Biotechnology Timeline 1977

1977 - Present: The Dawn of Biotech

Genetic engineering became a reality when a man-made gene was used to manufacture a human protein in a bacteria for the first time. Biotech companies and universities were off to the races, and the world would never be the same again. In 1978, in the laboratory of Herbert Boyer at the University of California at San Francisco, a synthetic version of the human insulin gene was constructed and inserted into the bacterium Escheria coli. Since that key moment, the trickle of biotechnological developments has become a torrent of diagnostic and therapeutic tools, accompanied by ever faster and more powerful DNA sequencing and cloning techniques.

1977

Genentech, Inc., reports the production of the first human protein manufactured in a bacteria: somatostatin, a human growth hormone-releasing inhibitory factor. For the first time, a synthetic, recombinant gene was used to clone a protein. Many consider this to be the advent of the Age of Biotechnology.

Sixteen bills introduced in Congress to regulate recombinant DNA research. The bills called for the development of bacteria and plasmids that could be prevented from escaping from the laboratory environment. None of the bills passed.

Bill Rutter and Howard Goodman isolated the gene for rat insulin.

Walter Gilbert and Allan Maxam at Harvard University devised a method for sequencing DNA using chemicals rather than enzymes.

1978

Genentech, Inc. and The City of Hope National Medical Center announced the successful laboratory production of human insulin using recombinant DNA technology.

Harvard researchers used genetic engineering techniques to produce rat insulin.

Stanford University scientists successfully transplanted a mammalian gene.

Studies by David Botstein and others found that when a restrictive enzyme is applied to DNA from different individuals, the resulting sets of fragments sometimes differ markedly from one person to the next. Such variations in DNA are called restriction fragment length polymorphisms, or RFLPs, and they are extremely useful in genetic studies.

William J. Rutter's lab at UCSF cloned a coat protein of the virus that causes hepatitis B.

1979

John Baxter reported cloning the gene for human growth hormone.

1980

The U.S. Supreme Court ruled in that genetically altered life forms can be patented a Supreme Court decision in 1980 allowed the Exxon oil company to patent an oil-eating microorganism. This ruling opened up enormous possibilities for commercially exploiting genetic engineering.

Researchers successfully introduce a human gene--one that codes for the protein interferon--into a bacterium.

Kary Mullis and others at Cetus Corporation in Berkeley, California, invented a technique for multiplying DNA sequences in vitro by, the polymerase chain reaction (PCR). PCR has been called the most revolutionary new technique in molecular biology in the 1980s. Cetus patented the process, and in the summer of 1991 sold the patent to Hoffman-La Roche, Inc. for $300 million.

1981

Genentech, Inc. cloned interferon gamma.

Bill Rutter and Pablo Valenzuela published a report in Nature on a yeast expression system to produce the hepatitis B surface antigen.

Scientists at Ohio University produced the first transgenic animals by transferring genes from other animals into mice.

Mary Harper and two colleagues mapped the gene for insulin. Mapping by in situ hybridization became a standard method.

Hoechst AG, a West German chemical company, gave Massachusetts General Hospital, a teaching facility of Harvard Medical School, $70 million to build a new Department of Molecular Biology in return for exclusive rights to any patent licenses that might emerge from the facility.

Congressman Al Gore held a series of hearings on the relationship between academia and commercialization in the arena of biomedical research. He focused on the effect that the potential for huge profits from intellectual property and patent rights could have on the research environment at universities. Jonathan King, a professor at MIT speaking at the Gore hearings, reminded the biotech industry that "the most important long-term goal of biomedical research is to discover the causes of disease in order to prevent disease."

1982

Genentech, Inc. received approval from the Food and Drug Administration to market genetically engineered human insulin. 1982 The U.S. Food and Drug Administration approves the first genetically engineered drug, a form of human insulin produced by bacteria.

Applied Biosystems, Inc. introduced the first commercial gas phase protein sequencer, dramatically reducing the amount of protein sample needed for sequencing.

Lindow requested government permission to test genetically engineered bacteria to control frost damage to potatoes and strawberries.

Michael Smith at the University of British Columbia, Vancouver, developed a procedure for making precise amino acid changes anywhere in a protein.

Richard Goldstein and Richard Novick called for the prohibition of the use of RNA technologies in the development of biological weapons.

1983

Eli Lilly received a license to make insulin.

Syntex Corporation received FDA approval for a monoclonal antibody-based diagnostic test for Chlamydia trachomatis.

Stanford Research Institute International filed for a patent for an E. coli expression vector.

Jay Levy's lab at UCSF isolated the AIDS virus at almost the same moment it was isolated at the Pasteur Institute in Paris and at the NIH.

U.S. patents were granted to companies genetically engineering plants.

A study of an extended family in Venezuela with Huntington's chorea demonstrated that family members with the disease show a distinct and characteristic pattern of restriction fragment lengths, leading to a new screening test. The same methods of investigation revealed patterns for cystic fibrosis, adult polycystic kidney disease, Duchenne muscular dystrophy, and others.

Marvin Carruthers at the University of Colorado devised a method to construct fragments of DNA of predetermined sequence from five to about 75 base pairs long. He and Leroy Hood at the California Institute of Technology invented instruments that could make such fragments automatically.

1984

Cal Bio scientists described in Nature the isolation of a gene for anaritide acetate, which helps to regulate blood pressure and control salt and water excretion.

The Plant Gene Expression Center was established.

Stanford University received a product patent for prokaryote DNA.

Chiron Corp. announced the first cloning and sequencing of the entire human immunodeficiency virus (HIV) genome.

Charles Cantor and David Schwartz developed pulsed-field gel electrophoresis.

Alec Jeffreys introduces technique for DNA fingerprinting to identify individuals.

1985

Genetic fingerprinting enters the court room.

Axel Ullrich reported the sequencing of the human insulin receptor in Nature. Bill Rutter's UCSF team described the sequencing in Cell two months later.

Cal Bio cloned the gene that encodes human lung surfactant protein, a major step toward reducing a premature birth complication.

Cetus Corporation's develops GeneAmp polymerase chain reaction (PCR) technology, which could generate billions of copies of a targeted gene sequence in only hours.

Genetically engineered plants resistant to insects, viruses, and bacteria were field tested for the first time.

The NIH approved guidelines for performing experiments in gene therapy on humans.

Genetic Sciences surreptitiously performed the first deliberate release experiment, injecting genetically engineered microbes into trees growing on the company's roof, while waiting for approval from the EPA to conduct a different deliberate release experiment involving strawberry plants.

1986

UC Berkeley chemist Peter Schultz described how to combine antibodies and enzymes (creating "abzymes") to create pharmaceuticals.

Orthoclone OKT3Ž (Muromonab-CD3) approved for reversal of acute kidney transplant rejection.

A regiment of scientists and technicians at Caltech and Applied Biosystems, Inc., invented the automated DNA fluorescence sequencer.

The FDA granted a license for the first recombinant vaccine (for hepatitis) to Chiron Corp.

The EPA approved the release of the first genetically engineered crop, gene-altered tobacco plants.

1987

Genentech received FDA approval to market rt-PA (genetically engineered tissue plasminogen activator) to treat heart attacks.

Calgene, Inc. received a patent for the tomato polygalacturonase DNA sequence, used to produce an antisense RNA sequence that can extend the shelf-life of fruit.

Advanced Genetic Sciences, Inc. conducted a field trial of a recombinant organism, a frost inhibitor, on a Contra Costa County strawberry patch.

Maynard Olson and colleagues at Washington University invented "yeast artificial chromosomes," or YACs, expression vectors for large proteins.

Centocor's CA 125TM, diagnostic serum tumor marker test for ovarian cancer, is approved by the FDA.

Recombivax-HBŽ (recombinant hepatitis B vaccine) approved.

1988

Harvard molecular geneticists Philip Leder and Timothy Stewart awarded the first patent for a genetically altered animal, a mouse that is highly susceptible to breast cancer.

SyStemix Inc. received a patent for the SCIDHU Mouse, an immune-deficient mouse with a reconstituted human immune system. The mouse was engineered for AIDS research.

Genencor International, Inc. received a patent for a process to make bleach-resistant protease enzymes to use in detergents.

Hoffmann-La Roche, Inc. and Cetus Corp. negotiated a licensing agreement for two anti-cancer drugs, Interleukin-2 and Polyethylene Glycol Modified IL-2. This agreement became the prototype for cross-licensing between companies with parallel patents.

1989

UC Davis scientists developed a recombinant vaccine against the deadly rinderpest virus, which had wiped out millions of cattle in developing countries.

Creation of the National Center for Human Genome Research, headed by James Watson, which will oversee the $3 billion U.S. effort to map and sequence all human DNA by 2005.

EpogenŽ (Epoetin alfa) a genetically engineered protein introduced, providing a means to help patients with kidney failure.

1990

UCSF and Stanford University were issued their 100th recombinant DNA patent license. By the end of fiscal 1991, both campuses had earned $40 million from the patent.

ActimmuneŽ (Interferon gamma-1b) approved for treatment of chronic granulomatous disease.

AdagenŽ (adenosine deaminase) approved for treatment of severe combined immunodeficiency disease.

The first successful field trial of genetically engineered cotton plants was conducted by Calgene Inc. The plants had been engineered to withstand use of the herbicide Bromoxynil.

The FDA licensed Chiron's hepatitis C antibody test to help ensure the purity of blood bank products.

Michael Fromm, molecular biologist at the Plant Gene Expression Center, reported the stable transformation of corn using a high-speed gene gun.

Mary Claire King, epidemiologist at UC-Berkeley, reported the discovery of the gene linked to breast cancer in families with a high degree of incidence before age 45.

GenPharm International, Inc. created the first transgenic dairy cow. The cow was used to produce human milk proteins for infant formula.

The first gene therapy takes place, on a four-year-old girl with an immune-system disorder called ADA deficiency. The therapy appeared to work, but set off a fury of discussion of ethics both in academia and in the media.

The Human Genome Project, the international effort to map all of the genes in the human body, was launched. Estimated cost: $13 billion. 1990 Formal launch of the international Human Genome Project.

Publication of Michael Crichton's novel Jurassic Park, in which bioengineered dinosaurs roam a paleontological theme park; the experiment goes awry, with deadly results.

1991

The celebrated reference work "Mendelian Inheritance in Man," was made available through an on-line computer network. The catalogue lists some 5,600 genes known or thought on good evidence to be inherited in Mendelian patterns.

Analyzing chromosomes from women in cancer-prone families, Mary-Claire King, of the University of California, Berkeley, finds evidence that a gene on chromosome 17 causes the inherited form of breast cancer and also increases the risk of ovarian cancer.

1992

The U.S. Army begins collecting blood and tissue samples from all new recruits as part of a "genetic dog tag" program aimed at better identification of soldiers killed in combat.

American and British scientists unveil a technique for testing embryos in vitro for genetic abnormalities such as cystic fibrosis and hemophilia.

1993

Kary Mullis won the Nobel Prize in Chemistry for inventing the technology of polymerase chain reaction (PCR).

Chiron's Betaseron is approved as the first treatment for multiple sclerosis in 20 years.

The FDA declares that genetically engineered foods are "not inherently dangerous" and do not require special regulation.

The Biotechnology Industry Organization is created by merging two smaller trade associations.

George Washington University researchers clone human embryos and nurture them in a Petri dish for several days. The project provokes protests from ethicists, politicians and critics of genetic engineering.

An international research team, led by Daniel Cohen, of the Center for the Study of Human Polymorphisms in Paris, produces a rough map of all 23 pairs of human chromosomes.

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.

1994

The first genetically engineered food product, the Flavr Savr tomato, gained FDA approval.

Genentech's Nutropin is approved for the treatment of growth hormone deficiency. The first breast cancer gene is discovered.

The BRCA1 gene, previously implicated in the development of rare familial forms of breast cancer, also appears to play a role in much more common types of non-inherited breast cancers,

A multitude of genes, human and otherwise, were identified and their functions described. These included:

Ob, a gene predisposing to obesity
BCR, a breast cancer susceptibility gene
BCL-2, a gene associated with apoptosis (programmed cell death)
hedgehog genes (so named because of their shape, these produce proteins which guide cell differentiation in advanced organisms)
Vpr, a gene governing reproduction of the HIV virus.

Linkage studies identified genes for a variety of ailments including: bipolar disorder, cerulean cataracts, melanoma, hearing loss, dyslexia, thyroid cancer, sudden infant death syndrome, prostate cancer and dwarfism.

Genetic researchers successfully transferred the CFTR (cystic fibrosis transmembrane conductance regulator) gene into the intestines of mice. This appears to be a major step towards gene therapy for patients with cystic fibrosis. Researchers reported early success with a liposomal method for delivering the CFTR gene in humans.

The past year also saw the approval of genetically engineered version of human DNAase, which breaks down protein accumulation in the lungs of CF patients. It was the first new therapeutic drug for the management of cystic fibrosis in over 30 years.

Another group of researchers reported the first successful systemic selective inhibition of gene expression using antisense oligonucleotides.

Centocor's ReoPro is cleared for marketing in United States by the FDA and by the European Union's regulatory body, CPMP for patients undergoing high-risk balloon angioplasty.

Genzyme's CeredaseŽ/ CerezymeŽ (alglucerase/ recombinant alglucerase) approved for type 1 Gaucher's disease.

The first crude but thorough linkage map of the human genome appears.(See Science, v.265, Sep.30, '94, for the full color pull-out).

The year also saw an increase in squabbling over who owns what parts of the genome. The scientists and research corporations have worked out a way to share access to a computerized database detailing 35,000 human genes.

Researchers at the University of Texas reported that the enzyme telomerase appears to be responsible for the unchecked growth of cells seen in human cancers. The discovery could lead to many new diagnostic and therapeutic applications.

Recombinant GM-CSFapproved for chemotherapy-induced neutropenia.

1995

A European research team has identified a genetic defect which appears to underlie the most common cause of deafness.

Researchers at Duke University Medical Center transplanted hearts from genetically altered pigs into baboons, proving that cross-species operations are possible.Later, the first baboon-to-human bone marrow transplant is performed on an AIDS patient.

The first full gene sequence of a living organism other than a virus is completed for the bacterium Hemophilus influenzae.

Former football player O.J. Simpson is found not guilty in a high-profile double-murder trial in which PCR and DNA fingerprinting play a prominent but apparently unpersuasive role.

A new coalition of mainstream religions launched a campaign seeking to overturn current laws allowing the patenting of genes used for medical and research applications. The group also includes Jeremy Rifkin, the controversial and outspoken critic of the biotechnology industry.

Investigators at the Centers for Disease Control and Prevention confirmed that the Ebola virus is behind outbreak of hemorrhagic fever in Zaire. Interview and resources

Hitherto unrecognized properties of RNA add further support to the idea that RNA was the central molecule in the origin of life, report researchers. Interview

Leptin, a protein product of the recently identified obesity gene (ob) appears to cause weight loss in experimental animals.

A new gene mapping technique, STS gene mapping, could greatly speed the work of geneticists involved in the international Human Genome Project.

A single gene has been identified that appears to control the growth and development of eyes throughout the animal kingdom.

A new transgenic mouse carrying a gene for human Alzheimer's disease is developed.

Gene therapy, immune system modulation and genetically engineered antibodies enter the clinic in the war against cancer.

1996

UK government announces that 10 people may have become infected with the BSE agent through exposure to beef. Interview

Biogen's recombinant interferon drug. AvonexŽ is approved for the treatment of multiple sclerosis.

A collaboration of scientists reports sequencing of the complete genome of a complex organism, Saccharomyces cerevisiae, otherwise known as baker's yeast. The achievement marks the complete sequencing of the largest genome to date - more than 12 million base pairs of DNA. I

Analysis of a small meteorite that landed on Antarctica some 15 million years ago has sparked what may be the greatest scientific discovery ever, possible evidence of life on Mars. Follow-up

The sequencing of the genome of ancient organisms, archaea, found in inhospitable climates deep in thermal vents under the sea should greatly advance understanding of the evolution of life on Earth. The microorganisms are neither eukaryotes nor prokaryotes.

T-cell researchers determed the three-dimensional structure of these critical components of the immune system.

A new inexpensive diagnostic biosensor test for the first time allow instantaneous detection of the toxic strain of E. coli E. coli strain 0157:H7, the bacteria responsible for several recent food-poisoning outbreaks.

The discovery of a gene associated with Parkinson's disease provides an important new avenue of research into the cause and potential treatment of the debilitating neurological ailment.

Surveys indicate the public regards research into the workings of the human genome and gene therapy with a combination of fear and mistrust,

1997

Researchers at Scotland's Roslin Institute report that they have cloned a sheep--named Dolly--from the cell of an adult ewe. Polly the first sheep cloned by nuclear transfer technology bearing a human gene appears later.

Artificial human chromosomes created for the first time.

Follistim, a recombinant follicle-stimulating hormone, approved for treatment of infertility.

A group of Oregon researchers claim to have cloned two Rhesus monkeys.

Leading geneticists expressed shock and dismay as word spread of the US Patent and Trademark Office announcement that it would allow patents on expressed sequence tags (ESTs), short sequences of human DNA that have proven useful in genome mapping .

Orasure, a bloodless HIV-antibody test using cells from the patient's gums approved.

Clock, the first gene providing the circadian rhythm of mammalian life identified.

Using a bit of DNA and some commonplace biological laboratory techniques, researchers have now engineered the first DNA computer "hardware" ever: logic made of DNA.

A new E. coli vaccine for prevention of urinary tract infections developed.

The complete genome of the Lyme disease pathogen, Borrelia burgdorferi, is sequenced, along with the genomes for E. coli and H pylori.

The FDA approves Rituxan, the first antibody-based therapy for cancer (for patients with non-Hodgkin's lymphoma).

A new DNA technique combines PCR , DNA chips, and computer programming providing a a new tool in the search for disease-causing genes.

1998

University of Hawaii scientists, clone three generations of mice from nuclei of adult ovarian cumulus cells.

The FDA grants marketing clearance to RemicadeTM (infliximab), a novel monoclonal antibody for treatment of Crohns disease.

Two research teams succeed in growing embryonic stem cells, the long sought grail of molecular biology.

Scientists at Japan's Kinki University clone eight identical calves using cells taken from a single adult cow.

Favorable results with a new antibody therapy against breast cancer, HER2neu (Herceptin), herald a new era of treatment based on molecular targeting of tumor cells

Fomivirsen becomes the first approved therapeutic agent developed with antisense medical technology.

Research with tumor starving biologicals including angiostatin and endostatin begins to show promise in the clinic.

The first complete animal genome the C.elegans worm is sequenced.

A rough draft of the human genome map is produced, showing the locations of more than 30,000 genes.

1999

A new technique based on unique individual antibody profiles offers an alternative to current DNA fingerprinting methods.The method is simple to use and has attracted considerable attention from law enforcement.

A new medical diagnostic test will for the first time allow quick identification of BSE/CJD a rare but devastating form of neurologic disease transmitted from cattle to humans,

Research continues and ethical debates grow. There are 1,274 biotechnology companies in the United States alone, with at least 300 biotechnology drug products and vaccines currently in human clinical trials and hundreds more in early development. These products include medicines and diagnostic tests, biopesticides and genetically altered crops. The Human Genome Project is on time and under budget, with the complete human genome map expected within five years or less.