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This article was published in U.S. 1 Newspaper on December 8,
1999. All rights reserved.
From Genes to Drugs: GPC
Last week, an international team of scientists funded
by the U.S. and other governments and Britain’s Wellcome Trust reached
a major milestone on the road to sequencing the entire human genome:
they deciphered and released onto the Internet the complete sequence
of the 33 million building blocks of the genetic code of an entire
chromosome. You can see it at
One chromosome down, 22 chromosomes to go, in the international effort
known as the Human Genome Project. A significant achievement,
but really just the first step in the first step. Mapping our genes
is one thing. Figuring out what they actually do is something entirely
One of the many companies already trying to answer the question of
how our genes function is Genome Pharmaceuticals Corporation (GPC),
a German company that recently opened its first American outpost at
Princeton Corporate Plaza. GPC is trying to map genes that may be
implicated in such diseases as multiple sclerosis, cancer, and
Disease, through a field of study known as functional genomics.
GPC hopes to radically accelerating the process of translating gene
discovery into drug discovery with a set of technologies that the
company hopes will help scientists understand not just the structure
of genes, but also their function.
To understand GPC’s technologies, you need to know a little about
how genes work — how they actually communicate messages from the
genes out to the cells and tissues they control. Genes are made of
something called DNA, or deoxyribonucleic acid. DNA itself is composed
of a number of constituent parts, the most important of which are
the bases A, C, T, and G, for chemicals called adenine, cytosine,
thymine, and guanine. The arrangement or sequences of these bases
on the helix structure of DNA famously discovered by Watson and Crick
in 1953 is how the genes actually contain their genetic information.
But then the DNA needs to get the information out to the cells and
structures it controls. It does this by sending out little genetic
messengers, known as messenger RNA (for ribonucleic acid) or mRNA.
Like DNA, mRNA is made up of chains of bases held together by some
other chemicals. But unlike the genes that express them, mRNA contains
smaller, more specific bits of genetic information that tell cells
what proteins to form and thereby enables the body to use the genetic
information contained on the genome.
Think of the relationship between DNA and mRNA as the relationship
between an architect and a builder. An architect creates a plan for
a house, say, that includes a lot of information — all the
in fact needed to create the house. Those plans are kind of like DNA.
But if you have ever looked at architect’s plans, you know that there
are a lot of details that go into it — a drawing of the framing,
the electrical plan, the kitchen cabinets. These details are something
like mRNA, which communicate to the builder not just the idea of
but all the specific structures needed to create it.
But even with these detailed plans, you still don’t have a house until
people take the plans and actually build them. In terms of
how genes work, you can think of the carpenters, the electricians,
the cabinetmakers and all the rest, as being similar to the proteins
that create the structure and functions of cells and tissues.
Which brings us back to GPC. GPC’s integrated technology platform
includes something called OliCode, a method to identify large,
segments of the genome known as gene families, which scientists
may cause many diseases. Continuing with the house metaphor, this
part of GPC’s technology seeks to discover the body’s architectural
plans in the form of DNA.
These plans or gene families are then further studied in concert with
the company’s ExpressCode technology, a high-throughput technique
for isolating the mRNA active in tissues known to be implicated in
disease states. Back to the metaphor, these would be the details of
the overall plans. Using both technologies, the company hopes it will
be able to find and map the mRNA sequences active in diseases —
the detailed plans — and then match them to the DNA on the genome
that produced them — the overall plan.
But we still don’t have a house. Crucially important
in understanding the genetic basis of disease in GPC’s model is
out who the carpenters and electricians and cabinetmakers are and
figuring out what they’re up to. This requires an in-depth
of the proteins involved in actually building the structures of our
bodies and the very complex ways in which these proteins interact.
For this, GPC has a technology called PathCode, a proprietary and
highly automated method of understanding those proteins and what they
And here’s where the drug discovery potential of GPC’s multifaceted
functional genomics technologies can be found. Imagine that you want
to build a house, but the carpenters show up with the wrong plans
and start building a gas station instead. The builder would arrive
one morning and holler, "Stop!" That would be simple. While
far more complex than hollering "Stop!" GPC’s technologies
may enable their big pharmaceutical partners to find drugs to act
like that builder, that figure out what wrong plans the body is using
to create diseases and how to get the proteins to stop what they’re
Using these technologies, GPC has already identified 20 possible
targets for antimicrobial drugs and has an alliance with a German
drug company called Evotec to develop new, genomics-derived
Other targets are infectious diseases of the immune system, cancer,
autoimmune disorders, lymphoid malignancies, stomach ulcers,
arteriosclerosis, Alzheimer’s disease, rheumatoid arthritis, multiple
sclerosis, and transplant rejection.
Founded in 1997 to enable the government-funded Max Planck Institute
to commercialize its discoveries, 70-employee GPC has raised more
than $35 million in venture capital and German government funding.
Its CEO, Bernd Seizinger, is a former director of the Molecular
Laboratory at Harvard/Mass General and until 1996 was vice president
of oncology at Bristol Myers-Squibb.
Vice president for bioinformatics Gregory Hamm was until recently
director of the molecular biology computing laboratory at Rutgers,
and is the founder of the data library at the European Molecular
Laboratory in Heidelberg. The company has partnerships with six
pharmaceuticals, including Hoechst Marion Roussel, Boehringer
Evotec, and Byk.
These companies are not well known in the U.S., but are important
in Europe, and they seem to believe that GPC has a technology well
worth supporting. But as is true throughout biotech, and especially
on the scientific cutting edge, nothing is certain. GPC’s technologies
may lead to useful discoveries, or they may not.
"It’s like looking at a city from 100,000 feet up and trying to
understand how it functions," says GPC director of database
Shahid Imran of the company’s functional genomics efforts. "You
try to track what’s going on."
— Barbara Fox and Christopher Mario
Hamm, vice president. 732-355-1222; fax, 732-355-1225.
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