ENCODE

Listen to Tim Triche from Children's Hospital Los Angeles for very long and you’ll get excited again about cancer research. I couldn’t stop listening. Which is why his interview is being published in two parts.

Now sure, like other guests we’ve had on the show, Tim calls this the “absolute golden age of biomedical research.” But Tim has a unique story. He has been, and is still - though less so now, he says - an outlier in cancer genomics. Whereas most cancer researchers talk about genes, Tim is more interested in non-coding RNA.

An avid user of microarrays, Tim begins Part 1 of the interview with a reference back to “a very interesting experiment” done at the Affymetrix research lab when the first arrays were being designed. The Affy research team put (nearly) the entire stretch of chromosome 21 onto a wafer, and in a “beautiful Science paper” showed the importance of the non-coding or inter-genic region of the genome.

Using the Affymetrix Exon array that was developed as a result of the experiment, Tim has continually demonstrated that there are indeed useful diagnostic and prognostic cancer biomarkers to be found in the non-coding RNA.

And speaking of technology from the early 2000’s, Tim argues that we should reconsider GWAS studies. Perhaps there are still some simple answers to be found when considering the whole genome and not just genes.

In Part 2, Tim vows the incredible staying power of the array technology in the clinic as well as research. He also responds to recent skepticism over whether the age of genomics is delivering on its promise.

Editor's Note:  In this interview, Tim refers to an older generation Affymetrix array (GeneChip^(R) Exon 1.0 ST Array).  The newest array (GeneChip^(R) Human Transcriptome Array 2.0) is able to measure gene and exon level expression of coding and long non-coding RNA with the ability to detect alternative splicing events.

Guests:

Christopher Mason, PhD, Assistant Professor, Weill Cornell Medical College

Listen (5:59) ENCODE and the functional genome

Listen (6:00) 59,000 genes in the human genome

Listen (9:00) Huh? Genes can be patented?

Listen (2:36) Did the Supreme Court get the right balance in Myriad case?

Listen (6:26) Genome Liberty - opening up the flood gates for genetic testing

Today we continue our exploration of the recent Myriad gene patent case and what it means for research and the life science industry.

Chris Mason, a professor of genomics at Weill Cornell Medical College, has always greeted the idea of gene patents with disbelief. Working in his lab to "understand the human genome down to every base and every base modification," Chris has been involved with the Myriad/ACLU case from the beginning, serving at times as an expert witness.

In today's interview, Chris discusses his involvement in the case which included some basic scientific training of the lawyers at the ACLU. He also shares his thoughts on the outcome of the big decision. Did SCOTUS strike the right balance? And what practical implications will the decision have?

One of the outcomes is a new company, co-founded by Chris, called Genome Liberty. The company launched last week with the goal of "opening up the flood gates for genetic testing."

Chris is passionate not just about "genomic liberty", but about basic genomic science as well, citing a "duty to the universe" to get it right.

"It's my favorite thing to do," he says in the interview, "to make sure that any new text that is published is obsolete within a year."

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Guests:

Ross Hardison, PhD, Professor of Biochemistry and Molecular Biology, Penn State University Bio and Contact Info

Listen (3:39) ENCODE has provided valuable data

Listen (3:36) Lineage specific selection

Listen (6:50) Looking for specific biochemical activities that are important

Listen (9:28) It's not so simple as big science vs small science

Listen (4:08) Have the critisicms changed your mind at all?

Listen (4:11) The debate itself a great outcome

In an earlier show, we interviewed Dan Graur and Michael Eisen about the ENCODE project, a massive research undertaking to further characterize the human genome. It’s been done by over 400 researchers at a cost of over $400 million. Both of the guests were quite critical of the published findings of the project and of big projects like this in general.

To represent the ENCODE project we're joined by Ross Hardison, a professor of Biochemistry and Molecular Biology at Penn State University and a collaborator on the ENCODE project from the beginning. Ross says he is delighted with the debate about how much of the genome is functional that the Graur paper has excited. And he makes a strong argument that the ENCODE team was focused on specific biochemical activities, and that these are important. He says Graur's charge on our previous show that the project might have called 100% of the genome functional because all DNA replicates, "just silly." He also says that Graur's and Eisen's rants about Big Science don't mean much to him. He considers himself a researcher funded by RO1's just as they are. It's not as simple as Big Science vs. Small Science. What was the goal of ENCODE and are they reaching that goal, we ask Hardison in Part II of Debating Encode.

Podcast brought to you by: See your company name here. - Promote your organization by aligning it with today's latest trends.

Guests:

Dan Graur, PhD, Professor, University of Houston Bio and Contact Info

Listen (4:45) Active does not equal functional

Listen (3:44) ENCODE claims play into the hands of creationists

Listen (2:24) Big Science never accomplished anything

Listen (3:01) ENCODE should have claimed that 100 percent of genome is funtional

Listen (2:19) Why the strong tone?

Michel Eisen, PhD, Associate Professor of Genetics, Genomics and Development at University of California, Berkeley Bio and Contact Info

Listen (3:54) 80% claim, silly and disingenuous

Listen (3:30) Scientists responsible not the press

Listen (2:23) Is there an appropriate tone for scientific publications?

Listen (9:02) Big Science is a fundamental shift to Soviet style

Listen (4:56) BONUS: Why are you not happy with the White House response to Open Access Petition?

Last week, Twitter went ablaze with the hashtag #ENCODE. ENCODE (the Encyclopedia of DNA Elements) is a massive, multi-phase research project costing over $400 million done by over 400 researchers. Project findings, published last September in more than 30 scientific papers, were centered around the claim that though 80% of the genome doesn’t contain genes, it still plays a role in health. The media was quick to pick up on such a claim. The headline "Death of junk DNA" went around the world. Even Science Magazine was quick to issue the Eulogy for Junk DNA.

Now, a group led by Dan Graur, a professor from Houston University, have just published a paper criticizing the ENCODE project and their findings. The Graur et al critique is the third major paper to do so, but went more forcefully after the ENCODE claim that the genome is 80% functional. There were lots of tweets supporting the scientific validity of the Graur paper, but expressing disappointment with it's tone.

We're joined first on today's program by Dan Graur. If you didn't pick it up from the title of his paper (On the Immortality of Television Sets), Dan is an hilarious speaker, and leaves nothing to guesswork as to his position. He is clear on what constitutes "functional" in his view and replies to the charge that his tone was over the top mean.

We're joined next by Michael Eisen, the co-founder of PLOS, for a third party take. Eisen is equally blunt in his answers. He is heavily critical, not only of the ENCODE publications (agreeing more with Graur's definition of "functional"), but also of the ENCODE project in general. When asked about the appropriate tone for a scientific publication, Eisen answers, "the truth." He further surmises that the strength of Graur's tone is more than venom for one claim, paper, or even project. It is a frustration with the NIH over their priorities. A biology professor himself at UC Berkeley, Eisen feels that Big Science projects such as ENCODE and the recently announced brain mapping project are a fundamental shift that threatens molecular biology research in America.

We reached out to some leaders of the ENCODE project but unfortunately were not able to schedule any of them in time for today’s show. We hope to have one of them on soon.

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Guest:

Church George, PhD, Professor of Genetics, Harvard Medical School and Professor of Health Sciences & Technology, Harvard and MIT.
Bio and Contact Info

Chapters (Move marker to advance)

0:35 Ars Electronica

1:55 The first encoding of digital art into DNA

4:20 The ENCODE project

7:14 Are scientists the new world rulers?

9:24 Teased by the future

At Mendelspod we like to showcase a different side of the industry leaders. Last month we caught up with Dr. George Church after the Burrill Personalized Medicine Conference. He had just returned from Linz, Austria where he gave the keynote address to the Ars Electronica Show. What was he doing at an art show, we ask him along with some other favorite questions.

"Are you playing God. . . . because you certainly have the beard for it." Stephen Colbert in an interview with Dr. Church