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6 June, 2019 - 09:50 By Tony Quested

Cambridge scientists drive drug discovery revolution

Jonathan Milner Meltwind

Life science entrepreneur Dr Jonathan Milner has praised Cambridge for taking a lead in the reduction of animal testing in drug discovery.

Dr Milner, founder of world leader Abcam, applauds the decisions by Sanger and Cambridge University to reduce animal experimentation wherever possible and says a cohort of Cambridge companies have also pioneered cellular alternatives. Many of them, including Elpis, are in his rapidly growing Meltwind investment portfolio.

Elpis’ breakthrough technology combines synthetic and stem cell biology, enabling a new generation of cell therapies, providing the best human cells for research and drug discovery, and allowing the control of advanced synthetic biology circuits for biomanufacturing.

In life science globally, animals are used to develop medical treatments, determine the toxicity of medications, check the safety of products destined for human use and other biomedical, commercial, and health care uses. 

Research on living animals has been practiced since at least 500 BC. But Dr Milner says the mood and the reality are changing and that Cambridge’s pre-eminence in stem cell technology will be a driving force for a revolution in the way new drugs are tested in future.

Dr Milner told me: “I have always said we should try to minimise use of animals for drug experimentation as much as possible. We couldn’t eliminate the use of mice in pre-clinical testing in the past because the alternative technology didn’t exist; but it does now and I am really excited about the number of Cambridge companies that have come up with alternatives – companies such as Elpis, Horizon Discovery, Axol Bioscience, Healx and many more. The new models invented by these businesses has reduced the requirement for animal testing.”

One perceived obstacle to eliminating animal experimentation has been the demand by the US drug gatekeeper FDA that new drugs must be tested in animals before tried in humans.

Most drugs that undergo preclinical (animal) testing never even make it to human testing and review by the FDA. 

The drugs that do must undergo the agency’s rigorous evaluation process, which scrutinises everything about the drug – from the design of clinical trials to the severity of side effects to the conditions under which the drug is manufactured. But the FDA has supported efforts to reduce animal testing. FDA also says it has R & D efforts underway to reduce the need for animal testing and to work towards its replacement.

Two major alternatives to in vivo animal testing are in vitro cell culture techniques and in silico computer simulation – using a computer mouse rather than the animal variety – and Cambridge is at the forefront in both.

As well as ethical objections about using animals in experimentation, some studies have shown that animal studies can predict toxicity correctly in only 70 per cent of cases. So time and resource-pressed researchers are often pushing down a blind alley.

Dr Milner says: “Companies are doing a lot of hopeful testing on mice but human beings are not mice so the aim has to be to use alternative techniques to get new drugs into human trials as swiftly and safely as possible.

“I am particularly excited about Healx in Cambridge which has developed an AI platform to repurpose existing drugs to treat rare diseases. Their in silico model is using drugs that have already been developed and are already out there.

“The world is moving away from animal experimentation. Sanger and the University of Cambridge are absolutely right in exploring cellular alternatives to animal testing because you can get misleading results.”

One of the most significant advancements in stem cell research of the past decade has been the development of organoid systems. Organoids are three-dimensional cell cultures that incorporate some of the key features of the represented organ. 

These in vitro culture systems contain a self-renewing stem cell population which differentiates into multiple, organ-specific cell types that exhibit spatial organisation similar to the corresponding organ and are capable of recapitulating some functions of that organ providing a highly physiologically relevant system.

This is another powerful weapon in the armoury for life science companies committed to reducing the need for animal experimentation; scientists can pick up potential toxicity issues without reaching for the nearest rodent.

“I am forever the optimist but I genuinely believe we are moving in the right direction in terms of finding alternatives to animal testing,” says Dr Milner. 

“As they say, Rome wasn’t built in a day but the progress Cambridge is making is highly encouraging. There has never been such a good time to be working in life sciences in the Cambridge cluster generally. There is a massive opportunity for Cambridge to pioneer a lot more innovation.

“We are starting to attract a lot of talent – especially from the US. Cambridge always had super science and technology but often lacked the knack of commercialising it - that has always been a problem. But not any longer.

“That is further evidenced by the increasingly large amounts of investment now being injected into the cluster from UK and European sources and also from the US and Asia. Cambridge’s brand is bringing us access to this new finance; our star is rising. 

“There are world-class companies wherever one looks along the corridor – in north Cambridge with the Science Park, to the biomedical research campus at the Addenbrooke’s site – and extending to Babraham, Granta Park and Chesterford Research Park.

“Encouragingly, there is a lot of space at these locations for further expansion of our life science capability.

“And before anyone raises the question of a lack of housing, the solution would appear to be pretty straightforward – build more houses. Marshall’s decision to relocate the aviation and aerospace and defence business will help tremendously in that regard.”

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