Startups come and go. Few start with $3 billion in the bank. Altos Labs is in a fortunate position. The firm formally announced itself on January 19th, after months of rumors, and it's likely that it's a candidate for the title of "best financed startup in history". Even at $3 billion, it might be seen as cheap. The founding fathers of the alchemy, Rick Klausner, Hans Bishop, and Yuri Milner, hope that one day the world will be an elixir of life.
Others have tried this before. Larry Page, one of the firm's founders, was an interested party in the creation of the outfit called Calico Life Sciences. It hasn't generated a product yet. Craig Venter and Peter Diamandis, who started the X Prize Foundation, got together to launch Human Longevity in the same year, but they fell out. The company has gone quiet. There are many other hopefuls in the field, with billionaires like Dr Milner and Mr Page in the background. Altos will not confirm that Jeff Bezos is an investor in the company, but it is possible that he is interested in prolongation of life, a field that seems particularly attractive to the man who otherwise has everything.
There is a walk in the hills.
The Altos founders seem serious about what they are doing. They believe they have glimpsed the outline of an answer to the question of how to reverse the process of cellular aging. They have recruited a star- studded scientific cast to help them track that answer down. Diabetes and associated metabolic problems, as well as cancer, are illnesses potentially in their cross-hairs. In the end, dealing with these might not extend average lifespans. It would surely increase what is known as healthspan.
Dr Klausner, a former head of America's National Cancer Institute, and Dr Milner, an entrepreneurial and venture capitalist, dreamed up the idea of Altos, a hilly area in Los Altos. They recruited Mr Bishop, the former boss of GRAIL, to be the business brains.
Yamanaka transcription factors and the integrated stress-response pathway are two of the findings built by the firm. Yamanaka factors are four genes that return a cell to factory settings. pluripotency is a state that is enjoyed by embryonic stem cells. A pluripotent cell can give rise to descendants capable of differentiating into many different types of cells.
Tumours called teratomas were caused by early experiments involving the Yamanaka factors in laboratory animals. A partial reset avoiding this problem can be achieved by turning the relevant genes on only briefly. This results in a return to youthful rude health. Experiments on mice have shown that progeria can be stopped and that it can promote the healing of injured muscles, and that it can protect the liver from damage.
The Yamanaka factors have a discovery date, but the idea of an ISR pathway has emerged gradually. One of the most important concepts in biology is the maintenance of a constant internal environment in the face of external pressure to change. This is done at a cellular level by the ISR. If a source of cellular stress is detected, the ISR will switch on an emergency program to reset. If this doesn't clear the problem, it will blow up the cell in order to stop it from becoming a disease.
Pick a mix.
The two discoveries offer ways to bring sick cells back to health by resetting malfunctioning ISR pathways, and to give healthy cells that are getting on a bit in years a tonic. The initial plan is to look into this at three campuses, in Cambridge, England, the Bay Area of California and San Diego. Wolf Reik, Peter Walter and Juan Carlos Izpisua Belmonte are the leaders of the institutes. Half a dozen research groups are investigating various aspects of the problem.
Dr Reik is an expert in the field of epigenetic gene regulation. The Yamanaka factors operate in a similar way to the way genes are controlled by the way DNA is packed into chromosomes. Dr Walter is currently at the University of California, San Francisco. He was involved from the beginning. Dr Izpisua Belmonte, who ran the Gene Expression Laboratory at the Salk Institute in San Diego, is also studying the Yamanaka factors. He spotted their potential to rejuvenation without a full factory reset, with all the potential medical consequences that can arise. Stem-cell therapies to regenerate tissues already in the body and also the idea of growing organs for transplant were previously looked at by those seeking to turn Yamanaka factors to medical advantage. Altos seeks to exploit the third avenue of rejuvenative possibility.
Dr Yamanaka will not be paid because he volunteered. He was the one who became interested in the question of rejuvenation and aging. He was one of the first recipients of a prize that was dreamed up by some Silicon Valley bigwigs to try and catch up to the prize money of the Nobel Foundation. He will help gather a network of people in his native country, even though he won't run an institute.
Artificial intelligence is the last piece of the scientific jigsaw. One of the leading lights in DeepMind is now the purview of Thore Graepel. Modelling what is going on inside cells, which are composed of millions of molecules of thousands of varieties, is a problem that would be impossible without artificial intelligence. The recent success of DeepMind's AlphaFold program, which is able to predict from aProtein's chemical structure how it will fold up into a functional shape, shows that the field is starting to grapple with it. Dr Graepel will try to make sense of the data from the investigators.
The board of the firm has three other people on it, including David Baltimore, a biological polymath, who won his for his work on viruses.
Will it all play out? The participants may have jumped too early. In their old jobs, they would have been doing the same things in the firm's salad days. There is nothing immediately to hand that could be developed into a commercial product.
Three billion dollars is a big amount of money. It allows for changes of direction and recovery from mistakes. It will also allow Altos to build its own development arm, and not have to rely on other companies, as lesser startup often do, as Bob Nelsen's firm, ARCH Venture Partners, is on board to the tune of a sum north of $250m.
Not having a clear product from the get-go does not seem to be a problem, though Mr Nelsen does mention boosting T-cell responses in the immune systems of the elderly and dealing with badly functioning islet cells in the pancreases of people with diabetes as early possibilities. Everyone seems confident that salable products will emerge.
Don't fade away, re-record.
Altos is a kind of Bell Labs except without Ma Bell, then America's telephone monopoly, at their back. Bell let bright people get on with it. The transistor and laser were created. Those were products of physics. The Altos approach seems similar to that taken by Calico Life Sciences, which has not worked so well, though Hal Barron, Altos's chief executive, was once Calico's head of research.
There are doubts about the underlying biology of aging. Multicellular organisms do not wear out in the same way that machines do. The process of senescence is regulated by natural selection. The details are being debated. The disposable-soma theory seems to govern what is happening.
The premise of disposable-soma theory is that death is inevitable for an individual. You will get in the end if you get an accident, infection, predator or a rival. It makes sense for evolution to care more about individuals when they are young than when they are old, since by then they may have died or been killed.
There are a lot of things that make sense. Good genes can have bad effects in old age. Repairs are good enough to keep the show on the road. Anti-cancer mechanisms need to be top-notch for the first decades of life, but can get slacker with time. The immune system can. Altos's researchers will have to incorporate more aspects of molecular biology than they are beginning with in order to cover these bases.
Dr Klausner and his colleagues argue that resetting the clock is a natural process. It happens to everyone. Each time, the reproductive cells get a fresh start. They return to factory settings. If the clock can be reset for those cells, why not others? The answer to that question will determine whether or not the firm sees a return on its investment. It will be interesting to see it asked.
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