In February 2001 the first working draft of the human genome—90% of the sequence of the genome's three billion bases—was published in special issues of the journals Nature (February 15, 2001) and Science (February 16, 2001). Nature detailed initial analysis of the descriptions of the sequence generated by the public HGP, and Science contained the draft sequence reported by private projects conducted by Celera.
One of several surprises from the first draft was that prior estimates of gene number appeared to have been wildly inaccurate. Most pre-genome project estimates predicted that humans had as many as 60,000 to 150,000 genes. The first draft of the complete genome sequence indicated that the true number of genes required to make a human being was less than 40,000. By comparison, yeast have about 6,000 genes, fruit flies have 14,000, roundworms have 19,000, and the mustard weed plant has 26,000. Another surprise was the observation that humans share 99.9% of the nucleotide code in the human genome. Notably, human diversity at the genetic level is encoded by less than a 0.1% variation in DNA.
First Draft Is Headline News
President Clinton and Prime Minister Blair celebrated the completion of the first survey of the entire human genome by holding a press conference together at the White House. President Clinton expressed his desire to translate findings from the project into strategies to diagnose and treat disease, and he reiterated his belief that genetic information should not be used to discriminate against individuals or groups. A June 26, 2000, press release predicted some of the anticipated medical outcomes of the project. These included the ability to:
- Alert patients that they are at risk for certain diseases. Once scientists discover which DNA sequence changes in a gene can cause disease, healthy people can be tested to see whether they risk developing conditions such as diabetes or prostate cancer later in life. In many cases this advance warning can be a cue to start a vigilant screening program, to take preventive medicines, or to make diet or lifestyle changes that may prevent the disease.
- Reliably predict the course of disease. Diagnosing ailments more precisely will lead to more reliable predictions about the course of a disease. For example, a genetic fingerprint will allow doctors treating prostate cancer to predict how aggressive a tumor will be. New genetic information will help patients and doctors weigh the risks and benefits of different treatments.
- Precisely diagnose disease and ensure that the most effective treatment is used. Genetic analysis allows us to classify diseases, such as colon cancer and skin cancer, into more defined categories. These improved classifications will eventually allow scientists to tailor drugs for patients whose individual response can be predicted by genetic fingerprinting. For example, cancer patients facing chemotherapy could receive a genetic fingerprint of their tumor that would predict which chemotherapy choices are most likely to be effective, leading to fewer side effects from the treatment and improved prognoses.
- Developing new treatments at the molecular level. Drug design guided by an understanding of how genes work and knowledge of exactly what happens at the molecular level to cause disease will lead to more effective therapies. In many cases, rather than trying to replace a gene, it may be more effective and simpler to replace a defective gene's protein product. Alternatively, it may be possible to administer a small molecule that will interact with the protein to change its behavior. This is the strategy behind a drug in development for chronic myelogenous leukemia, which targets the genetic flaw causing the disease. It attaches to the abnormal protein caused by the genetic flaw and blocks its activity. In preliminary tests blood counts returned to normal in all patients treated with the drug.
On June 26, 2000, the world's premier scientists and politicians were also quoted in the media. Venter spoke for many researchers when he said, "I think we will view this period as a very historic time, a new starting point." Michael Dexter of the Wellcome Trust echoed Venter's sentiments when he ventured, "This is the outstanding achievement not only of our lifetime, but in terms of human history. I say this because the Human Genome Project does have the potential to impact on the life of every person on this planet." Randy Scott, president of Incyte, another private firm involved in genomics research, predicted that "the availability of genome sequence is just the beginning. Scientists now want to understand the genes and the role they play in the prevention, diagnosis, and treatment of disease." Mike Stratton of the Cancer Genome Project was equally optimistic when he said that "it would surprise me enormously if in twenty years the treatment of cancer had not been transformed." The Nobel Prize–winning English biochemist and professor Frederick Sanger, the pioneer of DNA sequencing, expressed the collective awe of the scientific community when the HGP was completed earlier than anticipated. Sanger admitted, "I never thought it would be done as quickly as this."
In the United Kingdom the June 27, 2000, edition of the Mirror trumpeted, "It's one small piece of man … one giant leap for mankind," running a headline that read, "Joy as scientists crack DNA code of life." The press strove to top one another with their headlines proclaiming publication of the first draft. The Times termed it the "The book of life," and the Guardian
FIGURE 7.5
From DNA to humans
The U.S. media celebrated the achievement with a flood of press releases and features. The June 22, 2000, edition of the New York Times described the eleventh-hour truce negotiated between the private and public HGP initiatives in "Rivals in the Race to Decode Human Genome Agree to Cooperate." The following day the New York Times described Collins's concerns about the implications of the use of HGP data in features entitled "Genomic Chief Has High Hopes" and "Great Fears for Genetic Testing." The February 13, 2001, issue of the New York Times offered articles with the headlines "Genome's Riddle: Few Genes, Much Complexity," "The Silence Is Broken," and "The Genome Speaks, and Double Helix with a Twist."
Efforts were also made to explain this monumental achievement to the public and to educate students. The DOE Human Genome Program provided a wealth of information about the HGP and its findings on the Internet. Figure 7.5 is an example of the information the DOE made available to the public. Table 7.3 presents some of the potential environmental benefits of the HGP that may be realized in the future.
The announcement of the first draft also tempered the rivalry between the public and private human genome sequencing initiatives. In the United Kingdom the Guardian wrote, "Scientists revel in day of glory," while the Telegraph characterized the final leg of the public-versus-private race to complete the sequence as "Vietnam veteran makes peace with ex-hippie."
TABLE 7.3
Projected national benefits of genomics research, 2020–2050
| Within a decade | Long term | |
| 2020 | ||
| Develop knowledge base for cost-effective cleanup strategies | Save billions of dollars in toxic waste cleanup and disposal | |
| 2040 | ||
| Understand earth's natural carbon cycle and design strategies for enhanced carbon capture | Help stabilize atmospheric carbon dioxide to counter global warming | |
| 2050 | ||
| Increase biological sources of fuels and electricity | Contribute to U.S. energy security • Biohydrogen-based industry in place |
Whose Genome Was Sequenced?
In "Single Nucleotide Polymorphisms: … To a Future of Genetic Medicine" (Nature, vol. 409, no. 6822, February 15, 2001), Aravinda Chekravarti recalled that at the beginning of the HGP there was spirited debate about whose genome was to be sequenced. Some people thought it might be the genome of a single individual, a celebrity, or possibly even Watson. Others thought several genomes from many individuals should be studied. Chekravarti interpreted this debate, however lighthearted it may have been, as being at the very core of genetics study. Chekravarti wrote, "As the study of inherited variation between individuals, genetics might not immediately benefit from the sequence of a single genome. But even one genome would be immensely revealing to the science of deciphering the molecular blueprint of a species." Interestingly, when Celera decided to compete with the publicly funded human genome sequencing initiative, the genome they sequenced was Venter's, rather than a composite genome as the firm's initial plans had stated.
User Comments Add a comment…