From The CENtral Science Blogs
Terra Sigillata
Jan 28th, 2012Was Demi Moore smoking synthetic marijuana?
By David KrollThe Safety Zone
Jan 27th, 2012Friday chemical safety round-up
By Jyllian KemsleyThe Chemical Notebook
Jan 27th, 2012Eastman Buying Solutia
By Alex TulloThe Haystack
Jan 26th, 2012Celgene & Avila Forge Permanent Ties
By Lisa JarvisNewscripts
Jan 26th, 2012Amusing News Aliquots
By Lauren WolfArtful Science
Jan 19th, 2012Bringing A Controversial Mural in LA Back To Life
By Sarah EvertsJust Another Electron Pusher
Jan 17th, 2012Chemist stars in “Piled Higher and Deeper” The Movie
By Christine HermanThe Editor's Blog
Jan 15th, 2012A Royal Encounter in Thailand
By Maureen Rouhi
All Latest Posts
Was Demi Moore smoking synthetic marijuana?
My substance abuser writer and researcher friend DrugMonkey (@drugmonkeyblog) just tweeted a CNN story suggesting that actress Demi Moore may have suffered adverse reactions after smoking a synthetic cannabimimetic product:
A woman called 911 soliciting help for actress Demi Moore, whom she said was “convulsing” and “burning up” after “smoking something,” according to a recording of the call obtained Friday from the Los Angeles Fire Department.
[. . .]
“She smoked something — it’s not marijuana, but it’s similar to incense. And she seems to be having convulsions of some sort.”
Reports of tremors and seizures have been accumulating in association with synthetic marijuana products. These products are generally composed of an herbal material that is spiked with one or more synthetic compounds that act at cannabinoid CB1 receptors.
The “burning up” described by the 911 caller in the story would be consistent with some reports of serotonin-like syndrome associated with synthetic marijuana use.
The US Drug Enforcement Agency is currently regulating some of the psychoactive compounds as Schedule I substances, illegal for use or sale as they are deemed as having no medical value. Individual states have also issued bans on compounds containing even more related compounds in these products. However, marketers have been skirting laws by using compounds not expressly deemed illegal in state or federal statutes.
Moreover, analytical crime laboratories across the nation have suffered extensive budget cuts making it difficult to keep up with the demands in determinig which products are illicit.
On a personal note, the synthetic marijuana story that DrugMonkey, dr_leigh, and I have been writing about for two years is growing increasingly disturbing. I just received my second reader email in three months from a father whose son shot himself to death while allegedly addicted to synthetic marijuana products. We’ve been in touch with the US DEA to inquire as to whether similar cases are currently under investigation.
Just as DrugMonkey wrote awhile back (I have to find the post), adverse drug effects with celebrities are usually required before aggressive government action is taken against illicit drugs (death of University of Maryland basketball player Len Bias from cocaine and a congenital cardiac abnormality).
Friday chemical safety round-up
Chemical health and safety news from the past week:
- Curious Wavefunction weighed in on the circumstances surrounding the death of UCLA researcher Sheri Sangji
- Chemjobber asked how to talk about chemical safety
- The University of North Carolina is reemphasizing personal protective equipment in its laboratories “because of recent accidents at university labs across the country”
- In Canada, the Ottawa-Carleton Catholic District School Board now faces charges for an incident in which a shop student died when an oil drum exploded as he was cutting into it; the charges include “failing to provide instruction or supervision, failing to take every reasonable precaution to protect the workplace and failing to properly acquaint a supervisor with hazards associated with the handling of equipment at the shop”
- On Apple contractor factories in China: improper hazardous waste disposal and indifference to worker conditions, including hexane exposure and poor dust control
“We’ve known about labor abuses in some factories for four years, and they’re still going on,” said one former Apple executive who, like others, spoke on the condition of anonymity because of confidentiality agreements. “Why? Because the system works for us. Suppliers would change everything tomorrow if Apple told them they didn’t have another choice.”
“If half of iPhones were malfunctioning, do you think Apple would let it go on for four years?” the executive asked.
- Newly-available documents relating to a fire at a hazardous waste treatment facility in Australia reveal a history of concerns about the company
- The Chemical Safety Board reported that many of its recommendations stemming from a West Virginia propane explosion five years ago have been implemented
- January 22-28 is Hazardous Materials Awareness Week in Florida
Fires and explosions:
- A fire at Chemical Technologies in South Africa killed two workers
Leaks, spills, and other exposures:
- A November spill at a Suncor Energy refinery in Colorado is still sending benzene and other chemicals into nearby Sand Creek and South Platte River
- Permanganate turned the Allegheny River purple in Pennsylvania
- Hydrochloric acid, about 1 L, spilled at Winthrop University in South Carolina
- I’m a little confused by this story, but I think maybe an entire shelf–40 L–of tetrahydrofuran came crashing down in a University of Wisconsin, Madison, biochemistry laboratory (or stockroom?); one person received a minor cut
- And I had to laugh at this one: A Scottish hospital building was evacuated when “a leaking container” of either dry ice or liquid nitrogen was found. “It appears the lid was not securely fastened, allowing the smoke-like gas to escape from the bottle.”
- On roads, railways, and shipyards: “a material used to make glue”, “a product used in ranching”, some sort of cleaning liquid, fumitoxin (aluminum phosphide)
Not covered: meth labs; ammonia leaks; incidents involving floor sealants, cleaning solutions, or pool chemicals; and fires from oil, natural gas, or other fuels.
Eastman Buying Solutia
I arrive the office this morning, bright and early, as usual.
“Your Top 50 U.S. chemical company survey will get smaller by one company,” C&EN assistant managing editor, Mike McCoy, said.
“Do you want me to guess?” I said.
“Solutia is one of the firms.”
“That is the company being acquired,” I reply.
“That’s right.”
“PPG is buying them,” I guessed.
“No, but that’s an interesting guess,” Mike says. It was a very good guess.
“Ashland?”
“No, too soon.” Ashland, Mike realized, just bought ISP.
“Eastman!”
“Very good!” Mike exclaimed, very impressed.
Indeed, Eastman is buying Solutia in a $4.7 billion transaction. The relevant details are in my Latest News story here.
I have a few observations:
1) It seems like a nice, square deal for all parties. My calculations put the cash and stock portion of the deal at $3,357 million and the debt at $1,377 million, combining for the ~$4.7 billion price. The cash and stock represent a 13.8x multiple over adjusted earnings of $243 million.
2) Since declaring bankruptcy in 2003, Solutia has honed its business where it has a strong position such as hydraulic fluids and polyvinyl butyral (PVB) interlayers for windshields. The cash cow of the portfolio is the technical specialties business, which generated a 38% EBITDA margin. It makes the hydraulic fluids, heat transfer fluids, and insoluble sulfur, used to vulcanize rubber.
3) Integration? PVB is made by reacting polyvinyl alcohol, which Solutia makes, with n-butyraldehyde. It just so happens that Eastman is America’s largest producer of n-butyraldehyde, which it uses to make oxo derivatives like 2-ethylhexanol. (The Chemical Notebook is on to you, Eastman! Actually, there isn’t a replay yet of the conference call. That will be out Monday. And I missed this morning’s live 8 a.m. call due, in part, to a breakfast consisting entirely of cheese. It could be that Eastman just came out and said it.)
4) Solutia is an ex-Monsanto business. Sterling, which Eastman acquired last year, is a former Monsanto unit. Spooky? Yes. Coincidence? Probably.
Celgene & Avila Forge Permanent Ties
Today brought a spate of M&A activity in the biotech space, with Amgen unveiling a $1.2 billion bid for Micromet, and Celgene agreeing to pay up to $925 million for Avila Therapeutics. Both deals brought the acquirer a drug in development to treat blood cancers, while also adding a platform technology to their research engines.
Being all about the chemistry, The Haystack is particularly interested in the Celgene/Avila deal, which involves covalent drug development technology. Celgene is paying $350 million upfront, with the promise of up to $195 million more if Avila’s lead covalent drug candidate, AVL-292, reaches the market. Pushing other covalent drugs through the pipeline could garner Avila shareholders another $380 million.
So what is a covalent drug, anyway? As C&EN’s Lila Guterman described last fall, covalent drugs form a permanent link with their target. By comparison, most conventional drugs are designed to reversibly bind to their targets—in other words, they can stick and “un-stick” to a protein.
The beauty of a covalent drug is that its specificity and potency means it can be given in low doses. As Guterman explains, patients only be given enough of the drug for molecule to reach each target protein molecule, and then another dose only when the body has generated more of that target protein. The low dose means less potential for drug-drug interactions and off-target effects.
Indeed, for years, scientists avoided developing covalent drugs out of fear that serious toxicity will arise if a covalent drug happens to permanently stick itself to the wrong protein. Check out Guterman’s piece for a cautionary toxicity tale from none other than “Rule-of-Five” inventor (and former Pfizer researcher) Christopher Lipinski.
The current generation of covalent drugs, however, is designed to assuage those fears through their highly selective and weakly reactive nature. Avila isn’t the only one banking on better molecular design leading to successful drugs: Zafgen’s obesity drug candidate ZGN433 also covalently binds to its target, an approach that—if it works—could enable it to sidestep the side effect issues that have plagued the obesity drug space.
So are these covalent drugs worth the price tag? Avila’s pipeline is relatively young, meaning there isn’t a lot of data to go on: AVL-292 is in Phase I studies in lymphomas; a compound targeting mutant EGFR is also in Phase I trials; meanwhile, two Hepatitis C drug candidates in preclinical studies. The company has also made public preclinical date on its PI3Kα-selective inhibitor (the same target as Intellikine’s INK1117, one of the drivers behind Takeda’s $190 million acquisition of Intellikine.).
#SheriSangji case: The limits of oral transfer of knowledge
As others have also reported, a second Cal/OSHA report has surfaced on the circumstances surrounding the death of University of California, Los Angeles, researcher Sheharbano (Sheri) Sangji from a laboratory fire. The first report, which I covered extensively back in 2009, was the one that led to civil sanctions against UCLA. As is standard in a California workplace fatality, once the civil case was completed, it was turned over to Cal/OSHA’s Bureau of Investigations (BOI) to determine whether it might warrant criminal prosecution. The newly-available report is the one that the BOI sent to the Los Angeles County District Attorney, who filed criminal charges against UCLA and chemistry professor Patrick Harran.
The report paints a pretty damning picture of overall UCLA safety culture at the time of the incident. To quote from the report’s conclusions (report page 90):
Based upon the investigation, it is apparent that the laboratory safety policies and practices utilized by UCLA prior to Victim Sangji’s death, were so defective as to render the University’s required Chemical Hygiene Plan and Injury and Illness Prevention Program essentially non-existent. The lack of adequate lab safety training and documentation, lack of effective hazard communication practices, and repeated failure to correct persistent and repeated safety violations within University labs, were all causal deficiencies that led to a systemic breakdown of overall laboratory safety practices at UCLA.
Much of the report just gives added detail to what was already known about the case or documents conventional wisdom about poor lab safety culture in academia. In one interview, postdoctoral researcher Paul Hurley noted that lab coats were seen as optional rather than required in every academic lab he’d worked in. “That’s how my experience has been pretty much everywhere I’ve been, apart from my current job actually,” the report quotes Hurley. Where does he work now? In industry.
The report does reveal, however, a bit more of how Sangji was supervised and trained. To recap the incident, Sangji was using a syringe to transfer about 53 mL of tert-butyllithium (tBuLi), a pyrophoric substance that ignites spontaneously in air, when the barrel came out of the syringe. The chemical splashed on Sangji, who was wearing neither a regular nor a flame-resistant lab coat, and set her clothes on fire. She was burned on more than 40% of her body and died of her injuries.
The report confirms that Sangji did not handle pyrophoric reagents as an undergraduate or during a few months of work at Norac Pharma. At UCLA, Sangji worked in Harran’s lab. Harran told the Cal/OSHA investigator that he observed Sangji do an initial experiment to gauge her experience and competency (the summary of Harran’s interview starts on page 67). Assuming that the experiment Harran referred to is the first entry in Sangji’s lab notebook–the second is her first tBuLi reaction–the procedure involved working in a glove bag and syringing no more than a few milliliters of air-sensitive, non-pyrophoric material. Although some of the fundamental techniques might have been the same, I think many people would argue that in scale and hazard that first reaction was a far cry from Sangji’s tBuLi experiments (synthetic chemists: feel free to weigh in on this point in the comments).
As for handling tBuLi, Harran reportedly told Sangji to ask Hurley for help. Hurley told the Cal/OSHA investigator that he didn’t follow standard operating procedures or other written protocols; rather, he was trained and in turn trained others by word of mouth (the summary of Hurley’s interview starts on page 59). Hurley also couldn’t recall the specifics of his interactions with Sangji. The way Hurley described handling pyrophoric reagents, however, echos some of what contributed to the lab fire that ultimately killed Sangji:
- Hurley said in the interview that “most people…more often than not did not clamp the bottle” and instead held it with one hand while syringing with the other. Aldrich recommends (pdf) clamping the bottle, which leaves both hands free to manipulate the syringe. (Sangji compounded this by using a 60-mL syringe with a short needle, so would have had to tip the bottle up to get the needle into the liquid while trying to handle a large syringe with one hand.)
- Hurley said that he always used plastic syringes. Aldrich does not specifically prohibit using plastic syringes, but it does recommend drying syringes in an oven, which effectively means that glass must be used. (Sangji used a plastic syringe. Another postdoc in the lab, Hui Ding, commented that plastic syringes can swell, making them difficult to operate.)
- Hurley said that he would use a syringe size as close to the reagent volume as possible. Aldrich recommends using a syringe at least twice the volume of the reagent volume, precisely to guard against taking the plunger out to the end of the barrel. (Sangji used a 60-mL syringe for 50 mL or more of material. Ding knew about the twice-the-volume rule.)
- Hurley said that he would physically pull on the plunger to pull up the reagent. Aldrich recommends using low-pressure, inert gas to push the material into the plunger rather than risk pulling too hard on the plunger and drawing in air. (It’s not clear which approach Sangji used. When Harran was interviewed by Cal/OSHA investigators in the civil investigation, he also said that he’d pull on the syringe. Aldrich scientist Mark Potyen has previously told me that plastic syringe plungers can’t be pushed up by low-pressure gas.)
(What’s not addressed in the report is the issue of transferring material by syringe versus a double-tipped needle, or cannula. On the day of the incident, Sangji was supposed to transfer a total of about 160 mL. For that amount, a cannula is the accepted practice rather than multiple smaller transfers. It’s not clear that anyone ever said that to Sangji. Certainly no one told her to read the Aldrich protocol.)
The Hurley interview clearly illustrates the limit of oral transfer of knowledge. As in a game of telephone, what gets passed on can change over time. Written protocols help guard against that. And making lab workers (re-)write protocols that faculty then review helps to ensure that everyone does, in fact, know what they’re supposed to do.
Other points of note: Sangji started in the lab in October, 2008. Hurley left the lab in November. According to the report, on the day of the incident in December, Harran knew that Sangji was planning to scale up the tBuLi reaction but told the investigator that he didn’t know by how much. Harran seems never to have discussed the hazards or use of tBuLi with Sangji.
Around the web today, I’ve seen a couple of people ask why the DA didn’t file charges against Hurley. My guess is that it comes down to the legal statute, California Labor Code Section 6425, which specifies “Any employer and any employee having direction, management, control, or custody of … any other employee.” Harran clearly fits that description–he hired Sangji, directed her work, and was ultimately in charge of his lab. I don’t see that it applies to Hurley, who was not explicitly assigned to supervise Sangji’s work and who was gone from UCLA by the time of the incident.
Last but not least, one caveat about the report: It is basically a summary of what the investigator found. The full package appears to involve five binders of information, which I do not have (nor, as far as I know, does anyone else outside of Cal/OSHA or the DA’s office). When reading the report, I think it’s important to remember that you’re not getting the full interview transcripts and we don’t know what the investigator may have left out. (I tried to get everything back in 2010, but was told that because the report was part of an ongoing criminal investigation, it was exempt from disclosure under California’s Public Records Act [pdf summary].)
President Obama Champions Manufacturing In The SOTU
During last night’s State of the Union address, the president spent roughly the first quarter of the speech talking about manufacturing. Does Obama have the right solutions? Time will tell. (It is an election year, so little will get done anyway.) But the Administration has certainly identified the right problem: the need to turn around manufacturing in the U.S.
The speech began with the auto companies:
On the day I took office, our auto industry was on the verge of collapse. Some even said we should let it die. With a million jobs at stake, I refused to let that happen. In exchange for help, we demanded responsibility. We got workers and automakers to settle their differences. We got the industry to retool and restructure. Today, General Motors is back on top as the world’s number-one automaker. (Applause.) Chrysler has grown faster in the U.S. than any major car company. Ford is investing billions in U.S. plants and factories. And together, the entire industry added nearly 160,000 jobs.
We bet on American workers. We bet on American ingenuity. And tonight, the American auto industry is back. (Applause.)
What’s happening in Detroit can happen in other industries. It can happen in Cleveland and Pittsburgh and Raleigh. We can’t bring every job back that’s left our shore. But right now, it’s getting more expensive to do business in places like China. Meanwhile, America is more productive. A few weeks ago, the CEO of Master Lock told me that it now makes business sense for him to bring jobs back home. (Applause.) Today, for the first time in 15 years, Master Lock’s unionized plant in Milwaukee is running at full capacity. (Applause.)
Let’s make one thing clear: “bankruptcy” isn’t the same thing as “going out of business”. The public seems to conflate those two things, perhaps for understandable reasons. Usually the 11 o’clock news stories about bankruptcy filings are discussing local retailers. Retailers are usually laden with a lot of working capital—namely inventory—and not a lot of fixed assets (Usually some readily sellable real estate and store infrastructure). Such retailers are easily liquidated and simply disappear.
Big manufacturers have a lot of equipment that isn’t as easily transferrable to other firms. If there had been a normal bankruptcy procedure, GM and Chrysler, could very well have emerged as successful car companies. LyondellBasell went through bankruptcy around the same time. It emerged, and it is now making manufacturing investments again.
However, it is also likely that the government-controlled procedure might have allowed for a more orderly process, especially in regards to a labor-management agreement. And the government likely offered the financing on more attractive terms than private banks would have been able to provide in the middle of the financial crisis.
Much of the remarks had to do with tax policy:




