• Wisconsin Crop Innovation Center (WCIC) holds a prominent place in Agricultural Biotechnology history. 

• Originally known as Cetus of Madison, Inc. in Middleton, WI, the facility was started under the direction of former UW-Madison Emeritus Professor, Winston Brill in 1981 and owned by the [Cetus Corporation] of Emeryville, CA. 

• The Wisconsin Alumni Research Foundation (WARF) played a key funding role in the early days of the company as well. 

• Cetus of Madison, Inc. was initially focused on evaluating and testing a wide variety of natural rhizobium species to better understand their role in nitrogen fixation and nodulation in legumes with the hope of some day enabling maize to have that capacity. 

• As the interest in biotechnology increased in the early 80s, the focus changed to inventing and innovating ways to introduce genes into plants. 

• In 1984, [Cetus Corporation] sold half of its interest in Cetus of Madison, Inc. to the [W.R. Grace and Company] and subsequently the name of the company changed to Agracetus, Inc. (combining Grace/Cetus together). 

• During this time Agracetus developed an electric “gene gun” and transformation methods that revolutionized the plant transformation process.

• Many plant species were subsequently transformed including; Tobacco, Peanut, Sunflower, Soybean, Maize, Cotton, Canola, Poplar, Wheat, Rice, among others. 

• Research into cotton fiber quality, transformation process improvements, PCR method development, insect and disease resistance, and herbicide tolerance was ongoing in various labs in the facility. 

• In 1990,  [W.R. Grace and Company] acquired full ownership of Agracetus.

• During the early 1990’s Agracetus ventured into research in DNA vaccines (using their improved “gene gun”) and contracted their plant transformation services to others within the industry, including the Monsanto Company. 

• After successfully generating plants that eventually became commercial products for Monsanto, including Roundup Ready Soybeans and Bollgard Cotton, the facility was acquired by Monsanto in 1996. 

• Over the next 20 years, Monsanto used the facility as its primary site for soybean and cotton transformation.  Other R&D at the site included, corn, canola, wheat, rice, and alfalfa transformation, gene expression, molecular testing, and seed chipping/genotyping.  The site was considered a “center of excellence” for Monsanto due to its highly innovative employees, high throughput transformation capabilities,  and its ability to consistently perform above and beyond expectations.  In 2015 due to business consolidation considerations, Monsanto decided to relocate a number of their remote functions back to their main site in St. Louis, MO.  Through negotiations with the University of Wisconsin and in hopes that the site would continue on for the betterment of agriculture, Monsanto generously donated the facility to the University Research Park and the UW-Madison in December, 2016.

[...]

It was, therefore, not surprising when the pharmaceutical company Eli Lilly recently agreed to acquire Hybritech, a San Diego-based company that manufactures monoclonal antibodies, which are artificially produced proteins that identify and attack specific disease organisms in the body. The purchase agreement: at least $300 million.

Over the long haul, only a few of the hundreds of existing biotech companies are expected to become successful independent businesses. Furthermore, a company that hopes to have products in areas outside its specialty will need not only financial backing but also alliances with established leaders in the various fields. As Bob Fildes has said, ''The only way to get into a shark-infested world is to go in on a shark.'' [Cetus Corporation], for example, last year formed an agricultural joint venture with [W.R. Grace and Company], called [Agracetus, Incorporated], in which Grace has pledged at least $60 million for a 51 percent interest. Joint ventures have also been negotiated with Nabisco Brands (before it became an R. J. Reynolds subsidiary) for research into food and food additives, and with Weyerhaeuser, a leading forest-products company, for possible wood by-products.

''We knew from the beginning that there would be a long time line for developments in agriculture, and that even with good products you need a strong and large marketing arm like Grace,'' says Cape.

[...]

In a significant step for the biotechnology industry and agriculture, scientists and technicians planted genetically engineered tobacco on a Wisconsin farm today to begin the first outdoor test of plants modified by artificial manipulation of their genetic structures.

The field test was conducted by Agracetus, a small biotechnology company in Middleton, Wis., that is jointly owned by the Cetus Corporation, a biotechnology concern in Emeryville, Calif., and W. R. Grace & Company, the diversified New York producer of chemicals and consumer products.

The modified tobacco plants are the second living genetically engineered organisms to be deliberately released into the environment. Last year, the Department of Agriculture approved field tests in the Middle West of a gene-altered virus in a swine vaccine, and in January it granted an Omaha-based animal health-care company the first license to market a living genetically engineered product.

The field test, according to biotechnology analysts, opens what many new companies hope will be a vast market for custom-designed crops that will lower farm production costs and lead to less environmental damage from toxic farm chemicals. $9 Billion Potential American farmers currently spend roughly $9 billion a year on farm chemicals and fertilizers to help crops grow bigger and faster while protecting them from diseases and pests. The technology in which genes from different species are mixed, however, provides plant breeders with a powerful tool for producing crops that could reduce the use of farm chemicals.

Many biotechnology companies are studying methods for engineering corn, wheat, rye, cotton, and citrus crops that would resist insects. Others are developing systems for enabling crop plants to manufacture their own nitrogen fertilizer. Some scientists are even exploring means for increasing crop productivity by doubling the rate of photosynthesis in plants.

Jack Doyle, agriculture analyst with the Environmental Policy Institute in Washington, said: ''W. R. Grace clearly sees the writing on the wall in terms of the future of hydrocarbon chemistry in farming. Major companies are entering this field because they see that eventually this technology can make chemicals obsolete.''

Regulators Are Unsure

The field test comes amid uncertainty in Washington on the regulation of biotechnology. Federal administrators are awaiting a decision by President Reagan on new policies to determine how the Department of Agriculture and the Environmental Protection Agency oversee genetically engineered products to be used by farmers.

Moreover, public protests have taken place in Missouri and California in recent months near sites where biotechnology companies sought to spray living microbes that had been genetically altered. But experiments involving genetically engineered plants have come under less criticism because in most cases they are easier to control, scientists say.

Dr. Winston Brill, vice president of research and development at Agracetus, said the test was planned for today to coincide with the growing cycle of tobacco in Wisconsin. Moreover, said Dr. Brill, the field test had been thoroughly examined by scientists with the National Institutes of Health and the Department of Agriculture, and approved in November. The Wisconsin Department of Natural Resources also reviewed the test and approved it.

Dr. Brill said relief outweighed happiness among the companies' top executives. Agracetus has been developing the gene-altered tobacco plants for more than three years, and company officials worried that critics might protest the field test. One prominent critic of the industry, Jeremy Rifkin, president of the Foundation on Economic Trends in Washington, said today that he did not feel the Agracetus project raised any fundamental issues and that he would not oppose the test.

No Champagne for Him

Dr. Brill said: ''My wife asked me if we're going to get champagne for the company. I chose not to because this is a historic event, perhaps, but not a commercially important event. It is the first of many, many thousands of plants that will be coming out over the next decade here and around the world. There certainly is some excitement about it, but we're also fed up with it. We really want to get on to the next things, which are much more important.''

Today, Agracetus planted 200 four-inch, gene-altered tobacco seedlings on a plot the size of a front yard near Middleton, in south-central Wisconsin near Madison. The company would not disclose the location of the site because it feared the experiment could be sabotaged by protesters.

The tobacco plants, according to Agracetus, are resistant to crown gall, a bacterial disease. The resistance trait was developed by incorporating a single gene from a common yeast, Saccharomyces cerevisiae, into the tobacco plant's genetic structure.

Agracetus executives say the altered tobacco plant will not become a commercial product. Rather, scientists are testing the system for moving genes into crop plants. They hope to show that adding a gene will produce the desired characteristic and not interrupt other biological traits, such as high yield.

If the tests are successful, said executives, it could help Agracetus engineer disease resistance into major crops like corn, cotton and soybeans.

Genetic engineering, the most powerful and precise biological tool for manipulating life ever devised, has reached a milestone.

Fourteen years after scientists first spliced genetic material from one microbe into another to create a bit of life that never before existed, genetic alterations once confined to science fiction are becoming ever more common.

Now the United States Patent and Trademark Office has ruled that genetic engineers may patent higher life forms - even mammals. The decision promises to widen vastly the commercial and agricultural applications of novel methods of producing new kinds of life.

Industrial leaders say they must be able to patent new life forms and processes if they are to protect their investments and move forward in a field full of innovation and risk. But the patent office ruling has also revived anxiety about the safety and morality of tampering with life forms.

Hearings Planned This Week

That concern prompted a Congressional committee to schedule hearings this week on ethics and regulations in the field of genetic engineering. Last month, the Senate approved a measure that would prevent the Patent Office from spending money on reviewing patents for animals, but it still faces a conference committee vote.

In the near future biotechnology may see these developments:

• In laboratories across the country, the genes of viruses and bacteria will be placed in plants to enable them to produce their own insecticides or fertilizers. These so-called transgenic plants will be field-tested, and farmers will begin using them in place of conventional crop varieties.

• Researchers will manipulate the primordial cells that produce sperm and eggs to enable breeders to select the characteristics of animals, including gender.

• Scientists will routinely transplant a gene from one species to another.

A Rust-Colored Pig

As the debate unfolds, many eyes will turn to a rust-colored pig in Beltsville, Md., with the growth hormone gene of a cow. That pig represents success to the genetic engineers and, because of its pathetic infirmities, new reason for concern to those who fear that mankind now has too many tools for meddling in the complex matter of life.

In recent months most of the concern about genetic engineering centered on the release into the environment of newly devised organisms in the form of bacteria designed to help plants resist pests, diseases and bad weather. With the new patent ruling, however, the concern has begun to shift to more complicated genetic manipulation in higher life forms -mammals - resulting in transgenic creatures like the pig with a cow gene.

In the long run, opponents and proponents of genetic engineering see a vast array of potential applications, including plants and microbes designed to produce fuel; cows that produce medicines instead of milk, or even babies destined to have a particular height, hair color or other traits.

The genetic traits of plants and animals have been manipulated for centuries. But until now animal breeding and the hybridization of crop plants have been slow, cumbersome and difficult. Furthermore, until now, breeders were never able to introduce genes from one species into another or to make such extensive changes. Redesigning Man? Because many breeding techniques, such as artificial insemination, in vitro fertilization and embryo transfer, have already made their way into medicine, there are some who fear it may not be long until the manipulation of animal traits will extend to human traits as well.

''Important legal, constitutional and policy issues were raised by this decision,'' said Representative Robert W. Kastenmeier, a Wisconsin Democrat who heads the House Judiciary Subcommittee on Courts, Civil Liberties, and the Administration of Justice, which will hold the hearing Thursday on the Patent Office ruling.

The commercial applications of genetic engineering are already apparent. Sales of genetically engineered products, most of them new pharmaceuticals, have almost doubled annually in recent years and topped $350 million last year, according to industry analysts. The Congressional Office of Technology Assessment has identified almost 400 companies seeking to develop products with genetic engineering and other modern biological technologies. More than $3 billion, two-thirds of it provided by the Government, will be invested this year in biotechnology research, according to the General Accounting Office and industry analysts.

Yet as the ambitions and accomplishments of genetic engineering increase, awareness of its power and potential is generating a mixture of fascination and hope, aversion and misunderstanding.

A survey of 1,273 American adults published in May by the Congressional technology office found that while a majority of those interviewed believed that the potential benefits of genetic engineering outweighed its risks, they were disturbed by some applications, particularly the release of manufactured life forms into the environment and manipulations in human embryos. Sharp Disagreement Over Possible Dangers ''People understand at a gut level that there is something wondrous, and perhaps perilous, about a technology that changes the blueprint of life and will force us to make choices that are likely to be more profound than anything we, as a society, have ever faced,'' said Senator Albert Gore Jr., a Tennessee Democrat who has studied the biotechnology industry.

Though scientists generally agree the field offers great promise, there is sharp disagreement over its potential perils.

''We are bringing a completely human-centered utilitarian attitude toward life,'' said Dr. Michael Fox, a veterinarian and scientific director of the Humane Society of the United States. ''All of earth's living things will simply become items to exploit.''

Other scientists and many biotechnology industry executives insist that genetic manipulation will hasten the development of cures for diseases like AIDS, lead to solutions for toxic chemical pollution, produce a new agricultural cornucopia and open an industrial era based not on fossil fuels and chemicals, but on new, non-polluting substances produced by genetically engineered plants or microbes.

Genetic engineering was recognized as a momentous development in 1973, when [Dr. Stanley Norman Cohen (born 1935)] of Stanford University and [Dr. Herbert Wayne "Herb" Boyer (born 1936)] of the University of California at San Francisco snipped a piece of the genetic code out of one bacterium and inserted it into another.

But that experiment was followed almost immediately by a host of safety and ethical questions, many of which remain unresolved. Are living, gene-altered microbes safe to release outdoors? What is the best way to assess the risk from such uses? Is it ethical to alter the genetic codes of animals? What about people? How can a society know whether a new technology should be pursued or ignored?

''The issues range from ethics within universities, to the environment, to eugenics, to definitions of nature, to religious thought, to what it is to be human,'' said Dorothy Nelkin, a professor in Cornell University's Program on Science, Technology and Society. ''Other disputes over technology have been much simpler and mostly focus on health concerns.''

Rearranging Gene Chemicals

The source of the excitement and the conflicts is a technique, conceptually simple but in practice quite complex, for rearranging basic hereditary material: the deoxyribonucleic acid, or DNA, that makes up genes.

DNA molecules are long, twisted ladders of chemicals called nucleotide bases: adenine, thymine, guanine and cytosine. More than 30 years ago, scientists determined that adenine always pairs with thymine, and cytosine with guanine. These chemical connections are called base pairs; a single gene, a section of DNA, is typically made up of 10,000 to 20,000 base pairs. Human beings, it is estimated, have between 100,000 and 200,000 genes, or up to 4 billion base pairs, organized on 46 chromosomes.

Though the numbers of genes in mammals, plants, and microbes differ, their ladder-like molecular structure does not. Scientists are now able to identify and isolate specific genes and remove them with proteins, called restriction enzymes, that slice DNA in specific places. The enzymes cause the pairs on either end of the gene to split, leaving nucleotide bases without corresponding mates. Scientists call the unpaired bases ''sticky ends'' because, seeking the correct chemical fit, they easily merge with another organism's genetic structure.

Yet simply isolating a gene from one animal and plugging it into another does not mean that the gene will produce the desired result. A gene's functions are determined by its location on a chromosome, the workings of neighboring genes and other factors that are still mysteries. Current Limitations And Possibilities So far, genetic engineers are largely limited to transferring single genes into microbes, plants and animals, or taking single genes out of bacteria and viruses. Alterations involving more than one gene, such as creating crops that produce their own insecticides and fertilizer, or cows that produce medications in their udders instead of milk, are still years away.

Assertions that genetic engineering will produce unrecognizable plants or monstrous animals are considered by many researchers to be scientifically absurd.

''There are severe limits to the extent of the modifications we can make,'' said Dr. Bernard D. Davis, a microbiologist at Harvard Medical School. ''If you mix genes from genetically distant organisms that don't fit each other well, you will not have an organism that can live.''

''We're not going to make weeds out of non-weedy species,'' said Dr. Winston Brill, vice president of research and development at Agracetus, a plant biotechnology company in Middleton, Wis. ''We're not going to have Frankensteins crawling around.''

Nevertheless, transfers involving a single gene can yield striking physiological changes.

A Pig Unlike Any Other

For example, the transgenic pig, a rust-colored boar born last November at the Department of Agriculture's experiment station in Beltsville, now weighs as much as its natural cousins; unlike them, little of its bulk is fat. But it has trouble walking on short legs swollen by arthritis. Its eyes, peering from a broad and wrinkled face, are slightly crossed. If it is like its father, who was one of the world's first transgenic farm animals, it will not live to be 2 years old.

Nothing about producing transgenic animals is easy. Genes are injected into fertilized animal eggs. Piercing cell walls kills between half and three quarters of the eggs, said Dr. Vernon G. Pursel, the research physiologist conducting the swine experiments. In four years, scientists injected more than 8,000 fertilized eggs to produce just 43 transgenic pigs.

It is little wonder, then, that researchers at Beltsville consider the birth of the rust-colored pig to be a scientific success. The young boar inherited the gene that scientists inserted into its father, and the gene expressed itself. Scientists are now working to control the gene so that it produces animals that grow fast, eat less, and produce more lean meat, without the complex of crippling diseases afflicting the boar.

The Foundation on Economic Trends, a small public policy group that opposes genetic engineering, and the Humane Society of the United States unsuccessfully filed suit in Federal Disrict Court three years ago to halt the research that produced the rust-colored boar's father. They said the research was cruel, violated the innate dignity of animals and would have significant social and economic effects by producing bigger, more expensive animals that would cause dislocations in the farm economy.

''That kind of scientific reductionism undermines the respect for life and future generations will come to regret it,'' Jeremy Rifkin, president of the foundation, said recently.

The two groups are also protesting the new Patent Office policy. In this battle they are joined by farm organizations, consumer groups, environmental groups and most major animal welfare groups.

''Farmers believe they will be facing fewer choices in terms of breeds available to them and will be paying far more for animals,'' said R. Keith Stroup, legal counsel for the League of Rural Voters, a family farm advocacy group that opposes the policy. ''There's another issue here, too. Most farmers who deal with animals on a day-to-day basis want to be very thoughtful and careful about tampering with life. Clearly we have not explored fully the repercussions, morally and ethically, of what these patent applications seek to do.''

Fifteen applications have been filed, but the office does not release descriptions of patent proposals until they are approved.

Dr. Pursel said he was sensitive to the protests but unsure how to respond. ''We are not doing anything out here that is cruel,'' he said, adding, ''The research could have a tremendous practical value.''

Less Invasive Applications

Other applications of genetic engineering technology are less invasive and also less divisive. Scientists have discovered several methods for moving bacterial and viral genes into plants to make them more resistant to insects and diseases. Field tests were conducted last year in Wisconsin, North Carolina and Mississippi and this year in Missouri without protest.

Researchers at the University of California at Davis are working to develop plants that produce their own fertilizers. Around the country, scientists are studying genetic manipulations to increase the rate of photosynthesis to hasten plant growth.

In the pharmaceutical industry, four drugs produced by genetically engineered bacteria have been approved by the Food and Drug Administration. The agency has been asked to approve another new drug made by genetically altered bacteria, tissue plasminogen activator, to be used in treating heart attacks. Its manufacturer, Genentech of South San Francisco, predicts that sales of the drug could reach $800 million a year. Genentech has also inserted human genes into bacteria to produce insulin, growth hormone, and alpha-interferon, which is used to treat hairy cell leukemia.

Until recent weeks, the most raucous battle in biotechnology focused on releasing living, gene-altered bacteria outdoors. Two field tests in California in April had been delayed three years by protests and challenges and then were marred by vandalism as a result of initial scientific concerns that the microbes would spread beyond the test site. They did not.

Implications for Change In Human Genetic Code

The conflict took a new turn in April after the Patent Office decision to patent new forms of animal life, a ruling some opponents of genetic engineering characterized as a rifle shot at the human genome.

It is already possible to detect some of the 3,000 genetic diseases. It will be possible, scientists say, to cure genetic disorders by removing or adding genes. But what should the proper limits be for intervening in the human genetic code? Is asthma a genetic disease, and should that be cured genetically? What about baldness? And if diseases are curable genetically, that may also mean that traits could be added to the human genetic code, such as hair color or height.

Since 1975, the National Institutes of Health has refused to provide funds for research involving human embryos or fetuses. Senator Gore, vice chairman of the two-year-old Congressional Biomedical Ethics Board, said the panel was planning hearings on whether such grants should be reinstated.

Like every other twist in genetic engineering, the patenting of higher life forms is certain to heat emotions and generate contention among scientists. The technology is powerful and complex; if allowed to blossom, it could enable people to make direct genetic choices for their offspring and begin to determine human evolution.  

A NEW kind of vaccine, which uses direct injections of DNA particles instead of the whole virus to induce immunity, has proved effective in protecting mice against influenza A.

The new method delivers "naked" DNA directly into a cell, prompting the mice to manufacture foreign proteins and then antibodies against them, holding out promise for vaccination against other infectious diseases, scientists reported recently in the journal Science.

Immunization with DNA mimics an actual infection more closely than a traditional vaccine does. With a traditional vaccine, an artificial virus protein, or antigen, acts as a stimulus for antibody production. But with a DNA vaccine, the virus protein is made in the cell rather than in the laboratory.

As a result, the antigen in DNA immunization stimulates not only an antibody response, but also a response known as cellular immunity, in which the body manufactures so-called killer T cells to destroy infected cells.

Implications of Findings

"This technique has conceptually raised the field of vaccine research to another level," said Dr. Carole Heilman, chief of the respiratory diseases branch at the National Institute of Allergy and Infectious Diseases in Bethesda, Md. "The implications are much broader than for influenza vaccine. In theory, this technique should work for just about any infectious pathogen."

It could also pave the way for a new kind of treatment for genetic disease, autoimmune disease and cancer, scientists said. But they stressed that human application was still several years away.

"What we've been trying to do with many vaccine formulations is to present antigen so it looks like it's coming from the inside out, rather than from the outside in," said Dr. Frederick Vogel, a microbiologist in the vaccine branch of the division of AIDS at the institute. "This is actually doing that."

But some scientists say the system's reliance on killer T cells is its weakness. "The cellular immune response is a transient response," said Dr. Brian Murphy of the institute. "Unless the virus establishes a persistent infection, the T cells disappear after about two weeks and have to be replicated from memory" after a subsequent infection. This reactivation takes two to five days, he said, by which time the virus could have taken hold.

Unlike other systems intended to deliver genes into cells, DNA immunization requires no packaging. This direct injection of pure DNA is cheaper and probably safer, since other delivery systems pose a small risk of causing infections because they use immobilized viruses as DNA carriers.

Another advantage of the new system is its stability, an important factor in distributing vaccines in third-world countries. "DNA is stable at room temperature," said [Dr. Jon Asher Wolff (born 1956)], director of biochemical genetics at the University of Wisconsin, a co-discoverer of the delivery technique described in Science. "So these vaccines probably wouldn't have to be refrigerated, the way vaccines containing viruses have to be."

An Accidental Discovery

Dr. Wolff traced the vaccine's development to a fluke discovery. "At first I thought my technician, Phil Williams, had made a mistake," he said. Dr. Wolff and his collaborators at [Vical Incorporated], a San Diego biotechnology company, were using a fatty protein to package DNA for delivery into the muscle cells of mice. Proof of their success would be evidence that the cell was manufacturing the foreign protein coded for by the DNA.

As a control, they injected DNA without the protein into a comparison group of mice. But to their astonishment, the mice that received only DNA actually took up more DNA, and produced higher levels of the foreign protein, than the mice that received the DNA-plus-lipid package.

"It was so beautiful," said [Dr. Margaret Ann Liu (born 1956)], director of immunology at the Merck Research Laboratories in West Point, Pa., who later collaborated with the Vical scientists on the DNA flu vaccine. "People tried so hard with very complicated things to get DNA into cells. There was all this noise and thunder, and then in the quiet it turns out we have a very simple way of making this work."

At about the same time, scientists at other laboratories were independently making similar findings.

"When I first presented my work with what I called 'gene vaccines' in July 1992, the response was one of disbelief," said Dr. Harriet Robinson of the University of Massachusetts in Worcester, who experimented on chickens as well as mice, and inserted DNA directly into skin and mucosal cells. "The first question I was asked was, 'You don't think this will ever be useful, do you?' "

But by last September, at a scientific meeting in Cold Spring Harbor, L.I., the attitude toward gene vaccines had already changed. "All of a sudden it was working in too many laboratories to be ignored," Dr. Robinson said. "There was an appreciation that this was a very powerful, very promising, very exciting approach."

Use of DNA Gun

She and her collaborator, Dr. Joel Haynes of [Agracetus, Incorporated], in Middletown, Wis., have been delivering pure DNA into animals with a "DNA gun," which shoots gold beads coated with DNA from an influenza virus gene directly into skin cells.

The skin cells take in the DNA and make the influenza protein it directs them to make. The immune system responds with appropriate and effective antibodies and killer T cells.

Dr. Robinson said this technique induces immune protection with one one-thousandth of the flu DNA used in the Merck/Vical model.

"This system will be exceptionally useful for infections other than flu that we've never developed vaccines for," Dr. Robinson said. She said it held great promise for the control of viruses that cause measles, hepatitis and AIDS, as well as rotaviruses, which cause diarrhea in children.

INTRODUCTION

RESULTS

Monkey Model