precision medicine


Turning on Your DNA with Justin Kao, Helix

They’re getting a lot of buzz this week. We’re pleased to have Justin Kao, a co-founder of Helix on the program today for the first time.

Launching formally yesterday, Helix has generated a good amount of enthusiasm—in no small part because they raised $100 million and are backed by Illumina. And the Helix business plan is definitely a bold one. They aim to become the DNA testing platform that supports and partners with direct-to-consumer (DTC) and clinical apps, offering genomic tests that are both medical and non-medical. Helix's part is to collect the samples, do the sequencing (exome plus), and be the app hosting platform.

23andMe co founder, Anne Wojcicki, said once on this program that “DTC testing is a whiplash culture.” This year, with a lighter hand at the FDA during the Trump administration when it comes to genetic tests, entrepreneurs are showing more boldness. This is one of those leaps forward.

“Consumer interest in DNA is exploding,” Justin says today. “The genealogy industry itself has been doubling every year for the past few years.”

Justin lists some of the app partners with which they are launching, and says they will soon be adding more, including a partnership with the clinically focused, InVitae. He says Helix has a CLIA certified lab and has been working with the FDA since they began.

Is there an inherent conflict in the attempt to host both medical genomic tests—such as the 59 ACMG recommendations--and tests that help us pick the right scarf or wine? According to the vision of Helix, DNA is DNA.

Justin compares the Helix platform to the basic enabling technology of GPS.

“What if I said to you, I’m going to the gym, and I’m going to do my standard 30 minutes on a treadmill because that’s what everyone does? In a few years, you’re going to turn to me and say, ’well that’s odd, your body and my body are different. Don’t you turn on your DNA?'"

We Need a Google Maps for Metagenomics, Says Rob Knight, UCSD

When will we see the results of microbiome research in our every day lives? And what will that look like?

Rob Knight joins us for the first time today. He’s a professor at UC San Diego and Director of the Center for Microbiome Innovation. He is well known for co-authoring a paper showing that the microbial populations in the guts of obese mice differentiate from those in lean mice.

In addition to studies on obesity, Rob is also interested in the connections of the gut micriobiome with brain disorders, the possibilities for fecal transplants, and also the impact of microbial communities on drug interactions.

On the tools side we hear a lot about the success of single cell sequencing for human genetics; what impact are these new tools having on metagenomics? And if consent is often a thorny issue for studies in humans, what are the ethical issues studying microbes?

Rob says that in the next five to ten years we will be “taking control over our microbiomes,” meaning that we will be able to measure our microbial communities and use this information to improve our diet or to optimize a therapeutic. The big piece missing for translating microbiome research, he says, is better user interface or apps that would abstract away all the technical information. We need to go from the world of GPS coordinates to using Google Maps, he says.

Move Over PDL1: New Test Combo Adds RNAseq to Better Track Immune Escape

Reports from ASCO, the nation’s biggest cancer conference, this year again were full of stunning stories about the success of older and new immuno therapies. The race has never been hotter for biomarkers to target patient groups. Most of this new class of drugs--which harnesses the immune system to go after the cancer--inhibit an immune checkpoint called programmed cell death protein 1 or PDL1. So frontline cancer treatment these days typically includes a test for the PDL1 biomarker. But there are a breadth of potential targets in the immune system that promise to make this class of cancer drug even more effective.

Today we talk with Mark Gardner, CEO of OmniSeq, who has just received approval from New York State (the company is in Buffalo) to launch their new Immune Report Card.

“The biology is complicated. Even for folks that are PDL1 high, in the majority of cases those patients are not going to respond to these drugs. The average number of responders is 20-30%. So we know something else is going on. It turns out we’ve known some of the mechanisms for how the tumors are achieving "immune escape.” What we’ve not had the ability to do is to simultaneously measure across the range of hypotheses for how that tumor is escaping."

Omniseq's Immune Report Card includes mutational burden and MSI testing, which is common practice today. The two additional “legs” of the report are copy number variation for PDL1 as well as RNAseq.

The Last Major Disease To Be Studied? Ron Davis of Stanford Thinks So

Let’s say you’re a biomedical researcher looking for a place to make your mark. You find out that there is still a major disease that affects more than 2 million people in the US, and we still know virtually nothing about this disease at the molecular level. Wouldn't that stand out?

It certainly has to today's guest, Ron Davis, who is also a father searching for answers for his son. Ron has been the Director of the Stanford Genome Technology Center for decades. He collaborated on the first DNA microarray and made a major contribution to the Human Genome Project. For five years now, Ron has directed his comprehensive skill set in bioengineering--and his vast connections--to work on a cure for ME/CFS, or Chronic Fatigue Syndrome, a disease which has ravished his son, Whitney Dafoe.

With no funding from the NIH so far (he says they're not good at starting things), Ron is working to characterize the disease at the molecular level. A new device developed at his center that he calls a "nano needle" could enable the first definitive diagnostic test for patients with CFS.

The history of this disease is of patients desperate with hope but always facing a major stigma. Many medical professionals are still not on board with diagnosing a patient with CFS. Ron says this stigma and lack of interest by the research community has created a big chance.

“This is a tremendous opportunity. Here’s a major disease which at the molecular level you don’t know anything about. This has got to be the last disease like this."

Find an extensive recent written interview with Ron here.

On Bioinformatics Data Sharing and Collaboration: Andrew Carroll, DNAnexus

What does it take to collaborate in genomics?

A platform, for one thing. Over the past few years bioinformaticians have been speculating about a dominant "go to” site that would serve the software needs of those in genomics. Would it be a private company, a Google of genomics? Or would it be a non profit consortium? Would it be created at the government level?

Today we talk to Andrew Carroll, the VP of Science at DNAnexus, a company which has come about the closest of any to being that community platform. Over a year ago, they won a challenge to host PrecisionFDA, a community platform developed for exploring just how to evaluate and regulate NGS assays.

Beginning as a cloud storage company for genomics back when Amazon was just beginning to look to the sky, DNAnexus then evolved into an iTunes-like platform for various genomics software apps. One bioinformatics software on the platform might be great at variant calling, while others specialize in tertiary analysis.

“From the visibility I have, I estimate around a four to five fold increase year over year in the volume of sequencing," says Andrew. "Bioinformatics has grown to the point that it doesn’t pay to be a jack of all trades. A few years ago a project that was a thousand or ten thousand exome scale was a big deal. These days projects are coming up on hundreds of thousands of exomes, even hundreds of thousands of whole genomes."

DNAnexus’ platform isn’t just about a bunch of bioinformatics apps, it’s also a portal where different kinds of organizations can find each other and collaborate; for example, a healthcare provider and a sequencing center. In addition to PrecisionFDA, DNAnexus has been announcing these partnerships, one after another: Regeneron/Geisiner, Rady Children’s Institute for Genomic Medicine, Stanford Genomics Center. The company hasn’t sat back and waited for customers, but have been cultivating a proactive vision for genomic medicine by helping organizations be as open and collaborative as possible with their data.

"The work that we do through our partners actually tells the best story," says Andrew.

Is Population Medicine Failing Us? Michel Accad

Is health the same thing for an individual as it is for a population? This question goes to the foundation of how we practice medicine today and that of most of genomic research.

Michel Accad is a cardiologist in San Francisco and the author of a new book, Moving Mountains: A Socratic Challenge to the Theory and Practice of Population Medicine, in which he uses Socrates to spar with Geoffrey Rose, a British physician and one of the architects of modern medicine.

As early as the 1950’s, Rose advocated for the idea that individuals should be treated based on bell curves of an entire population, essentially risk based medicine. This philosophy would lie at the heart of not only the British National Health Service but many public health programs. It informed the famous Framingham studies here in the U.S. In fact, the term “population medicine” is a very positive term for those working in healthcare today. Genomic medicine has been an outgrowth of population medicine.

Michel says this philosophy is failing us at the level of individual health. Third party payers, be they governments or insurance companies, are in their offices working a system based on large datasets. They develop algorithms using all kinds of risk studies. But these payers have little to no contact with the actual patients. Ironically, he says, we call it personalized medicine. Michel points to hypertension, a disease area where sixty years after Rose pushed for risk studies, cardiologists are still divided into camps over whether to treat a patient if their blood pressure lies above the average. Michel argues that population medicine is utilitarian and ultimately utopian. What are framed as scientific studies are really social engineering.

What about clinical trials, we ask Michel. Don't population studies bring doctors and patients many good drugs?

In the second half of the interview, Michel points out that a mechanistic view of biology dominates clinicians and scientists today. It’s true. Our guest last week, a well known geneticist from Stanford, compared people to cars, arguing for the need to wear health data gathering sensors.

"Right now among philosophers of science, there’s a recognition that “mechanism” is inadequate to explain cellular organisms."  The study of biology also has often been developed with tautologies, he says.  "For example, say you’re studying the beaver and you ask what is a beaver. The standard answer is to go to the genetic sequence. From the genetics, you say you have a beaver. But you have to know what beavers are in the first place in order to study a beaver. It’s a circular argument."

So what other models might we use in biology? And what can we do in healthcare if we’re not using large population studies--go back to blood letting?

(Amazon link)

Deep Omics Profiler, Mike Snyder, Now Turns to Wearables

Mike Snyder is well known in the genomics community for his iPOP (integrated personal omics profiling) study. Profiling himself with hundreds of thousands of measurements each day over a period of seven years and a group of a hundred others for about three years, he and his team at Stanford have shown that sequencing and other omics data can be used to predict Type II diabetes, cancer, heart problems and other disease. He’s also published numerous papers comparing NGS instruments. Now he is expanding iPOP with a whole new set of tools: over the counter wearable devices.

Though Fitbit’s sales may be down, Mike says wearables are hot. His team has found that there are over 1,000 health related wearable devices on the market today. He predicts that we will all be wearing them, using data that will be centralized onto the "dashboard" of our smart phones to drive our health decisions.

Those who have used wearables have used them mostly as “activity monitors,” and they tire of the devices after about three months. His lab, says Mike, is looking at wearables differently by using them as “health monitors.”

“The power of these devices is that they will measure continuously your basic physiological parameters, and we think that complements the other sorts of data that we’ve been collecting quite nicely. We actually think these devices can be used to tell when you’re getting sick.”

Just as when omics data predicted his own onset of Type II diabetes, Mike says wearables data helped him quickly diagnose his contraction of Lyme disease. The data in the recent two year study also showed when three others were getting sick—their heart rates went way up over baseline.

What about all the wild goose chases and the chance for hypchondria?

“I’m a believer in letting the data tell us what’s going on,” he says. "I didn’t know my blood oxygen level dropped on flights. In hindsight, it makes a lot of sense. And that’s what everyone says, 'it makes a lot of sense.' But most people didn’t know that. This could be a big issue for those with pulmonary illnesses.”

We end with a brief discussion of Mike’s new book: “Genomics and Personalized Medicine: What Everyone Needs to Know."

  

How to Improve Lab Tests in the Absence of FDA Regulation?

Rubbing shoulders at molecular medicine conferences these days one senses a sigh of relief when you talk about laboratory developed tests (LDTs). With the FDA’s decision to put regulation on hold coupled with the expected confirmation of Scott Gottlieb as FDA commissioner, those in the lab testing business seem to be confidently settling back to the status quo. And those who were arguing that all we need is a “beefed up” CLIA to hold labs to better testing standards don’t appear to be motivated to do so anymore.

Several questions arise when it comes to LDTs. First of all, if regulation was truly important for enabling this revolution we call precision medicine, then why couldn’t the Obama administration get it issued? In other words, is the status quo so bad? Secondly, without the FDA even threatening to regulate, will we see the “beefed up” CLIA that many labs argued is the best way forward? Without the stick of the FDA, is the carrot gone too?

Russell Garlick is the CSO of SeraCare, a private company that has worked to improve clinical laboratory standards for over thirty years. The company recently added a new business unit for precision medicine diagnostics, and Russell was brave enough to come on today and address these questions.

As for the status quo being good enough, Russell isn't happy.

“Many of the organizations undertaking clinical trials to recruit oncology patients have lost confidence because LDTs in one geography of the United States don’t perform the same as in other parts of the United States,” he says.

Russell has worked many years with labs on IVDs--the already regulated group of diagnostic tests. He sounds disappointed that the FDA has dropped their focus on LDTs, but is hopeful that existing organizations, such as the College of American Pathologists, or even private companies such as SeraCare might step in and seize an opportunity to improve things.

“There’s a lot of status quo. And frankly it’s a little bit disappointing,” he says, “because the laboratories can benefit from [improved standards]. It’s that inertia to do something new and different."

Known for Medical Devices, 116 Yr Old BD Makes a Bold Move in Genomics

Talk to someone who attended this year’s AGBT, and you’ll know the big buzz was about single cell genomics. One of the exciting new platforms came from a new player in the genomics space and yet from a very old company.

Founded at the end of the 19th Century, Becton Dickinson (BD) has been one of America’s great medical device innovators. They made the first syringe designed specifically for insulin injections. Their BD Vacutainer became the standard for blood collection in the U.S. They designed the first “intelligent” insulin pump. At this year’s AGBT conference, BD showed up with a new genomics division announcing their new Resolve(TM) Single-Cell Analysis Platform.

Today we talk with the VP of BD Genomics, Stephen Gunstream. Stephen says life science researchers already know BD through the BD Biosciences unit which over the past thirty years has been perfecting flow cytometry for their single cell analyzers and sorters. Acknowledging that BD has been going through “a culture shift the past five to ten years,” Stephen says their history with flow cytometry made their recent move into single cell genomics tools a natural one.

“People talk about a resurgence in single cell genomics, but I wouldn’t really call it a resurgence,” says Stephen. "We’ve been analyzing cells for 30 years with flow cytometry. What has really changed is that the capabilities of next gen sequencing has allowed us to do this in a highly parallel manner at a cost which is a lot more affordable.”

So how will BD stand out in a rapidly maturing marketplace? What research does Stephen think the new platform will most impact? And perhaps most importantly, will BD with their century old history of experience with clinical products be able to significantly help guide genomics research products into the clinic?

Proposed NIH Cuts, Undermining GINA, and Game Changing Drugs: March 2017 with Nathan and Laura

The largest cut to NIH budget ever, rolling back genetic non-discriminatory law—the bad news continues to roll from Washington. But there was great news this month as well.

Both Nathan and Laura are fuming about HR 1313, or a Republican bill to roll back GINA protections. Laura points out that the proposed law builds on an exemption in GINA for wellness programs—a category difficult to define. And Nathan reminds us that families and children could be hurt by the new bill. Theral asks since when did privacy become partisan? GINA passed in ’08 with a vote of 95-0 in the Senate, 414-1 in the House (Ron Paul playing the weirdo there), and it was signed by George Bush.

Then on to some “game changing” drugs for multiple sclerosis and eczema and a successful gene therapy trial for severe sickle cell anemia. Not only are there new therapies, drug manufacturers seem to be getting the message on pricing.



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