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When is an explosion really an explosion

A letter in this week’s issue of C&EN takes us to task on our word choices:

I was disappointed to see the words “blast” and “explosion” used to describe the incidents at both Williams Cos. and at CF Industries in Louisiana (C&EN, June 24, page 5). Although both incidents involved fatalities, the CF Industries accident appears to have been caused by the rupture of a nitrogen line or vessel by overpressure. The mainstream press may think that is an explosion, but heaven help us if C&EN does.

Richard Rosera
Scotch Plains, N.J.

This is certainly something that I’ve thought about when reporting on incidents and compiling the news round ups. The challenge is that in a lot of cases, I don’t see good alternatives to “blast” or “explosion.” Complete this sentence: “The reaction released carbon dioxide, so pressure built up in the flask and it _________.”

I understand what I suspect is Rosera’s point, which is that a pipe or vessel rupture due to corrosion or pressure is a different scenario from something involving an explosive material, but does the answer lie in different vocabulary or giving the the details of what happened to put words like “explosion” in the appropriate context? The referenced story did that for the CF Industries incident, but similar details were not yet available with the Williams Cos. plant.

Amusing News Aliquots

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Dieting?: Orange you glad we told you to smell this? Credit: gcardinal/Wikimedia Commons

Silly samplings from this week’s science news, compiled by Sophia Cai, Bethany Halford, and Jeff Huber.

Craving that chocolate bar? Go smell an orange. Tempted by cookies in the office? Go smell an orange. [NPR]

Studies have shown that tall people earn more money and have a better view at rock concerts. But short people live longer, giving them more time to spend their smaller salaries and to stare at the backs of tall people at rock concerts. [Slate]

Another one from the “Who Funded This?” files: Researchers try to see if people really know what cats are meowing about. [Seriously, Science?]

Gearing up for a vacation? Why not take one of these 25 road trips for nerds? [PopSci]

Finally, a marathon-training tactic that doesn’t involve grueling exercise—or any movement at all, really. Just dream about the race in your sleep. [Guardian]

Slow animal meets fast food: Man tries to sneak his turtle onto a plane by hiding the pet inside a KFC burger. [United Press International]

How likely is a shark attack? More common ways to go: sinkholes, ocean tides, and tornadoes. Shark-free tornadoes, to boot. [Washington Post]

An emu, native to Australia, shows up on the side of a British Columbia road. Somehow, its long legs don’t entice passing cars to stop and give it a ride. [CBC]

What’s better than watching chimps at the zoo? Watching chimps on a sugar high at the zoo. [Metro]

Behind the bench, storeroom managers and department coordinators play an important role in safety

By Russ Phifer

Efforts to improve safety culture in chemical research laboratories generally focus on bench chemists, principle investigators, and laboratory managers. The backbone of these labs in both academic and industrial R&D, however, is frequently those working behind the scenes in positions such as storeroom managers or chemistry department “coordinators.” The professional organization for this group of people is the National Association of Scientific Materials Managers (NAOSMM). As I attend the organization’s annual meeting in Niagara Falls this week, I’m struck by how unpretentious the members are and how much of their jobs concern safety.

People in these positions rarely have advanced degrees, and many worked their way to their current positions from other facets of the chemical enterprise. Nonetheless, they are often the primary problem solvers in their workplaces. Having attended more than a hundred national and regional meetings of various scientific groups over the past 40 years¸ I can say unequivocally that NAOSMM members are among the most active and dedicated people when it comes to encouraging safe laboratory operations. NAOSMM meeting programs are typically incredibly diverse and cover topics such as laboratory inspections, waste management, lab animal care, inventory management software, and, this week, the science behind wine making. The sessions are full, often with standing room-only crowds despite many concurrent sessions. The NAOSMM e-mail list also maintains a lively discussion on laboratory management and safety.

As we work to improve laboratory safety across the wide horizon of academic and industrial R&D laboratories, I find it heartening to know that this group has the energy, desire, and means to work behind the scenes to encourage improvement in all aspects of laboratory safety.

To Pee, Or Not To Pee? That Is The #ChemSummer Question

I don’t really remember the first time I peed in the ocean.

But it must’ve been when I was a girl, during one of my family’s numerous summer vacations to the Jersey shore. We rented the same property in Wildwood Crest year in and year out: a modest 3-bedroom apartment just blocks from the beach.

What I do remember is a yearning to never leave the water, for my dad to throw me into a salty green wave one more time while shouting “Uh-oh Spaghetti-o!”

I’d have to guess that it was during one of those marathon splash sessions when I first did it. If you spend enough time in the ocean that your fingers get wrinkly, your lips turn blue, and you have sand in unspeakable places, trudging back across the white-hot pavement to a rental house isn’t really an attractive bathroom option. I’m sure my parents weren’t in favor of escorting their dripping, pruney child to and fro throughout the afternoon and gave their consent.

Today, my husband and I continue the Jersey shore visits—now a tradition—with my niece, taking her to the southern beaches each year for some fun in the sun … and surf. During our first year in the water, at the tender age of 8, she was hesitant. I told her she could relieve herself in the water, and she looked at me with embarrassment, the way only a child could look at an adult. Clearly, I was not hip. CLEARLY, I had missed that day of potty training.

Jumping the waves in Jersey ... or are we? Credit: Courtesy of Lauren Wolf

Jumping the waves in Jersey … or are we?
Credit: Courtesy of Lauren Wolf

Fast-forward four years, and my darling niece pees in the ocean with the best of ‘em. It’s now my husband that needs the convincing: He refuses to go. To address his noncompliance, my niece and I have become a floating vaudeville act, forcing my husband between us as we put on a show.

Me:  “Hey there, you said you had to pee.”

Darling niece: “Yup. I just did.”

Me: “Oh good, me too. So that’s done with. Hey hubs, you feel that warm spot?”

Before I go any further, I should interject here to say that I do not advocate peeing in pools or other small bodies of water—ponds, pristine lakes in the Alps, etc.

But oceans?

Having so far failed with our comedic act, my niece and I this year changed tactics. We decided to turn to science (and chemistry) to reason with our reluctant (yet very tolerant) companion. Using the WiFi at the beach house, we mounted our case.

Exhibit A:

Urine is the vehicle by which your body gets rid of undesirable chemical compounds. But that doesn’t mean the compounds you’re peeing out are necessarily harmful to anyone (although, again, I should interject here and say I don’t recommend drinking pee or getting it in one’s eyes). For instance, according to NASA Contractor Report No. CR-1802, put together in 1971, the average human’s urine is more than 95% water, and it contains 1-2 g/L of sodium and chloride ions. Okay, so water + salt.

These happen to be molecular species found in seawater. According to Encyclopedia Britannica, the ocean is about 96.5% water, and it contains a lot more salt–about 19 g/L of chloride and 11 g/L of sodium. So far so good.

There are other salt ions in each of these liquids at lesser concentrations. For instance, potassium in urine has a concentration of about 0.75 g/L, and potassium in seawater is at 0.4 g/L. Nothing drastically different here.

Urea, #handdrawn goodness.

Urea, #handdrawn goodness.

Where the composition of a person’s urine strays a bit from that of seawater is with the components creatinine and urea. Both compounds are routes the body uses to get rid of nitrogen. Creatinine is a nitrogen-heavy cyclic compound that is a breakdown by-product of energy-laden molecules in muscle. It’s only present in the average person’s urine at about 0.7 g/L. Urea, on the other hand, is more concentrated: It’s present at about 9 g/L. Because it’s high in nitrogen, the molecule is frequently used as a fertilizer, but it’s also applied in topical creams as a moisturizing factor.

Creatinine

Creatinine

Exhibit B:

Everything’s relative. It seems like urea might be a problem, given that it comes rushing out of us humans at rather high concentrations. When it breaks down in water, it forms ammonium—a charged molecule sucked in by plants and converted into nutrients. Again, according to the Encyclopedia Britannica, nitrogen-containing compounds are important parts of seawater because “they are important for the growth of organisms that inhabit the oceans and seas.”

But again, maybe 9 g/L is too much. So I give you a little calculation: Continue reading →

Roche’s GA101 (obinutuzumab): Engineering an antibody to beat Rituxan

The following is a guest post from Sally Church (known to many in the twittersphere as @MaverickNY), from the Pharma Strategy Blog.

Survival rates for people with B-cell driven blood cancers, such as non-Hodgkin’s Lymphoma and chronic lymphocytic leukemia, have vastly improved in the last decade thanks to the introduction of Rituxan, marketed by Biogen Idec and Genentech. But the drug, a chimeric monoclonal antibody targeting CD-20, a protein that sits on the surface of B-cells, has its limitations: not all patients respond at first, and others become resistant to the drug over time.

As a result, companies are tinkering with the sugar molecules that decorate antibodies in hopes of coming up with a drug that binds better to its target and, ultimately, is more effective at battling cancer. At the American Society of Clinical Oncology annual meeting, held earlier this year in Chicago, Roche offered Phase III data showing its glycoengineered antibody GA-101 worked better than Rituxan at delaying the progression of CLL. If all goes well with FDA, the drug could be approved by the end of the year.

BACKGROUND:

Although the CD20 antigen is expressed on both normal and malignant cells, it has proven to be a useful target therapeutically.  Rituximab, ofatumumab and most of the anti-CD20 antibodies in earlier development are Type I monoclonal antibodies, which means that they have good complement-dependent cytotoxicity (CDC) and Ab-dependent cell mediated cytotoxicity (ADCC), but are weak inducers of direct cell death.

In contrast to Type I monoclonal antibodies, next generation monoclonals are increasingly Type II, such as GA101 (obinutuzumab) in CLL and NHL and mogamulizumab (anti-CCR4), for T-cell leukemias and lymphomas.  They have little CDC activity, but are much more effective at inducing ADCC and also direct cell death, at least based on in vitro studies performed to date.

How does glycoengineering make a difference?

Glycoengineering is the term used to refer to manipulation of sugar molecules to improve the binding of monoclonal antibodies with immune effector cells, thereby increasing ADCC.

Obinutuzumab is a very different molecule from rituximab, in that it is a novel compound in its own right (originally developed by scientists at Glycart before being bought by Genentech).  It is not a biosimilar of rituximab.  It is also a glycoengineered molecule designed specifically to improve efficacy through greater affinity to the Fc receptor, thereby increasing ADCC activity.GA101

The overall intent with the development of obinutuzumab was to significantly improve efficacy over rituximab and Type I monoclonal antibodies in B-cell malignancies using glycoengineering techniques.

At the recent ASCO annual meeting, data from a phase III trial was presented to evaluate rituximab or obinutuzumab in combination with the chemotherapy chlorambucil versus chlorambucil alone in newly diagnosed CLL.  Patients elderly and had co-existing co-morbidities, excluding them from standard chemotherapy with fludarabine and cyclophosphamide (FC).

This two part trial sought to compare both combinations to the chemotherapy initially, and then against each other in a head-to-head comparison once the survival data matured in the second phase.  Data from the first phase of the study was reported at this meeting.

What did the results show?

When looking at the response rates, both obinutuzumab and rituximab combinations had a higher overall response rate (ORR) than chemotherapy alone (75.5% and 65.9% vs. 30.2% and 30.0%).  Importantly, the combinations had a great proportion of complete responses (CR) i.e. 22.2% and 8.3% compared to 0% in the chlorambucil arms.

Minimal residual disease (MRD), a measure of the number of leukemia cells remaining in the blood, was 31.1% in the peripheral blood of the obinutuzumab combination compared with 0% in the chemotherapy arm.  Corresponding values in the rituximab and chlorambucil arms were 2.0% and 0%, respectively.

Median progression-free survival (PFS) i.e. the length of time during which people lived without their disease worsening for the obinutuzumab plus chlorambucil arm were impressively higher than chemotherapy alone.  PFS was more than doubled (23 months compared to 10.9 months, HR=0.14, p <.0001 when compared to chlorambucil alone. the corresponding outcome data for rituximab combination were versus months alone p>

Since ASCO, Roche have announced that the FDA granted Priority Review for obinutuzumab in CLL (in addition to the Breakthrough Designation already received in May, when the company filed a new drug application for obinutuzumab), meaning that the PDUFA date is set as December 20th.  In addition, the Data Monitoring Committee decided that the interim data analysis was sufficient to meet the primary endpoint of the trial, ahead of schedule.  The data confirms that obinutuzumab was superior to rituximab in terms of the disease worsening (PFS).  The full data will be presented at ASH in December, when overall survival data (ie did the patients live longer) may be available.

The adverse event profiles were slightly different between the monoclonal antibodies.  Patients in the obinutuzumab arm experienced more infusion site reactions, and a slightly higher degree of myelosuppression (thrombocytopenia and neutropenia), but lower infection rates.

Overall findings

The study demonstrated that both obinutuzumab and rituximab were more beneficial to elderly patients living with CLL and co-existing medical conditions than chemotherapy alone.  The final head to head analysis of the two combinations will be available once the second stage of the study has mature data.  Based on the progress to date, the signs are very encouraging that the chemical engineering behind the development of obinutuzumab may potentially have produced a superior compound to rituximab for treatment of B-cell malignancies.

Should the mature outcome data show a positive survival advantage in obinutuzumab’s favour over rituximab, we may well see similar glycoengineering techniques applied to other monoclonal antibodies in the near future, potentially leading to further improvement in outcomes.

 

In Print: When Zombies Help Us Escape

The Newscripts blog would like to be closer Internet buddies with our glossy print Newscripts column, so here we highlight what went on in last week’s issue of C&EN.

Postapocalyptic films, video games, and nightmares typically involve escaping from zombies. But in the Science Museum of London’s ZombieLab exhibit, visitors were asked to help virtual zombies escape in an emergency. In turn, scientists behind the museum’s video game got to learn a little bit about human behavior in emergency evacuations.

The exhibit featured many zombie-based experiments that observe human behavior, asking questions such as “Can you act rationally during a zombie apocalypse?” and “Can virtual reality create the illusion that you’re dissociated from your own body?” They even delved into moral dilemmas that arise from acting violently in self-defense.

BRAINS!! Sure, this evacuation plan looks stupid, but your brain works differently in an emergency. Credit: ZombieLab

BRAINS!!!: Sure, this evacuation looks stupid from the outside, but your brain works differently in an emergency. Credit: ZombieLab

In an experiment that associate editor Andrea Widener writes about in this week’s column, 185 volunteers were asked to navigate their zombie avatars into a building and find a specific room. They were then instructed to guide their zombies to a new target outside of the building. There were two exits: the one that player had entered and another almost identical exit that was clearly visible but hadn’t been used by the player. Some players were told it was a race and some were not.

The players who weren’t rushed were equally likely to guide their zombie pals out either exit, leading to an efficient evacuation. But the players who were told bigger, badder zombies were coming and to hurry up (okay, that’s some embellishment on Newscripts’ part) were more likely to race their zombies back out the door they entered, even if that meant there was a bottleneck at this door and not at the other one (as depicted in the accompanying graphic).

The scientists see this as an opportunity to help out with crowd control at major venues such as sporting events, Andrea says, which she thinks is a good idea, given the results. “In real life, it’s actually much more logical that people choose the way they have been before since they don’t know what they are going to get the other way,” she says. “But sometimes they will just run by other clearly marked exits, which is dangerous in an actual emergency.”

So in the event of an emergency, remember to use your brains. And in the event of a zombie apocalypse, remember to protect your brains.

 

What Makes This Massive Blossom Smell So Bad?

Today’s post is by Cheryl Hogue, a senior correspondent at C&EN who loves to botanize. She won third place at her county fair for a scary-looking succulent she grew on a windowsill.

Something was making a stink on Capitol Hill this week and it wasn’t Congress.

Corpse flower: Because not everything pretty can smell good.

Corpse flower: Because not every pretty flower can be fragrant. This one smells like dead flesh, then dead fish.  Credit: Cheryl Hogue

The malodorous scent wafted from the titan arum blooming in the U.S. Botanic Garden on the grounds of the U.S. Capitol. This plant, Amorphophallus titanum, also known as the corpse flower or stinky plant, has the largest unbranched flower stem (or in botanist-speak “inflorescence”) on Earth.

I jumped at the chance to have a wondrous and slightly gross experience with this plant, a native of the jungles of Sumatra that rarely blooms.  Yesterday, I queued up in a line that snaked around the exterior of the botanic garden’s glass-enclosed conservatory.  The oppressive District of Columbia heat and humidity failed to deter anyone waiting from their quest to view—and, with hope, to sniff—the stinky plant.

After 20 minutes in line, I entered the conservatory and beheld the titan arum at the peak of its splendor. I was suitably impressed at the yellowish, club-like spadix—the central part that holds tiny female and male flowers—surrounded by the shawl-like maroon spathe.  The bloom is over 5 feet tall.

But alas! There was no smell. Well, I did catch a brief whiff of something that smelled like a food dumpster that had baked in the July sun all day—but that might have been an actual dumpster. A botanic garden volunteer explained to me that the titan arum off-gasses its putrid odor at night, attracting beetles and other pollinators.

What makes the corpse flower smell so nasty? A decade ago, chemists interviewed by C&EN had good hypotheses but hadn’t come up with definitive answers.  In 2010, a group of researchers in Japan clinched the analysis, determining that dimethyl trisulfide was the main chemical that accounted for the titan arum’s stink, which they described as the “rotting animal-like odor” (Biosci. Biotechnol. Biochem., DOI: 10.1271/bbb.100692).

Dimethyl trisulfide, the researchers reported, is among the volatile compounds in cooked onions, cabbage, decayed meats, and, interestingly enough, ulcerating lesions with dead tissue that are associated with some cancers in humans.

Dimethyl trisulfide: Because not every symmetrical molecule can smell nice. This one has a "rotting animal-like odor."

Dimethyl trisulfide: Because not every symmetrical molecule can be aromatic. This one has a “rotting animal-like odor.”

Other compounds contributing to the titan arum’s bouquet are methyl thiolacetate, 3-methyl butanal, acetic acid, and isovaleric acid, according to the 2010 analyses.  The researchers also reported that at the end of the 24- to 48-hour blooming time, the plant’s funk changed to a rotten fish smell. Trimethylamine is the compound responsible for this scent, they found.

No matter how awful this buffet of chemicals smells, I bet botanic gardens could sell tickets for nighttime visits to a blooming stinky plant.  Botany enthusiasts like me want to get a schnoz-full.

 

In Print: How To Be A Cool Scientist

In a sick twist of evolutionary fate, the stereotypical scientist has been deemed uncool by society. But now, hip-hop artist and playwright Baba Brinkman is attempting to bring science to the public through a teenager-approved vehicle: rap music.

As Associate Editor Corinna Wu writes in this week’s column, Brinkman raps about brainy topics such as “The Canterbury Tales” and Darwin’s theory of evolution. His latest track, “Revenge of the Somatic,” is rapped from the point of view of a cancer cell, which he considers a good entry point into his long-term plan of producing a rap guide to medicine.

Corinna first heard Brinkman perform at the 2012 International Conference on Neuroesthetics, in Berkeley, Calif. (Watch above.) “He performed songs from his ‘Rap Guide to Evolution,’ accompanied by some entertaining slides,” she says. “At the breaks, he would perform very funny, ‘wrap-up’ raps riffing on the content of the other talks. He was mobbed by people buying his CDs and asking to get them autographed.” Autographs, guys. Seriously, get on this rap train.

One of Corinna’s favorite Brinkman songs is “I’m a African” (yes, that’s the title, Corinna says). It’s a remake of a song by a gangsta hip-hop duo called Dead Prez, she explains. Dead Prez originally meant the song to be a black nationalist anthem—an exclusionary song—but the duo unwittingly wrote an all-inclusive song, because all of our human ancestors originated in Africa. Brinkman changed the lyrics to highlight that point, and he even managed to get the Berkeley conference’s diverse attendees to pump their fists in the air and shout the “I’m a African!” chorus along with him, she recalls. You a African? You a African?/Do you know what’s happenin’?/I’m a African, I’m a African/Geneticists know what’s happenin’ …

Coolness factor, we’re tellin’ ya.

For her next Newscripts item, Corinna wrote about something distinctly uncool for rappers: pearls. “I suspected that pearls would not be a rapper’s bling of choice, but I wanted to check,” say says.

Continue reading →