The Urgent Debate

Tuesday, 4 November 2014

The urgent debate, in Universities and pharmaceutical companies alike, is in how to get the best out of the knowledge we’ve accumulated; how to translate revelations in our understanding of genetics and disease into actual medical benefit? There’s no shortage of scientists trying to translate our knowledge to practical outcomes; conferences about HIV nowadays gather about 20,000 professionals and 2,000 journalists. Such meetings are not unlike Star Trek conventions; the passion is the same and the heroes are equally revered. Both are ignited by imagination and wonder. But the paramount fact distinguishing scientists from their science fiction counterparts is that they are also driven by an important real cause; to create new medicines.

Some think the key issue in getting to new medicines is to perform experiments in which everything is as close as possible to being physiologically right – using real viruses and doses that would occur naturally. Others, while they agree this is important, also advocate other approaches, such as computer simulations of immune responses. My own view is that it’s actually very hard to know what’s best to do next. It’s relatively easy to do something new; very hard to do something truly important – because, as Einstein put it: ‘Not everything that can be counted counts.’

The enormous complexity of human biology is not just of academic interest. Side-effects of any new drug, for example, usually only becomes apparent during a clinical trial because they are so hard to predict in advance. In fact, it’s been estimated that about 90% of drugs fail to reach the marketplace because of unexpected side-effects – a direct consequence of the complexity and inter-connectedness of human biology. The problem is that even with just 10 genes, the number of possible interactions between them is about 10^18 (a one followed by eighteen zeroes – or a billion billion). And of course we don’t each have 10 genes; we have 25,000. The raw data alone from the sequence of genes in 1000 individuals amounts to over 10^12 bytes. The thought that most life processes don’t work in a straight forward linear way might be a source of despair.

But perhaps there are radically different approaches we could try?

The Manchester Collaborative Centre for Inflammation Research is a new initiative joint between the University of Manchester, AstraZeneca and GSK. The remit: to address inflammatory disease with out-of-the-box thinking. Here, academics and – crucially – two different pharmaceutical companies brainstorm scientific ideas together. This new initiative is young but already there are some success stories. Research between my lab team and AstraZeneca looked at what makes antibodies better or worse at specific types of therapy. We discovered that rituximab, which is commonly used to treat lymphoma and leukaemia, has particular properties that directly help white blood cells called Natural Killer cells kill cancer cells. With colleagues at GSK, we carried out related research which indicated a crucial importance for the size of antibody-based drugs in some potential therapeutic applications.

Making new medicines is obviously not easy. But there are bottlenecks in our understanding that all pharmaceutical companies struggle with. And there are areas ripe for explorative research, that are of undoubted pharmaceutical interest. We need to move beyond targeted collaborations that are more typical between industry and academia. We must seek step-changes in how new medicines can be developed.

To read more about AstraZeneca’s collaboration with the MCCIR, click here

A large part of this article is excerpted from ‘The Compatibility Gene’ by Daniel M. Davis, published by Penguin books in the UK, 2014; and as ‘The Compatibility Gene: How Our Bodies Fight Disease, Attract Others, and Define Our Selves’ by Oxford University Press in the USA, 2014