Botanical Genetics

Chemical Synthesis

Corrections or additions?

These articles by Barbara Fox were prepared for the December 6,

2000 edition of U.S. 1 Newspaper. All rights reserved.

Genetic Crops: Tinkering With Our Greens

Jane E. Brody, science writer for the New York Times,

compares the current furor over genetically modified crops to the

brouhaha initially raised over magnetic resonance imaging or MRIs.

When MRIs were first introduced, they had the unfortunate name of

NMRs (nuclear magnetic resonance). Even though the nucleus referred

to was the nucleus of a cell, not a bomb-producing energy source,

this term unnecessarily frightened the public. Seventy percent of

the public, Brody writes in a December 5 New York Times column,


of using biotechnology in food and agriculture, yet those same people

oppose the use of genetically modified (GM) foods.

When it comes to GM foods, agrobusiness is in a holding pattern, at

least for now. The big companies — Novartis, Monsanto,


American Cyanamid — are merging or threatening to merge, and


consumers have signaled American consumers to be worried about


dangers of GM crops. Though scientists need to make long-term plans

— it takes a long time to develop a new strain, grow it, test

it, and get approvals — they find themselves at least partially

hamstrung by uncertainties.

One new R&D company at Princeton Corporate Plaza on Route 1, ignoring

this controversy for the moment, hopes to dramatically speed up the

development of genetically modified plants. Icon Genetics Inc. is

working on a botanical genetic tool kit, one that will create a


operating system to streamline development of new plants.

It has recently secured new financing of $12 million. These investment

and matching funds, which should take the company through the second

quarter of 2002, are coming from government sources in Germany (the

Bavarian Ministry of Economy, Traffic, and Technology) and from the

Audax Group, which has offices in New York, Boston, and Los Angeles.

Icon Genetics incorporated in February, 1999, opened labs here last

April, and now has 12 employees at 1 Deer Park Drive. It has also

established labs in Germany, one outside of Munich and another outside

of Leipzig, in Halle.

Icon Genetics’ tagline is "gene management for the post genomics

era." But the firm is not developing any particular strain of

plant, says Newell Bascomb, the president. Its methods are not


and, in fact, the interchangeability of its technology is reflected

in its name, which represents the "icon" of Windows-based


Like software, when it was available only on floppy disks, plant


is in a early stage of development, says Bascomb. Before today’s


was developed, personal electronic equipment required a different

machine for each operation. You had to switch floppy disks for each

new operation. But under the Windows operating system, there are a

number of programs in each computer, and you can click on an icon

to make the computer do what you want to do.

It’s the same with plant gene manipulation. "Now, when a plant

goes out to the field, it has a set of traits in it, but that’s all

it has," he says. "If you want that plant to do something

different, it is a long process. A lot of companies are doing gene

sequencing and gene identification, but moving a gene into


important crops is the longest process, especially to get it into

many varieties. Corn and soybean have 500 varieties in U.S.


In fact, moving a gene into a commercially important crop can take

five to seven years with traditional methods, and genes are not easily

transferred to the commercial "elite" varieties. "We have

developed new tools for rapidly moving genes into the elite line,"

says Bascomb.

How it works: The researchers add DNA, transforming the cells with

a gene gun or an electrical current. They culture the transformed

cells in a petri dish containing a growth medium. In this growth


is a selective agent that allows only the transformed cells to grow.

Under the right conditions the new plantlets can grow from these


cells — as pictured on the cover of this issue.

"Our research has gone very well," says Bascomb. He declines

to disclose the firm’s proprietary methods, but some of the technology

was licensed from inventors in Kiev and Germany through Yuri Gleba,

whom he met at a former employer, American Cyanamid. "We have

four patents filed and many more in progress," says Bascomb. "Two

technologies that allowed us to get started were licensed from the

International Institute of Cell Biology in the Ukraine." Gleba

was director of the institute. Valentin Negrouk and Gerald Hall are

the group leaders and Lynne Watkins is the site manager.

Bascomb grew up on Long Island, where his father had a dry cleaning

store and his mother worked in the public school system. He went to

Juniata College in Huntingdon, Pennsylvania, Class of 1978, and has

a master’s degree from Virginia Tech and a PhD from the University

of Florida. He had worked at Enichem Americas at Jersey Metroplex

and at American Cyanamid on Route 1, where he was doing crop


chemical screens. In the late 1990s he had a sideline company, Mercer

Datasafe, a Lawrenceville-based automatic remote computer backup


and disaster recovery planning firm.

Yes, there is controversy about bioengineered plants, Bascomb admits,

and the most virulent fuss centers on StarLink, a new strain of corn

developed by Aventis CropScience. StarLink contains a bacterial


that could conceivably produce an allergic reaction in some people,

and it was not approved for human consumption. Experts such as Brody

are concerned about introducing possible food allergens and note that

it is hard to predict how new proteins will affect those with


A coalition of environmental and consumer groups discovered that the

company had allowed StarLink to make its way into yellow taco shells,

and the resulting scandal paralyzed U.S. exports of corn crops.

Opposition from Europe may restrict use of the technology in locations

where improving food production is not a matter of lifestyle choice

but of need. "I am surprised at the intense reaction in


says Michael Moynihan of Interlink Biotechnologies, an R&D consulting

group at Montgomery Commons. "The United States response is more

lackadaisical, that there might be something to worry about. The


in Europe seems to be `even if the risk is trivial, we just don’t

need it.’ They don’t even want to discuss the issue, versus maybe

it should be labeled but it is probably still OK. The fear of being

shut out of European markets is putting the brakes on GM crops


At least partly in response to what is being called

the New Luddite movement, Monsanto Corporation (an Aventis competitor)

recently issued a major policy statement, admitting it had not paid

enough attention to consumer concerns and will go forward in a



But Bascomb believes that, down the road, when the agricultural


industry brings more products to market, the so-called New Luddites

will see how helpful these products are.

He gets agreement from Peter Day, director of the biotechnologies

center for agriculture and the environment at Rutgers Cook College

(E-mail: "All of the basic information

is that GM crops are safe. There is no evidence that they are


says Day. "The apparent difficulties with genetically engineered

crops are going to disappear. I see the application of biotechnology

to plant improvement as something that is inevitable, and there are

going to be an increasingly large variety of ways of doing it."

Day is, nevertheless, pessimistic about Icon Genetics’ technology.

"I don’t see how they can ensure getting the information into

the plant each time." He also points out that getting the gene

into the plant is just the first part of the process. The plant still

must be grown and tested. "However you have made a new plant,

you have to show it is any good by the same techniques that any


would use," says Day.

Michael Lawton, an associate professor at the Cook College biotech

center, is more sanguine. He notes that products already on the market

are based on approaches that are 15 or 20 years old. One technique

is to use a bacterium that can deliver the gene into the nucleus.

Another is to use a gene gun. But to use these techniques for


a particular gene to a particular site is a clunky process. The


must modify the plant so it has a "docking" site. "You

put the complementary DNA pieces on your gene," Lawton explains,

"and it will preferentially go to the docking site." This

conversion takes time and must be repeated with each new plant


but it is essential. "If you know where the gene goes, you don’t

have to worry about it disrupting other genes," says Lawton.

"It takes a long time, a lot of effort and labor, to make


plants and it is very expensive," says Lawton. "Time is the

problem. It would be nice to more easily and directly introduce the

gene you are interested in — to cut to the chase, to go straight

to the variety that will be grown. If you speed things up you reduce

the cost. If you reduce the cost, you can apply it to many more


This small company is one among many who are working on this problem.

"Probably all the major companies have programs to deliver genes

to particular places within the chromosomes, for the purposes of


and regulation," says Lawton.

"People here understand the urgency. If we don’t produce these

tools, somebody else will do it," says Bascomb. "We know if we

are not inventive and hardworking in a couple of years we won’t be


— Barbara Fox

Icon Genetics Inc., 1 Deer Park Drive, Princeton

Research Center, Suite C, Monmouth Junction 08852. Newell Bascomb,

president. 732-329-1600; fax, 732-329-1616. Home page:

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Botanical Genetics

Several big companies and a handful of small ones in

the Princeton area are doing research on genetic manipulation for

crops. Celgro, the agro-division of the pharmaceutical company


is not in this category, strictly speaking, because it is engineering

genes for herbicides, not the actual plant material. Neither BASF

(formerly American Cyanamid) nor FMC Corp. are particularly anxious

to reveal what they are working on.

In fact, the agricultural biotechnology that Cyanamid was doing at

the Quakerbridge Road site are being moved to Raleigh, North Carolina,

where BASF’s Plant Science division is located. This transfer should

take place by the end of the year, says Susan O’Connor, communications

manager for BASF Corporation. The subject is so fraught with


that O’Connor declines even to define agriculture biotechnology,


only that it is "an extremely small part" of Cyanamid’s


in Princeton. "What we have always concentrated on," she says,

"is developing insecticides, herbicides, fungicides."

Interlink Biotechnologies at Montgomery Commons, however, has some

important expansion news. Interlink’s Michael Moynihan is relocating

to Santiago, Chile, where he will be the vice president of research

at BioGenetic, a joint venture between Interlink and a nonprofit tech

transfer organization named Fundacion Chile. This company is doing

genetic engineering of fruit trees and forestry trees.

Another high profile firm has strong connections to the Forbes family

and is already public. Senesco Technologies based its initial


on work being done in Canada to extend the shelf-life of produce.

"We have demonstrated the efficacy and the proof of concept of

our technology by extending the shelf life of a tomato by 100


says Steven Katz, president.

His office on Chambers Street has six people plus the nine people

at the University of Waterloo in Toronto, where the scientific work

is being done. Katz, who joined the company last January, went to

City College of New York, Class of 1969, and has a master’s degree

from CCNY. He is negotiating licenses and strategic alliances with

more than a half dozen major companies and is "not very far from

closing alliances on two or three."

Among the Princeton-area agricultural research firms:

BASF/American Cyanamid Agricultural Products Research

Division ,

Quakerbridge Road, Box 400, Princeton 08543-0400; Jurgen Odeweme,

agricultural and biotechnology research, a subsidiary of BASF. Founded

1907. Phone: 609-716-2000. Home page:

FMC Corp., Route 1 and Plainsboro Road, Box 8, Princeton

08543-0008; chemical research and development, agricultural chemical

and chemical products group divisions (ACG and CPG) of firm based

in Wayne, New Jersey. Founded 1886. Richard Police, facility director.

Staff size: 450. Phone: 609-951-3000.

Celgro Corporation, 661 Route 1 South, Technology Center

of New Jersey II, North Brunswick 08902; agrochemical research and

development, gene engineering for better herbicides. wholly owned

subsidiary of Celgene Corporation. Founded 1996. George W. Matcham,

senior vice president, Celgro. Staff size: 20. Square feet: 18,000.

Phone: 732-509-2020. Home page:

Interlink Biotechnologies LLC, 215 Commons Way, Montgomery

Commons, Princeton 08540; biotechnology assessment, planning and


also microbial products and services with InterLink Microbials


agribusiness. Founded 1991. Ramon L. Garcia, president. Staff size:

5. Square feet: 2,000. Phone: 609-252-0446. Home page:

NuCycle Therapy Inc., 1 Deer Park Drive, Princeton


Plaza, Monmouth Junction 08852; use of plants for nutritional mineral

supplements, formerly Phytotech (U.S. 1, January 19, 2000). Founded

1992. Burt Ensley, CEO. Staff size: 5. Square feet: 5,000. Phone:


Seed Genetics Inc., 3131 Princeton Pike, Building 5, Suite

200, Lawrenceville 08648; technology transfer (licensing) of hybrid

corn, genetics, and genes. Founded 1989. Bob Teweles, president. Staff

size: 2. Phone: 609-896-3200.

Senesco Technologies Inc., 34 Chambers Street, Princeton

08540; agrobiotechnology — developing gene technology to extend

the shelf-life of produce (U.S. 1, January 19, 2000). Ruedi Stalder,

chairman and CEO. Phone: 609-252-0680. Home page:

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Chemical Synthesis

Chemspeed Inc., 7 Deer Park Drive, Suite L,


Junction 08852. Ernest Sobkow, business manager. 732-329-1225; fax,

732-329-1226. Home page:

Ernest Sobkow has opened a sales office and laboratory for a chemical

synthesizer manufacturing company that is based in Basel, Switzerland.

Typically these chemical synthesizers are used for combinatorial


medicinal chemistry, or in process development. "New Jersey is

a nice place to be for pharmaceuticals and specialty chemicals, such

as Merck, Dow Chemical, and DuPont, and we also serve material


says Sobkow.

"This machine is novel in that it can do very difficult chemistry

and a wide variety of things," says Sobkow. The key attribute

of Chemspeed’s apparatus is the ability to do multi-step chemistry

— both solution and solid phase chemistry. "The number of

steps you can use is infinite," says Sobkow, "but the more

steps you have, the fewer samples you can use."

Cost? From $25,000 up to $250,000. The lower priced system is manual,

compared to the top end, which is automated. "It allows us to

synthesize compounds, work them up, and send to an interfacing


for purification or analysis, all without intervention from a human

hand. You can do that all on one platform without intervention,"

says Sobkow.

The son of a tool and die maker, Sobkow went to Allentown College

of St. Francis, Class of 1973, and has a master’s degree from the

University of Scranton. He worked in sales for the Waters Corporation

in Morristown before opening this New Jersey office.

How it works: First put the necessary reagents in their proper


Then tell the computer where those reagents are, how to mix them,

how long, and at what temperature. Then "work them up,"


the desired compound and doing some preliminary cleanup, which


involves some type of extraction. This apparatus can also do the


— solid, liquid, or evaporation.

The company employs a total of 44 people, including those in


and the United Kingdom. "We are pretty new in the market —

we only started selling this instrument only last year," says


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