Prospects for rejuvenation
How a Startup is Fighting Death with the Help of Billions of Bezos and Nobel Laureates
Elizaveta Vecherova, Forbes
Altos Labs startup, which launched in mid-January, attracted $3 billion in investments at the start: a former co-owner invested in it Mail.Ru (today VK) and one of the most influential investors in the technology sector, Yuri Milner and billionaire Jeff Bezos. With this money, the company has already started hiring the best specialists to develop rejuvenation technologies. Will Altos Labs be able to cheat death?
The fact that the new startup Altos Labs with billion-dollar investments is going to cheat death was written in mid-January by a variety of media, from financial to tabloids. The technologies of partial cellular reprogramming taken by him as a basis promise to rejuvenate the cells of the body to their embryonic state. Such stem cells generate all the other cells of the body — skin, liver, brain, nerve endings, so they contribute not only to rejuvenation, but also to the cure of diseases.
Among the people whom Altos Labs managed to attract to cooperation is the Nobel Prize winner in Medicine Shinya Yamanaka, who discovered this method of reprogramming in 2006. Although since that time many have tried to commercialize the discovery of the Japanese scientist, no one has finally succeeded until now; besides, it is unknown how many times it will be possible to reprogram the body in this way and how safe it is. A representative of Altos Labs in an interview with the Financial Times cautiously clarified that the startup's task is not so much to cheat death as to prolong the active part of a person's life with a healthy body, and an increase in life expectancy at the same time will be rather an "accidental consequence".
Who is fighting for immortality
Altos Labs plans to open two divisions in California and one in the UK — in Cambridge; in addition, a significant part of the research will be conducted in Japan, where Shinya Yamanaka works, who will act as a consultant. Attention to the startup was attracted not only by Yamanaki technology, but also by the names of investors, explicit and assumed — the company does not disclose the names of some, saying only that they are "well-known creators of companies and investors," however, in its official press release, it named the amount of attracted investments. $3 billion is an unprecedented amount of initial investment in a biotech startup. For comparison, Moderna raised $604 million for the IPO, and this was a record among biotech companies.
The first to report that Yuri Milner and Jeff Bezos, who resigned as CEO of Amazon in July, invested in the company, citing their sources, was reported in September last year by MIT Technology Review. Since then, this information has been replicated by all the world's media, and none of the mentioned investors has refuted it. Yuri Milner's DST Global Foundation, where Forbes asked for confirmation, declined to comment.
Altos Labs officially launched on January 19, 2022, at the same time it became known that the CEO of the startup will be the chief researcher of one of the largest pharmaceutical companies in the world GlaxoSmithKline Hal Barron. At the same time, the startup intensified the search for the best experts on life extension. Right now, the company is looking for specialists in computational biology, biophysics and biochemistry. Altos Labs promises that they will be able to freely conduct research on how cells age and how to reverse this process. In addition, the salaries in the company are quite high: for example, Manuel Serrano from the Institute for Biomedical Research in Barcelona told MIT Technology Review that Altos will pay him 5-10 times more than he earns now.
The company's founder, Richard Klausner, is a former head of the National Cancer Institute, co—founder of Juno Therapeutics (a biopharmaceutical company developing cancer drugs) and Grail (a company developing early cancer screening tests for people who have no symptoms). Prior to Hal Barron's assumption of office, he acts as the main person in the company. The second founder, Hans Bishop, holds the position of president. Bishop was previously CEO at Juno Biotechnology and Grail. Klausner, Bishop and Barron will become co-chairs of the company's board of directors.
Altos already has several Nobel laureates on staff, among them the winner of the Nobel Prize in Chemistry in 2020 Jennifer Dudna, winner of the 2018 Nobel Prize in Chemistry Francis Arnold, winner of the 1975 Nobel Prize in Physiology or Medicine David Baltimore and the already mentioned Shinya Yamanaka.
It seems that Altos has gathered the best scientists who are somehow dealing with the problems of aging. The team was joined by such science stars as Juan Carlos Ispisua Belmonte, a Spanish biologist who became famous for his research on human-monkey crossing, confident that with the help of technology, the average life expectancy of a person can be increased by at least 50 years. "I am sure that a child who will live to be 130 years old has already been born," he said in an interview with MIT Technology Review in 2019.
Another expert in the startup team who became famous for his invention is Steve Horvath, a professor at the University of California at Los Angeles and the developer of a biological clock that can "predict" the date of a person's death by changes in cytosine, an organic compound that is part of DNA. Other valuable acquisitions of Altos Labs include Peter Walter, whose laboratory at the University of California, San Francisco is developing a memory—enhancing molecule, and Wolf Rake, a genome reprogramming specialist who recently resigned as director of the Babraham Institute in the UK to move "to another research organization." Apparently, it was about Altos.
Reprogramming cells is an axe
Altos technology is largely based on the discovery of Yamanaki. Back in 2006, he discovered that if only four proteins regulating genes are added to cells, they can be reprogrammed, that is, they can return to a younger and much more adaptable form of them — embryonic stem cells. This process is compared to restoring the factory settings of a smartphone.
Stem cells are the raw materials from which all other cells of the body are generated: skin, liver, brain and nerve cells. Under natural conditions, in the laboratory or in the body, stem cells will divide, forming even more cells. These embryonic stem cells can be used to regenerate or restore diseased tissues and organs, and even to rejuvenate the entire body.
During clinical trials of Yamanaki technology, some mice developed tumors, but others did show signs that their tissues were rejuvenating. Further experiments on mice show that, among other things, reprogramming cells can stop the progression of rare genetic diseases (for example, progeria — premature aging of the body), accelerate the healing of injured muscles and protect the liver from damage by paracetamol. "Although there are many hurdles to overcome, the technology has huge potential," Yamanaka said in an email to MIT Technology Review.
At the same time, as the head of the company for the development of gene therapy rejuvenation YouthBio Therapeutics Yuri Deigin, Shinya Yamanaka in the company acts more like a wedding general and is needed mainly for status and PR, and partial programming in Altos Labs is the same axe from the Russian fairy tale about porridge from the axe: he was declared as central technology, but in reality the company's approach is much broader. "They have recruited a huge number of different scientists and, in fact, they want to develop in all directions. Each of them will implement their own ideas," says Deigin.
Another key area of Altos Labs is the study of "complex stress response" (CRS) in humans. Scientists have proven that high levels of stress can damage the cells of the human body. If these damaged cells undergo cell division, new cells will also be damaged. When the CATTLE detects a problem, it can turn on the emergency reset program. If this does not work, the CATTLE destroys the damaged cells to stop the spread of damage.
However, the cattle paths may malfunction, and this problem will be the focus of Altos Labs' research. The company uses artificial intelligence to improve understanding of the mechanisms of these cells. Altos will also work with the appropriate technology to measure the relative age of a cell or a person. This method of biological clocks, first proposed by Steve Horvath, involves measuring epigenetic labels on genes — they turn genes on and off, but with age their structure is destroyed. Such an aging biomarker could be an important way to measure the effect of any drug being developed that increases life expectancy or slows down aging.
Alex Zhavoronkov, founder of Insilico Medicine and Deep Longevity, associate professor at the Buck Institute for Aging Research, believes that the world will see the results of Altos Labs' research in 7-10 years: "The drug development process takes about that long, plus they need to build the necessary infrastructure."
Yuri Deigin is more optimistic, although he also says that such large companies always spend a lot of time on pitching — they build offices, equip laboratories, hire people. According to him, these processes will take from several months to a year, and we will see the first results on animals within one and a half to two years. At the same time, he notes that although the probability of success in such a complex area as life extension technologies increases from the amount of money invested, the billions spent, as the experience of Calico Labs shows, do not guarantee it.
"A giant pile of gold" and immortality for the rich
The most obvious competitor of Altos is Calico Labs, a company dedicated to longevity, the creation of which was announced in 2013 by one of the founders of Google, Larry Page. Calico hired famous scientists in the same way, allocated generous budgets to them and opened a laboratory specializing in reprogramming the genome and ways of complex response to stress. It is unclear whether the Google subsidiary has made significant progress: they are not conducting any clinical trials on humans at the moment. Despite this, over the past year, the company's shares have grown by 38.37%, and over the past five years — by 207%.
Yuri Deigin notes that Altos Labs and Calico Labs have a lot in common: "As long as they act according to the same scenario, they attract stars in the market. The standard scheme of a billionaire is to try to cheat all the coolest, promising them huge salaries, and make loud statements. But Calico hasn't done anything significant over the years." Zhavoronkov also speaks about the similarity of the companies: "Calico has been around for nine years, and so far we have not seen clinical trials. I hope that the Altos process will go faster."
"Reprogramming aimed at rejuvenating parts or the entire human body raises hundreds of millions of dollars in investments," he says David Sinclair, a researcher at Harvard University, who last December reported on the restoration of vision in mice using this technology. Sinclair describes this field as nascent, but believes it has unique perspectives.
Reprogramming technologies are already being explored by other startups, including Life Biosciences, Turn Biotechnologies, AgeX Therapeutics and Shift Bioscience in the UK. The British billionaire Jim Mellon also created his own life extension company, Juvenescence, although no research has yet led to clinical trials of any treatment methods in humans.
The anti-age market in the world is about $4-6 trillion a year, says Alexey Antonov, chief analyst at Alor Broker, but mostly cosmetologists and checkups mimic this sector.
Svetlana Zakirova, Nanolek's Deputy General Director for Research and Development, explains to Forbes that most companies are going to rejuvenate human systems and organs, but Altos has a different goal: "Altos Labs aims to carry out cellular reprogramming of all body tissues. To develop a method that will make the cells of human body tissues younger."
Alexey Strygin, founder of the CNS anti-aging startup Gray Matter (part of the Lactocore Group), says that all technologies are still at the stage of early exploratory research or preclinical trials: "Most likely, at least one of the developments will enter the first phase of clinical trials within two to three years, that is, the appearance of these therapies on the market is unlikely to be expected before 2030."
Svetlana Zakirova also supports him: "It's too early to count on artificial organs. It is quite difficult to grow tissues, many organs have not been fully studied and assembled in vitro, and the three-dimensional structure of the liver and kidneys has not yet been created at all."
Martin Borch Jensen, chief researcher at the biotech company Gordian Biotechnology, assures that reprogramming technology is a "giant pile of gold" and should be invested in immediately. "There's a lot at stake right now," says Jensen. "If reprogramming and biomarkers of aging work, it will have a huge impact on the market."
However, Antonov from Alor Broker is skeptical: "So far, such startups look like parasitism on a fashionable topic, and for sure some of the money that turns into them is aimed at tax evasion and other optimizations." He believes that it is naive from the point of view of investors to expect profit from the results of such research, although already now the longevity market is receiving increased attention from investors and billionaires of Silicon Valley.
In Russia, this sector remains risky. Antonov says that now, on average, even investments in fitness are unprofitable, because there is no concept of body care and in general the concept of self-care is very weak: "The average household in Russia spends no more than 5% on medical services, and this is the cost of treatment, not prevention."
Other skeptics note that even now the opportunity to live longer is a privilege for the richer, and with the advent of new expensive technologies, the division of society into rich centenarians and poor mortals may become even more noticeable. However, according to Strygin, now it is impossible to estimate how expensive the treatment will be: "The price largely consists of the costs incurred by the company for clinical trials, market conditions and competitive environment. Due to the fact that the direction is still very young, there is a lot of uncertainty in the dosages and methods of drug delivery. However, after the patents expire, the basic cost of such therapy is likely to be available to most of the world's population."
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