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Official History & Timeline 2002 capture

Genentech was founded in 1976 by venture capitalist Robert A. Swanson and biochemist Dr. Herbert W. Boyer. In the early 1970s, Boyer and geneticist Stanley Cohen pioneered a new scientific field called recombinant DNA technology.

Excited by the breakthrough, Swanson placed a call to Boyer and requested a meeting. Boyer agreed to give the young entrepreneur 10 minutes of his time. Swanson's enthusiasm for the technology and his faith in its commercial viability was contagious, and the meeting extended from 10 minutes to three hours; by its conclusion, Genentech was born.

Though Swanson and Boyer faced skepticism from both the academic and business communities, they forged ahead with their idea. Within a few short years, they had proved their detractors wrong and invented a whole new industry.


Robert Swanson and Dr. Herbert Boyer founded Genentech on April 7.


Genentech produced the first human protein (somatostatin) in a microorganism (E. coli bacteria).


Human insulin cloned by Genentech scientists.


Human growth hormone cloned by Genentech scientists.


Genentech went public and raised $35 million with an offering that leapt from $35 a share to a high of $88 after less than an hour on the market. The event was one of the largest stock run-ups ever.


First recombinant DNA drug marketed: human insulin (licensed to Eli Lilly and Company).


First laboratory production of Factor VIII, a clotting factor for bleeding in hemophiliacs. Genentech announced agreement to grant license of worldwide production and marketing of Factor VIII to Cutter Biological.

(side note Cutter is the same company who had killed millions w pooled Factor VIII tainted blood)


Genentech received approval from the U.S. Food and Drug Administration (FDA) to market its first product, Protropin® (somatrem for injection) growth hormone for children with growth hormone deficiency - the first recombinant pharmaceutical product to be manufactured and marketed by a biotechnology company.


Genentech's interferon alpha-2a - licensed to Hoffmann-La Roche, Inc. as Roferon®-A - received approval from the FDA for the treatment of hairy cell leukemia.

Genentech instituted the Uninsured Patients Program, providing free growth hormone for financially needy, uninsured patients in the United States.


Genentech received FDA approval to market Activase® (Alteplase, recombinant), a tissue-plasminogen activator (t-PA), to dissolve blood clots in patients with acute myocardial infarction (heart attack).


Genentech's Uninsured Patients Program expanded to cover Activase®.


Genentech opened its day-care center, Genentech's Second Generation, one of the largest corporate-sponsored day-care centers in the U.S.


Genentech received FDA approval to market Actimmune® (Interferon gamma-1b) for the treatment of chronic granulomatous disease, a rare, inherited deficiency of the immune system resulting in frequent and severe infections. Actimmune® was added to the Uninsured Patients Program.

Genentech received FDA approval to market Activase® for the management of acute massive pulmonary embolism (blood clots in the lungs).

Genentech and Roche Holding Ltd. of Basel, Switzerland completed a $2.1 billion merger. Genentech's Hepatitis B vaccine - licensed to SmithKline Beecham Biologicals S.A. - received FDA approval.


Two licensees received approval to market t-PA in Japan and began selling it there.


Genentech and Roche announced a collaborative agreement for the development, registration and marketing of Pulmozyme® (dornase alfa, recombinant) Inhalation Solution in all major countries in Europe.

Genentech entered into research and development collaborations with Roche for- biotechnology-based automated screening of Roche's chemical library to identify new small-molecule drug candidates; a custom immunoadhesin protein based on the tumor necrosis factor (TNF) receptor.

Genentech opened the Founders Research Center, the largest biotechnology research facility in the world. The center was dedicated to founders Robert Swanson and Dr. Herbert Boyer in appreciation of their vision and determination to pursue the promise of biotechnology.


Genentech received FDA approval to market Nutropin® [somatropin (rDNA origin) for injection] for treating growth failure in children with chronic renal insufficiency before they undergo kidney transplantation.

Genentech introduced the Genentech Foundation for Growth and Development, an independent non-profit organization to advance the understanding of growth and development of children and to encourage and create research opportunities for practicing physicians and nurses who often have not had such opportunities in the past.

Genentech received approval to market Pulmozyme® for treating cystic fibrosis from regulatory agencies in the United States, Canada, Sweden, Austria and New Zealand.

Genentech's Factor VIII - licensed to Miles Inc. (formerly Cutter Biological) in 1984- received FDA approval for the treatment of hemophilia-A.

Genentech's bovine growth hormone - licensed to Monsanto Corporation and distributed under the name Posilac - received FDA approval.

The 41,000 patient GUSTO trial (Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries) showed that an accelerated infusion of Activase® combined with IV heparin reduced heart attack patient mortality by nearly 14 percent over streptokinase (a brand of Kabikinase).

Genentech was granted a permanent injunction against the Wellcome Foundation that prevents Wellcome from marketing t-PA in the United States until Genentech's patent expires in 2005.

Genentech launched Access Excellence, a $10 million nationwide communications network program designed to enable high school biology teachers across the country to access their peers as well as experts.


Genentech introduced the Pulmozyme Patient Pledge to ensure that every qualified cystic fibrosis patient in the United States who needs Pulmozyme® and its related equipment can obtain it and that Genentech's research in cystic fibrosis will continue at an aggressive pace.

Genentech received approval from regulatory agencies in the United Kingdom to market Pulmozyme® for treating cystic fibrosis.

Genentech received FDA approval to market Nutropin® for the treatment of children with growth failure due to inadequate levels of the natural growth hormone in their bodies.

Genentech announced it would locate its new $150 million manufacturing facility in Vacaville, California.


Genentech and Eli Lilly and Company settled all pending patent infringement, breach of contract, and related claims, ending a long-standing dispute regarding recombinant human growth hormone.

Genentech entered into an agreement with Alkermes, Inc. to develop sustained release formulations of up to two Genentech proteins utilizing Alkermes' proprietary ProLease® microencapsulation technology.

Genentech entered into an agreement with IDEC Pharmaceuticals for the development of IDEC's anti-CD20 monoclonal antibody, C2B8, for the treatment of non-Hodgkin's B-cell lymphomas.

Genentech received FDA approval to market an accelerated infusion regimen of Activase® for the management of acute myocardial infarction.

Genentech announced an agreement with Roche Holding, Ltd. to extend for four years Roche's option to purchase the outstanding redeemable common stock of the company at a predetermined price that escalates quarterly up to $82.50 a share. As part of the agreement, Genentech began receiving royalties rather than recording sales on European sales of Pulmozyme® and Canadian sales of all Genentech products as Roche assumed responsibility for those sales.


Genentech celebrated the 20-year anniversary of its founding.

Genentech received FDA approval to market Nutropin AQ® [somatropin (rDNA origin) injection], the first and only liquid (aqueous) recombinant human growth hormone, for treating growth failure in children with chronic renal insufficiency before they undergo kidney transplantation and for the treatment of growth hormone deficiency in children.

Genentech received FDA approval to market Activase® for the treatment of acute ischemic stroke or brain attack.

Genentech received FDA approval to market Nutropin® for the treatment of short stature associated with Turner syndrome.

Genentech received FDA approval to market Pulmozyme® for treating cystic fibrosis patients with advanced disease.


Genentech and partner IDEC Pharmaceuticals, Inc. received FDA approval to market Rituxan® (Rituximab) for the treatment of patients with relapsed or refractory low-grade or follicular, CD20 positive, B-cell non-Hodgkins lymphoma.

Genentech received FDA approval to market Nutropin AQ® for the treatment of short stature associated with Turner syndrome.

Genentech received FDA approval to market Nutropin® and Nutropin AQ® for the treatment of growth hormone deficiency in adults.

Genentech launched a service to growth hormone patients, oncology patients and their physicians called SPOC - Single Point of Contact - to provide customer-focused reimbursement assistance.

Genentech was granted patents for methods of treating hemophiliacs with recombinant human Factor VIII and recombinant human Factor VIII as a pharmaceutical product. A corresponding European patent was granted in 1991.

In recognition of the importance of Genentech in establishing the biotechnology industry in South San Francisco, the city renamed the 400 block of Point San Bruno Boulevard to DNA Way, giving Genentech the new street address 1 DNA Way.


Genentech received approval from the FDA to market the humanized monoclonal antibody Herceptin® (Trastuzumab) as a first line therapy in combination with paclitaxel and as a single agent in second and third line therapy for patients with metastatic breast cancer who have tumors that overexpress the HER2 (human epidermal growth factor receptor2) protein.

Genentech entered into an agreement with Roche providing Roche exclusive ex-U.S. marketing rights for Herceptin®.

Genentech's and IDEC Pharmaceutical Corporation's international partner Roche received approval from the European Commission in the European Union to market MabThera (known as Rituxan® in the United States). MabThera was approved for treating non-Hodgkin's lymphoma (NHL) patients who have had two or more relapses or are resistant to chemotherapy.

Genentech received FDA approval for a change in labeling for Pulmozyme®, which includes the safety and alternative administration of Pulmozyme® in cystic fibrosis patients under the age of five.

Genentech received FDA approval for the large-scale (12,000-liter) manufacture of Rituxan, enabling Genentech to supplement the Rituxan® manufactured by partner IDEC.

Genentech dedicated its new $250 million manufacturing facility in Vacaville. The 310,000-square-foot operation is the world's largest biotech manufacturing facility for the large-scale production of pharmaceutical proteins.

Genentech settled patent litigation on Novo Nordisk A/S and Genentech patents relating to human growth hormone and insulin. Novo Nordisk and Genentech cross-licensed worldwide certain patents relating to human growth hormone. Novo Nordisk received a worldwide license under Genentech patents relating to insulin and Genentech received certain payments.

Genentech signed multiparty agreements with Schering-Plough Corporation, Biogen, Inc. and Roche, settling a 1996 lawsuit that Biogen filed against Roche and Genentech related to a disputed alpha interferon invention. As a result of the settlement, the U.S. Patent Office is expected to issue a patent to Genentech/Roche for the disputed interferon alpha claim. Genentech expects to receive certain future payments.


Genentech co-founder Robert Swanson was awarded (posthumously) the National Medal of Technology for his foresight and leadership in recognizing the commercial promise of recombinant DNA technology and his seminal role in the establishment and development of the biotechnology industry.

Genentech was named one of Fortune's “100 Best Companies to Work for in America.”

Genentech reached a settlement agreement with the U.S. Attorney for the Northern District of California regarding Genentech's promotion of human growth hormone in the late 1980's and early 1990's. The $50 million settlement amount was recorded as a special charge to Genentech's first-quarter 1999 earnings.

Genentech entered into an agreement with Immunex to grant rights under Genentech's immunoadhesin patent portfolio to Immunex for its product ENBREL®.

Roche exercised its option to cause Genentech to redeem all of its outstanding special common shares not owned by Roche. Roche announced its intent to publicly sell up to 19 percent of Genentech shares and continue Genentech as a publicly traded company with independent directors.

Genentech filed with the Securities and Exchange Commission a registration statement relating to a proposed public offering of Genentech shares owned by Roche Holdings, Inc.

On July 20, after about a month long hiatus due to the Roche redemption, Genentech returned to the New York Stock Exchange (NYSE) with a public reoffering of 22 million shares by Roche, in what is considered the largest public offering in the history of the U.S. health care industry. The stock closed the first day of trading at $127, over 31 percent above the public offering price of $97. This was also the first introduction of Genentech's new NYSE trading symbol, DNA.

For the ninth time, Genentech was named one of the “100 Best Companies for Working Mothers” by Working Mother magazine.

Roche conducted a secondary offering of 20 million Genentech shares on October 20. The shares were priced at $143.50 per share, making it the largest secondary offering in U.S. history.

Genentech and CEO Art Levinson received the 1999 Corporate Leadership Award from the National Breast Cancer Coalition (NBCC) in recognition for the company's groundbreaking partnership with breast cancer advocates in the research process for Herceptin®.

Genentech and IDEC Pharmaceuticals, Corp. were honored with the 1999 Trailblazers Award from the Cure for Lymphoma Foundation for their groundbreaking research and development of Rituxan®.

Genentech and The University of California (UC) agreed to a settlement of the patent infringement lawsuit brought by UC relating to the company's human growth hormone product, Protropin®. Under the terms of the settlement agreement, Genentech will pay the University of California $150 million and make a contribution in the amount of $50 million toward construction of the first biological sciences research building at Mission Bay, a new 43-acre research and teaching campus of the University of California, San Francisco (UCSF). Both parties agree that this settlement is not an admission that Genentech infringed UC's patent or used the genetic material in question.

Genentech received FDA approval of additional efficacy results for its growth hormone products - Nutropin® and Nutropin AQ® - on the effects of growth hormone replacement therapy on spine bone mineral density in young adults with childhood-onset growth hormone deficiency (GHD).

Genentech and partner Alkermes, Inc. received FDA approval to market Nutropin Depot® [somatropin (rDNA origin) for injectable suspension] for the long-term treatment of growth failure due to a lack of adequate endogenous GH secretion.


Genentech was named to Fortune Magazine's list of “100 Best Companies to Work for in America.” In the 2000 list, Genentech rose to number 32 from its number 52 ranking the previous year.

Roche conducted a third offering of up to 19 million shares of Genentech stock at $163 per share.

Genentech received the Multiple Myeloma Research Foundation (MMRF) Corporate Leadership Award.

Genentech was presented with the 5th Annual Helix Award at the BIO 2000 International Meeting and Exhibition in Boston. The Helix Award is the highest award of excellence for the biotechnology industry.

Genentech announced the purchase of a cell culture manufacturing facility in Porriño, Spain. The facility has been established as a wholly-owned subsidiary company, “Genentech España S.L.,” and will supplement Genentech's existing bulk cell culture production capacity in South San Francisco and Vacaville.

Genentech's new state-of-the-art manufacturing facility in Vacaville, CA received FDA licensure as a multi-product facility.

Genentech received FDA approval of TNKase™ for the treatment of acute myocardial infarction (heart attack). TNKase™ is the first “clot-buster” that can be administered over five seconds in a single dose. With TNKase™, Genentech set a company shipping record for newly-approved products: The first package was shipped 9 days and 21 hours after FDA approval.

Herbert W. Boyer and the late Robert A. Swanson of Genentech were named recipients of the 2nd Annual Biotechnology Heritage Award (sponsored by BIO and the Chemical Heritage Foundation) for their contributions in shaping the biotechnology revolution.


Genentech celebrated the 25th anniversary of its founding.

For the third consecutive year, Genentech was named one of Fortune's “100 Best Companies to Work For in America.”

Cathflo™ Activase® (Alteplase), a tissue plasminogen activator (t-PA), was approved by the FDA for the restoration of function to central venous access devices (CVADs). Cathflo Activase is the only marketed thrombolytic available for this indication and offers medical professionals a viable treatment option for a CVAD complication that can hinder patient care.

The U.S. Patent and Trademark Office granted Genentech and the City of Hope a patent relating to fundamental methods and compositions used to produce antibodies by recombinant DNA technology. The decision follows almost 10 years of proceedings in the Patent Office and in the U.S. District Court to determine whether the invention covered by the patent was invented first by scientists at Genentech and City of Hope National Medical Center or by scientists at Celltech in England.

Genentech was named one of the “100 Best Companies for Working Mothers,” in the October issue of Working Mother Magazine. This was the 10th time the company has made the list.

The Genentech Foundation for Biomedical Sciences was recognized by the U. S. House of Representatives for its contributions to the education of the students in San Mateo County.


For the fourth consecutive year, Genentech was named one of Fortune's “100 Best Companies to Work For in America.”

For the second year in a row, Red Herring magazine named Genentech to its “Red Herring 100” list of companies most likely to change the world.

The FDA approved Nutropin AQ PEN™ for delivery of Nutropin AQ® recombinant growth hormone.

A Los Angeles County Superior Court jury voted to award the City of Hope (COH) $300 million in additional royalties and $200 million in punitive damages in the retrial of a contract dispute lawsuit brought by COH against Genentech. Genentech announced it will appeal the judgment in the case to the California Court of Appeal.

Genentech was named “Biotechnology Company of the Year” by Med Ad News in the magazine's July 2002 issue.

The San Francisco Business Times ranked Genentech #12 on its first annual list of corporate philanthropists in the Bay Area. 1)


by Leonard G. Horowitz and Sherri Kane

Conflicting interests damagingly taint health science and medicine. The media has been most influential in this process. Pharmaceutical propaganda facilitates geopolitical and financial agendas particularly obvious in recent years concerning the H1N1 pandemic. In this regard, social conditioning, legislation, and health care administration has been profoundly impacted by propaganda.

Hostile Takeover of American Medicine

This study examines a new genre of public health-related Hollywood films, advanced by Michael Moore, funded by “genetopharmaceutical” industrialists and media propagandists. The authors evidence a “hostile takeover” of health science and medicine that has occurred, affecting care providers and consumers worldwide. They urge consideration of the financial forces involved advancing centralized international governance, World Health Organization directives, and a new society assimilating eugenic theology merged with biotechnology for “genetopharmaceutical” industrialization.

In 2002, The Lancet1 declared the practice of medicine “heavily, and damagingly” tainted by conflicting interests. Alarmed by unethical practices in drug sales and science, the editors envisioned the crippling of the profession due to widespread fraud.

Examples included the genetic biotechnology firm Genentech, acquired by Gilead Sciences, and more recently Roche, makers of Tamiflu, an influenza drug questioned for its creation and official sanction under the administration of previous U.S. Secretary of Defense, Donald Rumsfeld.2, 3, 4

The media, according to Albert Bandura,5 influence the medical “mind-set” and behavior of people worldwide most powerfully. Stronger than the influence of parents, teachers, and peers, is the persuasive role television and film plays in learning, behavioral conditioning, and social engineering..5

Horowitz evidenced the extensive use of propaganda more recently in the documentary In Lies We Trust: The CIA, Hollywood & Bioterrorism,9 in which official censorship of science was advanced by the US Department of Health and Human Services in their “History of Bioterrorism,”10 undermining the credibility of “emergency preparedness” appeals.2)

Spring 2001 American Heritage Magazine

The DNA Dilemma

At the dawn of genetic engineering, scientists and citizens had to balance freedom of inquiry against public safety. They did surprisingly well. BY T. A. HEPPENHEIMER

IN THE LAST HALF-CENTURY, HISTORY HAS TAUGHT SOME POWERFUL LESSONS about the need to look before leaping into untested and potentially hazardous technologies. All too often we have addressed such issues only after the fact. With internal-combustion automobiles and coal-fired power plants, for example, we learned quite belatedly to address the pollution they had long been creating. And we made extensive use of pesticides such as DDT until the naturalist Rachel Carson warned of their harmful effects.

Such warnings are indispensable, but if exaggerated, they can stifle valuable research and keep beneficial innovations from reaching those who need them. As in so many areas of life, relative costs and benefits always need to be balanced in deciding how to regulate a new technology. A classic example of this give-and-take occurred irr the 1970s, as molecukirjpiologists learned to work with the processes that form the very basis of life.

Within an organism, each living cell amounts to a highly complex chemical plant that operates under the control of a computer. The cell’s computer program is embodied in its genes, which are long strings of the substance known as deoxyribonucleic acid (DNA). A piece of DNA can be thought of as a length of magnetic tape, and sometimes quite a long one: The DNA in a human cell has the width of a molecule but would stretch to a length of some nine feet. DNA has a code, a sequence of tiny submolecules designated A, T, C, and G (for adenine, thymine, cytosine, and guanine). Using this code, each gene translates into the precise specification for a well-defined protein molecule. Proteins, such as enzymes, conduct the day-to-day work of a cell: obtaining energy from food, recognizing and repairing internal damage, growing and dividing to form new cells, and otherwise contributing to the operation of whatever organ the cell is part of.

A leading researcher called for safety procedures so tight that no one could accuse the scientists of being self-serving. Later, the guidelines could be weakened.

These basic facts about DNA were established during the 1940s and 1950s. The genetic code was in hand by 1966. Soon after, scientists began to envision ways in which they might reprogram the DNA of simple organisms by inserting new genes, thus producing “recombinant DNA.” Between 1967 and 1971, investigators developed a biochemical tool kit to accomplish this, with the tools taking the form of specialized enzymes.

The first of these tools were the DNA ligases, discovered in 1967. They amounted to molecular Scotch tape, joining lengths of DNA together at their ends. In nature, these ligases help repair damaged DNA in cells. Another class of tools, discovered soon afterward, was the restriction enzymes. These enzymes, found in certain bacteria, were tantamount to molecular scissors and could cleave or cut a DNA molecule in specific and well-characterized ways. Restriction enzymes restrict the inflow of harmful genes into a bacterium by recognizing them and chopping them up, thereby protecting the organism from parasitic viruses.

The ethical confrontation surrounding genetic research began in 1971, when Paul Berg of the Stanford University Medical Center became the first molecular biologist to create gene-spliced DNA from different species, a feat that, along with his continued work in the field, would win him the Nobel Prize for chemistry in 1980. Berg joined the DNA of two viruses, a common laboratory type known as SV 40 and another called lambda phage. (A phage is a virus that preys on bacteria by injecting its own DNA into them. The new DNA then takes over the biochemical machinery of the host, which gives itself over to making many more copies of the original phage.)

Berg wanted to make duplicates of his hybrid DNA for use in subsequent experiments. To do this, he proposed to use his modified lambda phage, which contained the SV 40 genes, to infect a widely used laboratory bacterium, Escherichia coli. At this point he quickly met criticism from his colleagues, led by Robert Pollack of Cold Spring Harbor Laboratory.

E. coli lives in the human intestine; the species name coli means “of the colon.” Scientists knew that SV 40 causes tumors in mice and can turn human cells cancerous. What would happen if E. coli cells bearing SV 40 genes escaped from Berg’s lab? Might these altered bugs cause a massive outbreak of colon cancer? Berg could not rule this out, so he abandoned that part of his research.

Soon, however, others took up where Berg had left off. During 1973 Stanley Cohen of Stanford and Herbert Boyer of the University of California introduced gene-splicing techniques that were simpler than Berg’s and had considerably broader application. Berg’s process had used a phage as a biological intermediary, which was inefficient because the phage could introduce its own unwanted genes. Cohen and Boyer found a way to insert new genes much more directly into the DNA of E. coli, with the bacterium accepting the new genes as if they had been part of its genetic complement all along. Their method made use of plasmids, small circular DNA molecules that exist in a cell separate from its chromosomes. Cohen and Boyer extracted a plasmid from a bacterial cell, inserted new DNA into the plasmid, and then reinserted it into the cell.

At first Cohen and Boyer limited themselves to transplanting genes from other bacteria. Then, to show the strength of their technique, they inserted genes from a higher animal, the African clawed frog. They verified that their E. coli cells duplicated the new frog genes along with their native genes when reproducing. They did this by showing that the bacteria also produced molecules that were characteristic of this frog.

With these successes, molecular biology could look ahead to new and highly promising vistas. Scientists could now investigate some of the deepest questions about the fundamental processes of life by deleting or adding genes to E. coli and observing the consequences. Besides yielding new insight into diseases, the technique could make it possible to turn microbes into protein factories, churning out medically useful hormones such as insulin.

These matters drew attention in June 1973, when the nation’s molecular biologists gathered in New Hampshire at their annual Gordon Research Conference. Berg and Pollack had already hosted an initial discussion on potential hazards in biological research. At the Gordon meeting, Cohen presented his work with E. coli. Then, at a special session held after the main meeting, participants talked about both the promise and the potential risks of the new genetic techniques.

The impromptu session brought broad agreement that the issue demanded closer attention. Two conference co-chairs, Maxine Singer of the National Institutes of Health (NIH) and Dieter Soil of Yale, took the initiative in sending letters to the presidents of the National Institute of Medicine (NIM) and the National Academy of Sciences (NAS). Summarizing recent work on gene-splicing, they wrote that “such hybrid molecules may prove hazardous to laboratory workers and to the public.” They added that many of the Gordon attendees wanted the NIM and the NAS to “establish a study committee to consider this problem and to recommend specific actions or guidelines. …”

The NAS responded by asking Berg to head the study group. His fellow panelists would include Boyer; Cohen; David Baltimore, who later became the president of Caltech; and James Watson, whose 1953 discovery (with Francis Crick) of the molecular structure of DNA had laid the groundwork for all subsequent research in the field.

These scientists expected that E. coli would continue to be the focus of molecular biologists’ work. It had been in common use for decades, it was easily grown, and it adapted readily to life in the laboratory without being virulent or requiring exceptional precautions. Indeed, so many microbiologists had worked with it that it could be described as the best-understood species in the world, man included.

In July 1974, as an interim measure, Berg’s group published a letter in the journals Science and Nature, both of which are read by scientists throughout the world. The letter proposed sharp limits on some of the most interesting areas of research. It recommended an international moratorium on transfers of genes that might promote cancer, even though the origins of cancer were a matter of great medical importance. The moratorium would also prohibit work that could enhance the ability of bacteria to produce toxins or to resist antibiotics, even though toxin production and antibiotic resistance were topics of considerable significance. More broadly, the letter urged great care with transfers of animal DNA into microbes, because long strings of DNA from such sources might contain hidden or dormant DNA common to viruses, which could spring to life and turn E. coli into a source of cancer.

Around the world, with no organized opposition, researchers agreed not to pursue such studies. Next, in February 1975, an international meeting on the subject was held in Asilomar, California. Much of the discussion dealt with technical issues. However, the attendees also listened to talks by lawyers, who spoke of potential legal liability and multimillion-dollar lawsuits.

Berg’s moratorium did not cover all gene-splicing experiments, or even most of them. It was aimed specifically at work that might turn DNA into a severe health hazard, such as by creating an E. coli strain that could produce diphtheria toxin or a pneumonia germ resistant to penicillin. The participants in the Asilomar meeting drafted some preliminary guidelines for safety. Sydney Brenner, one of the conference leaders, pointed out that a successful guideline would be one that in the future could be made weaker. He called for safety procedures so tight that no one could ever accuse the scientists of being cavalier or self-serving.

Particular concern surrounded proposals to transplant genes from birds and mammals, including humans, into bacteria. The prospect of producing tumors in this way was purely speculative. No researcher had ever done so, not even in laboratory mice that had been bred to show strong susceptibility to cancer. Still, no simple test could rule it out; elaborate and lengthy studies would have been required, involving transplants of many types of DNA segment from all interesting donor species.

The attendees at Asilomar built their guidelines around the existing protocols for safety in microbiology labs. The lowest level of protection, designated “minimal-risk” containment, merely called for such standard practices as wearing lab coats and promptly disinfecting any source of contamination. This safety level was reserved for transplants of DNA from microbes that could already exchange genes with E. coli naturally.

After that, the precautions ratcheted up sharply. A “low-risk” lab restricted access and used airfiltering safety cabinets, some of whose interiors could be reached only with built-in gloves. Such safeguards had long been adequate even when dealing with microbes that cause typhus, botulism, and cholera. At Asilomar, however, it was decided that they would accommodate only DNA from nonpathogenic microbes, plants, fishes, insects, and reptiles or amphibians. DNA from higher animals demanded even greater protection.

DNA from mammals and birds constituted a “moderate risk.” This involved more extensive use of glove boxes and reduced air pressure in the lab to ensure that any flow of air would be inward. DNA from known pathogens called for “high-risk” containment, with safeguards suitable for a military germ-warfare research center. These included air locks and specialized clothing, with exhaust air being heated to a very high temperature or passed through special filters. Besides these physical methods, the Asilomar attendees also anticipated biological containment. They called for the use of a modified strain of E. coli that was genetically enfeebled and incapable of surviving outside a laboratory. Even if any of these microbes did escape, they would quickly die.

These guidelines became the basis for a more formal set of rules that the NIH issued in June 1976. The NIH standards were even more restrictive than those of Asilomar. They defined the safety levels Pl through P4, corresponding approximately to the Asilomar report’s minimal risk through high risk. The NIH adopted a simple rule of thumb: The more closely a donor species was related to humans, the greater the risk. Even so, just as in Asilomar guidelines, the highest level of containment was reserved for particularly deadly microorganisms like anthrax bacilli and smallpox viruses. But finally, with the rules in place, most experiments could go forward, at least in principle. In practice, few research centers had the costly P3 or P4 facilities, and enfeebled strains of E. coli were not immediately available. So most investigators were effectively limited to work with DNA from amphibians, fishes, and invertebrates.

Controversy arose anyway. Since DNA was nothing less than the essence of life, gene-splicing amounted to creating new life forms. Many people worried that this came perilously close to playing God. Moreover, skeptics found it hard to imagine that scientists would design and implement laboratory safeguards strong enough to protect the public if it meant hobbling their research programs. If scientists conceded the existence of potential dangers, it was reasoned, the real hazards must be far greater than they were willing to admit. If they saw the need to introduce an enfeebled E. coli strain, this could only mean that the standard strain was too dangerous for common use. If work with primate DNA demanded facilities suitable for research on germ warfare, then bacteria carrying such genes might well have the power to wipe out entire cities.

Brenner’s approach had backfired: Adoption of the severest possible guidelines had served to inflame public fears among some people, rather than to soothe them. Gene-splicing evoked thoughts of Frankenstein and Brave New World, and as the NIH guidelines reached final form, the controversy entered the realm of public debate. This happened particularly vividly in Cambridge, Massachusetts.

Cambridge, the home of Harvard University and MIT, is largely a bluecollar town. In 1976 senior faculty members at Harvard wanted to install a P3 lab within an existing campus building. The building was old and infested with cockroaches and ants, which heightened uneasiness over the proposed research. The mayor, Alfred Vellucci, liked to play to his constituents by thumbing his nose at Harvard. He was well known for having suggested that the university chop down its majestic elm trees and turn Harvard Yard into a parking lot to serve a Harvard Square that would be renamed the Piazza Leprechauna.

The scientists’ cautious approach backfired, as adoption of the severest possible guidelines served to inflame public fears instead of soothing them.

Mayor Vellucci learned of the proposed lab from a longtime scientific gadfly, the Nobel Prize -winning Harvard biologist George WaId, and from a local left-wing newspaper, the Phoenix. He was outraged. “They may come up with a disease that can’t be cured,” he warned. “We want to be damned sure the people of Cambridge won’t be affected by anything that would crawl out of that laboratory.” Heated and passionate public meetings were held in June and July 1976, at which Vellucci sought an outright two-year ban on DNA research. After learning that the city council lacked the necessary legal authority, he agreed to accept a voluntary three-month moratorium on P3-level research.

The council set up a citizens’ committee to make recommendations. No molecular biologists sat on the committee, but its members took their work seriously and put much effort into learning about the pertinent issues. Their report, approved by the city council in February 1977, endorsed the NIH guidelines but recommended making them even tighter. All P3 work was to use enfeebled rather than standard E. coli (by then such weakened strains were widely available). Other rules guaranteed that standard E. coli would not enter the intestines of lab workers as a contaminant, ensured that experiments would follow the NIH rules even when not funded by that institution, and mandated tests to monitor the possible survival and escape of mutant bacteria.

For the scientists of Cambridge, this conclusion gave hope that they could hold their own in a democratic debate, even when pressured by the populist Vellucci and by a knowledgeable but alarmist Wald. Unfortunately, many other cities and states were threatening to enact their own restrictions, with real teeth, and there was no guarantee that the outcome would be as well considered as in Cambridge.

Thus far, enforcement of the restrictions and guidelines had relied largely on scientists’ good faith. Berg’s 1974 moratorium had been maintained through peer pressure. The 1976 NIH guidelines rested on the authority of the NIH to terminate a grant to any researcher who failed to comply, but this sanction was less severe than it might have been, since the pharmaceutical industry had plenty of money to throw around. Now, however, a law with all the force and authority of the state was making its way through the New York legislature. Robert Pollack, who had warned Berg of DNA hazards years before, opposed this statute because it would turn the county health commissioner into “the sole arbitrator of our individual research efforts, with the power to levy a $5000/day fine if he and an investigator differed on any point of scientific procedure.” There would be no right of appeal to the NIH.

In Washington the habitually interventionist Sen. Edward Kennedy of Massachusetts held hearings on a proposed strict law that would pre-empt state and local ordinances. Scientists reacted predictably. “There are a whole bunch of regulators here who have discovered that we have been doing genetics for 30 years without permission,” an MIT biologist told Science.

Other draft bills proposed prison sentences or fines of $10,000 per day for violations. Scientists conducting DNA research were to be “strictly liable, without regard to fault”—a provision sufficiently sweeping as to shut down virtually all work on gene-splicing. One researcher who had been on Berg’s 1974 review committee, Norton Zinder, wrote in December 1977 that such bills would have “set up vast bureaucracies, cumbersome licensing, harsh penalties and tedious reporting procedures. Their rhetoric implied that scientists were guilty until proven innocent and hence the bills contained search and seizure provisions. They read like a narcotics bill.”

Leaders of the scientific community responded to the threat of harsh legislation by lobbying. The presidents of major professional groups, including the American Society for Microbiology, called for laws that would merely enact the NIH guidelines, without criminal penalties. The NAS passed a similar resolution. In June 1977, attendees at that year’s Gordon Conference signed a letter warning that new laws could “inhibit severely” their work with DNA. The letter also took a strong stand against “exaggerations of the hypothetical hazards” of this research “that go far beyond any reasoned assessment.”

The New York State law was an initial target. Zinder declared in 1977 that it was so badly drafted that its restrictions might extend to the whole field of molecular biology. Scientists failed to kill the bill while it was in the legislature, but when it reached the desk of Gov. Hugh Carey, he showed courage by vetoing it. Carey declared that any regulation of science should follow a national standard, and any law intruding on freedom of inquiry must be narrowly and precisely drawn. (In 1978 he signed a bill essentially requiring compliance with the NIH guidelines.) Significantly, his act stirred no firestorm of public outrage. Voters were concerned but not panic-stricken. This lack of political consequences persuaded Kennedy to withdraw support for his bill in September, and Congress soon tabled its other DNA bills as well.

By then, research results were suggesting that the NIH guidelines could actually be weakened considerably with no loss of safety. An important contribution to the debate came from Roy Curtiss of the University of Alabama. He had envisioned particularly severe hazards from gene-splicing and had called for Berg’s moratorium to be extended to virtually all such experiments. But in April 1977 he declared that he had changed his mind, since numerous gene-splicing experiments had been conducted with no apparent harm.

“I have gradually come to the realization that the introduction of foreign DNA into [E. coli] offers no danger whatsoever to any human being,” he wrote, adding that “the arrival of this conclusion has been somewhat painful and with reluctance because it is contrary to my past ‘feelings’ about the biohazards.” An MIT researcher later commented, “The Curtiss paper has had a big impact because he started from the other side and is a very credible guy.”

That June, 50 invited specialists in E. coli gathered at a workshop in Falmouth, Massachusetts. Following their two-day meeting, they concluded unanimously that this bacterium could not be turned into a dangerous pathogen through inserts of DNA. Concern had centered on the prospect that an experiment that had been presumed safe would inadvertently create a dangerous mutant. But Berg and Cohen noted that “during the past four years, more than 200 scientific investigations involving recombinant DNA have been published, and literally hundreds of billions of bacteria containing a wide variety of recombinant DNA molecules have been grown and studied, with no indication of harm to humans or to the environment. Despite extensive efforts to detect some evidence of actual or potential hazard, none has been found.”

Even in its standard lab version, E. coli had been so weakened through long adaptation to life in laboratories that it could not colonize human or animal digestive tracts. Enfeebled strains prepared by Curtiss were safer still; even if they somehow managed to escape from a lab, they would simply self-destruct. The addition of outside genes made these germs weaker still.

Environmental groups, however, continued to urge a tightening of the rules. The Natural Resources Defense Council (NRDC) suggested scrapping the NIH guidelines and simply rating experiments as Prohibited, Very Hazardous, and Hazardous. Friends of the Earth filed a lawsuit challenging the legality of DNA research unless it was accompanied by a laborious environmental impact statement.

The environmentalists met strong opposition from their own scientific advisers. Lewis Thomas, president of the Memorial Sloan-Kettering Cancer Center, resigned from the Friends of the Earth advisory council, citing his “flat disagreement on straightforward scientific grounds” with its “rigid position.” Paul Ehrlich, author of The Population Bomb, attacked the same organization for its concern with “imagined risks.” René Dubos, another well-known author and a trustee of the NRDC, wrote that the group had “no competence” in offering advice on DNA research and was promoting “a cause that I regard as ridiculous.”

Amid this change in the scientific climate, the NIH went forward with a major relaxation of the rules. The new guidelines, adopted early in 1979, allowed most experiments to proceed at level Pl or P2. The more stringent P3 would be reserved for DNA from sources that were pathogenic or produced toxins. Few, if any, experiments would require P4.

To further test the safety of gene-splicing, NIH staff scientists intentionally sought to create dangerous forms of E. coli. This work was so hazardous that it required both a P4 facility and the use of an enfeebled strain. They used the complete gene sequence of a virus that easily causes cancer in mice, though it was not known to infect humans.

The researchers inserted this sequence into their enfeebled E. coli, verified that the desired genes were present, and then injected their mutant germs into the mice. They found that these gene-spliced bacteria were less than one-billionth as carcinogenic as the naked virus and published the results in March 1979. With this deliberate attempt to create danger having failed, it looked less likely than ever that inadvertence could lead to monsters from the lab. Within months, the NIH responded by markedly easing procedures for compliance with the rules. Two years later it went further, virtually eliminating federal regulation of DNA research. The new rules changed mandatory restrictions into voluntary guidelines and removed penalties for violations.

Scientists deliberately sought to create a dangerous strain of E. coli. The result was less than a billionth as carcinogenic as the virus they had taken the DNA from.

These developments encouraged venture capitalists and entrepreneurs who were working to launch a gene-splicing industry in Silicon Valley. Herbert Boyer, who had been among the first to insert genes directly into E. coli, was in the forefront of this new activity. In 1976 he cofounded the firm of Genentech. Its goal was to turn gene-splicing into a practical technology by using modified E. coli to produce substances that would be useful in medicine.

A series of research successes quickly gained the new company a strong reputation. In 1977 Boyer and his colleagues announced a process to produce the hormone somatostatin, which acts in the body to regulate the secretion of other hormones. In 1978 Genentech came out with a process for human insulin, a potential replacement for the insulin from cattle and pigs that diabetics had been using for decades. In 1979 the company successfully produced human growth hormone, which prevents dwarfism. The following year, it announced a process for Interferon, which had shown promise in fighting cancer. Also in 1980, it went public by issuing stock on the New York Stock Exchange.

The first public sale came on October 14, when it opened at $35 a share. Twenty minutes later it was at $89; it closed the day’s trading at $71.25. At that moment, the value of all its stock theoretically totaled $529 million, one-twelfth the value of the chemical giant Du Pont. Clearly, brokers were bullish on bacteria. Wall Street had awaited Genentech’s debut with eagerness, but even veteran traders were astonished by this performance.

A year later, the University of Maryland set up the nation’s first program to train genetic engineers, and Genentech announced another success, with a vaccine against hoof-and-mouth disease in cattle. Science reported in April 1981 that since October 1979 the NIH had approved 18 proposals to apply recombinant DNA on a commercial scale. The firms included such pharmaceutical giants as Eli Lilly, Schering-Plough, and Hoffmann-La Roche.

The realm of gene-splicing expanded further during the 1980s. Another startup firm, Amgen, introduced a protein called Epogen that controlled anemia. Epogen went on to become the most successful product in the biotechnology industry. A long-established medical firm, Merck Laboratories, along with the Chiron corporation, pushed the field into the domain of human vaccines with Recombivax HB, which protected against a form of hepatitis.

The new successes brought new controversies. A case in point was bovine growth hormone, which raised hackles among consumers. It stimulated milk production in cows, but it was like giving steroids to athletes, and people were frightened by the specter of hormones in their hamburgers. Dairy farmers also balked, for fear that small numbers of supercows would glut the market with milk.

These bovine hormones continued to come from genespliced E. coli strains. During the 1990s, several firms went a step farther, splicing genes into the seeds of food crops. This triggered more controversy. Monsanto, for example, has sold large quantities of a genetically altered soybean seed called Roundup Ready. It confers resistance to Monsanto’s own Roundup herbicide, allowing farmers to spray at will without damaging their crops. This encourages them to use more Roundup, and environmentalists have complained that the result is more pesticide residue.

A more benign pesticide, known as Bt, consists of a common soil bacterium, Bacillus thuringiensis. The toxins it produces are a safe and effective natural insecticide and are popular with organic farmers. Monsanto and other firms have transplanted the pertinent bacterial genes into corn and cotton seeds. The resulting crops are naturally resistant to the European corn borer and the cotton bollworm, for the new genes enable them to produce their own Bt toxin. A study in Arizona has shown farmers cutting their use of chemical insecticides by 75 percent with the seeds.

Still, questions remain. Activists have made much of a 1999 experiment in which a Cornell University entomologist, John Losey, fed corn pollen containing Bt genes to monarch butterfly caterpillars. Many of the caterpillars died, raising the prospect of danger to the insect population. Other critics have asked if pests might develop resistance to Bt, forcing farmers to turn to stronger chemicals.

A sore point to some activists is a 1992 ruling by the Food and Drug Administration that gene-spliced foods don’t require labeling or tests for safety. Farmers have responded enthusiastically. Today some one-fourth of the nation’s corn is genetically altered, while 70 percent of processed food contains ingredients from transgenic corn, soybeans, and other plants. Critics have demanded, as a minimum, that gene-spliced food be so labeled. Manufacturers have resisted, declaring that consumers would wrongly infer that the foods were unsafe.

The protests have had some success. The environmental group Greenpeace has prevailed on Gerber to keep transgenic ingredients out of its baby foods. Yet the most plausible potential danger from such foods would appear to be allergies, which arise often enough from unmodified products. Even this may prove to be another conjectural hazard that fails to materialize in the real world. Some people have complained of illness after eating genetically modified corn, but scientists have been unable to show that genetically altered food was the cause.

Moreover, the prospect now exists that genetically altered crops may aid the struggle against world hunger. A pair of European scientists have crafted a modified strain of rice that produces beta carotene, a building block of vitamin A. Rice, a staple in much of the world, naturally lacks this vitamin, a deficiency of which kills more than a million children a year and blinds hundreds of thousands more. The new rice may in time prevent this. (note see epic failure of Golden Rice myth)

Today, 20 years after Genentech became the darling of Wall Street, the world of recombinant DNA shows many solid achievements, but all of them have been fairly modest in scale, limited to specific ailments and not always common ones. Work with DNA has yet to produce accomplishments on a par with the antibiotics and polio vaccines of the postwar years. In agriculture, gene-spliced crops have not approached the importance of hybrid corn or of the Green Revolution, whose increased yields now feed half the world.

Nevertheless, the debate during the 1970s stands out as a fine example of democracy in action. The field of molecular biology was highly abstruse; the potential for widespread panic was high. Yet on the whole, most of the participants in the debate behaved admirably. The public stayed cool, avoiding extremes of credulity or hysteria. Congress and other government officials avoided a rush to judgment that would have treated scientists like heroin dealers. When ordinary citizens came face to face with technical issues, as on the Cambridge advisory committee, they worked seriously to learn the subjects, and their recommendations were well founded. Then, when specialists came forth with strong evidence that greatly reduced the prospect of danger, they succeeded in swaying the NIH. In turn, the agency responded with integrity, refusing to play to the galleries. In demonstrating that such a consensual process could deal fairly and effectively with even this most recondite of controversies, the nation’s DNA researchers made perhaps their greatest contribution to the nation’s well-being.

T. A. Heppenheimer is a frequent contributor to Invention & Technology.3)

FREE Zone Foreign Labs for Banned Research

The Italian Business Council Dubai hosts a business luncheon with DuBiotech Free Zone Executive Director

United Arab Emirates: Wednesday, March 24 - 2010 at 12:04

The Italian Business Council Dubai (IBCD) hosted a business luncheon with special guest Dr. Marco Baccanti, Executive Director of Dubai Biotechnology and Research Park (DuBiotech) - the major life sciences hub in the Middle East and a member of Tecom Investments - at the Shangri La Hotel.

Dr. Ottavia Molinari, President of the Italian Business Council Dubai after welcoming the numerous guests introduced Dr. Marco Baccanti, Dubiotech Free Zone Executive Director who delivered a speech with special topic `Benefits of the free zone for the Life Sciences Industry in Dubai`.

Dr. Marco Baccanti, said; “Launched in 2005, the Dubai Biotechnology and Research Park, has the mission to create the biggest life sciences cluster in the Middle East, adopting a sustainable strategy. Its business model is based on providing the best environment for major players in the life sciences industry and research through leveraging the benefits of its location in Dubai, offering free zone benefits and creating world class infrastructure.”

Dr. Baccanti explained that the free zone currently hosts already 65 major pharmaceutical firms including Pfizer, Genzyme, Merck -Serono and Amgen as well as companies specialized in biomedical and scientific devices, biotechnology, cosmesis, and enzymes.

He added, “DuBiotech offers flexible laboratory space as one of the key components of the sprawling business park. In addition to hosting a range of assets varying from offices to warehouses and land for manufacturing, the 22 million sq. ft. biotechnology cluster enjoys a strategic location with world-class infrastructure. A number of free zone-associated incentives such as full ownership, tax-free profit repatriation and business friendly environment that DuBiotech offers makes the cluster an ideal destination for life sciences companies seeking to address the fast growing regional markets.”

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Funding Universe DuPuy Pharma Lineage

1992: DePuy forms alliance with Genentech, Inc

Key Dates:

1895- Revra DePuy founds DePuy Manufacturing in Warsaw, Indiana.

1921- Revra DePuy dies; his wife Winifred takes control of the company.

1949- Winifred dies, and passes control of company to her second husband, Herschel Leiter; Herschel Leiter marries Amrette Webb Ailes.

1950- Leiter dies.

1951- Amrette Leiter marries Harry Hoopes; the couple run DePuy jointly.

1965- A group of investors, led by Bill Weaver, purchases DePuy from the Hoopeses.

1968- DePuy is acquired by Bio-Dynamics; DePuy enters hip replacement sector; DePuy purchases Kellogg Industries.

1974- DePuy is acquired by Boehringer Mannheim Companies (owned by Corange Ltd.).

1987- DePuy forms a partnership with E.I. duPont de Niemours and Co.

1990- Boehringer Mannheim purchases Charles F. Thackray Ltd.

1992- DePuy forms alliance with Genentech, Inc.; DePuy acquires the Rotek Company.

1993- DePuy enters into a joint venture with Biedermann Motech dubbed DePuy Motech.

1994- Corange purchases ACE Medical Products and forms new company, DePuy ACE Medical Co.

1996- DePuy acquires Landanger-Camus; Corange announces an IPO for DePuy.

1998- Roche Holding Ltd. purchases Corange in a transaction that includes DePuy; DePuy acquires AcroMed Corp., thereby becoming the world's second largest spinal implant company; Johnson & Johnson purchases DePuy from Roche.4)

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