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Genome Breakthrough

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6/27/00 11:00 a.m.
Genome Breakthrough
A good day for the world.

By Ronald Bailey, science correspondent, Reason magazine

iotechnologist Craig Venter is a true scientific hero. His company, Celera Genomics, along with the government-backed Human Genome Project, announced yesterday at the White House that it had completed sequencing the entire human genome. In other words, Celera has read the vast majority of the 3.15 billion DNA base pairs that are the digital recipe for making a human being.

Venter and Celera began their quest just two years ago. From the outset, Venter was vilified by many scientists working with the official Human Genome Project (HGP); chief among his critics was Francis Collins, director of NIH's National Human Genome Institute. Collins repeatedly assured the media and the Congress that Venter's breakthrough technique for sequencing genomes would not work and that Congress should continue to back the government project. It is now clear that without the spur of competition from Celera, the HGP would have taken another two to three years to sequence the human genome. However, when it became apparent that Venter was sequencing at blistering speed, attempts were made to establish an alliance of the HGP and Celera. Those negotiations broke down, reportedly because an obstinate Collins kept objecting to working with the private sector.

What a difference a couple of months make! Evidently, when the HGP and its partner labs in Britain, France, Germany, Japan, and China realized that Venter would likely take the prize and claim sole scientific credit for sequencing the human genome this summer, they hastened to patch things up with Celera. The rapprochement between Celera and the Human Genome Project led directly to the White House ceremony on June 26. The Feds got to share the limelight on this historic occasion, while Venter got to announce his company's achievement in the bully pulpit of the White House — and is spared further sniping from jealous bureaucrats. At the ceremony, Collins ate plenty of crow and fulsomely praised his private-sector rival.

Putting politics aside, sequencing the human genome is just the beginning. Decades of work will have to be done before humanity will reap the benefits of genomic research. The four DNA bases — adenine, thymine, cytosine, and guanine (ATCG) — combine into 64 three-letter genetic "words" called "codons" that specify a set of 20 amino acids and three stop signals. These amino acids, when linked together by reading the recipe from the DNA bases in various genes, create the hundreds of thousands of different proteins that make up the human body.

Strange as it may seem, knowing all the human DNA base pairs doesn't tell researchers what or where specific genes are. In fact, among geneticists there is a betting pool on the number of human genes that ranges from a low of around 40,000 to more than 100,000. Even stranger, 97% of the human genome isn't composed of proper genes at all. Our genome appears to be mostly so-called "junk DNA," composed of parasitic sequences like human endogenous retroviruses and transposons, that do nothing but replicate themselves. Scientists are rushing to uncover the genetic differences between individual human beings, including their varying susceptibilities to disease. For example, you and a neighbor might have two different versions of the same gene, differing only by single base pair. These variations in base pairs are called single nucleotide polymorphisms (SNPs, pronounced "snips"). Your version might make you less likely to suffer heart disease than does the version your neighbor has. Researchers believe that understanding these differences will lead to better medicines. Drugs could be customized to work with your specific genetic profile. Celera and the HGP plan to find and catalog between 300,000 and 1 million of the most common SNPs.

The genome readout looks like so many random As, Cs, Gs, and Ts. To understand what a sequence means, it helps to compare it to the genomes of other species like that long-time lab favorite, the fruit fly. Celera, working with a university consortium, announced the sequencing of the entire fruit-fly genome in March. It turns out that 50% of fly proteins are similar to known mammalian proteins. More significantly, Celera expects to sequence the mouse genome by the end of this year. More than 90% of mouse proteins are similar to known human proteins. This information allows scientists to experiment with mice as a way to find out what the homologous gene does in us.

At bottom, genes are recipes for proteins, which do the actual work. Biotechnologists, working in the new field of proteomics, would like to find out what a specific protein looks like--by calculating its shape and function from gene information alone--in order to match drug molecules against it.

IBM announced late last year that it was building a computer dubbed "Blue Gene" that will be 500 times more powerful than any working today. Despite its computational power, Blue Gene will still take one whole year to calculate how just one protein folds into its proper shape. Defects in protein folding can cause disease, and understanding these defects could lead to new medical treatments.

To understand some diseases, researchers also need to know how proteins interact with one another. Figuring that out is an awesomely daunting task. As complexity theorist Stuart Kauffman of the Santa Fe Institute pointed out in Scientific American, a network of 100,000 variables (e.g., genes) that can be turned on or off can have 10-to-the-30,000th possible states. Bear in mind that the number of particles in the universe is only 10-to-the-80th power. To analyze the flood of data, and uncover the sources of disease and aging, Celera and other biotech companies are fast developing bioinformatics, which marries vast computing power to novel mathematical tools. The cures for cancer, diabetes, dementia, and even aging may really be only a decade or two away.

But let's leave tomorrow's challenges for tomorrow. Today, the achievement of Venter, and also of Collins, should be celebrated as one of the crowning glories of our civilization and as a wonderful gift to all of humanity. As Collins rightly declared, "It is a good day for the world."

And, oh yes, President Clinton and Prime Minister Tony Blair were at the press conference, but said nothing noteworthy.

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