history of science

Eric Green on the Future of the NHGRI

Dr. Eric Green has been the Director of the National Human Genome Research Institute (NHGRI) at the National Institutes of Health (NIH) since 2009. Two years ago, he and his colleagues at the Institute came up with a strategic plan for the next ten years. Today we discuss the plan with the director and get his outlook on the future of human genomics.

Dr. Green says human genomics can be roughly divided into four chapters.

"Each chapter has come out of similar strategic planning processes. The first chapter was the human genome project, a very valuable start for the field of genomics. In 2003, we asked what next and we published a plan which was about the first use of this information that was provided by this first genome. Now we had to understand what the 3 billion letters of the genome meant. It was a new era for genomics and it was wide open. That was chapter 2 from 2003 to 2011, and it put us on a solid trajectory to get to the $1,000 genome. We sequenced a lot of people and a lot of animals. Then published in 2011 was the strategic plan for chapter three which would bring us into the clinic where all of a sudden we could see how genomics could be used in a powerful way to understand human disease but also other applications in genomics that would become part of medicine. And right now we are writing the story of chapter four of human genomics."

Though he is hesitant to name the fourth and current chapter ("you never like to write your headline until you've lived it out"), we do tease this out of him: "Making genomics mainstream and equitable in medicine."

Now that we have high accuracy long reads, would Dr. Green like to see larger population studies done with better quality? Where is the NIH at with the All of Us project? And how does the director see his mandate when it comes to balancing between basic and translational research?

On that last question, Dr. Green says being a physician, he may have pushed the translational side heavily, but overall he tries to keep a very diverse portfolio.

"We do not have the best technology for sequencing DNA. They need to be better. We don't want a $1,000 genome, we want a $100 genome, and maybe eventually get a $10 genome. So we want to continue to develop new technologies. And then on top of it, I need to study things in the clinic to see how they work. And the hard part will always be that balancing act. There's never quite enough money. You're just trying to figure out where am I going to get the biggest bang for my buck. And keeping your eye on the landscape because it's not all about NIH. Lots of people are doing genomics research, and what can we do better than others and what should we cede to others to do."

We finish with some personal questions about Dr. Genome, his name among colleagues.

We Have to Get Sequencing Back to Moore’s Law: Gilad Almogy, Ultima Genomics

There was a tweet thread at the end of the recent Advances in Genome Biology and Technology (AGBT) conference where researchers took a moment of silence for all the sequencing companies that have announced big plans at the conference and then died. It was clearly aimed at this year’s sequencing tools entrant and buzz-generating Ultima Genomics. The company emerged from stealth the week before AGBT announcing the $100 genome with a purse of $600 million backed by funders including Khosla Ventures, Andreessen, and Founders Fund.

Leading this ambitious newcomer to the sequencing field is Gilad Almogy, a former engineer at Applied Materials. As with others we have met here on the program who have crossed over from tech to healthcare, he believes that sequencing must continue to scale at least in the way computer chips have to achieve more clinical breakthroughs.

What is not being done now that might be done with a $100 genome?

Gilad says, “it’s about getting sequencing back to Moore’s Law. Moore’s Law is not only about getting computer chips cheaper. It’s about people knowing that they will. It’s not only about discounting sequencing costs by 10. It’s about all those folks--scientists and researchers—making trade-offs, should I sequence this or that, this gene panel or that exome, or can I do exome plus? All those trade-offs that are constantly slowing folks down. We just want to say, hey, you don’t have to. Stop thinking within the constraints. Moore’s Law has two sides. Us delivering the lower costs, and folks believing us and others that the costs are coming down and developing applications that make full use of those lower costs.”

"It doesn't make sense that every hospital has an MRI and a CT and maybe a PET scan and doesn't have a sequencer."

We talk about where the company is now, when Ultima will offer their commercial release, and what challenges they face in meeting that date.

It can be quite easy for those of us who have watched this space for some time to slip into skepticism, sensing a mature market. It’s also still very easy to remember when Illumina was making their name in arrays and DNA synthesis or when Oxford Nanopore raised suspicion with talk of handheld nanopore sequencers.

For Gilad, and perhaps for us all, it's still early days in DNA sequencing.

The History of mRNA Vaccines with Elie Dolgin

"Scientists have been putting RNA into cells through a lipid delivery system for 44 years,” says Elie Dolgin. “And that’s ultimately the vaccine that has gone into millions of arms.”

Elie is the author of a recent piece in Nature magazine, The Tangled History of mRNA Vaccines.  He joins us to talk about his quest to uncover the winding journey that led to the cure that is moving the world forward.

“The path to mRNA vaccines drew on the work of hundreds of researchers,” he writes in the piece. One of those scientists, and the first to take notes and write down some early IP, was Robert Malone, a grad student at the Sulk Institute. Elie comes back to him again and again in the piece and shows a fascination for him in the interview.

The story moves on to modified RNA and the two star companies, Moderna and BioNTech. Elie moves beyond his article at the end of the show with some suppositions about the future of mRNA technology. Will a new mRNA flu vaccine come next?

Is This A Unique Time for Science? We Ask Sci-fi Writer Kim Stanley Robinson

Has this pandemic presented a unique moment for science in our history? Or is it just a strange and temporary moment of science fiction? Or both?

Sci-fi author Kim Stanley Robinson (The Mars Trilogy, The Ministry of the Future) recently penned an essay in the New Yorker about how the virus has “changed our imaginations” and created a new “structure of feeling.”

Being a utopian sci-fi writer, Kim Stanley is in the business of looking for silver linings to major human tragic events such as the one we’re in. We wanted to have him on to see whether this event will cause a lasting change to the way people think about science.


End-of-Decade Review, What's Next? with Nathan and Laura

It's our special look back over the entire decade which has Nathan and Laura firing on all fours. Not only do we discover their genomic highlights of the last ten years--ups and downs-- they also pull out their special "future glasses" and come up with a provocative list for the next ten. You don't want to miss this.

But first, we do cover December and that kerfuffle over the George Church dating app. And the genomics of income--really? Did you go for that?

Theral, Nathan, and Laura for an extended broadcast. Happy 2020!

The Gene Edited Babies Saga - A Year Later with Hank Greely

On November 25th, 2018, the world was shocked to find out a Chinese scientist, He Jiankui, had edited the germline of twin girls-and the twins had been born. Many in the scientific community remember that Sunday afternoon well as the story broke on MIT's Tech Review, "EXCLUSIVE: Chinese scientists are creating CRISPR babies."

Today’s guest can even tell you what he had for dinner that Sunday and just what was his reaction. "Holy Shit!"

Hank Greely, a law professor at Stanford and author of "The End of Sex: the Future of Human Reproduction", has followed the “CRISPR baby” story just about as close as anyone we know. He joins us today to look back on that momentous week and reflect.

What was his and the scientific community’s immediate reaction? Now, a year later, what have we learned? How has the story evolved? And what is the future of germline editing?

"What strikes me most is the arrogance, the hubris, the foolishness, of He thinking he's going to be able to do this and be acclaimed as a hero. And maybe it wouldn't be immediately, but he would be Galileo who would ultimately be recognized as being ahead of his time. I think he was criminally reckless and so full of his own dreams and glory that he risked the lives and health of babies. And that's unforgivable to me."

Was That Anti-Scientism Article in Nature Just a Fancy Rant or Some Real Breakthrough Stuff?

I’m afraid it was a missed opportunity.

Let's applaud the Johns Hopkins science historian, Nathaniel Comfort, for testing out the tires--and carburetor--of his new tenureship and publishing a piece on scientism.  And in one of science’s top journals at that.   Obviously Comfort touched a nerve, generating a wave of reaction on Twitter, including a rebuke from the top celebrity Enlightenment fundamentalist evangelist, Steven Pinker. 

Where I Agree and Disagree with Precision Medicine’s Chief Critic, Michael Joyner

Precision Medicine is more than a narrative, a story.  Hundreds of thousands of patients take drugs every day that are precision medicine drugs.  Thousands of women have been tested for BRCA genes and thousands of others diagnosed with lung cancer tested for EGFR mutations.  This has been more than a story for them.  It has saved their lives.  From rare disease diagnoses and therapies to the entire field of non-invasive prenatal testing, genomics has revolutionized medicine. 

The Internet of Biology Revolution-For Real This Time, with Brett Goldsmith, Cardea

Talk to anyone who’s been around diagnostics or blood sampling for long, and they’ll tell you that nanotechnology is nothing new.

Today’s guest, Brett Goldsmith, the Chief Technology Officer at Cardea, says he was involved in the nano revolution that was and then wasn’t 20 years ago. (The older veterans among us might date it back even further, to forty years ago.) So what are Brett and Cardea buzzing about early this year in a new Nature paper?

Biosensors.   They say thier new--and significantly cheaper--ones are capable of integrating the world of biology and digital that will give us instant access to the networks of biological information used by our bodies.  The sensors bypass our existing testing gadgets that use labels and lights and measure directly the biological interaction.  One can imagine "Googling" biological data about yourself.   The argument here isn't new, nor is the technology.  What is new and shown by the Nature paper is a dramatically changed economy of scale for producing the biosensors. Brett claims it is something along the lines of going from $120K down to just $20-30 each.

If you look at Moore’s Law and the dramatic reduction in the price of sequencing as what fed two revolutions, it does appear there’s a case to be made for a similar revolution to be had with biosensors and the possible applications they could enable.

What are the details of the paper? How do Cardea’s sensors work? To whom are they selling them now?

And what kind of data does Cardea have to put out to show the world that they are not Theranos No. 2?!


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