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Microbes—tiny organisms too small to be seen with the naked eye—have altered human history.

Life forms such as bacteria, yeasts, and molds can cause sickness or restore health, and help produce foods and beverages.

Scientists, in partnership with industry, have developed techniques to harness the powers of these microbes. In recent years, headline—grabbing technologies have used genetically modified bacteria to manufacture new medicines.

A glimpse into the past reveals a history of human enterprise that has adapted these tiny organisms for health and profit. This exhibition explores some of the processes, problems, and potential inherent in technologies that use life.

Microbes—tiny organisms too small to be seen with the naked eye—have altered human history.

Life forms such as bacteria, yeasts, and molds can cause sickness or restore health, and help produce foods and beverages.

Scientists, in partnership with industry, have developed techniques to harness the powers of these microbes. In recent years, headline—grabbing technologies have used genetically modified bacteria to manufacture new medicines.

A glimpse into the past reveals a history of human enterprise that has adapted these tiny organisms for health and profit. This exhibition explores some of the processes, problems, and potential inherent in technologies that use life.

Graphic illustrations of various microbes numerically numbered

Half-Hours with the Microscope, Edwin Lankester, MD, illustrated by Tuffen West, 1860

Courtesy National Library of Medicine

Introduction

Tinkering with DNA

All organisms, from microbes to humans, are governed by the genetic code embedded in their DNA. In the 1970s, scientists inserted a human gene into the genetic material of a common bacterium. This so—called "recombinant" microorganism could produce the protein encoded by the human gene.

Eager to explore the potential of this recombinant DNA technique, investors joined forces with research scientists to develop industrial applications. Two of the earliest products to reach the market were human insulin, used to treat diabetes, and human growth hormone, used in children with pituitary gland disorders.

Recombinant technology provided a commercially viable way to make proteins for medical use and gave rise to a new industry—dubbed "biotech."

Microphotograph of two E. coli bacteria exchanging DNA through conjugation.  Four views of E. coli bacteria by scanning electron microscope

Top: E.coli bacteria exchanging genes
Courtesy of Charles C. Brinton Jr.
Bottom: Views of E. coli bacteria by scanning electron microscope
Courtesy of David Scharf Photography

Escherichia coli (E. coli) bacteria are the workhorses of recombinant DNA technology. The ability of bacteria to easily exchange and absorb new pieces of DNA made them good vehicles for genetic engineering techniques.

Box and three small, labeled vials of Protropin

Protropin, human growth hormone, 1987
Courtesy National Museum of American History

The Food and Drug Administration approved Protropin, human growth hormone made using genetically modified bacteria, for therapeutic use in 1985.

Seated man in a white lab coat with a diagram of the structure of insulin made out of colored spheres superimposed on a black background.

“First Man-made Protein in History,” LIFE, May 8, 1964
Courtesy © 1964 Time Inc. Reprinted with permission. All rights reserved. Image by Fritz Goro. ©Time Inc. Used with permission. All rights reserved.

In this illustration the sequences of colored balls represent the steps in a complex chemical process for building insulin molecules. Although this achievement was important for research, the process was not feasible for commercial insulin production.

Pink computer generated model of the three dimensional structure of human growth hormone on a black background.

“Ribbon Diagram” of human growth hormone, 2013
Courtesy National Center of Biotechnology Information (NCBI)

Ribbon diagrams are a graphic tool that helps researchers to visualize protein structures such as growth hormone. Understanding the relationship between DNA, genes, and protein structures led to the birth of genetic technologies including recombinant DNA.


In 1988, the National Center for Biotechnology Information was established at the National Library of Medicine to provide a central source for genetic and molecular data, including the gene sequences and structures of the proteins essential to human health.

How did they make insulin from recombinant DNA?

Introduction

Harvesting Hormones

Hormones are complex molecules that regulate vital functions, including growth and development. In humans and animals, hormones are produced in glands and organs such as the pituitary, thyroid, and pancreas.

Before recombinant DNA technology, drug manufacturers extracted hormones, including insulin and growth hormone, directly from animal or human glands. Human growth hormone (hGH) required a supply of pituitary glands from human cadavers that was difficult to obtain.

The new technology ensured an abundant supply of these drugs. In the case of hGH, the number of children requiring it to treat pituitary gland disorders is quite small. However, with the supply secure new markets and applications emerged. The drug is used to increase height in otherwise healthy children, to enhance athletic performance, and to rejuvenate aging bodies.

Drawing of a cutaway view of the inside of a human male head in profile.  Inset shows a closeup of the pituitary gland and surrounding area.

“The position of the pituitary gland within the skull,” from The Pituitary Gland: Clinical Application of its Hormone Factors, Armour Laboratories, 1940s
Courtesy National Library of Medicine

The pituitary gland, the size of a chickpea, situated in the center of the brain, secretes nine different hormones, one of which regulates human growth.

Two photographs: A short teenage boy and a tall young man, both in uniforms, stand side by side. A man measures the height of the teenage boy.

“How HGH Made One Dwarf Tall” LIFE, October 14, 1966
Courtesy © 1966 Time Inc. Reprinted with permission. All rights reserved. Images courtesy Royal Canadian Air Force.

A young man featured in Life magazine in 1966 gained 15 inches with the help of growth hormone injections. Although the extracted hormone was available for therapeutic use by the late 1950s, its availability was severely restricted by the limited supply of human glands.

Line drawing of a steer with the locations of its glands labeled.

“The Steer” from Armour’s Endocrine and Other Organotherapeutic Preparations, 1940s
Courtesy National Museum of American History

Diagram of glands and organs used for making pharmaceutical preparations.

White plastic test tubes with caps in white plastic test tube holder. Tubes and holder have labels written on them in ink.

Insulin plasmid tubes, 1970s
Courtesy National Museum of American History

These tubes contained samples of bacterial DNA which had been genetically modified to contain the human insulin gene. Researchers used the DNA in the original experiments to produce human insulin from recombinant bacteria.

Five labeled glass bottles and one box containing pituitary gland tablets and powders.

Pituitary gland products, 1910s–1950s
Courtesy National Museum of American History

These bottles contain medicines made from the pituitary glands of cattle. Although these tablets and powders were widely available, they were not effective. Any hormones present were destroyed by the human digestive system before they could work. In the 1940s, researchers isolated pure growth hormone from cattle glands. This hormone could be injected, but due to differences between species, bovine hormone was not effective for human use.

Hardcover book with prominent blue text on cover: “Grow Young with HGH.”

Grow Young with HGH by Dr. Ronald Klatz, 1998
Courtesy Harper Collins and National Museum of American History

Magazine article with child’s growth chart on left page, and a smiling boy hanging by the arms from gymnastic rings on right.

“My Little Brother on Drugs,” by Jenny Everett, Popular Science, April 2004
Used with permission of Popular Science Copyright ©2013. All rights reserved.

The experience of a young boy on hGH therapy prompted his sister to ask, “Should we treat stature as a medical condition?”
Blue and white box with three white syringes, a needle, and a package of four needles displayed around the box.

Posilac, recombinant bovine growth hormone, Monsanto Company, 1994
Courtesy National Museum of American History

Following the success of human growth hormone (hGH), researchers developed a recombinant bovine (cow) growth hormone, which became available in 1994. The drug did not treat a disorder in cattle, but instead drug companies marketed the substance to dairy farmers to increase milk production.

Introduction

Making Yellow Magic

Microbes are equipped with defense mechanisms to help ensure their survival. Penicillium, the bluish-green mold that grows on stale food, produces a substance that has the power to kill its bacterial competition. Many of these bacteria are also deadly to humans.

In the years leading into World War II, British scientists established the life-saving potential of Penicillium's natural antibiotic. Prompted by the war emergency, the United States government teamed with drug companies to mass-produce penicillin. The ability of the drug to prevent fatal infections among the wounded inspired the nickname "yellow magic."

The anti-infective power of penicillin and other antibiotics has led to their overuse in medicine and agriculture, resulting in the emergence of drug-resistant bacteria that threaten human health.

A woman seated at a laboratory bench examines a petri dish under a magnifying glass. In the background a man examines an industrial fermentation tank.

“The Era of Antibiotics,” painted by Robert A. Thom for Parke, Davis & Company, 1950s
Printed with Permission of American Pharmacists Association Foundation. Copyright 2009 APhA Foundation.

Penicillin research and production are depicted in this painting by Robert A. Thom, commissioned by Parke, Davis & Company as part of their “Great Moments in Pharmacy” advertising campaign in the 1950s.

Magazine page featuring an illustration of a military field medic administering an injection in the arm of a soldier lying on the ground.

“Thanks to Penicillin…He Will Come Home!” penicillin advertisement, Schenley Laboratories, 1944
Courtesy Schenley Laboratories, Inc.

Advertising played a role in establishing the image of penicillin as the wonder drug.

Drawing of strands of Penicillium mold as they appear through a microscope

“Fibres and spores of Penicillium notatum” papenicillin advertisement, Squibb Laboratories, 1944
Courtesy National Museum of American History

“Growing in a liquid medium, this mold gives out golden droplets rich in penicillin—but the liquid must be concentrated over 30,000 times to obtain pure penicillin.”

Two women in surgical gowns, masks, and head coverings in a room stacked with square ceramic penicillin vessels

Penicillin manufacture at Oxford University, early 1940s
Courtesy Sir William Dunn School of Pathology, Oxford University

Six “Penicillin Girls” nurtured the growing mold and harvested the penicillin from the hundreds of culture vessels at the manufacturing operation established at Oxford University in 1940.

Two sides of a square-sided, flat ceramic vessel with short cylindrical spout near one corner

Penicillin culture vessel, 1940
Courtesy National Museum of American History

Seven labeled glass vials and ampules of penicillin

Penicillin products from American manufacturers, 1940s
Courtesy National Museum of American History

Unable to establish large–scale commercial production, the British turned to the United States in 1942. More than twenty American drug companies joined the U.S. government’s penicillin production effort. Industrial fermentation tanks replaced small vessel production and by 1944 penicillin supplies met military needs.

Clear plastic envelope containing a sample of dirt and a paper card with blue ink handwriting.

Soil sample, Charles Pfizer and Company, 1949
Courtesy National Museum of American History

Soil, naturally rich in microbial life, became an important source for antibiotic discovery. The Pfizer company alone tested over 100,000 soil samples from around the world, as drug companies competed to develop new products. This envelope of soil, from a cornfield in the Midwest, yielded a winning microbe and led to a successful new antibiotic named Terramycin.

Magazine ad featuring a photograph of a hand grabbing dirt and particles spilling out back onto a beach.

“A handful of earth that may save your life“ penicillin advertisement, Parke, Davis & Company, 1962 Copyright © Pfizer Inc. All rights reserved.

The Parke Davis company tested thousands of soil samples each year for new microorganisms. Advertisements in popular magazines highlighted the enormous research effort required to produce one or two useful products.

Box, bottle, and dispensing cup for oral antibiotic product

Polycillin oral antibiotic, Bristol–Myers Company, 1977
Courtesy National Museum of American History

New penicillins, such as ampicillin (brand name Polycillin) developed in the 1960s, were effective for treating many common infections. Oral formulas made taking the medicine more convenient. Doctors and patients came to rely on antibiotics even in uncertain diagnoses.

A piglet in a mesh cage drinking milk from a plastic spout as milk runs down its chin

“Pig’s Progress” LIFE, December 3, 1951
Courtesy © 1951 Time Inc. Reprinted with permission. All rights reserved. Image by Albert Fenn. ©Time Inc. Used with permission. All rights reserved.

A piglet thrives on a formula of artificial milk and Terramycin, an antibiotic, developed to accelerate growth in animals.

Magazine spread featuring an illustration of a smiling man, woman, and blond girl; a family of four at a dinner table; three cows; the dome of the U.S. Capitol

“How Meat Serves Everybody!“ Life, November 14, 1949
Courtesy National Museum of American History

Meat production and consumption expanded rapidly along with the prospering American economy in the years following World War II. This advertisement from the American Meat Institute emphasizes the benefits of meat for human health, the economy, and soil conservation.

Infographic on how penicillin was made.

How did they make penicillin?

Introduction

Living Factories

Humans and animals have natural defense systems that produce antibodies in the blood to combat bacteria and other harmful substances invading the body. In the late nineteenth century, scientists investigating this immune response in animals developed new methods for treating diseases in humans.

One of these early therapies used blood serum, collected from animals inoculated with toxins from bacteria. The natural protection these animals developed against the toxin could be passed to humans through injections of the serum. In commercial production, horses and other large animals served as living serum factories to grow the so—called "antitoxins" for human use.

Serum therapy provided an effective cure for diphtheria, an often fatal childhood disease. The demand for serum established a new drug industry that required the use of large numbers of animals for production.

Four men in white smocks extract blood from two horses in a stable

Recovering the diphtheria serum from horse blood in Marburg, Germany, drawn from nature by Fritz Gehrke, 1890s
Courtesy of National Library of Medicine

Two guinea pigs on a rough wood surface with a few stalks of alfalfa

Guinea pigs used for testing serums and toxins at Parke Davis & Company, ca. 1925
Courtesy National Museum of American History

Interior view of room with long rows of wire cages holding guinea pigs

Guinea pig room at Parke Davis & Company, ca. 1925
Courtesy National Museum of American History

A man in gown gives an injection to a small child laying on a table. Two women in nursing gowns and caps attend to the child at its head and side.

Injecting diphtheria antitoxin, 1895
Courtesy The Historical Medical Library of The College of Physicians of Philadelphia

Black and white magazine spread with photographs of women working with laboratory flasks and men bleeding horses and injecting them with toxins

“How New York City’s Health Department Makes Serums and Vaccines for the United States Army?” Popular Science, December 1917
Courtesy Smithsonian Libraries, The National Museum of American History Library

Drawing of a hand holding a guinea pig in a cylindrical guinea pig holder.  Guinea pig is in the holder head first with its hind feet sticking out from the open end

“The Voges holder for guinea–pigs” from The Principles of Bacteriology by Alexander Crever Abbott, 1899
Courtesy National Museum of American History

This tube was used to immobilize guinea pigs during inoculations. Injections of toxins and serums were administered through the cut–out window. Although their role was less publicized, small mammals, such as the guinea pig, were essential to the serum manufacturing process.

Copper cylinder with one end closed and perforated with small holes and a long rectangular window cut into one side

Guinea pig holder, early 20th century
Courtesy National Museum of American History

Lined card with printed heading, handwritten notations, and rough outline drawing of a guinea pig

Animal Record Card from Hygienic Laboratory Bulletin No. 21, 1905
Courtesy National Library of Medicine

Animal Record Card for a guinea pig used in serum and toxin testing. Pig No. 1567 is identified by a rough sketch of its color markings.

Leather horse harness, coiled horse’s lead with “First Flight” woven into fabric, and a small labeled glass vial

Harness and lead for the horse “First Flight” and a bottle of botulism antitoxin, 1970s
Courtesy National Museum of American History

The thoroughbred horse “First Flight” was used to produce serum for botulinum toxin, the deadly bacterial poison often spread through foods. He produced the antitoxin for the U.S. Army from 1978–1993.

Black and white photograph of a child on the bare back of a dark colored horse in front of a stone building

A photo of Old Faithful in Who’s Who Among the Microbes by William H. Park and Anne W. Williams, 1929
Courtesy National Library of Medicine

“Old Faithful,” was a horse that produced antitoxins for the city of New York in the early twentieth century. A few of the individual horses used for serum production were celebrated for their service to humankind.

A handwritten ledger page

Animal record book, New York City Department of Health, 1897–1898
Courtesy National Museum of American History

In the 1890s the New York City Department of Health kept a logbook of the horses used for antitoxin production. The entries for each animal provide a record of toxin injections and bleedings, the amount of blood collected and serum produced, and the animal’s death.
Infographic of how diphtheria antitoxin was made.

How Did They Make Diphtheria Antitoxin?

Introduction

Brewing Mysteries

Beer making is an old technology that relies on microorganisms. Brewers, however, barely knew of the existence of microbes, much less the critical role they played in their livelihood. Problems encountered in beer production, motivated scientists to study the secrets of this "invisible world."

In the mid—19th century, chemist Louis Pasteur worked with French beer makers to discover what was causing their product to spoil. Through his investigation into the "diseases" of beer, Pasteur demonstrated the essential role that yeast, a tiny living organism, played in the fermentation process and identified microorganisms that caused beer to go bad.

Breweries, as well as other fermentation based industries, adopted new scientific tools and techniques in order to better control the productive and destructive power of microorganisms.

A man stands next to a large cylindrical beer vat and gazes into the vat through a small opening in the conical cover

Engraving of a beer vat designed by Louis Pasteur, ca. 1880
Courtesy National Library of Medicine

The closed fermentation tank prevented air–borne bacteria from entering and spoiling the brew.

Three men working at large uncovered wood beer vats under a high vaulted structure

“The Brewer,” engraving by Jost Amman, 16th century
Courtesy National Museum of American History

Black and white drawing of various flasks, laboratory set ups, and microorganisms from Louis Pasteur’s research on fermentation

Drawings by Louis Pasteur of microscopic organisms, culturing vessels and equipment from his experiments, 1861
Courtesy Library of Congress

Head and shoulders drawing of Louis Pasteur surrounded by a starburst pattern

French chemist Louis Pasteur, 1889
Courtesy National Library of Medicine

Pasteur’s work is celebrated as laying the foundation for the science of bacteriology. His investigations on the behalf of French industry established tools and techniques necessary for controlling the productive and destructive power of microorganisms.

White ceramic filter tube with nipple on one end and metal pipe-like case for the ceramic filter

Pasteur Chamberland filter, early 20th century
Courtesy National Museum of American History

Bacterial filters were an essential tool for securing a supply of uncontaminated water and for purifying products in industrial applications. This porcelain filter, developed in Pasteur’s laboratory, had tiny pores that allowed fluids to pass through while holding back bacteria and other microorganisms.
Drawing of filter seated in metal pipe-like case with spigot on top, shown with a cut-away view of the same filter

“Section and elevation of Chamberland’s filter” from Microbes, Ferments and Moulds, Edouard Louis Trouessart, 1891
Courtesy National Library of Medicine

Bulb–shaped glass flask with two long thin necks sits next to an upright brass microscope on a small metal stand

Pasteur flask, early 20th century and Microscope, made in France by Nachet et Fils, ca. 1860

Pasteur used special tools and methods for studying the activity of microorganisms in the brewing process. Flasks with long curved necks allowed oxygen to get in while keeping unwanted microbes out. Improvements in microscope lenses made the identification of different microorganisms possible.

Black and white drawing of yeast cells as seen through a microscope

Yeast, Études sur la Bière (Studies on Beer) by Louis Pasteur, 1876
Courtesy National Library of Medicine

An illustration in Pasteur’s book shows what healthy and worn–out yeast cells look like when viewed through the microscope.

Diagram of cylindrical beer vat and a cross-section of the same beer vat showing various parts

Diagram and cross-section of beer vat, Études sur la Bière (Studies on Beer) by Louis Pasteur, 1876
Courtesy National Library of Medicine

Four glass test tubes with paper labels and cotton plugs. Dried culture media is in three tubes and a metal cotton swab is in the fourth.

Prepared culture tubes and sterile swab, Parke, Davis & Company, 1898
Courtesy National Museum of American History

These culture tubes were used to grow microbes for identification. They contain a special preparation of nutrients in a jelly–like base. A sterile instrument like the swab was used to transfer the test substance to the tube.

Color plate with ten illustrations of lactic acid bacteria growing in test tubes and on culture plates

“Bacterium Acidi lactici,” Atlas of Bacteriology, 1897 Courtesy National Library of Medicine

Lactic–acid bacteria, a major cause of spoilage in the brewing process, are shown growing on a variety of culture media.

Drawing of an incubator with its door open to show flasks and culture tubes inside

“Incubator,” from The American Handbook of the Brewing, Malting and Auxiliary Trades by Robert Wahl, PhD, and Max Henius, PhD, 1901
Courtesy National Museum of American History

Brewing handbooks described the tools and techniques needed for the study of yeasts and bacteria encountered in the brewing process.

Three black and white drawings of globules of yeast. Yeast are represented by groups of spheres arranged in small clusters

Drawing of Yeast by Anton van Leeuwenhoek, 1680
Courtesy National Library of Medicine

Dutch lens maker Anton van Leeuwenhoek was probably the first person to see yeast. He made this drawing in 1680, after viewing beer through his primitive homemade microscope.

“How did they ferment beer?”

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