genomic medicine

"We like to refer to it as consumer initiated, but physician supervised,” says Eric Schadt today when asked if his new test is direct-to-consumer.

Eric is the Dean for Precision Medicine at the Icahn School of Medicine at Mount Sinai in New York and since 2016 has served as CEO of Sema4, a spinoff that he founded out of the Mount Sinai Health System. Sema4 launched a newborn screening panel, Sema4 Natalis, in February of this year covering over 190 disorders.

With 400 people already employed, Sema4 is based largely on genetic testing, data science, bioinformatics, and software development teams that were built up at Mount Sinai prior to the spinout. New panels will be marketed directly to parents around the country, many of whom have already bought other prenatal screening tests from Sema4.

From 2011 to 2017, Eric served as the Founding Director of the Icahn Institute for Genomics and Multiscale Biology at Mount Sinai. He says he founded Sema4 to achieve a greater scale than could be had within a single hospital system. For him and Sema4, the end game is to "partner with" tens of millions of patients for ongoing studies. He calls it his "growth hack" strategy.

The Natalis panel is a practical place to start. Many of the additional rare childhood disorders that expand the panel beyond the conventional heel prick testing of 30-50 disorders are the result of new research and the latest technology and are a no brainer. This will bring some uniformity across states. And the new testing can be done from a cheek swab rather than the more invasive heel prick.

Still, some argue, Sema4 Natalis really amounts to doing research on parents. For the panel includes cancer risk tests as well.

Does Eric plan to do any follow up studies with parents? Mount Sinai is the sole owner of Sema4. Has any other major healthcare provider made a play similar to this?

Sequencing geeks are fresh off the trail from AGBT, and it’s time for our annual look at the sequencing tools space. This year we sit down with the longtime Omics! Omics! blogger, Keith Robison, who not only can answer all your questions about the topic, he even knows which sequencer you’re using right now, and in which department.

Keith jauntily runs through the Big 3--Illumina, Pac-Bio, and Oxford Nanopore--and has a few odds and ends to say about the "niche developers."

We finish by asking Keith what new trends and new instruments he's looking at. He says his son is a senior in high school where Keith has offered to go in and demonstrate the MinIon nanopore sequencer.

"Imagine if the next generation of kids all learns sequencing on this little device. It starts becoming a practical reality where kids in high school--even middle school--learn sequencing and then learn data analysis."

The Flongle Generation, anyone?

Nanopore sequencing has arrived. Passing test after test this past year--including one we discuss today--this technology which was being hyped decades ago is delivering on its promise.

Winston Timp joins us today. He's an assistant professor at Johns Hopkins and one of the leaders on a recent large scale project to directly sequence RNA on an array of nanopores. Winston's is the first in a series of shows we've lined up with users of Oxford Nanopore's technology.

Why RNA-seq? Hasn’t this been done for years?

Yes, says Winston, but in the past no one has been looking at the RNA itself. They’re usually making cDNA from the RNA and sequencing that.

“One of the big advantages to nanopore sequencing, is that you can characterize any polymer you can put in the pore.”

Nanopore sequencing is polymer agnostic.

So what good does it do to look at the RNA directly? Ever heard of epitranscriptomics? Winston has worked for a while on DNA methylation in his lab. Now he’s looking at RNA methylation. Not only is he seeing basic biology that we've never seen before (unique isoforms, exon connectivity that has been imputed by informatics but never seen directly), he’s coming up with new translational questions for health and disease.

When we started Mendelspod seven years ago, the next gen sequencing race was in full swing. It was all about the push to bring down the price of sequencing. The lower cost brought an excitement to the world of biology with all the new projects it made possible. But we found out there were was a major limitation to the technology. Read length. Over the past couple years, PacBio paved a whole new world with their long reads that enabled many new genomic projects. BioNano gave us the big picture with their optical mapping. Today users of nanopore sequencing are generating reads of 1 megabase and the versatility of the nanopore is giving scientists even newer views of biological activity. The race is still very much on.

Reproductive testing is one of the hottest fields in which genetics is going mainstream, a field hurdling us rapidly into the future. It’s an area we’ll be following closely in 2018.

Gary Harton serves as the Chief Operating Officer in the US for Igenomix, a company in the reproductive testing space with a vast global presence. The company has labs in the US, Japan, India, Turkey, Rome, Brazil, Mexico, Canada, and are headquartered in Valencia, Spain.

This international operation across so many cultures and national borders has its logistical and regulatory challenges, but it also offers the company an opportunity to introduce tests to cultures which are early adopters in a field fraught with big ethical and cultural decisions. With these more open cultures, the company can develop new tests and supporting clinical data.

The company’s most common test is preimplantation genetic screening (PGS) where embryos are checked during an IVF cycle for chromosomal abnormalities. According to Gary the test has gone mainstream in the US, but not in Europe. Yet in Europe, there can be wide variability. Spain and Italy tend to be early adopters and open to new testing technologies, whereas France is highly regulated.

One of Igenomix's newer tests is preimplantation genetic diagnosis (PGD). This offers parents who have a disease such as Huntington’s or cystic fibrosis--or are disease carriers--to eliminate that disease from their embryos through genetic testing. There is widespread support for PGD being used for this purpose. However the test can also be used for enhancements, or the grey area between disease and enhancements. Here, of course, decisions get much more complicated. For example, Gary says that recently the company had a request from deaf parents to select for deafness with their embryos. Should the company offer such a test?

How does Igenomix decide which traits to select for? Are there governing regulatory bodies that issue guidelines? A year ago we interviewed Hank Greely, author of The End of Sex, who argued that in 20-40 years parents would not use sex to reproduce. Does Gary agree with Hank's bold prediction?

We also talk with Gary about some less thorny issues. Years ago, the industry used FISH technology for testing then switched to arrays. Now most everything is done with NGS. How has NGS and new automated liquid handling technologies impacted the field? Has this raised the quality of testing?

It's a rare glimpse into life for some pioneers taking genetics into the future, and Gary is open and transparent.

Our first show of the year is an outlook on genomics for 2018. To do this we’re joined by our regular commentators, Nathan Pearson and Laura Hercher, and also by a special guest to mix things up a bit, Misha Angrist, Associate Professor at Duke University and Editor in Chief of Genome Magazine.

Misha wrote a seminal book on the rise of next gen sequencing and personal genomics (Here is Human Being: At the Dawn of Personal Genomics). After working at Knome, Ingenuity, and the New York Genome Center, Nathan recently founded his own company, Root, which works closely with tissue donor registries to give back DNA information to consumers for free. Laura is recognized as a leader in the field of genetic counseling, being a counselor herself and training many of today's working counselors.

Join us as we ask, where are we in genomics today?

Each year at this time we bring on a guest who is somewhat out of the way of our normal lineup, for example, a science fiction writer or a philosopher. Today Theral interviews a law professor who loves to philosophize and write about the impact of biotechnology on our lives now and in the near future. His newest book out this year, “The End of Sex and the Future of Human Reproduction,” is another comprehensive and provocative example of what has made Stanford’s Hank Greely such an in-demand speaker both to scientist and non-scientist audiences alike.

“My prediction in the book is that in twenty to forty years, most people with good healthcare will conceive their children in a lab using stem cell derived eggs--and sometimes sperm—and then do whole genome sequencing preimplantation genetic diagnosis and pick the embryo they want,” says Hank at the outset of today’s extended interview.

Whereas sci-fi writers and the mainstream press often play into what Hank calls "our need for scary bedtime stories," he seeks to understand and elucidate the actual--and less dramatic--"muddling through" of new technologies into our lives.

In addition to discussing the book, we talk with Hank about his relationship to his colleague scientists at Stanford, what he thinks is the breakthrough technology of 2016, and the future of the FDA in the era of Trump.

While everyone is asking what will become of Obamacare, we ask our regular commentators, Nathan Pearson and Laura Hercher, specifically about genomics and medicine.

Nathan begins by saying that data scientists everywhere should be humbled. Does the failure to predict the election send out warnings about big data predictions in genomics?

Laura points out that Obamacare covers many of the new genetic tests which have become available in the past decade, such as screening tests for hereditary breast and ovarian cancer syndrome and lynch syndrome. Coverage for these tests is now up in the air.

"It is cruelly absurd to talk about the value to the human race of identifying the people with these syndromes if we don't then give them the ability to act on the information," she says.

No matter what happens to Obamacare, isn't there bipartisan support for genetic testing and for research funding? (See the passage yesterday of the 21st Century Cures Act.)

Both Nathan and Laura agree that genomic medicine will continue apace. However, they worry that under a Trump administration the less fortunate will become even more vulnerable and have less access to improvements in healthcare. They point to an area of testing that is already highly politicized: prenatal screening. Will women lose access to testing in an era that reverses gains made in women's reproductive rights?

We finish with a local election in the Florida Keyes where residents approved the use of Oxitec's genetically modified mosquitos. Fear, Laura points out, can quickly change suspicion into acceptance.

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?

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!"