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DTC Genomics: Opportunity Lost?

Author: 
Eric Schuur

Once I warmed up to the idea of startup companies offering to sequence the DNA of anyone capable of ordering from Amazon.com, I began to look forward to what might come of this nascent industry. Enabling individuals to have their DNA sequenced certainly seemed like an out-of-the-box idea at the time and I wondered if a so-called paradigm shift might arise from placing genetic information, unfiltered and unadvised, in the hands of its owner.

I had(and still have) two chief hopes for "paradigm shifts" that might come from throwing the genetics box wide open:

Breaking the “chain of command” on health information by handing out genetic information might help change how we think about healthcare. The initial response from the medical world to the DTC genomics industry was less than enthusiastic, ostensibly because of the potential for harm when the uninformed masses got their hands on their gene sequences. This turns out not to be true—there is no evidence of harm from accessing one’s own DNA sequence information. Furthermore, there has been neither a flood of buyers nor a spate of lawsuits. The collective yawn over the availability of DNA sequencing (initial excitement not withstanding) suggests that DTC genomics as practiced now might be more of a baby step along the way than a giant leap.

Putting this information in the hands of all who wish to know will help change how we think about genes. We have become quite genocentric, attributing an out-sized weight to the role of genes in biology. We call genes the “blueprints of life” and consider them an identifiable “first cause” that drives everything else in the living world. "We are our genes" in this view. The way I think of it genes are a part of a system we call an “organism” and they are no more or any less important than proteins, carbohydrates, etc that comprise that organism. Prior to our genetic era, an abundance of great research was done on biochemistry and metabolism, illustrating their roles in cellular phenotype. We seem to have forgotten a lot of that research, but it may be resurfacing as the 'omics era reaches beyond genes. I'm confident that balance will return.

My hope with the emergence of the DTC genomics industry is that crowdsourcing genetic research might provide new direction and new ideas on its role in health and society. Might we get really novel answers to thorny genetics questions such as “what happens to missing heritability and is it important anyway?” Might it also be enough of a nudge to permanently put the paternalistic relationship between physicians and patients in the past? Might the DTC genomics industry help us reach a more sophisticated view of the role of DNA in living organisms more quickly?

For the moment at least, it appears that time is taking the wind out of the sails of the industry. As evidence, here are some recent developments:

-Over the summer Navigenics was bought by Life Technologies, Inc. Gone was an industry pioneer.

-This fall, deCODE was bought by Amgen. Not a surprising end to deCODE’s rocky road, but gone is another industry pioneer.

-Recent developments announced by 23 and Me (patent received, grants funded, seeking FDA approval for products) sound suspiciously conventional. Has 23 and Me lost its will to break the mold?

Will there be a DTC genomics industry 2.0? The failure of pioneering companies in any new industry is not unusual. Will these shifts will still happen? I'm hopeful that new entrants will pick up the banner. It seems likely, though, that it will be new companies to move the field forward and that (as usual) it will take longer than it initially seemed it would.

Creating the Future: Why I Am Taking Sci-Fi More Seriously

Author: 
Theral Timpson

Writers, Artists, and the Intelligentsia

I majored in English Literature--otherwise known as the Booze and Sex Department. For many years I thought that writers and artists were the greatest intellects around. They told us what was going on in our world, what had happened, and what would happen in the future. Let me try to convince you with a few examples.

In 1922, T.S. Elliot published "The Wasteland," one of the most important poems of the 20th Century. It defined the time and prophesied the future. (If the 20's gave him a wasteland, what would today's Facebook generation offer?)

Around the same time, Picasso gave us cubism, a visual demonstration of the emerging modern era. Cubist paintings reflected the disjointed life that came about from the liberation of perspective. Past, present, and future were fashioned into one simultaneity. (An English degree teaches you to write fancy sentences like that.)

The modern poet, Maya Angelou, was chosen by Bill Clinton to give her “On the Pulse of the Morning” for his inauguration. She was the second poet to participate in a presidential inauguration, the first Black and woman. In light of the recent election, the dawn of a new era for minorities and women, we see Maya was indeed ‘on the pulse.’

Scientists and Engineers

And what does this have to do with the life sciences?

I’ve been in the industry for many years now, first as a marketer, now as journalist. In the two years since we came up with the idea for Mendelspod, I’ve had an ongoing internal debate (crisis) about who creates the future. For it appears more and more that it is the scientists and engineers, not the writers and artists, who are setting the direction of our species.

Just today, I heard from a geneticist at Stanford, Mike Snyder, that health is merely a product of our genes, proteins, microbes, etc. That we will be able to manipulate it by understanding the molecules. It appears that it is the Mike Snyders of the world, or George Church, Ron Davis, Art Levinson, Bill Gates and Serge Brin who seem to be making the most difference in modern life. The cold fact is that scientists and engineers are reshaping our lives almost daily with new technologies: They are giving us powerful new ways of connecting, which is causing revolutions, not only politically, but in our private lives as well. Notions of identity and privacy are being challenged like never before in this genomic age. In fact, it looks probable that we will be able to live longer than ever before. Some of them talk of the end of aging.

Let me suggest a literary project. Do away with the concept of death and then go find any meaning in any great piece of literature since the Epic of Gilgamesh.

You see my crisis. Have writers and artists, the old leaders of intelligentsia, become less important? For millenia it was the bible (literature) which gave us notions of our place in the cosmos. Then we had Herman Hesse. Now it's Deepak Chopra teaming up with Rudolph Tanzi on brain science. Now it’s scientists like Richard Dawkins, author of The Selfish Gene, who recently made the bold claim at an Apple conference that “philosophy is dead.” Philosophers have not kept up with current physics, he says, and are therefore becoming irrelevant.

(If you have an idea how to argue with this, please email me.)

Sci-Fi and the Futurists

This year we’ve had several ‘futurists’ on the program. Folks like Sultan Megjhi and Joseph Jackson who are completely at home talking about the way things will be fifty years from now. In fact, many of the scientists we’ve had to the program could be called futurists. George Church talks about living to 200. I ask, who knows more than they do about what our lives will be like on this planet in a couple hundred years?

I peppered Dr. Church in an interview last year with the question: are you a visionary? He shied away from the term saying it wasn’t good “being too far ahead of one’s time.” But I wonder if his hesitance has something to do with getting funded and being commercially relevant. George’s big aim is to create technology that can be commercialized and make a difference. He’s been at the center of $1,000 genome movement. He is a visionary.

Where do these scientists and engineers that come on the program get their ideas? More often than not, when asked, they reply that I should read this or that science fiction novel. Hey, wait a minute. Are we saying that the writers are still calling the shots afterall?!

Humanity+ Conference

You can no doubt appreciate my delight in hearing about the Humanity+ Conference that took place in SF last weekend with the tag line, Writing the Future. (I've been around the futurists long enough to know that for them, this line is without hubris.) Let me tell you about Humanity+. It is an organization born from the philosophy of transhumanism. Humanity+ advocates for the ethical use of emerging technologies to enhance human capacties. Hence, trans-human. You humans are so yesterday. Yes, I guess we should start figuring out the liability of the Google Car, or whether IBM's Watson is entitled to personhood. The conference began with a lineup of science fiction writers. What did they talk about? The future, of course.

I confess here that I was never keen on science fiction. Why take most of the time creating gobledy-gook and leaving precious little space to talk about real issues?

Kim Stanley Robinson is author of the prize winning Mars Trilogy about the settlement of Mars. I have just begun the series, and find myself having some profound new thoughts in between trying to forget about my Mormon upbringing and the theology that one day I will be a God and populate my own planet. Perhaps I've been too earth-centric all this time. At least since I left Mormonism. In his talk, Robinson pointed back to the work of filmmaker H. G. Wells as a big influence not only on him, but on the direction of science. As for the future, Robinson quoted William Gibson, “the future is already here - it’s just not distributed evenly.”

How true. It seems I've been missing my own daily dose.

Many scientists point to Robinson’s Mars series as a major influence. They think that along with solving aging (did I just write 'solving aging?'), we must get off this planet for the survival of the human race. (See our recent show with John Cumbers, a synthetic Biologist at NASA.)

David Brin, another sci-fi author speaking at the event, isn’t shy about man’s future either. He stressed the importance of the crowd speaking with the "lobotomized who voted for [Romney]" so that they, the transhumanists, don't end up in the shoes of Giordano Bruno and burned at the stake. Are those with the technology really that powerless, Mr. Brin? “We may be the only hope for the galaxy,” he said in earnest, via Skype. “The galaxy is waiting for us.”

We want to do our part at Mendelspod. We certainly wouldn't want to let the galaxy down. We’ll be running a series, “Creating the Future,” where I’ll be talking to some sci-fi authors and other hefty intellectuals about not only their thoughts on the future, but on their role as influencers of the future through scientists. Perhaps you've picked up some skepticism, even sarcasm. It's just the sound of my feet dragging on the pavement as I'm pulled into the future. I am keenly interested in the topic. I aim to make sure the future gets more evenly distributed, over me. More than needing to know what will happen to the race in the future, I’d like to start by knowing just who is running things around here at the present. I hope you’ll find as much delight in the discussions as I do. Please send in your suggestions for guests and questions as we probe the great beyond.

Time to Rethink Cancer Therapy?

Author: 
Eric Schuur

In an earlier post, I wondered a bit about the ultimate causes of cancer. For the last several decades cancer has been labeled as a genetic disease, an idea which we have chased with great fervor. Yet, It feels to me sometimes as though the evolving story of the causes of cancer is like a hall of mirrors in an amusement park in that there seems to be an ever receding chain of causal genetic alterations fueling cancer’s inexorable progression.

The most visible of these alterations are in the growth modulating molecules of the cell. Over expressed growth factor receptors or transcription factors, mutant signaling molecules, etc. How did these components come to be broken? Genetic insults of various kinds have been discovered, studied, and labeled as causes of cancer. We are actually getting pretty good at intervening in some of these malfunctioning growth pathways that have been co-opted by cancer. For example, antibodies that block the activity of HER2, the human epidermal growth factor receptor that seems in some cases to drive breast cancer proliferation are quite effective.

Yet, even when we do intervene with seeming effective tools, such as trastuzumab for HER2 over-expressing breast cancer, the cancer seems in most cases to rebound by activating still other pathways of growth. It has come to be reminiscent of the proverbial leaky dike and us with not enough fingers to plug the leaks.

The genomic instability that is so characteristic of most cancers seems to be the driver of genetic diversity that provides resistant variants. It appears that cancers “evolve” to a state of significant heterogeneity and the genomic instability seems to be a player in that process. But, where does the genomic instability come from? We can then propose a change in cells that causes genetic instability. But, where then does that come from? See what I mean?

This genetic, linear causation idea is the foundation on which our cancer therapy strategy is built. Naturally, our combat strategy is direct. Cut it out. If you can’t cut it out, hammer it with chemicals or radiation. If a little doesn’t work, then try a lot. Too much cell division and DNA replication? Inhibit DNA replication. Too much RAF signaling? Inhibit RAF signaling. Battle this problem where it occurs: inside the cancer cell itself. This strategy has produced some remarkable results; however, for most cancers, the fact remains that some cells inevitably escape destruction to arise as an even more fulminant tumor later.

The feeling of frustration in chasing cancer up the path only to have it resurrect out of seemingly nowhere still further upstream is a signal to me. I have sensed in this frustration a signal to think about cancer pathogenesis and treatment in new ways, like I’m sure others have. Recently I have been gratified to hear a number of researchers propose new views of what cancer is and new strategies for treating it.

I have been a member of a tumor microenvironment interest group for a while, mostly to keep an ear to the ground in that area. Having spent many years trying to grow cancer cells in various ways, it is clear to me that they depend heavily on their microenvironment to survive.

Over the summer I noticed a few publications (see this news story in Nature Medicine for more details) suggesting that resistance to chemical therapy may be mediated by more than just the response of the tumor cells. These studies suggest that the tumor microenvironment may provide protection from anti-cancer agents by secreting of growth factors from stromal cells intermingled with the tumor cells. In one study, WNT16B growth factor secretion was induced in stromal fibroblasts, which in turn protected the cancer cells from programmed cell death. In another pair of studies (here and here), stimulated secretion of hepatocyte growth factor from stromal cells attenuated the sensitivity of melanoma cells to BRAF inhibitors, one of our newest targeted therapeutic classes. It seems that the effects of treatment are more complicated than we had thought. Our cell-autonomous approach to drug development is probably too simplistic. In retrospect, it seems obvious that we should account for the effects of other cells that, with the tumor cells, create the environment in which the cancer develops.

Rethinking cancer therapy has been proposed by Robert Gatenby and colleagues for some time now (see, for example, their article in Cancer Research in 2009). Over the summer, Gillies, Gatenby, and colleagues published another paper describing how these concepts impact targeted therapy as progress in cancer therapy. These folks have brought concepts from evolutionary biology and the control of invasive species to bear on cancer therapy.

Gatenby and colleagues describe a model for how evolutionary dynamics operate in the tumor microenvironment: phenotypic diversity, courtesy of genetic instability, provides the substrate for selective forces, provided by cytotoxic drugs, resulting in selection of tumor cells that can survive almost any insult. Under this scenario, toxic drugs will select for some variant that will then proliferate to fill the niche vacated by the cells killed by the therapy. Adaptive therapy is described as a potential solution to this problem. In essence, adaptive therapy uses interventions that strategically impose a substantial evolutionary cost on cancer, thereby reducing its fitness to survive and ability to adapt to its new environment.

A high evolutionary cost means that interventions are difficult to evolve around. To illustrate what these might be like, they draw examples from control of invasive species. Might cancer be better handled as if it were an invasive species? Two points that they make are 1) that eradication is often not possible and control of population size is the goal; and 2) the high-evolutionary cost interventions are often biological.

Although the cancer genome is an important component of the disease, it is becoming clear that there are additional facets of the disease, such as the interaction of the cancer genome with genomes in its environment. Consideration of the role of tumor microenvironment modulation of therapy is a welcome expansion of how we think about cancer and our response. Likewise, radically new strategies for cancer therapy, possibly like adaptive therapy, are welcome, as well. Incorporating these new concepts into our view of cancer helps put us on the path to effective new treatments.

Are We Graduating from Reading to Writing? The First SynBioBeta Conference

Author: 
Theral Timpson

We hear a lot about how DNA sequencing is changing the world. Our ability to read the code of life is taking us a level deeper in our understanding of the human body and of the other life forms around us. Sequencing is all about “reading.” Occasionally, not very often, we’ll get someone to the program who talks about “writing” the code of life. Isn’t this where we’re going? To a world where, OK, now we understand the code, let’s write our own.

Yes, nature has given us an incomprehensible diversity of food and materials to make us happy. But now we’re graduating from the class of reading, of using and at times manipulating what’s already there, to the class of writing where we make new life forms which can do even more for us. Ask any scientist what synthetic biology is, and you’ll get just as many answers as you do to the question, who/what is God. Last week I attended the inaugural conference for synthetic biology entrepreneurs, the SynBioBeta conference held in Menlo Park, CA. (The site will be a resource for synbio startups and stay up through the year.)

For today’s show, I interviewed the founder and creator of the conference, John Cumbers, and the Director of Research Programs at Amyris, Tim Gardner, a speaker at the event. Listen to their interviews to see how they define synthetic biology. 

“Biology is just another code,” we heard mid-morning from Omri Amirav-Drory. He’s the founder of Genome Compiler Corp, a new venture developing the software that really democratizes creation itself. With his software, you can go in and build a genome. That’s all. I’d like some of this, some of that, and a few of those, please. With a few of these thrown in for good measure. It appears the path to the future will also be a matter of what we sit and do every day: cut, copy, and paste. With colored boxes for different genes, the software looks so simple that even I could build myself a cute little genome. It’s easy to see at the SynBioBeta how the imagination can take flight into a world of synthetic possibilities. And some of this field belongs to what Tim Gardner from Amyris calls the “sci-fi crowd. “Well, if you’re not in the sci-fi crowd, which crowd are you in?” I ask Gardner as we walk to a quiet room to record his interview. “My passion comes in working on problems that we face now, everyday. At Amyris we’re working for the day when you can pull your car up to the gas station and choose biofuel as an option, at no more expense than the current market price.” Gardner’s low key manner grounds his practical approach. (For more about Amyris, see the interview.)

SynBioBeta

Slide from John Cumbers' Presentation at SynBioBeta

Other highlights from the show for me were first, the explosion of startups in the field. To begin the conference, Cumbers put up a slide showing, with a virtually exponential curve, the number of synbio startups over the last few years. I asked several of the founders whether synthetic biology was more some answers looking for solutions.

It was evident from the presentations that to succeed many of these fledgling companies had pivoted at least once to new markets. Company founders replied that it would go back and forth. They entered into a project via one application, found a technology, then when the first application didn’t work out, looked around for another way to commercialize. In the case of Amyris, they are going into a range of markets, from fuels to perfumes, all with just one molecule.

Cumbers says that we’re seeing the transition synthetic biology is making from being pretty much exclusively research to the commercial world. Michael Koeris is a co-founder of Sample6 Technologies based in Boston. “We had to pivot twice, now it looks like it’s working,” the entrepreneur told me at the break. The company is engineering viruses that attack bacteriophages to detect bacterial contamination in agricultural applications. Michael’s colleage, Tim Lu, another co-founder was profiled in this BBC article earlier in the year.

I found the panel on CAD tools for synbio most intriguing. Carlos Alguin from Autodesk Research spoke. His company is responsible for a great deal of 3D modeling, including the work for the blockbuster movie, Avatar. It wasn’t clear how Autodesk’s platform would practically aid the synbio businesses in the room, but this is was not a conference about connecting every dot on the spot. “What will the next generation of designers be able to do when they grow up with these tools,” Carlos provoked the crowd. It’s a great question.

New Funding Models Emerge During Tough Times for Biotech

Author: 
Theral Timpson

Is 2012 the bottom of the barrel for biotech business hopes? Or is it full of opportunity?

Steve Burrill's annual book on the biotech industry this year is titled, "Innovating in the New Austerity." The editors at Xconomy took that title as a challenge this week in producing their Bay Area event, Reinventing Biotech Business Models. Luke Timmerman, the national biotech editor for Xconomy, has been writing on the austerity side of late. One piece entitled Betting on Biotech to Catalyze U.S. Job Growth? Don’t Count On It took a look at the scant numbers of job postings at the leading biotechs. In another recent piece, Who’s Still Active Among Early-Stage Biotech VCs? Luke bemoans the trend that less money is going into the biotech industry today. It was with this downbeat news and the big question of who will fund early stage innovation that Timmerman opened up Xconomy’s latest biotech event.

Xconomy

Xconomy's "Reinventing Biotech Business Models" at Onyx in S. San Francisco

Onyx, Exelixis, and Cytokenetics

The Xconomy lineup focused on new funding models, and the day’s speakers, particularly the three CEOs on the first panel, chose to go the optimism route. According to Tony Coles of Onyx, Mike Morrisey of Exelixis and Robert Blum of Cytokenetics, their companies are doing quite well.

Each of the three CEOs claim that raising money has not been an issue for them. Onyx, who hosted the event, has had two FDA approvals this year. It doesn’t really get much better than that. Unless they come up with another Lipitor sometime soon. CEO Coles pointed out some of the positive trends that he believes will make biotech a healthy industry. The first is a new way of working with innovation sources, be they start-ups or university research centers.

“We are developing a new system for the efficient transfer of assets,” he said.

Second, Coles believes that genomic or personalized medicine will bring about better chances for success, citing the common example of Zelboraf. Coles doesn’t think that everyone should run to genomic medicine, though. He says that there are still a lot of opportunities for products where there are not specific genomic indicators.

Mike Morrisey of Exelixis and Robert Blum of Cytokenetics, both housed just down the street from Onyx in biotechlandia or So. San Francisco, sounded similarly positive.

Speaking of trends in biotech, Morissey said, “It’s totally Darwinian. Capital limitations drive efficiency. A flow of innovation will come-just differently.”

Blum of Cytokenetics talked about his company’s recent round of funding and suggested that the “financing model needs to adapt to the needs of the discovery industry.”

Versant Has an Idea

If talk of new funding models dominated the day, then Versant Ventures emerged as the star player. Versant, a VC firm focused on healthcare, has invested in three companies built on “option-based deals.” With this model, Versant teams up with big pharma from the get-go to create a drug development company with the goal that the pharma company will buy an asset at an agreed upon price. The startup gets an up front payment from a pharma who buys the option to license the product later on. This was the case with the recent deal between Roche, Versant and the new creation, Inception Sciences.

Brian Atwood was on hand to represent Versant Ventures and give more details. This is a new model for them, and he sees the firm doing more similar deals.

“Could one of these deals pay for a fund?” asked Timmerman, who sat on stage throughout the afternoon querying the speakers.

Atwood replied in the affirmative. What kind of returns, Luke went on. Well, we’re a 10x company Atwood said assuring Luke that that is what he expected from these new deals.

Versant is innovating by matching the cycles of drug discovery to the needs of VCs. But were there any attempts being made to create VC models that match the typical drug discovery timeline, as Robert Blum had earlier suggested. I asked Atwood.

“No.” Came his simple answer. Timmerman pressed him to say more. Atwood was firm. “It can’t be done. Our LPs want a return in 10 years and biotech is taking 17 or more years."

What About the Space?

Diego Miralles from Janssen added some life to the end of the event talking about Janssen Labs, J & J's new “innoavtion center” in San Diego. Referring to a model similar to San Jose Biocenter, Miralles pointed out that the project was lowering the bar for companies to get started.

“All a company needs is $100,000 and they are in business,” Miralles asserted.

Similar incubator models are being set up by Bayer and Pfizer as well as at research parks around the country. These new incubators are primarily focused on the “space” aspect of drug discovery. But, as Miralles suggested, the space can create new opportunities that aid with the money side of things.

Xconomy Events

Speaking of reinventing models, the Xconomy event had some nice interaction. As I mentioned, Luke was on stage with each speaker asking them questions and keeping them honest and on target. He also turned each guest to the audience for questions. I found it much more engaging than the typical long company presentations. It was as though Luke's office was on stage and we could participate in the discussion. Timmerman writes almost daily for Xconomy and is up to speed on not only the trends of the industry but also shows remarkable ease with all kinds of industry details.

Xconomy

Xconomy's National Biotech Editor, Luke Timmerman with Chief Correspondent, Wade Roush

Xconomy puts on six events each year in each of the major areas where they are based, according to their chief correspondent, Wade Roush. The events are part of Xconomy's business model. They are sponsored by the company's underwriters and cost attendees around $200. Timmerman is not ALL doom and gloom, and he acknowledged at the outset that the biotech NASDAQ index was outperforming the broader NASDAQ this year. One could add that a biotech drug is on track to be the best selling drug of the year. And the recent buyout by Gilead made Pharmasset the best performing stock ever. Times are tough. Financing is tight. Yet biotech is finding ways to fulfill the promise of some great new science.

For more on this topic, see our recent show with Bruce Jenett of DLA Piper, The Best of Times, The Worst of Times. See also our upcoming interview with Brian Atwood of Versant Ventures.

Is Science Causing a Crisis for Art?

Author: 
Theral Timpson

Guest:

Barry Bunin, PhD, CEO, Collaborative Drug Discovery Bio and Contact Info

Chapters (Move marker to advance)

0:00 The parallel between art and science

3:55 Benefit of mixing disciplines

6:25 Is science causing a crisis for art?

A few months back we did a show with Barry Bunin, the CEO of Collaborative Drug Discovery. Little did I know that Barry would end up rhapsodizing on the relationship of art and science like a university professor. We decided to turn the camera back on and produce the segment as a separate show.

What is the parallel between art and science? Is science causing a crisis for art? These are a few of the questions Barry bravely and unassumingly tackles.

Personalized Medicine: A New Industry Struggles Toward Birth

Author: 
Theral Timpson

Some argue that medicine has always been personal. Personalized medicine as we think of it today has become the industry that is advancing the understanding of the human body at the molecular level. Since the sequencing of the human genome, this new industry has topped the news, often with much hype but little to show. Last week, Burrill and Co put on their 8th Annual Personalized Medicine Conference in San Francisco.

More and more, the focus at PM conferences is on reimbursement. Afterall, healthcare is an industry, an economy. Mendelspod is partnering with Personalized Medicine World Conference in January, 2013, and I just heard that the theme there is reimbursement. In the summer, I attended a conference put on by IBC focused on diagnostics, Drug and Diagnostic Development, and attended a terrific panel with Elaine Jetter of Palmetto (Medicare contractor) and Liz Mansfield of the FDA sloshing it out. I just received a program from CHI for an entire conference based on reimbursement.

The Burrill 2012 conference was no different in focus. To quote Steve Burrill, if you can’t get paid, it ain’t gonna happen.

PM to the Rescue

Steve begins his conferences with a sort of State of the Union address. Where are we at, where have we been, where are we going? Steve pushed this year’s audience--a room full at the Bently Reserve Hotel in San Francisco--to think of the struggling healthcare system. Giving the familiar lines about the soaring costs and aging population, Steve suggests that the birth of personalized medicine is part of the rescue.

Steve’s style is to provoke creativity and innovation. He has general comments and questions. How will we improve healthcare without increasing costs? Should we spend on the old or the young? Who should pay for healthcare? We ARE going to ration. A dead patient is a cheap patient. Etc.

I’ve heard this all from Steve before. But I felt this year he pushed us harder to look at healthcare in new ways. If the current path is unsustainable, what will the new model look like? I’m impatient. Surely from his seat on Mt. Olympus Steve knows where things are headed. After all, he just came back from a meeting with world leaders in Europe talking about the big issues. What did he learn? At the break, I teased him. Come on Steve, I prodded, you know where this is going. Just tell us. He smiled and replied, “I’ll tell you this. Innovation will come from the U.S, yet we will be late adopters.”

That’s tough for the investors, I replied.

“It depends on where and how you invest,” he came back.

The Georges

Two main fixtures of the world of PM were there. The two Georges each took a keynote. George Church talked about two new methods of DNA sequencing and about work the PGP is doing. Dr. Church has spent a lot of time investing in the idea of consenting patients for research. I asked him if he looked enviably on the UK’s recent decision to open up all the healthcare records of the NHS to research. He asked, “what do you mean open? They’re redefining the word ‘open.’ It’s not really open.” Dr. Church says the PGP is still the only place where complete genomic and clinical information is available for anyone around the world to access.

George Post of ASU employs a carpet bombing strategy to make his point about the complexity of PM. A quarter the way through his presentations I have enough questions to pursue for a year. By the time he’s done, I’m like, “George, I give--you got us all. Let’s just put our hands up in the air and give up.” For example, Dr. Poste thinks “genes for . . .” is an insidious phrase that does us no good. It’s more complicated than a gene for this and a gene for that. Going through the different fields, from genomics to proteomics to epigenomics to the microbiome, he leaves no rock uncovered and a terrible mess in his wake.

He is passionate about the need for standards. So the data can begin to be integrated. But this is a catch 22. Last year Cliff Reid, CEO of Complete Genomics, urged caution in this area. Standards too soon in an industry are not good. Yet if there are no standards, the different domains of data don’t communicate among each other. There’s a struggle between the freedom to let the data go its way, and the need to create standards that everyone can agree upon.

(Cliff Reid was originally on the program but didn't participate this year. I understand his absence now with the news this morning that Complete Genomics is merging with BGI.)

The Data Issue

A panel focused on making the data actionable included Illumina, LifeTech, Oracle, GE Healthcare and 23andMe. There’s tons of work to be done here. And the five companies are all pursuing different avenues. Illumina is betting on an iPad app. LifeTech, leveraging the recent purchase personal genomics company, Navigenics, is pursuing this community based program where they are starting with a focus on the patient first, then going back up the chain to doctor, provider, lab, etc. Oracle, naturally, stressed the importance of integrating not only omics data and clinical data, but also the economic data. Entire conference could be held on this topic.

Reimbursement

The crowning session for the conference was a panel of the pioneers in diagnostics showing the way on reimbursement. CardioDx has needed a strong, energetic spokesman pushing to get paid for what is a cool test, Corus CAD. They have one in Deb Kilpatrick. “Payers were terrified by the size of our market,” she exclaimed, referring to her struggle. Deb was congratulated by the others--XDx, diaDexus, Biodesix--on the recent Palmetto (Medicare contractor) approval of the CardioDx test. As the name suggests, the test is a first of its kind blood test to non-invasively assess whether a patient's symptoms are due to obstructive coronary artery diseasse (CAD). I've been in Deb's market. Several months ago I ended up in the emergency room thinking I was having a heart attack only to find out after thousands of dollars of tests that it was just heart burn!

One of the trends in the booming diagnostics industry is to go to Europe first. Yet this has its problems. Matthew Meyer of XDx said “it’s a big struggle to get the same reimbursement amounts for diagnostics in Europe than they get in the U.S.” There’s that word ‘struggle’ again. Brian Ward, CEO of diaDexus picked up the theme. “Prevention hasn’t caught on in Europe yet--especially in Eastern Europe.”

In a different note from last year, all four companies were optimistic about capital markets. Noting that it may not be as good as that for biotechs, raising money is not a problem for them. CardioDx announced just a couple weeks ago that they had closed a round of $58 million.

Seeing the Forest for the Flowers

A small beautiful moment in the conference gave me some pause. When we’re in the details, we can lose the bigger picture. We get caught up in the struggle. I feel the pioneer’s pain, especially in the diagnostics companies, who have had a rough road with no light to show them their way.

This moment brought me out of the labor and struggle. Sitting with Dr. Church at lunch, we were chatting along, and suddenly he pointed to the centerpiece on the table, a beautiful flower arrangement. What is that flower, I’ve never seen it before, he asked. A smaller flower, about an inch in diameter, with small globe blossoms themselves forming a kind of globe was mostly outdone by the dahlias and mums. Very delicate. And unusual. Heck, I hadn’t even noticed there was a flower arrangement on the table. Dr. Church pulled out his phone and took a picture of the strange blossom. We joked about what he’d do with the picture. Would he go look it up when he got home? Would he send it to a new Google program which identifies objects? Here was a scientist doing what scientists do. Spontaneously and effortlessly. Observing the world around him, and cataloguing what he sees.

It’s the science that has driven the industry of personalized medicine. And it’s the science that will hold the answers. Science unfolds like Dr. Church taking a picture of this new flower. Unfolds like a flower itself. It will not be rushed. Business is in such a hurry. I’m not so naive as to think that science is not itself a business. But at its best, science proceeds with awe and discovery. The business side could be more like that. Personalized medicine is being born. Even those who are involved in the birth can step back and look on in awe and wonder.

“Personalized medicine is the kind of thing that is overrated in the short term and underrated in the long term.” Steve Burrill.

The genetics of the Olympics

Author: 
GenomeEngineering

The London 2012 Olympic Games might have come to an end but the Paralympic Games begins on 29 August, running through to 9 September, and throughout the whole event so far there has been a lot of talk about the role of genetics in elite sport. So, are Olympic athletes genetically better at sport? According to an article in Nature, "almost every male Olympic sprinter and power athlete ever tested carries the 577R allele, a variant of the gene ACTN3". This gene is expressed in skeletal muscle fibre and could have an effect on athletic performance – in total, more than 200 genes have been linked with athletic performance, including variants that improve endurance, or increase the numbers of red blood cells, so upping oxygen carrying capabilities in the blood.

This leads a number of questions:

  • Sports are already segregated according to sex – if there were genes that improved someone's chances in a particular sport, should they also be segregated genetically?
  • Should the athletes without the genetic mutations be allowed to have gene therapy to 'upgrade' themselves? Or should this so-called gene doping be outlawed, much as drug doping is (it is already outlawed in the US)? Widespread use of gene therapy in sport is unlikely to happen very soon.
  • Should the athletes with the genetic advantages carry 'handicaps' to bring them down to the level of the 'normal' athletes?
  • Should any athletes who have had gene therapy to cure disease be excluded?
  • And there is an ethical question too, raised at the Progress Educational Trust's Genetic Medalling event – could knowing about a gene for sporting prowess put too much pressure on individuals, especially as children? And on the flip side – would not having that gene make a child (or an adult) decide that it just wasn't worth trying?

As we learn more about genetics, we understand that in most cases a single mutation does not act alone. According to Ted Friedmann, chair of the genetics panel of the World Anti-Doping Agency: "Genes work in an enormously complicated set of interactions, and no gene works by itself. If you have the gene for speed or endurance, all the other genes you carry that [help] or work against that will affect how that gene expresses itself."

So whether athletes have no genetic mutations, one mutation, or a set of mutations, it still requires a combination of opportunity, environment, attitude, environment, determination and training, to make an Olympic athlete. It is still a lot of hard work.

This post first appeared on Genome Engineering - go to the blog for more posts.

How to Rescue the Life Sciences from Technological Torpor

Author: 
Bill Frezza

Having spent my career in two fields grounded in the physical sciences that made better, faster, cheaper a core driving principle—telecommunications and semiconductors—it’s hard not to cast a jaundiced eye at the sorry state of the pharmaceutical industry. To paraphrase the immortal Dean Wormer in Animal House, ineffective, slower, and more expensive is no way to go through life!

With the exception of DNA sequencing, which has enjoyed Moore’s Law-like improvements for a decade, drug discovery and development has failed miserably when it comes to harnessing a virtuous circle of ever increasing effectiveness and efficiency. In fact, it is moving in the opposite direction. This does not bode well for the future of a business under assault on so many fronts. Rearranging the deck chairs through waves of mergers and layoffs may temporarily fatten shareholder returns and executive bonuses, but such financial engineering will not cure cancer.

Real engineering is called for, but the pushback is enormous. The senior scientists and executives now running pharma often say that biological systems are too complex to decompose, model, emulate, and control using the systematic analysis, design, and development methodologies that propel the world of electronics. Perhaps that was true back when those industry leaders were first trained. But technology has taken great leaps forward, while most of them seem mired in the past.

It is precisely the success of modern electronics and computing that has made it possible to design, manage and operate the kinds of advance tools, simulation and automation techniques that will be needed to shift the life sciences over to practices that have been advancing the physical sciences for years.

Changing Culture

In order to do this the culture must change. Mathematics is the language of engineering and life scientists can no longer take a pass on it. A system that cannot be modeled cannot be understood, and hence cannot be controlled. Statistical modeling is not enough, for the simple reason that correlation is not causation. Life science engineers need to catch up with their peers in the physical sciences when it comes to developing abstract mathematical representations of the systems they are studying. Progress comes from constantly refining these models through ever more detailed measurements. R&D should be all about finding ways to couple the two.

Forty years ago, when I entered MIT, a great division took place my freshman year. Those who could handle the math stuck with engineering or the physical sciences, while those who couldn’t found their way into biology, chemistry, or medicine. The former imbued a language of precision, a respect for systematic problem solving, and a penchant for measurement and reproducibility. Meanwhile, the latter entered a phenomenological jungle where nomenclature reigned supreme, intuition substituted for rigor, and guess-and-check methodologies guided experimental investigation. This classic approach may have been useful for harvesting low-hanging fruit, but the thinning drug pipeline demonstrates that this strategy is running out of gas.

Sure, enormous amounts of data are required to get to the root of how living machines function, and collecting this Big Data requires Big Automation. Yet there is a stupefying amount of work that is still done by hand in most life science labs. This is enabled by the chronic glut of grad students, Ph.D.s, and post docs—an oversupply driven by public policy and federal spending that has allowed researchers to stave off automation.

The title of a recent news story in the Washington Post says it all:"U.S. pushes for more scientists, but the jobs aren’t there.” “Despite $10 billion in federal stimulus funds funneled through the NIH to “create or save” 50,000 science jobs, Ph.D. chemists and biologists are increasingly going begging.

A recent National Science Foundation survey tells the sorry tale. Three to five years after graduation, biological and life science doctorates are dead last in finding tenured or tenure-track faculty positions. Instead, many become part of what one economist calls a “pyramid scheme that enriches — in prestige, scientific publications and federal grant dollars — a few senior scientists at the expense of a large pool of young, cheap ones.”

Running this kind of medieval guild system at taxpayer expense not only dulls the minds of young scientists by forcing them to spend far too much time doing repetitive tasks, it pollutes the discovery and design process with non-systematic errors, confirmation bias, and the indiscriminate discarding of data from “failed experiments.” Is it any surprise that (at least according to one pharma company) two-thirds of the experimental results published in peer-reviewed life science journals cannot be reproduced?

The key to making Moore’s Law work is to scale everything. The popular press focuses on the ever shrinking physical dimensions of transistors, but the entire semiconductor ecosystem had to scale to keep pace, including the way it conducted science. This was made possible by the relentless detection and expunging of systematic error, which is only produced by machines. Human labor is not systematic, and therefore cannot scale. That brings us to the final piece of the puzzle.

The sophistication and reliability of the robotic systems that enable modern semiconductor plants to operate with atomic precision needs to be brought to bear on the woefully inadequate fluid handling, data collection, and assay technologies that beset the life sciences. And not just in high throughput screening but in the balance of research, all the way through to manufacturing.

Advancing the frontier of semiconductor research necessarily leveraged the same equipment and tools used in the factories. To this day, test wafers that form the platform for science experiments work their way through the semiconductor process flow right alongside product. A vast technology gap between R&D and manufacturing cannot be sustained.

Yes, Big Pharma uses sophisticated robotics to screen millions of compounds for potential hits. And then? They hand promising leads off to an army of medicinal chemists who labor by hand to turn them into drugs. That’s like driving a Porsche from New York headed for Boston just to get off in Hartford to take a horse the rest of the way.

Thankfully, these lessons are not lost on everyone. A new generation of computational biologists cross-trained in the engineering disciplines, now in their late twenties and early thirties, is beginning to make its impact on the industry. From my perch as an angel investor in a new-era pharmaceutical startup, still in stealth mode, I am beginning to see what happens when you turn these young people loose, unencumbered by oldthink.

Stand back and watch them rescue a business long overdue for change.

Bill Frezza is a Fellow at the Competitive Enterprise Institute and a Boston-based venture capitalist. He can be reached at bill@vereverus.com. If you would like to subscribe to his weekly column drop a note to publisher@vereverus.com.

This article was originally published in Bill Frezza's column, Skeptical Outsider, at www.bio-itworld.com

It's Settled: We have a Candidate for First Mayor of Mars

Author: 
Theral Timpson

Let me share a bit of my past. There’s some fine irony here to enjoy.

I grew up fundamentalist Mormon. Mormons believe that we are practicing to be gods ourselves. Fundamentalist Mormons believe that Adam is God. That God himself came to earth to start the whole human race. And so too, (“and so too” is a nice Mormon phrase) we may become Gods ourselves. And then go build our own planets. And people them too. (That's right, the presidency is really just a stepping stone for Mitt Romney. He'll have more wives and many more kids when he gets his own planet someday.)

As a side project, my partner Ayanna and I have been working on a new business, called Think Big. We will act as planet decoration guides to the new crop of gods coming up. One has to have some fun. As I’ll probably not be a god (I left the church), I’ll have to settle for some kind of business tailored to the needs of the gods. Better I get to it.

Enter the futurists.

No sooner did Ayanna and I get our new business started, then the right folks for the job have been showing up. We’ve been meeting synthetic biologists at NASA who are working on the materials we’ll need. We’ve met those who are creating the new economies that will enable such commerce.

And recently we met Sultan Meghji. Sultan is volunteering to be the first Mayor of Mars. He just submitted his resume to Neil de Grasse Tyson.

Sultan may be familiar to some of you from our interview with him.

We had Sultan over for dinner last month to talk about what he’s doing at Appistry, a big data company who has just set up shop in the life sciences. And to let us know what he’s thinking. And we found out.

Sultan's one of those guests who, just after you've interviewed him, you want to turn around and do it again. His father was a geneticist, and he went into IT with a government grant as early as high school. He developed the first non-mainframe market system, has worked in defense, and now brings that experience to biological data. These big data folks from other disciplines come to bio and say "hey, what's the big deal--let's get it done."

"The thought process that got me so that I could take what Appistry is doing . . . and turn it into a genetics platform is the exact same process I used eleven years ago when we built the first non-main frame market systems," he explains in some video we captured.

The promise of personalized medicine is just Number 1 of Meghji's ambitions.

Number 2: He'd like to see an entire new way of doing finance that is more consumer relevant. "There's a way to . . . set up a company to replace all retail banking and all retail loans to consumers with a single unified entity that would be more cost effective, easier to manage, and fit into the lifestyle of everyone in the world."

Number 3: To be off this planet. "A single asteroid could kill us all. And frankly, we need the cultural differentiation-we need the exploring to make our culture more vivid and more exciting."

Little did Ayanna and I know when we started our business to guide the new gods in decorating their own planet that we'd have such expert help.




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