How to make a science out of drug discovery
Canada really needs a national drug development niche
Last Updated: Friday, May 30, 2008 | 9:04 AM ET Comments3Recommend2
Stephen Strauss CBC News
Apparently one of the greatest mysteries in science is how to make a
science out of drug discovery.
Let me refer you off the top to Aled Edwards and his blistering
critique of today's drug development procedures: "What is crippling
the development of new medicines is the fact that as we discover
potential new medicines and we start to test them in people, 90 per
cent fail.
"And the 90 per cent fail not because scientists are dumb or they
make mistakes," Edwards, who is head of collaboration between the
University of Toronto, the University of Oxford, and Sweden's
Karolinska Institute called the Structural Genomics Consortium,
recently told me. "They fail because we have a very poor
understanding of human physiology or pharmacology. We just don't
know. You could put 82 eggheads in a room, each with eight Nobel
Prizes each, and give them 10 medicines and say 'which one is going
to work in a person' - and none would be able to predict."
Ouch — but the blistering continues.
"The pharmaceutical industry is less productive every year and has
been for the last three decades," he says. "People make chairs more
productively, hamburgers more productively, cars more productively,
everything else in the world except medicines.
"And it's not a problem with the industry and the structure of
industry and the structure of biotechnology or academia. It's that we
don't understand human disease, and until we get that done, we ain't
gonna make medicines better."
'People make chairs more productively, hamburgers more productively,
cars more productively, everything else in the world except
medicines.'
— Aled EdwardsThis is not just one basic scientist's reveling in
hyperbole.
In 2004, the U.S. Food and Drug Administration dropped a bomb on the
pharmaceutical world in a report entitled Innovation or Stagnation.
It suggested that while U.S. biomedical research funding had gone to
$94 billion in 2003 from $37 billion US in 1994 (a 57 per cent
increase when inflation was taken into account), a new drug entering
early stage clinical trials had only an 8 per cent chance of reaching
market.
This was down from 14 per cent about 15 years before. The year 2004
represented a 20-year low in the numbers of new molecular therapies -
truly new drugs reaching market. Failure rates during final-stage
clinical trials were as high as 50 per cent, up from 20 per cent a
decade before.
All this is within the context of the fact that the cost of getting a
drug to market is somewhere between $800 million US and $1.7 billion.
The report pointed out if you could weed out 10 per cent of likely
failures before they enter clinical trials it would save companies
$100 million per drug.
What to do to make the system more rational?
Well, Edwards and his Swedish and English collaborators are studying
the shapes of the body's proteins and then making their results
freely available on the internet. It turns out the shape of proteins
is vital knowledge when trying to develop a drug to block the actions
of some disease causing body molecule. And their view is that this is
knowledge that all companies need to have for free as a precursor to
drug development.
Their analysis suggests they can reduce early drug discovery time by
as much as 18 months and do the work at anywhere from a third to an
eighth of the price of traditional academic and industrial research.
I like the sound of that, but also fear that things will still get
stuck later on. And indeed, the U.S. Food and Drug Administration
(FDA), when it looked at the problem, came up with at least six
sticking points in the U.S. for rational and efficient drug
development.
To my mind, the biggest problem is that even though drug companies
have invested billions in trying to make their process more
efficient, they are not in the business of unplugging the entire
system. Au contraire. If they come up with, say, a cellular assay
that lets them choose potential drug winners from losers earlier, it
is actually in their financial interest to keep this information from
potential competitors. They want their rivals to be inefficient.
Perhaps equally important, they aren't in the "selling-a-more-
efficient-process" business. They're drug companies, after all. They
want a $5 billion-a-year "treatment" for male impotence and not a
bundle of assays or imaging technology to make the whole process
better for everyone.
Which leads me in a rather roundabout way to a national pitch.
Canada as a country is great at medical research - per capita we're
right at the top in the world - but we ain't so great at turning
those drugs into products. Sure, there was insulin and the three-drug
cocktail for AIDS, but the reality is that we are a branch-plant
economy for foreign drug companies. And this is extremely worrying in
an age when the best future jobs are seen to be in places like
biomedicine and not, um, well, car plants in Ontario or clothes-
manufacturing plants in Quebec.
A few places in this country - Montreal, the new MaRS facilities in
Toronto, Vancouver, Alberta, Nova Scotia, Saskatchewan and even
little Prince Edward Island - understand this and have tried to
create what are called bioclusters. These are centres of excellence
that integrate research and industry. But the truth is there are
dozens and dozens and dozens of these bioclusters in every developed
and developing country around the world. If we were a relentlessly
entrepreneurial country we might forge ahead, but well, again, we
ain't.
So what I think Canada really needs is a national drug development
niche.
OK, maybe the earliest of the drug development stuff is best left to
Open Access, a la Edwards's model, but we could make it our national
calling to nourish companies that specifically try to improve the
rational discovery process down the pipeline: companies that try to
come up with things like heart stem cells you can test drugs on to
see if they might ultimately cause heart damage, or new kinds of
imaging technology to watch how living human cells respond to
treatment and how living animals experience them.
Take aim at the boring middle ground of rational drug development and
not the sexy billion-dollar final product. That won't be easy.
"Convincing scientists that an assay has a commercial value is tough,
and patenting an assay is very tough," Mark Poznansky, former
president and scientific director of the Robarts Research Institute
in London, Ont., recently warned me when I ran the idea past him.
Nonetheless, it seems to me in a highly competitive world where good
jobs slip away in a blink, Canada needs to mark out a patch of
medical research and say, "This is us. This is our national
expertise. And we're betting this is where our biomedical BlackBerry
will come from."
http://www.cbc.
drugresearch.
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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