Flat Earthers Have Company

Apparently there’s an insurrectionist branch of the Catholic Church in Chicago that’s pushing the church reject Galileo (again) and embrace a geocentric universe. I’ve always wondered how these folks explain the fact that our space probes managed to sail by the outer planets, taking plenty of pictures, land on Mars, land on Venus, and visit asteroids. All the mathematical calculations for guiding these probes is based on a heliocentric solar system.

This whole gravity thing is a conspiracy by the orthodox science establishment man!

The Problem of Drug Discovery

Well, this is my last week of employment, and while I am no longer actually working, I’m still having a hard time not thinking about work. It is very difficult to accept that the idea I signed up with at the very beginning ten years ago may be dying. Despite the dissolution of my current employer, a few of us true believers stood a good chance of saving the idea by forming a new entity, with a leaner and more focused organizational structure. This was possible since we had people who seemed willing to give us money. Unfortunately, the party with the most money is probably walking away, which if it does not spell the end, will definitely make putting something together take longer than most of our wallets can tolerate. We are not giving up, but we do need a paycheck.

One of the great difficulties in biotech is that everything is expensive, and you basically can’t operate in this business without venture capitalists, or without cozying up to a company in the Big Pharma club. That’s difficult for a discovery based company. Venture Capitalists are hesitant to invest in companies that are discovery stage, and Big Pharma is reluctant to pay large sums of money for pre-clinical compounds, unless they are hot and difficult targets they themselves have not been able to make any headway on, and even then you’re talking a million or so up-front, typically, with most of the money coming down the road with milestones and royalties.

We figured to run a program to the point where we can partner it it would cost about a million and a half dollars. It might end up being cheaper, but that depends on a lot. A sum such as that is beyond what you can easily finance with angel money, unless you can find an angel, or several angels, with really really deep pockets. Most individuals don’t have that kind of money to drop on a gamble. And because the drug business is a gamble, you will probably need several shots on goal before you’re going to hear the ca-ching of being a winner. Really, you probably want to have enough to do 3 to 4 programs. That means tapping VCs.

Typically how this would work is you develop a compound to a certain stage in the drug life-cycle, then partner it. Obviously, the farther you take it yourself, the more it’s worth when you partner it. It’s feasible for a well financed biotech to take compounds into Phase-II clinical trials. Phase-III is typically the most expensive, since you’re blowing you trials out to large numbers of patients. But going into the clinic is very expensive. Even going into animals like rats isn’t cheap. So the question is where the sweet spot is, where you can make back your cost, have enough to fund another program, but not dump so much money going into the clinic that you assume a large amount of risk yourself. Many biotechs have taken single products into the clinic, had them fall out, and then closed their doors. But taking risk in this business pays, so there’s a balance.

The biggest problem in seeking Big Pharma partners is that the business is so turbulent right now, it’s difficult to work out deals. We had more than several cases of partners either pulling out of deals, or canceling projects in place because of internal politics in the partner, or because management at a higher level in the Big Pharma partner decided to can the work on the project. Internally to Big Pharma, that happens all the time, but if you only have a few partners, and one walks away, it can be devastating to a biotech.

The Venture Capital landscape isn’t much better. VCs seem to prefer investments in companies that have compounds in the clinic. There is money out there for discovery stage compounds, but the bar is set very high for those companies. You won’t raise any money talking about how wonderful your idea is, or how great your people are. They probably won’t understand your idea, and if you don’t have the pedigree to back up how great you are, and by pedigree I mean either you’ve won the nobel prize, have already made million in biotech, or are known in the industry for having produced a blockbuster drug, they basically don’t want to talk to you.

I’ve spent the vast majority of my career in this business, and I’ve been questioning it. The fundamental problem with biotech and pharma is that the barriers to entry are so damned high. Even if you decide to depend on a Big Pharma partner for the most expensive part — clinical trials — experimental science is still awfully expensive. In other technological fields, like software and computers, the barriers are so low it’s not all that out of the question that if you grow lethargic, arrogant, and wasteful, some punk-ass kid right out of college is going to come along an own you. I like that kind of competitive environment, because in businesses like that, people tend to stay sharp, focused, open to new ideas, and open to change. That is not the drug business.

The good reason to stay in pharma/biotech is that if you do it right, there are fortunes to be made. If you produced a drug that people will take every day for the rest of their lives, in areas like cholesterol, blood pressure, or inflammation, you basically have a license to print cash by boxcar load for as long as the patent lasts. Typically in biotech, there’s a provision for a royalty to be paid if the compound is approved by the FDA and makes it to market. This is typically a few percent. But think about this: Lipitor did close to 13 billion dollars in global sales last year. Even one percent of that is nothing to laugh at. But even though the sums of money are huge, you’re going to end up sharing more of it with VCs than you would in many other industries, because of the costs involved.

What 5MB Used to Look Like

From Old Picture of the Day, courtesy of Instapundit. One of the great ironies of liquidating my company has meant going back ten years to when a terabyte was quite a lot of storage. Now I can put that on a portable USB drive. Our current technological infrastructure would be tight on a 20TB san. To me the next great leap will be shedding mechanical hard drives. After seeing Bitter’s MacBook Air, Solid State Hard Drives (SSDs) are definitely the way things will go.

I guess what’s also astonishing is that the technology that the 5MB drive was transported on is completely recognizable to us today, 55 years later. Computer technology has advanced far faster than transportation technology, or even our cultural ability to handle what the advances in computer technology is bringing.

Relaxing with X-Plane and the Embraer ERJ-140

One way I relax, and get my mind off nearly everything is tooling around in the X-Plane Flight Simulator. I downloaded a new jet model some time ago that I haven’t had much time to try out. I’ve flown on this plane before, and chances are many of you have as well. The manufacturer is Embraer, and it’s one of the many signs that Brazil is aiming to be a major player in the world economy. It takes a certain amount of sophistication to be able to produce airplanes; even the Russians and Chinese haven’t really managed an airliner that you’d want to take your wife and kids on, but the Brazilians have, and Americans are flying on them in droves every day. Dan Klaue has created a fantastic X-Plane model of this Regional Jet, which my video doesn’t really do justice. Flight is from Atlanta’s Hartsfield-Jackson International (KATL) to Cleveland Hopkins (KCLE), near dusk:

As a 3D model this plane is tip top, though it still needs some work in the systems simulation category. Nonetheless, it’s a great platform, and is X-Plane 10 compatible whenever that ends up coming out. I’ve preserved all the sounds on my video, which are pretty true to what I can remember flying on Embraers. You can see in this video some of the deficiencies of the X-Plane 9 model, including having to bake lighting features on to scenery, with the rest being pitch dark and unrealistic looking at night. Twilight is spectacular though, which I’ve always thought X-Plane renders quite well. You can also notice the rather ad-hoc nature of building scenery when you get close to it in the X-Plane 9 model. X-Plane 10 will have global illumination, where even cars on the roads will have light sources in their headlights. It will also base its mapping data on Open Street Maps, and generate plausible communities based on that data. I’m really looking forward to X-Plane 10, and hope it’ll be out before the end of the year.

I do all my own piloting in these, which shows in the takeoff and landings being far less than you would expect from a professional. In particular I flared a little early on the landing, drifting a bit in the crosswind and putting the left rear wheel down on the runway before the right, and slamming the nose down a bit hard. Live and learn.

Technology Transitions Gun-Related Purchases

It’s not a shocker to anyone who regularly reads blogs, but I thought a few of these questions & answers with the CEO of Cabela’s were interesting on the shift of how they sell over the last 5 decades:

Q. Cabela’s started as a catalog company and then added retail stores and online shopping. What’s the future mix?
A: The common thread that runs through our 50 years is an absolutely maniacal approach to customer service. Being the best at customer service has simply taken us where the customer wanted us to go. … So where our (sales) channels go in the future, our customers tell us and we will follow them there. We listen.”

Q. What are you hearing now?
A: Email, as you and I know it, has become less and less relevant to the generation in high school and college, and maybe just out of college. For that generation, it’s all about social media and texting. … Plugging into that stream will be the next thing. We track it. We’re on Facebook. We have more than 600,000 Facebook fans. We’re involved with Twitter.

Q. How important is the printed catalog in 2011?
A: The catalog is becoming less of a shopping vehicle and more of a prompt to get all of us to go to the Internet. There’s less density there about product specifications. It’s more informational. How to use something. It’s all designed to pique your interest and get you to come to the Internet, where you can see the full array of everything we have to offer.

The interview also addresses some questions about why Cabela’s is opting for smaller stores and other business-type issues. It’s an interesting little peek at the company, even if not the most detailed.

Several years ago, I started to notice that I only viewed catalogs in order to get an idea of what to look for on a website. I don’t read or view those two things in the same way, so it was sometimes helpful to find things I might not otherwise have considered. But now we just toss the catalogs completely. I’m pretty sure the only catalog I’ve thought about in the last year was for Godiva, but that was simply because I was part of a nearly year-long focus group.

Finally, Color E-Paper

Sony has unveiled color e-paper. One thing I had hoped with the iPad was that the screen would be some kind of new, advanced color e-paper, since rumors were they were going to market it as a reader.

If this works well enough, I’m pondering whether or not it’ll work well enough for digital picture frames. Judging from the display appearing in the article, it would be. I like digital picture frames, but I hate the backlighting. This makes them difficult in a bedroom, living room, or any place where you might be distracted by the soft glow of fluorescent backlighting.

At the least color e-paper will mean readers like the Kindle can host color content, for things such as magazines. I doubt Apple would want to go that route with the iPad, now that it’s out, and it’s pretty clearly a more general purpose tablet computing device. This should keep the Kindle and Nook competitive with content, like magazines, that demand color.

Centrifugal Force

At least one other person shares my only major complain about Atlas Shrugged, the Movie:

I was uncomfortable with a train going 250 MPH on those curves with the passengers standing up. Sorry, but I don’t think they ran the numbers through the physics equations before they filmed those scenes. And the curves had better have some appropriate slope to them to keep the train from rolling over or pushing the tracks off the railway bed.

I think I annoy Bitter by being annoyed by such things, but high speed rail lines have to be pretty straight for a reason.

This Describes Me Well

A New York Times article on the demise of the phone call:

“I literally never use the phone,” Jonathan Adler, the interior designer, told me. (Alas, by phone, but it had to be.) “Sometimes I call my mother on the way to work because she’ll be happy to chitty chat. But I just can’t think of anyone else who’d want to talk to me.” Then again, he doesn’t want to be called, either. “I’ve learned not to press ‘ignore’ on my cellphone because then people know that you’re there.”

I can’t remember the last time I answered an outside call on my office phone. When you’re in some kind of IT or tech field, 95% of the time it’s someone calling to try to sell you something you don’t want or need. Someone important will leave a message.

Update on Nuclear Hysteria

I’ve found this blog from MIT’s Nuclear Science and Engineering department to be a great source of information on what’s actually going on in Japan from people who actually know this stuff. Clayton Cramer offers this interesting radiological travel log of a Southwest vacation.

Future Pundit ponders what design changes could have been made. We know from reports that there was an attempt to bring in a mobile generator to provide power for the cooling pumps, but that it did not succeed because of power incompatibility issues. We also know that for at least eight hours after backup power failed, the reactors coolant was circulated successfully by battery power. So we know we have time even in a very dire situation. I’m honestly rather shocked by the idea that there would be a power incompatibility with a mobile generator. I would imagine you could run such a system off standard 480V three phase AC power that any number of industrial mobile generators could provide. This would allow a generator to be trucked or flown in by helicopter, easily connected, and that could provide enough power for critical cooling systems at the plant. Just checking, there are tractor trailer sized generators that can provide up to 1.5 megawatts of power off a diesel engine. That’s enough power to run 1500 homes. I would imagine it would be enough to run emergency systems at a nuclear facility, but maybe I’m wrong about that. If I am, I’d like to understand why.

More on Japanese Reactor Woes

Why I’m Not Worried About Japan’s Nuclear Reactors

I am writing this text (Mar 12) to give you some peace of mind regarding some of the troubles in Japan, that is the safety of Japan’s nuclear reactors. Up front, the situation is serious, but under control. And this text is long! But you will know more about nuclear power plants after reading it than all journalists on this planet put together.

Read the whole thing.