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In the world's fastest-aging societies, regenerative therapies attract the rich and curious.
Today, the fruits of Lim's investment can be found at the Southern end of the Malay Peninsula, in the city of Iskandar Puteri, which is mostly home to people working in downtown Singapore, an hour away by train.
But a trickle of ultra-wealthy people are commuting in the other direction, their destination a futuristic building decorated with Saturnian rings and skywalks that houses Regenosis. For those willing to pay a presumably astronomical price tag, which Regenosis will not disclose, they can attempt to cheat death with stem cell therapies.
Lim recently told media in Singapore what drove him to start the company that year: "Imagine the very real possibility of being at 90 years old but biologically looking and functioning like you're in your 40s, humans living to 200 or more years!" His stated aim is to push the boundaries of death, and to sell that aspiration to patients: The clinic makes no secret that their clients must be wealthy to afford the treatments.
"Complimentary longevity and anti-aging therapies are perceived as luxuries," Donovan L. Reeves, marketing department manager at Regenosis, told Nikkei Asia. He said he could not provide a typical range of prices because doctors' recommendations may differ according to each patient's condition. However, he said, "it is predominantly for high net worth and ultrahigh net worth ... individuals with a net worth of $1 million and above from China, Vietnam, Malaysia, Indonesia and Singapore."
Citing confidentiality, Reeves also declined to make any patients available for interviews. The patients are placing their trust, and considerable fees, in as yet unproven science, with many treatments yet to undergo clinical trials.
Regenosis is one of a number of clinics that cater to regenerative medicine and anti-aging research that have begun to cluster in the greater Singapore area, which offers a haven for sometimes controversial research into stem cells.
With a population that is aging more rapidly than almost anywhere else in the world, Singapore has ample reason to be interested in an industry devoted to prolonging life. Over the last decade, companies devoted to biomedical research and regenerative medicine have found an eager patron there with plentiful funding opportunities, a deep pool of highly trained scientists and wealthy potential patients, not to mention flexible legislation allowing cutting edge research that would be out of bounds in many parts of the world.
According to its website, Regenosis is out to "challenge the norms of how illnesses and age-related diseases are viewed and treated," with diagnoses, procedures and therapies based on "the latest biotechnologies."
Challenging the norms of aging
Silicon Valley billionaires have monopolized most of the attention in the field of anti-aging research with eye-popping investments into projects designed to hack the aging process. The ventures include Altos Labs, reportedly backed by former Amazon CEO Jeff Bezos and early Facebook investor Yuri Milner, as well as Google's Calico. Paypal co-founder Peter Thiel has been particularly vocal about his vast investments into biotech startups that promise to "cheat death."
However, as businesses like Regenosis demonstrate, the weight in the field is increasingly shifting toward Asia, the world's fastest-aging region. By 2040, Euromonitor International predicts that three of the world's five oldest populations will be in Asia: Japan, South Korea and Singapore. According to the Asian Development Bank, by 2050, one in four Asia-Pacific inhabitants will be 60 or older.
The significant progress made by biomedical scientists since the beginning of the 21st century has led some Asian governments to champion the field in hopes that it could reduce the social burden of a graying population.
Singapore, a small but overdeveloped territory with a quickly aging population, has been at the vanguard of this potential revolution.
Singapore's multibillion-dollar Biopolis, launched in 2003 with $550 million of initial funding under the supervision of the Agency for Science, Technology and Research (A*STAR) is an attempt at making Singapore a leader in biomedical research and regenerative medicine. In the wake of the investment, private companies like Regenosis have been growing and maturing.
A large part of Regenosis' medical offerings are based on stem cell science. Stem cell therapy is used to help slow and even repair the signs of aging. According to Regenosis's website, the clinic's treatments "mitigate any health and aging concerns, keeping [patients'] physical and mental performance at its optimum."
Although a lot of the therapies offered in private clinics remain unproven and need to undergo clinical trials, researchers thus far have focused heavily on the therapeutic potential of stem cells, as they are extraordinary. "Use of cells, tissues, and gene therapy products for the treatment of diseases or physiological conditions has become of wide interest due to their potential to address serious unmet medical needs," according to a World Health Organization report released in December that discussed the regulation of cell and gene therapy products.
Scientific research has shown that contrary to mature cells, stem cells have high plasticity and an unlimited capacity for self-renewal. They can potentially make and fix any human organ or tissue, and cure a lot of varying conditions, like Parkinson's, diabetes, AIDS and macular degeneration (age-related blurred vision or blindness). Treatments usually involve introducing stem cells into the bloodstream through an IV drip or injection.
Although there are stem cells in the adult body, the most valuable ones are found in human embryos during the earliest stage of development, starting a few days after fertilization.
Human embryonic stem cells were first cultured in 1998; there have been major bioethical debates ever since. Isolating these stem cells could harm or cause the death of a human embryo, which is why the creation of stem cell lines (a group of stem cells that is cultured in vitro that can be propagated indefinitely) has long been strictly regulated in many countries.
Private stem cell and cord blood banking -- stem cells can also be found in the umbilical cord's blood -- is still restricted in European countries like France, where authorities say it is unethical for individuals to buy their own personal "biological insurance."
Stem cell transplantations also carry risks as patients can develop tumors, experience immune rejection or become infected.
Singapore's long-term hopes
The complicated questions surrounding stem cells have created a comparative advantage for countries willing to push the ethical envelope. Beyond building the Biopolis innovation cluster, Singapore has gained its stem cell advantage mostly by being liberal when it comes to bioethical regulations. Most countries have implemented conservative policies. In 2002, Singapore's Bioethics Advisory Committee declared that "a human embryo has a special status as a potential human being," but is not of the same status as a living child or adult.
"Such respect, however, is not absolute and may be weighed against the recognized benefits arising from the proposed research," the committee found.
This utilitarian stance could have provoked controversy elsewhere, but in Singapore there was little opposition, except among the city-state's minority Catholic population (15% of the country's total).
A year earlier, then-U.S. President George W. Bush implemented a policy to limit the number of embryonic stem cell lines, a restriction that was lifted under then-President Barack Obama in 2009.
As Tamra Lysaght and Benjamin J. Capps, bioethics specialists at the National University of Singapore, noted in an article in 2012, "Singapore's permissive regulatory approach and laissez-faire economic policies have been applauded by the international scientific community. Singapore has since recruited a number of high profile scientists with generous research budgets and the freedom to pursue innovative lines of research."
Famous recruits have included husband and wife duo Neal Copeland and Nancy Jenkins, who were appointed to A*STAR's Institute of Molecular and Cell Biology in 2007, and Alan Colman, who was formerly with the U.K.'s PPL Therapeutics. According to Colman, Singapore was attractive because it lacked "unduly onerous political or legislative restrictions" on the use of human embryonic stem cell research.
Regenosis has benefited from a trend of foreign scientists seeking greater freedom to pursue research. It is not the only private clinic offering stem cell therapies in Singapore but it boasts the most impressive medical advisory board.
The chief scientific officer is Brian Kennedy, an American biochemistry specialist and a leader in his field, having previously served as CEO of California's Buck Institute for Research on Aging until stepping down in 2016. Kennedy now holds the position of distinguished professor at the National University of Singapore and is director of the university's Centre for Healthy Aging.
Lim reportedly chose Kennedy for the role at Regenosis after seeing him in the geroscience documentary that originally inspired the business.
"Personally," Kennedy told Nikkei, "I went to Singapore because it was an opportunity to create a pipeline of research, from fundamental science to translation to clinical interventions to target aging. Singapore is a rapidly aging population, and it can become an example of the benefits of targeting human healthspan instead of only treating diseases."
Yet, his job at Regenosis does not appear on Kennedy's official academic page. When asked about this, he replied: "I have a number of private sector relationships that are disclosed in papers when pertinent. I don't see a major conflict."
Even Singapore is feeling the pressure over ethical issues in biomedicine, however. When Kennedy arrived in Singapore in 2017, the country was starting to rein in its ultraliberal attitude toward research ethics, passing the Human Biomedical Research Act in 2015 and further regulations in 2017. These broadly restricted all research with humans and human tissues, which include stem cells from human embryos. "I do believe we need to re-evaluate these regulations as they are becoming more restrictive and inhibitory to progress," Kennedy said.
A continental race within a global race
The gold rush around stem cells and regenerative medicine is Asiawide: While Singapore was launching Biopolis, China was simultaneously working to expand its scope of stem cell research, with the National Natural Science Foundation of China investing millions of dollars to support research programs.
Between 2002 and 2012, the annual number of Chinese scientific publications on stem cell research went from around 300 to 3,000, allowing it to rank second in the world behind the U.S., which published around 8,000 papers in 2012.
In May of this year, a team from the Chinese Academy of Sciences announced it had created "vampire" mice, injecting older mice with the blood of younger mice to make them live longer. The "rejuvenation" discovery was met with great media enthusiasm and seen as a confirmation that China is on track to become a science superpower.
In Japan, stem cell scientist Shinya Yamanaka won a Nobel Prize in 2012 for successfully generating pluripotent cells from adult cells -- answering the question of whether "normal" mature cells could be turned back into pluripotent ones like those found in human embryos. His discovery removed the necessity for embryos in stem cell research and treatment.
But the field is known for its share of scandals and treachery. On May 12, 2006, Hwang Woo-Suk, a South Korean professor of biotechnology at Seoul National University, was charged with embezzlement and bioethics law violations after it emerged most of his stem cell research had been faked. In 2004 and 2005, he had published articles in which he reported having created human embryonic stem cells by cloning. Before that, the media called him "the pride of South Korea." Hwang even had a postage stamp to his glory. His fall scarred the country.
Another Japanese discovery nearly outshone Yamanaka's in 2014, when researcher Haruko Obokata published an article claiming that ordinary cells could be turned into pluripotent stem cells even more quickly by subjecting them to profound stress.
Obokata was later accused of scientific misconduct, and the articles were withdrawn. Yoshiki Sasai, her supervisor at the prestigious Riken Institute, was found dead in August 2014, an apparent suicide by hanging.
The progress made by science is impressive, according to Norio Nakatsuji, professor emeritus at Kyoto University in Japan and former head of the Institute for Integrated Cell-Material Sciences. However, he said, the "reversal or halting of the total aging process, is still a hypothetical idea and dream. I cannot imagine anything near immortality ever realized."
He went on: "I should point out that there are many articles or advertisements in media that may mislead patients and make people misunderstand treatments of individual symptoms for the total anti-aging therapy."
Said Kennedy: "There are a number of exciting strategies and new approaches. I am confident we will become increasingly effective at slowing aging. The question of whether aging can be reversed is largely unanswered at present."
Defying aging in style
While the global market is still dominated by American companies like Athersys, Cytori Therapeutics and Vericel, big Asian players have emerged. In close connection to the emergence of these suppliers, private clinics offering anti-aging stem cell therapies have also blossomed across the continent.
And there is one country that epitomizes all the issues related to the industry's growing salience: Japan.
On the 11th floor of a skyscraper overlooking the glittering azure of Tokyo Bay, far-removed from the scorching tarmac and buzzing traffic, is Star Clinic, Japan's longest-standing stem cell therapy clinic.
The center, which opened nine years ago, offers a range of regenerative medical treatments -- from skin care to sports injury rehabilitation -- for prices that start at around $500 and run as high as $13,200.
"We are trying as hard as we can to reduce the price of our treatments and make them more accessible," Akio Abiko, founder of Star and chairman of the Tokyo Stem Cell Foundation, told Nikkei. "But our prices are some of the most reasonable you will find, in terms of what you get for your money."
From the moment patients step out of the elevator, Star offers luxury. Two glossy-haired, large black dogs greet clients at the door, tails wagging. Patients are then ushered onto the leather sofas of the clinic's lobby, where floor-to-ceiling windows provide an unimpeded view of the bay below, with Tokyo's silver skyline in the background.
Tall men in suits are on hand to offer drinks as patients wait for treatment, while the well-trained dogs provide company and entertainment.
"We pride ourselves on safety and efficacy," Abiko said. "Quality control is very important to us -- we make sure that we give patients fast and noticeable results, while not compromising on health and hygiene."
Treatment at Star, Abiko explained, starts with a free counseling session with one of the clinic's doctors, all of whom are specially trained in regenerative medicine. "There are some people who come to us to just learn more about stem cell therapy, with no plan of actually getting treatment," Abiko said. "In those cases, we happily chat to them about what we are doing, free of charge."
For patients seeking treatment, counseling is followed by a short operation, where cells are extracted from body fat, usually in the stomach. The process takes no longer than half an hour. "It's very quick and smooth," Natsumi Suzuki, Star's managing director and proud owner of the clinic's dogs, told Nikkei. "First-time patients can be in and out of the clinic in less than 90 minutes."
Following the operation, the patient's cells are transferred to Star's in-house lab, where they undergo the complex and lengthy process of being transformed into stem cells. This takes about four weeks, then treatment can begin. "The length and nature of treatment varies between patients, because each course is carefully tailored to the individual's needs," Suzuki said. "Usually, patients come in and receive their treatment via an IV drip twice a year."
In the nine years since its founding, Star Clinic has not once been featured by Japanese media, nor engaged in any kind of marketing. News of the clinic spreads by word-of-mouth among patients, some of whom travel to Tokyo from abroad specifically to be treated. "A lot of our patients are high-profile individuals," Abiko said, "and a lot of them know each other."
According to the clinic, the number of male and female patients is roughly equal, and ages range from people in their 20s up to their 90s. Foreign patients come mainly from Vietnam and China, although a few travel from as far as Europe.
One Star patient, a woman in her late 40s who asked to remain anonymous, works in South Korea but returns to Japan regularly for treatment. She was introduced to the clinic by a friend who began stem cell therapy after being diagnosed with a serious illness in 2020.
"When my friend suggested I try [stem cell therapy], I wasn't actually ill, but I had started to feel my general health deteriorating since hitting my 40s," she said. "I had developed some skin allergies and was getting really bad eczema, along with general fatigue and some aches and pains. I could also feel a change in my hormones, and was getting some menopausal symptoms."
Since beginning treatment at Star a few months ago, the patient says her eczema has disappeared, her energy levels have rebounded and her general well-being has improved. "I have a very demanding job, with long hours and little time to sleep," she told Nikkei. "Recently, even younger colleagues have been asking me, 'How do you do it? How do you work so much and still seem so energetic?' And I'm sure it's because of this treatment."
Another Star patient -- a woman of around the same age who works in Japan and has been receiving stem cell therapy for two years -- said she is convinced the treatments are the reason she has not caught COVID-19.
The clinic says it is too early to say whether stem cell treatments are effective in preventing COVID-19, but researchers believe they help strengthen the immune system. Star claims that 90% of its patients have yet to contract the virus.
Japan: The perfect testing ground
For many reasons, Japan makes for an ideal test market. More than 29% of its population is 65 or older, the highest proportion in the world and a figure that is projected to reach over 31% by 2040, according to Euromonitor International. In 2019, the Japanese government announced its "age-free society" project, with a request for companies to continue employing workers beyond the age of 65.
Following Yamanaka's discoveries, Japan quickly became a "magnet for scientists and entrepreneurs looking for a rapid route to commercializing products and therapies," according to the science journal Nature.
The country's 2014 Act on the Safety of Regenerative Medicine had a large role to play in this. The Act set standards to ensure the safety of stem cell research and treatments, and permits medical institutions to outsource cell processing and culturing to private companies.
"Under the new Japanese regulation system, we have a 'conditional approval' which may be given to a new therapy by submitting evidence on the safety and speculation (but not yet solid evidence) of benefits to patients," Kyoto University's Nakatsuji told Nikkei.
"This may accelerate the patient's treatment, but also it may increase risk of giving false expectations and generate a waste of medical costs," he said.
Nakatsuji went on: "There are over-expectations and hype about cell therapy and regenerative medicine, which were excessively promoted by the media and other sectors, including the government and even some medical scientists ... It may be difficult for patients to have a balanced understanding of the benefits and drawbacks of [some] 'conditionally approved' therapies."
Nakatsuji told Nikkei he was concerned that the widespread "hype" surrounding stem cell therapies offered by private clinics in Japan "could increase the risk of medical malpractice."
Similar concerns are mounting in South Korea, where the clock on a demographic time bomb is ticking due to a shrinking population and a low total fertility rate of 0.81. The bomb promises labor shortages and a growing social burden of providing for the elderly.
South Korea's private cell therapy clinics are concentrated in Gangnam, Seoul's wealthiest district. According to the Korea Herald, former President Park Geun-Hye in 2017 secretly received regenerative treatments at a clinic in Apgujeong, a ward in Gangnam famous for setting trends.
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Who wants to become a vampire?
The ethical questions that anti-aging research poses are not limited to stem cells; they also touch on the broader question of what this kind of medical treatment might do to society. The industry holds the potential to exacerbate wealth inequality in the rawest terms imaginable.
China's "vampire" technique discovery provides a useful metaphor to examine the industry: Would people want to live in a world where poor, young people sell their blood to companies that inject it into old, rich people so that they can live longer?
Humanity may be closer than it realizes to such a scenario.
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