Human Genome Map Has Scientists Talking About the Divine:

Surprisingly low number of genes raises big questions

Aftershocks of the human genome announcement rippled through San Francisco all weekend as the annual meeting of the American Association for the Advancement of Science brought thousands of thinkers here to mull the surprising fact that humans have only a few more genes than mice.

But to my mind, the most memorable moment in these last few weeks of genetic astonishments came during an interview with computer scientist Gene Myers at the Maryland headquarters of Celera Genomics, just a few days before the genome maps were made public.

I reached Rockville exhausted from overnight travel and bug-eyed from poring over the maps that I had been given in advance. In return I promised to keep the findings hush-hush while I spent several days interviewing the mapmakers about their findings.

Celera was a frenzy of activity when I arrived. Television crews were shooting interviews. Phones were ringing off the hook. Myers, pressed for time, grabbed a salad from the company cafeteria and managed a few mouthfuls in between sound bites. Celera spokeswoman Heather Kowalski popped in and out of the room where Myers and I met, but paid us little mind, her nose glued to the pager that inundated her with messages and e-mails.

I mention all this because it is in such settings that people like me–your eyes and ears–are supposed to plumb the mysteries of our time. In this case, everyone who had seen the map realized that our gene deficit raised enormous questions: If we had roughly the same gene count as mammals that never flew across country on the red eye, or took notes on a steno pad, what interplay of inanimate molecules could possibly explain our complex and curious selves?

Of course, even obnoxious types like me find it tough to barge in and broach such issues in the first breath, but as I kept asking questions and Myers slowly finished his salad, we gradually warmed up to the mystery of how this incredible genetic code came into being.

“We’re deliciously complex at the molecular level,” Myers said, gesturing with his fork. “We don’t understand ourselves yet, which is cool. There’s still a metaphysical, magical element.”

Myers was the guy who put together Celera’s genome map. Celera’s sequencing machines had broken the 3 billion chemical letters in a strand of DNA into millions of fragments, each a few hundred letters each. His software put the fragments back in order just days before Celera and the leaders of the Human Genome Project shared a stage with former President Clinton, last June, to say that they knew the sequence of the genome from end to end. Talk about deadline pressure!

Now, with the pressure off, this former University of Arizona professor waxed philosophical on the code his team had cracked. “What really astounds me is the architecture of life,” he said. “The system is extremely complex. It’s like it was designed.”

My ears perked up.

Designed? Doesn’t that imply a designer, an intelligence, something more than the fortuitous bumping together of chemicals in the primordial slime?

Myers thought before he replied. “There’s a huge intelligence there. I don’t see that as being unscientific. Others may, but not me.”

About that time, Kowalski popped in to move Myers to a TV interview and told me she had rearranged things to make sure I interviewed Celera President Craig Venter early enough for me to catch my flight home.

Since that hurried exchange, Myers’ words have rattled around in my brain. It’s not the sort of sentiment one puts in an article, unless it’s being written for one of those papers with screaming headlines sold in supermarket checkout lines: “Genome Mapper Sees Hand of God!”

Myers’ sentiment reminded me of another mystery I’d encountered a little over a year ago, during a weeklong “boot camp” at the Knight Center for Science Journalism in Cambridge designed to indoctrinate civilians like me on the genome.

It was our last day and the hard disk between my ears was darn near full when David Bartel of the Massachusetts Institute of Technology walked in and explained how scientists were trying to show how RNA might have been the origin of life. He said DNA was too complex to have been formed by the random encounters of chemicals back when the earth was barely cool.

I remember sitting in class stunned to think that scientists, who could track the origin of the species through the fossil record, and trace genes jumping from organism to organism over time, had lost the scent at the primordial pool.

What Bartel had described was the concept of the RNA world, and if all life had started with RNA that would have been fine with me. Unfortunately, scientists aren’t yet sure how RNA came into being.

I recently traded e-mails with Andre Brack, a biologist at the Centre de Biophysique Moleculaire in France and president of the International Society for the Study of the Origin of Life. “The direct formation of RNA is not a generally accepted model for the origins of life,” he wrote. Synthesizing RNA out of chemical scraps has turned out to be a problem so far. Brack postulates that a more primitive molecule evolved into RNA, but as for what it might be, “We don’t know yet.”

A Web search for the term “RNA world” also turned up some interesting writings by Leslie Orgel, a researcher at the Salk Institute in San Diego, about the chicken and egg issue involving proteins. In modern cells, proteins help make RNA and DNA–just as DNA and RNA help make proteins. So it turns out science still can’t explain the chemical interactions that gave rise to the DNA, RNA and protein molecules that form the triumvirate of life.

So scientists can’t explain the chemical genesis of the DNA, RNA and protein molecules that form the essential trinity of life.

But such scientific uncertainty lay outside my purview. My job was to cover the race between Celera and the publicly funded Human Genome Project, to explain what the genome told us about ourselves, and not to ruminate on mysteries best left to chemists.

So I kept evolution’s big unknowns locked in my mind for months, until Myers’ comment and the surprising news about the gene count emboldened me to ask aloud: Could science tell us for certain whether life arose randomly or resulted from a directed design?

“It’s a wonderful, big, deep question,” said Harvard professor Wally Gilbert, whose 1986 essay titled “RNA World” started scientists thinking about how disorderly molecules might suddenly have snapped to attention and formed the long, self-replicating chains that are the hallmarks of life as we know it.

Gilbert and I had a brief, fun telephone chat. I mentioned the new creationist [sic] critique of evolution embodied in books like Lehigh University biochemist Michael Behe’s “Darwin’s Black Box.” Behe celebrates the fact that science cannot demonstrate how the molecules that are the foundation of life came into being spontaneously.

Gilbert listened kindly and didn’t make me feel a fool for asking whether, in the absence of proof to the contrary, people shouldn’t be free to consider the code of life the handiwork of God.

“Of course one is free to believe that for any little piece of the detail, God did it,” Gilbert said, untroubled by the absence of proof at the root of evolution.

“From the viewpoint of science, we’re surrounded by uncertainty,” he continued. “The parts we look at are the parts we don’t understand . . . But the scientific belief is that in due course, an explanation will be found.”

I thanked Gilbert and said goodbye, and somehow it made me feel better to know that no matter what I chose to believe about the origin of life, that it was faith that would drive my decision, whether it was faith in a maker or faith in our ingenuity to puzzle out the mystery of from whence we came.

© 2001 San Francisco Chronicle