Today, the ability to innovate is an essential factor in survival for individuals, firms
and nations. Although it is true that development cannot and must not be halted, it is not
always easy to adapt to change or manage its consequences within a framework of global
equity that ensures real progress shared by all.
The discoveries of basic research are being transformed every more rapidly into
applications that modify the organization of society and production, as well as individual
patterns of life and thought. But advances in knowledge do not always produce tangible
benefits for everyone.
The path of innovation is more fraught than ever with ethical, economic and political
choices, which call for a closer relationship between researchers and decision-makers.
Such links must also seek to guarantee equal opportunities to all and ensure that an
improvement in the quality of life of a few does not increase inequality at the global
level.
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Inventing New Drugs: From Biological
Questions to Therapeutic Tools
Milan, 3 December 1999
Centro Congressi Cariplo
The search for new drugs, as I have known it for 40 years,
would follow one of three traditional routes. The first two routes – Medicinal
Chemistry and Experimental Pathology – were very much in vogue when I joined the
pharmaceutical industry in 1958.
The third and more modern route is based on Analytical Pharmacology, a new subject which
has been developing in the last 50 years. Its greatest discovery has been that drugs with
highly selective actions at the physiological level turn out to be acting at molecular
sites at which the body’s own molecules interact. The pharmaceutical industry has
been able to use these advances to discover new drugs intelligently.
However, within the last few years a revolution has taken place, driven by extraordinary
advances in genetics, molecular biology and organic chemistry. This revolution has led to
methods of assay of the properties of new molecules thousands of times faster than
traditional bioassay (e.g. HTS, High Throughput Screening, and combinatorial chemistry).
Thus far, no new drugs have come from the new technology. So, it is far too early to know
if the new approach will be as productive let alone more productive than the traditional
strategies, which though slow had a successful track record.
However, as far as I can see the whole, vastly expensive, exercise is predicated on the
supposition the new drugs they are seeking to treat disorders such as cancer, inflammation
and dementia will be similar to those already found to be able to reduce high blood
pressure, heal stomach ulcers and relieve pain. I am concerned that this expectation may
not be fulfilled.
Trying to find drugs to treat disorders of what I call irreversible processes is high on
the agenda of pharmaceutical research today. All of these are processes that cannot be
reversed like an increase in heart rate, so that if they are activated inappropriately
then very damaging, and even lethal, effects can ensue.
The striking feature of all of these processes -- usually gene-driven -- is that large
numbers of hormone-like molecules are involved, known as growth factors or chemokines.
Various biotechnology companies have been very successful at inventing drugs for
individually and selectively blocking the actions of these molecules. However, in every
case, laboratory success ended up in clinical failure. At some point we must ask whether
the model or our way of thinking is wrong.
I think that the pharmaceutical industry has an, as yet, unperceived need to know more
about the control of physiological processes, to learn more about biological complexity.
Searching for new medicines in the years ahead will, I believe, be dependent on basic
academic studies on physiological control processes, on non-linear dynamical systems,
order at the edge of chaos, fractals, hierarchies and trajectories. |
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