Is Red Tape Depriving Patients of Life-Altering Therapies?
Medical treatment represented on a world map.
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."
Here's how one doctor overcame extraordinary odds to help create the birth control pill
Dr. Percy Julian had so many personal and professional obstacles throughout his life, it’s amazing he was able to accomplish anything at all. But this hidden figure not only overcame these incredible obstacles, he also laid the foundation for the creation of the birth control pill.
Julian’s first obstacle was growing up in the Jim Crow-era south in the early part of the twentieth century, where racial segregation kept many African-Americans out of schools, libraries, parks, restaurants, and more. Despite limited opportunities and education, Julian was accepted to DePauw University in Indiana, where he majored in chemistry. But in college, Julian encountered another obstacle: he wasn’t allowed to stay in DePauw’s student housing because of segregation. Julian found lodging in an off-campus boarding house that refused to serve him meals. To pay for his room, board, and food, Julian waited tables and fired furnaces while he studied chemistry full-time. Incredibly, he graduated in 1920 as valedictorian of his class.
After graduation, Julian landed a fellowship at Harvard University to study chemistry—but here, Julian ran into yet another obstacle. Harvard thought that white students would resent being taught by Julian, an African-American man, so they withdrew his teaching assistantship. Julian instead decided to complete his PhD at the University of Vienna in Austria. When he did, he became one of the first African Americans to ever receive a PhD in chemistry.
Julian received offers for professorships, fellowships, and jobs throughout the 1930s, due to his impressive qualifications—but these offers were almost always revoked when schools or potential employers found out Julian was black. In one instance, Julian was offered a job at the Institute of Paper Chemistory in Appleton, Wisconsin—but Appleton, like many cities in the United States at the time, was known as a “sundown town,” which meant that black people weren’t allowed to be there after dark. As a result, Julian lost the job.
During this time, Julian became an expert at synthesis, which is the process of turning one substance into another through a series of planned chemical reactions. Julian synthesized a plant compound called physostigmine, which would later become a treatment for an eye disease called glaucoma.
In 1936, Julian was finally able to land—and keep—a job at Glidden, and there he found a way to extract soybean protein. This was used to produce a fire-retardant foam used in fire extinguishers to smother oil and gasoline fires aboard ships and aircraft carriers, and it ended up saving the lives of thousands of soldiers during World War II.
At Glidden, Julian found a way to synthesize human sex hormones such as progesterone, estrogen, and testosterone, from plants. This was a hugely profitable discovery for his company—but it also meant that clinicians now had huge quantities of these hormones, making hormone therapy cheaper and easier to come by. His work also laid the foundation for the creation of hormonal birth control: Without the ability to synthesize these hormones, hormonal birth control would not exist.
Julian left Glidden in the 1950s and formed his own company, called Julian Laboratories, outside of Chicago, where he manufactured steroids and conducted his own research. The company turned profitable within a year, but even so Julian’s obstacles weren’t over. In 1950 and 1951, Julian’s home was firebombed and attacked with dynamite, with his family inside. Julian often had to sit out on the front porch of his home with a shotgun to protect his family from violence.
But despite years of racism and violence, Julian’s story has a happy ending. Julian’s family was eventually welcomed into the neighborhood and protected from future attacks (Julian’s daughter lives there to this day). Julian then became one of the country’s first black millionaires when he sold his company in the 1960s.
When Julian passed away at the age of 76, he had more than 130 chemical patents to his name and left behind a body of work that benefits people to this day.
Therapies for Healthy Aging with Dr. Alexandra Bause
My guest today is Dr. Alexandra Bause, a biologist who has dedicated her career to advancing health, medicine and healthier human lifespans. Dr. Bause co-founded a company called Apollo Health Ventures in 2017. Currently a venture partner at Apollo, she's immersed in the discoveries underway in Apollo’s Venture Lab while the company focuses on assembling a team of investors to support progress. Dr. Bause and Apollo Health Ventures say that biotech is at “an inflection point” and is set to become a driver of important change and economic value.
Previously, Dr. Bause worked at the Boston Consulting Group in its healthcare practice specializing in biopharma strategy, among other priorities
She did her PhD studies at Harvard Medical School focusing on molecular mechanisms that contribute to cellular aging, and she’s also a trained pharmacist
In the episode, we talk about the present and future of therapeutics that could increase people’s spans of health, the benefits of certain lifestyle practice, the best use of electronic wearables for these purposes, and much more.
Dr. Bause is at the forefront of developing interventions that target the aging process with the aim of ensuring that all of us can have healthier, more productive lifespans.
