Monday, July 23, 2012

Worshipping the funding mountain

It was announced last week that an anonymous benefactor is to donate £20 million to be split between the University of Southampton and Cancer Research UK (CRUK), which will conduct its work in the new Francis Crick Institute, currently under construction in London. This money is going to be used primarily in the advancement of cancer immunotherapies, a branch of cancer treatments in which the patient's immune system is harnessed to fight cancerous cells. I wrote briefly about the use of the immune system in the fight against cancer in a post a few months ago, but since this field is now in the spotlight (in the UK, at least!) I thought I'd give you a short update on the kind of work that's being done and why £20 million is significant.

Targeting the traitors

Cancer, as you're probably aware, is the condition that arises when an individual cell or subpopulation of cells accumulates sufficient mutations in the genes that control cell division as to become rogue entities within the body - replicating indiscriminately and dangerously. As a species we are highly susceptible to cancer because we just live so damn long and generally don't die from the things that kill most other species (hunger, illness, predators etc.), and finding effective treatments remains one of the major goals of medical research. If  a cancer forms a tumour and stays like that then treatment is simple surgery to remove it and is highly effective. The killer scenarios are either when tumourous cells metastasise and circulate in the body as individual cells, establishing too many new tumours to be removed; or when the original cell is one that does not form a tumour, as is the case for leukaemia or lymphoma. In these cases, chemotherapy or radiotherapy is commonly used to attack the cancerous cells but often ineffectually and almost always with nasty side-effects. The idea behind cancer immunotherapy is to nudge the immune system into attacking these cancerous cells, thereby clearing the disease with minimal damage to other tissues. 

Getting the immune system to target these cells, however, is far from easy. The organisation of the immune system is designed to prevent it from attacking the body's own cells (more about this here) and any cell that steps out of line is quickly and harshly dealt with! Many immunotherapies currently in development involve the extraction of T cells from within the parent tumour, as these are more likely to have specificity for molecules on the surface of the cancer cells (a reminder of how T cells target antigen can be found: here) and so are more able to kill them in a specific manner. The extracted cells are then expanded (i.e. forced to divide many times to boost their number) and sorted to purify just the killer T cells that are normally responsible for killing infected cells. These are then injected back into the patient along with immune-boosting drugs to try and promote a maximal response, and then we wait for the cells to work their magic! 

Many such approaches have run into trouble because the reintroduced cells are immediately shot down by the military police of the immune system: regulatory T cells (Tregs). This isn't exactly surprising because from the body's perspective these cells have appeared out of nowhere and are suddenly attacking what seem to be perfectly normal host cells! They don't stand much chance against the formidable forces of the immune system's self-regulatory law-enforcement. To get around this, much current work is focussed on either hiding the boosted cells from Tregs or on calming down the Tregs within the body in order to let the anti-cancer T cells do their thing! Ironically, this is almost the exact opposite goal from much of the work being done in the treatment of hypersensitivity and autoimmunity, where researchers want to make Tregs aware of the damage being done by mis-targeted T and B cells. 

The field of cancer immunotherapy is still in its infancy and yet has already offered therapies with huge potential - indeed many people (myself included) believe that immunotherapy is ultimately the only way in which cancer will ever truly be conquered. The organisation of the immune system has only really been broadly understood in the last 20 years or so, and many of the finer points are still under investigation. There are still myriad potential avenues for research into fighting cancer using the immune system and the next 50 years or so are going to be extremely exciting not only to those in the field, but increasingly to the general public as there treatments become more widely used and high-profile.

The military budget

Despite the promise shown by the field, researchers have found it increasingly difficult to come by funding in recent years. This is perhaps unsurprising given the stalling of the global economy and the general reduction in funding across most of science. To some extent, medical sciences have been partially protected from the funding drought because people are often more willing to fund things that might save their lives than work that is similarly fascinating and important but less immediately practical. Nonetheless, many promising therapies have fallen by the wayside because of lack of funding. Indeed, CRUK has been having such a hard time securing money that it has had to establish a £25 million investment fund in order to bring in revenue by more conventional commercial means.

The £20 million pledged by this generous donor is not enormous in terms of the economy of science or  the UK, but it is how it is being distributed that will hopefully make a big difference in the funding of this kind of work. The establishment of a collaborative network between CRUK and the University of Southampton will help to focus resources and to solidify the position of the UK as a leader in the study of immunology. This should hopefully lead to more efficient research as collaboration becomes smoother and resources easier to come by at a reasonable price. Spending £20 million now in the right way should bring returns equivalent to spending a lot more less efficiently. 

One way in which money can be used wisely is in trying to bridge what is known as the 'valley of death', which is the gap between basic science and pharmaceutical development. So many potential therapies are cast into the valley of death because commercial developers are unwilling to put the money in to make them economically viable in the long term. Funding such therapies to get them over the void will then encourage big pharma to take them on and develop them into refined treatments, which will then justify the expenditure on the basic science through the increased happiness and well-being of patients. In practice, this means funding early stage clinical trials (which are often prohibitively expensive) to establish the validity of an approach, thus giving pharma companies greater assurances that it is worth investing in.

Hopefully the kind donation from this anonymous philanthropist will help to advance the field and bring in more resources to move science from the bench to the clinic. Nevertheless, it is ultimately a small sum of money that can only do so much. I very much hope that in the storm of economic instability, politicians and policy-makers do not lose sight of the long-term goals of science and do not make decisions that might close off fascinating and potentially life-saving avenues of research.


  1. If your side are going to actually cure cancer one day, then my side better get our bloody act together in colonising space or the Earth is going to get very crowded, very soon.

    Though the internet just told me that cardiovascular stuff kills more people in the developed world through heart and stroke related events than cancer does. I guess when the machinery wears out it just one day stops working no matter how much we conquer the internal (and external) pathogens. Though what was possible with this woman suggests we might one day not face the wearing out of the machinery problem either.

    I guess at that point it will simply be how long a brain can last that dictates life-spans. In which case I imagine we'll all go mad long before we actually die.

    1. Actually, I think I'm being a bit ambitious claiming that "my side" will colonise space. The colonisation of space would (will?) be done by engineers and "my side" will probably just end up watching and giving enthusiastic encouragement (along with everyone else).