Science: Genome Project
Landmark gene studies released (CNN, 010212)
Blue Print of the Body: On the threshold of a brave new world (CNN, 010212)
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WASHINGTON -- Science passed another milestone on Monday with publication of the first description of the human genome, an advance likely to revolutionize the understanding and treatment of disease.
Dr. Francis Collins of the National Human Genome Institute in Washington said the studies were significant both for their discoveries and the speed by which scientists have unraveled at least part of the genetic mystery.
“These revelations arrive almost five years early from the original predictions of not having this information until 2005, and here we are. We have the first draft of our own book of life and we’ve read it from cover to cover, and we’ve discovered some pretty amazing surprises,” Collins told CNN.
Scientists say they have learned that humans don’t have as many genes as previously thought -- not all that many more than in a fruit fly.
The research also confirmed that males can take the blame -- or credit -- for creating most inherited genetic mutations.
Genes determine everything from eye and skin color to vulnerability to illness. Human have about 30,000 genes, the scientists found.
Scientists have also learned that the genetic differences between any two people are relatively small.
The analyses were performed by the two teams that made headlines last year for determining nearly all the “letters” of the human DNA code.
That three-billion-letter code, called the genome, is a chemical sequence that contains the basic information for building and running a human body.
“We suddenly have the global view, the view of the Earth from the moon, and it’s pretty thrilling,” said Dr. Harold Varmus, a former director of the National Institutes of Health who now heads the Memorial Sloan-Kettering Cancer Center in New York.
Celera Genomics, a private company based in Maryland, is publishing its findings in Science. A public international effort, led by the United States, is publishing its analysis of the genome in Nature, a British journal.
The two teams, which worked independently, estimated roughly the same number of human genes: About 26,000 to 39,000 according to Celera, and about 30,000 to 40,000 according to the consortium. Scientists with both groups said the best bet is something fewer than 35,000.
That’s surprisingly low, leaders of both scientific teams said.
Cracking the genetic code could help scientists and doctors find disease and illness.
“I think it means that we’ll be able to track down the actual causes of disease,” said Eric Lander of the Whitehead Center for Genome Research. “Most folks don’t realize we don’t know the cause of asthma, of heart disease, of diabetes or hypertension.”
Collins said it will take “a long time” to apply the information toward fighting --even curing -- some diseases. “But we are that much closer having this foundaton now in front of us,” he said.
On another front, Collins said federal legislation was needed to protect against the misuse of genetic information in the work place or by health insurance companies.
“We can see the path that needs to be traveled,” he said. “Let’s get on with it and put that protection where it needs to be so the public doesn’t get injured by very valuable information that we all may wish to have.”
Disease, addiction traced to DNA
Mapping the chemical sequences for human DNA -- the chemical “letters” that make up the recipe of human life -- is a breakthrough that scientists expect will lead to new cures for cancers, heart disease, drug addiction and mental illness.
One in three people in the western world will develop cancer, and one in five will die from the disease, so the search to find the maybe 20 abnormal genes in any of the 200 types of cancer is a daunting task, but one that will be facilitated by the genome sequence.
“All cancers are caused by abnormalities in DNA sequence,” said Dr Michael Stratton, the head of Britain’s Cancer Genome Project.
As for addressing addictions, medical research suggests that about 50 percent of the risk is genetic.
“That would make addiction more inheritable than diseases we commonly think of as genetic, such as adult onset diabetes or common hypertension,” said Eric Nestler, the head of the department of psychiatry at the University of Texas Southwestern Medical Center.
About 100 genes and their products have been shown to influence the process by which animals become addictive. Nestler believes the sequencing of the human genome, as well as the completed genomes of the mouse and rat, which are expected soon, will narrow the search.
But so far scientists haven’t been able to identify any genetic abnormalities in humans that contribute to the risk of addiction in humans.
‘More powerful tools’
The biggest initial impact of the human genome is expected to be on drug development, customizing drugs to individual genetic profiles and earlier diagnosis of disease.
Currently there are fewer than 500 targets for all the drugs on the market. Scientists predict the sequencing will increase that number to several thousand, sparking a boom in genomic research in the pharmaceutical industry.
“There are potentially a huge number of targets that can be investigated for potential drugs. There is also the personalization of medicine,” said Tim Hubbard of the Sanger Center in Cambridge, England.
He likened the human genome to an automobile manual used by mechanics to determine what is wrong with a car that isn’t running properly.
“We’re going to provide doctors with much more powerful tools to diagnose exactly what is wrong with somebody.”
Dr. Michael Dexter, director of the Wellcome Trust, which funded the British part of the Human Genome Project, has said before that mapping the human genome “has been compared with putting a man on the moon, but I believe it is more than that.
“This is the outstanding achievement not only of our lifetime but perhaps in the history of mankind,” he declared.
Specific sequences of DNA characters form the genes that make us what we are, govern our biological functions and determine our susceptibility to illnesses like cancer or diabetes.
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(CNN) -- Two separate groups of researchers who announced in June 2000 that they had completed rough drafts of the master blueprint of a human are publishing their findings in scientific journals.
The private U.S. research team, Celera Genomics, will publish its results in the U.S. magazine Science on February 12. The findings of the publicly funded Anglo-U.S. Human Genome Project will be released simultaneously in the British journal, Nature.
The database opens the door to the possibility of tailor-made treatments based on an individual’s unique genetic makeup, and the use of gene therapy to cure, or even eliminate, devastating inherited disorders. It could also lead to a brave new world of “designer” babies and genetic discrimination.
Despite the ethical uncertainties and technical challenges ahead, the 10-year effort to unlock the mystery of our biological essence is being hailed as one of the greatest scientific undertakings of all time.
The race to sequence the human genome pitted an international, publicly funded consortium against a private, upstart laboratory. The competition appears to have ended in a draw, with both sides announcing their achievements at press conferences in Washington and London on June 26.
“It’s hard to overstate the importance of reading our own instruction book, and that’s what the Human Genome Project is all about,” Dr. Francis S. Collins, director of the National Human Genome Research Institute in Bethesda, Maryland, told CNN.
Collins heads the Human Genome Project, a consortium of 1,100 scientists from four large genetic centers in the United States, the Sanger Center near Cambridge, England, and labs in France, Germany, China and Japan.
The international team -- financed primarily by the National Institutes of Health in the United States and the philanthropic Wellcome Trust in London -- began working on sequencing the human genome a decade ago.
Researchers used powerful computers to sort through the 3 billion bits of DNA contained in every human cell to identify the 80,000-100,000 genes that determine our inherited physical traits and many of our behaviors.
Now that the human genome has apparently been sequenced, scientists can use the information to try to decode the set of instructions contained in each gene.
The next step is the “interpretation phase,” said Craig Venter, president of Celera Genomics in Rockville, Maryland. Venter said his private laboratory has completed its own gene-sequencing project simultaneously with the Human Genome Project.
“We finally have the complete order of all the layers of genetic code and [now] we have to discover what it all means,” Venter said.
“You’re going to see a proliferation of discoveries about the genetic contributions to diabetes and heart disease and high blood pressure and schizophrenia and multiple sclerosis and on down the list,” Collins said. “Conditions that we know have genetic contributions but which have been rather difficult to nail down, this set of power tools that the genome project is producing will accelerate this discovery process rather dramatically.”
‘A whole new frontier’
“It’s comparable to Darwin’s theory of evolution,” said Dr. Steve Kay, a geneticist at the Scripps Research Institute in La Jolla, California. “I have never, ever been so excited at the rate of change we’re experiencing in biology. This opens a whole new frontier.”
Before the sequencing of the genome, scientists studying genetics were essentially “watching a soap opera on a TV screen with only two or three pixels illuminated,” Kay said. “Now, lots more pixels are filled in and we’ll get a much more clearer picture. Instead of looking at two or three genes at a time, we’ll be able to observe groups of 20,000-30,000. It gives us a global view of biology, enabling us to understand much better how a cell works.”
The sequencing of the human genome is expected to eventually lead to more effective therapies for everything from cancer to overeating. Individuals can be also be screened to determine whether they are at risk to develop certain diseases or whether they might react adversely to a particular drug.
“It will be a long time before each of us has our own genetic bar code when we go into the drug stores,” Kay said. “But not that far away is the ability to develop more drugs a lot more quickly.”
It takes an average of $500 million and 14 years to get a drug to market, Kay said, partly due to the problem of adverse reactions that set back progress of clinical trials. The ability to scrutinize the genes of individual test subjects is expected to greatly reduce the time and effort involved.
Patenting genes
As private laboratories rush to tap the gold mine of the human genome, legal quandaries, such as who owns genetic information, are coming to the forefront.
U.S. President Bill Clinton and British Prime Minister Tony Blair issued a joint statement in March 2000 declaring that the basic information on the human genome is public property.
“To realize the full promise of this research, raw fundamental data on the human genome, including the human DNA sequence and its variations, should be made freely available to scientists everywhere,” the Clinton-Blair statement said.
“Unencumbered access to this information will promote discoveries that will reduce the burden of disease, improve health discoveries around the world and enhance the quality of life for all humankind,” they said.
The statement added, however, that “intellectual property protection for gene-based inventions will also play an important role in stimulating the development of important new health care projects.”
Celera Genomics has made it clear that it entered the gene-sequencing race intending to eventually cash in on its findings, perhaps through applying for patents on individual genes.
“People think that patenting genes is patenting life, that’s the cliche you constantly hear,” Venter told CNN. “But genes are not life. They’re just strips of chemical information that can be used in lots of important ways.”
By June 2000, the U.S. Patent and Trademark Office had awarded 2,000 gene patents and had more than 25,000 patent applications on human genes pending.
“People seem to assume that there’s some nefarious reason for getting patents on genes,” Venter said. “It’s treated like it’s some evil thing that industry is doing, [but] if industry wasn’t doing that, we would not have any new treatments.”
‘The results should not be hyped’
The U.S.-led international genome project set aside 3 percent of its budget to study the implications of the commercialization of genome research and the other ethical, legal and social issues associated with the discoveries the research likely will generate.
Among the key questions the project has identified are:
Should insurers, employers, courts, schools or law enforcement agencies have access to an individual’s genetic information and how should it be used?
Should people be tested to determine whether they might later develop a disease if there is no cure for that disease?
Should fetal genetic testing extend beyond the health of a baby to screen for desirable physical and mental traits?
“Politicians and medical policy makers are going to have to do a lot of catch-up to keep pace with the science of genetic research,” Kay said.
The potential benefits of gene-based treatments do not come without risk. The Food and Drug Administration shut down gene therapy trials at the University of Pennsylvania in January 2000 because of the death of a research subject.
Eighteen-year-old Jesse Gelsinger died in September 1999 after receiving an experimental gene therapy for an inherited liver disease, OTC deficiency. His father, Paul Gelsinger, testified at a U.S. Senate hearing that the researchers acted irresponsibly and downplayed the risks involved when his son agreed to become a test subject.
“When lives are at stake, when my son’s life was at stake, money and fame should take a backseat,” Gelsinger testified. “The concern should not be on getting to the finish line first, but making sure no unnecessary risks are taken, no lives filled with potential and promise are lost forever. No more fathers lose their sons.”
Ruth Macklin, a professor of bioethics at the Albert Einstein College of Medicine in New York, said that the first social responsibility in regard to the human genome breakthrough is to not give people false hopes that all their health problems will soon be solved.
“The results should not be hyped,” she said. “The first gene transfer research was done in 1990 [for cystic fibrosis]. There has been very, very, very little progress. After 10 years of research there is still no cure. It’s true that genetic information is a new and growing area but people should not hold it up as if it’s a magic bullet.”
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Human Body
The machine that is the human body is so dependable, so familiar that we are often surprised at its amazing inner complexity. Bone, fluids, muscle, skin and all the other parts are constructed of cells. Brain cells remember. They react to information, to stimuli, then send electrical commands through nerve cells to muscle cells: constrict!
As you are reading these words with the cells in your eyes, please pause and lift your right index finger and touch the tip of your nose. Notice the smoothness of operation. Millions of cells in your body participated smoothly in that motion. Each of us is an electrochemical machine --animal -- being -- composed of cells. What gives life to our cells?
Your left hand
Please bring your left hand closer to your eyes. Focus on the tiny lines of your skin. The lines are valleys, separating broad, pliable plateaus. Skin cells form a rather thin covering around our wet muscles, bones, nerves and tubes made of cells. On your hand, can you see blood vessels beneath your skin? What are you made of?
Cell workings
The building blocks of your body are small masses of protoplasm bounded by a membrane. Cells are the fundamental units of any living organism. It is a busy, watery place inside a cell. Virtually every cell in your body contains a complete copy of your genome, the genetic material of you as an organism.
Imagine the genome as the United States. Each chromosome is a different state. As many as 100,000 genes are the cities and towns.
Organizing genes
A chromosome is a small package of genes in the nucleus of a cell. Different kinds of organisms have different numbers of chromosomes. Homo sapiens have 23 pairs of chromosomes, 46 in all, including two sex chromosomes. In mating, each parent contributes one chromosome to each pair, so a child gets half of his chromosomes from his mother and half from his father.
Files of fate
Much about your life, your proclivity for mental or physical ailments, the color of your eyes, is determined inside your chromosomes. A human chromosome is extremely small. But it may contain a string of DNA 2.8 inches (7 centimeters) long -- perhaps as long as your little finger!
The importance of proteins
A gene, which is a length of the DNA double helix, is a unit of heredity, passed from parent to offspring. Genes are pieces of DNA, and most genes contain the formula for making a specific protein. Not much happens in our bodies without proteins. They labor inside cells and perform many jobs, working as enzymes, hormones, antibodies. Each protein is the product of a particular gene.
Designer kid?
The encircling structure is made of sugar and phosphate. Like a twisting ladder, the famous double helix holds the recipe for life itself. The rungs of the DNA ladder are made of four chemicals known by the letters A, T, G and C. They come in pairs and spell the words, give the commands. Human beings have about 3.2 billion pairs.
As we expand our knowledge of how these codes control our bodies, our lives, scientists may be able to return sight to blind eyes, may be able to give you a “designer kid.” How tall, how smart? How much money would you pay to give your child an additional 50 I.Q. points?
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A
Amino acids -- A group of small molecules that join to form proteins, amino acids are often referred to as the building blocks of proteins. Although more than 100 amino acids occur naturally, only 20 are usually involved in the synthesis of protein -- and humans can synthesize at least 100,000 different proteins. The 20 amino acids have the same backbone, but each has a separate side chain -- known as an R-group -- that distinguishes it from the others.
Antibody -- A protein produced by the immune system that helps the body fight a particular disease or develop an immunity to it. The human body is capable of generating more than a trillion different antibodies.
B
Base pair -- The basic units of DNA and RNA, base pairs are chemical structures made up of the chemicals adenine, thymine, guanine and cytosine, which are designated by the letters A, T, G and C, respectively. Adenine always pairs with thymine and guanine always pairs with cytosine, creating the pairs or nucleotides in which genetic information is found.
C
Cell -- The basic unit of any living organism. It is a small, watery compartment filled with chemicals and a complete copy of the organism’s genome.
Chromosome -- One of the threadlike “packages” of genes and other DNA that is compressed and wrapped around protein in the nucleus of a cell. Different kinds of organisms have different numbers of chromosomes. Humans have 23 pairs of chromosomes, 46 in all.
D
DNA -- Deoxyribonucleic acid. The material inside the nucleus of a cell that carries the genetic instructions for making living organisms.
Double helix -- The spiraling lattice of double-stranded DNA that contains the genetic information pertinent to the organism. The sides of the lattice -- its spine -- are composed of sugar and phosphate molecules. The crosspieces, or rungs, are made up of base pairs, also known as nucleotides.
G
Gene -- The basic unit of heredity, the gene contains the functional and physical characteristics passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.
Gene mapping -- The process of determining the positions of genes on a chromosome and the distance between them.
Gene therapy -- The introduction of healthy genetic material to replace, augment or influence genes that do not function properly. In some cases the material can be injected with what is known as a genetic vaccination. In other cases the material is introduced through bioengineered viruses that carry the therapeutic gene to the cell. Globules known as liposomes can also be used to carry therapeutic genes to specific cells.
Genetic code -- The instructions in a gene that tell the cell how to make a specific protein. A, T, G and C are the “letters” of the DNA code; they stand for the chemicals adenine, thymine, guanine and cytosine, respectively, which are the basic chemical units of DNA. Each gene combines the four chemicals in various ways to spell out 3-letter “words” that specify which amino acid is needed at every step in making a protein. The precise order that spells out these “words” is the genetic code.
Genome -- All the DNA in an organism, including its genes. The DNA is found as tightly coiled threads in the nucleus of every cell. The threads are composed of paired strands of nucleotides or base pairs. There are 3.2 billion base pairs in the human genome and 80,000 to 100,000 genes.
M
Mutation -- A permanent structural alteration in DNA. In most cases such DNA changes either have no effect or cause harm. Occasionally, however, a mutation can improve an organism’s chance of surviving and passing the beneficial change on to its descendants.
N
Nucleus -- The central cell structure that houses the chromosomes.
P
Protein -- A large complex molecule made up of one or more chains of amino acids. Proteins perform a wide variety of activities in the cell.
R
RNA -- Ribonucleic acid. Sometimes confused with DNA, RNA is a group of nucleic acids that along with DNA comprises the genetic material of the cell. Genetic information is stored by DNA in the nucleus of cells, and RNA carries that information to other parts of the cell where it is converted into protein.
S
Sequencing -- The process of identifying the order in which chains of repeating units of base pairs appear in DNA and identifying the order of amino acids in proteins. Researchers label copies of a DNA sequence with fluorescent markers, then run them through a sequencing machine. In proteins, amino acids are removed one at a time from the end of a protein and identified with an automated system.
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What is the Human Genome Research Project?
An international research project to discover and map all of the 80,000 to 100,000 human genes and to determine the exact sequence of the 3.2 billion basic units of human DNA. Primary funding for the research comes from the U.S. National Institutes of Health and Wellcome Trust, a philanthropic organization in London. Other countries participating in the project include Australia, Brazil, Canada, China, Denmark, the European Union, France, Germany, Israel, Italy, Japan, South Korea, Mexico, the Netherlands, Russia, Sweden and the United Kingdom.
What is a genome?
A genome is all the DNA in an organism, including the genes that carry the information necessary for the synthesis of proteins required by all organisms. These proteins dictate the characteristics and functions of the organism, and sometimes even its behavior. In most cases this genetic material, which includes 23 pairs of chromosomes in the human body and 80,000 to 100,000 genes, are found in each of the approximately 100 trillion cells in the human body.
What is meant by “mapping and sequencing” the human genome?
Mapping is the process of determining the positions of genes on a chromosome and the distance between them. Sequencing identifies the order in which the basic chemical units of DNA appear. It is the order that the chemical units appear in the DNA that is the basis of all diversity, and determines not only eye color and hair texture, but whether an organism is a human, a fruit fly or an elephant.
What are the potential benefits of this research?
Although DNA dictates everything a cell does, the purpose of most DNA is not yet known. What is known is that changes in the DNA can lead to illness, to disease and to more subtle things, such as how the body responds to various substances.
Decoding DNA is expected to lead to enormous improvements not just in the diagnosis and treatment of disease and illness, but also in new sources of energy, healthier crops and livestock -- even improvements in criminal investigation and detection.
What exactly is DNA?
DNA -- deoxyribonucleic acid -- consists of long chains of chemical compounds with repeating structural units called base pairs or nucleotides. In a DNA molecule, two strands of nucleotides wrap around each other and look like a twisting ladder known as the double helix.
The long sides of the ladder are made of sugar and phosphate molecules. The rungs are composed of the chemicals adenine (A), thymine (T), cytosine (C) and guanine (G), which combine to form the base pairs. The way the 3.2 billion base pairs are arranged is called the DNA sequence.
Unraveled and tied together, the strands of DNA in humans would be more than 5 feet long, but only 50-trillionths of an inch wide.
How did the research idea get started?
Interest in the mapping and sequencing of the human genome began gaining momentum with scientists in the 1980s. In 1990, the U.S. Congress approved a 15-year research plan presented by the Department of Energy and the National Institutes of Health that was to be coordinated with research taking place in other countries.
Has the research focused only on humans?
No. Scientists also have worked on the genome of less complicated organisms such as yeast and the fruit fly. Knowing how the genomes of simpler organisms work is expected to contribute to the understanding of more complex organisms, such as humans. In its research on humans, the Human Genome Research Project uses DNA taken from volunteers whose identities will be withheld to ensure their privacy.
What role has technology played in the research?
Computers were used to break the DNA into sections the length of 35,000 “letters” -- or chemicals -- and to determine how they were arranged on the chromosomes. Then work was begun on the more difficult task of determining the precise sequence of the 3.2 billion pairs.
Why were there two competing groups working on the human genome?
In 1998, a private company, Celera Genomics Inc., negotiated with the government-subsidized Human Genome Research Project to bring in new technology that would speed up the research.
Central to Celera’s effort was the use of lasers and other new technologies that enabled researchers to detect sequences several thousand letters long -- letter by letter. J. Craig Venter of Celera says the company’s researchers are able to sequence between 100,000 and 200,000 samples a day, and that each produces about 600 letters of genetic code.
Ultimately the government project and Celera were unable to agree on a working relationship and went their separate ways. In June 2000, however, both parties and a third participant, the Sanger Center in London, coordinated their announcement that they had successfully sequenced the human genome.
Are the findings identical?
That is what interested bystanders would like to know. Both sequences are to be published in scientific journals later this year, however, and both are expected to be available on the Internet. Celera’s will be on celera.com. The government’s will be on the Human Genome Project’s site http://www.ornl.gov/hgmis/project/progress.html.
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