regimen for these blood cancers prescribed six cycles of chemotherapy, but no one knew why. "The number seemed to be drawn out of a hat," Kurtz says. Some patients felt much better after just two doses, but had to endure the toxic effects of the entire course. For some elderly patients, the side effects of chemo are so harsh, they alone can kill. Others appeared to be cancer-free on the CT scans after the requisite six but then succumbed to it months later.
"Anecdotally, one patient decided to stop therapy after one dose because he felt it was so toxic that he opted for hospice instead," says Kurtz, now an oncologist at the center. "Five years down the road, he was alive and well. For him, just one dose was enough." Others would return for their one-year check up and find that their tumors grew back. Kurtz felt that while CT scans and MRIs were powerful tools, they weren't perfect ones. They couldn't tell him if there were any cancer cells left, stealthily waiting to germinate again. The scans only showed the tumor once it was back.
Blood cancers claim about 68,000 people a year, with a new diagnosis made about every three minutes, according to the Leukemia Research Foundation. For patients with B-cell lymphoma, which Kurtz focuses on, the survival chances are better than for some others. About 60 percent are cured, but the remaining 40 percent will relapse—possibly because they will have a negative CT scan, but still harbor malignant cells. "You can't see this on imaging," says Michael Green, who also treats blood cancers at University of Texas MD Anderson Medical Center.
The new blood test is sensitive enough to spot one cancerous perpetrator amongst one million other DNA molecules.
Kurtz wanted a better diagnostic tool, so he started working on a blood test that could capture the circulating tumor DNA or ctDNA. For that, he needed to identify the specific mutations typical for B-cell lymphomas. Working together with another fellow PhD student Jake Chabon, Kurtz finally zeroed-in on the tumor's genetic "appearance" in 2017—a pair of specific mutations sitting in close proximity to each other—a rare and telling sign. The human genome contains about 3 billion base pairs of nucleotides—molecules that compose genes—and in case of the B-cell lymphoma cells these two mutations were only a few base pairs apart. "That was the moment when the light bulb went on," Kurtz says.
The duo formed a company named Foresight Diagnostics, focusing on taking the blood test to the clinic. But knowing the tumor's mutational signature was only half the process. The other was fishing the tumor's DNA out of patients' bloodstream that contains millions of other DNA molecules, explains Chabon, now Foresight's CEO. It would be like looking for an escaped criminal in a large crowd. Kurtz and Chabon solved the problem by taking the tumor's "mug shot" first. Doctors would take the biopsy pre-treatment and sequence the tumor, as if taking the criminal's photo. After treatments, they would match the "mug shot" to all DNA molecules derived from the patient's blood sample to see if any molecular criminals managed to escape the chemo.
Foresight isn't the only company working on blood-based tumor detection tests, which are dubbed liquid biopsies—other companies such as Natera or ArcherDx developed their own. But in a recent study, the Foresight team showed that their method is significantly more sensitive in "fishing out" the cancer molecules than existing tests. Chabon says that this test can detect circulating tumor DNA in concentrations that are nearly 100 times lower than other methods. Put another way, it's sensitive enough to spot one cancerous perpetrator amongst one million other DNA molecules.
"It increases the sensitivity of detection and really catches most patients who are going to progress," says Green, the University of Texas oncologist who wasn't involved in the study, but is familiar with the method. It would also allow monitoring patients during treatment and making better-informed decisions about which therapy regimens would be most effective. "It's a minimally invasive test," Green says, and "it gives you a very high confidence about what's going on."
Having shown that the test works well, Kurtz and Chabon are planning a new trial in which oncologists would rely on their method to decide when to stop or continue chemo. They also aim to extend their test to detect other malignancies such as lung, breast or colorectal cancers. The latest genome sequencing technologies have sequenced and catalogued over 2,500 different tumor specimens and the Foresight team is analyzing this data, says Chabon, which gives the team the opportunity to create more molecular "mug shots."
The team hopes that that their blood cancer test will become available to patients within about five years, making doctors' job easier, and not only at the biological level. "When I tell patients, "good news, your cancer is in remission', they ask me, 'does it mean I'm cured?'" Kurtz says. "Right now I can't answer this question because I don't know—but I would like to." His company's test, he hopes, will enable him to reply with certainty. He'd very much like to have the power of that foresight.
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
How to have a good life, based on the world's longest study of happiness
What makes for a good life? Such a simple question, yet we don't have great answers. Most of us try to figure it out as we go along, and many end up feeling like they never got to the bottom of it.
Shouldn't something so important be approached with more scientific rigor? In 1938, Harvard researchers began a study to fill this gap. Since then, they’ve followed hundreds of people over the course of their lives, hoping to identify which factors are key to long-term satisfaction.
Eighty-five years later, the Harvard Study of Adult Development is still going. And today, its directors, the psychiatrists Bob Waldinger and Marc Shulz, have published a book that pulls together the study’s most important findings. It’s called The Good Life: Lessons from the World’s Longest Scientific Study of Happiness.
In this podcast episode, I talked with Dr. Waldinger about life lessons that we can mine from the Harvard study and his new book.
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More background on the study
Back in the 1930s, the research began with 724 people. Some were first-year Harvard students paying full tuition, others were freshmen who needed financial help, and the rest were 14-year-old boys from inner city Boston – white males only. Fortunately, the study team realized the error of their ways and expanded their sample to include the wives and daughters of the first participants. And Waldinger’s book focuses on the Harvard study findings that can be corroborated by evidence from additional research on the lives of people of different races and other minorities.
The study now includes over 1,300 relatives of the original participants, spanning three generations. Every two years, the participants have sent the researchers a filled-out questionnaire, reporting how their lives are going. At five-year intervals, the research team takes a peek their health records and, every 15 years, the psychologists meet their subjects in-person to check out their appearance and behavior.
But they don’t stop there. No, the researchers factor in multiple blood samples, DNA, images from body scans, and even the donated brains of 25 participants.
Robert Waldinger, director of the Harvard Study of Adult Development.
Katherine Taylor
Dr. Waldinger is Clinical Professor of Psychiatry at Harvard Medical School, in addition to being Director of the Harvard Study of Adult Development. He got his M.D. from Harvard Medical School and has published numerous scientific papers he’s a practicing psychiatrist and psychoanalyst, he teaches Harvard medical students, and since that is clearly not enough to keep him busy, he’s also a Zen priest.
His book is a must-read if you’re looking for scientific evidence on how to design your life for more satisfaction so someday in the future you can look back on it without regret, and this episode was an amazing conversation in which Dr. Waldinger breaks down many of the cliches about the good life, making his advice real and tangible. We also get into what he calls “side-by-side” relationships, personality traits for the good life, and the downsides of being too strict about work-life balance.
Show links
- Bob Waldinger
- Waldinger's book, The Good Life: Lessons from the World's Longest Scientific Study of Happiness
- The Harvard Study of Adult Development
- Waldinger's Ted Talk
- Gallup report finding that people with good friends at work have higher engagement with their jobs
- The link between relationships and well-being
- Those with social connections live longer
The Friday Five: A new blood test to detect Alzheimer's
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
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Here are the promising studies covered in this week's Friday Five:
- A blood test to detect Alzheimer's
- War vets can take their psychologist wherever they go
- Does intermittent fasting affect circadian rhythms?
- A new year's resolution for living longer
- 3-D printed eyes?