Jamie Rettinger with his now fiance Amie Purnel-Davis, who helped him through the clinical trial.
Melanoma is the deadliest form of skin cancer. About 85,000 people are diagnosed with it each year in the U.S. and more than 8,000 die of the cancer when it spreads to other parts of the body, according to the Centers for Disease Control and Prevention (CDC).
There are two peaks in diagnosis of melanoma; one is in younger women ages 30-40 and often is tied to past use of tanning beds; the second is older men 60+ and is related to outdoor activity from farming to sports. Light-skinned people have a twenty-times greater risk of melanoma than do people with dark skin.
"When I graduated from medical school, in 2005, melanoma was a death sentence" --Diwakar Davar.
Jamie had a follow up PET scan about six months after his surgery. A suspicious spot on his lung led to a biopsy that came back positive for melanoma. The cancer had spread. Treatment with a monoclonal antibody (nivolumab/Opdivo®) didn't prove effective and he was referred to the UPMC Hillman Cancer Center in Pittsburgh, a four-hour drive from his home in western Ohio.
An alternative monoclonal antibody treatment brought on such bad side effects, diarrhea as often as 15 times a day, that it took more than a week of hospitalization to stabilize his condition. The only options left were experimental approaches in clinical trials.
Early research
"When I graduated from medical school, in 2005, melanoma was a death sentence" with a cure rate in the single digits, says Diwakar Davar, 39, an oncologist at UPMC Hillman Cancer Center who specializes in skin cancer. That began to change in 2010 with introduction of the first immunotherapies, monoclonal antibodies, to treat cancer. The antibodies attach to PD-1, a receptor on the surface of T cells of the immune system and on cancer cells. Antibody treatment boosted the melanoma cure rate to about 30 percent. The search was on to understand why some people responded to these drugs and others did not.
At the same time, there was a growing understanding of the role that bacteria in the gut, the gut microbiome, plays in helping to train and maintain the function of the body's various immune cells. Perhaps the bacteria also plays a role in shaping the immune response to cancer therapy.
One clue came from genetically identical mice. Animals ordered from different suppliers sometimes responded differently to the experiments being performed. That difference was traced to different compositions of their gut microbiome; transferring the microbiome from one animal to another in a process known as fecal transplant (FMT) could change their responses to disease or treatment.
When researchers looked at humans, they found that the patients who responded well to immunotherapies had a gut microbiome that looked like healthy normal folks, but patients who didn't respond had missing or reduced strains of bacteria.
Davar and his team knew that FMT had a very successful cure rate in treating the gut dysbiosis of Clostridioides difficile, a persistant intestinal infection, and they wondered if a fecal transplant from a patient who had responded well to cancer immunotherapy treatment might improve the cure rate of patients who did not originally respond to immunotherapies for melanoma.
The ABCDE of melanoma detection
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Clinical trial
"It was pretty weird, I was totally blasted away. Who had thought of this?" Jamie first thought when the hypothesis was explained to him. But Davar's explanation that the procedure might restore some of the beneficial bacterial his gut was lacking, convinced him to try. He quickly signed on in October 2018 to be the first person in the clinical trial.
Fecal donations go through the same safety procedures of screening for and inactivating diseases that are used in processing blood donations to make them safe for transfusion. The procedure itself uses a standard hollow colonoscope designed to screen for colon cancer and remove polyps. The transplant is inserted through the center of the flexible tube.
Most patients are sedated for procedures that use a colonoscope but Jamie doesn't respond to those drugs: "You can't knock me out. I was watching them on the TV going up my own butt. It was kind of unreal at that point," he says. "There were about twelve people in there watching because no one had seen this done before."
A test two weeks after the procedure showed that the FMT had engrafted and the once-missing bacteria were thriving in his gut. More importantly, his body was responding to another monoclonal antibody (pembrolizumab/Keytruda®) and signs of melanoma began to shrink. Every three months he made the four-hour drive from home to Pittsburgh for six rounds of treatment with the antibody drug.
"We were very, very lucky that the first patient had a great response," says Davar. "It allowed us to believe that even though we failed with the next six, we were on the right track. We just needed to tweak the [fecal] cocktail a little better" and enroll patients in the study who had less aggressive tumor growth and were likely to live long enough to complete the extensive rounds of therapy. Six of 15 patients responded positively in the pilot clinical trial that was published in the journal Science.
Davar believes they are beginning to understand the biological mechanisms of why some patients initially do not respond to immunotherapy but later can with a FMT. It is tied to the background level of inflammation produced by the interaction between the microbiome and the immune system. That paper is not yet published.
Surviving cancer
It has been almost a year since the last in his series of cancer treatments and Jamie has no measurable disease. He is cautiously optimistic that his cancer is not simply in remission but is gone for good. "I'm still scared every time I get my scans, because you don't know whether it is going to come back or not. And to realize that it is something that is totally out of my control."
"It was hard for me to regain trust" after being misdiagnosed and mistreated by several doctors he says. But his experience at Hillman helped to restore that trust "because they were interested in me, not just fixing the problem."
He is grateful for the support provided by family and friends over the last eight years. After a pause and a sigh, the ruggedly built 47-year-old says, "If everyone else was dead in my family, I probably wouldn't have been able to do it."
"I never hesitated to ask a question and I never hesitated to get a second opinion." But Jamie acknowledges the experience has made him more aware of the need for regular preventive medical care and a primary care physician. That person might have caught his melanoma at an earlier stage when it was easier to treat.
Davar continues to work on clinical studies to optimize this treatment approach. Perhaps down the road, screening the microbiome will be standard for melanoma and other cancers prior to using immunotherapies, and the FMT will be as simple as swallowing a handful of freeze-dried capsules off the shelf rather than through a colonoscopy. Earlier this year, the Food and Drug Administration approved the first oral fecal microbiota product for C. difficile, hopefully paving the way for more.
An older version of this hit article was first published on May 18, 2021
Sparklers produce a beautiful display of light and heat by burning metal dust, which contains iron. The recent work of Canadian and Dutch researchers suggests we can use iron as a cheap, carbon-free fuel.
Iron as a fuel
Iron is abundantly available and cheap. More importantly, the byproduct of burning iron is rust (iron oxide), a solid material that is easy to collect and recycle. Neither burning iron nor converting its oxide back produces any carbon in the process.
Iron oxide is potentially renewable by reacting with electricity or hydrogen to become iron again.
Iron has a high energy density: it requires almost the same volume as gasoline to produce the same amount of energy. However, iron has poor specific energy: it’s a lot heavier than gas to produce the same amount of energy. (Think of picking up a jug of gasoline, and then imagine trying to pick up a similar sized chunk of iron.) Therefore, its weight is prohibitive for many applications. Burning iron to run a car isn’t very practical if the iron fuel weighs as much as the car itself.
In its powdered form, however, iron offers more promise as a high-density energy carrier or storage system. Iron-burning furnaces could provide direct heat for industry, home heating, or to generate electricity.
Plus, iron oxide is potentially renewable by reacting with electricity or hydrogen to become iron again (as long as you’ve got a source of clean electricity or green hydrogen). When there’s excess electricity available from renewables like solar and wind, for example, rust could be converted back into iron powder, and then burned on demand to release that energy again.
However, these methods of recycling rust are very energy intensive and inefficient, currently, so improvements to the efficiency of burning iron itself may be crucial to making such a circular system viable.
The science of discrete burning
Powdered particles have a high surface area to volume ratio, which means it is easier to ignite them. This is true for metals as well.
Under the right circumstances, powdered iron can burn in a manner known as discrete burning. In its most ideal form, the flame completely consumes one particle before the heat radiating from it combusts other particles in its vicinity. By studying this process, researchers can better understand and model how iron combusts, allowing them to design better iron-burning furnaces.
Discrete burning is difficult to achieve on Earth. Perfect discrete burning requires a specific particle density and oxygen concentration. When the particles are too close and compacted, the fire jumps to neighboring particles before fully consuming a particle, resulting in a more chaotic and less controlled burn.
Presently, the rate at which powdered iron particles burn or how they release heat in different conditions is poorly understood. This hinders the development of technologies to efficiently utilize iron as a large-scale fuel.
Burning metal in microgravity
In April, the European Space Agency (ESA) launched a suborbital “sounding” rocket, carrying three experimental setups. As the rocket traced its parabolic trajectory through the atmosphere, the experiments got a few minutes in free fall, simulating microgravity.
One of the experiments on this mission studied how iron powder burns in the absence of gravity.
In microgravity, particles float in a more uniformly distributed cloud. This allows researchers to model the flow of iron particles and how a flame propagates through a cloud of iron particles in different oxygen concentrations.
Existing fossil fuel power plants could potentially be retrofitted to run on iron fuel.
Insights into how flames propagate through iron powder under different conditions could help design much more efficient iron-burning furnaces.
Clean and carbon-free energy on Earth
Various businesses are looking at ways to incorporate iron fuels into their processes. In particular, it could serve as a cleaner way to supply industrial heat by burning iron to heat water.
For example, Dutch brewery Swinkels Family Brewers, in collaboration with the Eindhoven University of Technology, switched to iron fuel as the heat source to power its brewing process, accounting for 15 million glasses of beer annually. Dutch startup RIFT is running proof-of-concept iron fuel power plants in Helmond and Arnhem.
As researchers continue to improve the efficiency of burning iron, its applicability will extend to other use cases as well. But is the infrastructure in place for this transition?
Often, the transition to new energy sources is slowed by the need to create new infrastructure to utilize them. Fortunately, this isn’t the case with switching from fossil fuels to iron. Since the ideal temperature to burn iron is similar to that for hydrocarbons, existing fossil fuel power plants could potentially be retrofitted to run on iron fuel.
This article originally appeared on Freethink, home of the brightest minds and biggest ideas of all time.
Leaps.org talks with Dr. Tom Oxley, founding CEO of Synchron, a company that's taking a unique - and less invasive - approach to "brain-computer interfaces" for patients with ALS and other mobility challenges.
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In our conversation, Dr. Oxley talks about “Bluetooth brain”; the critical role of AI in the present and future of BCIs; how BCIs compare to voice command technology; regulatory frameworks for revolutionary technologies; specific people with paralysis who’ve been able to regain some independence thanks to the Stentrode; what it means to be a neurointerventionist; how to scale BCIs for more people to use them; the risks of BCIs malfunctioning; organic implants; and how BCIs help us understand the brain, among other topics.
Dr. Oxley received his PhD in neuro engineering from the University of Melbourne in Australia. He is the founding CEO of Synchron and an associate professor and the head of the vascular bionics laboratory at the University of Melbourne. He’s also a clinical instructor in the Deepartment of Neurosurgery at Mount Sinai Hospital. Dr. Oxley has completed more than 1,600 endovascular neurosurgical procedures on patients, including people with aneurysms and strokes, and has authored over 100 peer reviewed articles.
Links:
Synchron website - https://synchron.com/
Assessment of Safety of a Fully Implanted Endovascular Brain-Computer Interface for Severe Paralysis in 4 Patients (paper co-authored by Tom Oxley) - https://jamanetwork.com/journals/jamaneurology/art...
More research related to Synchron's work - https://synchron.com/research
Tom Oxley on LinkedIn - https://www.linkedin.com/in/tomoxl
Tom Oxley on Twitter - https://twitter.com/tomoxl?lang=en
Tom Oxley TED - https://www.ted.com/talks/tom_oxley_a_brain_implant_that_turns_your_thoughts_into_text?language=en
Tom Oxley website - https://tomoxl.com/
Novel brain implant helps paralyzed woman speak using digital avatar - https://engineering.berkeley.edu/news/2023/08/novel-brain-implant-helps-paralyzed-woman-speak-using-a-digital-avatar/
Edward Chang lab - https://changlab.ucsf.edu/
BCIs convert brain activity into text at 62 words per minute - https://med.stanford.edu/neurosurgery/news/2023/he...
Leaps.org: The Mind-Blowing Promise of Neural Implants - https://leaps.org/the-mind-blowing-promise-of-neural-implants/
Tom Oxley