genomic medicine

Matt Might came knocking on the door of genomic medicine out of pure necessity. After a four year diagnostic odyssey that led them to Duke University, Matt and his wife, Cristina, finally found out through exome sequencing that their son, Bertrand, was suffering from a rare disease known as NGLY1 deficiency. That was three years ago.

In today’s interview, we focus on what Matt did after he received this diagnosis. Through various means, mostly involving the internet, he has been able to connect with the parents of thirty seven other children with the same rare disease. As the group of patients grows, so do the options for studying the disease and for developing a therapy.

Since the president launched his Precision Medicine Initiative, we've heard from a new round of critics that genomics research just isn’t paying off. Matt’s story contradicts these criticisms.

In fact, he comes right out and says he’s on a campaign "to end the phrase, ‘non actionable.’” To Matt--who’s career has been in computer engineering--science is medicine. Matt’s connection with the rare disease community was kicked off with a personal blog he wrote that went viral, Hunting Down My Son’s Killer. Matt says with Google, blogging, and social media parents everywhere can do science. 

Prior to recording this interview, Matt was at the White House for a couple weeks helping out with the president’s new initiative. What is his take on that, and, as an outsider, what is the number one thing he would change about biomedical research?

Last year, pharma giant Roche went on a buying spree, picking up one company after another. In December, when it was announced they had bought out Bina Technologies, many of us were playing catch up. Who is Bina, and how do they fit in the overall bioinformatics space?

Today we hear from Bina's CEO, Narges Bani Asadi. As with many new bioinformatics companies, Bina has changed their service and product since they spun out of Stanford and UC Berkeley four years ago. Narges says that the biggest demand from customers is to provide a comprehensive solution for the entire organization. Often, she says, she encounters brilliant bioinformaticians working at customer organizations who are completely overwhelmed by all of the various informatics tools available. Many of these tools are offered free over the internet, and, she says, it’s creating “open source overload.”

Bina has been a very ambitious company from the start, working to provide NGS users with a comprehensive informatics solution, from beefy, fast infrastructure to an interface for the various kinds of users in an organization, to high powered analytics. And Narges is excited about the Roche buyout, saying that it will speed up their plans. Indeed, just providing bioinformatics solutions to Roche in both their drug and diagnostic divisions is already a huge project.

What was Bina doing so well that attracted Roche, and what will the future NGS informatics ecosystem look like? Join us for an inside look at the world of bioinformatics with one of the space’s most dynamic leaders.

In the second part of our interview with Tim Triche, Director of the Personalized Medicine Center at Children’s Hospital Los Angeles, Tim says that micro arrays are still a vital technology for today’s cancer researcher. Making use of both next-gen sequencing and arrays for his research, Tim confirms that arrays still have advantages in the clinic as well, such as quicker turn around time. 

Tim also weighs in on some ongoing questions about whether poor biospecimen quality is hampering research efforts and whether genomic medicine is paying off for patients. 

Go to Part 1:  Want Answers? Look to the Non-Coding Region of the Genome, Says Cancer Researcher, Tim Triche

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.

When science journalist Ivan Oransky co-founded Retraction Watch, a blog with the express purpose of making scientific retractions more public, he didn’t think he would be posting much.

“Adam Marcus, my co-founder, was quoted as saying, ‘yeah, we figured we’d post periodically, our mothers would read it, they’d be very happy, nobody would read it other than them.’ Obviously that hasn’t been the case,” says Oransky in this first of a series of podcasts on scientific integrity.

Now putting out almost a post a day and funded in party by a grant from the MacArthur Foundation, the blog has revealed - and no doubt helped drive - a boom in retractions the last few years.

What is leading to so much bad research, and just how is Oransky’s blog keeping scientists honest?

Oranksy points to science career pressures and financial incentives as part of the problem. He also explores the issue of cell line authentication, a particular quality concern in cancer research.

We couldn't resist the chance to pull this veteran journalist into our recent debate over whether the genomics revolution is delivering on its promise.   

And finally, Oransky was at the now infamous woman's luncheon in South Korea last month when a nobel laureate, Tim Hunt, blew the crowd away . . .  and not with brilliance.

Pharma companies have always had their chief medical officers (CMOs). Now, as the diagnostics industry grows, many kinds of life science companies are filling this important position as well. Sequencing tool makers, direct-to-consumer firms, bioinformatics companies—they’re all appointing CMOs.

Paul Billings was the first and only CMO at Life Technologies before they got bought out by Thermo Fisher. Now he’s filling that role at Omicia, the genome interpretation company where he manages clinical cases and the transmission of information to doctors and patients. He also handles regulatory issues and clinical trial selection. And, as eloquently demonstrated in today's show, he represents his company externally, a vital and delicate function in a rapidly changing, heavily regulated industry.

This position gives Paul a clear window into some of the most important topics and debates we’ve discussed on the program: patient consent, direct-to-consumer testing, the use of arrays vs. sequencing, and the regulation of laboratory developed tests (LDTs).

We were off last week, so there’s plenty to talk about.

The big news has been about human germline modification.  Do you know about this?  MIT’s Tech Review put out an article early in the month that was kind of an expose suggesting that scientists around the world are beginning to modify the human germline.  Now, this is not the germs you pick up in a public restroom.  No, we’re talking the reproductive cells, our sperm and eggs.  We’ve been changing human genes before, it’s called gene therapy,  but never the germline because then the changes get passed on to future generations.   So it could be a good thing.  But it might be really bad.  Someone might make a mistake and create a new disease. 

And this danger has the scientific community up in arms.  Two groups of scientists took to the prestigious journals last week with papers, one in Science Magazine, the other in Nature.  

The Nature paper came out and said flatly:  Do not modify the human germline.  The Science Magazine paper, however was more . . . you might say optimistic.  This paper said let’s be careful.    If the authors of the Nature paper were setting themselves up as God  writing one of the holy Ten Commandments of Life Science with His finger: Thou Shalt Not Modify the Human Germline, then the authors of the Science paper were playing the loving gentle father who takes his son aside one day, and puts his arm around his shoulder, and says, son, or daughter, there’s something I should tell you about the world.  Just because you can fly a plane, doesn’t mean you should fly it into the side of a mountain.  And son, or daughter, looks dad back in the eye, and says,  but dad, no one would do that.

Speaking of cold mountains in Europe.  A treasure trove of genomic data was released out of Iceland this week.  Huh? Iceland?  Well yeah, after going bankrupt, the country may have just found their next big hidden natural resource:  genomic data. 

This is a treasure for two reasons:  first, the homogenous nature of the population.  There’s not much genetic mixing going on . . . because who the hell wants to  go and live on Iceland?

And two:  in hoping to benefit from this new natural resource, the citizens have been very willing to consent.  

So we’re seeing some cool stuff in this week's publication of the data.  There's been discovery of new disease causing genes.   For example, the MYLF gene was found in only eight people, and all eight have early onset atrial fibrillation.  There’s also a rare mutation that influences the thyroid.

Unfortunately, they haven’t found the gene yet that explains why someone would want to live on the North Pole.

Daniel MacArthur--he’s a geneticist at Mass General who’s in charge of the genomic data for the whole world--he says the work is very impressive, but completely unfair. He says deCODE, the company that generated the data, has now managed to get more genetic data than he has, and he’s funded by the Broad!  It’s just completely unfair.

No he didn’t say that.  

People in cold country are not the only ones being sequenced.  A report out of Saudi Arabia this week says that marriages are being called off due to genetic incompatibility!  One Saudi prince said that before he takes that fourth wife, he wants to be sure this time that she has no 'dominant' genes.

Speaking of arranged marriages, we attended the Techonomy Bio conference this week.  It’s an attempt to bring together tech and bio folks and see what happens.  One of the pairings was Marc Benioff, you know the tech billionaire and  CEO of Salesforce, interviewing Susan Desmond Hellman, the CEO of the Gates Foundation.  Benioff told Sue that he loved what she’s done with her bio, and Sue told Benioff she loves what he’s done with his tech.  And then they kissed.

No they didn’t.  They’re married--to other people.  But wouldn’t it be great to have one of these tech moguls marry a biotechie and then have techbio babies.  Benioff said that the place where tech and bio will meet is in digital health.  So they would be digital health babies.  But not everyone is on board with that.  One of the most tweeted lines of the day came from an investor, Greg Simon, who said he wasn’t convinced.  He said, “wearing your Fitibit into Dunkin Donuts does not a digital health revolution make.”

And that’s our show for March 27th.  Have a great weekend everyone.

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Guest:

Elaine Lyon, Former President, AMP; Medical Director of Molecular Genetics, ARUP Laboratories Bio and Contact Info

Listen (4:37) What is at stake here?

Listen (6:16) Is your message being heard?

Listen (8:03) Current guidance would shut down two thirds of current tests

Listen (2:33) What would be the best outcome with guidance?

Today we begin a Special Report on LDTs Series. LDTs, or Laboratory Developed Tests, have been used in healthcare for years to aid in diagnosis and treatment of illness. In the age of genomics, the number of these tests has boomed and become ever more complex. It was not until last year that the FDA, who had long been suggesting it, put out the first version of a draft guidance, or terms of regulation for LDTs. Implementation is expected to take about ten years.

Last week the FDA held a community feedback workshop at the NIH and heard from dozens of stakeholders from around the country. Today we’re joined by one of the speakers at the workshop, Elaine Lyon, the Medical Director of Molecular Genetics at ARUP Laboratories. Elaine was the President of AMP or Association of Molecular Pathologists for 2014.

Elaine joined us on the program last year just before the FDA issued the guidance to make the argument that actually what her lab performs are LDPs or Laboratory Developed Processes and not tests. Because they are processes that require a medical professional, this service is more akin to the practice of medicine and therefore not to be regulated by the FDA, she believes.

Nonetheless, guidance has been issued, and it looks like it will go forward. Elaine and other stakeholders around the community have given their input. Will they be heard? What is Elaine’s best hope for an outcome that will work for laboratories across the country and satisfy the FDA?

Stay tuned for interviews with Liz Mansfield of the FDA and the feedback of other stakeholders in this ongoing series.

Guest:

Geoffrey Ginsburg, Director, Duke Center for Applied Genomics and Precision Medicine Bio and Contact Info

Listen (6:58) Genomic medicine occuring across the lifespan

Listen (2:40) What have been the key events since the Human Genome Project?

Listen (7:12) What do you make of opt-out databases?

Listen (9:57) What role will EMRs play in genomics?

Listen (3:07) What drives your optimism?

Genomic medicine is now being adopted across human lifespan, says Geoff Ginsburg in today’s interview.

Geoff is the director for Duke’s Center for Applied Genomics and Precision Medicine and joins us for the next installment in our series, Genomic Medicine Today: Where Are We?

Geoff starts by listing the various applications of genomics in medicine from prenatal screening to oncology to pharmacogenetics. He says that too much was promised too early with the first Human Genome Project, but he is optimistic that we are now setting better expectations and healthcare is seeing the benefits of genomics.

“We’re certainly not at the full realization of genomic medicine, but there are clear sign posts that it’s being applied to clinical medicine,” he says.

What role will electronic medical records play in taking genomics into mainstream clinical practice, we ask Geoff, and how are we doing with the consent issue?

Podcast brought to you by: Omicia - Offering end-to-end genome interpretation and reporting solutions to help diagnostic labs and research institutions unlock the potential of individualized medicine.

Guest:

Thomas Quertermous, Director of Research, Division of Cardiovascular Medicine, Stanford University Bio and Contact Info

Listen (7:45) Close, but not quite there

Listen (5:34) How good are the commercial bioinformatics providers?

Listen (8:19) The challenge of education

Listen (5:12) Genetics and heart disease

Listen (2:55) Where do you put the price for whole genome interpretation?

Listen (2:32) Are long reads a big deal?

Thomas Quertermous co-chairs a pretty spectacular committee at Stanford. Called the Dean’s Panel on Clinical Genomic Testing, the committee makes the call on which genetic tests are ready for prime time in the clinic. Thomas joins us to launch our new series, Genomic Medicine Today: Where Are We?

The goal of this series is to find out just what practical progress we’ve made in commercializing whole genome sequencing. What are the success cases? How many are there really? What are the obstacles and keys to progress?

TQ, as he's known in the industry, recently co-authored a paper published in the Journal of the American Medical Association (JAMA) that provided a snapshot of just where we’re at today with genomic medicine. The conclusion? We’re close, but not quite there.

The key to clinical whole genome sequencing, he suggests, is to come to it with the question of "what you hope to learn from the adventure."

“I think it’s good if you start with a goal and try to stick to that goal rather than create an all encompassing analysis of the genome," he says in today’s interview.

As for challenges, TQ says that we need better healthcare informatics solutions, and always, better education at the provider level.

What are his thoughts on the leading commercial solutions for whole genome interpretation, and does it really cost $100,000? What does TQ think about the rise of long read sequencing led by PacBio this past year?

Join us as we begin a new series probing the front lines of clinical genomics.

Podcast brought to you by: Omicia - Offering end-to-end genome interpretation and reporting solutions to help diagnostic labs and research institutions unlock the potential of individualized medicine.