A missed creative science opportunity?

Either Science or Nature (I can't find the item now) had a blurb noting that a Chilean observatory will play a prominent role in an upcoming James Bond movie -- the hideout of the villain (original press release here). A bit later in the item it is mentioned that the observatory will basically be simply compensated for its costs.

Given the state of public science funding, it's too bad they didn't extort something more. This isn't somebody's production-costs-charged-to-my-personal-Visa indie film, but 007 himself. Budget never seems to matter much in those films, so why not extract a bit of cash?

The movie is at least titled 'Quantum of Solace', so maybe that's some science there. If the observatory could have held out a bit longer, perhaps they could have gotten something better. Imagine, for instance, the effect on interesting young males in science if Bond's love interest was an astronomer, with a requisite seduction scene taking place around a telescope! Imagine the classic Bondian double entendre opportunities!

Ah well, perhaps it's just jealousy. Nobody builds funky buildings for biologists in stunningly scenic locations (the Salk Institute perhaps excepted). Q's gadgets haven't yet involved synthetic biology (I suppose it doesn't film well) -- alas, no devices made from codons.

Space, the final bio-frontier?

In case it hasn't been obvious from the occasional post, I am a spaceflight aficionado. As a very young child I watched some of the last moon landings. Many hours of play were spent imagining riding a rocket, playing with toy rockets, and building Lego spaceships.

At some point I realized I really didn't quite have the Right Stuff. Clearly I was never going to cut it as a pilot (I carry scale models of Hubble's corrective lenses on my nose daily), and in the end my scientific interests weren't really going to support traveling to space. So it became purely an observational hobby, though the dream has been rekindled a bit by the notion of buying a rocket ticket (alas, 2001 has come-and-gone without the vision of 2001). When Millennium changed travel agents a few years back & we needed to fill out new travel preference forms, I put Virgin Galactic as my preferred carrier.

A more inner struggle, one reflected in much of the space community, is the appropriate role of humans in space, or perhaps more pointedly, of government funding of humans in space. It is one thing for some gazillionaire to pay multi-millions to take a joy ride (anyone want to spot me $50M for a week PLUS a spacewalk?); it's another for governments to continue to spend billions to put people up there. Manned flight is thrilling, but robots tend to get more data.

An item in The Scientist (free registration may be required) points to this debate again, and close to my scientific home. Lobbying is firing up again for biology research in orbit, and given that the company (Spacehab) lobbying for it builds manned research gear, they're pushing the manned angle.

Space research has yielded many earthly benefits, but they're mostly in areas such as communications & remote sensing. It is difficult to really prove a case for very many other areas. Spaceflight remains rare, unpredicable & expensive, three qualities that few like to associate with their research programs.

Two biotech claims are advanced to support space research. One is the long-standing issue of crystallography -- the claim is that crystals for X-ray diffraction studies can be grown in space that are either higher quality than ground samples or which simply can't be made on the ground. The other is a very new claim of vaccine research.

If anyone knows of a good, balanced (not in the Fox News sense!) review of space-based crystallography, I'd love to have a pointer. I'm not in that community, but my general impression is that while useful data has been collected on space-grown crystals, it really hasn't taken that community by storm. Perhaps if flights were cheap & frequent it could, but other approaches such as high-throughput condition screening have had a bigger impact.

The vaccine claims are based on a paper published last year in PNAS (also covered in The Scientist) which found that spaceflight changed some key gene expression programs in Salmonella and that the space-flown bugs were more virulent. A quick scan suggests that the paper is reasonably well done on the transcriptional profiling side (both biological & technical replicates). But, it also points to the challenge of space research -- when is the next flight opportunity to determine how general the effect is?

I do believe there are a lot of fascinating fundamental questions to ask about biology in space. Many would be in the developmental & cellular world: to what degree does gravity influence various developmental processes. Some other research might be less about space & more about behavior: Skylab astronauts had spiders spin webs, and it took a number of trials for the spiders to learn to do it in Zero-G. It could be a fascinating way to study such behaviors & how an animal adapts to a changed environment. But, most space biology questions have an importance scaled to our commitment to manned presence in space. I'm a bit skeptical that the Salmonella experiments really help understand virulence on the ground (or more importantly, are going to be generally relevant -- but sometimes it doesn't hurt to be lucky!), but I'd sure want that line of work driven hard if I was going to spend months in space!

Bizarre inanity from the financial analysis world

In general I try to ignore the various bleatings of stock pickers. Given the mountain of evidence in favor of the efficient market hypothesis, claims of successful stock picking should be generally lumped in with schemes for perpetual motion machines.

However, sometimes something truly ludicrous crosses my eyes & keeps them crossed. I've previously http://omicsomics.blogspot.com/2007_06_01_archive.html, but now I get to pick on someone calling a stock a buy.

The stock is (surprise!) Millennium, which Zacks.com is diligent to inform us is still a buy in their opinion. When I saw the headline I did a double-take, and then had to read the article. It's just as bizarre as I expected. The author describes a complex analysis leading to a target price of $25, miraculously the same as what Takeda is offering. They note all sorts of good news which might occur to Millennium.

But that's irrelevant, as Takeda has set the price for MLNM: $25/share. Given that MLNM has accepted the offer, the price ain't going higher without another bidder -- and unlike eBay auctions bidders don't tend to swoop in at the last minute. Indeed, Zacks isn't saying "buy this because the price will go higher". Yes, MLNM is currently priced a bit south of $25, but that's because there is really a difference of getting $25 when the deal closes versus getting money today. The gap prices in the transactional costs, the time value of getting (or giving) money now, and the tiny risk the deal won't go through -- but Zacks doesn't comment on any of those. Nope, according to them you should buy because MLNM might have good news!

It should be noted that Zacks in Feb called MLNM a buy with a target of $18. Either they got lucky or they really can pick. However, nowhere do they explain how the calculations really changed between then and now -- supposedly they plugged new numbers in and got a new value. But which numbers changed & why? No talk there.

Scrambling E.coli

On a more scientific and interesting note, a new paper in Nature reports on what happens to E.coli if you mess with its regulatory network in a big way. Not only is the paper interesting, but fellow blogger Pedro Beltrao is one of the authors.

The paper takes various promoters and various transcriptional regulators and reassorts which are attached to which. Nearly 600 such combinations were constructed in wild-type E.coli, meaning that the same regulator was also present in its normal regulatory context. The regulators tested also had GFP downstream, so fluorescence could be used to get a rough guide to the level of transcription in the construct.

It is perhaps surprising that most such rewirings are viable; only a few couldn't be built. But, all sorts of perturbations in growth patterns were observed. Some were even more fit than wild type.

Bacteria generally appear to be genetic carpet sweepers, taking in all sorts of genes & trying them out. While most of those genes will be structural, some will be regulators which may bind to existing regulatory motifs (or random motifs in promoters) and activate those genes. Perhaps it is not surprising that E.coli can tolerate many rewirings, as such rewirings must frequently occur naturally -- and activators are often located near the potentially useful genes they activate. If you get the good stuff, you are likely to import an activator, so its useful to be able to adjust to it.

Death, Taxes & Shareholder Lawsuits

With depressing predictability, the Takeda purchase offer of Millennium has been followed by the filing of a shareholder lawsuit claiming that the MLNM Board of Directors has breached their fiduciary duty.

It is hard not to see this as anything other than a shakedown attempt, figuring that the companies would rather pay to see it go away. Or even more unscrupulous, somebody being conned into suing to provide a revenue stream & publicity for some shady lawyers. Or perhaps a bit of both.

Such a suit ignores the fact that Takeda is buying MLNM for a 50% premium over the previous days price. That price was lower than the recent peak, but not by much -- the Takeda offer represents about a 30% premium over the highest price in many years -- indeed, it was 6 years ago it was so high. So, MLNM was hardly sold cheap.

Of course, there are three other ways the suit could claim merit: either MLNM sat on some explosive positive information, the market was persistantly undervaluing MLNM by a lot, or MLNM directors colluded with Takeda. All highly unlikely.

Such suits are all too commonplace. They simultaneously demean & clog the legal system. Real corporate malfeasance does occur, but this ain't it.

The Day AFter

Okay, a day of reflection, buzz -- and two articles in the Boston Globe on the Millennium buyout. One leads from the front page & is a pretty neutral news item. But in the business section is a second piece that works on the theme that genomics was overhyped and has under-delivered. And who hyped it? "Nobody did more to raise those unrealistic expectations than Mark J. Levin"

Oh, really? Okay, I'll confess to not being a neutral bystander. I like Mark. He inspires you. He's also down-to-earth. He's genuine. And yes, he did tout genomics in general and Millennium in particular. But William Haseltine at HGS and Randy Scott at Incyte were hardly shrinking violets. J.C. Venter would never be confused with J.D. Salinger when it came to media access. Drs. Collins, Hood & Lander were hardly silent.

The article is actually a strange mix. It actually starts out with some balance, with an academic commenting how much genomics has forever altered basic biology. There are blurbs from Steve Holtzman (credited in the article as being a key architect of Millennium's business strategy) and Nick Galakatos (whose MLNM employment goes unmentioned), both sobered up but still convinced (as I am) that genomics continues to make an impact on medicine.

The article also repeats the canard about Millennium's drugs not being from genomics. Yes, the two marketed cancer drugs (Velcade & Campath) have very little to credit to genomics (not that we didn't try with Velcade!). On the other hand, unremarked is the pipeline of compounds that Takeda is presumably paying a lot for -- most if not all of those have some genomics heritage, though it is fair to say none of them can only trace back. That's the complexity ignored in articles such as this: genomics has perhaps failed to revolutionize drug discovery, but it has certain become many of the threads in the warp & woof of the drug discovery loom.

The other question that goes unasked is who exactly collaborated in hyping genomics? Hint: remove the silent 'e' & you get Glob. During Millennium's rise the Globe was remarkably charitable to Millennium, with many glowing pieces & routine coverage of every little deal on the front page of the business section. Only well after the genomics bubble burst did that cozy relationship noticeably cool, and indeed through stories such as the failed AnorMed acquisition attempt it seemed to be gone. Perhaps we in the genomics companies were hawking moonshine & snake oil, but the Globe certainly wasn't digging under then. Now, of course, they feel the need to bend over backwards the other way.

Sayonara Millennium?

Boy, if today's news can't break me out of my blogging neglect, then nothing can. Japanese pharma Takeda is buying my old shop for a 50% premium, putting MLNM's share price to a level it hasn't seen since before the Cor merger mistake & market cap at a level unseen since the genomics bubble.

Reports are still coming in, but apparently Takeda is really buying the company -- it is not a raid for the pipeline assets but an attempt to get more or less the whole enchilada. Retention plans are rumored to be in place & it's claimed Dunsire will be staying on. On the other hand, time will tell if Sidney Street will soon feel like a tepanaki table (at least I got the cuisine right this time!) with the chef twirling a large cleaver. A lot of the key folks from Cor were supposed to drive MLNM forward, but they pretty much all bailed after a while.

Management always wanted to get a Japanese deal going, but nothing ever seemed to go beyond secretive hints. Finally, it comes in and it is the ultimate deal.

Many thoughts spring to mind, and perhaps I'll try to cover some later. But in particular, was this the result of a deliberate selling attempt or just some talks that blossomed? Two years ago MLNM refused to sell to an unnamed suitor (though one friend of mine joked about it with a lawyer at a local biotech & decided he'd love to play poker with the lawyer, given the size of the 'tell'); this time Takeda was apparently welcomed with open arms. It will be interesting to see what the merger materials say about the timeline of the deal.

Another key question is how tightly will Takeda attempt to integrate with Millennium? MLNM isn't the same loose place it was when the CEO dressed in drag every October (and just before I got there the high jinx bordered on Animal House), but it still had a soupcon of a laid back atmosphere. Last time I was in the lobby there was a display of each year's T-shirt; not your usual corporate display. I haven't had much dealing with Japanese companies, but this certainly doesn't fit the stereotype. Perhaps Takeda will see the wisdom in a largely hands-off approach, much like Warren Buffett does with his acquisitions -- the parent company funds the subsidiaries but otherwise just acts like a typical board member (though with Buffett, that's still a bit activist). Notable Buffett companies include a prominent local furniture store (where you can go to the movies or try to get free furniture if the Sox sweep the Series again) and the one insurance company unafraid to admit to a reptilian quality.

On the other hand, in theory the greatest value comes from integrating -- cross synergies, reduced duplicative effort, etc. My skepticism of such an approach scales with the distance both physical & cultural, so I doubt it would work. I've recently heard from a former colleague now in a large multi-national pharma how badly its integrated, and it's a company which has had years to do so & common language and nationality.

In any case, I'm sure the weekly sushi day in the cafe will be more popular than ever.