Reclassifying disease
– the new frontier in medicine

We stand at a major frontier in medicine where we will witness a vital
reclassification of disease based on molecular pathways and biomarkers. This will
give us a much deeper understanding of the underlying complexity of disease and
lead to a restructuring of the pharmaceutical and biotechnology industries so they
can develop a new generation of, not only drugs, but systems-based therapy
solutions to treat this new range of disease states. This was the thrust of the
presentation by Dr Elias Zerhouny, former director of the United States National
Institutes of Health, at the recent BioQatar symposium. Middle East Health reports.

The BioQatar symposium was held in November in Doha with the aim of fostering the growth of a biotechnology industry in Qatar. It was addressed by several eminent speakers, leaders in their respective fields, such as Professor Sir Martin Evans, winner of The Nobel Prize in Medicine in 2007; Professor Sir Christopher Evans Chairman of Merlin, Biosciences, UK, considered one of Europe’s leading entrepreneurs in the biotech industry; and Philippe Froguel, Professor and Chair in Genomic Medicine, Imperial College London.

The symposium was jointly organised by the Qatar Foundation Research Division and Qatar Science & Technology Park. Middle East Health, in attendance at the two-day symposium, focuses on the presentation by Dr Elias Zerhouny, former director of the United States National Institutes of Health.


Explaining the challenges we face in healthcare as we enter the 21st Century, Dr Zerhouny said there has been a major change in the landscape of disease over the past 50 years. In the past, many more people suffered from short-term, acute, often lethal diseases, whereas today, because of progress in medicine, there is a shift from more acute to more chronic conditions, such as diabetes and heart disease that will affect a person for decades.

“This is the major driver for change in healthcare and therefore in science and biotechnology,” he said. He added that in evolved economies there is a set of additional challenges which will need to be tackled.

These are neurodegenerative diseases which are “going to become very important”. In many Developing Countries, he pointed out, we are seeing a “double” burden of diseases as they face both acute and chronic diseases.

Another challenge is the disparity in healthcare even within evolved economies where you find large disparities between economic strata within cities and the outlying regions. The growing number of infectious diseases is a trend is creating another challenge to healthcare. “In the past 20 years we’ve seen 20 new infectious diseases in places where they were not known before,” he said. “We’re also dealing with emerging non-communicable diseases, such as obesity and the impact of mental health.”

New paradigm

Alongside these many challenges, perhaps the most challenging is the transition from an age-old paradigm of curative medicine to a preventive archetype. “We also moving from an old paradigm of medicine to a new one,” Dr Zerhouny explained.

“The old paradigm is one which has been around for 5,000 years and is one in which you wait for the patient to become ill, until they are sick and in pain, before they visit the doctor.

We realise now that if we are going to tackle diseases of the modern age we really are going to have to intervene, sometimes years before the disease strikes. “This is a change from the curative to the pre-emptive paradigm.

“Many diseases can be ameliorated with early intervention – a good example is diabetes. It does not occur overnight and there is a very good chance of reversing it if you catch it early.” He noted that healthcare costs are the number one cause of above economic growth expenditures in evolved economies.

“If you look at the market size of healthcare – in the US it is about US$2.2 trillion, worldwide it is about $4.5 trillion – it will double in the next 10 years, no matter what we do. So in some respects it is a great challenge for policymakers and great opportunity for industry, for biotechnology, to come up with new ideas, to provide solutions that we do not have today.

“If we practice medicine the way we do now, 25 years from now, we will have failed,” he warned. “There is no way that you can sustain the cost and burden of disease with the current methods that we have.

And that means there is a scientific challenge that we have to overcome. This challenge fundamentally relates to complexity. As we have learned more and more about the molecular pathways of disease we are realising that diseases aren’t homogeneous, rather they’re very heterogeneous.

From the standpoint of medical observation the disease may look exactly the same, yet when the molecular pathway is viewed it is very different.

Frontier of medicine

“This is the frontier of medicine, and I think were going to see a very important effort at reclassification of diseases so that we can understand them at a much deeper level mechanistically than we do today.”

Dr Zerhouny explained that this would lead to more effective translation strategies. “There is quite a bit of evidence that we are less and less effective at the industry level, biotechnology and pharmaceutical level, than we should be simply because we have underestimated the complexity in the idea of developing magic bullets for treating cancer or any other disease.

He said that we are beginning to realise that what we are uncovering is a complexity of disease that will require different approaches to science. However, Dr Zerhouni also recognised that there has been an explosion in knowledge recently and gave as an example the exponential growth in the number of genome-wide disease associations since the human genome map was completed in 2003.

“In 2003 and 2004 there were no genome-wide disease association discoveries. However, the technology of sequencing was making huge progress which allowed us to study more diseases. In 2005 there was one discovery.

In 2006 there were three discoveries. In 2007 in the first quarter there were six more and it has grown exponentially from there to a point where we now have more than 150 disease associations. “An association doesn’t mean a causation,” he noted, adding, “So we still have a lot of work to do to unravel the underlying complexity of biology in health and disease.” There is a need for renewed, different and smart approaches in industry.

“One blockbuster product is not going to be sufficient anymore, you are going to have to develop a family of products, because the disease that we think is just one disease may actually be five or 10 diseases.

“So I predict, for example, today we have type 1 and type 2 diabetes, but I think in the future we will have diabetes type 1, 2, 3, 4, 5, 6 etc depending on the biomarkers that we use to sub-classify the type of abnormalities that we have to understand. This will lead to a major shift in market demands and strategies.”

Dr Zerhouny pointed out that we have already embarked on this road and highlighted as an example a gene chip that has been developed for breast cancer that will determine if a patient will respond to chemotherapy or not. “This is an enormous change in the way we treat disease, because now even though it is called breast cancer, we have many subtypes that need to be treated and managed differently based on these biomarkers.

“So we will need to move from a world where there is one drug for one disease to multiple drugs for many diseases that are combined in different ways. That means industry will have to restructure. Biotechnology will play an important role whereby you’ll have to supply the diagnostics classification at the same time as you deliver the drugs, so that you provide not a product but a therapeutic solution – a systems-based approach to therapy.”

ate of upload: 25th January 2009

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