Speech (speaking notes) opening Pharmaceutical Sciences World Congress
• More than a century ago, in 1889 to be exact, Josef von Mering and Oscar Minkowski wanted to gain greater insight into the workings of the digestive tract. So they surgically removed the pancreas of a dog. The day following the operation and experiment, an employee pointed out to them that the dog’s urine attracted a large number of flies, noticeably more than the urine of the other animals in the lab. Curious as to why this should be, they took a sample of the urine and analysed it. They found that it contained glucose. As you might already suspect, this eventually led to the discovery of the substance used to control diabetes.
• Von Mering and Minkowski understood that – unintentionally - they had brought on the development of diabetes in the dog by removing his pancreas. They theorised that the removed pancreas produced a substance that plays a role in the sugar metabolism. They were later able to prove the connection and this launched the search for the mysterious substance. Years later, in 1923, Banting and MacLeod would share the Nobel Prize for their discovery of insulin.
• This example shows that research can lead to ‘accidental’ discoveries, provided the researchers know how to interpret an unexpected outcome accurately. This is: “looking for a needle in the haystack and finding the farmer’s daughter”.
• Traditional pharmaceutical research can be considered as a systematic search for such luck. To discover new medicines, millions of substances are tested for their effects and properties. A limited number of them prove to be very promising in the lab and are therefore further researched using lab animals. A small number of these substances prove to be effective and are then tested in human trials. During this phase, a great many of the substances fail the set criteria and finally a single safe and effective medicine remains. Paradoxically, this often turns out to be a medicine for something other than the purpose for which the research was originally started - which of course brings us to the farmer's daughter.
• In many cases, only then does research begin that seeks to establish why exactly a particular medicine works; and researchers are not always successful in finding the answer. We still do not know, for example, why lithium is often effective in treating bipolar disorders.
• In view of this serendipity-driven research, it is not at all surprising that medical research over the last century and a half has progressed at such a slow pace. The benefits won for human health during this same period are much more the result of better hygiene (sewerage systems and clean drinking water) than new medicines.
• Nixons ‘war on cancer’ in the 1970s did not lead to the eradication of cancer. It did not even result in accelerating improvements in treatments for cancer or to a decrease in mortality.
• Turning the process around would be a much more rational approach: instead of first looking for a medicine and then researching why it works, we should first study how the mechanism of a disease works, and then develop a medicine to intervene in this mechanism.
• With a few of the most effective treatments, this is the approach that was taken: for example with antibacterial vaccines and in surgery.
• Until recently, however, for most diseases it was not possible to realise such a turnaround in the development process (first understanding and then intervening). Our basic biological knowledge was simply insufficient to accomplish this.
• But this is now changing rapidly as a result of two fundamental developments from the first half and the middle of the twentieth century: physics (Bohr and others) and unravelling the structure of DNA (Watson and Crick).
• Physics has led to ICT, imaging technology and now also construction methods at the nano level. This has made it possible, among other things, to gain a picture of what exactly happens both in diseased people and in healthy people. The unravelling of DNA structure produced the impetus for the rapid development of molecular biology. Beginning in the early nineteen eighties, following the discovering of PCR, molecular biology has developed at an increasing pace with ever-faster sequencing methods: through genomics, proteomics and all the other "omicses". This acceleration in development is further fed by ICT, imaging and nano methods.
• The molecular-biology revolution makes it possible to analyse how life works at the molecular level and therefore how diseases work. This in turn makes it possible to design drugs and to make them do precisely what is needed. The time to develop new drugs is much shorter now. The year of 1998 when my best friends received a Nobel prize, was the turnaround.
• For the first time, we no longer have to look for a needle in a haystack in order to find the farmer's daughter in the end: we can now, in principle, clone the farmer's daughter directly. But the traditional process has also benefited from the molecular biology revolution: a much higher degree of precision can now be achieved in diagnostics, making it possible to determine more accurately which medicine will work for which person; the testing of substances for effectiveness can be completed faster thanks to the labs on a chip; and we can now analyse why something works much faster.
• Many people have correctly realised that the fact that there are now so many fundamental new insights has created a backlog in the application of these insights. This is a gap between basic biologics and the clinical application of this knowledge. That is why large investments are being made in bridging this gap through translational research.
• The furthest along are the developments in infectious diseases, cancer, cardiovascular diseases and neuro-degenerative diseases such as Alzheimer's. Worldwide, increasing sums of money are being invested in translational research in these fields.
• Our country occupies an excellent position to play an important role in this development. Biomedical research here is highly developed: 30 per cent of all public research and 50 per cent of university research is biomedical research. And even though we are a relatively small country, our research ranks among the best in the world. Our country has more than eight university medical centres that work closely together.
• Forty per cent of our international scientific publications (public and private) comes from the biomedical sector. With an average impact factor of 1.4, we are among the top three in the world.
• It is therefore a good thing that the previous government put every effort into strengthening translational research in this country. Additional hundreds of millions of euros were invested in the Top Pharma institute, the Centre for Translational and Molecular medicine and an advanced network of disease-related bio-banks of the university medical centres. In the past we had given a boost to both fundamental and applied genomics research through the National Genomics Initiative.
• Such initiatives must continue. But we must not forget one essential thing here: in order to conduct translational research, there must be something to translate. That is why more money must be invested in basic biological and medical research. In my view, that is the big challenge we face: finding a balance between the two. Perhaps this means that we should take another careful look at the priorities set within medical research. Maybe we should spend less money on attempts to discover new medicines and therapies (the proverbial looking for the ‘needle in the haystack’). And devote a larger part of the budget to gaining the basic knowledge needed to design new medicines and therapies (cloning the farmer's daughter directly).
• I am convinced that, whatever we do, we should especially give the best researchers plenty of freedom to do what they think is the most sensible. There should therefore not be too much top down planning and management from above. Instead, we should ensure that the money gets to the best people. And give considerable attention to young talent.
• Another major challenge in front of us is the education of our doctors and health workers. Within a number of years, they will need to have entirely different skills from the ones they now possess. They will have to know more about physics, chemistry and, of course, molecular biology. And we will not have enough of them. I am glad to know that the Medical Scientific Council of the Royal Netherlands Academy of Arts and Sciences called for attention to be given to this subject in a recent recommendation they issued. For my part, I will bring the same point to the attention of universities.
• I am proud of the fact that our country may host the FIP, the international umbrella organisation for pharmacists, during such exciting times. The world needs better medical drugs, and it is our duty to discover and develop them. I am greatly honoured to have been given the opportunity to open this conference. I welcome you in our great country. Amsterdam, as I am sure you know, is a great city, and you may have the time to discover that the rest of the country is equally beautiful and interesting.
• It is therefore my great pleasure to open the Pharmaceutical Sciences World Congress. The programme is very interesting. I wish you all the greatest success in the days to come.