... For the past decade, 'hot new technologies' have promised to revolutionize
the drug discovery process, but these benefits have not materialized. Why
should we therefore believe thot the 'hot new technologies' of the present
will do any better?
I guess whenever something new comes up, a new perspective is gained and
some people (usually those that do not understand the complexity of the
biology and of drug discovery) get totally hyped up. They just think that this is a
new way of doing things that will make everything easier, and that if only we
just follow these new paradigms, we will be hugely successful. Anybody who
has studied the history of drug discovery and other fields of biology and
medicine knows that breakthroughs do happen. The elucidation of the human
genome, for example, will certainly be classified as such a breakthrough.
However, breakthroughs not only make certain new things possible, but also
show where the limits are. Things have to be added to these breakthroughs
to make them really productive.
The main mistake people made when genomics came along was to say the
following: we will know all the genes and will have combinatorial chemistry,
so let us play a 'big numbers' game with all the potential targets (instead
of validated targets) instead of trying to understand everything. This approach
was then expected to result in leads and developmental compounds by
purely empirical methods and thus to increase productivity. That has not
played out as expected. We have increased our raw data numbers by orders
of magnitude: numbers of a typical screening programme for a large
company have risen from ~250,000 data points per year in the early 1990s
to 60-100 million now. However, this has not led to a corresponding increase
in productivity because most hits are meaningless. I therefore think people
have now understood that you need a better understanding of things first,
which is why structural genomics, proteomics, X-ray crystallography and
molecular modelling are now coming to the fore. They are being used to
narrow the number of possibilities to really play this game in a more intellec-
tual and more thoughtful way. ...