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致力于生物技术投资;生物技术的福音传道者.
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January 24

Five Biotechnologies That Will Fade Away This Decade

Zt from Stephen Friend 1/6/10

[Editor's Note: This is part of a series of posts from Xconomists and other technology leaders from around the country who are weighing in with the Top 5 innovations they've seen in their respective fields the past 10 years, or the Top 5 disruptive technologies that will impact the next decade.]

We look at amazement at strange technologies from the past. How did people function in worlds with quill pens or connect with each other by Morse code and telegrams? Within biotechnology’s short history, we have already seen approaches from the ’90s such as Southern blots that look at sizes and amounts of DNA, and antisense therapies, are being replaced. I guarantee you at least 50 percent of what we think of as the enabling technologies and approaches to biological knowledge will be relegated to museum displays in the next five (OK, maybe 10) years.

Here are five that are ready to be replaced:

1. Genome-Wide Association Studies (GWAS) studies based on single nucleotide polymorphisms (SNPs). This is the approach that does high-speed scanning for markers across the complete sets of DNA, or genomes, among many individuals to spot small variations that might be associated with a particular disease. Single nucleotide polymorphisms (SNP) analysis isn’t going to last long as a major driver of biologic insight. Within the next one to two years, people will wake up to “ITEGS”—”It’s the entire genome, stupid.” Technologies are poised to allow analysis of variations in thousands to even hundreds of thousands of people. Do not be surprised when all the people with a disease such as Huntington’s are analyzed for DNA alterations across their entire genome. Groups such as Cure Huntington’s Disease Initiative are already preparing for this world.

2. Proteomic Approaches as an end solution to understanding diseases: Many people believe that following quantitative proteomic analysis which looks at a wide array of proteins that carry out the functional instructions from DNA, will be the key to the next wave of biologic insights. Many today yearn for a world where we could know the levels of all the proteins in a cell to finally functionate the cell—as if knowing all the elements allows one to understand all chemical structures—NOT. It’s unlikely the levels of protein components are the sufficient keys to the puzzle. It’s more likely they will become yet another layer of key information along with readouts on metabolites and RNA. The real decoding of diseases will be driven by those that know what to do with the component lists—be they DNA, RNA, or proteins. The next wave of insights will be in the hands of those that can build network models of what went wrong in the disease states.

3. Biomarker signatures as commercially viable robust markers akin to cholesterol or estrogen receptor positivity for breast cancer. Identifying signatures of certain genes or proteins is currently all the rage among those finding the right drug for the right patient. For the most part, these signatures are done on populations of hundreds to thousands of patients. Many hope to turn these into definitive markers that will guide treatment over decades. But hey VCs, you might want to try investing in other areas. It is likely that all these signatures will be replaced continually. Each time a larger sample is gathered it will allow a refinement that warrants replacing the last signature. Moreover, each time scientists can subdivide patients into more coherent sets of patients new markers will be more predictive. Prepare to live in a world where the platform owners and database organizers have a greater proportion of the value proposition. VCs would be smart to invest in platforms and those who can offer up access to the evolving models of disease from which will spring the dynamic biomarkers.

4. Indications for drugs will be determined by clinical trials performed by the biotech/pharma company developing the therapy. Most drugs today get approved by the FDA even if they only work in a small fraction of patients. This practice is going to end, because once a drug is approved with regards to its safety profile it may well be that the definition of who should get the drug is modified continuously by large trials organized by payers and patients. In real time, these groups will evolve the criteria of who should get which drug by participating in ongoing trials even after the drug has “been approved.” This is something to look forward to, as it will take much of the trial-and-error nature out of prescription medicine. It will be a world of real evidence based therapies

5. Hunter-gatherer approaches where large groups collect massive clinical and genomic information and expect that they as the data generator will be the data analyzer. Funding of large cohort studies like the famous “Framingham Heart Study” that has been following the health of patients in Framingham, MA for more than 60 years have been extremely valuable. The old methods used for these studies assumed that the analysis would be done by the small group of primary collectors of the samples and data. This model, too, will be fading as distributed groups of scientists evolve the knowledge faster and more efficiently than those who generated the data. Remember, this is already how physicists work today. Also remember Jim Gray of Microsoft Research, and his ideas on “The Fourth Paradigm,” which says that scientific theory, experimentation, and large-scale computational simulation will begin to interact and reinforce each other in ways that will speed up scientific progress.

We will need to do biology research in fundamentally different social contexts as we move into this next decade. This means biologists will need to start pooling their knowledge through social networking channels, not unlike how computer scientists have long done for open source software development.

Stephen H. Friend is president, CEO and a co-founder of Sage Bionetworks, an international genomic research collaborative.

January 18

有希望就好!

发一封邮件,播种一个希望。

January 09

House, travel, and dream

1
只要半个平米的价格,就能将日韩新马泰都逛一圈;
一两个平米的价格,欧美列国也转回来了;
几年下来,等你周游完全世界,可能钱还没花完一个厨房的价钱;
但却有可能已经改变了世界观。

December 31

Nanotech, Single-Molecule Methods, Personalized Medicine Remain Top of Mind for VCs(ZT)

This is part two of a two-part series examining the venture capital landscape in the life science research tools and molecular diagnostics markets. To read part one, click here.

NEW YORK (GenomeWeb News) – Despite the recently soured economy, venture capitalists have remained relatively optimistic about investment opportunities in the life science research tools and molecular diagnostics sectors, according to industry insiders.

In particular, the VC landscape for life science tools and molecular diagnostics may be buoyed by advances in nanotechnology, particularly nanofluidics, high-throughput and single-molecule genomics and proteomics, and technologies enabling individualized health, venture capitalists from three early-stage life science investment firms told GenomeWeb Daily News recently.

However, the VCs also said that their optimism was tempered by a host of inherent problems with investing in the research tools space – in particular, higher risk aversion among potential acquirers and the lack of an IPO market has dampened the chances of early-stage investors landing a profitable exit. In addition, pending public policy surrounding the way early-stage investments are taxed has the potential to discourage VCs from taking a long-term investment stance, they said.

So how are life science tool investors skirting these issues?

"We're very selective right now with our investments in companies that are going to be extremely capital efficient," Josh Phillips, a general partner with Boston-based Catalyst Health Ventures, told GWDN recently. "We've just launched a new incubator in the medical technology space where we'll be leveraging a single team and doing multiple projects in a very capital-efficient way – outsourcing where we can; reducing overhead; not incurring fixed costs."

Catalyst has adopted this strategy primarily to combat what Phillips perceives as a dwindling number of potential exits for investors due to the reluctance of potential technology acquirers to buy in anything but well-established companies with relatively mature technologies, as well as a nearly non-existent IPO market.

Sue Siegel, a partner with Menlo Park, Calif.-based Mohr Davidow Ventures, agreed with a general consensus among VCs that the life science tools space is "not completely immune to the financial meltdown," and that investors have become much more selective.

"The great news about times like this is that huge things come out of people," Siegel said. "There is real creativity, and there is no scarcity of innovation. You see a lot of different technologies coming through, and you scratch your head on some and wonder how they are going to get to market. You sort of get a buzz around a few, but you just don't get many like that. So our investments haven't stopped; we've just become more selective about what we invest in."

Siegel also echoed Phillips' qualms regarding the dwindling number of potential exits for investors by also citing an increasing reluctance by pharmaceutical companies to create early-stage partnerships.

"In the past, pharma was willing to take more risks and collaborate with very small innovative companies that had technologies that they believed would be very enabling," Siegel told GWDN. "Now, pharma will do some collaborations, but they won't pay as much for them. They won't get into the complexity of past deals. And they're looking for the technologies to be much more turn-key."

Despite this, she said that pharma is looking much more closely at, and may be willing to make acquisitions and bigger collaborations in the molecular diagnostics space, including pharmacogenomics and pharmacogenetics. Part of the reason for this, she added, is that pharmaceutical companies in general are eager to identify companion diagnostics that can be coupled with their compounds or research areas of interest to help guide treatment and efficacy.

"We're seeing a lot of big companies looking at this space," she said. "Novartis is building out its molecular diagnostics efforts, and looking to collaborate, so they might become acquisitors. Abbott took that path years ago, and continue to look," said Siegel. "Roche has also had a presence because of their molecular diagnostics division, and we've seen some sniffing around from Sanofi-Aventis, Pfizer, and Johnson & Johnson, among others."

Within the molecular diagnostics space, Siegel believes the market is moving toward the convergence of "online tools that will enable behavior change in people like you and me, so when they go online they are able to use tools that allow them to engage.

"It's about more than just biomarkers, it's about individualized health – business models that combine science and the ability to interact online," she added, citing MDV portfolio company Navigenics as an example. "It's about understanding your predispositions to certain actionable conditions."

Steve Gullans, a managing partner with Boston's Excel Venture Management, agreed that "innovations around reducing costs and improving outcomes are a very high priority. In the past, if somebody brought in a new device that was absolutely going to make diagnosis or treatment better, you didn't ask so many questions about the economics. Today, the economic model is as important as is the technology," he said. "The acquirers of these, the big companies, will be doing their own economic analyses."

Catalyst's Phillips also pointed out another burgeoning problem within the molecular diagnostics space: a lack of synergy between diagnostics companies and tool providers.

"There is this reliance upon each other where the tool providers, the platform technologies, are trying to figure out how to do diagnostics; and the diagnostics companies are trying to figure out which platform to perform the diagnostic on," Phillips said. "That has yet to be figured out."

Both sides, he said, are not demonstrating as great an understanding about the other as needed to progress the space. "The two of them have to go hand in hand," Phillips said. "That is going to be a point of convergence going forward, where these two sides are going to have to get together to figure this out."

Beyond the molecular diagnostics space, other areas being eyed by VCs include nanotechnology, especially nanofluidics, and higher-resolution and higher-throughput analytical techniques in genomics and proteomics.

"We're quite bullish about the opportunities where you see materials science, physics, nanofluidics, and chemistry coming together," Gullans said. "We're seeing lots of opportunities of what we're looking for in the tools space – nanofluidic devices; less expensive detection systems; high-throughput genomics and proteomics – just giving more data per dollar. As with all early technologies, though, there is always a learning curve about what it is good for, and where it might provide ambiguous answers."

Gullans also said that the DNA sequencing space is evolving the most quickly "simply because the cost per base is plummeting. It's impossible to pick a winner, right now, though. If you have to pick the company that's going to be the winner five years from now, you just couldn't pick that today."

Areas of interest to Siegel and partners at MDV include technology platforms that can examine biology at the single-molecule or single-cell level, and the firm has already demonstrated its affinity for that space by investing in nanofluidics company RainDance Technologies; single-molecule sequencing outfit Pacific Biosciences; and cancer diagnostics startup On-Q-ity, which is using technology that captures and examines single circulating tumor cells.

"That's where it's all headed – single-cell analysis, single-molecule analysis, really trying to build up our understanding biology from the single cell, versus where we've always had it before, which is the population," Siegel said. "Pharma companies are definitely looking at creating models along these lines."

Siegel also cited the need for tools that enable fast, inexpensive studies around stem cells and siRNAs.

"Lastly, we're looking for tools that potentially could replace PCR, and do it in an isothermal fashion where you wouldn't have the cycling potentially occur," Siegel said. "That's a tough one, though, because will it truly be able to replace the standard that has become PCR? Are you willing to take on that challenge?"

To be sure, there is no shortage of increasingly entrepreneurial academic scientists that are willing to take on that challenge, among others. But they won't be able to do it alone and will invariably need increased collaboration with industry, according to Catalyst's Phillips.

"I think part of the issue is that you have the established platform guys – Life Technologies with PCR, which is the gold standard; and Illumina and Affy with established assay technologies, and platforms that perform those technologies," Phillips said.

"It's going to be very difficult for a new platform to come along and displace those technologies, because they are the accepted standards," he said. "They're behemoths now. Those companies have huge sales forces, and the technologies are ubiquitous."

December 28

小岛

For Gilbert, home was no longer a place of sweet sanctuary.
For now that he had seen something of the world,
he could see how small his island was.
Every day, he could feel his hopes for the future shrink within its borders.
And with it, his potential.
But then, hopeis often the last thing to die in a man.