Corrections or additions?

This article by Barbara Fox was prepared for the

April 18, 2001 edition of U.S. 1 Newspaper. All rights reserved.

Life in the Fast Lane: Valigen

A 1979 Time magazine cover heralded the nascent

industry

of biotech, says Richard Metz, executive director of product

development at ValiGen, and it inspired his career. This cover

pictured

Interferon — a newly available drug — as a silver bullet that

could produce the cure for cancer. "That was the time," Metz

says, "when the biotech industry became valuable, when you could

purify protein in a flask and produce millions of pounds of something

that was successful."

Metz speaks on an "Introduction to Biotechnology" panel at

the biotech conference in Atlantic City (see story starting page 6).

He will

summarize molecular biology in laymen’s terms, tell about the

important

uses of genomics, and explain why genomics will factor into new drug

discovery.

Next August ValiGen (U.S.) Inc. (formerly called Kimeragen) is

scheduled

to move its laboratory 17 miles from 45,000 square feet in Newtown,

PA, to 72,000 feet in the former AT&T building on Carter Road. It

is well funded; before the stock market declined last year ValiGen

made a private placement of $26 million.

Headed by Douglas Watson, who is also speaking at the

conference,

ValiGen has 50 employees in Newtown (13 people at other locations)

and expects to add about 20 people on Carter Road.

One basic question that Metz will discuss: With the genomic

information

being discovered, how do we extract valuable information from 3

billion

sequences? "Part of that comes from understanding the genetic

variations between people, how these differences contribute to

disease,

and how our technology can aid in understanding how these differences

lead to function differences," says Metz.

His company does "gene repair," using a synthetic piece of

DNA to make site specific changes in living cells. With this,

scientists

can determine how a sequence change leads to phenotype (biochemical)

change in the cell. "Even though you don’t know what the gene

does, you can modify it or inactivate it and then look to see whether

there is a change in the function of the cell."

The old, long way to understand the function of a particular piece

of DNA is to dissect it biochemically, which could take several years.

ValiGen’s way is to alter its function or activity and look for old

or new properties of the cell.

Here’s how it works: As cells divide, their enzymes make mistakes.

But each cell has a set of machinery to repair the mistakes. His

company’s

technology, called Genoplasty, adds pieces of artificial DNA called

oligonucleotides, which are almost identical to the cell’s original

DNA sequence. The cell’s machinery uses the information from the

invading

strand of DNA as a template to repair the resident strand; it changes

the cell to match the intruder.

The end product for this is not some scary form of gene therapy, which

would introduce a gene into a living animal in order to fight disease.

Instead, the results are used as a tool in a drug screening process.

"If we can grow a cell and modify the gene so it is a model for

cancer, we can use those cells to screen for and develop anti-cancer

drugs," Metz says. "You can make a precise change in the cell

and see the results of the change you made."

All this research was made possible only after the 1980s, says Metz,

when the first gene was put together by combining a lot of

oligonucleotides,

to make artificial insulin. It was a "proof of principle"

experiment. Before that time, DNA wasn’t readily available to the

researcher.

This change was what sparked Metz’ interest in biotechnology. He grew

up in Pittsburgh, where his father was an artist who worked

in advertising and his mother was a teacher, and he majored in

biochemistry

at Purdue, Class of 1988. Intrigued by the cloning of Interferon,

he went to the Weizmann Institute in Israel and to New York University

Medical Center for a PhD, followed by post-doctorate work with Nobel

prize winner Eric Kandell at Columbia and at Bristol-Myers Squibb. He

was director

of molecular biology at Quality Biotech (now Viromed) in Collingswood,

and then came to Kimeragen (now ValiGen) nearly four years ago.

Thanks to the Human Genome Project, scientists can now name the genes,

but have not yet discovered all their functions, and Metz aims to

help ValiGen do that. "We need to know their functions in order

to claim rights, to focus our research, and to validate the target

— to link the function of the gene to a particular disease

indication."

ValiGen (U.S.) Inc., 350 Carter Road, c/o 300

Pheasant Run, Newtown 18940. Douglas G. Watson, president and CEO.

215-504-4444; fax, 215-504-4545. Home page: www.valigen.com.

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