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Rousing a Revolution: Open Access and 'Startup Science'

Author: 
Theral Timpson

Joseph Jackson has come up with another conference to further open science and disrupt the status quo.

“Startup Science” ran June 15-16 in South San Francisco starting with a line-up of Joseph’s peers in the open access community. Disguised as a conference to promote startups in the hard sciences and engineering, the new meeting is quite similar to Jackson’s other conference, the "Open Science Summit." Friday's schedule included some well known names in the Open Access community--William Gunn of Mendeley, John Wilbanks from the Kauffman Foundation, and Richard Price of Academia.edu. The big score for Jackson was getting Pete Binfield, co-founder of the new PeerJ in the same week the new publishing service debuted.

Jackson is a futurist who came to Silicon Valley with some strong ideas. He quotes economists, philosophers, and scientists like he just had lunch with all of them yesterday. I just interviewed him for our program, and he talks about humans living indefinitely like it had already happened. He constantly questions the purpose of concepts we take for granted each day. Like net profit. What is it, he asks, and why do we need it?

If going through all the details to put on a conference wasn’t formidable enough, there appears to be not much money (yet) for open science. Who wants to sponsor a conference about open access journals, open marketplaces, and--here’s a new word I learned at the meeting--altmetrics?

These ideas are clearly the way forward. And their value will be realized. And there will be sponsors and investors. But in the beginning, it can be slim. Which is why, Jackson acknowledged, he opted for a conference focusing on encouraging entrepreneurs to start those businesses that will lead us into a new world.

Open Access Gaining Ground

PeerJ

PeerJ is a new open access journal that was launched this week by the former publisher of PLoS ONE, Pete Binfield, and VP of R&D at Mendeley, Jason Hoyt. Under Binfield’s leadership, PLoS ONE has grown into the largest peer reviewed journal in the world. As many of you know, the open access journal brought new editorial models that are being adopted today.

The essential innovation with the new PeerJ is the business model. “We knew it was a good thing to do for the world, so we just needed to find a business model that works,” said the optimistic Binfield.

His aim is to bring down the cost of publishing for the researcher. Even with open access journals such as PLoS ONE, publishing an article costs the researcher an average of $1,400. With the new PeerJ, the researcher will pay to become a member. There are three tiers of membership. $99 gets you membership for life with the rights to publish one paper per year. $169 gets you two papers per year and $259 gets you unlimited publication rights for life.

Will such an inexpensive model prove profitable? Binfield says yes. What numbers does he have access to that we don’t have? He did share one at the meeting. There are 10 million publishing academics in the world with 1/2 million new ones and 1/2 million “dropping off” each year. Do the math.

CurEUs

Presenting a new publication platform for the medical industry was John Adler of CurEUs. Adler says that ultimately the world needs just one publishing house. “So much of the content I want is not in the journals to which I subscribe,” he complained. “When we publish, we all start out with the New England Journal of Medicine. But usually we end up getting published in the Medical Journal of Bulgaria or something like that.”

For Adler and Binfield, the real value comes from crowd sourcing. These publishers are determined to do peer review in a new way, with members of the community who are not behind a paywall. And the software will be open source.

Mendeley

As we transition to a world of open access journals, there is one site which is proving handy for researchers who seek access to articles in the traditional journals as well as the new platforms such as PeerJ. Mendeley is both a place to search for academic research and is a reference organizer with software that can be downloaded to your desktop. William Gunn from Mendeley says his site could actually be the platform for peer review.

Mendeley also offers other metrics than the traditional ones such as citations. Researchers can find out who is reading their papers. Libraries can learn which papers are most popular and better allocate their limited resources.

Academia.edu

Richard Price, founder of Academia.edu had his own response to this. “No one walks down to the library and reads the journal anymore.” He might have been kidding, but with nearly 1.5 million academics using his site, he probably wasn’t. A good sign for the other entrepreneurs in the room, last November, Price's company raised $4.5 million.

Total-Impact and 'Altmetrics'

Total-Impact is a new company that specializes in other metrics such as those Gunn mentioned. And they take it further. Type in a paper to their search engine, and they’ll tell you how many times it’s been tweeted (known affectionately as a “citwation”) or posted on Facebook along with other traditional statistics. These additional metrics are what is known as altmetrics. This is a new term for me. The idea behind it is that commercial success should be valued along with scholarly endeavor. According to Heather Piwowar from Total Impact, the next generation of science will be built on a new metrics infrastructure. And if you’re not on social media yet? As long as you publish somewhere, it’ll be out there and others will spread it for you.

“Not having a Mendeley or Academia.edu address will be like not having an email address is today,” she said.

#OpenAccessMonday

John Wilbanks is becoming the Open Access man who goes to Washington. In his talk Wilbanks related the story of #OpenAccessMonday. This is a Twitter hashtag which also became the name for a White House petition to extend the open-access policy that the NIH has in place to the other 15 funding agencies in government. The NIH’s Public Access Policy requires that all investigators funded by the agency make their research public within 12 months from the official date of publication. However, Wilbanks says that leaves $30 billion in funding from other agencies without such a policy.

John Wilbanks

John Wilbanks at 'StartUp Science'

The petition spread quick, picking up 5,000 signatures in the first day, and 15,000 in the first week. The 25,000 needed to garner a response from the White House came soon after. According to Wilbanks, he and a couple others are the only ones in Washington pushing for open access, compared to hundreds of lobbyists for the publishing industry. To leverage his efforts, Wilbanks is relying on an already powerful movement within the research community.

“We want to put the fear of SOPA into the White House on this issue,” he said, referring to the grassroots effort that stopped a congressional bill aimed at limiting the internet. “Know that they’re very well aware of us in the West Wing,” he claimed. “And they weren’t before.”

The conference went on to feature other topics such as “Ecommerce meets E Science” and “Big Data Science.” (Several of the presenters have been guests at mendelspod:Kevin Lustig of Assay Depot, Barry Bunin, CDD and Elizabeth Iorns of Science Exchange) The second day began with a roll of business plan presentations. The winners will be announced in October and awarded with some funding that Jackson raised from the Kauffman Foundation.

Jackson is to be lauded for tireless work in bringing together those who live in the future. It’s a young crowd with great ideas. Joseph is generous with audience participation, so talks tend to run over. And last minute speakers are squeezed in. It would have been nice to have more time for networking. One-on-one chats are as important as what happens over the loud speakers. Who knows? Perhaps the bit of chaos one feels at these events is a good thing. These are folks deep in the industry who want to go after the root problems-now.

John Adler of CurEUs is a practicing physician at Stanford. “The revolution will start with disillusioned insiders,” he rallied the crowd.

Watch for upcoming interviews with Joseph Jackson, William Gunn of Mendeley, Richard Price of Academia.edu, and John Wilbanks.

$1,000 Genome No Good

Author: 
Theral Timpson

There comes a time when powerful memes that have become widespread begin to lose their value. Is it that time for ‘The $1,000 Genome?’ Mark Boguski thinks so. At the first annual Clinical Genome Conference in San Francisco this week, Dr. Boguski from Harvard Medical School said that the term is actually fallacious. The price of sequencing has come down. And now there are many other considerations, such as the fact that genome analysis will be done several times over the course of treatment he said in a talk entitled “Pathology and the Third Wave of Medical Genomics.” According to Dr. Boguski, the first wave was SNP detection and the second was GWAS studies. Now the clinical genome has its own conference.

Put on by the always capable CHI, the conference has evolved into its present form (last year it was called Beyond Sequencing), and I’d venture a guess that it will go by the new name for some time to come. The room was full. The speakers were top experts from the front lines. I mentioned Harvard Med above, the Mayo Clinic was also represented as well as the Medical College of Wisconsin--the institution which treated Nick Volker.

The conference was perhaps more tweeted than a Justin Bieber concert. I urge you to follow the hashtag #TCGC for a play by play account by the prolific @KevinDavies, who (I think) somehow manages to tweet for @BioITWorld, and @GholsonLyon and others who’ll give you notes from each of the talks.

We are now watching the labor pains and anticipating the delivery of this enormous, complicated fellow, the clinical genome. The conception came over a decade ago, and the baby has grown and grown in complexity and value. Is it already born? Some at this conference would say yes. Some say we’re still getting there. What no one says is that it won’t be.

Some notes I took on the first day included the talk by the bioinformatics star, Atul Butte. We had Atul on the program recently and he talked about how the environment is a big part of our health. “Genetics loads the gun,” he likes to say, “and environment pulls the trigger.” At the conference, Dr. Butte, who is an MD as well as PhD researcher, talked more about the importance of focusing on the environment than I remember from earlier presentations. “The environment can be a perscription,” he asserted, noting that once we know our genome we can seek out conditions that will be good for our genes. “Environmental factors still beat any odds ratios that we’re looking at for genotypes,” he reminded us.

The thought came to me as Atul talked that it would be great to have a conference dedicated to just this topic of genomics and the environment. I mentioned this to Kevin Davies and he directed me to the GET, or Genomes Environments and Traits, Conference started by George Church at Harvard Medical School.

Atul said that “teaching is the biggest challenge” for the clinical genome. There is so much work to be done educating doctors who know little about genomics.

Dr. Boguski from Harvard Med picked up on a comparison made by Atul between the number of clinical geneticists and the number of radiologists. There are 1,000 clinical geneticists and you can add 2,000 genetic counselors for a total of 3,000 experts on the clinical genome. And there are 30,000 radiologists in the country. More and more, radiology is used as the example for genomics. Many years ago experts had to be trained to read an Xray just as someone will have to learn what to do with gigabytes of personal genomic data. Dr. Boguski said that it’s the pathologists, not the medical geneticists who will do the interpretation of the genome.

Then there’s the matter of incidental findings. Should they be reported to the patient? Dr. Robert Green from Brigham and Women’s Hospital again used radiology for comparison. Let’s say a patient has a broken rib and goes to the clinic, he proposed. An Xray is taken and is analyzed by the radiologist. “Do you think if the radiologist sees a tumor or something wrong with the heart he’s not going to tell the patient?”

Dr. Green further provoked the crowd by saying that medicine is not an exact science. “We need to recognize what a mess this pseudo-scientific field of clinical medicine is. It’s complete horse shit!”

“Physicians are only going to learn this when they have to,” Dr. Green says. “We have to send them reports. Even though evidence is insufficient, the clinician must still provide advice, patients must make choices and policy makers must establish policies.”

Again I urge you to follow the hashtag #TCGC for more insight on an exciting field. “We’re watching an industry grow up right before our eyes,” beamed the exuberant editor of Bio-IT World.

Kevin and his colleagues are not just watching this industry grow, they’re doing their part to shepherd it along. Davies has profiled most of the new big data and analysis companies that are emerging at BioIT World.

He’s also the author of a book, “The $1,000 Genome.” It appears the industry is ready for a new title, Kevin.

Here’s a suggestion, “The Clinical Genome: Coming to a Hospital Near You.”

The Economy Tops the List at BIO Convention

Author: 
Theral Timpson

Jennifer Boggs at BioWorld forecasts the annual BIO convention that began in Boston today. She compares 2012 with the biggest year for BIO, 2007, the year before the devastating economic crisis.

"Back in 2007, we had 400 public biotechs, and we were pretty much at the top of our game," she quotes Jim Greenwood, president and CEO of BIO. "Now we have 300."

Noting some good news about 2011 such as increased funding and about a dozen IPOs, Boggs reiterates the challenge with the embattled global economy. As with the recent Burrill Book, "Innovating in the New Austerity," the common theme among sessions is innovation, both in scientific pursuits and in business models.

Catch the full post here.

In the Shoes of the Biotech CEO

Author: 
Theral Timpson

To raise awareness of and preview the upcoming sessions at the BioExec Institute, Prescience (with UC Berkeley and Deloitte as partners) has been putting on some terrific discussion nights with thought leaders of the biopharma industry. Last night, at one of their typical hip venues in San Francisco, they hosted a panel discussion titled The Corner Office, What Is It Really Like to Be a Biotech CEO? Leading the discussion was Jim Schaeffer from Merck. The panel of CEOs were Pim Stemmer of Amunix, Rich Heyman of Aragon, David Pritchard of KaloBios, Gonul Velicelebi of CalciMedica, and Jay Short from BioAtla. These events are a great chance for industry veterans to pass on wisdom, and I jotted down some highlights from the discussion.

Corner Office

Source: Prescience Intl

Being Scientist an Advantage

The first issue that came up relates to my blog from the last Prescience event, Will Scientists Take Back the Pharma Industry? Herself a scientist from Torrey Pines Therapeutics, panelist and now CEO, Gonul Velicelebi, said being a scientist as CEO is an advantage.  It’s ideal if you have an MBA as well, but if you had to choose one, science gives you an edge. “Technology drove the investment. And science drives the business,” she went on.

Pim Stemmer took a direct hit at MBAs. “There’s a value to learning in practice and not in business school. CEO’s get a fair amount of abuse and the ability to think for yourself is extremely important.” Dr. Stemmer is a successful Bay Area biotech entrepreneur who pioneered the development of DNA shuffling, a technology which provided the basis for the spin-off of Maxygen from Affymax in 1997.

Motivation

The discussion went on to best ways to incentivize CEOs. BioAtla’s Jay Short said that in every company he’s been in, the science has been the biggest motivation for everyone. “Stock options have little relevance compared to the science,” he challenged. Jay hasn't done bad himself. After being courted to run Invitrogen, he opted for a $1 million signing bonus to be CEO of Diversa Corp which is now British Petroleum. With Diversa, Jay achieved the largest biotech IPO at the time of over $200MM.

The Board

How do you interact with the board, discussion leader Jim Schaeffer wanted to know. Dave Pritchard jumped in saying that a good board will be functionally diverse with each member bringing a deep level of expertise. He stressed that a functional board is preferred over a VC board. “There will always be tension between the CEO and the board,” he said. “This is a crazy industry, and CEOs have a tough job. A CEO has to go to the board and say, ‘there’s a 1 in 1000 chance we’ll make it and it will take 15 years.  But at the end we’ll get a billion dollars.  Who’s in?’”

Pandora’s Box-The Funding Issue

The hottest part of the discussion, on what turned out to be a very hot night on Market Street in San Francisco, came at the end. In an attempt to wrap up the formal part of the evening before networking and drinks, Prescience host Melinda Richter asked if there were any burning questions. She opened a bit of a Pandora’s box as a discussion about being CEO quickly turned into a lively back-and-forth around the room on how to get funding in bio these days.

Oleg Nodelman, a portfolio manager at the Biotechnology Value Fund, sat at the center of this conversation from his table in the audience. I recently heard Nodelman at a conference and he’s not shy. “The difference with this panel today and 15 years ago, is that everyone here is talking about exits.  It used to be that we were talking about building a great company.” This provoked immediate laughs in the group, perhaps half in acknowledgement and half in a disbelief of Nodelman’s naivety. But I don’t think Oleg is naive. He’s pushing for new (or older) values in biotech funding. Another member of the audience took him up on his comment asking why VCs aren’t creating 20 year funds. Oleg replied that people will take money wherever they can get it, which often means funding by shorter term funds.

A final issue emerged--as it has in recent conferences we’ve attended--and, as usual, with no answer: who is going to fund early stage companies? Oleg pointed to discussion leader Jim Schaeffer of Merck and suggested big pharma ventures would fill in. “Pharma venture is the new dumb money,” he joked.

During the networking part of the evening, I met Peter McWilliams, managing director of the VC company, Sanderling Ventures. Peter said Sanderling’s focus is entirely with early stage companies. “We’re very traditional in that way. This is what VCs have always done and we believe it’s what we should continue to do.” Peter confirmed that the industry is “absolutely capital constrained.” I asked if this meant he’s seeing better deals. “Yes, he said, but the problem is it’s much harder to get money.” In 2005, he recalled, there was $30 billion in VC funding. By 2010 there was half that amount. “When I check my email, let’s say I get 10 messages: five from companies looking for funding, say 3 from my wife, one junk mail, and one from a limited partner who has invested in the fund. Without hesitation, I pick up the phone and immediately talk to the limited partner.”

I couldn’t help but wonder during the evening who actually wants to be a CEO in biopharma these days with the tremendous current funding challenges. Is this a cyclical issue that will go away soon, or is there a structural problem to the funding system? If there is a problem, how will it be remedied? If it's just part of a cycle, a strong CEO who's been around is a big part of the answer to driving companies through the 'down' period. And who are we kidding? Everyone wants to be CEO.

There’s a natural synergy with the Prescience events and what we do at mendelspod.com. Their speakers are expert and the audience full of those seeking answers. Their educational program, the BioExec Institute, offers industry execs training in high level strategy, and best practices at a critical time. Catch an upcoming interview with Prescience co-founder, Melinda Richter in a discussion of the BioExec Institute and her involvement with the innovation incubators, the BioCenter in San Jose and the incubator at Janssen Labs in San Diego.

Life Science Version of "Cosi Fan Tutte" Plays in Napa, CA

Author: 
Theral Timpson

Recently I met Dr. Robert Lee Kilpatrick, co-founder of TVG or Tech Vision Group. Robert is an industry thought leader who’s been around the life sciences for a long time and produces global life science events. Robert sees himself as a biotech gadfly, or one who shakes things up. I might call him an impresario, one who produces high level events with flair and taste. Robert has made sure that I don’t refer to his meetings as conferences. What then should we call them?

Susan and Steve

Panelists left to right Oleg Nodelman, Susan Molineaux, and Steve Engle

Last week we attended TVG’s C21 BioVentures, a meeting to connect life science investors and entrepreneurs held each year in Napa, CA. Robert is entertaining and he goes for something that stands out above the normal run-of-the-mill show. The C21 is sponsored in part by the law firms DLA Piper and Latham & Watkins, and the Deloitte Recap consulting firm. The get together attracts many of the life science venture folks. Included were two sessions for start-ups to present their case to these investors. There were no keynote talks or single lectures, but rather one interactive panel after the other. And some of them were downright entertaining. If we push the metaphor a bit further, and say that the impresario, Dr. Kilpatrick, had produced an opera, this is my quick review.

Our interview with Dr. Kilpatrick at this year's annual C21 BioVentures

Set in the beautiful Meritage Resort just south of downtown Napa, and surrounded by vineyards sporting a vibrant spring green, the production really could be called a tragi-comedy. These are tough times for life science VC. Still, this is not a crowd to get depressed. The industry is more capital constrained than it's been in many years--maybe since its early days.

After a stimulating overture of wine tasting in the Meritage wine cave to buoy the spirits of the audience and singers, the opera’s opening song was sung by Dr. Kilpatrick himself, “We don’t make the waves, we ride them.” A quartet of pharma ventures followed. Highlights from their scene included “Your baby isn’t ugly, there’s just too many around,” sung beautifully and to applause by Dr. Steven Kuemmerle of Abbott Biotech Ventures and “We’re gonna walk before we run,” sung by Dr. Sam Wu of MedImmune Ventures.

A reproduction of the Dave Letterman Show played next with the “Top Ten Ways You Know You’re Not Connecting with that VC in Front of You” led by Mr. Brian Atwood of Versant Ventures playing “Dave.” Each of the ten reasons turned into trios for three of the leading VCs in the industry: “Contact in pharma said they’re not shopping,” “You believed the FDA in your pre-IND?” and “Bruce Booth just tweeted a no go.” They were decently delivered. Brian turned out to be a convincing “Dave” with an impeccable sense of timing and a nice flick to the wrist as he tossed each of the 10 cards to the back of the stage. Dr. Kilpatrick made a surprise appearance as band leader Paul Shaffer.

Here the opera took a tragic turn as the death of 50 or so VCs in the last few years was lamented and more deaths predicted. Indeed, when listening to “We haven’t reached the bottom yet,” there were audible sighs in the crowd. Currently there are about 50 life science VCs left, but it’s anticipated that in 5 years only 15 will remain standing. A lesson for the future was included in this lament in the form of two arias, the first by Dr. David Kabakoff of Sofinnova entitled “When you get feedback from the FDA, you better damn well listen,” and the second sung in fresh originality by Dr. Srini Akkraju of New Leaf, “There’s no reason for turning away from something good for the patient.” The panel finished off with a bit of nostalgia in a look back to the 90’s when almost every start-up was chosen for funding. Today, as we know, the opposite is true.

But as I say, this wasn’t a full on tragedy. The suggestions given for the future took me back to Cosi Fan Tutte, Mozart’s comic opera where two lovers claim that there loves are faithful forever only to be proven in a delightful plot that they are wrong. “Trust up-front is key for the VC,” “Why not consider a ‘no-exit’ model,” and “Big D (dilution) before big B (bankruptcy)” were sung to great enthusiasm. Cosi Fan Tutte is often translated as “they are all like that.” We could be talking about the VCs here in that way, none of whom took themselves too seriously. The final aria brought the house down, “Don’t listen too much to VC’s doom and gloom.”

If one was too overcome with grief, or just plain bored, wine receptions surrounded the opera. In addition to the first night’s wine tasting, each of the two days were followed with networking sessions with the finest libation, the first of which was held at the impressive Chateau Domaine Carneros. Standing on the porch of this grand house, a glass of dry Champaign or an elegant pinot noir in hand, looking out over the vineyards in the twilight, we all toasted to each other.

A flight of whites to the present plight, a flight of reds to our future meds.

synbio

TVG co-founder, Dr. Birgit Weskamp

NASA and Singularity U Partner to Create SynBio Launchpad

Author: 
Theral Timpson

In a first of its kind, a new incubator modeled on the well known Y Combinator has been started for emerging synthetic biology companies. SynBio Launchpad is a joint effort by Singularity University, provider of higher education in exponentially advancing industries, and their landlord, NASA. The program came about from a discussion between Andrew Hessel, co-chair of SU’s Biotechnology and Bioinformatics track, and John Cumbers, Deputy Managing Director of Synthetic Biology at NASA. Intending first to put together a weekend business plan competition, the two found support from both their institutions and private investors to fund the four month program. Last Thursday the “Bio Combinator” officially kicked off with the announcement of three fledgling participants.

synbioSource: Singularity University

Synthetic biology is an exciting frontier with great promise for solving many of the problems that stare us in the face as the world’s population continues to increase at an unsavory rate. When Craig Venter showed he could create a synthetic life form, there was a wee bit of hoopla about the creation of bioengineered microorganisms that will be able to produce new drugs, destroy cancer cells, detect toxic chemicals, break down pollutants, and provide less expensive and sustainable food for the growing number population. The most promising immediate commercial application of synthetic biology has been in the area of biofuels. Investors, including the US and other governments, rushed to support the production of hydrogen through newly engineered bacteria or plants.

Yet as of today, none of these well funded enterprises has delivered. Details recently emerged showing why the synbio company, Amyris, is putting a halt to its biofuels business. The company has been charging an average of $29 per gallon, a price which cannot compete with petroleum-based diesel. Nor is this high price enough to bring the products’ income statement to break even. Last week, Wired Magazine reported that the House of Representatives seeks to ban the Defense Department from making or buying an alternative fuel that costs more than a “traditional fossil fuel.”

What, I asked on my way to the kick-off event at the NASA Ames campus in Mountain View, could these new companies be up to? Yes, the promise is there, but the challenges seem incredibly daunting. This is not an NIH or DARPA funded university program. This is making and selling products in the real world. Well funded companies like Amyris and George Church’s endeavor, LS9, haven’t yet commercially succeeded. How are these yet-to-be funded start-ups going to fare?

As it turns out, none of the three participants are working on biofuels. Out of dozens of applicants, the chosen start-ups are Evolutionary Solutions, Modern Meadow, and SoilGene. Their names are giveaways to what they attempt. Evolutionary Solutions is developing a genome synthesis device using microfluidics. The company was founded by the young team, Kettner Griswold and Paul Sebexen, both from Georgia Tech. Griswold and Sebexen have already been working on their device which they say will change the oligo and gene synthesis industry by drastically reducing the cost of goods. I know the oligo business well and am familiar with the low prices in this commoditized industry. Still, my skepticism couldn’t shake the confidence of Kettner and Sebexen as they eagerly explained their technology. It was one of those moments where ask to yourself, who knows--they’re young and perhaps they could deliver a disruption. Both of them are Thiel Fellows who each received $100,000 to drop out of the university and be entrepreneurs.

Modern Meadow, co-founded by Andras Forgacs, is applying tissue-engineering techniques to produce high volumes of animal protein for food and textiles. “You mean, burgers grown in the lab,” I ask Forgacs. “That’s right. But we need a better name than 'lab meat.' He encourages me to brainstorm with him. The best we come up with is 'sustainable meat.' “Think about it,” he urges with undeniable exuberance, “animals are highly inefficient manufacturing plants.” OK. He has a point. Forgacs, who has already had success with a tissue company that just went public, Organovo, can go on and on about the environmental impact and more humane ways of harvesting animal protein. He says that the company could produce the lab burgers right away, but for obvious marketing considerations, they are going to start with leather production. It is easier for the consumer to buckle up a belt produced in the lab than plow into a juicy steak from a 'system' that didn’t graze on grass. This weekend, I found Modern Meadow to be a great conversation piece at parties. Next time you’re out at the pub with your friends, ask them if they’d be ok with a synbio burger.

The night ended before I could talk to the founders of SoilGene, Zachary Apte and Robert Lim. But the press release put out by SU says the company “combines metagenomic and bioinformatic approaches to survey land opportunities for he natural resources and agriculture sectors.” Nice and vague.

At the end of four months, the three companies are supposed to have a prototype of their products. For lab space, they will be housed at both the DIY Lab, BioCurious, and at Triple Ring Technologies over in Newark. Priding themselves on being innovative and risk taking, Triple Ring sees the program as a great fit for their own vision. The new founders will be rubbing shoulders with an established company and also mentored by some of the best researchers and entrepreneurs from the Bay Area synbio community. Many of the mentors showed on opening night and gave the launchpad a solid launch itself. Whether these three companies succeed in their present iteration wasn’t on the minds of the SU staff in the room. “It was always about starting companies, not just the classroom,” said Managing Director of New Venture Development at SU. “We want to build a synbio community that will create companies to change the world.”

“Ours is not a near term focus,” added Modern Meadow’s Forgacs.

Join us in the future for a series of podcasts on synthetic biology. We will be speaking with Forgacs, Cumbers, Hessel, and others associated with Synbio Launchpad.

Will Scientists Take Back the Pharma Industry?

Author: 
Theral Timpson

“Do not fear to be eccentric in opinion, for every opinion now accepted was once eccentric.” Bertrand Russell

Retirement can do a lot for someone who’s been bottled up in a big company for thirty years. Especially if they don’t actually retire. Bernard Munos spent thirty years at Lilly where for the last ten years he was focused on disruptive innovation. But it didn’t happen there. So he’s out to see if he can ignite a fire for disruption in the industry before it’s too late.

Leading as full a life as ever, Bernard travels the world with his ideas about what’s wrong with the pharma industry, and more importantly, how to fix it. One week in India, the next in Dubai, then off to Europe, his busy schedule brought him back to the Bay Area this week for a ‘Fireside Chat’ hosted by the BioExec Institute. Though we had Bernard on the show for a two part series recently (Part I and Part II), it’s hard to pass up the chance to hear one with such a provocative message. I was also anxious to see the crowd he could draw and what response he’s getting.

Bernard can draw a crowd. In what felt like a grassroots gathering, there were folks from all over the industry, and not just the typical networking crowd. CEO’s (including Sangamo’s Edward Lanphier and Susan Molineaux of Calithera) and other high level executives from local Bay Area pharma and biotech filled the room at the TRES Lounge in San Francisco. And there was discussion.

All over his material like a seasoned campaign veteran, Bernard has become quite comfortable with his presentation. He lets the audience choose from a list of issues the industry is facing, knowing that no matter which door you walk in, you’ll end up in the same place. The core problem for Bernard is that the industry has had a change in values. These values are set by the CEOs of the big pharma companies. What Munos doesn’t come right out and ask, but hangs at the end of each of his provocative turns: When are the industry’s participants-and more importantly, scientists--going to take back the industry?

The CEO’s of big pharma are for the most part businessmen and not scientists, he says. Most have little appetite for risk and bold innovation. Bernard flips through slide after slide seemingly at random with charts and graphs showing an industry poised for disruption. With facts such as that near 80% of prescriptions are filled by generics today, Bernard’s hypotheses are hard to reject. When members of the audience push him further on different points, Bernard is only too happy to oblige and find further worrisome facts.

The name Art Levinson (Chair and former CEO of Genentech) came up several times as an example of a leader who was himself a scientist and had a large appetite for risk.

“Once I heard Art give a presentation,” Munos recalled. “And it was overwhelming. Here was a CEO who talked about deep science with passion. I could not help make comparisons, and think how empowering he must have been for scientists working at Genentech, because no matter how bold they were, they could not be bolder than the boss.”

A former employee of Genentech who worked under Art was in the audience concurred that he was a leader driven by passion, but suggested that one of the big problems is that there aren’t enough biological targets to go around. That the industry had reached a certain point of saturation.

“We would get new hires,” he went on “and they would sit down with us and see the drug targets that we were pursuing and say ‘these are the same ones we were working on over at you-name-it company.’” (I didn’t catch the name of the commenter.)

To respond, Bernard was ready with another slide showing the waves of innovation that have driven the industry for the last sixty years, graphed per disease. In one instance there was a flood of new drugs for schizophrenic disorders in the 60’s and 70’s, and then a 15-year drought.

“This is the way science goes,” Munos reminded the crowd. “Biology is not predictable. CEOs who insist that it should be will end up wasting tons of money chasing innovation where it is not ready to thrive”.

Bernard says that about every 15 or 20 years every industry faces radical disruption. That moment is here for pharma today. He’s even willing to talk about which big pharma companies will survive the next few years and which won’t. He’s thinks Novartis and Sanofi are taking necessary steps to avoid catastrophe, but is much less sure about AstraZeneca and Pfizer.

The audience was engaged and most of those who spoke up were scientists. I had the feeling that these were folks who cared about the bigger picture and were determined to take on Bernard’s challenge. To take back the industry for science.

I should mention the UC Berkeley BioExec Institute who put on the event. The Institute is housed over at UC-Berkeley’s Center for Executive Education and provides Director and VP-level executives with training to develop leadership skills in the industry and learn new tools for marketing and branding. The program is taught by industry leaders, such as Bernard, offering attendees six days of interactive programming from October through December. The fireside chats are led by Institute teachers and spaced throughout the year. Former speakers/panelists have been Paul Hastings, Board Chairman for BayBio and CEO of OncoMed Pharmaceuticals and Barbara Handelin, CEO of BioPontis Alliance (Listen to our upcoming interview with Barbara).

Bernard calls himself the Apostle of Innovation. Perhaps this religious term is a bit out of place in a scientific industry. But going with his allusion, the Voice for disruptive change is finding followers.

Listen to a two part interview with Bernard. Part 1 Part 2

An Ambassador for Art and Science

Author: 
Theral Timpson

We keep running into scientists who are artists as well. A few months ago, I wrote a blog, Art and Science, exploring the idea of the renaissance person, someone who is proficient at many different disciplines. If scientists are to become experts in their field, must they proceed at the exclusion of other interests, I asked. Since then we’ve met a few more successful scientists who are proficient as artists as well.

Philippe Lamesch is a young scientist and artist from Luxembourg. Receiving his Ph D at Harvard Medical School, Philippe then came to California to work at the Carnegie Institution for Science at Stanford as well as at the Luxembourg Trade Office. In 2006 Luxembourg began a new Personalized Medicine Initiative, and Philippe has made good headway seeking American partners for his home country’s assertive move into bio.

While in Boston, Philippe became interested in the medium of print making and began developing his own art in copper etching and monoprinting. In California, Phillipe became a part-time artist in residence at the Kala Art Institute in Berkeley. His works have been exhibited in shows in San Francisco, New York City, and Luxembourg City. He was twice a finalist at the international art competition “XXIeme Biennale d’Esch” in Esch/Alzette, Luxembourg. Recently he was picked by the digital art gallery, Kiptonart in New York City, as one of “Ten Artists You Need to Know Now.”

We met up with Philippe at the Kala studio in Berkeley to learn more about how copper etchings are made and to see him at work. In this short interview, Philippe talks about his work as scientist and artist and the parallels between the two.

BioGENEius Competition Shows Sophistication of America’s Future Scientists

Author: 
Theral Timpson

“It’s ok to be a geek. Be proud of your nerdy interests. We need you.” David Lacey, Bay Area BioGENEius Challenge emcee and former site head, Amgen San Francisco

What did you do for your high school science project? Let me tell you what Natalie Ng from Monta Vista High School in Cupertino, CA did for her’s this year. She developed a novel biomarker discovery tool to identify clinical signatures of cancer from statistically deconvoluted expressions. And Nikhil Buduma of Bellarmine College Prep in San Jose--he found that the pertussis toxin in a vaccine for the whooping cough was inhibiting lymphoscyte trafficking in lung tissue. This causes a delayed response to the vaccine of up to four weeks, making an infant unnecessarily vulnerable. Not bad, eh?

Each year America’s top high school science students are welcome to participate in the <a href=http://www.biotechinstitute.org/programs/9" target="_blank">International BioGENEius Challenge, a competition recognizing original research in biotechnology. The competition proceeds in stages, first at the local level, then on to national, and culminates in the international competition (Canada, United States, Australia) at the annual BIO convention. The level of leading edge science that high school kids these days are involved in baffles me and gives us all a nice shot of optimism for the future.

When I got a call from the <a href=http://www.baybio.org/about/about-baybio-institute" target="_blank">BayBio Institute, home of the education and entrepreneur programs of our local life science trade group, asking me if I wanted to come to this year’s competition, I jumped at the chance. Last year at the BayBio convention I talked to a couple of the twelve local competitors and got a glimpse of the level of sophistication of the projects. This would be a great chance to see some cool science students again and show them off to a wider audience.

As with last year, what struck me most was the extraordinary high level of the students’ work. Given five minutes to present their projects to two groups of judges (local industry veterans and academics), these high-schoolers showed impressive poise, brilliance, and confidence in their grasp of the subject matter.

I sat in on a few of the presentations and learned about new anti-cancer compounds and drug targets for alzheimer’s.

“These could be Ph D thesis projects,” said Amena Rahman, one of the judges and a friend of mine.

I expected the students to show some frustration with the short time they had, but no. The presenters I saw used all of their time and finished within a few seconds of the five minute mark. Then there were two minutes each for questions by the judges. The students answered these questions with an impressive knowledge of their project, often having a chance to explain why they didn’t pursue this or that angle. The only limiting factors for these projects were budget and time constraints, not the students’ education.

“I could have used a microarray for this, but it was too expensive for my school,” one student pointed out.

When asked why she didn’t do some 6, 12, and 18 hour experiments in addition to her 24 hour work, one student replied, “I had to go to my other classes. I couldn’t check it that often.”

Other projects included testing deer antler material on the proliferation of endothelial cells. Vishnu Shankar, also from Monta Vista High School and showing the first bit of hair on his upper lip, presented an algorithm for simulating the onset and spread of a pandemic. Okay then. If I’d been in a different room and didn’t know about the competition, I’d think it was a presentation to members of the World Health Organization.

Presented here are interviews with Natalie and Nikhil, the 1st and 2nd place winners (there were three winners out of 33) of the local competition. They talk about their individual projects and their plans for the future. (Check out the confidence level.)

In addition to the presentations and competition, BayBio treated the students to a keynote speaker and the chance to quiz a “career panel.” <a href=http://www.calithera.com/about" target="_blank">Susan Molineaux, CEO of Calithera Biosciences, a company developing cancer therapeutics, used the keynote to relate stories from her own life. Her father, who’d made it from nowhere to Columbia University, gave her a microscope at the age of eight. Dr. Mullineau’s path went from academic research into industry, and she was keen to let the students know that she had followed her passion.

“I couldn’t leave a problem alone--I just wanted to know,” she said of her time as a student and then as a researcher in the lab of her mentor, the Nobel Laureate, Richard Axel. “Find a mentor,” she advised.

A panel of scientists led by Dave Lacey, formerly of Amgen, discussed how each of them chose their careers.

What’s the difference of working in academia versus industry, the students asked. And how do you know when it’s time to change to something else?

Answers came back assuring the students that they could pursue a career in science and maintain other interests as well.

“We’re still thinking about what we want to do when we grow up,” said Paul Kassner, who had worked at more failed than successful biotech start-ups before becoming Director of Research at Amgen.

The team at the BayBio Institute helped by Amgen's primary sponsorship did a great job with the competition. It’s one of the nicest events I’ve been to in a while. Here were industry insiders volunteering their time and recognizing these promising scientists of tomorrow at a tender time in their life. It was obvious that the inspiration was flowing in both directions.

“The stuff these kids are doing puts my high school project to shame,” said one of the panelists to me as the students milled around after the event. “Know what I did?" he asked. "I took a piece of bread and wiped the bathroom and grew mold!”

Tumor Heterogeneity and Personalized Medicine

Author: 
Eric Schuur

My recent blog post, Tumor heterogeneity, revealed…, discussed the New England Journal of Medicine article by Gerlinger and colleagues describing the genetic heterogeneity found both within a patient’s individual tumor nodules and between spatially separate nodules. There has been a substantial amount of discussion of this work and angst about how it might signal the end of personalized medicine even before it really got started. I don’t believe that will be the case at all. To the contrary, this paper made interesting contributions in three conceptual areas that may help pull the field forward. These areas are the 1) relevance of prognostic gene expression profiles, 2) the nature of “driver” genetic mutations, and 3) the pathogenesis of cancer itself. All of these areas are, in my opinion, very important to make headway in before personalized cancer medicine can become a truly effective tool in medicine.

Heterogeneity in gene expression profiles across the tumor specimen

The result that most seized on to proclaim the demise of personalized medicine was the finding that gene expression signature from spatially separated parts of a tumor nodule yielded different assessments of prognosis. The implication is that a single biopsy specimen is inadequate to generate an accurate prediction of clinical course or response to treatment. Most likely that is at least partially true. However, the issue is with sampling, rather than the molecular biology. We have known for decades that tumors have variable histology within their mass, with some regions indicating poorer prognosis than others via their histologic grade. Rather than reflecting a conceptual disconnect that dooms a new paradigm, it looks more like a technical problem to solve, which should be no surprise along this new path.

Convergent evolution

Both the Gerlinger paper, as well as others (e.g. Walter et al, NEJM), using NGS have now demonstrated that within a single patient the same gene can be found to be mutated multiple independent times, suggesting that this mutation creates a change in gene function that participates in the development of the cancer. This had not been shown in humans before. This finding will be useful for clinical diagnostics and it may be game changing in basic research. In clinical diagnostics identification of a multiply-mutated gene would give additional confidence that the damage it represents is causal and may help select targeted therapy. In basic research, identification of such genes would represent novel evidence of the causality of specific genetic changes in the disease process. This type of evidence is a smoking gun, a sign post saying “Needs to be mutated to reach this disease state”. This type of evidence, which only deep sequencing can yield, is a new and useful application of NGS that was not previously available.

Pathogenesis

The picture that the Gerlinger paper, Walters paper, and others paints is one of clonal evolution of cancer. This type of work paints this picture with clarity that has not been achievable before. What is striking to me is that these results make it harder to ignore the concept that these genetic alterations, as important as they clearly are in the progression of cancer, may not be the cause of cancer. They beg the question, “what initiated this evolutionary process?”. Certainly, oncogenes, tumor suppressors, and the like are a part of cancer pathogenesis, carrying the developing disease along. But it seems to me that there is still a “first cause” of some sort that we have not put our collective fingers on. Genomic instability is certainly key, but then what is the genesis of the genomic instability? What are the inputs that kick this process off? Efforts to answer these questions will move us closer to effective treatments for cancer and other diseases that may share these pathogenic processes.




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