Humanity’s pursuit of longevity has yielded impressive results over the last century. Life expectancy is up dramatically in most parts of the world, and new medical breakthroughs are tackling the most prolific of killers – cancer and heart disease. But the mission to radically extend life has hit something of a ceiling, as we realise that healthy living and exercise will only take us so far.
There’s a reason the oldest human on record, Jeanne Calment, reached 122 years old despite being a heavy smoker and eating a poor diet: her genes. We can make incremental changes to our health through smart lifestyle choices, but ultimately we’re all at the mercy of the genetic code which determines our vulnerability to disease and ultimately our deaths. However, our destiny may not be foretold in our genes for much longer. Gene therapy, which genetically modifies cells to fix problems in our bodies, has already been used to cure significant diseases. The rapid advancement of the field has led some to speculate it could hold the key to unlocking longer life.
Among those keenly observing gene therapy’s potential are immortalists, a global offshoot of the transhumanist movement who believe they can live for ever. Longevity enthusiasts, a much more populous group of people who chase extended life through science, also have their eye on the medical technology.
Both groups place a great deal of hope in gene therapies to radically extend the average human lifespan. But they’re already tired of waiting for access to the technology. Frustrated that the science is moving too slowly, some have started doing their own research into the field. In some cases, this has involved self-administering treatments, outside legal jurisdictions, using treatments not yet approved by any trusted medical bodies.
Are they falling for humanity’s oldest vice, and hopelessly pursuing a modern version of the fountain of youth? Or are they doing the world a favour by ushering in a new therapy with the potential to increase humanity’s lifespan and tackle the many problems associated with age?
Scientific breakthroughs
Many consider gene therapy to be one of the most exciting areas of medicine. The last 30 years have seen a series of significant breakthroughs, often in cases of disease that would otherwise be untreatable. In 2021, gene therapy partially restored a man’s eyesight. The man, who hasn’t been named, suffered from retinitis pigmentosa – where light-sensing cells on the surface of the retina die – and was completely blind. The treatment first utilised the genes of algae. Genetic instructions for making proteins called rhodopsins were taken from the algae and given to cells deep in the retina at the back of the patient’s eye. When light hit these new proteins, it sent an electrical signal to the brain, but not one that could be deciphered – at least not yet.
The proteins only respond to amber light, so the man had to wear goggles with a video camera on the front. This captured what was happening in the world and fired a version onto the back of the eye in the right wavelength. The patient then waited several months for the levels of rhodopsins to build up in the eye, and for the brain to learn a new way of interpreting sight. He first realised the treatment was working when he went out on a walk with the goggles and saw the white stripes of a pedestrian crossing. He has since been able to grab and count objects on a table in front of him.
These kinds of breakthroughs have given hope to many others who suffer from diseases born out of faulty genes. Gene therapy appears to be entering into a new age of progress, but there are still worries about the pace of change – concerns that have been voiced since the practice was first developed.
Relative to the history of medicine, gene therapy is still fairly new. In 1972, Theodore Friedmann and Richard Roblin published a paper titled “Gene Therapy for Human Genetic Disease?” in the journal Science. The two American scientists outlined the potential of inserting DNA sequences into a patient’s cells to treat genetic disorders. Each of our cells contains thousands of genes that provide the information needed for the production of proteins and enzymes that make our bones, blood and muscles. Issues arise when a whole or part of a gene is defective or missing. This can occur before birth, or a gene can mutate later on, disrupting how proteins are made and causing major health problems or diseases.
Genetic diseases were seen as completely incurable until the 1972 paper proposed a solution. However, the two authors urged caution on the development of the technology and opposed any attempts at gene therapy in human patients, due to inadequate understanding of the concept and its potential side effects. The scientific community took note and waited 18 years, conducting a lot of research before launching the first gene therapy trial in 1990. Ashanthi DeSilva, a four-year-old girl suffering from a rare genetic disease known as severe combined immunodeficiency, underwent a 12-day treatment involving gene therapy. Her condition meant she lacked an enzyme called adenosine deaminase (ADA), rendering her immune system almost completely useless. This put her at risk of dying from infection and forced her to live in isolation.
To boost DeSilva’s ADA levels, doctors introduced a functional copy of the gene that encodes the enzyme into the immune system. As you might imagine, it’s not easy to insert a gene directly into a person’s cells. It has to be delivered via a carrier, known as a vector. The most common gene therapy vectors – used on DeSilva – are viruses, because they can identify certain cells and carry genetic material into the genes of that cell. In order to make it safe, researchers remove the disease-causing genes from the virus and replace them with the helpful genes. When the viral vector containing the gene therapy was introduced, DeSilva’s immune system improved, and she was able to live a normal life.
The case was celebrated around the world, kicking off numerous other trials in the field during the 1990s. But just nine years later, that progress was brought to a sudden halt when a clinical trial went tragically wrong.
Approach with caution
In 1999, Jesse Gelsinger, an 18-year-old suffering from the genetic condition ornithine transcarbamylase deficiency, signed up for an experimental gene therapy trial at the University of Pennsylvania. The disease, which was caused by a genetic mutation, stopped his liver’s ability to break down ammonia, causing the toxic substance to accumulate in the blood. The trial introduced a functional copy of the missing gene to Gelsinger’s liver cells, using a modified common cold virus as a vector.
But four days after the treatment, Gelsinger suffered a catastrophic immune reaction and died. His death shocked scientists in the field and received widespread media attention. The FDA criticised the design of the trial and suspended the University of Pennsylvania’s entire gene therapy program, which was one of the largest in the world. The regulator also launched investigations into 69 other gene therapy trials underway in the US. In the fallout, gene therapy was accused of moving too fast, and viral vectors in particular were called into question. Progress slowed considerably.
Research has rebounded since, but the comeback has been gradual. In 2003, China approved its first gene therapy, called Gendicine, which treated head and neck cancer. Russia gave the green light to Neovasculgen, a therapy for peripheral artery disease, in 2011. But even when a treatment is approved it may not be commercially viable. The year after the breakthrough in Russia, the European Commission approved Glybera, a gene therapy treating lipoprotein lipase deficiency, an ultra-rare disease. But while it was heralded at the time as a great success for Europe, Glybera was a commercial failure. The therapy came with a €1 million price tag, making it the most expensive treatment in the world. [See Peter Forbes’ report in the Winter 2019 edition of New Humanist.] By the time it was withdrawn in 2017, the treatment had been prescribed to just one patient.
Here’s where the immortalists and longevity fanatics come in. Frustrated that the science is moving too slowly, some have taken matters into their own hands. And one anti-ageing entrepreneur has taken drastic steps to ensure gene therapies to reverse ageing are at least being tested on humans.
Patient zero
Liz Parrish, then a housewife and part-time advocate for stem cell therapies, first became interested in gene therapy after learning that her nine-year-old son had been diagnosed with type one diabetes. She was outraged by the amount of time and money it took for experimental treatments to reach patients. She began to travel to medical conferences, badgering experts in the hallways, looking for potential cures for diseases like that which afflicted her son. In her frantic pursuit of treatments, she eventually convinced herself that by curing ageing, everyone – including children – would suffer less.
In 2015, at the age of 44, Parrish flew to Bogotá, Columbia, to receive dozens of experimental gene therapy injections, with the goal of turning back her biological clock. By that time, she had founded her own company, BioViva. For her first public appearance as CEO, she had chosen to address the immortalist group People Unlimited, where she told a receptive crowd that she wanted to cure ageing, and do it fast enough that they could all benefit. That year, she raised enough cash to fund the Bogotá experiment. The plan was to become patient zero.
A video of Parrish’s procedure is available online. Prior to the treatment, she made jokes to the doctors. “I’m supposed to go in the corner, grab my face and shake around, and turn around and be young, right?” she laughed. “It’s not going to happen like that.” Wearing a white medical gown, she sat back for hours while a doctor and nurse administered more than 100 injections in her triceps, thighs, buttocks, face, and below her kneecaps. By the time she was done, past midnight, she had created medical history as the person to receive the most potent dose of gene therapy ever, all in the quest to fight ageing.
In the aftermath, Parrish and BioViva were bombarded with attention, some good, some bad. A reporter contacted the company for a story about the ethical issues of the treatment, claiming nobody could really know the risks and give informed consent. There was a lot of pressure, Parrish told me in a video call in 2021. “People are constantly looking at me and saying, ‘Do you look younger? Do you feel younger?’ I’m a guinea pig.” The criticism didn’t just come from the press. George Martin, a gerontologist and member of BioViva’s scientific advisory board, resigned soon after.
Among the longevity and immortalist crowds, however, Parrish was an instant hero. Finally, someone was taking the initiative in the mission to beat ageing. A year after the treatment, BioViva issued a press release with the results. The company compared blood drawn from Parrish before and after the procedure and found her white blood cells’ telomeres had increased in length by nine per cent. Telomeres are often compared to the plastic tips on the end of shoelaces. If telomeres shorten too much over time, the cells, like a shoelace, become exposed and begin to fray and are damaged. By lengthening the telomeres, Parrish was theoretically improving the health of her cells.
But this was just one person’s results, and no study was published. There was not enough data to measure. The news was dismissed as inconsequential by the scientific community.
Regulatory battles
Parrish, however, has not given up. She is now focused on battling against the current system of regulation, which she believes is holding back crucial medical technologies. When we spoke in 2021, she was writing her thesis for an MBA on a new regulatory system she is proposing called Best Choice Medicine. She wants to make it easier for gene therapies and other regenerative medicines to enter human testing trials.
“These gene therapies are already performing better, hitting more points of metabolic disorder and dysfunction that happens with ageing in animal models, and yet we continue to do animal models, and no humans get access to this?” she said. “That’s what we were saying when I took the gene therapies in 2015. We were saying no, we have to jump, at some point you have to jump, and if you don’t jump you die of the same predictable diseases.” She believes that while animal testing is important to gauge the effectiveness of a treatment, it can never really replicate human interaction. She wants treatments to be tested on humans much sooner, at the cost of the caution that regulates the medical industry.
But Parrish is not a scientist. I wanted to talk to someone respected in the gene therapy space, who also had an opinion on what entrepreneurs like Parrish were trying to achieve. So I contacted George Church, an adviser to BioViva. Church teaches genetics at Harvard Medical School and MIT and is also director of the US Department of Energy Technology Center, as well as the NIH Centers of Excellence in Genomic Science. His list of achievements is just as impressive as his job titles. He developed the first direct genomic sequencing method in 1984 and helped initiate the Human Genome Project that same year. In 2005, he helped launch the Personal Genome Project.
Unsurprisingly, given his résumé, Church is well connected. He has founded and advised numerous biotech startups and is seen as a major contributor to Crispr technology, which edits genes. On our video call, Church, who sports a bushy beard and glasses, told me Parrish was not the only person he knew who had conducted self-experimentation attempting to advance science. He thinks there is some value in the work that she and others are doing as pioneers.
“If you have enough resources, it’s totally obvious what you should do – a full-fledged clinical trial. But it helps to do these little things because at a minimum it shows it’s not toxic. And if it’s nontoxic, a whole variety of people will want to try it out, and then you’ll find out if it’s toxic in a wide variety of people,” he said. “It’s hard to show efficacy, that’s the other thing you have to do, you have to very carefully do baseline. And if you know you’re getting the experimental over the control there are going to be all types of placebo effects . . . it’s much better if you don’t know which treatment you’re getting.”
He encourages anyone doing self-experimentation to use a double-blind placebo crossover trial, where there are two samples, one a placebo and one the real thing. The researcher then injects themselves, not knowing if it’s the real thing or not, and a few days or months later injects the other sample. That means at some point they get both the placebo and the real thing, but they don’t know what order they had them in. Church described this as a cheap and easy way to make self-experimentation results more useful.
Church doesn’t see much hope in record-breaking humans like Jeanne Calment. “We’ve sequenced them, and we hoped we would learn something, but it’s very challenging because there are 3 million differences between each of them, and each other, and us as well. It’s underpowered statistically. We were hoping something would jump out at us, it might still . . . I don’t think we’ve learned that much from supercentenarians yet.”
Heroic or reckless?
Instead, he is looking in other directions. In 2017, he co-founded the gene therapy company Rejuvenate Bio, launched from Church’s lab at Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering. The company wants to reverse ageing in dogs through treatments that have shown promise in worms, flies and mice. Church believes any treatment that would make dogs live longer would be hugely popular and fund the next stage: clinical trials in humans.
For the immortalists and longevity fanatics, that day can’t come soon enough. In the meantime, they will continue to lobby for earlier access to experimental medicines that could extend their lives. The question remains, however: are they putting themselves at unnecessary risk chasing an unobtainable goal or are their actions heroic?
Medical technology has never been more exciting. Some of the breakthroughs we read about appear to be straight out of science fiction, and groups like the immortalists follow them with the fervour of sports fans. But the gap between research and implementation is large for a reason: safety. The libertarian, anti-regulation leanings of those pursuing extended life may result in fraudsters and conmen queuing up to exploit them.
Gene therapy, despite recent high-profile breakthroughs, is still a young scientific field. The potential is so huge that it’s easy to see why people are enthusiastic about the technology, including those seeking to extend their lifespan. But there is much to be done, and the risks associated are not to be underestimated. Whether or not pioneers like Liz Parrish continue to conduct their experiments independently, we are at the beginning of this scientific journey. Meanwhile, failed or reckless experiments may set us back. The potential is exciting, but our deaths may be written in our genes for many decades to come.
This is an edited extract from Peter Ward’s book "The Price of Immortality" (Penguin Random House), from the spring 2023 edition of New Humanist. Subscribe now.
