Translating research on both sides of the Atlantic – interview with Professor Allan Bradley
Professor Allan Bradley, former Director of the Wellcome Sanger Institute and entrepreneur behind Lexicon Pharmaceuticals, Kymab, and T-Therapeutics among others, was invited to speak at the EpiCrossBorders Symposium hosted by the Institute of Genetics and Cancer. EpiCrossBorders is a collaborative PhD programme between Helmholtz Munch and The University of Edinburgh covering a broad range of topics linked to bio and biomedical sciences.
How did you get started in your career?
I started as an undergraduate at the University of Cambridge and ended up in my final year doing genetics. In that period, I was lucky enough to do a research project in the laboratory of Martin Evans. I was asked to isolate cell lines from mouse embryos to confirm the cell lines Martin Evans had previously found. These eventually became known as embryonic stem (ES) cells.
I stayed on in Cambridge and did a PhD, also in Martin’s lab, to explore the developmental potential of ES cells, which I did by learning how to inject them into mouse embryos. I, along with Liz Roberson, a postdoctoral fellow in Martin’s lab, discovered that embryonic stem cells could be transmitted through the germline of mice.
It turned out to be a very important result. Part of my PhD thesis was published as a paper in Nature and it was an important aspect of Martin getting a Nobel Prize for his ES cell work.
Why did you move to the USA?
I was recruited to set up a laboratory at Baylor College of Medicine in Houston, Texas, and I was able to get a lot of good support. I was subsequently appointed as a Howard Hughes Medical Institute Investigator.
I was there for 13 years and it was a very successful period. We established technology which allowed us to explore the function of many genes in different areas of biology as well as developing genome engineering technologies.
In those days, you couldn’t just look up a gene in a browser; you had to clone it and map its structure. Using ES cell technology, we were the first lab to describe mice missing the Trp53 gene – showing it was a tumour supressor, identify the DNA repair role of BRACA and identify a gene called p63 which was critical for the development of skin and appendages like limbs.
What were your first spin-out companies?
I co-founded Lexicon Genetics while at Baylor to commercialise the embryonic stem cell technology we’d developed in the lab. We had the ability to knock out a gene at will which helped us understand what genes do – if you make a mouse missing a gene and it displays a consequence – you can work out what that gene is for.
Lexicon focused on genes of interest to the pharmaceutical industry providing information to allow decisions on which ones to target for drug discovery.
Towards the end of my time in the US, I set up Spectral Genomics. The lab had very good and well-mapped genome libraries. Spectral was set up to conduct high resolution and rapid genome analysis on samples from children born with what appeared to be a genetic defect and allowed rapid and high-resolution genetic diagnosis.
Both companies were led by researchers from the team, providing a different pathway for people in the lab aside from the standard academic journey. Lexicon went public on NASDQ while Spectral was eventually sold.
What brought about your move back to the UK?
I returned to UK in 2000 to become Director of the Wellcome Sanger Institute.
At Sanger my job was to refashion the science done at the institute. It was a genome factory when I arrived – there was great support and infrastructure for sequencing, but little else.
Over a decade, it was converted into an academic centre with huge impact. I recruited 40 young PIs working in mouse, human and pathogen genetics. Sanger was my exclusive focus for 10 years. When I stepped down from the institute, I delivered one thing which I had promised to do – commercialise aspects of the science from Sanger.
Kymab was the first company launched. It was set up to develop therapeutic antibody medicines for humans using engineered mice.
Subsequent to that, PetMedix was launched with a similar plan – but for cats and dogs. That company was acquired last year by Zoetis, which used to be a division of Pfizer.
What are you working on now?
Just before the pandemic, I moved my team from Sanger to the University of Cambridge. The principal reason for that was Sanger had decided it would shut its animal facilities and because my team is obviously dependent on mouse models, it was no longer feasible for me to remain there. In the period up to that move, we had been working on engineering a platform for human T cell receptors.
In 2022, I founded T-Therapeutics to commercialise that activity. I decided I would become CEO of the company and close the lab so I could fully exploit that opportunity. I could bring in an order of magnitude more money than I could ever get from a grant to focus on one project. Last year we raised £48 million to develop novel T cell receptor therapeutics for cancer indications and inflammatory disorders.
The other element that can be done in a company is build a collection of teams; creating something from nothing is a very, very rewarding thing to do. To develop a project in the commercial sector which brings significant benefits to patients is a fantastic thing to contribute to. The lab has gone, but it was the foundation of this opportunity.
In this context, this is the focus for me for the next many years. The company is only 18 months old; we have barely started on the journey. It is well resourced to have a big impact.
What do you attribute your successes to?
Everything I have done is facilitated by having fantastic people around me.
I could not have refashioned Sanger without support. It was very much a team activity. I’ve been lucky to work with and attract amazing colleagues who I trust. I’m very comfortable delegating, fostering an ‘intellectual village’ and steering. With a great team you can achieve a lot.
What is your greatest achievement?
First of all, the people who have trained in the lab. It has been an extraordinary privilege to witness the growth of so many young scientists during their time in the lab and subsequently. I’m also proud of the manner in which I restructured Sanger from a sequencing factory to an academic genome centre. And finally, the companies and the drugs they have produced that will become visible in time. To develop a drug in one’s lifetime with the potential to change people’s lives is a significant contribution but it’s a team effort, not an individual thing.
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