Is Red Tape Depriving Patients of Life-Altering Therapies?
Rich Mancuso suffered from herpes for most of his adult life. The 49-year-old New Jersey resident was miserable. He had at least two to three outbreaks every month with painful and unsightly sores on his face and in his eyes, yet the drugs he took to control the disease had terrible side effects--agonizing headaches and severe stomach disturbances.
Last week, the FDA launched a criminal investigation to determine whether the biotech behind the vaccine had violated regulations.
So in 2016, he took an unusual step: he was flown to St. Kitt's, an island in the West Indies, where he participated in a clinical trial of a herpes vaccine, and received three injections of the experimental therapeutic during separate visits to the island. Within a year, his outbreaks stopped. "Nothing else worked," says Mancuso, who feels like he's gotten his life back. "And I've tried everything on the planet."
Mancuso was one of twenty genital herpes sufferers who were given the experimental vaccine in tests conducted on the Caribbean island and in hotel rooms near the campus of Southern Illinois University in Springfield where the vaccine's developer, microbiologist William Halford, was on the faculty. But these tests were conducted under the radar, without the approval or safety oversight of the Food and Drug Administration or an institutional review board (IRB), which routinely monitor human clinical trials of experimental drugs to make sure participants are protected.
Last week, the FDA launched a criminal investigation to determine whether anyone from SIU or Rational Vaccines, the biotech behind the vaccine, had violated regulations by aiding Halford's research. The SIU scientist was a microbiologist, not a medical doctor, which means that volunteers were not only injected with an unsanctioned experimental treatment but there wasn't even routine medical oversight.
On one side are scientists and government regulators with legitimate safety concerns....On the other are desperate patients and a dying scientist willing to go rogue in a foreign country.
Halford, who was stricken with a rare form of a nasal cancer, reportedly bypassed regulatory rules because the clock was ticking and he wanted to speed this potentially life-altering therapeutic to patients. "There was no way he had enough time to raise $100 million to test the drugs in the U.S.," says Mancuso, who became friends with Halford before he died in June of 2017 at age 48. "He knew if he didn't do something, his work would just die and no one would benefit. This was the only way."
But was it the only way? Once the truth about the trial came to light, public health officials in St. Kitt's disavowed the trial, saying they had not been notified that it was happening, and Southern Illinois University's medical school launched an investigation that ultimately led to the resignation of three employees, including a faculty member, a graduate student and Halford's widow. Investors in Rational Vaccines, including maverick Silicon Valley billionaire Peter Thiel, demanded that all FDA rules must be followed in future tests.
"Trials have to yield data that can be submitted to the FDA, which means certain requirements have to be met," says Jeffrey Kahn, a bioethicist at Johns Hopkins University in Baltimore. "These were renegade researchers who exposed people to unnecessary risks, which was hugely irresponsible. I don't know what they expected to do with the research. It was a waste of money and generated data that can't be used because no regulator would accept it."
But this story illuminates both sides of a thorny issue. On one side are scientists and government regulators with legitimate safety concerns who want to protect volunteers from very real risks—people have died even in closely monitored clinical trials. On the other, are desperate patients and a dying scientist willing to go rogue in a foreign country where there is far less regulatory scrutiny. "It's a balancing act," says Jennifer Miller, a medical ethicist at New York University and president of Bioethics International. "You really need to protect participants but you also want access to safe therapies."
"Safety is important, but being too cautious kills people, too—allowing them to just die without intervention seems to be the biggest harm."
This requirement—that tests show a drug is safe and effective before it can win regulatory approval--dates back to 1962, when the sedative thalidomide was shown to have caused thousands of birth defects in Europe. But clinical trials can be costly and often proceed at a glacial pace. Typically, companies shell out more than $2.5 billion over the course of the decade it normally takes to shepherd a new treatment through the three phases of testing before it wins FDA approval, according to a 2014 study by the Tufts Center for the Study of Drug Development. Yet only 11.8 percent of experimental therapies entering clinical tests eventually cross the finish line.
The upshot is that millions can suffer and thousands of people may die awaiting approvals for life saving drugs, according to Elizabeth Parrish, the founder and CEO of BioViva, a Seattle-based biotech that aims to provide data collection platforms to scientists doing overseas tests. "Going offshore to places where it's legal to take a therapeutic can created expedited routes for patients to get therapies for which there is a high level of need," she says. "Safety is important, but being too cautious kills people, too—allowing them to just die without intervention seems to be the biggest harm."
Parrish herself was frustrated with the slow pace of gene therapy trials; scientists worried about the risks associated with fixing mutant DNA. To prove a point, she traveled to a clinic in Colombia in 2015 where she was injected with two gene therapies that aim to improve muscle function and lengthen telomeres, the caps on the end of chromosomes that are linked to aging and genetic diseases. Six months later, the therapy seemed to have worked—her muscle mass had increased and her telomeres had grown by 9 percent, the equivalent of turning back 20 years of aging, according to her own account. Yet the treatments are still unavailable here in the U.S.
In the past decade, Latin American countries like Columbia, and Mexico in particular, have become an increasingly attractive test destination for multi-national drug companies and biotechs because of less red tape.
In the past decade, Latin American countries like Columbia, and Mexico in particular, have become an increasingly attractive test destination for multi-national drug companies and biotechs because of less red tape around testing emerging new science, like gene therapies or stem cells. Plus, clinical trials are cheaper to conduct, it's easier to recruit volunteers, especially ones who are treatment naïve, and these human tests can reveal whether local populations actually respond to a particular therapy. "We do have an exhaustive framework for running clinical trials that are aligned with international requirements," says Ernesto Albaga, an attorney with Hogan Lovells in Mexico City who specializes in the life sciences. "But our environment is still not as stringent as it is in other places, like the U.S."
The fact is American researchers are increasingly testing experimental drugs outside of the U.S., although virtually all of them are monitored by local scientists who serve as co-investigators. In 2017 alone, more than 86 percent of experimental drugs seeking FDA approval have been tested, at least in part, in foreign countries, like Mexico, China, Russia, Poland and South Africa, according to an analysis by STAT. However, in places without strict oversight, such as Russia and Georgia, results may be fraudulent, according to one 2017 report in the New England Journal of Medicine. And in developing countries, the poor can become guinea pigs. In the early 2000s, for example, a test in Uganda of an AIDS drug resulted in thousands of unreported serious adverse reactions and 14 deaths; in India, eight volunteers died during a test of the anti-clotting drug, Streptokinase—and test subjects didn't even know they were part of a clinical trials.
Still, "the world is changing," concludes Dr. Jennifer Miller of NYU. "We need to figure out how to get safe and effective drugs to patients more quickly without sacrificing too much protection."
Story by Freethink
Try burning an iron metal ingot and you’ll have to wait a long time — but grind it into a powder and it will readily burst into flames. That’s how sparklers work: metal dust burning in a beautiful display of light and heat. But could we burn iron for more than fun? Could this simple material become a cheap, clean, carbon-free fuel?
In new experiments — conducted on rockets, in microgravity — Canadian and Dutch researchers are looking at ways of boosting the efficiency of burning iron, with a view to turning this abundant material — the fourth most common in the Earth’s crust, about about 5% of its mass — into an alternative energy source.
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.
Tom Oxley is building what he calls a “natural highway into the brain” that lets people use their minds to control their phones and computers. The device, called the Stentrode, could improve the lives of hundreds of thousands of people living with spinal cord paralysis, ALS and other neurodegenerative diseases.
Leaps.org talked with Dr. Oxley for today’s podcast. A fascinating thing about the Stentrode is that it works very differently from other “brain computer interfaces” you may be familiar with, like Elon Musk’s Neuralink. Some BCIs are implanted by surgeons directly into a person’s brain, but the Stentrode is much less invasive. Dr. Oxley’s company, Synchron, opts for a “natural” approach, using stents in blood vessels to access the brain. This offers some major advantages to the handful of people who’ve already started to use the Stentrode.
The audio improves about 10 minutes into the episode. (There was a minor headset issue early on, but everything is audible throughout.) Dr. Oxley’s work creates game-changing opportunities for patients desperate for new options. His take on where we're headed with BCIs is must listening for anyone who cares about the future of health and technology.
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.
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 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/