A Fish That's Almost Human?

Partly through trial and error, Lane and her associates determined that the embryo changed dramatically, depending on when that particular gene was altered. It had to be available to complete the good things it's supposed to do, like determine the size of the eyes, before it could be eliminated and thus reduce the chance of cancer.

The researchers are able to exercise some control over the gene by using a technique that seems simple, at least compared to the complexity of the problems they are trying to solve. They use a thin glass tube, which is heated and drawn to a sharp point, making a very tiny needle. Various chemicals can be inserted into the embryo, thus causing the gene to become more or less expressive, or even die. Then they sit back and watch the results.

That allows them to determine which changes in the embryo are caused by which genes. And that is a big part of the puzzle.

"When we look at the embryo we want to know how this egg becomes an embryo, and how this embryo becomes a fish," Lane said. "It uses genes, but which genes and when, and how does it use them and what do they do?"

The zebra fish is nearly a perfect platform for that, but no platform is perfect. The researchers can't direct the chemicals to a specific gene. They can simply inject the chemicals into the embryo, or fish, and hope they find the right gene. It works some of the time, so to be sure they have enough samples, a lot of zebra fish join the effort.

"You inject 500, which you can knock off in a day or two, and you'll get a bunch of good ones," Lane said.

It's a pot luck?

"Yup."

Pot luck, of course, isn't good enough for human application, so before any of this makes it to your neighborhood clinic, all the details have to be worked out. There can be many unanswered questions, and it will take many years to answer them all.

Still, it's an amazing improvement over the scientific world that Lane first entered.

"When I started grad school in 1988, a lot of very, very smart people, including some Nobel Prize winners, were saying that humans and flies and mice have a few common genes, but their genomes [or genetic codes] are going to be very different."

In other words, a zebra fish couldn't be all that helpful, because everyone knows a fish is very different from a human.

Wrong, as it turns out.

"This was the big shock at the end of the last century [remember, that's just seven years ago]," Lane said. "I think it's something like 80 percent of all zebra fish genes have a human homologue [a similar gene.] There's even some similarity at the organizational level."

"Nobody expected this."

And it's safe to add that nobody expected genes to be so complicated, and so tricky. Some day, perhaps, enough of the questions will be answered to make those genes behave the way they're supposed to, thus wiping out a wide range of human genetic illnesses.

But as Lane said, "It's a long road."

Lee Dye is a former science writer for the Los Angeles Times. He now lives in Juneau, Alaska.

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