Genome: the Secret of How Life Works

Discovering the secret

For most of human history we didn’t know why offspring looked like their parents. It took a monk working in a garden of peas to discover the truth. This began the first wave of genetic discoveries.

1865 Heredity rules

Gregor Mendel

By raising peas, an Austrian monk named Gregor Mendel discovered how heredity works—parents pass on specific traits to offspring by way of “factors,” as Mendel called them. Unfortunately, his work was ignored until the early 1900s.

1909 A new word

Wilhelm Johannsen, a Danish botanist, coined the term "gene" from the Greek word meaning "to be born." His word replaced the term "factors," which Mendel had suggested were involved in passing on traits. Genes now had a name, but no one knew what they were or how they worked.

1911 Genes on chromosomes

Since the 1880s scientists had observed threadlike structures in a cell's nucleus; they named those structures "chromosomes." In 1902, Walter Sutton, a graduate student at Columbia University, suggested that chromosomes contained genes. Thomas Hunt Morgan, also at Columbia, proved him right in 1911. Working with fruit flies, he and his students found that genes seemed to be fixed in place along chromosomes. They were indeed the units of heredity.

What are genes?

No one knew. Scientists knew genes were on chromosomes and chromosomes were made of protein and DNA. Because many believed that protein was the important component of genes, research efforts focused on proteins. Scientists thought DNA was too simple a molecule to play a major role in genes and heredity.

1943 Could genes be DNA?

In the 1920s Frederick Griffith, at the British Ministry of Health in London, had noticed that harmless bacteria turned deadly when mixed with harmful bacteria. Were the harmful bacteria passing on their genes? In 1943 American researcher Oswald Avery, at the Rockefeller Institute in New York, discovered that the harmful bacteria were passing on DNA. Were genes therefore made of DNA? Avery thought so. But as most scientists still considered protein the carrier of genes, Avery's work wasn't accepted until the 1950s.

1944 Jumping genes

Corn doesn't always follow Mendel's rules of inheritance, and Barbara McClintock, who worked at Cold Spring Harbor Laboratory in Long Island, New York, wanted to know why. To everyone's surprise (and disbelief) she found that some genes weren't fixed on chromosomes-they slid around and even jumped to different chromosomes. In 1983 she won a Nobel Prize for discovering "jumping genes."

1952 Genes are DNA

Viruses infect bacteria by injecting their genes. Alfred Hershey and Martha Chase at Cold Spring Harbor Laboratory wanted to know if those genes were protein or DNA. In a simple experiment involving a kitchen blender, they discovered that viruses inject bacteria with DNA, not protein. Back in 1943 Avery had been right. Genes are DNA.

1953 "We found the secret of life." Francis Crick

What is DNA and how does it work? The answer to that question came from American biologist James Watson and British physicist Francis Crick, both at Cambridge University in England. Building "tinkertoy�" models largely based on the research of other scientists, they discovered DNA's shape-a double helix. From the two-stranded shape they also saw how it worked. Each strand served as a mold or template for reproducing itself. This has been called the most important biological discovery of the 20th century. In 1962 Watson and Crick, with fellow researcher Maurice Wilkins, won the Nobel Prize.

Cracking the code

Discovering DNA's double helix was an amazing breakthrough, but it created many questions. What do all those DNA letters mean? What's the code? How do recipes in the nucleus travel to protein factories outside the nucleus? How does the protein-making process work? The next wave of discovery resulted in cracking the code of life's genetic recipe.

1957 A missing link?

DNA wasn't the only molecule involved in the making of proteins. RNA, a chemical cousin to DNA, was a part of the mix, too. That was discovered by Elliot Volkin and Lazarus Astrachan, working at what's now the Oak Ridge National Laboratories in Tennessee. To everyone's surprise, it seemed that RNA, not DNA, controlled translating genetic recipes into proteins.

1961 A messenger called RNA

How does a gene's recipe move out of the cell's nucleus? A messenger delivers it. That was the discovery of British scientist Sydney Brenner working at Cambridge University. He found that RNA acts as a messenger (called mRNA), carrying the DNA message to protein "factories" (ribosomes) in the outskirts of the cell. Now the link from DNA to RNA to proteins was complete.

1961 Code cracking

Marshal Nirenburg

How does DNA tell RNA to make proteins? The answer came when Marshall Nirenberg and his colleagues at the National Institutes of Health in Bethesda, Maryland, cracked the code for a three-letter word (called a codon) in the genetic recipe for life. A codon comprises the recipe for an amino acid, which is a building block for a protein. By 1966 scientists could read codons for all of our 20 protein-building amino acids.

Cut and paste

Now scientists were ready to uncover the function of specific genetic recipes and specific proteins. One way to discover how something works is to remove a part and see what happens without it. To do this, scientists invented techniques for cutting and pasting genes. This wave of discovery provided the basic tools for reading the codes in an entire genome.

1968 Just snip here ...

To cut and paste you need scissors. The first "molecular scissors" (called restriction enzymes) were discovered by Hamilton Smith, at Johns Hopkins University in Baltimore. With these scissors scientists could snip pieces of DNA from a genome and experiment with specific genes to find out what they do. For this discovery Smith shared a Nobel Prize in 1978 with colleague Daniel Nathans.

1973 Genetic factories

Herbert Boyer

Can you cut a gene out of one species and paste it into another? That's what Stanley Cohen and Herbert Boyer, at the University of California at San Francisco, did-they snipped out a virus gene and pasted it into bacteria. When the bacteria reproduced, they made copies of the virus gene. The researchers showed that bacteria could be made into protein-producing factories. By recombining genes in this way, Cohen and Boyer founded "recombinant" DNA technology.

1975 Speedy sequencing

Scientists were able to read the order, or sequence, of millions of DNA letters, but only one by one. That tough, time-consuming work got a lot easier when Fred Sanger, at Cambridge University, developed the first fast "sequencing" method-called the chain termination method. In 1980 Sanger won the Nobel Prize for his invention, along with Walter Gilbert, of Harvard University, who invented another sequencing process. Sanger's method is the basis for today's automated DNA sequencing technology.

1977 "Junk" DNA

For decades, scientists thought that most of DNA contained genes and all of a gene was a recipe for a protein. Two Americans, Phillip Sharp, at M.I.T., and Richard Roberts, of Cal Tech shattered that idea. They found that most DNA doesn't seem to be a recipe for anything, and within a gene are long sections of seemingly useless DNA. Sharp and Roberts won the Nobel Prize in 1993 for discovering this "junk" DNA.

1981 Gene swapping

If the genes of bacteria and viruses could be recombined, why not the genes of mammals? To better understand genes, Frank Costantini and Elizabeth Lacy, at Cold Spring Harbor Laboratories, experimented with injecting rabbit genes into the fertilized eggs of mice. The resulting mice looked and acted like mice, but made rabbit blood cells. Research with "transgenic" animals like these offers scientists new ways to test how genes work.

Racing to the frontier

By the 1980s, geneticists were cutting, pasting and copying genes with ease. As they deciphered genomes of several viruses and bacteria, a radical idea emerged-why not tackle all the code in human DNA? This wave of discovery led to one of our greatest scientific achievements-sequencing the entire human genome.

1983 DNA copy machine

Studying genes required vast quantities of expensive genetic material. Biochemist Kary Mullis, at that time with Cetus Corporation in Emeryville, California, revolutionized genetics. While driving along the coast one evening, he dreamed up a fast and cheap way to make lots of copies of a little bit of DNA. His technique, called polymerase chain reaction or PCR, is especially important in genetic testing and DNA fingerprinting. In 1993 Mullis won the Nobel Prize for his discovery.

1986 Faster, faster!

Even "fast" methods for sequencing genes were slow-scientists could read only about 500 DNA letters a day. Leroy Hood and his colleagues at Cal Tech invented the first automated sequencing machine. It could read 15,000 or more letters a day. For the first time scientists' grand dream of reading the entire human genome seemed close to reality.

1990 At last � the Human Genome Project

All the discoveries of the previous 150 years led to a monumental undertaking-sequencing the entire human genome. Scientists estimated it would take 15 years to sequence the estimated 3 billion letters, but they were confident it could be done.

1998 New technologies

The first DNA sequencer (a recipe-reading machine) designed for industrial-scale work was introduced by a company named Applied Biosystems. Many of these sequencers were used by the Human Genome Project, as well as private companies, in their work to map the human genome.

2000 "With this profound new knowledge, humankind is on the verge of gaining immense new power to heal ... " President Bill Clinton

On June 26, 2000, the first draft of the human genome was completed-ahead of schedule. The hard work of hundreds of scientists in more than 20 publicly funded laboratories around the globe, as well those in a privately funded company, Celera, in Rockville, Maryland, had paid off. The world celebrated: we had the recipe book for a human being.

What's the next wave?

"Today is � not the end of genomics, but perhaps it's the end of the beginning. Together we must develop the advances in medicine that are the real reason for doing this work. And with just as much vigor, we must provide the protections against potential misuses of genetic information � we must apply just as much energy and attention to solving the ethical, legal and social issues as we do the bench research."
—Dr. Francis Collins, director of the National Human Genome Research Institute, June 26, 2000

"Some have said to me that sequencing the human genome will diminish humanity by taking the mystery out of life. � Nothing could be further from the truth. The complexities and wonder of how the inanimate chemicals that are our genetic code give rise to the imponderables of the human spirit should keep poets and philosophers inspired for millenniums."
—Dr. J. Craig Venter, then president of Celera Genomics, June 26, 2000