Actually, sharks do get cancer but a 15-year-old book by William Lane led people to think otherwise, launching investigation of shark cartilage as a source of antiangiogenic, anticancer compounds. While there is one promising shark cartilage extract (Neovastat) in clinical trials for multiple myeloma, most oral preparations on health food store shelves aren’t stabilized and characterized well-enough to guarantee stability of antiangiogenic compounds.

But it gets worse with this news today from FDA’s MedWatch program that illustrates once again the safety problems of some dietary supplements – shark cartilage may just not work; it might also give you Salmonella poisoning:

NBTY and FDA informed consumers and healthcare professionals of a nationwide recall of 3 lots of Shark Cartilage Capsules the company manufactured in 2004 and distributed to consumers through mail and internet orders, and retail stores throughout the United States. The product was recalled because of possible contamination with Salmonella, an organism that can cause serious and sometimes fatal infections in young children, frail or elderly people, and others with weakened immune systems. Healthy persons infected with Salmonella often experience fever, diarrhea, nausea, vomiting and abdominal pain. In rare circumstances, infection with Salmonella can result in the organism getting into the bloodstream and producing more severe illnesses such as arterial infections, endocarditis and arthritis. Customers can return the product back to the place of purchase for a full refund. Read the press release for specific names and lot numbers of the recalled product.

What is most concerning is that the wholesaler distributed the tainted extract to no fewer than seven manufacturers, some among the most commonly encountered brands in pharmacies and health food stores like Nature’s Bounty and Rexall Sundown.

If you have any elderly relatives or friends and family who are otherwise immunocompromised, make sure they are not taking any of the listed shark cartilage preparations.

In fact, I wouldn’t take any shark cartilage preparations outside of a clinical trial. Once again, be careful out there.

Family of dead scientist ignorant of his secret world

The secret world of Terry Jupp slowly began to emerge as he lay fatally injured in hospital. Between 60 and 90% of his body was burned when he was engulfed in a fireball at the [Ministry of Defense]‘s test firing range – operated by private contractor QinetiQ – at Foulness Island in Essex.

Mr Jupp, a senior chemist with the Forensic Explosives Laboratory, had been working with a 10kg (22lb) mixture of three substances in a paint container when it unexpectedly ignited.

The plan had been to prime the mixture and then take it to a remote part of the range where it would be detonated, far away from the small group of scientists and experts.

There had already been several similar test firings, using different combinations and ratios of various materials.

But on 14 August 2002 something went tragically wrong and Mr Jupp died from his injuries six days later, leaving behind his wife Pat and two children, then aged 11 and 15.

MoD criticised over death of leading explosives expert

[The jury] concluded that planning and risk assessment procedures had not been carried out properly, and that a small-scale test involving the potentially dangerous chemicals should first have taken place. …

The jury also decided that adequate regard had not been paid to personal protective equipment on the test site, and highlighted communication and organisational problems.

I looked briefly to see if the full inquest report is available online anywhere but couldn’t find it. If anyone else tracks it down, would you post a link in the comments?

I’ll leave the in-depth analysis to ScriptPhD, but I thought this commercial played out like a mini-movie. I wonder what kind of feedback Pfizer will get on this “More Than Medication” campaign.

Credit: Pascal Blachier via Wiki commons

When humanity’s predilection for perfume meddles with the sense of smell of insects and animals, it can sometimes be fortuitous. Case in point: the discovery that Calvin Klein’s Obsession perfume lures jaguars, tigers, and other big cats to expectant nature photographers and videographers. But meddling with odor receptors of other creatures can prove problematic. For example, the cosmetic and food fragrance 1-methylbutyl 3-methylbutanoate elicits aggressive defense behaviour in hornets. Sometimes people meddle with an insect’s ability to smell sexual pheromones as a means to combat invasive species. In 2007, California’s agricultural industry tried spraying an overwhelming amount of invasive moth species pheromone onto fruit crops because they hoped the signal overload would confuse the male moths and disrupt the species’ mating cycle–a solution that led to serious controversy.

The question that Richard Bolek, a PhD student, and his adviser, Klaus Kümmerer, at the University of Freiburg Medical Center, in Germany, want answered is whether some of the fragrances we use—in perfumes, personal care products, and cleaning agents, which get released into the air or down the drain–are inadvertently interrupting some of the chemical communication networks that benign or beneficial insects and animals rely on.

Is our obsession with smelling nice disrupting networks, such as, say, the fascinating ménage à trois network reported in last month’s Science? In that study, moth larvae (Manduca sexta) feeding on tobacco plants leave behind spit chemicals that isomerize some of the plant volatiles floating out of the munched-up leaf. These isomerized plant volatiles then attract predators (Geocoris), which find the larvae delectable.

Some people’s perfumes, and the fragrance of some bathroom cleaners, certainly drive me to near aggression. Bolek is trying to find out if insects and animals feel the same way. As he pointed out at the EUCHEMS conference this week in Nuremberg, Germany, not all fragrances are biodegradable, and there are three times more fragrances used in laundry and other cleaning products now in Germany than just a few decades ago–fragrances that inevitably end up down the drain or in the air. The project is just getting started: Bolek is currently analyzing levels of fragrance molecules he sampled from hospital waste streams, an experimental setting chosen because hospital administrations keeps track of how much and which brands of cleaning products are used. It’s the beginning of something worth keeping an eye (nose?) on.

CADE says it found evidence, through wire taps and searches, of an elaborate arrangement to divvy up the market by assigning customers to particular industrial gas companies.

“CADE understands the actions of those companies that were investigated resulted in grave damage to industry and the public health of Brazilians,” the regulator said in a statement. (Warning: I translated that myself.)

White Martins faces the largest fine, $1,273 million. Air Liquide is on the hook for $143 million. Air Products is looking at $130 million. And Linde may be responsible for $137 million.

The fines made Praxair mad. “Praxair strongly believes that the allegations of anticompetitive activity against our Brazilian subsidiary are not supported by valid and sufficient evidence,” the company said in a statement. “We further believe that the fine represents a gross and arbitrary disregard of Brazilian law.” The firm promises that it will “prevail on appeal.”

To Laurence Alexander, an equity analyst that covers Praxair for Jeffries & Co., the fine isn’t a shocker. “The threat of potential sanctions has been apparent since 2004, when CADE announced an investigation into alleged price fixing on public tenders as part of a broader government initiative to ‘help tame inflation’,” he wrote to clients. Alexander expects appeals to drag out five to ten years.

Renewable Crude by KiOR, Credit: KiOR

First I need to go back in time a little bit (to Aug. 17) and commend Range Fuels on getting its commerical cellulosic biofuels plant up and running near Soperton, GA. Range Fuels uses thermochemical processes (heat, pressure and steam) to convert woody biomass to synthesis gas (often called syngas). The gas is passed over a catalyst to produce mixed alcohols. The current product of the Soperton plant is methanol, which will be used to produce biodiesel. The plant will also have ethanol output beginning in the third quarter, according to the company.

Its been a long road for Range. (Though the commerical-scale biofuel road will be even longer for most other firms, as commercial facilities are as rare as ice in the Sahara [or you can insert your own lame metaphor]) Originally, the firm was to be on stream in 2008. By April 2009 they’d pushed the date back to the second quarter of 2010. The plant was ‘sposed to be making ethanol at the get-go – 40 million gal per year at full steam, with the ability to scale up to 100 million gal. The company plans to begin its first expansion – to 60 million gal – next summer. The slow and small start of commerical-scale ethanol facilities has been a thorn in the side of the EPA’s efforts to set targets in the nation-wide renewable fuels standard.

And yesterday, Mascoma said it has acquired SunOpta Bioprocess Inc. (SBI) in a vertical-integration move for its cellulosic ethanol activities. SBI has expertise in fiber preparation and pretreatment of cellulose. Mascoma’s focus is on a yeast/bacteria process that breaks down digestible cellulose into sugar. (The consolidated process competes with the normal bio-routine which uses biologically derived enzymes to break down the cellulose and yeasts to ferment it.) SBI’s parent company SunOpta says it will get about $51 million worth of Mascoma shares in the transaction.

Speaking of cellulosic feedstocks, the state of Miss. added a $75 million loan sweetener to its development package for KiOR, a renewable oil start up. The firm says it will build 5 plants in all where woody biomass will be converted into a type of crude oil that can be further processed into various transportation fuels. The first three plants are expected to come online by 2015, and employ 1,000 Mississippians.

In a non-Khosla bit of news, waste-to-fuels firm Enerkem began construction of an $86 million plant that will consume non-biodegradable municiple waste from the city of Edmonton, Alberta. The facility will produce enough ethanol to fuel over 400,000 cars per year running on a 5% ethanol blend, according to the company. Its 25-year pact with the city will bring 100,000 tons of solid waste to the plant annually. The idea is that feeding the plant would be cheaper than landfilling the garbage.

Alberta’s Premier Ed Stelmach, who was present for the groundbreaking ceremony, reminded the audience of the province’s $15 per ton carbon levy that is paid by the largest CO2 emitters. The money goes in to a fund to support R&D research for renewable energy. Alberta, as you’ll recall, is the home of oil sands, natural gas, and coal. Producing energy is a way of life up there.

In the deal, Orexigen gets $50 million upfront from Takeda and could nab up to $1 billion more, depending on whether Contrave meets certain regulatory and sales milestones. Further details about the agreement are available on an Orexigen press release.

Contrave refresher: Contrave is a combination of two drugs already on the market: naltrexone, which is typically used to manage alcohol or opioid dependence, and the antidepressant bupropion. Orexigen’s developed a sustained-release formulation of those active ingredients. This is thought to alleviate the nausea that cropped up in clinical trials, but also could come in handy in terms of real-world prescriptions if the drug is approved. People might want to save money by taking the generic versions of Contrave’s two components but it isn’t clear how that would work for them.

In July we covered the first partnership deal in the obesity drug race, that of Eisai and Arena Pharmaceuticals, which is developing the obesity drug candidate lorcaserin. It’s worth stepping back to compare and contrast the deals.

At a glance, much looks the same. U.S.-based biotech company developing a potential obesity medication partners with a company based out of Japan. Biotech gets $50 mil upfront, with a tantalizing promise of more if certain milestones are met.

But Arena’s press release about the Eisai deal contains a few more specifics about pricing. I don’t see comparable language in the Orexigen release. From Arena’s release:

Under the terms of the agreement, Arena will receive an upfront payment of $50 million from Eisai and, upon regulatory approval and the delivery of product supply for launch, up to an additional $90 million in milestone payments. Arena will sell lorcaserin to Eisai for a purchase price starting at 31.5% of Eisai’s annual net product sales, and the purchase price will increase on a tiered basis to as high as 36.5% on the portion of annual net product sales exceeding $750 million. Arena is also eligible to receive $1.16 billion in one-time purchase price adjustment payments based on annual sales levels of lorcaserin and up to an additional $70 million in regulatory and development milestone payments.

John Carroll of FierceBiotech noticed something’s been missing from the obesity drug deals: U.S. companies.

Noticeably absent from the deal-making are the U.S. pharma companies, several of which have been badly burned by obesity drugs’ troubled safety record.

He also noted that none of the three contenders has landed “a blockbuster-sized upfront check–a sign of the serious concerns about potential safety issues at the agency.”

Now that Orexigen and Arena have both found partners for their obesity drugs, you have to wonder whether Vivus will ink a deal for its obesity drug Qnexa. If safety truly is king in the minds of potential partners, then July’s FDA panel thumbs-down for Qnexa has to be a disappointment. Still, FDA doesn’t always follow a panel’s recommendation, so it will be interesting to watch what happens next.

Bonus ‘mark your calendar’ content: Sept. 16th is the day that the FDA’s panel will meet to discuss Arena’s lorcaserin. This could give us something to compare the Qnexa decision to and give us a better idea of how the obesity race will shake out. So stay tuned.

UPDATE 10:37 AM 9/2: Added $OREX stock link.

UPDATE 1:58 PM 9/2: Healthcare-focused investment banking firm Leerink Swann released a note to investors today, wherein analysts Steve Y. Yoo and Joshua Schimmer called the terms of the deal “excellent,” adding “We see this as an important derisking event from the commercial perspective, as Takeda is a well-funded company with good experience in the metabolic space (Actos) and clearly focused on obesity ([Amylin Pharmaceuticals] development partnership).”

Takeda’s partnership with Amylin includes an exclusive license on Amylin’s obesity drug candidate. Like Orexigen’s Contrave, Amylin’s leading drug is also a combo, but of two different entities, metreleptin and pramlintide.

In reality, his perceived folds of flab were a result of unfortunate camera angles (I swear, dear. Your chin is splendid.). But if a day comes when he genuinely suffers from chin bulge, Bayer might have just the solution. Yesterday, the company agreed to fork over $43 million upfront and upwards of $300 million in milestone payments for Kythera Biopharmaceuticals’ ATX-101, an adipolytic agent “designed to reduce small volumes of facial fat.” Yes, that’s right, folks: it’s a chin fat drug.

Because I tend to cover pharmaceuticals that are more in the disease-modifying category rather than those in the aesthetics-modifying category, I was pretty shocked by the price tag. Then I took a look at Allergan’s sales forecast for its wrinkle smoother Botox—the company is predicting it will bring in about $1.3 billion this year. (Well, that’s before subtracting out the $600 million Allergan agreed to pay today to settle criminal and civil charges related to the marketing of Botox.)

In other words, the potential market for ATX-101 seems pretty vast. Indeed, I imagine my husband isn’t the only one to look at a photo (poorly angled or not) and cringe. ATX-101 is in Phase II studies, and seems to be administrated in a relatively painless injection.

All this made me wonder how one goes about getting rid of small fat deposits without, well, sucking them out. It looks like the folks at Kythera, which is conveniently based in Los Angeles, first thought the active component in the formulation of ATX-101 was phosphatidylcholine, a major component of biological membranes that sports a polar head and fatty acid tails. However, further studies showed that deoxycholate, a secondary bile acid put into the formulation to make the phosphatidylcholine micelles soluble, was actually the secret to getting rid of unsightly chin fat. Deoxycholate, a detergent, causes a shift in the osmotic balance of a cell–in other words, water rushes into the fat cell, causing it to burst.  The finding was curious, as deoxycholate appeared to be only affecting fat tissues when administered in vivo. Kythera eventually determined that deoxycholate isn’t necessarily selective for fat cells, but that tissues in the subcutaneous fat that are protein rich are resistant to its effects. Hence, when administered locally, it appears to be able to get rid of the fat without impacting other tissues. And there you have it, drug goes in, fatty chin goes out. Since later stage trials are pending, the chin-fat sensitive will have to stick to photoshop for now.

In this front page article, “Running Jogs the Academic Mind,” by Don Troop, several academicians hold forth on the value of physical activity, running in particular, as a means to trigger thinking about research problems.

Religious “pilgrims have long understood this,” says Sarah Barringer Gordon, a professor of history and constitutional law at the University of Pennsylvania and an avid runner. “You have to exhaust the physical self first. You really have to get kind of empty, and then it all roars in.” Ms. Gordon says that every chapter of her new book, The Spirit of the Law: Religious Voices and the Constitution in Modern America (Harvard University Press, 2010), contains an insight gained on one of her long runs.

I have to say that I am really, really looking forward to getting back to running after a frightening bout of pneumonia earlier this year. As you read in the previous post, I spent a good amount of time in Colorado as a junior faculty member. In fact, this coming week is one of my favorite races, The Breckenridge Crest Mountain Marathon, a 24.8 mile trail run on the ridge above the ski town that averages an altitude of 11,000 ft/3,350 m above sea level. I did it twice together with a member of our departmental promotion and tenure committee (I “let” him beat me.). The race was a remarkable experience that has stayed with me – I’ll never run a flatland marathon on asphalt.

And I have to say that the combination of exhaustion and hypoxia not only makes the colors more intense, but it certainly gives on plenty of time to gather thoughts about manuscripts, grants, and lectures.

Have you ever specifically observed your physical activities improving the quality of your work in the lab or on the computer?

Two postdocs were working in the glovebox next to me. They spilled some MeLi and were mopping it up with kimwipes. They knew it would be dangerous when they pulled it out of the antechamber, so they prepared an EtOH bath (which, to be fair would safely neutralize a small amount of MeLi, iPrOH would have been better). One postdoc opens the antechamber and, as quickly as possible, took the kimwipes out and dunked them in the EtOH bath, only problem was, the kimwipes burst into flames as soon as the kimwipes were exposed to air, setting the bath on fire. In the panic, one of the postdocs went to get MORE ETOH and poured it on the fire. The bath overflowed, she started yelling for liquid nitrogen, I got out of my box and started running towards the liquid nitrogen. The next thing I know, i hear screaming, the postdoc walks out of the lab (right under a safety shower, without pulling the water release) with her entire pantleg on fire. I cant find LN2 so I take off her labcoat and snuff out the fire on her leg. The other postdoc managed to put out the EtOH fire, but he didnt remember how he did it. They both went to the hospital, one of them stayed for 2 weeks. That was my first summer in a lab, right before sophomore year.