Somewhere in life I've heard a children's/novelty song about a one ton tomato; eventually (if I remember correctly) it ends up as a similar quantity of ketchup.
Nearly half-ton pumpkins show up pretty regularly at the big agricultural fairs every fall, but tomatoes aren't in that league. But, the difference between an ancestral tomato (small berries) and a multi-pound beefsteak is nothing to sneeze at. Domestication has made great strides.
A paper last month in Nature Genetics laid out part of this process. Interestingly, there are two different developmental processes that have been utilized to enlarge tomatoes. A tomato fruit is composed of multiple subunits, the carpels. One change has increased the number of cells per carpel by tinkering with the cell cycle -- a much more delicious change than what a similar process will yield in a person. The new work details the genetic change which increased the number of carpels.
Of course, of interest is how universal these mechanisms are. Most domestic fruits are greatly enlarged over their wild counterparts -- though perhaps raspberries show very little enlargement & blueberries it is a small multiple. On the other end are those monster curcurbits at the fair and their watermelon cousins.
But getting back to the title. Now the question is whether these mechanisms have reached their biological maximum or simply what a few mutations can do (there are also practical considerations, such as the stem strength required to support larger tomatoes). Or, can we use this new knowledge to bring up the laggards -- or figure out why there are no fist-sized raspberries or basketball-like blueberries? A strawberry the size of my dog? Of course, purely economic forces might lead to the fruits commanding the most money per unit weight -- perhaps pomegranates will have an order of magnitude more seeds! Healthy for you -- so long as you watch where you eat them.
Monday, June 30, 2008
Friday, June 20, 2008
Don't do it Josh!
The Globe this week had a number of articles on the passing of the $1B biotech bill in Massachusetts and the proxy fight for Biogen Idec. But a third item really raised my eyebrows.
Vertex's CEO Joshua Boger announced that Vertex is contemplating moving out of the state. The apparent driver of this is a concern that Vertex might outgrow the Boston area and that now might be the time to move, before the company grows even larger. Previous discussion of moving had produced a striking plan to relocate to the Boston waterfront.
Now, I'll confess a certain personal interest. I'm probably going to be in this area for most of my employment life, so I don't want to see employers leave (I can see Vertex headquarters from my office). Furthermore, I believe big companies like Vertex, BiogenIdec and such have a beneficial effect on their overall corporate neighborhood -- they tend to grow more talent than they need and those persons tend to start new ventures near the old ones.
Which is the point -- people don't really like to move. Yes, some folks will follow their job to the ends of the earth, but a lot of folks won't. So atop the disruption & distraction of moving, a lot of good people will leave in a short timespan. My general prejudice is that planners recognize such costs but then grossly underestimate them.
Why might Vertex be contemplating such a move? The most cynical explanation is to try to extract tax incentives from either Massachusetts or wherever they move to. Such incentives have driven previous moves or new sites, with mixed success. Rhode Island trumpeted extracting Alpha-Beta from Massachusetts, until Alpha-Beta failed in the clinic and disappeared into the dust.
More practically Boston does have its drawbacks & tradeoffs. Traffic is awful; but that's true of a lot of America. Housing prices are insane. Neither of these encourages new workers. On the other hand, the academic & hospital environment is huge and Boston has a decent transit system, which somewhat offsets the traffic issue. It is striking that so many large biotech & pharma have been trying to move in to Cambridge/Boston over the last decade or so (Merck, Novartis, Schering, Astra, Amgen, Sanofi-Aventis, etc).
But in any case, I return to my main argument. I'm sure Vertex could thrive in many places -- Boston is not Mecca, and if they moved they would recover and thrive again -- but after paying a steep price of disruption & lost talent.
Are there other options? One of course is to stick it out in Boston. Another is to have multiple locations, which incurs its own inefficiencies. No solution is perfect. But please leave migrations for the birds!
Vertex's CEO Joshua Boger announced that Vertex is contemplating moving out of the state. The apparent driver of this is a concern that Vertex might outgrow the Boston area and that now might be the time to move, before the company grows even larger. Previous discussion of moving had produced a striking plan to relocate to the Boston waterfront.
Now, I'll confess a certain personal interest. I'm probably going to be in this area for most of my employment life, so I don't want to see employers leave (I can see Vertex headquarters from my office). Furthermore, I believe big companies like Vertex, BiogenIdec and such have a beneficial effect on their overall corporate neighborhood -- they tend to grow more talent than they need and those persons tend to start new ventures near the old ones.
Which is the point -- people don't really like to move. Yes, some folks will follow their job to the ends of the earth, but a lot of folks won't. So atop the disruption & distraction of moving, a lot of good people will leave in a short timespan. My general prejudice is that planners recognize such costs but then grossly underestimate them.
Why might Vertex be contemplating such a move? The most cynical explanation is to try to extract tax incentives from either Massachusetts or wherever they move to. Such incentives have driven previous moves or new sites, with mixed success. Rhode Island trumpeted extracting Alpha-Beta from Massachusetts, until Alpha-Beta failed in the clinic and disappeared into the dust.
More practically Boston does have its drawbacks & tradeoffs. Traffic is awful; but that's true of a lot of America. Housing prices are insane. Neither of these encourages new workers. On the other hand, the academic & hospital environment is huge and Boston has a decent transit system, which somewhat offsets the traffic issue. It is striking that so many large biotech & pharma have been trying to move in to Cambridge/Boston over the last decade or so (Merck, Novartis, Schering, Astra, Amgen, Sanofi-Aventis, etc).
But in any case, I return to my main argument. I'm sure Vertex could thrive in many places -- Boston is not Mecca, and if they moved they would recover and thrive again -- but after paying a steep price of disruption & lost talent.
Are there other options? One of course is to stick it out in Boston. Another is to have multiple locations, which incurs its own inefficiencies. No solution is perfect. But please leave migrations for the birds!
Sunday, June 08, 2008
Visiting a time capsule
The Next Generation & I went to the Boston Museum of Science today (we're members this year) and one of the exhibits where he lingered was the one of biotechnology.
I was a bit surprised to find that it dated to 1993; I didn't remember it always being in the spot it's in, so either my memory is flaky (not an unreasonable idea) or it was moved or in storage at some time. But it has been out for a while.
Simply looking at the list of sponsors is a bit of a memory jogger. While some are unchanged (BASF, Genencor), some simply went bust (Alpha-Beta), some were absorbed in corporate actions (Genetics Institute, Perseptive Biosystems) while others remain but under somewhat different names (lawyers Hale & Dorr have several more '&' in the name now; Biogen is now Biogen Idec).
Reading the text is interesting too. For example, we can learn that the human genome maybe, possibly might be sequenced one day.
One of the displays proposes that the dye indigo might one day be synthesized by bacteria (which had been demonstrated) instead of synthesized from petroleum (which had supplanted the original natural source about a century ago); that process has apparently not (yet?) become commercially feasible.
One of the games involves performing gene therapy for cystic fibrosis using a cold virus. That's certainly still a dream, but not for lack of trying.
Another game has you adding an antifreeze gene to tomatoes to prevent their freezing; this was once an active pursuit, but I haven't heard anything lately. Certainly the no-soften tomato was a commercial flop; I'm still eagerly awaiting some tomasil seeds.
This isn't meant to ridicule the display; in general I think it was well done & carefully thought out (Aspirin has been misspelled on the display all these years, but oh well!). Making interesting, interactive exhibits on molecular biology themes remains challenging.
Perhaps what has aged the least on the displays was the addressing of ethical concerns -- when does gene therapy go too far, what privacy rights do we have to our genes, etc.
I was a bit surprised to find that it dated to 1993; I didn't remember it always being in the spot it's in, so either my memory is flaky (not an unreasonable idea) or it was moved or in storage at some time. But it has been out for a while.
Simply looking at the list of sponsors is a bit of a memory jogger. While some are unchanged (BASF, Genencor), some simply went bust (Alpha-Beta), some were absorbed in corporate actions (Genetics Institute, Perseptive Biosystems) while others remain but under somewhat different names (lawyers Hale & Dorr have several more '&' in the name now; Biogen is now Biogen Idec).
Reading the text is interesting too. For example, we can learn that the human genome maybe, possibly might be sequenced one day.
One of the displays proposes that the dye indigo might one day be synthesized by bacteria (which had been demonstrated) instead of synthesized from petroleum (which had supplanted the original natural source about a century ago); that process has apparently not (yet?) become commercially feasible.
One of the games involves performing gene therapy for cystic fibrosis using a cold virus. That's certainly still a dream, but not for lack of trying.
Another game has you adding an antifreeze gene to tomatoes to prevent their freezing; this was once an active pursuit, but I haven't heard anything lately. Certainly the no-soften tomato was a commercial flop; I'm still eagerly awaiting some tomasil seeds.
This isn't meant to ridicule the display; in general I think it was well done & carefully thought out (Aspirin has been misspelled on the display all these years, but oh well!). Making interesting, interactive exhibits on molecular biology themes remains challenging.
Perhaps what has aged the least on the displays was the addressing of ethical concerns -- when does gene therapy go too far, what privacy rights do we have to our genes, etc.
Saturday, June 07, 2008
Isn't The Great Filter something in the Whatman catalog?
Twice in the last week the Globe has run pieces on a concept called 'The Great Filter', once on the Op-Ed page and now in the Star Watch astronomy column. I've read both, and the pseudo-statistical thinking in them just irks me.
The headline on the star watch column suggests the hubris that is perhaps what is goading me: "Why a microbe on Mars would change humanity's future". I'd completely agree that discovering microbial life on Mars would be exciting, but where it goes from there is bizarre.
The gist of the argument can be found in this quote
Given that we haven't yet found signs of other advanced life (or any life) elsewhere
Okay, just where to start. First, the current Mars mission finding life on Mars is a far cry from finding that life arose independently on Mars. We know that rocks make the transit occasionally, and while we think we sterilized all the probes, the possibility that any life form found really shares a common heritage must first be ruled out. Gary Ruvkun has suggested an experiment for a future probe to look for & sequence ribosomal RNA (if I remember correctly); that would be an appropriate follow-up.
There's also the problem of an N of one: Mars is one planet. Maybe you count an N of 2 with Earth as the second case, though since you're trying to predict on it that's a case of training on your test set. Mars is hardly an independent sample; the same solar system, which may or may not have some unusual properties.
But perhaps more irksome is conflating the reasonable idea that there are difficult barriers against spacefaring species to arise with the rather silly one that there is a single "Great Filter". Mars is a particularly poor example, as we would have a good guess what the filter is there: the planet quit being a nice place to live.
How improbable is life? How often do planets get life but it stays unicellular? How often multicellular but never ambulatory, sentient beings? How often do those sentient beings come up with some way to prevent travel to the stars -- a religion that forbids it, self-extermination (which our species has toyed with). Perhaps some inhabited planets have a super Van Allen belt which dissuaded their residents from becoming star travelers. Perhaps there are intelligent cultures far away -- but with a timing such that their signals can't yet reach us.
The fact is, any estimates of the probability of any one of these (or anything else you can imagine) are nothing but personal priors, wild guesses without much basis in fact. Feel free to make them, but spare us the headlines about predicting doom and gloom.
The headline on the star watch column suggests the hubris that is perhaps what is goading me: "Why a microbe on Mars would change humanity's future". I'd completely agree that discovering microbial life on Mars would be exciting, but where it goes from there is bizarre.
The gist of the argument can be found in this quote
If life arose independently twice in just one solar system, it would mean that the life formation process is easy and common. Life would be abundant everywhere. Most starts have planets, os the entire universe would be teeming with living things..
Good news? No. The chance for humanity's long-term survival would immediately look worse.
Follow carefully now. Whether or not simple life is common, we know that intelligen, technological life -- like us -- is probably rare. Otherwise, goes the arugment, it would have noticed such a good planet as Earth and come here to colonize as early as hundreds of millions of years ago
Given that we haven't yet found signs of other advanced life (or any life) elsewhere
If life is common, something apparently stops it from developing to the point of gaining interstellar travel and settling the galaxy...Apparently, some kine of "Great Filter" preveents life from evolving to the point of getting starships. If the Great Filter lies early in evolution -- such as if the origin of life itself is a rare fluke -- then we, humanity, have already gotten through it. If the Great Filter lies ahead of us -- such as, for instance, if technological civilizations always destroy themselves as soon as they get to power -- then we have no more chance of making it than all the others who have failed and left the cosmos silent.
The more advanced the fossils of living things that Mars may hold, the greater the chance that the Great Filter lies not behind us but ahead.
Okay, just where to start. First, the current Mars mission finding life on Mars is a far cry from finding that life arose independently on Mars. We know that rocks make the transit occasionally, and while we think we sterilized all the probes, the possibility that any life form found really shares a common heritage must first be ruled out. Gary Ruvkun has suggested an experiment for a future probe to look for & sequence ribosomal RNA (if I remember correctly); that would be an appropriate follow-up.
There's also the problem of an N of one: Mars is one planet. Maybe you count an N of 2 with Earth as the second case, though since you're trying to predict on it that's a case of training on your test set. Mars is hardly an independent sample; the same solar system, which may or may not have some unusual properties.
But perhaps more irksome is conflating the reasonable idea that there are difficult barriers against spacefaring species to arise with the rather silly one that there is a single "Great Filter". Mars is a particularly poor example, as we would have a good guess what the filter is there: the planet quit being a nice place to live.
How improbable is life? How often do planets get life but it stays unicellular? How often multicellular but never ambulatory, sentient beings? How often do those sentient beings come up with some way to prevent travel to the stars -- a religion that forbids it, self-extermination (which our species has toyed with). Perhaps some inhabited planets have a super Van Allen belt which dissuaded their residents from becoming star travelers. Perhaps there are intelligent cultures far away -- but with a timing such that their signals can't yet reach us.
The fact is, any estimates of the probability of any one of these (or anything else you can imagine) are nothing but personal priors, wild guesses without much basis in fact. Feel free to make them, but spare us the headlines about predicting doom and gloom.
Thursday, June 05, 2008
Cuddle up to a phage!
While searching Amazon for a book, I came across a very funny (in a geeky way) line of plush toys: all sorts of microbes! GiantMicrobes.com has quite a taxonomy of them. I think my visual favorite is the T4 phage 
, but there's lots of other fun stuff here.
You can get a whole range of common (E.coli) and nasty (a whole line of venereal disease agents. Human pathogens are not monopolized: to terrorize Miss Amanda (or make voodoo chew toys) there's mange, rabies & heartworm.
The E.coli are a flagellated strain. You can buy one or a trio (Petri dish)
. Surprisingly, there isn't a package deal on T4+E.coli, nor do they (yet?) have a pBR322 to accessorize your E.coli. Perhaps a future product line extension will include GFP-expressing glow-in-the-dark variants, or perhaps some scent-enhanced ones.
, but there's lots of other fun stuff here. You can get a whole range of common (E.coli) and nasty (a whole line of venereal disease agents. Human pathogens are not monopolized: to terrorize Miss Amanda (or make voodoo chew toys) there's mange, rabies & heartworm.
The E.coli are a flagellated strain. You can buy one or a trio (Petri dish)
. Surprisingly, there isn't a package deal on T4+E.coli, nor do they (yet?) have a pBR322 to accessorize your E.coli. Perhaps a future product line extension will include GFP-expressing glow-in-the-dark variants, or perhaps some scent-enhanced ones.
Monday, June 02, 2008
House ATG.GAC.
I don't watch a lot of network television, but there are a handful of programs that have latched onto me. At the end of this season, there were just two and by accident rather than design (or perhaps it is the current plethora of such) they are both hospital-based. Last week I viewed the last of the new episodes off my PVR – so in place of a new episode this week, I’ll try to sketch out my own
House M.D. is an hourlong drama focusing on Dr. Gregory House, a brilliant diagnostician who is also an extremely difficult human being. He terrorizes his three junior colleagues, who are trapped in his orbit like the inner moons of Jupiter -- and subject to similar violent (though only psychologically) tidal forces. Three previous assistants have attained somewhat more distant orbits, though one has spiraled back in. His boss & a colleague attempt to be friends, but get much grief for their efforts.
As with most series TV, there is a basic formula, a framework which the writers decorate or modify each week, rarely breaking it entirely. The scheme here generally starts with a patient arriving with some strange, dramatic set of symptoms (usually exposited prior to the opening credits). House is either intrigued or blackmailed by his boss into taking the case Lots of diagnostic dead ends follow (and new symptoms appear), accompanied by exorbitant amounts of testing. House's assistants provide the union of all high tech medicine & are capable of running any diagnostic under the sun (somehow, the hospital lacks lab techs!). By the end, the case is solved -- and more often than not the patient survives (a few lose the lottery).
One thing you actually DON'T see much of is DNA testing -- once in a while, but it hardly shows up as much as on a CSI/Law & Order type police procedural. DNA testing just doesn't televise well; the best you can do is show someone drawing their own blood (what, no buccal swabs?). In contrast, the MRI room has lots of fun angles -- private conversations behind the console, bouts of claustrophobia, or dramatic races to reach the suddenly stricken patient. Sequencers just aren't very dramatic.
So, I'm going to suggest an episode. Perhaps this qualifies as a "treatment" in Hollywood-speak. I have no desire for a career there, but if the writers take the idea I'd hardly turn down a walk-on.
A patient arrives at Princeton-Plainsboro seeking House due to a mysterious set of symptoms which has afflicted her for years. As usual with such, House is disdainful -- until the patient tries to hand him a DVD but dramatically collapses instead with some interesting symptom along the way. When the patient regains conciousness in a hospital bed, they start asking about the DVD again -- and then deliver the trump card: the DVD has her genome sequence on it.
House has no great interest in the DVD, and argues how useless it is. He's patently annoyed by it. One of the assistants makes the mistake of rising to the bait and proposing that perhaps a critical clue lies within -- and thereby gets assigned the task of cross-referencing EVERY polymorphism against the patient's symptoms. Several dead ends come from the DNA data, but nothing useful -- or in reality, just too many hypotheses which are too tenuous to do anything with. That doesn't stop the young assistants from batting some around and debating the now and future utility of such scans.
Now, as an aside, the story really (in my opinion) needs a complete genome scan. However, if there is a desire to garner some product placement that would narrow the candidates to one (Knome) at this stage. SNP scans are quite as dramatic!
At the end, the patient's puzzle is solved & they get to proceed in life knowing what they have & able to manage it. But, the kicker is that the assistant now cross-references the now known disease against the polymorphisms and comes up with an answer -- but it was buried deep within hundreds of other equally supported hypotheses. Finish the episode with some more back-and-forth amongst the characters about how this might play out the next time. How their careers might change. How well (or not so well) their training has prepared them for this.
House M.D. is an hourlong drama focusing on Dr. Gregory House, a brilliant diagnostician who is also an extremely difficult human being. He terrorizes his three junior colleagues, who are trapped in his orbit like the inner moons of Jupiter -- and subject to similar violent (though only psychologically) tidal forces. Three previous assistants have attained somewhat more distant orbits, though one has spiraled back in. His boss & a colleague attempt to be friends, but get much grief for their efforts.
As with most series TV, there is a basic formula, a framework which the writers decorate or modify each week, rarely breaking it entirely. The scheme here generally starts with a patient arriving with some strange, dramatic set of symptoms (usually exposited prior to the opening credits). House is either intrigued or blackmailed by his boss into taking the case Lots of diagnostic dead ends follow (and new symptoms appear), accompanied by exorbitant amounts of testing. House's assistants provide the union of all high tech medicine & are capable of running any diagnostic under the sun (somehow, the hospital lacks lab techs!). By the end, the case is solved -- and more often than not the patient survives (a few lose the lottery).
One thing you actually DON'T see much of is DNA testing -- once in a while, but it hardly shows up as much as on a CSI/Law & Order type police procedural. DNA testing just doesn't televise well; the best you can do is show someone drawing their own blood (what, no buccal swabs?). In contrast, the MRI room has lots of fun angles -- private conversations behind the console, bouts of claustrophobia, or dramatic races to reach the suddenly stricken patient. Sequencers just aren't very dramatic.
So, I'm going to suggest an episode. Perhaps this qualifies as a "treatment" in Hollywood-speak. I have no desire for a career there, but if the writers take the idea I'd hardly turn down a walk-on.
A patient arrives at Princeton-Plainsboro seeking House due to a mysterious set of symptoms which has afflicted her for years. As usual with such, House is disdainful -- until the patient tries to hand him a DVD but dramatically collapses instead with some interesting symptom along the way. When the patient regains conciousness in a hospital bed, they start asking about the DVD again -- and then deliver the trump card: the DVD has her genome sequence on it.
House has no great interest in the DVD, and argues how useless it is. He's patently annoyed by it. One of the assistants makes the mistake of rising to the bait and proposing that perhaps a critical clue lies within -- and thereby gets assigned the task of cross-referencing EVERY polymorphism against the patient's symptoms. Several dead ends come from the DNA data, but nothing useful -- or in reality, just too many hypotheses which are too tenuous to do anything with. That doesn't stop the young assistants from batting some around and debating the now and future utility of such scans.
Now, as an aside, the story really (in my opinion) needs a complete genome scan. However, if there is a desire to garner some product placement that would narrow the candidates to one (Knome) at this stage. SNP scans are quite as dramatic!
At the end, the patient's puzzle is solved & they get to proceed in life knowing what they have & able to manage it. But, the kicker is that the assistant now cross-references the now known disease against the polymorphisms and comes up with an answer -- but it was buried deep within hundreds of other equally supported hypotheses. Finish the episode with some more back-and-forth amongst the characters about how this might play out the next time. How their careers might change. How well (or not so well) their training has prepared them for this.
Saturday, May 31, 2008
Starting to add up to some real money
Last week's Globe carried an item that a real estate firm is planning a 5-year, $1 billion dollar, 1.5M square foot biotech complex in Cambridge. Given all the recent news about Gov. Patrick's $1 billion biotech initiative, perhaps Sen Dirksen was right. Predictably, one letter to the editor proposed that the private money obviates the need for the public mone.
Of course, they're addressing two different things, well, mostly. The original biotech proposal was going to be heavily research oriented, but now there is the earmarks for education & earmarks for local infrastructure. The real estate development is going to provide space for future growth, space that the company is hoping will exist.
Real estate in general & biotech specifically are a boom-and-bust phenomenon in Cambridge, though the trend is clearly weighted a bit towards boom. Even before the genomics boom there was a shortage of space & all sorts of old factory space was converted -- one MLNM site was known as the "Box Factory", as it had previously manufactured heart-shaped candy boxes for Valentine's Day. New buildings went up, such as the cluster of current & former MLNM buildings and the Cambridge beachhead for Partners Healthcare's research empire. The really big daddy's were the conversion of a candy factory to the Novartis site & Genzyme's beautiful building. When the tech boom crashed, space intended for companies such as Akamai was hastily converted.
Then the genomics era came crashing down, and suddenly MLNM wasn't gobbling up space but instead dumping it. Sites such as 640 Memorial Drive sat largely vacant, along with many smaller ones. Signs for 'Biotech Space Available'.
The pendulum is apparently closer to boom again, and several biotechs are heading to the suburbs for cheaper rents or more space. Cambridge will never be cheap, that's for sure.
A billion dollars is no pocket change. One unintentionally humorous element in the story was that no clients had been lined up yet -- like anybody in this business can plan 5 years ahead! MLNM got burnt multiple times on shorter term planning -- stuck in a long lease at 640, buildings configured for the wrong mix of chemistry & biology labs, etc.
Biotech buildings have all sorts of additional requirements, many of which I've only recently become aware of. Heavy-duty floors are needed to support equipment. Complicated ventilation infrastructure. Systems to pH neutralize waste water. Some companies have systems to move waste solvents downstairs; Cambridge's fire department has strict limits which grow tighter the higher the floor. Trying to get leeway there is a non-starter; a year and a half ago a non-biotech solvent explosion blew apart a neighborhood in a town north of Boston.
The location is very good; close to a lot of existing biotech, major road routes, and two mass transit lines -- one of which will probably be extended by the middle of the next decade. The area is already congested, but where isn't?
In the image, the Charles River is the dark slash in the lower right corner, and the Genzyme building anchors the lower left corner.
View Larger Map The big parking lot in the center would be a key site, and has begged for redevelopment for a while. The parking lot above it and to the right would also be included -- but also the low rise buildings going diagonally up to the upper left. These are apparently currently low-rent startup space, a useful commodity, but the new buildings will be much taller -- critical in the increasingly crowded biotech zone. A little bit of the space will be restaurant/retail, but with Kendall Square & the Cambridge Galleria nearby, it won't be lacking for eating & errands.
Of course, they're addressing two different things, well, mostly. The original biotech proposal was going to be heavily research oriented, but now there is the earmarks for education & earmarks for local infrastructure. The real estate development is going to provide space for future growth, space that the company is hoping will exist.
Real estate in general & biotech specifically are a boom-and-bust phenomenon in Cambridge, though the trend is clearly weighted a bit towards boom. Even before the genomics boom there was a shortage of space & all sorts of old factory space was converted -- one MLNM site was known as the "Box Factory", as it had previously manufactured heart-shaped candy boxes for Valentine's Day. New buildings went up, such as the cluster of current & former MLNM buildings and the Cambridge beachhead for Partners Healthcare's research empire. The really big daddy's were the conversion of a candy factory to the Novartis site & Genzyme's beautiful building. When the tech boom crashed, space intended for companies such as Akamai was hastily converted.
Then the genomics era came crashing down, and suddenly MLNM wasn't gobbling up space but instead dumping it. Sites such as 640 Memorial Drive sat largely vacant, along with many smaller ones. Signs for 'Biotech Space Available'.
The pendulum is apparently closer to boom again, and several biotechs are heading to the suburbs for cheaper rents or more space. Cambridge will never be cheap, that's for sure.
A billion dollars is no pocket change. One unintentionally humorous element in the story was that no clients had been lined up yet -- like anybody in this business can plan 5 years ahead! MLNM got burnt multiple times on shorter term planning -- stuck in a long lease at 640, buildings configured for the wrong mix of chemistry & biology labs, etc.
Biotech buildings have all sorts of additional requirements, many of which I've only recently become aware of. Heavy-duty floors are needed to support equipment. Complicated ventilation infrastructure. Systems to pH neutralize waste water. Some companies have systems to move waste solvents downstairs; Cambridge's fire department has strict limits which grow tighter the higher the floor. Trying to get leeway there is a non-starter; a year and a half ago a non-biotech solvent explosion blew apart a neighborhood in a town north of Boston.
The location is very good; close to a lot of existing biotech, major road routes, and two mass transit lines -- one of which will probably be extended by the middle of the next decade. The area is already congested, but where isn't?
In the image, the Charles River is the dark slash in the lower right corner, and the Genzyme building anchors the lower left corner.
View Larger Map The big parking lot in the center would be a key site, and has begged for redevelopment for a while. The parking lot above it and to the right would also be included -- but also the low rise buildings going diagonally up to the upper left. These are apparently currently low-rent startup space, a useful commodity, but the new buildings will be much taller -- critical in the increasingly crowded biotech zone. A little bit of the space will be restaurant/retail, but with Kendall Square & the Cambridge Galleria nearby, it won't be lacking for eating & errands.
Thursday, May 29, 2008
Misadventures in social networking
My one previous foray into social networking sites was LinkedIn. During one of MLNM's scythe-to-the-workforce exercises folks started setting up the sites, and it seemed like a good idea. Growth was slow at first -- which was fine by me as I've set a personal rule only to link to people I can actually remember interacting with. I also tended to only link to those already possessing accounts; little proselytizing for me. At one point though, I invited one person in just so I'd have one link with nothing to do with MLNM. However, Miss Amanda has shown no interest -- I suppose she won't until digital scent technology picks up)
Over time my network has grown & I have found the tool useful. For one, it's a way to keep connected to folks even as email addresses go dead due to job moves or internet provider changes. However, it's hardly foolproof there -- too often someone's LinkedIn account still points at the old email address. There's the related problem of someone having multiple accounts, having lost their access to one because it points to a defunct email. At least the last time I looked, LinkedIn's interface made it hard to distinguish them when you're trying to delete one -- you just see the person's name.
I also found it useful during my post-MLNM job search to scout out a company -- who do I know at company X?
Purely social sites such as MySpace don't have much appeal to me, but particularly in the past year I've gotten exposed to other sites -- usually by someone inviting me in. For example, SciLink is run out of Boston and the founder is a friend-of-a-friend, so we've actually met. This site starts building your network off your publications, a clever trick (though it does make me glad I'm not a John Smith).
For whatever reason, this morning I decided to check out some of those other invites that have been enjoying benign neglect in my email box. One thought was to get some minor fodder for this page. I uncovered the invite for Spock and also one for Doostang and thought about polishing up my SciLink entry.
For whatever reason, I picked Doostang first. Why I don't know. I sure don't understand the name. My quick associations to it are Durmstrang, boomslang & doofus. -- not good associations (I'm more of a Hogwarts partisan & I care not to meet a boomslang up close). But, what's the harm?
So I followed the link someone sent me & set up an account. Wrote up some skeleton information about my days of being blue & crimson and my job experience.
Now most of the sites have some feature to mine your email addresses for possible links. In keeping with past practice, I thought I'd use this to find others already on the site and try to link to them. Yep, just invite them, that's the plan.
The first inkling of disaster came when I got an email. From myself. Inviting me to Doostang. Actually, it wasn't addressed to me -- but to a Boston area informatics mailing list. OOOPS! Major social faux pas.
Then another email. From myself. This time to a company mailing list. Luckily, my colleagues had a sense of humor about it.
Then I check my email box: people are responding fast-and-furious. One person asks if my invite is spam -- hmmm, not quite sure how to answer that. Several are long lost colleagues, relatives & friends -- okay, that's a good thing. Many had nice things to say such as "thank's for thinking of me" -- I'm getting some social credit I probably didn't really earn.
Another is someone who's email address is a simple mutation away from my own -- people misaddress mail to me there. Nice to meet my not-quite-doppelganger, but pretty strange. Wierder is my inadvertant attempt to cozy up with by good buddies at subscriptions (at) nature.com -- yeah, they'll love me there!
Luckily, I've gotten out of the habit of debating science with crypto-creationists and have restrained myself from e-arguing with the staff right-winger at the Glob. Who knows how many Nigerian finance whizzes & providers of lists of MDs I'm now linked to! I probably should check my account to see what unsavory types I'm now e-collegial with. Please, no emails inviting me to join a network at www.MadeMan.com!
Well, the damage is done. I'll go easy on Spock & probably just return my invite to Meri Jeevan Kahani linger -- at least until I clear out all those messages from Doostang! I've always been aware I can be a bit socially awkward in real settings; now I get to bring that talent to the instant world of the Internet!
Over time my network has grown & I have found the tool useful. For one, it's a way to keep connected to folks even as email addresses go dead due to job moves or internet provider changes. However, it's hardly foolproof there -- too often someone's LinkedIn account still points at the old email address. There's the related problem of someone having multiple accounts, having lost their access to one because it points to a defunct email. At least the last time I looked, LinkedIn's interface made it hard to distinguish them when you're trying to delete one -- you just see the person's name.
I also found it useful during my post-MLNM job search to scout out a company -- who do I know at company X?
Purely social sites such as MySpace don't have much appeal to me, but particularly in the past year I've gotten exposed to other sites -- usually by someone inviting me in. For example, SciLink is run out of Boston and the founder is a friend-of-a-friend, so we've actually met. This site starts building your network off your publications, a clever trick (though it does make me glad I'm not a John Smith).
For whatever reason, this morning I decided to check out some of those other invites that have been enjoying benign neglect in my email box. One thought was to get some minor fodder for this page. I uncovered the invite for Spock and also one for Doostang and thought about polishing up my SciLink entry.
For whatever reason, I picked Doostang first. Why I don't know. I sure don't understand the name. My quick associations to it are Durmstrang, boomslang & doofus. -- not good associations (I'm more of a Hogwarts partisan & I care not to meet a boomslang up close). But, what's the harm?
So I followed the link someone sent me & set up an account. Wrote up some skeleton information about my days of being blue & crimson and my job experience.
Now most of the sites have some feature to mine your email addresses for possible links. In keeping with past practice, I thought I'd use this to find others already on the site and try to link to them. Yep, just invite them, that's the plan.
The first inkling of disaster came when I got an email. From myself. Inviting me to Doostang. Actually, it wasn't addressed to me -- but to a Boston area informatics mailing list. OOOPS! Major social faux pas.
Then another email. From myself. This time to a company mailing list. Luckily, my colleagues had a sense of humor about it.
Then I check my email box: people are responding fast-and-furious. One person asks if my invite is spam -- hmmm, not quite sure how to answer that. Several are long lost colleagues, relatives & friends -- okay, that's a good thing. Many had nice things to say such as "thank's for thinking of me" -- I'm getting some social credit I probably didn't really earn.
Another is someone who's email address is a simple mutation away from my own -- people misaddress mail to me there. Nice to meet my not-quite-doppelganger, but pretty strange. Wierder is my inadvertant attempt to cozy up with by good buddies at subscriptions (at) nature.com -- yeah, they'll love me there!
Luckily, I've gotten out of the habit of debating science with crypto-creationists and have restrained myself from e-arguing with the staff right-winger at the Glob. Who knows how many Nigerian finance whizzes & providers of lists of MDs I'm now linked to! I probably should check my account to see what unsavory types I'm now e-collegial with. Please, no emails inviting me to join a network at www.MadeMan.com!
Well, the damage is done. I'll go easy on Spock & probably just return my invite to Meri Jeevan Kahani linger -- at least until I clear out all those messages from Doostang! I've always been aware I can be a bit socially awkward in real settings; now I get to bring that talent to the instant world of the Internet!
Wednesday, May 21, 2008
When biotech pork doesn't mean GFP spare ribs
Tuesday morning's Globe carries a front page item, with the headline above the fold, outlining the wayward course which Governor Patrick's biotech initiative has taken. Originally outlined as a broad sweep to nurture biotech growth in the Commonwealth with an emphasis on academia, the project has morphed in the Legislature into a set of earmarks.
None of the earmarks are completely devoid of biotech relevance, but they certainly aren't going for broad strokes. $13M for an interchange (near where I live) to relieve commuter congestion around a big Wyeth biopharmaceutical production facility & $13M for a water treatment plant in Framingham which Genzyme needs to support an expanded production plant there. Both will help retain existing biotech facilities which are important employers, but neither of these is likely to drive any growth outside the specific plant targeted (should the Wyeth environs sprout a plethora of omics companies, I will happily figure out a way to eat crow during my exponentially shortened commute!).
Other funds are targeting state university favorites of legislators. U Mass was always going to get a new stem cell repository (which it was pointed out originally was a clever hand to Harvard, which wouldn't mind getting a graceful exit from that business), but the tab is now up to $195M. Nearly $50M will go to build a life science center at a Western Mass school not known for life sciences education; indeed, it doesn't even have a graduate program in the field -- but does have a powerful pol as an alumnus.
University professors & at least one biotech CEO (Genzyme's) are already crying foul, but this is unlikely to have much effect. Massachusetts is effectively a one party state with little involuntary turnover in the Legislature (or the U.S. Congress seats come to think of it). The pols already have retreated to "It's the public money & we have the perogative to spend it!" -- true, but not exactly a justification for how they're spending it.
Who is to blame for the mess? Governor Patrick need look no farther than his mirror. First he made insane estimates of the job creation it would drive -- something in excess of 4X the current employment in the entire existing life sciences sector. Then he burned all his political capital trying to get casino gambling legalized in the state, and then at the moment of the key vote was off to New York signing a book deal rather than corraling a few last votes. With no real leverage, he's at the mercy of the Legislature. The quote in the article suggests that he's ready to sign whatever comes his way, a hollow victory preferable to an honorable defeat.
One thing Patrick clearly underestimated, perhaps because he really is even newer to the state than I am (not quite to the 2 decade mark) is that there is an enormous geographical divide (not that I anticipated it when I initially reacted to it just over a year ago either!). The conditions that favor biotech tend to be in Boston, Cambridge and some surrounding areas -- with Worcester (about 1 hour away) the one other large outpost. Everyone feels that anyone closer to Boston is getting a better deal than they are. So a biotech bill likely to favor the apparently favored was going to have a hard time without a bit of bacon fat to grease the skids -- but once you wave some pancetta before the pols, it's hard to get them to stop.
None of the earmarks are completely devoid of biotech relevance, but they certainly aren't going for broad strokes. $13M for an interchange (near where I live) to relieve commuter congestion around a big Wyeth biopharmaceutical production facility & $13M for a water treatment plant in Framingham which Genzyme needs to support an expanded production plant there. Both will help retain existing biotech facilities which are important employers, but neither of these is likely to drive any growth outside the specific plant targeted (should the Wyeth environs sprout a plethora of omics companies, I will happily figure out a way to eat crow during my exponentially shortened commute!).
Other funds are targeting state university favorites of legislators. U Mass was always going to get a new stem cell repository (which it was pointed out originally was a clever hand to Harvard, which wouldn't mind getting a graceful exit from that business), but the tab is now up to $195M. Nearly $50M will go to build a life science center at a Western Mass school not known for life sciences education; indeed, it doesn't even have a graduate program in the field -- but does have a powerful pol as an alumnus.
University professors & at least one biotech CEO (Genzyme's) are already crying foul, but this is unlikely to have much effect. Massachusetts is effectively a one party state with little involuntary turnover in the Legislature (or the U.S. Congress seats come to think of it). The pols already have retreated to "It's the public money & we have the perogative to spend it!" -- true, but not exactly a justification for how they're spending it.
Who is to blame for the mess? Governor Patrick need look no farther than his mirror. First he made insane estimates of the job creation it would drive -- something in excess of 4X the current employment in the entire existing life sciences sector. Then he burned all his political capital trying to get casino gambling legalized in the state, and then at the moment of the key vote was off to New York signing a book deal rather than corraling a few last votes. With no real leverage, he's at the mercy of the Legislature. The quote in the article suggests that he's ready to sign whatever comes his way, a hollow victory preferable to an honorable defeat.
One thing Patrick clearly underestimated, perhaps because he really is even newer to the state than I am (not quite to the 2 decade mark) is that there is an enormous geographical divide (not that I anticipated it when I initially reacted to it just over a year ago either!). The conditions that favor biotech tend to be in Boston, Cambridge and some surrounding areas -- with Worcester (about 1 hour away) the one other large outpost. Everyone feels that anyone closer to Boston is getting a better deal than they are. So a biotech bill likely to favor the apparently favored was going to have a hard time without a bit of bacon fat to grease the skids -- but once you wave some pancetta before the pols, it's hard to get them to stop.
Monday, May 19, 2008
Sherlock Holmes, Omicist
A nice item in GenomeWeb about a new NIH initiative that's just brilliant -- using omics to try to solve rare disease mysteries. I've blogged on this topic before, and it's an obvious way to go -- particularly since the price of these genome studies is dropping so precipitiously.
As noted by the patient named in the report, finding a cause is not (alas!) the same as finding a treatment. But if many patients with mystery diseases are screened, there will almost certainly be some clues that do lead to useful remedies. It is also important to remember that very rare syndromes often shed important light on very common disorders. For example, a large number of rare tumor syndromes have illuminated key cellular mechanisms broadly relevant to tumorigenesis -- von Hippel-Lindau, neurofibromatosis, and many others. Having some molecular clue to the disease is infinitely better than a baffling list of symptoms.
As noted by the patient named in the report, finding a cause is not (alas!) the same as finding a treatment. But if many patients with mystery diseases are screened, there will almost certainly be some clues that do lead to useful remedies. It is also important to remember that very rare syndromes often shed important light on very common disorders. For example, a large number of rare tumor syndromes have illuminated key cellular mechanisms broadly relevant to tumorigenesis -- von Hippel-Lindau, neurofibromatosis, and many others. Having some molecular clue to the disease is infinitely better than a baffling list of symptoms.
Monday, May 12, 2008
When you care enough to send the very best DNA
Yesterday was Mother's Day, and while searching for a card I spied what looked like a double helix on the front of one card. Finding this odd, I checked the card in detail -- and indeed it was DNA!
DNA is clearly in the public consciousness -- years of Law & Order and CSI have ensured that, but I found it striking that the image of a double helix is deemed recognizable by as mainstream & middlebrow a company as Hallmark.
A nice twist is the card actually bore a message along the lines of 'even though you didn't give me any DNA...' -- a card for mother figures, not birth mothers. So this isn't a sign of rampant DNA deterministic thinking, but rather the imprint of DNA on the public (or at least corporate) mind
DNA is clearly in the public consciousness -- years of Law & Order and CSI have ensured that, but I found it striking that the image of a double helix is deemed recognizable by as mainstream & middlebrow a company as Hallmark.
A nice twist is the card actually bore a message along the lines of 'even though you didn't give me any DNA...' -- a card for mother figures, not birth mothers. So this isn't a sign of rampant DNA deterministic thinking, but rather the imprint of DNA on the public (or at least corporate) mind
Tuesday, April 29, 2008
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.
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.
Monday, April 28, 2008
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!
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!
Sunday, April 27, 2008
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.
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.
Thursday, April 17, 2008
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.
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.
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.
Friday, April 11, 2008
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.
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.
Thursday, April 10, 2008
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.
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.
Thursday, March 20, 2008
Do you prefer tomatoes or tomatomatoes?
My print version of Science showed up and the cover looks more like some foodie rag. I guessed wrong at first that they were peppers -- right family, wrong fruit. Nope, they are tomatoes.
I like growing tomatoes, though end-of-season output far outpaces my ability to consume them. It's fun growing different varieties, as there are so many different shapes, colors, sizes and flavors. Of course, all of the yard grown ones whip the store cardboard versions. On the other hand, it's hard to grow them around here this time of year -- though I once did have a rampant cherry tomato plant in the tearoom at Harvard (with bunsen burner supports & such staking it up!), though I didn't get any tomatoes until it dawned on me that I needed to play honeybee for the blossoms. When I interviewed at Millennium, someone had a tomato plant growing in the sequencing area (I'm sure the lab safety folks wouldn't let that happen any more!).
Anyway, the Science cover is for an interesting paper showing that a local gene duplication led to elongation of the fruit in one variety. Longer genes, longer fruit! The duplication is recent and was triggered by a retrotransposon, which altered the transcriptional environment around the gene. Cool!
I like growing tomatoes, though end-of-season output far outpaces my ability to consume them. It's fun growing different varieties, as there are so many different shapes, colors, sizes and flavors. Of course, all of the yard grown ones whip the store cardboard versions. On the other hand, it's hard to grow them around here this time of year -- though I once did have a rampant cherry tomato plant in the tearoom at Harvard (with bunsen burner supports & such staking it up!), though I didn't get any tomatoes until it dawned on me that I needed to play honeybee for the blossoms. When I interviewed at Millennium, someone had a tomato plant growing in the sequencing area (I'm sure the lab safety folks wouldn't let that happen any more!).
Anyway, the Science cover is for an interesting paper showing that a local gene duplication led to elongation of the fruit in one variety. Longer genes, longer fruit! The duplication is recent and was triggered by a retrotransposon, which altered the transcriptional environment around the gene. Cool!
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