A very big challenge for biopharma

Loose coupling and biopharma:
[Via business|bytes|genes|molecules]

A few days ago, via the typical following of links that is typical of a good search and browse section on the interwebs, I chanced upon a discussion about a presentation given by Justin Gehtland at RailsConf. The talk was entitled Small Things, Loosely Joined, Written Fast and that title has been stuck in my head ever since. Funnily enough, what was in my head was not software, and web architectures, cause today, I consider that particular approach almost essential to building good applications and scalable infrastructures, and most people in the community seem to understand that (not sure about scientific programmers though). What I started thinking about was if that particular philosophy could be extended to the biopharma industry.

Without making direct analogies, but without suspending too much disbelief, one can imagine a world where drug development is not done in today’s model, but via a system consisting of a number of loosely coupled components that come together to combine cutting edge research and products (drugs) in a model that scales better and does a better, more efficient job of building and sustaining those products. One of the tenets of the loose coupling approach to scalable software and hardware is minimizing the risk of failure that is often a problem with more tightly coupled systems and in many ways the current blockbuster model is very much one where risk is not minimized and one failure along the path can result in the loss of millions of dollars. I have said in the past that by placing multiple smart bets, distributed collaborations and novel mechanisms (like a knowledge and technology exchange), we can reboot the biopharma industry, reducing costs and developer better drugs more efficiently. I don’t want to trivialize the challenge, the numerous ways in which the process can go wrong, and the vagaries of biology, but resiliency is a key design goal of high scale systems, and is one we need to build into the drug development process, one where the system chooses new paths when the original ones are blocked.

How could we build such a network model? I know folks like Stephen Friend have their ideas. Mine are ill formed, but data commons, distributed collaborations, and IP exchanges are a key component especially in an age where developing a drug is going to be a complex mix of disciplines, complex data sets and continuous pharmacavigilance. I can’t help but point to Matt Wood’s Into the Wonderful which does point to some of those concepts albeit from a computational perspective


Designing great and awesome tools for researchers to use will be critical for successful drug development. But there also has to be a cultural change in the researchers themselves and the organizations they inhabit.

One is that the tools have to work the way scientists need them to, not what works well for developers. This is actually pretty easy now and many tools are really starting to reflect the world views of researchers in biotech, who, more times that expected, are somewhat technophobic.

This leads to the second area- researchers often need active facilitation in order to take up these sorts of tools. They need someone they trust to actually help convince them why they should change their workflows. Most will not just try something new unless they can see clear benefits.

Finally, the last thing is better training for collaborative projects. Most of our higher education efforts for training researchers makes them less collaborative. They are taught to get publications for themselves in order to gain tenure. Plus, with the competition seen in science, letting others know about your work before publication can often be harmful Large labs with many people often can quickly catch up to a smaller lab and its work.

Like in the business world, being first to accomplish something can be overtaken by a larger organization. So, many researchers are trained to keep things close to the vest until they have drained as much reputation as possible form the work.

But many of the difficult problems today can not be solved by even a large lab. It can require a huge effort by multiple collaborators. Thus, there is a movement towards figuring out how to deal with this and assign credit.

Nature just published a paper by the Polymath Project, an open science approach to the discovery of an important math problem. They addressed the problem of authorship and reputation:

The process raises questions about authorship: it is difficult to set a hard-and-fast bar for authorship without causing contention or discouraging participation. What credit should be given to contributors with just a single insightful contribution, or to a contributor who is prolific but not insightful? As a provisional solution, the project is signing papers with a group pseudonym, ‘DHJ Polymath’, and a link to the full working record. One advantage of Polymath-style collaborations is that because all contributions are out in the open, it is transparent what any given person contributed. If it is necessary to assess the achievements of a Polymath contributor, then this may be done primarily through letters of recommendation, as is done already in particle physics, where papers can have hundreds of authors.

We need to come up with better ways to design useful metrics for those that contribute to such large projects. Researchers need to know they will get credit for their work. As we do this, we need to also help train them for better collaborative work, because that is probably what most of them will be doing.

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Changing social rules

10 Golden Rules of Social Media:
[Via Nonprofit Online News]

Yes, the title is linkbait, but I like it anyway. Aliza Sherman has been doing this almost as long as I have and her digestion of 20 plus years of experience into 10 Golden Rules of Social Media are utterly simple and powerful. They could easily be a checklist for any social media project or campaign: (1) Respect the Spirit of the ‘Net. (2) Listen. (3) Add Value. (4) Respond. (5) Do Good Things. (6) Share the Wealth. (7) Give Kudos. (8) Don’t Spam. (9) Be Real. (10) Collaborate.

In fact, it makes me think that I ought to see if I could build some research around this list. Unfortunately, the most important one (indeed the one that leads to all the other nine, as far as I’m concerned) is a challenging one to test. “Respect the spirit of the Net.” I have a solid idea of what that means and oddly, I think it’s a large part of what people pay me for. But could I build an instrument for it? I’m not so sure.


One thing the Internet is doing is requiring us to change and adapt social interactions, to create rules that work in the new environment. Society does this in order to control behavior so that the interactions are the most productive.

We see this in many of our day-to-day interactions. It is found in how line cheats are frowned upon, how we decide who goes first through a door, how we move to the right when going up some stairs. There are many social rules that we use to function smoothly.

Now not everyone follows all the rules but the rest of us sure notice when they are broken. I would guess that much of the road range seen is due to the apparent breaking of social rules that may not actually be appropriate when in the car.

The Internet is also a new social environment and we are creating social rules just like anywhere else. These 10 rules of social media are a good start. They all help enhance what makes the web so powerful. As we gain more experience with this new social setting, we will do w better job of training each other how to behave.

Not that trolls and spam will disappear but, just as we do with someone who to break some of our current social rules, we will do a better job of isolating and ignoring their behavior so it does not do as much damage.

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Mashing up

200910202344.jpg by foodistablog

One of the great things about openness and transparency is the ability for people to mash together various things to suit themselves. So, look at this:

Listening to: Death of an Interior Decorator from the album “Transatlanticism” by Death Cab For Cutie.

I added that with a single click in ecto, the blog editing software I use to create and publish posts. Ecto has a nice add-on that grabs the info from the song I am listening to and puts it in the post. I can set up templates with formatting so it has the links, etc. But the original template created Google search links. I simply remade the template so it links to iTunes.

I’m doing the same thing with Twitterfeed. This has allowed me to push blog posts from my different blogs (Spreading Science, Path to Sustainable and A Man with a PhD). Now I’m seeing if I can push posts to my Facebook account.

So, a simple posting can also copy the post to both Twitter ad Facebook. It looks like I do a lot but it all comes from simply clicking one button. That is what open APIs and other aspects of the web allow us to do.

It all makes it easier for the right people to get the right information at the right time.

Red flags of understanding

red flag by Luke Hoagland

Five Red Flags to Watch Out For in a Biotech, From Dendreon Co-Founder Chris Henney

[Via Xconomy ]

henneyc1 Luke Timmerman wrote:

Yesterday, we provided a rundown of the six hallmarks of a successful biotech company, according to Christopher Henney, the biotech pioneer who co-founded three of Seattle’s top biotechs—Immunex, Icos, and Dendreon. He made his remarks to an audience of about 100 investing professionals at the CFA Society meeting on Oct. 8 in Seattle.

Today, we follow up with the five red flags Henney advised investors to watch for when they evaluate biotech investments. Here’s what he singled out as warning signs:

Top management without a scientific background. It’s not impossible for a biotech to succeed with a non-scientist at the helm, Henney said, but a smart investor must ask this non-scientific manager where the science comes from at the company. “The good answer would be, ‘It comes from my team of wonderful scientists who I recruited.’” A bad answer would be something like, “It comes from my scientific advisory board, which has two Nobel Laureates.” Henney added, “If you need to make an appointment to meet the guy who’s bringing you your science, then you don’t have much of a business.”

Henney wanted to make sure he wasn’t making a broadside attack against all non-scientific managers. One of his favorite biotech CEOs isn’t a scientist, but he adds, “You wouldn’t know it from talking to him.”

No worries. An investor should ask what the management loses sleep over. “If they say, ‘I sleep like a baby,’ that’s a big red flag,” Henney said. All companies have their problems, and top management had better know them inside out.

Hard-to-understand science. Ask the management to explain the science of their product in detail. “If they say something like the science is hard to explain, they can’t really explain it to you, that’s a big red flag.”

Geographic remoteness. This provides some insight into Henney’s thinking on why two of the companies for whom he serves as chairman—Oncothyreon and AVI Biopharma—recently moved their headquarters from Edmonton, Canada, and Portland, OR, respectively, to the Seattle area. “You need a quorum of players,” Henney said. “You need access to talent, you need to be able to recruit people.” Seattle has more talent than the other places, and an ability to recruit more people, he said.

Too many VCs. The board should be loaded with people that have experience running companies. “You shouldn’t have a board full of venture capitalists,” Henney said.

Family members in key roles. “These aren’t family businesses. If you see a board dominated by siblings, or a couple of siblings in key management roles, I’d run, not walk.”


I have always had a soft spot in my heart for Chris Henney. Those of us at Immunex in the early days all have our hilarious Chris stories, often involving his confusion with our very weird phone system.

But when I first started at Immunex, it took a month to get our house closed. Because of the situation, I ended up staying in a fairly cheap hotel out in Issaquah (perhaps 15 miles away from downtown Seattle). This was an unexpected expense of moving and caused a little bit of hardship paying for before my first paychecks arrived.

So I talked with Chris and he got Immunex to pay for some of the cost as part of my moving expenses. It told me a lot about the culture at the company when a newly hired scientist could walk up to one of the founders and ask for money. And get it.

Most of his red flags deal with the inability to communicate the scientific reasons for the existence of the company. No science in the management’s background, no worries and nonsensical science all indicate a fatal lack of understanding.

If you do not understand the fundamental science in a deep way, you can not tell the story. An inability to tell the story in a way that resonates will make it impossible to shake some money loose.

This is not about hype, which is a snake-oil salesman’s approach to selling anything. In fact, hype indicates a total misunderstanding of the science because most biotechs are founded more on hope and strong egos than anything really solid. That is, often the company must begin development of the science for commercialization before the complete knowledge of the system is extant.

This means that the path to a commercial product will be littered with false starts and the company’s management had better understand the science enough to surmount these roadblocks.

I’m now going to tell a story. Perhaps some of the details may be a little off but it does illustrate why having a deep understanding of the science can be so important.

For example, Immunex, in large part, was started based on the hope that a molecule called interleukin-2 would be very important for medical protocols. See, IL-2 was also known as T-cell Growth factor and had been shown by some of Henney and Gillis’ work, to be absolutely required for the growth of T-cells in culture.

Now, T-cells are incredibly important in fighting off a whole slew of diseases, including cancer. So being able to manipulate T-cell levels seems like it would be a very good thing to be able to do. So, let’s clone IL-2 and produce it in large amounts. The we can sell it a s a therapeutic for a wide range of illnesses.

Turns out the IL-2 is not as useful as originally hoped. Not to say it does not have important uses, even commercial ones. But at the time, it seems like a critical molecule, one that would be core to our repertoire of tools.

Yet, when mice are bred which have no functional IL-2, they actually appear relatively normal. That is, the lack of any IL-2 is not fatal to the mice. There are some interesting immunological irregularities that have led to some interesting observations. But IL-2 is not absolutely required for a viable mouse. The mouse and its immune system find some other way to deal with T-cells.

Luckily for Immunex, our founders, and the scientists they recruited, had a deep understanding of the science and this allowed us to delve quite quickly into other aspects of the immune system as we worked on IL-2. For the same technologies that could clone IL-2 could be used to clone a wide range of immunoregulatory proteins.

By the time it could be shown that IL-2, while an important molecule, would not be the huge commercial product originally envisioned, we had a handful of other proteins cloned which presented even greater possible riches than IL-2. This deep understanding of the science eventually led to Enbrel.

Thus, a critical reason to have a deep understanding of the science is that no research venture, especially commercial ones, goes according to plan. But, if you understand the science, you can often be adaptable enough to find a successful solution.

Those that do not fundamentally understand the science will just be stuck when the inevitable roadblock appears. Then everyone, including the investors, are just stuck.

Reducing the barriers to effective intranet use

wall by Giuseppe Bognanni
Barriers to Intranet Use from Forrester:
[Via The FASTForward Blog]

Forrester recently released a report on What’s Holding Back Your Intranet? They were nice to share a copy with me. They found that 93% of employee respondents said they use an intranet or company portal (Forrester uses the terms interchangeably) at least weekly, and more than half reported daily use. However, they found that these intranets were mostly accessed for basic functions such as company directory, benefits information, and payroll. Access to collaborative tools, what some might called an enterprise 2.0 capability was ranked fourteenth.

At the same time studies have shown that a highly functional intranet can provide great value. A 2009 study at BT found that every £1 invested in the intranet produced £20 in exploited value. This certainly is consistent with my experience implementing such system in the late 90s. Despite this firms are underutilizing their intranets. They found several reasons.


Why don’t employees use an intranet? Particularly if it can return twenty times on its investment?

One of the reasons is that the intranet is simply not geared to what the employees want and need. A lot of effort is often spent on optimizing an external website but little is often spent on doing the same for an internal site.

Then there is this:

Most current intranets also do not reflect and support the specific roles and responsibilities of their users. The one size fits all approach is consistent with an IT centric intranet as it is easier and cheaper to maintain.

Too often IT buys an application that promises a strong and collaborative intranet. But this one size fits all makes it very hard to provide something that works in the culture of the organization. That is why I like Open Source approaches. The open nature of the software not only means that it can often stay current with fast moving trends (something a proprietary solution can often be far behind in implementing) but it also provides a much easier opportunity for internal employees or external consultants to craft a solution that works best.

However, the major barrier is simply that few people see why they should change their workflow to adopt new online approaches. The online approaches are optimized for IT, not the employees. And no one really works to facilitate adoption of new approaches.

That is something I constantly harp on when I work with organizations. Few people use social media because it is good for the community. They use it because it helps them personally. Someone needs to actually show them how Enterprise 2.0 will change their personal workflow. Then people will start really using it.

And then the emergent properties of Web 2.0 – that it enhances normal human interactions in ways to really leverage group workflow – will become visible.

All these things will happen eventually. But part of the way to increase the rate of diffusion of change in a company is to decrease the time it takes to adopt new approaches. This is just one example.

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Connections that create new research areas

Science: Retrovirus Linked to Chronic Fatigue Syndrome:
[Via AAAS News – RSS Feed]

Science: Retrovirus Detected In Patients With Chronic Fatigue Syndrome-But Does It Cause the Disease?

As many as two-thirds of patients with chronic fatigue syndrome carry an infectious retrovirus in their blood cells, according to new research published in Science. But the study’s authors say it’s not clear whether the virus is the main cause or a co-conspirator in the disorder.

First, the interesting aspect of this story to me, since it illustrates how making connections can result in innovative science. This work discusses the correlation of a specific virus to CFS. This virus was first isolated in humans just a few years ago as a possible cause for a particularly virulent form of prostate cancer. How did these researchers make the connection between a virus from prostate cancer and CFS?

It turns out the virus-positive prostate cancers demonstrate an alteration in an anti-viral protein, RNase L. The CFS researchers happened to know that a similar defect was seen in CFS patients, so they just decided to see if the virus was present in their patients also. They had no reason to expect this to be the case but it was one of those connections that makes scientists go ‘Hummm.’

The data sure are exciting. The virus is Xenotrophic Murine Leukemia Virus-related Virus (XMLV). It is a retrovirus that can incorporate itself into the cellular DNA of infected people. Two-thirds of the people in the CFS cohort had detectible virus while less than 4% of the control group did. In addition, an even higher percentage of the CFS cohort had antibodies to the virus, demonstrating that they had been infected with the virus. They also showed that the virus in the plasma of infected people could continue to be infectious.

There is still a lot of work to be done to demonstrate that this virus is the cause of the disease. But we have made some real progress simply because of a seemingly random fact presented in a piece of research that ostensibly had no connection at all to CFS.

Some of the best work comes from making a connection to a bit of data that may appear to be inconsequential. Good social networks permit these bits of data to get to people that can actually do something with them.

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Thinking by design

For anyone not already in IDEO’s PR reach, Tim Brown’s presentation at TED in July has been posted. Tim does a great job talking about how design become a narrow profession—”a priesthood of folks in black turtlenecks and designer glasses working on small things.” And in talking about how design can become something more.


Design Thinking

Design thinking provides a nice model for fostering innovation. Many of my ideas deal with how to move innovations, particularly disruptive innovations, though a community.

But someone has to create the innovations to begin with.

The TED talk is wonderful because it brings a whole systems approach to the problem. Instead of thinking small and only focussing on one area, design thinking encourages people to see how everything fits together and design innovative approaches to achieve the goal.

The key is to then get these innovations adopted by the community. That can be tough.

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