He Beat Lymphoma at 31, While Pioneering Breakthroughs in Cancer Research
Taylor Schreiber, now 39, runs an immunotherapy company testing drugs that may be less toxic alternative to chemotherapy.
It looked like only good things were ahead of Taylor Schreiber in 2010.
Schreiber had just finished his PhD in cancer biology and was preparing to return to medical school to complete his degree. He also had been married a year, and, like any young newlyweds up for adventure, he and his wife Nicki decided to go backpacking in the Costa Rican rainforest.
He was 31, and it was April Fool's Day—but no joke.
During the trip, he experienced a series of night sweats and didn't think too much about it. Schreiber hadn't been feeling right for a few weeks and assumed he had a respiratory infection. Besides, they were sleeping outdoors in a hot, tropical jungle.
But the night sweats continued even after he got home, leaving his mattress so soaked in the morning it was if a bucket of water had been dumped on him overnight. On instinct, he called one of his thesis advisors at the Sylvester Comprehensive Cancer Center in Florida and described his symptoms.
Dr. Joseph Rosenblatt didn't hesitate. "It sounds like Hodgkins. Come see me tomorrow," he said.
The next day, Schreiber was diagnosed with Stage 3b Hodgkin Lymphoma, which meant the disease was advanced. He was 31, and it was April Fool's Day—but no joke.
"I was scared to death," he recalls. "[Thank] goodness it's one of those cancers that is highly treatable. But being 31 years old and all of a sudden being told that you have a 30 percent of mortality within the next two years wasn't anything that I was relieved about."
For Schreiber, the diagnosis was a personal and professional game-changer. He couldn't work in the hospital as a medical student while undergoing chemotherapy, so he wound up remaining in his post-doctorate lab for another two years. The experience also solidified his decision to apply his scientific and medical knowledge to drug development.
Today, now 39, Schreiber is co-founder, director and chief scientific officer of Shattuck Labs, an immuno-oncology startup, and the developer of several important research breakthroughs in the field of immunotherapy.
After his diagnosis, he continued working full-time as a postdoc, while undergoing an aggressive chemotherapy regimen.
"These days, I look back on [my cancer] and think it was one of the luckiest things that ever happened to me," he says. "In medical school, you learn what it is to treat people and learn about the disease. But there is nothing like being a patient to teach you another side of medicine."
Medicine first called to Schreiber when his maternal grandfather was dying from lung cancer complications. Schreiber's uncle, a radiologist at the medical center where his grandfather was being treated, took him on a tour of his department and showed him images of the insides of his body on an ultrasound machine.
Schreiber was mesmerized. His mother was a teacher and his dad sold windows, so medicine was not something to which he had been routinely exposed.
"This weird device was like looking through jelly, and I thought that was the coolest thing ever," he says.
The experience led him to his first real job at the Catholic Medical Center in Manchester, NH, then to a semester-long internship program during his senior year in high school in Concord Hospital's radiology department.
"This was a great experience, but it also made clear that there was not any meaningful way to learn or contribute to medicine before you obtained a medical degree," says Schreiber, who enrolled in Bucknell College to study biology.
Bench science appealed to him, and he volunteered in Dr. Jing Zhou's nephrology department lab at the Harvard Institutes of Medicine. Under the mentorship of one of her post-docs, Lei Guo, he learned a range of critical techniques in molecular biology, leading to their discovery of a new gene related to human polycystic kidney disease and his first published paper.
Before his cancer diagnosis, Schreiber also volunteered in the lab of Dr. Robert "Doc" Sackstein, a world-renowned bone marrow transplant physician and biomedical researcher, and his interests began to shift towards immunology.
"He was just one of those dynamic people who has a real knack for teaching, first of all, and for inspiring people to want to learn more and ask hard questions and understand experimental medicine," Schreiber says.
It was there that he learned the scientific method and the importance of incorporating the right controls in experiments—a simple idea, but difficult to perform well. He also made what Sackstein calls "a startling discovery" about chemokines, which are signaling proteins that can activate an immune response.
As immune cells travel around our bodies looking for potential sources of infection or disease, they latch onto blood vessel walls and "sniff around" for specific chemical cues that indicate a source of infection. Schreiber and his colleagues designed a system that mimics the blood vessel wall, allowing them to define which chemical cues efficiently drive immune cell migration from the blood into tissues.
Schreiber received the best overall research award in 2008 from the National Student Research Foundation. But even as Schreiber's expertise about immunology grew, his own immune system was about to fight its hardest battle.
After his diagnosis, he continued working full-time as a postdoc in the lab of Eckhard Podack, then chair of the microbiology and immunology department at the University of Miami's Leonard M. Miller School of Medicine.
At the same time, Schreiber began an aggressive intravenous chemotherapy regimen of adriamycin, bleomycin, vincristine and dacarbazine, every two weeks, for 6 months. His wife Nicki, an obgyn, transferred her residency from Emory University in Atlanta to Miami so they could be together.
"It was a weird period. I mean, it made me feel good to keep doing things and not just lay idle," he said. "But by the second cycle of chemo, I was immunosuppressed and losing my hair and wore a face mask walking around the lab, which I was certainly self-conscious. But everyone around me didn't make me feel like an alien so I just went about my business."
The experience reinforced his desire to stay in immunology, especially after having taken the most toxic chemotherapies.
He stayed home the day after chemo when he felt his worst, then rested his body and timed exercise to give the drugs the best shot of targeting sick cells (a strategy, he says, that "could have been voodoo"). He also drank "an incredible" amount of fluids to help flush the toxins out of his system.
Side effects of the chemo, besides hair loss, included intense nausea, diarrhea, a loss of appetite, some severe lung toxicities that eventually resolved, and incredible fatigue.
"I've always been a runner, and I would even try to run while I was doing chemo," he said. "After I finished treatment, I would go literally 150 yards and just have to stop, and it took a lot of effort to work through it."
The experience reinforced his desire to stay in immunology, especially after having taken the most toxic chemotherapies.
"They worked, and I could tolerate them because I was young, but people who are older can't," Schreiber said. "The whole field of immunotherapy has really demonstrated that there are effective therapies out there that don't come with all of the same toxicities as the original chemo, so it was galvanizing to imagine contributing to finding some of those."
Schreiber went on to complete his MD and PhD degrees from the Sheila and David Fuente Program in Cancer Biology at the Miller School of Medicine and was nominated in 2011 as a Future Leader in Cancer Research by the American Association for Cancer Research. He also has numerous publications in the fields of tumor immunology and immunotherapy.
Sackstein, who was struck by Schreiber's enthusiasm and "boundless energy," predicts he will be a "major player in the world of therapeutics."
"The future for Taylor is amazing because he has the capacity to synthesize current knowledge and understand the gaps and then ask the right questions to establish new paradigms," said Sackstein, currently dean of the Herbert Wertheim College of Medicine at Florida International University. "It's a very unusual talent."
Since then, he has devoted his career to developing innovative techniques aimed at unleashing the immune system to attack cancer with less toxicity than chemotherapy and better clinical results—first, at a company called Heat Biologics and then at Pelican Therapeutics.
His primary work at Austin, Texas-based Shattuck is aimed at combining two functions in a single therapy for cancer and inflammatory diseases, blocking molecules that put a brake on the immune system (checkpoint inhibitors) while also stimulating the immune system's cancer-killing T cells.
The company has one drug in clinical testing as part of its Agonist Redirected Checkpoint (ARC) platform, which represents a new class of biological medicine. Two others are expected within the next year, with a pipeline of more than 250 drug candidates spanning cancer, inflammatory, and metabolic diseases.
Nine years after his own cancer diagnosis, Schreiber says it remains a huge part of his life, though his chances of a cancer recurrence today are about the same as his chances of getting newly diagnosed with any other cancer.
"I feel blessed to be in a position to help cancer patients live longer and could not imagine a more fulfilling way to spend my life," he says.
Regenerative medicine has come a long way, baby
After a cloned baby sheep, what started as one of the most controversial areas in medicine is now promising to transform it.
The field of regenerative medicine had a shaky start. In 2002, when news spread about the first cloned animal, Dolly the sheep, a raucous debate ensued. Scary headlines and organized opposition groups put pressure on government leaders, who responded by tightening restrictions on this type of research.
Fast forward to today, and regenerative medicine, which focuses on making unhealthy tissues and organs healthy again, is rewriting the code to healing many disorders, though it’s still young enough to be considered nascent. What started as one of the most controversial areas in medicine is now promising to transform it.
Progress in the lab has addressed previous concerns. Back in the early 2000s, some of the most fervent controversy centered around somatic cell nuclear transfer (SCNT), the process used by scientists to produce Dolly. There was fear that this technique could be used in humans, with possibly adverse effects, considering the many medical problems of the animals who had been cloned.
But today, scientists have discovered better approaches with fewer risks. Pioneers in the field are embracing new possibilities for cellular reprogramming, 3D organ printing, AI collaboration, and even growing organs in space. It could bring a new era of personalized medicine for longer, healthier lives - while potentially sparking new controversies.
Engineering tissues from amniotic fluids
Work in regenerative medicine seeks to reverse damage to organs and tissues by culling, modifying and replacing cells in the human body. Scientists in this field reach deep into the mechanisms of diseases and the breakdowns of cells, the little workhorses that perform all life-giving processes. If cells can’t do their jobs, they take whole organs and systems down with them. Regenerative medicine seeks to harness the power of healthy cells derived from stem cells to do the work that can literally restore patients to a state of health—by giving them healthy, functioning tissues and organs.
Modern-day regenerative medicine takes its origin from the 1998 isolation of human embryonic stem cells, first achieved by John Gearhart at Johns Hopkins University. Gearhart isolated the pluripotent cells that can differentiate into virtually every kind of cell in the human body. There was a raging controversy about the use of these cells in research because at that time they came exclusively from early-stage embryos or fetal tissue.
Back then, the highly controversial SCNT cells were the only way to produce genetically matched stem cells to treat patients. Since then, the picture has changed radically because other sources of highly versatile stem cells have been developed. Today, scientists can derive stem cells from amniotic fluid or reprogram patients’ skin cells back to an immature state, so they can differentiate into whatever types of cells the patient needs.
In the context of medical history, the field of regenerative medicine is progressing at a dizzying speed. But for those living with aggressive or chronic illnesses, it can seem that the wheels of medical progress grind slowly.
The ethical debate has been dialed back and, in the last few decades, the field has produced important innovations, spurring the development of whole new FDA processes and categories, says Anthony Atala, a bioengineer and director of the Wake Forest Institute for Regenerative Medicine. Atala and a large team of researchers have pioneered many of the first applications of 3D printed tissues and organs using cells developed from patients or those obtained from amniotic fluid or placentas.
His lab, considered to be the largest devoted to translational regenerative medicine, is currently working with 40 different engineered human tissues. Sixteen of them have been transplanted into patients. That includes skin, bladders, urethras, muscles, kidneys and vaginal organs, to name just a few.
These achievements are made possible by converging disciplines and technologies, such as cell therapies, bioengineering, gene editing, nanotechnology and 3D printing, to create living tissues and organs for human transplants. Atala is currently overseeing clinical trials to test the safety of tissues and organs engineered in the Wake Forest lab, a significant step toward FDA approval.
In the context of medical history, the field of regenerative medicine is progressing at a dizzying speed. But for those living with aggressive or chronic illnesses, it can seem that the wheels of medical progress grind slowly.
“It’s never fast enough,” Atala says. “We want to get new treatments into the clinic faster, but the reality is that you have to dot all your i’s and cross all your t’s—and rightly so, for the sake of patient safety. People want predictions, but you can never predict how much work it will take to go from conceptualization to utilization.”
As a surgeon, he also treats patients and is able to follow transplant recipients. “At the end of the day, the goal is to get these technologies into patients, and working with the patients is a very rewarding experience,” he says. Will the 3D printed organs ever outrun the shortage of donated organs? “That’s the hope,” Atala says, “but this technology won’t eliminate the need for them in our lifetime.”
New methods are out of this world
Jeanne Loring, another pioneer in the field and director of the Center for Regenerative Medicine at Scripps Research Institute in San Diego, says that investment in regenerative medicine is not only paying off, but is leading to truly personalized medicine, one of the holy grails of modern science.
This is because a patient’s own skin cells can be reprogrammed to become replacements for various malfunctioning cells causing incurable diseases, such as diabetes, heart disease, macular degeneration and Parkinson’s. If the cells are obtained from a source other than the patient, they can be rejected by the immune system. This means that patients need lifelong immunosuppression, which isn’t ideal. “With Covid,” says Loring, “I became acutely aware of the dangers of immunosuppression.” Using the patient’s own cells eliminates that problem.
Microgravity conditions make it easier for the cells to form three-dimensional structures, which could more easily lead to the growing of whole organs. In fact, Loring's own cells have been sent to the ISS for study.
Loring has a special interest in neurons, or brain cells that can be developed by manipulating cells found in the skin. She is looking to eventually treat Parkinson’s disease using them. The manipulated cells produce dopamine, the critical hormone or neurotransmitter lacking in the brains of patients. A company she founded plans to start a Phase I clinical trial using cell therapies for Parkinson’s soon, she says.
This is the culmination of many years of basic research on her part, some of it on her own cells. In 2007, Loring had her own cells reprogrammed, so there’s a cell line that carries her DNA. “They’re just like embryonic stem cells, but personal,” she said.
Loring has another special interest—sending immature cells into space to be studied at the International Space Station. There, microgravity conditions make it easier for the cells to form three-dimensional structures, which could more easily lead to the growing of whole organs. In fact, her own cells have been sent to the ISS for study. “My colleagues and I have completed four missions at the space station,” she says. “The last cells came down last August. They were my own cells reprogrammed into pluripotent cells in 2009. No one else can say that,” she adds.
Future controversies and tipping points
Although the original SCNT debate has calmed down, more controversies may arise, Loring thinks.
One of them could concern growing synthetic embryos. The embryos are ultimately derived from embryonic stem cells, and it’s not clear to what stage these embryos can or will be grown in an artificial uterus—another recent invention. The science, so far done only in animals, is still new and has not been widely publicized but, eventually, “People will notice the production of synthetic embryos and growing them in an artificial uterus,” Loring says. It’s likely to incite many of the same reactions as the use of embryonic stem cells.
Bernard Siegel, the founder and director of the Regenerative Medicine Foundation and executive director of the newly formed Healthspan Action Coalition (HSAC), believes that stem cell science is rapidly approaching tipping point and changing all of medical science. (For disclosure, I do consulting work for HSAC). Siegel says that regenerative medicine has become a new pillar of medicine that has recently been fast-tracked by new technology.
Artificial intelligence is speeding up discoveries and the convergence of key disciplines, as demonstrated in Atala’s lab, which is creating complex new medical products that replace the body’s natural parts. Just as importantly, those parts are genetically matched and pose no risk of rejection.
These new technologies must be regulated, which can be a challenge, Siegel notes. “Cell therapies represent a challenge to the existing regulatory structure, including payment, reimbursement and infrastructure issues that 20 years ago, didn’t exist.” Now the FDA and other agencies are faced with this revolution, and they’re just beginning to adapt.
Siegel cited the 2021 FDA Modernization Act as a major step. The Act allows drug developers to use alternatives to animal testing in investigating the safety and efficacy of new compounds, loosening the agency’s requirement for extensive animal testing before a new drug can move into clinical trials. The Act is a recognition of the profound effect that cultured human cells are having on research. Being able to test drugs using actual human cells promises to be far safer and more accurate in predicting how they will act in the human body, and could accelerate drug development.
Siegel, a longtime veteran and founding father of several health advocacy organizations, believes this work helped bring cell therapies to people sooner rather than later. His new focus, through the HSAC, is to leverage regenerative medicine into extending not just the lifespan but the worldwide human healthspan, the period of life lived with health and vigor. “When you look at the HSAC as a tree,” asks Siegel, “what are the roots of that tree? Stem cell science and the huge ecosystem it has created.” The study of human aging is another root to the tree that has potential to lengthen healthspans.
The revolutionary science underlying the extension of the healthspan needs to be available to the whole world, Siegel says. “We need to take all these roots and come up with a way to improve the life of all mankind,” he says. “Everyone should be able to take advantage of this promising new world.”
Joy Milne's unusual sense of smell led Dr. Tilo Kunath, a neurobiologist at the Centre for Regenerative Medicine at the University of Edinburgh, and a host of other scientists, to develop a new diagnostic test for Parkinson's.
Forty years ago, Joy Milne, a nurse from Perth, Scotland, noticed a musky odor coming from her husband, Les. At first, Milne thought the smell was a result of bad hygiene and badgered her husband to take longer showers. But when the smell persisted, Milne learned to live with it, not wanting to hurt her husband's feelings.
Twelve years after she first noticed the "woodsy" smell, Les was diagnosed at the age of 44 with Parkinson's Disease, a neurodegenerative condition characterized by lack of dopamine production and loss of movement. Parkinson's Disease currently affects more than 10 million people worldwide.
Milne spent the next several years believing the strange smell was exclusive to her husband. But to her surprise, at a local support group meeting in 2012, she caught the familiar scent once again, hanging over the group like a cloud. Stunned, Milne started to wonder if the smell was the result of Parkinson's Disease itself.
Milne's discovery led her to Dr. Tilo Kunath, a neurobiologist at the Centre for Regenerative Medicine at the University of Edinburgh. Together, Milne, Kunath, and a host of other scientists would use Milne's unusual sense of smell to develop a new diagnostic test, now in development and poised to revolutionize the treatment of Parkinson's Disease.
"Joy was in the audience during a talk I was giving on my work, which has to do with Parkinson's and stem cell biology," Kunath says. "During the patient engagement portion of the talk, she asked me if Parkinson's had a smell to it." Confused, Kunath said he had never heard of this – but for months after his talk he continued to turn the question over in his mind.
Kunath knew from his research that the skin's microbiome changes during different disease processes, releasing metabolites that can give off odors. In the medical literature, diseases like melanoma and Type 2 diabetes have been known to carry a specific scent – but no such connection had been made with Parkinson's. If people could smell Parkinson's, he thought, then it stood to reason that those metabolites could be isolated, identified, and used to potentially diagnose Parkinson's by their presence alone.
First, Kunath and his colleagues decided to test Milne's sense of smell. "I got in touch with Joy again and we designed a protocol to test her sense of smell without her having to be around patients," says Kunath, which could have affected the validity of the test. In his spare time, Kunath collected t-shirt samples from people diagnosed with Parkinson's and from others without the diagnosis and gave them to Milne to smell. In 100 percent of the samples, Milne was able to detect whether a person had Parkinson's based on smell alone. Amazingly, Milne was even able to detect the "Parkinson's scent" in a shirt from the control group – someone who did not have a Parkinson's diagnosis, but would go on to be diagnosed nine months later.
From the initial study, the team discovered that Parkinson's did have a smell, that Milne – inexplicably – could detect it, and that she could detect it long before diagnosis like she had with her husband, Les. But the experiments revealed other things that the team hadn't been expecting.
"One surprising thing we learned from that experiment was that the odor was always located in the back of the shirt – never in the armpit, where we expected the smell to be," Kunath says. "I had a chance meeting with a dermatologist and he said the smell was due to the patient's sebum, which are greasy secretions that are really dense on your upper back. We have sweat glands, instead of sebum, in our armpits." Patients with Parkinson's are also known to have increased sebum production.
With the knowledge that a patient's sebum was the source of the unusual smell, researchers could go on to investigate exactly what metabolites were in the sebum and in what amounts. Kunath, along with his associate, Dr. Perdita Barran, collected and analyzed sebum samples from 64 participants across the United Kingdom. Once the samples were collected, Barran and others analyzed it using a method called gas chromatography mass spectrometry, or GS-MC, which separated, weighed and helped identify the individual compounds present in each sebum sample.
Barran's team can now correctly identify Parkinson's in nine out of 10 patients – a much quicker and more accurate way to diagnose than what clinicians do now.
"The compounds we've identified in the sebum are not unique to people with Parkinson's, but they are differently expressed," says Barran, a professor of mass spectrometry at the University of Manchester. "So this test we're developing now is not a black-and-white, do-you-have-something kind of test, but rather how much of these compounds do you have compared to other people and other compounds." The team identified over a dozen compounds that were present in the sebum of Parkinson's patients in much larger amounts than the control group.
Using only the GC-MS and a sebum swab test, Barran's team can now correctly identify Parkinson's in nine out of 10 patients – a much quicker and more accurate way to diagnose than what clinicians do now.
"At the moment, a clinical diagnosis is based on the patient's physical symptoms," Barran says, and determining whether a patient has Parkinson's is often a long and drawn-out process of elimination. "Doctors might say that a group of symptoms looks like Parkinson's, but there are other reasons people might have those symptoms, and it might take another year before they're certain," Barran says. "Some of those symptoms are just signs of aging, and other symptoms like tremor are present in recovering alcoholics or people with other kinds of dementia." People under the age of 40 with Parkinson's symptoms, who present with stiff arms, are often misdiagnosed with carpal tunnel syndrome, she adds.
Additionally, by the time physical symptoms are present, Parkinson's patients have already lost a substantial amount of dopamine receptors – about sixty percent -- in the brain's basal ganglia. Getting a diagnosis before physical symptoms appear would mean earlier interventions that could prevent dopamine loss and preserve regular movement, Barran says.
"Early diagnosis is good if it means there's a chance of early intervention," says Barran. "It stops the process of dopamine loss, which means that motor symptoms potentially will not happen, or the onset of symptoms will be substantially delayed." Barran's team is in the processing of streamlining the sebum test so that definitive results will be ready in just two minutes.
"What we're doing right now will be a very inexpensive test, a rapid-screen test, and that will encourage people to self-sample and test at home," says Barran. In addition to diagnosing Parkinson's, she says, this test could also be potentially useful to determine if medications were at a therapeutic dose in people who have the disease, since the odor is strongest in people whose symptoms are least controlled by medication.
"When symptoms are under control, the odor is lower," Barran says. "Potentially this would allow patients and clinicians to see whether their symptoms are being managed properly with medication, or perhaps if they're being overmedicated." Hypothetically, patients could also use the test to determine if interventions like diet and exercise are effective at keeping Parkinson's controlled.
"We hope within the next two to five years we will have a test available."
Barran is now running another clinical trial – one that determines whether they can diagnose at an earlier stage and whether they can identify a difference in sebum samples between different forms of Parkinson's or diseases that have Parkinson's-like symptoms, such as Lewy Body Dementia.
"Within the next one to two years, we hope to be running a trial in the Manchester area for those people who do not have motor symptoms but are at risk for developing dementia due to symptoms like loss of smell and sleep difficulty," Barran had said in 2019. "If we can establish that, we can roll out a test that determines if you have Parkinson's or not with those first pre-motor symptoms, and then at what stage. We hope within the next two to five years we will have a test available."
In a 2022 study, published in the American Chemical Society, researchers used mass spectrometry to analyze sebum from skin swabs for the presence of the specific molecules. They found that some specific molecules are present only in people who have Parkinson’s. Now they hope that the same method can be used in regular diagnostic labs. The test, many years in the making, is inching its way to the clinic.
"We would likely first give this test to people who are at risk due to a genetic predisposition, or who are at risk based on prodomal symptoms, like people who suffer from a REM sleep disorder who have a 50 to 70 percent chance of developing Parkinson's within a ten year period," Barran says. "Those would be people who would benefit from early therapeutic intervention. For the normal population, it isn't beneficial at the moment to know until we have therapeutic interventions that can be useful."
Milne's husband, Les, passed away from complications of Parkinson's Disease in 2015. But thanks to him and the dedication of his wife, Joy, science may have found a way to someday prolong the lives of others with this devastating disease. Sometimes she can smell people who have Parkinson’s while in the supermarket or walking down the street but has been told by medical ethicists she cannot tell them, Milne said in an interview with the Guardian. But once the test becomes available in the clinics, it will do the job for her.
[Ed. Note: A older version of this hit article originally ran on September 3, 2019.]