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DNA Diagnostics’ New Light: A Route 1 firm has an idea, cash, and a challenge
This story by Barbara Figge Fox was published in U.S. 1 Newspaper on January 20, 1999. All rights reserved.
To find the genetic background for a disease is probably
the fastest way to find a cure for that disease, and scientists the
world over are engaged in a fast and furious search to match each
malady with its telltale string of DNA. The first pioneering invention
for gene search, the polymerase chain reaction (PCR), opened the floodgates
for the first tidal wave of gene-sifting, but because the technologies
for the next stages are inefficient, geneticists desperately need
new tools to keep the channels of gene search open.
Wlodek Mandecki, 47, founder of PharmaSeq Inc., aims to supply one
of those gene-sifting and gene-searching technologies. He has invented
an integrated circuit for a microtransponder-based system that
is powered by light and is much smaller and, he says, much faster
than the state of the art DNA diagnostic equipment available now.
He is basking in the glow of receiving a grant that many larger companies
covet but never receive: $2 million from the Advanced Technology Program
(ATP) of the National Institute of Standards and Technology that will
cover his operating expenses for three years.
In spite of gaining this imprimatur, in spite of having a solid patent
position for a technology that could be worth millions, even billions
of dollars, Mandecki faces a daunting challenge. As of today he is
PharmaSeq’s only full-time employee; he went full-time on January
1 and needs to hire scientists and also senior operations and business
people. He has leased 1,500 feet space at 11 Deer Park Drive at Princeton
Corporate Plaza, but his laboratory has yet to be furnished. He has
prototypes, including some made by technicians at Sarnoff Corporation
acting as a subcontractor. Now he needs a second-stage prototype so
he can start testing. His challenge is to quickly develop his microtransponder-based
DNA diagnostic system and grab market share.
But he is confident. "The beauty is, the transponders are so small
that the numbers you can use are huge; you can put 10,000 of them
in a cc of liquid, like a teaspoon," says Mandecki. Competitive
microtransponders are about the size of a Tylenol capsule. In contrast,
he says, PharmaSeq’s microtransponders can be as small as the size
of two human hairs, 250 micrometers on each side.
He predicts that the DNA testing market alone will amount
to $2 billion in five years. "We have the grant that assures steady
growth for three years. I am in an exceptional position, and the technology
is hot," says Mandecki. "I have a lot of opportunities to
get grant money from the government and am taking advantage of that.
PharmaSeq will grow."
"Wlodek’s idea is futuristic — it takes a quantum leap. It
is an optical reader, not a chemical reader," says Abe Abuchowski,
founder of Piscataway-based Enzon and a trailblazer for biotech firms
in New Jersey. With his firm New Paradigm Consulting (http://www.npconsulting.com)
he works with PharmaSeq on an as-needed basis. "It goes from a
two-dimensional reader to a three-dimensional reader — a great
stride forward as a scientific tool. The number of analyses that you
can do are astronomical, compared to the others. That is the beauty
of this, its speed and accuracy."
Good technology, bad technology, the winner will be what works fastest
and cheapest. "It doesn’t matter whether the technology is one,
two, or three-dimensional as long as it is high throughput, efficient,
and cost effective," says Lee Silver, a nationally prominent geneticist
at Princeton University and author of one of the first books on the
cloning controversy, "Remaking Eden."
"All of these technologies are fantastic," says Silver. "Different
people are competing with different technologies to grab that market.
It is too early to know which one will win the market. Companies want
to spend the least amount of money to get the most information. His
is in the running if he can make it fit the parameters."
Mandecki is only too aware of the competition. "Good technologies
can lose to inferior technologies in the marketplace," he admits,
pointing out how the Beta format for videotapes lost out to the VCR
format because of market share. "People don’t like to retool.
It needs to be so much better that people have no choice but to use
Yet his optimism is buoyed by memories of how one of the first breakthroughs
in gene discovery, the polymerase chain reaction (PCR), took the biotechnology
world by storm. PCR is used to amplify DNA so that scientists can
make billions of copies of a DNA molecule swiftly. It is useful for
finding DNA sequences, to diagnose disease, to detect bacteria or
viruses, and to do DNA fingerprinting. The technology was discovered
in 1985, bought by Hoffman La Roche in 1991 for $300 million, and
is being licensed for thousands of applications. "My team likes
to think that the potential for applications for our product is just
as enormous," says Mandecki.
His microtransponders, he says, could replace current technologies
that are cumbersome. "For many PCR applications I will have a
corresponding transponder application. Microtransponder-based assays
can be used in research, in DNA diagnostics, for drug discovery, for
immunoassays, or for any assay for which the presence or absence of
many molecules or sequences needs to be established," says Mandecki.
Mandecki is also encouraged by the prospect of staving off the tragedies
of genetically-carried diseases. He is fond of recalling the scene
from a recent film, "Gattaca," starring Princeton Junction
native Ethan Hawke as a boy destined by his genes to be a janitor.
In the film’s genetically-engineered world, a man takes a sample of
his fiancee’s hair to a kiosk, and in 30 seconds has a sequence analysis
and the DNA properties of his future wife, "so he can make a rational
decision," says Mandecki.
He tells the true story of a friend, Christine, who learned that her son
carried the gene for a debilitating and fatal disease, Duchenne muscular
dystrophy, only after her son was four years old. She had to watch
him gradually deteriorate, "spending the next 12 years observing
his gradual death, symptoms that start with difficulties in walking
and end up with the inability to breathe."
"The mission of PharmaSeq Inc. is to develop technology to better
inform potential parents of the consequences due to the genetics of
their offspring," says Mandecki. "This may prevent the tragedy
that Christine and many mothers like her will go through. PharmaSeq’s
goal is to implement affordable methods to detect not only Duchenne
muscular dystrophy but also all other genetic diseases. And this is
just a beginning. The universal technological platform that PharmaSeq
pursues may also be used to detect infectious diseases and to discover
new pharmaceuticals in an efficient and cost effective manner."
The market will be so large that no single company, he says, can serve
all the needs. "We will license the technology but perhaps critical
applications will be developed by PharmaSeq," says Mandecki.
If he is dreaming of PCR’s profit margins, Mandecki is planning for
his venture to be very different from PCR in at least one respect:
he will own it. Kary B. Mullis, the scientist who came up with the
idea for PCRs, an idea that would later earn him the Nobel Prize for
chemistry, was working at the time for a company that paid him just
$10,000 for his brainstorm. In contrast, Mandecki planned to first
start his own company, and second, to patent the idea.
To position himself for growth Mandecki has tapped the combined expertise
from the formal and informal networks of scientific and financial
advisors in Central New Jersey. "I am amazed at how well developed
the infrastructure is, the network of the informal interactions in
New Jersey and more specifically in the Princeton area," he says.
He worked with the Technology Help Desk ("I can
recommend contacting them to anybody") to find his accountant,
Patrick Alia, of Amper Politziner Mattia. Dan Conley, of Silicon Garden
Angels + Investors, is the "on-call" chief financial officer,
charged with procuring venture leasing, venture lending, and early
stage private equity to leverage the $2 million grant and seed money
obtained from a private party (E-mail: oncallCFO@aol.com).
Mandecki’s Chicago-based pattent attorney is from Brinks Hofer Gilson & Lione,
which is, he says, one of the 15 largest patent law firms in the nation.
His biotech consultant is Abuchowski, one of the early movers and
shakers in New Jersey’s biotech community. He and Abuchowski wrote
the SBIR grant in August, 1997, and it came through in February, 1998.
The ATP grant was written last March and it came through on October
"Abe has a very good feel for the business strategy; he was CEO
for Enzon for 12 years, and he went through all the growth stages,"
says Mandecki. "He provided me with a better understanding of
how the `money people’ think. They don’t necessarily think about how
great the research is, but about how to make the business grow fast
in the shortest time possible; he helped me with the business plan."
As one of the "Best of the Best" presenters at the New Jersey
Entrepreneurial Network meeting on January 6, Mandecki was honored
for receiving the three-year $2 million ATP grant. To put the importance
of that grant in perspective, another ATP winner was Orchid Biocomputer,
the 65-employee Sarnoff Corporation spinoff, with laboratories on
College Road and Deer Park Drive, that offers so much promise in the
field of microfluidic DNA testing and drug discovery. (PharmaSeq is
not related to Seq Inc., the start-up funded by Robert Johnston that
occupies space on Princess Drive.)
"The purpose of the grant is to help technologies that are of
interest to the nation, that could have economic value to the country
in generating jobs," says Abuchowski. "They felt that this
is one of those technologies, and appropriately so. It will make a
To understand how Mandecki’s light-powered microtransponders work,
remember the last time your dentist gave you a brushing lesson. You
swished a red dye around in your mouth; it adhered to the plaque on
your teeth. You tried to brush the dye away, but you missed some parts,
and when you looked in the mirror you saw where the red dye had stuck
to some crevices.
"The objective of a DNA assay is to find out whether the gene
is a mutant or a normal gene," says Mandecki. The microtransponders
are cube-shaped, light-activated miniature radio-frequency transmitters
about the size of two human hairs. Each has an integrated circuit
that stores, in its electronic memory, information identifying the
sequence of an attached DNA probe.
To begin a DNA assay on PharmaSeq’s microtransponder, the patient’s
DNA is labeled with a fluorescent dye and applied to the surface of
a microtransponder that contains a particular synthetic gene sequence.
Light powers up the electronic circuitry within the microtransponder
and at the same time activates the dye on the surface of the microtransponder.
"DNA `hybridization’ occurs when two DNA molecules of complementary
sequences bind," says Mandecki.
When the patient’s DNA is washed off the surface, the remaining fluorescence
is measured. If any fluorescence remains, that shows a match was made
and that the patient’s DNA contains the particular gene sequence on
the transponder. The DNA has bound to the surface of that transponder.
If no fluorescence remains, the patient’s DNA did not match that transponder’s
One transponder is used for each sequence or gene mutation but up
to 1,000 or more tests can be done at a time with Pharmaseq’s method.
Each microtransponder will be good for only one gene or mutation
and one test.
Competitive methods include manufacturing DNA arrays
by photolithography process and solid-phase chemical synthesis (being
done at Affymetrix, using Hewlett Packard equipment to read the assay
results), using ink-jet printing (done by Incyte), or what is called
clone spotting using a robotic system (by Hyseq and Incyte).
Mandecki says his assay is novel because it is not indexed by two-dimensional
coordinates but takes place in three dimensions, in the test tube.
"This 3D array is disassembled for the fluorescence measurements
and analyzed as a linear string of solid-phase particles passing through
the flow chamber of the scanner."
Mandecki says he will be able to do faster testing at the same cost
as tests that are currently on the market.
Says geneticist Silver: "They are all just different technologies.
it is impossible to know what will be the most efficient in the long
run. The bottom line is how many genes can you assay at the same time."
"I also want to diversify and go into drug discovery," says
Mandecki. "Microtransponders can be tags for small organic molecules
as well. I believe that the first sales will be for using microtransponders
as tags on small parts, applications for which the barcode is being
used now. The integrated circuit is the same for both biochemical and taggling applications."
Wlodek Mandecki needed to become a geographical bachelor to start
this firm; his family is still in Chicago. Three years ago he rented
a house in Edison and he goes home only every three or four weeks.
"There is a lot of uncertainty in starting a new company,"
he says. "Now that I have the ATP grant I am relocating my family
in Princeton Junction."
A native of Warsaw, he was the only child of an economist and a pharmacist.
He has an undergraduate degree in physics from the University of Warsaw
(Class of 1974) and a PhD from Institute of Biochemistry of the Polish
Academy of Sciences. For his first post doctoral studies, in protein
analyses and sequencing in the medical school at UCLA, he had to leave
his pregnant wife behind and he did not see his son until he was 18
months old. "It was heartbreaking but what can you do? The airfare
to Poland was three months of my salary," he recalls.
Next he worked on how a gene expression is regulated, particularly
on E coli, in the molecular biology department at the University of
Wisconsin at Madison. "At that time DNA sequence analysis was
at the early stages. I was in one of the labs that pioneered sequence
analysis of DNA, with Bill Reznikoff." Then he worked at the University
of Colorado with Marvin Caruthers, whom he calls the "the father
of chemical synthesis of oligonucleotides (DNA)." In Chicago he
worked at Abbott Laboratories, starting as a
group leader and ending up as research manager, working in molecular
biology, genetic analyses, gene expression, protein engineering, protein
evolution. Thirty Abbott diagnostic products are based on his patents.
"Abbott is an exciting place to work," he says. Of the New
Jersey pharmaceuticals, he compares it to Hoffman-La Roche, because
of its diversification into drug discovery, pharmaceuticals, and diagnostics.
He knew he didn’t want to stay in Chicago to found his company, so
he had to leave his family behind. His wife, Wanda, writes Polish
literature textbooks for English-speaking students and teaches on
Saturdays at a Polish high school in Chicago. "She is well recognized
and rewarded; she has made a place for herself," she says. The
oldest son is now 19 and is majoring in business at the University
of Michigan. They have a 16-year-old boy and a 14-year-old girl.
"Not very many start-up biotech companies have succeeded in Chicago,"
he notes, "and New Jersey is one of four major hubs for biotech."
His choice was influenced by an offer to consult in Edison for DGI
Biotechnologies. He had worked on single chain antibodies and protein engineering at Abbott
Labs and continued in this area for DGI. After three years there he
went full-time into his own business as of January 1, 1999.
How he found his lab space is, he says enthusiastically, "one
of those unbelievable stories." Architect Harold Kent was designing
and furnishing the space at the lab where he was doing some consulting.
"I liked what he was doing, and he said he had some space at Deer
Park Drive. Amazingly enough, in two hours I had a facility. He runs
one of the very few centers that care for small business. Not too
many other places would rent 1,500 square feet, with laboratory furniture,
in a very attractive location, next to Wyeth Ayerst, Small Molecule
Therapeutics, and Orchid Biocomputer."
To put Mandecki’s technology in perspective, consider the news coming
from Iceland: a genetic information gathering project with enormous
impact. The country of Iceland has sold the rights to collect information
on its gene pool — famous for being homogeneous and therefore
very attractive to researchers — to Kari Stefansson and his firm
Decode Genetics. He will create a huge electronic database with which
researchers can hunt for the root-gene causes of hundreds of diseases.
The database can be parceled out to other pharmaceutical companies
Being able to use Iceland’s small gene pool dramatically improves
the odds of zeroing in on a particular gene. Instead of searching
for the particular grain of sand on all of the beaches in the world,
you can narrow your search to just one beach. But current searching
methods are limited to sifting the sand bucket by bucket. Imagine
how much faster it would be to sift truckload by truckload.
Is genetic research the truckload sifter, the fastest way to find
disease cures? Silver, the Princeton geneticist, insists that it is.
"No matter what the biochemists say, they are wrong. At this point
the geneticists have control," says Silver. "From the disease
you find the gene — you find out how it works. Once you understand
how it works properly, you find out how it works in diseased individuals
and that is the paradigm that everybody is using. Already there are
100 diseases being worked on for cures."
Cystic fibrosis is the first success story, Silver says, and he estimates
that 100 diseases are being researched for a genetic cure. "The
market for multiplexing genes is enormous, in the multi billions.
It is the future of medicine."
But all this is very early, almost `pie in the sky’ for PharmaSeq,
which does not yet have a fully working model. "The Eureka moment is
yet to come," admits Abuchowski. "But that will be some moment,
when it happens. If you can tag molecules, you can tag all kinds of
things. It doesn’t take a rocket scientist to realize what the applications
"He probably has an opportunity to sell the technology outright
to one company that could exploit it very quickly and also make a
lot of money," says Abuchowski.
"Don’t make me rich too quickly," says Mandecki.
Plaza, Suite 204, Monmouth Junction 08852. Wlodek Mandecki, president
and CEO. 732-355-0100; fax, 732-635-0428. E-mail: email@example.com.
— Barbara Figge Fox
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