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My first 6 months at Axol Bioscience: Here’s 8 things I’ve learnt about human iPSCs

My first 6 months at Axol Bioscience: Here’s 8 things I’ve learnt about human iPSCs


I recently passed the six-month landmark with Axol Bioscience, so it’s probably a good time to stop, take a moment and reflect on my learnings so far.

I find myself asking some key questions: what have I learned about the human iPSC world? Why is it so important? And where could it go, with the right level of support?

With each day bringing new lessons, opportunities and conversations, I’ve (attempted to) condense my thoughts into 8 key reflections.

#1: Firstly, the numbers are huge.

I’ve been reading lots about neurodegenerative diseases; even a cursory glance at disease incidence, clinical trial costs, success / failure rates and demographic trends has revealed so many huge numbers.

Here’s just a snapshot of the scale we’re talking about. In the UK, 34.5 million people know someone who has been diagnosed with a form of dementia- that’s about half the entire population. In the US, about 1 in 9 people (10.7%) age 65 and older have Alzheimer’s disease. A 2022 Parkinson’s Foundation-backed study reveals that nearly 90,000 people are diagnosed with Parkinson’s disease every year in the U.S. This represents a steep 50% increase from the previously estimated rate of 60,000 diagnoses annually. Alzheimer’s disease affects 24 million people worldwide, and dementia over 55 million.

From the world of drug discovery, only 1 in 10 drug candidates successfully pass clinical trial testing and regulatory approval, with a huge 25% misdiagnosis rate for Alzheimer’s. In an analysis of the drug development costs for 98 companies over a decade, the average cost per drug developed and approved by a single-drug company was $350 million. But for companies that approved between eight and 13 drugs over 10 years, the cost per drug went as high as $5.5 billion.
And yet. Effective treatments for Parkinson’s? None. Alzheimer’s? None. Dementia? None.

With all these numbers you can’t help to be reminded about the real and urgent demand to push forward to find new tools to de-risk drug discovery, reduce time, costs and increase success, better human disease models.

Because beneath all these statistics lies real people. People with wives, husbands, children, friends, and colleagues, all making up the society around us. With ageing populations and changes in lifestyle and diet, neurodegenerative diseases are inevitably going to affect us all in some way, whether directly or indirectly. It’s sobering stuff.

Recently, I had the pleasure to speak to Steven Brennan, a Lay Member of Court, Edinburgh Napier University, and Person with Parkinson’s. He told us, in no uncertain terms to ‘Hurry up’. There is currently no cure, but he says that science and ingenuity give him hope.

#2: We need better human disease models.

In part, my PhD was focused on understanding the relevance of a knockout mouse model, for gene therapy trials. So much of bench biology seems to be this way: here’s a model, but what does it tell us about the human condition? Hmm… it’s the classic bench-to-clinic conundrum, the translational gap that we must strive to close. And even now, 25 years after I finished my PhD, the pursuit of well-characterised, relevant models seems ever more pertinent.

Classical neurodegenerative models have added so much to our understand but there are still huge opportunities to improve. Remember, mice don’t get Alzheimer’s. In fact, mice don’t get a lot of things and, to quote Professor Weiner, “mice lie and monkeys exaggerate”. What does better look like? More scalable, more reproducible, more relevant surrogate models to expand our understanding of drug action, behaviour and safety. Where are we going to find these?

In December 2022, with the signing of the FDA Modernization Act 2.0, a clear challenge was put to drug discovery: if you think you can do better, if you think that cell assays or artificial intelligence is the way ahead, let’s explore together. The gauntlet was laid down to technology developers and users alike.
And so to human induced pluripotent stem cells (iPSCs). There is something inherently powerful about human iPSCs. The fact that the cells originate from a blood donation or a skin sample from a real (and generous) person must be important. When I sit in on meetings and see colleagues showing customers electrophysiology results from patient-derived lines vs control lines, with different firing patterns patterns, responding differently to compounds it’s really powerful stuff.

Then when you add in the increasing complexity beyond a single cell type to co- and tri-culture models, 3D organoids, scaffolds, organ-on-chip devices and other complex structures, it all points towards more physiologically relevant models. The need is there and human iPSC- based models look promising.

#3: Cell biology is technically challenging, iPSCs even more.

Confession – I’m more of a molecular biologist than a cell biologist at heart. I can connect more with the digital aspect of PCR reactions and genomics than with the art of administering transcription factors and patient, large- volume pipetting of expensive cell culture media on a Sunday morning.

Seeing my colleagues working in the labs and listening in on meetings, it’s a technically challenge corner of science. The new era of stem cells, iPSCs, emerged in 2006 with the famous Yamanaka paper. 17 years later, I hear my technical colleagues talk about the journey so far, what’s been learnt and the numerous hurdles.

In our service work, it’s been a real eye-opener to see just how much time and effort our team puts into the front end (characterisation of the materials that go into the project) and the back end (characterisation of the end-point and relevance). Quality control can be three quarters of the project. Much of this investment into quality control has its origins in the lab’s real (and sometimes, I hear, painful) experience where they’ve taken in other lines or third-party components that were supposedly ‘quality’ but, in reality, were far from it leading to time-wasting, head scratching and delays for everyone involved.

Axol isn’t alone in promoting ‘outsourcing’ for iPSC studies. We have, like I presume all industries, have competition. But with feelings ranging from disbelief to genuine concern, we read about ‘super-fast’ service jobs for less than the cost of the cell culture media we would buy… but guess what: cheap often means cheap, and it’s a real credit to both the Axol scientists and to our clients who share the value of do it once, do it right. Many new clients start by giving us a pilot project to work with. Makes perfect sense, test us out, test how the whole outsourcing thing works. It’s a great opportunity for us to demonstrated our attention-to-detail. We know from our sales numbers the very high rate of follow on work, so we will stick with prioritising quality…

#4: Stem cells are the Intel inside, the flour to make the bread…

What do Big Pharma want of stem cells? Reproducible models, consistency, relevancy, all at- scale?

Microfluidics, MPS, organ-on-a-chip; whatever the flavour and terminology you choose, these platforms are the basis for high-quality, physiologically relevant models. But to fuel them at scale, you need high quality, consistent iPSCs.

Whatever analogy you want to pick, whether that’s Intel inside or that we’re making the flour to make the bread, if we’re going to reach scale, it’s through productive partnerships between iPSC suppliers , platform providers and users. Our connection to Netri and many other platform suppliers is important to us and, ultimately, the route to realising the potential of iPSC-based models.

#5: We’re going to need to collaborate – a lot.

How are we going to see bigger utilisation of human iPSC models? Number one on this list must be collaboration. If we want to fulfil the full potential of this industry, we’ll need a high level of transparency and openness, with collaboration between everyone in the chain. From scientists (like those at the Crick Institute who developed new iPSC methodologies) to suppliers of excellent reagents & media, to IPSC suppliers, platform providers, those in charge of shipping and logistics and the users, full end-to-end discussion and communication is absolutely pivotal.

In my six months at Axol so far, I’ve seen the importance of shared values numerous times. We value collaboration and transparency, and we enjoy working with others who share our values.

We also need to share skills and experience to maximize potential. We have a great culture of skill-sharing with our own staff supporting more junior scientists with their developmental plans, but we also support customers and other scientists with the complexities of iPSC technology. To that end, we run ‘tech help’ clinics and look forward to inviting scientists to our labs to learn co-culture techniques; we are very aware that sharing our experience is key to both our success and the success of the industry as a whole.

#6: We can use stem cells to reflect a wider population in drug discovery.

I’ve written about this elsewhere, but drug discovery does go anywhere near reflecting gender diversity and ethnic diversity. It’s a poor state of affairs.

What if we could access large banks of human iPSCs from diverse populations and use them at scale for drug discovery and patient stratification? That’s an idea that greatly excites me. In the context of patient stratification, the argument is that clinical trials can fail because they don’t have the right people in them. But what if you could take 100 sporadic Alzheimer’s cases, plus another 100 control cases, and provide cohort-scale electrophysiology response analysis to drug treatments? What if you screen drugs against a large-scale screen using iPSC-derived cardiomyocytes from diverse ethnic populations or a more representative gender mix, wouldn’t that be powerful?

#7: Outsourcing project work is all about trust.

What does it mean to outsource scientific work to a 3rd party service company?

That’s what our customers do when they make the decision to trust Axol. When speaking to potential clients about axoServicesTM, I make a point to ask them: why are you thinking about outsourcing work?

There is a wide range of answers – some companies are completely virtual (they don’t have any labs), some are just too busy and need support. Others either do not have the cell culture facilities or the staffing expertise to take on the challenge confidently. Most just want it done once, done quickly and done well, and they trust Axol to deliver that.

Others recognise the technical complexity and the skill of our staff. I heard of a customer recently saying that they recognise the project was going to be very technically ambitious but, if anyone was going to get it to work, it was going to be us.

In all honesty, it’s quite humbling. Our customers are scientists, doing important research to develop drugs and medicines, and they are looking to put faith in our scientists to support their endeavours. Due to the confidentiality that surrounds much of the service work we do, we often don’t even know what the compounds are, or what they’re being used for, or sometimes even the purpose of the project! But it’s exciting to think that we are contributing towards a treatment that, perhaps, I might need myself in the future.

It’s also nice to see the number of repeat projects that we do, because this speaks directly to customer satisfaction. It’s enjoyable to sit in meetings where you can clearly see the Axol scientists and the client scientists building strong relationships, sharing information and openly discussing how best to support the goal.

#8: And lastly, people.

Work is all about people. The pleasure of any job is about people the people you interact with.

Who you work with is not an accident; teams and companies are formed through deliberate effort. Axol is the first place I’ve ever worked at where values & behaviours are truly part of the foundations of the company, and used without cliché. The six foundational pillars at Axol form the bedrock of what we do and how we act. They drive, and demand, collaboration and performance, encouraging self-reflection and continual improvement in an environment that is positive and energizing.

And this is the exactly the environment required to push forward the utility of iPSCs in drug discovery. So, after six months, I can safely say that I’m very optimistic and excited about what lies ahead, as we continue to build better human disease models.

Duncan Borthwick PhD is Head of Sales and Marketing at Axol Bioscience


Watch Duncan speak about his learnings here.

Axol Team Leader presents at global ALS conference
Upcoming Webinar: Using the power of iPSCs for patient stratification