precision medicine


Flint Whistleblower Says Today's Science Is to Blame for Its Own Lack of Public Trust

Marc Edwards is telling a different story than the one most of us have been reading and hearing lately. But then he’s used to it.

Marc was the engineer from Virginia Tech who was called one day in September, 2015, by a resident of Flint, Michigan. A Ms Lee Ann Walters wanted Marc to check out her water. When Marc and his team got to Flint they uncovered super high levels of lead in the potable water, with over 100,000 people exposed to high lead levels and 12,000 people with lead poisoning. You know the rest.

But you may not know that a very similar story to Flint played out in the nation’s capital in 2003. A Washington DC water crisis led to a hearing in which Congress found that the CDC had released “scientifically indefensible” reports on the water.

Marc Edwards exposed those reports and lost a contract with the EPA over it.

Aghast at the world of academic science which he says is "gamed by a system of quantitative incentives" and at government agencies who often overlook the truth, Marc now takes aim at the whole system of science. Last year he co-authored a report Academic Research in the 21st Century: Maintaining Scientific Integrity in a Climate of Perverse Incentives and Hypercompetition. The report warns of a tipping point where science “itself becomes inherently corrupt and public trust is lost, risking a new dark age."

The integrity of science has been a major theme here on the program, so while Marc is not a biomedical researcher, his experience in exposing bad science resonates within our own life science community.

In line after quotable line (“The idea of science as a public good is getting lost. In science our product is truth, and our brand is trust. The greatest proportion of truth seekers are not going into science as opposed to other human endeavors."), Marc fillets today’s scientists in government and academia, arguing that the system of science is skewed towards quantitative markers rather than quality: the pressure to publish more papers each year, citations, how much funding, etc.

Marc thinks things have gone so wrong that the war on science today (and yes, he does think there is a war on science), is more the fault of the scientists than any political movement. Somewhat with irony, but more with sadness, he says:

“The Flint water crisis was so bad it restored my faith in politicians. I mean that’s how screwed up it was. The politicians behaved themselves really well. The people who have been indicted are the scientists and engineers."

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?

By Changing a Basic Lab Step, Acoustic Liquid Transfer Having a Broad Impact

Freeman Dyson famously said, “the great advances in science usually result from new tools rather than from new doctrine.”

Today we talk with Mark Fischer-Colbrie, CEO of Labcyte, a company which has made some waves--literally-- in the life sciences by changing a very fundamental laboratory procedure: liquid transfer. For some years now, Labcyte has been selling machines that move liquid around with sound. By eliminating the need for pipette tips and other “solid” surfaces, the machines guarantee much more precision.

“Science demands precision and in ever-increasing amounts,” says Mark at the outset of today’s interview.

Acting like a rifle shooting liquid straight up, the new acoustic technology has made inroads into most life science applications. Mark talks about the Finnish Institute for Molecular Medicine (FIMM) using the new technology to do truly personalized medicine, by ex-vivo screening of cancer patient cells against hundreds of available drugs. There is often precious little sample to work with, and the errors from traditional pipetting might mean the difference of life or death. The machine is also used widely by the pharma and synthetic biology communities for its ability to reduce costs.

“Imagine saving four months on a single drug discovery cycle,” says Mark.

Recently, Astra Zeneca has integrated acoustic technology into mass spectrometry, showing the potential to immediately upgrade other tools which have been around for some time.

Should everyone change over to acoustic dispensing?

Many Biologists Today Don’t Have Enough Computer Science to Use the Databases

Moray Campbell was for all intents and purposes an accomplished and successful cancer biologist at the renowned Roswell Park Cancer Center. Then one day he woke up and realized he was becoming irrelevant. He was a traditionally trained wet lab biologist who was getting left behind by computer science. Any scientist must keep up with their field, but this was different. A few conferences and journals--reading the news everyday was not going to be enough. Facing reality, Moray enrolled in a bioinformatics masters program at Johns Hopkins.

That was in 2013.

"Biology is genomics. And genomics is basically computer science,” says Moray at the outset of today’s program. “In 2013 I would have said I look at the epigenetics of prostate cancer. Now I say that I look at the epigenomics of prostate cancer. I’ve become genomically literate."

What was it like for Moray to go back to school mid-career with teachers and homework and finals? Did he doubt his decision when the going got tough? Is it harder for biologists to learn coding or coders to learn biology?

Moray is now finished with his degree and in the process learned that as a discipline, we're still struggling with how to teach genomics to biologists.

He gives the example of datasets such as TCGA that many biologists today don’t even know how to use.

“These data are there. And they’re being used very deeply,” he says. "But I suspect by quite a restricted community. If you don’t even know how to download a file, how are you going to be able to analyze it?"

It's been a dramatic transition for Moray. Looking back now he says, "biology is dead; long live biology."

Cardiologists Love Genomics: Euan Ashley, Stanford

Euan Ashley is one of the big names in genomic medicine that has been missing from our guest list. We’re happy to correct that today.

In 2010, he led the team who did the first clinical interpretation of a human genome--that of his Stanford colleague, Steve Quake. Since then Euan, an MD PhD, has been driving to make the use of new genomic tools and discoveries a routine part of medicine at Stanford, particularly in his own discipline of cardiology.

A regular speaker on the conference circuit, Euan titles his talks, "Genomic Medicine Is Here."

"There were these one off examples of great stories that captured everyone’s imagination,” he says at the outset "but somewhere in there, what happened is it just became routine. And we started sending exome and genome sequences on patients and using that information to help find a cause, and in some cases, treatment for their condition. We were all waiting for it to happen, but it just happened under our noses.”

At the same time, Euan acknowledges that he “loses sleep at night” over “dark corners of the genome.” What are these dark corners? What recent findings were made by new long read sequencing? How has genomics impacted cardiology?

We begin with the question, if genomic medicine is here, why are there still so many skeptics?

Join us in our first interview with one of the few jazz saxophonists in our field, someone who knew he wanted to be a doctor at age four but wasn’t inspired by science--that is, until a high school teacher handed him a copy of Richard Dawkins' “The Selfish Gene” after class.

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."

Can You Name the World’s Largest Single Disease Research Charity?

Let’s take a break from the US and head over to the UK, home of the world’s largest single disease medical research charity.

Cancer Research UK (CRUK) raises five hundred million pounds a year for research and drug discovery into any and all of the two hundred plus types of cancer. The charity is extremely well integrated into U.K. culture, and uniquely English in that the donations are mostly small and come from all corners of society. A third of CRUK’s funding comes from donations averaging £10 or less.

Allan Jordan is head of chemistry for the drug discovery unit of CRUK. On today’s show he says that the democratic funding of the charity gives them a great deal of flexibility to do early stage drug discovery. Whereas a big pharma or biotech has to devote their resources to limited assets, or drugs, CRUK is able to spend more on basic biology research and follow the science into any type or cancer or multiple cancers.

There are very few conditions,” says Allan about his drug discovery unit in Manchester. "We don’t have to be specific about any particular disease area; we don’t have to be experts in one disease at the expense of all others. We can tap into that UK-wide expertise and network that can help us understand the biology.”

How is the charity working with the UK's national healthcare system? And does Allan hear the same kind of skepticism that we hear in the U.S. about precision medicine in oncology?

Luke Timmerman on His New Biography of Lee Hood

There is tons of life science journalism. Our coffee tables and inboxes fill up each week with that quarterly or that daily. We sift through headlines and product advertisements to assess what’s going on in our industry. It’s our job to know. In this age of several-times-per-day newsletters and 24 hrs a day Twitter, we catch what we can.

And occasionally, we come across a carefully written piece or a well done interview, and we take a moment to realize with some awe the history that is being made in our industry.

Occasionally. Which is why a new book out by veteran biotech journalist and the guest of today’s show, Luke Timmerman, is such a rare treat.

Hood is a thrilling ride through the life of the visionary biologist, Lee Hood, told by someone who is not afraid to show the shiny and the not so shiny. From his boyhood in Montana to being chair of the biology department at Caltech where he oversaw the invention of the automated DNA sequencer, to being recruited to Seattle by Microsoft’s Bill Gates, Hood’s journey becomes the perfect vehicle for Timmerman to probe into the messy corners of science and put an intimate, human face on the history of biotech. Covering Hood’s move to the University of Washington as a young Seattle based reporter, Timmerman has known Lee Hood for several years. It's a full scale biography, efficiently and confidently written with an insider's perspective and access. Timmerman says it's an “unofficial biography,” meaning Hood was supportive of the project, but Timmerman had full freedom.

Playing historian has been somewhat of a fantasy for the long time journalist.

"There are things that are happening in the moment which a journalist can call people on, but you don’t really get the whole story. There’s only so much people can say and there are not a whole lot of documents that come available when you’re on deadline. But when you’re a biographer, and you have the luxury of time, and people have moved on, things become a lot less sensitive. People become more willing to talk, and a whole lot of documents become available through the public record.”

Who is this man, Lee Hood, and how has he impacted our industry? In the book, we read of the time when Hood holds a press conference to announce his team has done it—they’ve got an automated DNA sequencer. But, standing at perhaps the pinnacle of his career, Hood forgets to mention the "team" part. It’s a flaw that will go on to haunt what by any measure has been a remarkably successful career.

What impact has the subject made on the author? And what does Timmerman hope for the book?

To round out the interview, we get Timmerman’s thoughts on his new gig, the Timmerman Report, and the recent Sarepta decision by the FDA.



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