Enterprising Minds

Live long and prosper

WHO? Daniel Ives, Cambridge alumnus, CEO and co-founder (with his dad) of Shift Bioscience.

WHAT? A Cambridge start-up trying to find a way to return cells and tissues to a youthful state. If successful, these rejuvenation therapies could be used to address the 200 diseases and disorders that are primarily associated with ageing.

WHY? As Rick Klausner said: “So that we die young, after a very long time.”

What sparked your interest in this field? After a degree and then a master's in biochemistry, I was thinking about next steps. That summer, my dad and I went to a small conference in Cambridge on ending ageing. It seemed like pretty wild science but there was nothing else like it. The message was 'we don't have to accept the inevitable: we can do something about it'. From that moment, I knew what I wanted to do.

I found out about a research project at the MRC Mitochondrial Biology Unit on the Cambridge Biomedical Campus, looking at the 'hallmarks of ageing' and how your function is gradually impaired as you age. The project was focused on mitochondria, which are found in our cells and have a number of important jobs, one of which is to produce energy.

But mitochondria can go wrong. They have their own genome and if that gets damaged they become dysfunctional and stop pulling their weight. We found a way to get rid of the bad mitochondria by encouraging the 'good' ones to reproduce more.

I started a PhD looking at how this technology could be applied to rare diseases, and that is now progressing to clinical trials. But all the time, I was thinking 'how can we apply this to ageing?'

When I finished my PhD I wanted to do some experiments in this new direction, but they were incredibly expensive. I couldn't persuade anyone to take the risk.

Then my postdoctoral research contract was cut short by a month. The silver lining was a redundancy payment which I spent with a contract research organisation in Cambridge, which allowed us to do a first experiment looking for mutations to the mitochondrial genome in people with age-associated Parkinson's.

Daniel Ives and the countdown to the launch of the 'Endure-1' experiment: Shift Bioscience's first attempt to rejuvenate human cells. 

Daniel Ives and the countdown to the launch of the 'Endure-1' experiment: Shift Bioscience's first attempt to rejuvenate human cells. 

Why did you decide to start a company? Around that time, the founder of Abcam and Cambridge investor, Jonathan Milner became aware of us. My dad (and co-founder) is a serial Cambridge entrepreneur and knew a lot of great people, including Hermann Hauser.

When Dad found some time to read my thesis, he started to get excited. He said we could move the research forward more quickly if we formed a company. He took the idea to Herman who said it was too early for him but suggested we talk to Jonathan.

Jonathan agreed the research was too early but asked us to give him first refusal if we made any progress. We went back to him in 2017 and that's when we received our first substantial investment and really got going.

It wasn't just money that we got from Jonathan. He asked us if we had heard of Steve Horvath and his epigenetic clock, a biochemical test that can be used to measure age. We hadn't, but we could immediately see its possibilities for our work.

We found out that Wolf Reik's team at the Babraham Institute had developed an epigenetic clock for mice. We wondered if it would be possible to use their mouse clock to see if the approach we were testing in mice would affect ageing, and we were able to embed a researcher in Reik's lab to work on this. Unfortunately, we ended up proving that what we were doing had no relationship with this clock whatsoever.

What did you do when you hit what looked like a dead end? At this point, we needed to look elsewhere and we embarked on a slow and painful pivot. I decided to go to Silicon Valley, hoping to solve all our problems by attracting big money from the Americans.

"Our job was to brainstorm a prize that someone might actually be able to win. All the stars of the longevity world were there."

How did that work out? It didn't. It was mostly pain and a learning curve. But one important thing came out of it. I was invited to join a workshop run by XPRIZE, an organisation that offers millions of dollars to people with industry-changing technologies.

Our job was to brainstorm a prize that someone might actually be able to win. All the stars of the longevity world were there. I was keeping quiet, trying not to make a fool of myself. But the discussion turned to how can we solve ageing if we can't measure it? I put my hand up to say that we already know how to measure it, by using Steve Horvath's clock.

At which point, Steve stood up and said, 'I'm here.' And that's how I met Steve. It was a moment which changed everything. We got on really well and I told him we'd been using mouse clocks to see if we could slow the clock down through mitochondria - and the results were unexpected. He told me that the person I really needed to talk to was back in the UK.

When we met Ken Raj at Public Health England we recognised he was on the very frontier of the science and had developed systems that would help us in our quest to develop drugs.

Around the same time, Jonathan Milner had given a talk at Churchill College and mentioned Shift Bioscience. A Cambridge PhD student, Brendan Swain, was in the audience. A few days later, he turned up on our doorstep asking if he could intern for us as part of his syllabus.

He was the type of person you find around Cambridge who has internal superpowers. He's now our Chief Scientific Officer and it was Brendan who eventually forged a new path, creating single cell clocks which would allow us to do a CRISPR screen for ageing.

"We seek enough funding to get us quickly to the next milestone. Right now we don't need to be a big company to do that. Being big would slow us down."

This sounds like an exciting new direction for the company? It was, but in trying to take it forward we hit another set of problems. This was a really difficult period when I was trying to roll Shift into a new company with new partners. It didn't work out and we had to walk away.

But things have worked out now? During that time, Altos Labs was being set up and attracting a huge amount of funding. Suddenly, there was a lot of interest and we were seen as legitimate and investable. We now have the investment we need to carry on.

We seek enough funding to get us quickly to the next milestone. Right now we don't need to be a big company to do that. Being big would slow us down.

Where are you now? We've come a long way very quickly by embracing machine learning. This powerful tool predicts a safe rejuvenation pathway and over the next 18 to 24 months we will be using our technology to prove out this prediction in human cells.

If our prediction fails, we build that failure into a new predictive model, so every experiment gets us closer to the answer.

And where do you hope to be in, say, five years' time? We expect to be deep in the pre-clinical development phase of a drug for cellular rejuvenation of one or more human organs. We don't know the identity of the minimal set of rejuvenation genes, so we can't say whether the future therapeutic will be one or more small molecules, or an mRNA based drug. What we can say is that we will developing the drug for a specific disease, which offers speed advantages, and this is thanks to a curious finding: the types of interventions that rejuvenate cells, also rescue or reverse disease phenotypes.

"One major benefit is safeguarding the fragile flame of human consciousness in a vast universe..."

What are some of the challenges you have faced? Trying to get people to believe in us. We are quite a young team and that means we’re perceived as a higher risk to most investors, which has led to some frustrating discussions.

What about when things got tough and you had to walk away from a new venture? At first, I didn't listen to the advice I was getting from Jonathan and my dad. But then I realised that these were two people who cared about me and their views deserved more attention. I've learnt that my dad has a good radar about people that I don't always have.

And what about working with your dad...? It's complicated because you have to share Christmas with that individual. If there's conflict at work, it does bleed over. You've almost got to be willing to risk the family relationship. Fortunately, we are both quite rational people and have been able to reason our way out of conflicts. But, yes, it's challenging.

If you do make the breakthrough you are hoping for, it will pose lots of ethical questions. Is that something you think about? Thinking about the new frontiers that open up with this technology serves as a continual source of energy and excitement. It's why lots of people want to get involved.

People are right to consider the risks and unintended consequences, but this has to be balanced against the benefits to society. One major benefit is safeguarding the fragile flame of human consciousness in a vast universe, an imperative frequently highlighted by Elon Musk. If we can live much longer lives in good health, we will be able to settle other habitable planets at a much faster rate and safeguard this flame.

But we still have a responsibility to address the ethical ramifications. Recently, I was asked to review a script for a fledgling film called ‘The Last Generation to Die’, to bring the science up to date. By using characters to explore the arguments about whether this is a good or bad thing to do, the film can help people form a more informed and sophisticated view on the technology.

Finally, what do you do in your spare time, if you have any? I used to fly first-person-view racing drones, tiny aircraft with an onboard camera that can travel at over 100mph. Now my spare time is mostly spent entertaining our two-year old son.

Quick Fire

Optimist or pessimist? Optimist, largely out of necessity.
People or ideas? The people, and increasingly, the very different people required to make a big thing happen.
On time or running late? On time – it’s a precious resource for everyone.
The journey or the destination? The journey – we can’t fully understand the magnitude of the challenge upfront, so we better find a way to love the long haul.
Team player or lone wolf? Team player - ego quickly becomes an obstacle to progress.
Novelty or routine? Routine is the foundation of a long-haul endeavour.
Big picture or fine detail? Scientific discovery requires both.
Lots of irons in the fire or all your eggs in one basket? All in as soon as you can.
Be lucky or make your own luck? Make luck.
Work, work, work or work-life balance? The challenge is to make a ‘work’ success, a ‘home’ success - otherwise you can slowly disappear from your family's universe. I'm trying to solve this by tying work success to fun family trips and by delegating more.

Enterprising Minds has been developed with the help of Bruno Cotta, Executive Director of the Entrepreneurship Centre at the Cambridge Judge Business School.

Photography by StillVision.

The text in this work is licensed under a Creative Commons Attribution 4.0 International License