Genomics, proteomics a nd future drug products

Modern drug discovery techniques are set to have a big effect on the nature of drug products. As Trevor Jones explains to Sarah Houlton, this will also have an impact on the way products are made and delivered to the patient

Pharmaceutical research is changing dramatically with the growth in modern reserch techniques. The ABPI's director general Trevor Jones has no doubt of the potential for innovative products that this has. 'Genomics, proteomics and genetics will give us the ability to interrupt disease processes,' he explains.

'Only five years ago, we had no real understanding of the genome of the human, let alone of the invasive bacteria and viruses that cause diseases. The massive advances in genomics that have taken place in the past five years mean we now have a rough map of the human genome, and very full maps of most of the invasive resistant organisms. However, they are only maps, and they do not tell us which parts of the map are responsible for diseases.'

Functional genomics are being developed so we can establish the precise function of these genes, and which genes cause diseases in a polygenetic way. This will lead to our understanding of basic causes of problems within the body increasing dramatically. 'We could alter the genetic code of bacteria or viruses that will make them more easy to destroy precisely, or prevent them becoming resistant to drugs,' he says.

transforming the industry

The emerging knowledge has the potential to transform the pharmaceutical industry, he says. 'Previously, we would say, "Let's take an animal model of a disease, throw chemicals at it and, if we get an effect, modify the chemicals to ensure they are stable, absorbed and metabolised." But we haven't really known why they have worked. The drugs have benefited patients with disease and debilitating illness, but we haven't changed the underlying situation — we don't cure much apart from infections! We don't cure arthritis, anxiety, depression, schizophrenia, Parkinson's, epilepsy, and so on: we simply treat them.'

He foresees that, in the not too distant future, we shall understand the way in which the genes cause effects in the body, how they make organs such as the brain or the kidney, and how they go wrong. This will allow us to interrupt genetic processes in a way that will dramatically change them.

This is not going to happen in five years, he warns. Knowledge of function will increase over the next 5;10 years, and this will lead an increasing ability to intervene in disease process.

'The science of proteomics is being developed in parallel to genomics,' Jones says. Proteomics is the science of how proteins are formed, and how they work. The results of this research, he thinks, are going to give us a much shorter term understanding of how proteins can be altered in order to change or correct activity in the body. 'Changing a gene is brave because of the possibility of causing a range of other side-effects, but proteins are one step down the chain so altering them is less drastic.'

But will the resulting drugs be chemicals, or will they be biologicals? Will the industry find small, or relatively small, chemicals that will interrupt protein processes, or will the products of the future use an element of the protein itself? Will the chemicals be fragile with a large molecular weight rather than smaller, more robust compounds?

'Most current drugs are chemicals that are fairly robust, despite some of the instability that is seen,' he says. 'I think that future drug products will be a mixture of the two. I don't see the day over the next 10 years where we will see a massive swing towards proteins rather than chemicals, and I think it's fair to say that in 2010 the tablet will still be the major form of drug therapy. But we will see more and more protein-derived drugs.'

The growing importance of these protein drugs will necessitate a different approach to manufacturing. 'You simply cannot thrash around an unstable large protein,' says Jones. 'You have to treat it with great care — not just in terms of the chemical environment in which it's made, but also the stirrers, the suspension technology and so on, will require a totally different type of approach to a traditional chemical reaction.

'I think the message is that we cannot expect to see massive change overnight, but unless the industry is preparing itself for this kind of technology we will be caught very short. If you imagine the next activity down the line, tissue engineering, this is even more acute.'

The transplantation of organs like kidneys and hearts is now considered to be routine, yet when these procedures were first performed, they were regarded as playing with nature. Developments in stem cell research will mean we will be able to take cells and let them generate in the adult what they would have developed in the foetus. 'Taking a stem cell and putting it into the brain of a person after a stroke, for example, should give the patient the capability to regrow the neurons and astrocytes that they've lost in their brain from a source that was growing them for the purpose of a brain in the first place.'

producing tissues

Alongside stem cell transplant work, numerous groups are working on whether it is possible to produce tissues such as skin, or even hair. Creating tissues for treating burns or removing scars is a prelude to growing organs. 'This whole project is in limbo at the moment while we work out whether we are transferring prions and other infectious organisms from xenotransplants,' says Jones.

Grown tissues will not have the same sort of problems with cross-species infection transfer as they are autologous to humans. 'In the longer term, in maybe 10 or 15 years, we should be able to grow organs,' he adds. 'And if you imagine, then, factories growing rafts of cells to replace, initially, damage from trauma or burns, moving to factories producing transplant organs, where does that take us? Are companies sitting down and looking at a strategy for, say, 10 years into the future, and saying, "How do we prepare ourselves for that?" Are companies looking sufficiently far ahead to make strategies to anticipate entering this sort of market, or will they slowly find, as their products come off patent, that technology's moved away? This is going to prove a big challenge as, frankly, most companies cannot envisage a programme more than five years ahead, if that.'

The great changes we are seeing in the macro nature of the industry and its global activity, and especially in the technologies involved, are beginning to have a knock-on effect on companies in terms of finding the right employees. 'In many parts of the world, there has been a swing against young people studying science,' Jones says, 'but there are still adequate numbers coming through at this time. But are we producing the kind of graduates and postgraduates that have the preparation, rather than just the training, for this type of changing world?'

integrated skill set

He explains that, particularly in terms of genomics, proteomics and genetics, the UK traditionally has not been producing graduates with these skills, whereas they have in the US. 'We produce very good organic chemists and very good pharmacologists,' he says, 'but producing scientists with the integrated skill set needed by today's changing industry is a big challenge. And I don't know whether in Europe we yet have a university system that allows us to develop that sort of multiskilled graduate or postgraduate.'

He adds that discussions are ongoing with university vice-chancellors on how future needs can be addressed. 'But this is for tomorrow: the training needs of today are still there. We have very well-developed training programmes for chemical plant operators, but as these new technologies come through, we just don't have the necessary training around.

'One or two groups that have expertise in biotechnology like the one at University College. But chemical engineering has to move towards biochemical engineering in a bigger way if this nation, or France or Germany or Scandinavia, is going to be a principal source of some of these new products. Having the willingness to do it, the finance to do it and the environment to do it are all very well, but unless there are the skills to do it, it will be difficult to see how we can succeed.'

He believes the industry in the US is much better prepared to face the future. 'The clusters that created biotech and related activities around San Francisco on the west coast and Cambridge, MA on the east, have also created the background resource that is needed. This means they have trained technicians, not just graduate researchers.'

With the revolution we are seeing in genetics and genomics and proteomics, there is great excitement in terms of what will be possible over the next 10 to 15 years. But we need to be able to capitalise on the potential to the full, and this will have to involve a change in distribution methods.

impact on delivery

'The e-revolution is already impacting on discovery, in terms of algorithms for genetic and genomic research,' Jones explains. 'It has been there in the infrastructure of the industry for some time in terms of warehousing and planning, but it's going to impact more on delivery in future. Every day, my newspapers are delivered, the milkman calls, I can get the supermarket to deliver in an hour or two, and Amazon.com can deliver books overnight. Why shouldn't my medicines be delivered that way? Why do I have to go to a pharmacy?'

He foresees an increase in the use of diagnostic chips that patients can use at home, allowing them to interface with a cyber-doctor. A good example would be a constant monitor of blood glucose levels in diabetic patients, linked with feedback to regulate the dose. It will start with straightforward areas, and move on to much more erudite monitors of body function.

If the industry does indeed move this way, then the way in which the product gets distributed will, out of necessity, have to change. So, instead of the industry selling its products through wholesalers to pharmacists, it will have to think of the logistics of delivering products straight to the consumer. 'The book industry's done it, the milk industry has been doing it for years, and I think there are all manner of logistical things we could do right now. It doesn't take a genius to see that a repeat prescription need not require you to keep going back to the pharmacist.

'There are social concerns about getting people out of their homes and the potential for being given other advice, but I think this poses a big challenge for the future as well. The classical industry finishes at the point of distributing products to the wholesalers, and I think this will change very dramatically with e-trade.