Sam Altman
Retro Biosciences is one more entrant in the long list of longevity aspirants. Like many others, it is bank rolled by yet another billionaire who has a brilliant track record – but all of it is outside of biology and health. Other aspirants in the race range from Kodoy and Twin in India to Altoslabs and Tony Robbins in the US.
Kodoy looks upon all these companies (including Retro), not as competitors (which they most certainly are for accessing capital) but as role models (to figure out what not to do) and as possible allies (to take to the Indian market what they can get working – but at more affordable price points.
The Kodoy team attempted to assess Retro on the three key parameters used for startups through a limited survey:
Likely start of commercial operations: C+
Team and funding: A-
Overall strategy and science: B+
In this blogpost, we try to find some basic answers about Retro from public sources – who or what is Retro Biosciences, who is the techie backing their mission and what exactly do they want to do ? What are their chances of succeeding ? What kind of time frame can they deliver in ?
Retro BioSciences
Retro Biosciences eased out of stealth mode in mid-2022. As per their website:
Our mission is to increase healthy human lifespan by ten years. This will be intensely challenging and require substantial resources. We are fortunate to have initial funding in the amount of $180 million, which will take us to our first proofs of concept, and secure operation of the company through the decade.
In the US, around 90 percent of our healthcare spending – over $3 trillion – goes toward age-related diseases and this trend is echoed throughout the world. The deeper, underlying causes of age-related diseases are the untreated mechanisms of aging itself. By focusing on the cellular drivers of aging, Retro will design therapeutics eventually capable of multi-disease prevention. This mission would have seemed too bold a decade ago but new methods such as single-cell multi-omics, pooled perturbations, and targeted delivery systems now enable us to understand and intervene directly.
We identify aging mechanisms for which interventions have shown robust proofs of concept in mammals and have a feasible path to translation to humans. To start with, we are focused on cellular reprogramming, plasma-inspired therapeutics, and autophagy. Our programs are diversified across mechanism and development stage. We have a molecule in our autophagy program that will enter the clinic in the next year. In our plasma program, we’re characterizing and optimizing plasma interventions in both preclinical and clinical settings, with the first development candidate expected in two years. Our cellular reprogramming effort is closest to fundamental research and farthest upstream in the mechanisms of aging. We will work towards a clinical proof-of-concept over the next four years. To support these three programs, we are investing heavily in single-cell multi-omics, machine-learning-based computational biology, and lab automation.
Joe Betts-LaCroix, Sheng Ding, and Matt Buckley founded Retro with the intention of building a generational pharma company proportional to the scale of our mission.
We explicitly filter for people who fit our culture: kindness and authenticity, rigor and rapid iteration, versatility and fluid intelligence. Because aging is complex we are building a team composed of multi-specialists who communicate fluently across domains and will produce therapies targeting multiple mechanisms of aging. We prioritize mission-driven team science, freed from the constraints of grant-writing. We prize speed, combining an ethos of rapid iteration with investment in vertical integration to tighten feedback loops. We bet on scientists who want to maximize themselves and their impact in this environment.
Retro Funding
MIT Technology Review has now revealed that the entire sum of USD 180 million was put up by Sam Altman, the 37-year-old startup guru and investor who is CEO of OpenAI. Altman’s investment in Retro hasn’t been previously reported. It is among the largest ever by an individual into a startup pursuing human longevity. Altman has long been a prominent figure in the Silicon Valley scene, where he previously ran the startup incubator Y Combinator in San Francisco. But his profile has gone global with OpenAI’s release of ChatGPT, software that’s able to write poems and answer questions. Altman’s wide-ranging investments have included early stakes in companies like Stripe and Airbnb.
Investor’s Philosophy
Sam Altman is putting his capital to work at a level he calls an “order of magnitude” greater than he could during his Y Combinator days. And he has been concentrating those bets into a few areas of technology he thinks will have the biggest positive impact on human affairs: AI, energy, and anti-aging biotech. All these companies, including OpenAI, are what Altman calls “hard” startups—those requiring large investments in order to make scientific advances and master difficult technology. Hard science companies are more expensive to fund, but Altman thinks their larger goals are more likely to attract talented engineers. In fact, Altman says, hard startups may stand a better chance of success than easy ones. That’s because there may be a thousand startups hawking photo-sharing apps, but there are only a few capable of building experimental fusion reactors or working towards extending life.
Retro Strategy
Retro seems to be pursuing research in so-called “young blood” research. There were studies in which scientists sewed young and old mice together so that they shared one blood system. The surprise: the old mice seemed to be partly rejuvenated. In 2018, Y Combinator launched a special course for biotech companies, inviting those with “radical anti-aging schemes” to apply, but before long, Altman moved away from Y Combinator to focus on his growing role at OpenAI. Then, in 2020, researchers in California showed they could achieve an effect similar to young blood by replacing the plasma of old mice with salt water and albumin. That suggested the real problem lay in the old blood. Simply by diluting it (and the toxins in it), medicine might get one step closer to a cure for aging.
These were studies in which scientists sewed young and old mice together so that they shared one blood system. The surprise: the old mice seemed to be partly rejuvenated.
Retro Leadership
Betts-LaCroix, is the cofounder and CEO of the company. He had once been the part-time biotech partner at Y Combinator and had worked with Atman. According to the Retro website:
Joe Betts-LaCroix began as a scientist at Harvard, MIT, and Caltech. He was part of a three-person team at Caltech that first elucidated the factors governing electron-tunneling rates in proteins, which is published in journals such as Science and JACS, with over 1000 citations so far. His first venture-funded startup, OQO, created the world’s smallest windows computer (Guinness world record 2006) with a team of 110 people, more than 100 patents, and over 10,000 units sold; and was sold to Google. His second startup, Vium, automated animal research to accelerate medical research. Vium, as a team of 75 people, created thousands of advanced mouse cages that monitor environmental factors and HD video in each cage using computer vision + deep neural networks to determine whether experimental drugs are working against models of disease. Recursion Pharma acquired Vium in 2020 and IPO’d in 2021. Joe spent 2.5 years as a part-time partner at Y Combinator and has mentored and invested in numerous bio startups. Joe is presently CEO of his third venture-funded startup, Retro Biosciences, which is creating therapeutics against targets elucidated by its research in aging biology, with the mission of increasing healthy human lifespan by ten years.
Betts-LaCroix’s new plan was to start a company to pursue cellular reprogramming—another hot area, involving techniques to make cells younger through genetic engineering. He’d already teamed up with a Chinese researcher, Sheng Ding, who’d developed new ways to reprogram cells. Betts-LaCroix also thought processes that cells use to dispose of toxins (known as autophagy) could be an important avenue to explore. Altman and Betts-LaCroix worked together to build a multi-program company around aging biology. This company was Retro Biosciences.
Challenges
Every technology also has risks. In the case of AI, it is chatbots that spew lies and misinformation. For age reversal, if it ever works, one often cited risk is public resentment, especially if it’s going to be made available to rich people like Altman first. In 2016, after Peter Thiel, one of Altman’s mentors, expressed interest in possibly getting age-defeating blood transfusions, he was mocked in the media as a vampire on the prowl for young victims. A year later, the HBO parody show Silicon Valley drove the stake in with an episode called “Blood Boy.” In it, a fictional tech CEO takes a meeting while his veins are connected to those of a handsome young man introduced as his “transfusion associate.”
For his part, Altman says his personal anti-aging regime consists of “trying to eat healthy, exercise, sleep enough” and taking metformin, a diabetes drug that has also become popular in Silicon Valley circles on the theory that it might be able to keep people healthier for longer. “I hope to use a Retro therapy someday!” Altman says.
OpenAI for longevity
One reason anti-aging research can seem like a promising area for investment is that it has not drawn much funding in the past, at least relative to the size of the problem. Nearly a fifth of the US GDP—$4.3 trillion, according to the Centers for Medicare & Medicaid Services—is spent on health care, and much of that is to treat the elderly. A widespread view among longevity researchers is that if aging could be delayed with a drug, it could help postpone a host of serious diseases, including cancer and heart disease. To make the widest impact, Betts-LaCroix says, he is looking for interventions that can be scaled up and reach “millions or billions” of people.
In comparison to these ventures, Altman’s bet now looks relatively small, even making Retro seem like an underdog. One of its projects is to test rejuvenation techniques on T cells, part of the immune system that play an important role in fighting infection and staving off cancer. These cells are especially useful because they can be removed, rejuvenated in the lab, and then returned to a patient. But other startups have similar goals, including Altos and NewLimit, a biotech company started by the cryptocurrency billionaire Brian Armstrong last year. Competition for research talent is especially stiff. Altos sucked up half the leading scientists in reprogramming when it convinced two dozen university professors to leave their jobs, offering million-dollar salaries, among other benefits.
But Betts-LaCroix has managed to lure some top minds as well. Last year, for instance, he jumped on a plane to Switzerland to woo Alejandro Ocampo, a researcher at the University of Lausanne whose initial efforts to rejuvenate mice in 2016 helped spark the current frenzy of longevity investment.
He also says Betts-LaCroix was open to his opinion that age reversal in humans isn’t going to happen anytime soon. Some of Ocampo’s recent experiments have explored why reprogramming, the method he studies, even ends up killing some mice instead of making them live longer. “There are optimists who think we’ll be immortal in 10 years, and there are pessimists who say we will never extend human life,” says Ocampo. “I am a realist, and my personal view is that everyone is doing the easy, fast experiment, and if we do that I don’t think we are going to get very far. It’s not going to be a simple path.”
Ocampo says Betts-LaCroix convinced him that Retro would be willing to use its money to explore those fundamental questions. “They wanted to advance the science, not only go after the low-hanging fruit,” he says. “Other companies need to find an immediate application, but in their case they can spend time exploring the basic science as well.”
Retro Team
Details of the Retro team as available on their website are included below:
Joe Betts-LaCroix. Cofounder, CEO
Jonathan “Joe” Betts-LaCroix (born Jonathan Betts February 26,1962) is an American scientist and entrepreneur known for his discoveries in biophysics and for creating the world’s smallest personal computer. He is working to optimize medical research priorities in the U.S. Beginning in earth sciences at Harvard, Betts-LaCroix contributed to the field of long-term regulation of oxygen on Earth over multi-100 Million-year timespans, quantifying the effect of the burial efficiency of organic carbon as a feedback mechanism.
At MIT, he designed and built an autonomous, robotic system that enables research into ocean circulation patterns and climate change, by operating untended for up to one year at sea on battery power and collecting hyper-pure water samples at predetermined intervals. In work at Caltech, Betts-LaCroix moved into biophysics, publishing a paper in Science that has been cited by more than 700 subsequent scientific works. In this work, he, along with David Beratan and José Onuchic proved for the first time that electron-transfer rates in proteins are determined by the electron orbital interactions in the protein structure.
Matt Buckley. Cofounder
Matt Buckley completed his PhD in the aging research lab of Dr. Anne Brunet at Stanford prior to co-founding Retro. He spent the last several years focused on scaling single-cell transcriptomics and applying machine learning techniques to quantify aging and the effects of age-related interventions. Prior to that he studied bioengineering at UC Berkeley and worked at Illumina. He believes that translating aging biology research into therapeutics is the most high-leverage way to improve the human condition, and that start-ups are a phenomenal way to do this. Outside of Retro, Matt enjoys reading broadly, with concentrations in history and science.
Sheng Ding. Cofounder
Sheng Ding is the Founding Dean and Bayer Distinguished Professor at the School of Pharmaceutical Sciences, Tsinghua University. He is also Founding CEO/CSO of the Global Health Drug Discovery Institute, a Gates Foundation-funded institute finding medicines for the developing world. Prof Ding is also Professor of Pharmaceutical Chemistry at UCSF and William K. Bowes, Jr. Distinguished Investigator at the Gladstone Institutes. He was previously Associate Professor at Scripps Research. Sheng is a scientific cofounder of 6 biotechs since 2007, with multiple IPOs.
Ieva Veya. VP of Operations
Trained in psychology, my work experience has been in Project and Operations management, specifically in onboarding complex R&D workflows. Before joining Retro I worked at Airbus R&D division (Acubed) where I wore a lot of different hats and learned that the more challenging the problem I have to solve, the more energy I feel. Building the operations team at Retro has so far been the most rewarding experience of my career, not only because of the complexity but also because of the sense of purpose toward Retro’s mission.
