commercializing diagnostics


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.

Grail Merger, Genomic Autopsies, Overtreatment Alarm, and Controversy at Ancestry.com: May 2017 Review with Nathan and Laura

Is Grail already merging? Genomic autopsies? Does the House's new healthcare bill turn mere genetic risk into pre-conditions? Nathan and Laura are back to find meaning in the rush of May's headlines.

Laura cites a disturbing survey of over 2,000 women diagnosed with breast cancer that found half of them had unnecessary double mastectomies after genetic testing. She says unabashedly, “In big letters, it’s an ADVERTSIMENT FOR GENETIC COUNSELING.”

Speaking of alarms, Nathan says attorney Joel Winston’s blog against Ancestry.com’s terms and conditions was fear mongering.

We end with comments on the passing of one of the creators of the orphan drug industry, Henri Termeer.

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?

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."

The Story of Geisinger and Doing Genomic Medicine at the Right Pace

Mike Murray and the crew over at Geisinger are making the implementation of genomic medicine look down right easy.

In today’s interview, Mike explains GenomeFIRST Medicine, a program at the Geisinger Health System in Pennsylvania to offer care “that is based on an individual’s DNA sequence.” The healthcare provider boasts its own biobank and has partnered up with Regeneron’s Genome Center to offer exome screening to self selected patients. As of DNA Day last year, April 25th 2016, 100,000 recruits had signed up.

What has made Geisinger, who was selected to join the nation Precision Medicine Initiative, so successful with genomics? Mike points to the leadership.

“We have incredible support from the highest levels of the organization. As we’ve rolled out genomics, they are supportive and interested. As long as we’re there to explain what we’re doing and why we’re doing it, we have them on our side,” he says.

Has there been any pushback from doctors or patients?

Mike says one of the challenges they hadn’t really considered has been a “naming issue.” Sometimes one of the variants a patient tests positive for “puts their clinical story together.” But other patients may test positive for something like lynch syndrome, for example, who haven’t really had any problems.

“They really don’t have lynch syndrome, “ he says, "they have a genetic variant that goes with it. Until they have problems associated with it, they just have risk for lynch syndrome. So the problem is how do you keep something like that high enough on the radar that people and their providers know what to look for, but not so high that insurers or other entities might say, we’re going to treat them like our standard approach to lynch syndrome?”

In fact, Mike and his team have thought quite far through this challenge of how to report genomic findings back to patients. He explains what they’ve come up with in this beautifully clear interview about one of America’s most genomically experienced and progressive health systems.

New Pocket Size Nanopore Device Could Revolutionize Diagnostic and Other Testing

First of all, watch the video below.

A Santa Cruz company is now previewing a nanopore device that could be a major disruptor in molecular testing. The device is the size of a glucometer and could take all kinds of testing—perhaps someday even cancer-tracking liquid biopsies—into the home with its ease of use and ability to work with thousands of different assays.

Two Pore Guys, named for the pores not the guys, is a spinout from UC Santa Cruz and one of a growing biotech community on the west side of Santa Cruz, CA. The company has yet to do beta testing and is focused now on scaling up manufacturing of the small, relatively simple devices. CEO, Dan Heller, says Two Pore Guys has no plans to develop their own tests but will stay focused on the platform.

“We could make ten or fifteen assays and go to market with them, but why not let others make thousands and thousands of assays?” Dan asks. "They’ve already spent billions of dollars and decades developing primers or capture molecules for antibodies. Why not just give it a new life and let them sell it into the market? It's a revenue share."

So what tools might this replace? Dan lists the standard lab machines for PCR, HPLC, and mass spec. “There’s many uses of existing lab equipment that could be done on our device more quickly, cheaply, easily,” says Dan.

Based on recently developed nanopore technology, the small device looks remarkably straight forward. A molecule—just about any molecule-- is pulled through a nanopore by an electric current. The impedance of the current is the measure of the molecule. Though the device does not currently sequence DNA, its possibilities to replace other large life science tools does seem all the more real in a time when Oxford Nanopore’s small sequencing devices--also partly developed at UCSC—are proving themselves powerful tools.

Listening to Dan, the broad range of molecules and applications becomes dizzying: diagnostic testing such as liquid biopsy tests for cancer (the company is currently doing a study with UC San Francisco for a KRAS liquid biopsy test), infectious disease, border security, agriculture, animal health, and environmental testing.

It leaves us with this question in the end: why was this not done before?

Want to Stop Smoking? Start with Epigenetic Biomarker that Tells Doc the Truth

Why are there no viable psychiatric genetic tests, we ask today’s guest.

Rob Philibert is a geneticist and psychiatrist working at the University of Iowa. He admits at the outset of today’s interview that the field of psychiatric genetics is in a “quandary.”

“The results are not matching the hype,” he says.

The place Rob has found some success is in studying epigenetics. His lab perhaps leads the world in understanding the effects of tobacco, alcohol and cannabis use on DNA methylation. An epigenetic biomarker test can tell doctors, for example, whether a person smokes and how much. Rob has founded a company, Behavior Diagnostics, to commercialize the test.

So how does this help a person quit smoking?

Rob says that there can’t be therapy until there is accurate testing.

“We like to fudge when we talk about smoking. When you look at studies, half of individuals who are smokers will misrepresent their smoking to their physicians, even when directly asked.”

Think of glucose testing for diabetes, argues Rob--reliable data about the patient is at the heart of any effective treatment.

The test wouldn’t be possible without digital PCR, Rob says, giving a shout out to technology made by Bio-Rad and funding provided from the NIH.

When an Exome Test Is Part of the Therapy and Not a Diagnostic: John West on Personalis and Personalized Cancer Vaccines

About six years ago there was a wave of genome interpretation startups getting their first rounds of funding. One of them was Personalis, a company founded by a well known group of Stanford geneticists and bioinformaticians.

John West is the CEO of Personalis, and he joins us today to talk about how the company is participating in the dramatic shift in drug development toward immuno oncology drugs. Our listeners might remember John from his days at Solexa where he served as CEO and presided over the sale of the company to Illumina.

At the same time Personalis came on the scene, the first drug that would harness the immune system to fight cancer was being approved by the FDA, Yervoy by Bristol-Myers Squibb. This was the first of four drugs known as checkpoint inhibitor drugs. These four drugs have had spectacular success and together generate revenue of over 6 billion per year, a level which has doubled in the past year.

John and Personalis are working with biotech companies on a new generation of immuno therapies known as personalized cancer vaccines. These new drugs are actually custom synthesized for each patient after an “immunogram” or genetic workup of the tumor has been done. We know today that tumor growth is driven mostly by neoantigens, or new antigens which arise from mutations that happen after the cancer first appears, says John. So an immunogram done by Personalis must look at all the genes (over 20,000) and not just the original driver mutations. An immunogram could only be done in the last few years with the latest developments in next gen sequencing and algorithm creation.

How far along are these new personalized cancer vaccines? And what is the commercialization challenge for Personalis?

“We are essentially an integral part of the therapy,” says John. "So we don’t think of it as a diagnostic test. We think about it as the initial part of the manufacturing of the therapy."

Biomarker Panel to Predict Type 1 Diabetes

When we talk precision medicine on Mendelspod, we’re usually talking about oncology. But today we shift our focus to diabetes.

Raghu Mirmira is an MD PhD at Indiana University who is working on a panel of biomarkers that would predict Type 1 diabetes. That’s right. Predict.

Having already found a DNA biomarker candidate which detects dying beta cells using the new technology of digital PCR, Raghu is now working to improve the panel with other metabolites.

Will we some day have a Myriad Genetics for diabetes? Raghu says, yes. But he warns that we must also develop new treatment options to go along with a predictive blood test.

“Before we get to the point where this is a commercially available test, we need to be doing further studies to figure out what’s the outcome of individuals who test in a particular way. And what kind of interventions could improve those outcomes in some way.”

October 2016 with Nathan and Laura

Today’s show was recorded on Halloween, which now feels so yesterday. Forgive us for some spookiness.

What doesn’t feel so yesterday is the launch this past month of Helix, a company spun out of Illumina that aims to add exomes to the lineup of direct-to-consumer testing. Nathan points out their model for delivering data incrementally through various apps. Laura questions how Helix will vet the apps.

This month the genomics community gathered in Vancouver for the annual American Society for Human Genetics conference. The commentators give their highlights. Then we double back on a genetic counseling conference from last month and a big topic that we missed in our last show: population screening for BRCA.

It’s a bird, it’s a plane, it’s a turducken gone crazy. . . . . No, actually, says Nathan, “it’s a virus inside a spider costume for Halloween inside a bacterium inside a fly!"



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