Thursday, November 6, 2008

UA genomics lab tackles Holocaust puzzle

[Source: Tom Beal, Arizona Daily Star] - Genetic technology developed to identify the remains of those killed in the terror attacks of Sept. 11, 2001, will be enhanced in a University of Arizona genomics laboratory to solve a more complex puzzle — identification of families separated for generations after the Holocaust.

In addition to possibly reuniting families, the DNA Shoah Project will collect a database that will aid identification of remains yet to be discovered and will develop forensic tools for use in other acts of genocide.

The project, an effort of the UA's Human Origins Genotyping Laboratory, is also creating an educational component that will allow the story of the Holocaust to be taught in scientific curricula.

It's not possible today to match relatives three generations apart, but that doesn't deter UA researchers, who say they'll solve that puzzle once the data are collected.

In the meantime, the DNA Shoah Project is racing to spread the word to Holocaust survivors, whose numbers dwindle by the day.

Tucson survivor Bill Kugelman, 83, said he intends to give a simple oral swab sample of his DNA to the project, though he expects no benefit from it. Kugelman, a survivor of three Nazi concentration camps, lost most of the European branch of his family in the Holocaust.

"All of the family I have, I have," said Kugelman. "Whoever is gone, is gone."

Matches of living relatives are a long shot, said Matt Kaplan, research director for the DNA Shoah Project, but he's confident some will be made and says the project will have many other benefits.

In addition, it represents an intriguing scientific puzzle for Kaplan and the lab he runs in the University of Arizona's Bio5 Institute.

He calls the technology developed for remains-testing at Ground Zero "high quality work" but also says "it was easy. It matched you to you. We're trying to do this for the Holocaust — 6,000 people a day killed, 9 million overall."

In addition to the numbers, the passage of time makes the task more difficult.

"Your DNA is a shuffled deck of cards you get from your mom and your dad."

With each succeeding generation, that shuffling makes identification of similarities more difficult.

Most of our DNA is identical, said Kaplan. "That's what makes a wildebeest a wildebeest. Or a human being a human being."

What the computers are looking for are those random mutations that not only identify "you as you," but you as the son or daughter of your particular parents. That gets tougher with each successive generation because you're losing half of the original material each time your DNA deck is shuffled.

"The more markers we can identify, the deeper in time we're going to be able to go back," said Kaplan.

Kaplan says he'll need a fairly large group of DNA, at least 10,000 samples, to begin looking for markers and matches.

He can't do that today, but he's getting close, Kaplan said. "Most of the things I do today were impossible three or four years ago."

It's made simpler by the infrastructure built by Arizona Research Labs at the UA's Bio5 Institute, where the Human Origins Genotyping Laboratory installed the technology to handle large-scale genotyping after it signed on to do the sampling from 260,000 people who have so far participated in the Genographics Project, run by IBM and National Geographic.

"In 2000, we did 300 samples," said Kaplan. "Now it's 1,500 to 4,000 a day."

His lab and his collaborators at the Genomic Analysis and Technology Core and the Biotechnology Computing Facility, now offer large-scale DNA testing for the entire UA campus, in addition to the outside projects.

The first step for the DNA Shoah Project is not testing, but collecting samples. Holocaust survivors, the first target of the campaign, are dying.

"It's a numbers game," said Lynn Davis, information specialist for the project. "We need to get around the world and build the biggest database we can to make it possible."

Right now, the DNA Shoah Project has fewer than 1,000 participants. Its outreach is going first to Jewish congregations and Holocaust survivors groups.

Next, said Syd Mandelbaum, the project's founder, they'll concentrate on second- and third-generation descendants of those orphaned, killed or displaced.

Mandelbaum, who now runs a nonprofit organization to feed the hungry in New York, was a geneticist earlier in his career. He is also the son of two Holocaust survivors, who always wondered if some members of the families they thought were wiped out might have been displaced and are still living somewhere in the world.

He began searching for a scientific way to answer his parents' questions after reading accounts of a mass grave that had been disturbed in the excavation for an airport expansion in Stuttgart, Germany.

He discovered there was no genetic database for comparing those remains.

A former colleague directed him to Kaplan's boss, UA geneticist Michael Hammer. He visited and was impressed with the UA's setup.

Then, Mandelbaum had a call from another former colleague, James Watson, whose theoretical work with Francis Crick on the structure of DNA led to a Nobel Prize in 1953.

Watson directed him to Howard Cash, of Gene Code Forensics, who had developed the genetic matching system that identified Ground Zero victims during the excavation of the World Trade Center in Manhattan.

Cash became a part of the project and donated his company's software to it.

For Kugelman, the Tucson Holocaust survivor, the odds of anyone finding lost family seem high but not impossible.

"Who says no? You don't know. You never know. My extended family in Poland was more than 100 people. After the war there was a handful left, except for the family we had in America."

He is also certain there are mass graves yet to be discovered. He was forced to dig graves in a camp near Dachau in Bavarian Germany during the war — the camp where his brother perished.

Kugelman began speaking out about his experiences long after the war. "It took me about 30 years to open my mouth. For 30 years, you try to erase from your memory the horrible things."

To Mandelbaum, the genetic history he is helping to record is part of that total history that should never be forgotten. "It's another way to keep the memory alive."

He thinks the project's potential impact on the young is the most important part of it.

"They read 'The Diary of Anne Frank' right now, but how about a DNA lesson in a science class to talk about the Holocaust?"

Davis said the project has already developed the first module of a curriculum that will harness the current interest in forensic science to interest students in both science and the history of the Holocaust.

No comments: