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Physicist, Startup Founder, Blogger, Dad

Sunday, January 12, 2014

Cancer genomics

A great article in Esquire on the frontier of cancer genomics. It's only a matter of time before many wealthy individuals diagnosed with cancer seek out this standard of care. (I'm told that sequencing alone can lead to actionable conclusions in more than a few percent of all cases, even now.) The resulting advances will hopefully eventually reach everyone else.


Biomathematician Eric Schadt, shown above.
Esquire: ... When [Schadt] graduated high school, he joined the Air Force with the idea of subjecting himself to the rigors of Special Forces training. Instead, he blew out his shoulder on a climb, and the Air Force tried to salvage its investment by putting him through a battery of tests. He took them; when the scores came back, he was asked by stunned superiors if math had always come easily to him. Then he was sent to college and undertook the task of complete intellectual self-transformation. He received an undergraduate degree in applied mathematics and computer science at Cal Poly and his master's in pure mathematics at UC Davis. Pure math was, to him, the Special Forces of the mind—he took it because it was so hard, and he wanted to find out just how smart he was. He was pretty smart, as it turned out, but he despaired of working on problems that existed on the level of pure abstraction and had no bearing on the problems of the world. It seemed like, well, a sin. He went to UCLA to get a Ph.D. in the emerging field of biomathematics. The one problem was that the degree required a Ph.D.-level mastery of molecular biology, and the last biology course he'd taken was in high school. So he taught himself by reading textbooks. It wasn't hard. Pure math was hard. Molecular biology, after pure math, struck him as ridiculously easy.

... Schadt told Merck that this was a strategy doomed to fail, because disease arose not from single genes or pathways but rather out of vast networks of genes and pathways whose interactions could be understood only by supercomputers guided by abstruse algorithms. Evangelical still, though now evangelical on behalf of irreducible complexity, he asked Merck to remake itself in the image of the network model he was determined to pioneer. Merck declined and Schadt headed to Silicon Valley, to the land of data.

... In September, Mount Sinai announced that he would be head of the newly created Institute for Genomics and Multiscale Biology. A little more than a year later, Sinai announced that Schadt's operation would be renamed the Icahn Institute, just as the entire medical school would be renamed the Icahn School of Medicine at Mount Sinai. For the privilege, Carl Icahn had given Eric Schadt $150 million to claim the future of biology.
The article focuses on the treatment of Stephanie Lee's colon cancer.

Esquire: ... The first thing that needs to be understood about Stephanie's data is that there would be a lot of it. From the samples of Stephanie's blood, the gene sequencers would generate the data about the genes in her "germline"—the genes (and the gene mutations) that she inherited from her parents and that existed in every cell of her body. From the samples sliced from her colon, the sequencers would generate data about her cancer and the mutations that produced it. But the data would be raw. It would contain millions of bits of genetic information, each one a sentence in the horror story that Stephanie's cancer was telling—and all those sentences, at least initially, adding up to a bewildering Babel. The data would exist right on the edge of incoherence; then Schadt and his scientists would strive both to make sense of it and complicate it. That's their trademark, and why they need a supercomputer. The genes that Stephanie was born with would be compared with the genes that were driving Stephanie's cancer. The genes that were driving Stephanie's cancer would be compared with the vast libraries of reference data-bases that already exist on all kinds of cancers. Then they would be plotted against the "network models" that the Icahn Institute is constructing, the millions of individual data points mined for their billions and even trillions of connections.

... Schadt's scientists—his biologists and his mathematicians—were from all over the world. Many had followed Schadt from the West Coast, but before they came to America, they lived in China and India and Russia. Now they had access to near infinities of information; indeed, they would soon have access to the near infinity of information generated by the DNA of a woman in Mississippi who had been given no information at all, except the information that she was going to die. It was a point lost on no one, least of all Schadt.

... A month earlier, Cagan had started doing something that he said "had never been done before." He started creating "personalized flies" for cancer patients. He took the mutations that scientists like Schadt had revealed and loaded them into flies, essentially giving the flies the same cancer that the patient had. Then he treated them. "Why a fly? You can do this in a fly. You can capture the complexities of the tumor."

... By October 11, however, Cagan already had "one possible drug suggestion for her"—or one possible combination of drugs, since he always tests at least two at a time.

... Now the oncologists at Mount Sinai were asking Schadt and Cagan if there was something they could do in their own intractable cases. And Dr. Holcombe was asking what studies had to be done to incorporate personalized therapy into the standard of care…a standard of care derived in part from none other than little ol' Stephanie Lee. There had been the imposition of obstacles at every step of the way, and the odds against her remaining on what Schadt called "a path to fight on" had beggared even his mathematical imagination. And yet here she was. Her tumor had become, in Ross Cagan's words, "at this point in time, the most fussed-over tumor that I'm aware of." ...
Here's a peek at some of the computing infrastructure behind this kind of work.

20 comments:

JorgeVidela said...

"Biomathematician Eric Schadt" is FAT.

"When [Schadt] graduated high school, he joined the Air Force with the
idea of subjecting himself to the rigors of Special Forces training." --- is a pwt IDIOT.

cancer is also a disease of civilization with few exceptions. no dairy with its igf, no polyunsaturated fat and grains, which are also igf promoting, low protein, also igf promoting, lots of drink, which reduces igf and doubles igf binding protein, and voila no cancer (except for some thropat cancer from the drink). sufficient imbibation halves risk of kidney cancer and non-hodgkins lymphoma.

Richard Seiter said...

Interesting back story on Mount Sinai. For anyone interested in Systems Biology they are offering a series of three courses on Coursera: https://www.coursera.org/mssm

M. Möhling said...

Jorge, I won't put in in all caps, hopefully you'll understand it anyway: you're quite a nuisance.

jorge_videla said...

m. mohling. you have no clue.

jorge_videla said...

you have no clue m mohling. this research is a TOTAL waste of time and resources. it's STUPID. would you suggest tailoring drugs for type ii diabetes or radiation sickness or smoking related cancer?



cancer isn't like dying from an avalanche, bad weather, or a serac fall. it's like climbing without ropes and falling or going up without oxygen and dying from HAPE.

David Coughlin said...

When I mull dropping out of the workforce and going back to school, it is to work on problems like this.

MtMeru said...

said the pope of martin luther. americans spend more on healthcare than they do on food. god knows how much the above boondoggle is costing.

you've got no clue "m mohling". this poor woman's cancer is the result of eating too much fried chicken.

like most you think of cancer as like an avalanche, a serac fall, or a
storm. nothing can be done to avoid it. but it is actually like going up
without oxygen and dying from HAPE or going up without ropes and
falling.

MtMeru said...

a cure for all cancers would increase life expectancy by about three
years. that's it. despite the tragedy of children and young adults
dying from cancer, such cancer is very rare.

yes. what the world needs is more clever people like yourself working on the
great conundrum of fried chicken caused cancer. why not solve the
problem of plutonium and smoking cancers too.

MtMeru said...

said the pope of martin luther. americans spend more on healthcare than they do on food. god knows how much the above boondoggle is costing.

you've got no clue "m mohling". this poor woman's cancer is the result of eating too much fried chicken.

like most you think of cancer as like an avalanche, a serac fall, or a
storm. nothing can be done to avoid it. but it is actually like going up
without oxygen and dying from HAPE or going up without ropes and
falling.

MtMeru said...

a cure for all cancers would increase life expectancy by about three
years. that's it. despite the tragedy of children and young adults
dying from cancer, such cancer is very rare.

yes. what the world needs is more clever people like yourself working on the
great conundrum of fried chicken caused cancer. why not solve the
problem of plutonium and smoking cancers too.

MtMeru said...

"So he taught himself by reading textbooks. It wasn't hard. Pure math was
hard. Molecular biology, after pure math, struck him as ridiculously
easy."


apparently "reportage" is a license to lie. my major was math. i made the high score in the country on the old SoA exam 100 when i sat for it. this is bs. hardy was right in ha "a mathematician's apology" as to the useless of his metier, so was a former boss of mine who said, "engineering is a lot of addition and subtraction."

Richard Seiter said...

David, if you are at all serious about this check out the Coursera courses I linked elsewhere. I think they (well at least the first two, which I have taken) offer an interesting (and relatively low expense/commitment) introduction to Systems Biology (I think the research in this article is best described as the intersection of genetics and systems biology -- the latter providing the "network models" above). It will be something to watch what these research fields produce. Personally I think there is too little effort being spent on low hanging low tech fruit in health (e.g. diet, exercise, basic biomarkers). My hope is that these high tech techniques will turn out to lead to low tech (i.e. easy/affordable) solutions. For example, combining genomic information with metabolic pathway analysis may enable targeted nutritional supplementation for people with certain issues (there are people working on things like this, but the ones I know about tend to be on the fringes). IMHO a big problem in health care/research is that everyone is pursuing patents with the goal of creating expensive solutions (with the holy grail being drugs they can sell to someone for the rest of their life). I think a good use of government money would be to develop affordable approaches to improving health.

David Coughlin said...

Cancer is a big, meaningful human problem, and that is what the appeal is. I would specifically chase climate problems.

Abruzzi spur said...

no it ain't dave. not anymore than obesity.

if all cancers were cured life expectancy in the us would increase by...drum role...three years. that's it. plus, it's 100% preventable with rare exceptions like retinoblastoma.

Abruzzi spur said...

again the human tendency to take the way things are as the way things must be is an "unkown known". cancer is almost 100% preventable. as i commented below laron dwarfs are IMMUNE to cancer.

the cancer researcher is like this guy:

Dan Patrick: Mr. Anderson, it appears you are also taking steroids.



Greg Anderson: Absolutely not. This has always been my natural physique.



Dan Patrick: Okay, let's take a look at a photo of you from five
years ago. [dissolve to a shirtless photo of Greg, showing a very
scrawny torso and arms]



Greg Anderson: I don't see your point.



Dan Patrick: Look, doctors have come forward and testified that you injected Bonds with steroids.



Greg Anderson: Doctors? You know, I'm tired of these doctors
and their accusations. Why don't these so-called doctors focus on real
problems like curing cancer, or back acne, or uncontrollable rage, or
man boobs?!

David Coughlin said...

I have had a half dozen friends and parents of friends pass of cancer in the last couple of years. Cancer is a terrible, savage way to go.

Abruzzi spur said...

i agree 100%. stomach cancer is likely the worst. but dave...going out is horrible whatever the cause. imho research dollars should be spent so as to maximize healthspan---healthy life expectancy.

prevention really is worth a pound of cure in the case of cancer. the money spent on research would be better allocated to subsidizing better food. that along with very heavy taxation on igf promoting foods would at least halve cancer incidence imho.

and so far, as one organic chemist commented to me, "if you get cancer in your 60s you're screwed." all the success has been in children and young adults. there are two reasons for this. 1) funding is doled out based on life years saved and 2) cancers in the young have fewer mutations, are more treatable. but such cancers, though tragic, are very rare.

Hacienda said...

It ain't the disease. It's the person.

Bobdisqus said...

I wonder what Illumina's annual production capability for these is?

http://www.illumina.com/systems/hiseq-x-sequencing-system.ilmn

jeffhsu3 said...

Schadt showed up to Cleveland in the middle of winter wearing shorts and sandals.

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