Friday Five: The Therapeutic Value of Bonding with Fellow Sports Fans
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 new scientific theories and progress to give you a therapeutic dose of inspiration headed into the weekend.
This episode includes an interview with Dr. Helen Keyes, Head of the School of Psychology and Sports Science at Anglia Ruskin University.
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- Attending sports events is linked to greater life satisfaction
- Identifying specific brain tumors in under 90 seconds with AI
- LSD - minus hallucinations - raises hopes for mental health
- New research on the benefits of cold showers
- Inspire awe in your kids and reap the benefits
Podcast: Has the First 150-Year-Old Already Been Born
Steven Austad is a pioneer in the field of aging, with over 200 scientific papers and book chapters on pretty much every aspect of biological aging that you could think of. He’s also a strong believer in the potential for anti-aging therapies, and he puts his money where his mouth is. In 2001, he bet a billion dollars that the first person to reach 150-years-old had already been born. I had a chance to talk with Steven for today’s podcast and asked if he still thinks the bet was a good idea, since the oldest person so far (that we know of), Jeanne Calment, died back in 1997. A few days after our conversation, the oldest person in the world, Kane Tanaka, died at 119.
Steven is the Protective Life Endowed Chair in Health Aging Research, a Distinguished Professor and Chair of the Department of Biology at the University of Alabama Birmingham. He's also Senior Scientific Director of the American Federation for Aging Research, which is managing a groundbreaking longevity research trial that started this year. Steven is also a great science communicator with five books, including one that comes out later this year, Methuselah’s Zoo, and he publishes prolifically in national media outlets.
See the rest of his bio linked below in the show notes.
Listen to the Episode
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Steven Austad is featured in the latest episode of Making Sense of Science. He's a distinguished professor of biology at the University of Alabama Birmingham and has a new book due to be published in August, Methuselah's Zoo.
Photo by Steve Wood
Show notes:
2:36 - Steven explains why a particular opossum convinced him to dedicate his career to studying longevity.
6:48 - Steven's billion dollar bet that someone alive today will make it to 150-years-old.
9:15 - The most likely people to make it to 150 (Hint: not men).
10:38 - I ask Steven about Elon Musk’s comments this month that if people lived a really long time, “we’d be stuck with old ideas and society wouldn’t advance.” Steve isn’t so fond of that take.
13:34 - Why women are winning maybe the most important battle of sexes: staying alive. This is an area that Steven has led research on (see show notes).
18:20 - Why women, on average, actually have more morbidities earlier than men, even though they live longer.
23:10 - How the pandemic could affect sex differences in longevity.
24:55 - How often should people work out and get other physical activity to maximize longevity and health span?
29:09 - Steven gave me the latest update on the TAME trial on metformin, and how he and others longevity experts designed this groundbreaking research on longevity not in their offices, not on a zoom call, but in a castle in the Spanish countryside.
32:10 - Which anti-aging therapies are the most promising at this point for future research.
39:32 - The drug cocktail approach to address multiple hallmarks of aging.
41:00 - How to read health news like a scientist.
45:38 - Should we try a Manhattan project for aging?
48:47 - Can Jeff Bezos and Larry Ellison help us live to 150?
Show links:
Steven Austad's bio
Pre-order Steven's new book, Methuselah's Zoo - https://www.amazon.com/dp/B09M2QGRJR/ref=dp-kindle-redirect?_encoding=UTF8&btkr=1
Steven's journal article on Sex Differences in Lifespan - https://pubmed.ncbi.nlm.nih.gov/27304504/
Elon Musk's comments on super longevity "asphyxiating" society - https://www.cnbc.com/2022/04/11/elon-musk-on-avoid...
Steven's article on how to read news articles about health like a pro - https://www.nextavenue.org/how-to-read-health-news...
AFAR's research on Targeting Aging with Metformin (TAME) - https://www.afar.org/tame-trial
New therapy may improve stem cell transplants for blood cancers
In 2018, Robyn was diagnosed with myelofibrosis, a blood cancer causing chronic inflammation and scarring. As a research scientist by training, she knew she had limited options. A stem cell transplant is a terminally ill patient's best chance for survival against blood cancers, including leukaemia. It works by destroying a patient's cancer cells and replacing them with healthy cells from a donor.
However, there is a huge risk of Graft vs Host disease (GVHD), which affects around 30-40% of recipients. Patients receive billions of cells in a stem cell transplant but only a fraction are beneficial. The rest can attack healthy tissue leading to GVHD. It affects the skin, gut and lungs and can be truly debilitating.
Currently, steroids are used to try and prevent GVHD, but they have many side effects and are effective in only 50% of cases. “I spoke with my doctors and reached out to patients managing GVHD,” says Robyn, who prefers not to use her last name for privacy reasons. “My concerns really escalated for what I might face post-transplant.”
Then she heard about a new highly precise cell therapy developed by a company called Orca Bio, which gives patients more beneficial cells and fewer cells that cause GVHD. She decided to take part in their phase 2 trial.
How It Works
In stem cell transplants, patients receive immune cells and stem cells. The donor immune cells or T cells attack and kill malignant cells. This is the graft vs leukaemia effect (GVL). The stem cells generate new healthy cells.
Unfortunately, T cells can also cause GVHD, but a rare subset of T cells, called T regulatory cells, can actually prevent GVHD.
Orca’s cell sorting technology distinguishes T regulatory cells from stem cells and conventional T cells on a large scale. It’s this cell sorting technology which has enabled them to create their new cell therapy, called Orca T. It contains a precise combination of stem cells and immune cells with more T regulatory cells and fewer conventional T cells than in a typical stem cell transplant.
“Ivan Dimov’s idea was to spread out the cells, keep them stationary and then use laser scanning to sort the cells,” explains Nate Fernhoff, co-founder of Orca Bio. “The beauty here is that lasers don't care how quickly you move them.”
Over the past 40 years, scientists have been trying to create stem cell grafts that contain the beneficial cells whilst removing the cells that cause GVHD. What makes it even harder is that most transplant centers aren’t able to manipulate grafts to create a precise combination of cells.
Innovative Cell Sorting
Ivan Dimov, Jeroen Bekaert and Nate Fernhoff came up with the idea behind Orca as postdocs at Stanford, working with cell pioneer Irving Weissman. They recognised the need for a more effective cell sorting technology. In a small study at Stanford, Professor Robert Negrin had discovered a combination of T cells, T regulatory cells and stem cells which prevented GVHD but retained the beneficial graft vs leukaemia effect (GVL). However, manufacturing was problematic. Conventional cell sorting is extremely slow and specific. Negrin was only able to make seven highly precise products, for seven patients, in a year. Annual worldwide cases of blood cancer number over 1.2 million.
“We started Orca with this idea: how do we use manufacturing solutions to impact cell therapies,” co-founder Fernhoff reveals. In conventional cell sorting, cells move past a stationary laser which analyses each cell. But cells can only be moved so quickly. At a certain point they start to experience stress and break down. This makes it very difficult to sort the 100 billion cells from a donor in a stem cell transplant.
“Ivan Dimov’s idea was to spread out the cells, keep them stationary and then use laser scanning to sort the cells,” Fernhoff explains. “The beauty here is that lasers don't care how quickly you move them.” They developed this technology and called it Orca Sort. It enabled Orca to make up to six products per week in the first year of manufacturing.
Every product Orca makes is for one patient. The donor is uniquely matched to the patient. They have to carry out the cell sorting procedure each time. Everything also has to be done extremely quickly. They infuse fresh living cells from the donor's vein to the patient's within 72 hours.
“We’ve treated almost 200 patients in all the Orca trials, and you can't do that if you don't fix the manufacturing process,” Fernhoff says. “We're working on what we think is an incredibly promising drug, but it's all been enabled by figuring out how to make a high precision cell therapy at scale.”
Clinical Trials
Orca revealed the results of their phase 1b and phase 2 trials at the end of last year. In their phase 2 trial only 3% of the 29 patients treated with Orca T cell therapy developed chronic GVHD in the first year after treatment. Comparatively, 43% of the 95 patients given a conventional stem cell transplant in a contemporary Stanford trial developed chronic GVHD. Of the 109 patients tested in phase 1b and phase 2 trials, 74% using Orca T didn't relapse or develop any form of GVHD compared to 34% in the control trial.
“Until a randomised study is done, we can make no assumption about the relative efficacy of this approach," says Jeff Szer, professor of haematology at the Royal Melbourne Hospital. "But the holy grail of separating GVHD and GVL is still there and this is a step towards realising that dream.”
Stan Riddell, an immunology professor, at Fred Hutchinson Cancer Centre, believes Orca T is highly promising. “Orca has advanced cell selection processes with innovative methodology and can engineer grafts with greater precision to add cell subsets that may further contribute to beneficial outcomes,” he says. “Their results in phase 1 and phase 2 studies are very exciting and offer the potential of providing a new standard of care for stem cell transplant.”
However, though it is an “intriguing step,” there’s a need for further testing, according to Jeff Szer, a professor of haematology at the Peter MacCallum Cancer Centre at the Royal Melbourne Hospital.
“The numbers tested were tiny and comparing the outcomes to anything from a phase 1/2 setting is risky,” says Szer. “Until a randomised study is done, we can make no assumption about the relative efficacy of this approach. But the holy grail of separating GVHD and GVL is still there and this is a step towards realising that dream.”
The Future
The team is soon starting Phase 3 trials for Orca T. Its previous success has led them to develop Orca Q, a cell therapy for patients who can't find an exact donor match. Transplants for patients who are only a half-match or mismatched are not widely used because there is a greater risk of GVHD. Orca Q has the potential to control GVHD even more and improve access to transplants for many patients.
Fernhoff hopes they’ll be able to help people not just with blood cancers but also with other blood and immune disorders. If a patient has a debilitating disease which isn't life threatening, the risk of GVHD outweighs the potential benefits of a stem cell transplant. The Orca products could take away that risk.
Meanwhile, Robyn has no regrets about participating in the Phase 2 trial. “It was a serious decision to make but I'm forever grateful that I did,” she says. “I have resumed a quality of life aligned with how I felt pre-transplant. I have not had a single issue with GVHD.”
“I want to be able to get one of these products to every patient who could benefit from it,” Fernhoff says. “It's really exciting to think about how Orca's products could be applied to all sorts of autoimmune disorders.”