1977 - 1999:
The Dawn of Biotech
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.
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.
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.
Rutter and Howard Goodman isolated the gene for rat insulin.
Gilbert and Allan Maxam at Harvard University devised a method for sequencing
DNA using chemicals rather than enzymes.
Inc. and The City of Hope National Medical Center announced the successful laboratory
production of human insulin using recombinant DNA technology.
researchers used genetic engineering techniques to produce rat insulin.
University scientists successfully transplanted a mammalian gene.
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.
J. Rutter's lab at UCSF cloned a coat protein of the virus that causes hepatitis
Baxter reported cloning the gene for human growth hormone.
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.
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.
Inc. cloned interferon gamma.
Rutter and Pablo Valenzuela published a report in Nature on a yeast expression
system to produce the hepatitis B surface antigen.
at Ohio University produced the first transgenic animals by transferring genes
from other animals into mice.
Harper and two colleagues mapped the gene for insulin. Mapping by in situ hybridization
became a standard method.
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.
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."
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.
Biosystems, Inc. introduced the first commercial gas phase protein sequencer,
dramatically reducing the amount of protein sample needed for sequencing.
requested government permission to test genetically engineered bacteria to control
frost damage to potatoes and strawberries.
Smith at the University of British Columbia, Vancouver, developed a procedure
for making precise amino acid changes anywhere in a protein.
Goldstein and Richard Novick called for the prohibition of the use of RNA technologies
in the development of biological weapons.
Lilly received a license to make insulin.
Corporation received FDA approval for a monoclonal
antibody-based diagnostic test for Chlamydia trachomatis.
Research Institute International filed for a patent for an E. coli expression
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.
patents were granted to companies genetically engineering plants.
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.
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.
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.
Plant Gene Expression Center was
University received a product patent for prokaryote DNA.
Corp. announced the first cloning and sequencing of the entire human immunodeficiency
virus (HIV) genome.
Cantor and David Schwartz developed pulsed-field gel electrophoresis.
Jeffreys introduces technique for DNA
fingerprinting to identify individuals.
fingerprinting enters the court room.
Ullrich reported the sequencing of the human insulin receptor in Nature. Bill
Rutter's UCSF team described the sequencing in Cell two months later.
Bio cloned the gene that encodes human lung surfactant protein, a major step toward
reducing a premature birth complication.
Corporation's develops GeneAmp polymerase chain reaction (PCR)
technology, which could generate billions of copies of a targeted gene sequence
in only hours.
engineered plants resistant to insects, viruses, and bacteria were field tested
for the first time.
NIH approved guidelines for performing experiments in gene therapy on humans.
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.
Berkeley chemist Peter Schultz described how to combine antibodies and enzymes
(creating "abzymes") to create pharmaceuticals.
OKT3� (Muromonab-CD3) approved for reversal of acute kidney transplant rejection.
regiment of scientists and technicians at Caltech and Applied Biosystems, Inc.,
invented the automated DNA fluorescence sequencer.
FDA granted a license for the first recombinant vaccine (for hepatitis) to Chiron
EPA approved the release of the first genetically engineered crop, gene-altered
received FDA approval to market rt-PA (genetically engineered tissue plasminogen
activator) to treat heart attacks.
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.
Genetic Sciences, Inc. conducted a field trial of a recombinant organism, a frost
inhibitor, on a Contra Costa County strawberry patch.
Olson and colleagues at Washington University invented "yeast artificial chromosomes,"
or YACs, expression vectors for large proteins.
CA 125TM, diagnostic
serum tumor marker test for ovarian cancer, is approved by the FDA.
(recombinant hepatitis B vaccine) approved.
molecular geneticists Philip Leder and Timothy Stewart awarded the first patent
for a genetically altered animal, a mouse that is highly susceptible to breast
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.
International, Inc. received a patent for a process to make bleach-resistant
protease enzymes to use in detergents.
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.
Davis scientists developed a recombinant vaccine against the deadly rinderpest
virus, which had wiped out millions of cattle in developing countries.
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.
(Epoetin alfa) a genetically engineered protein introduced, providing a means
to help patients with kidney failure.
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.
(Interferon gamma-1b) approved for treatment of chronic granulomatous disease.
(adenosine deaminase) approved for treatment of severe combined immunodeficiency
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
FDA licensed Chiron's hepatitis C antibody test to help ensure the purity of
blood bank products.
Fromm, molecular biologist at the Plant Gene Expression Center, reported the
stable transformation of corn using a high-speed gene gun.
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.
International, Inc. created the first transgenic dairy cow. The cow was used
to produce human milk proteins for infant formula.
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.
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.
of Michael Crichton's novel Jurassic Park,
in which bioengineered dinosaurs roam a paleontological theme park; the experiment
goes awry, with deadly results.
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.
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.
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.
and British scientists unveil a technique for testing embryos in vitro for genetic
abnormalities such as cystic fibrosis and hemophilia.
Mullis won the Nobel Prize in Chemistry for inventing the technology of polymerase
chain reaction (PCR).
Betaseron is approved as the first treatment for multiple sclerosis in 20 years.
FDA declares that genetically engineered foods are "not inherently dangerous"
and do not require special regulation.
Biotechnology Industry Organization
is created by merging two smaller trade associations.
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.
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
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
first genetically engineered food product, the Flavr
Savr tomato, gained FDA approval.
Nutropin is approved for the treatment of growth hormone deficiency. The first
breast cancer gene is discovered.
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
multitude of genes, human and otherwise, were identified and their functions
described. These included:
- Ob, a gene predisposing
- BCR, a breast cancer
- 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)
a gene governing reproduction of the HIV virus.
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.
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
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.
group of researchers reported the first successful systemic selective inhibition
of gene expression using antisense oligonucleotides.
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.
Ceredase�/ Cerezyme� (alglucerase/ recombinant alglucerase) approved for type
1 Gaucher's disease.
first crude but thorough linkage map of the human genome appears.(See Science,
v.265, Sep.30, '94, for the full color pull-out).
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.
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.
GM-CSFapproved for chemotherapy-induced neutropenia.
European research team has identified a genetic
defect which appears to underlie the most common cause of deafness.
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.
first full gene sequence
of a living organism other than a virus is completed for the bacterium Hemophilus
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.
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.
at the Centers for Disease Control and Prevention confirmed that the Ebola
virus is behind outbreak of hemorrhagic fever in Zaire.
Interview and resources
unrecognized properties of RNA
add further support to the idea that RNA was the central molecule in the origin
of life, report researchers.
Leptin, a protein
product of the recently identified obesity gene (ob) appears to cause weight
loss in experimental animals.
new gene mapping technique,
STS gene mapping, could greatly speed the work of geneticists involved in the
international Human Genome Project.
has been identified that appears to control the growth and development of eyes
throughout the animal kingdom.
mouse carrying a gene for human Alzheimer's disease is developed.
therapy, immune system modulation and genetically engineered antibodies
enter the clinic in the war against cancer.
government announces that 10 people may have become infected with the BSE agent
through exposure to beef. Interview
recombinant interferon drug. Avonex� is approved for the treatment of multiple
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
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.
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.
determed the three-dimensional structure of these critical components of the
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
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
Surveys indicate the public regards research into the
workings of the human genome and gene therapy with a combination of fear
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
created for the first time.
a recombinant follicle-stimulating hormone, approved for treatment of infertility.
group of Oregon researchers claim to have cloned
two Rhesus monkeys.
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 .
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.
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
A new DNA
technique combines PCR , DNA chips, and computer programming providing a
a new tool in the search for disease-causing genes.
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 Crohn�s disease.
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
Fomivirsen becomes the first approved therapeutic agent developed with antisense
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.
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,
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.
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