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September 2012

Canadian Chemical News | l’actualité chimique canadienne

SMALL-TOWN PHARMA burning biofuels under the hood Antibiotics in the wake of wonder drugs



Chemical Institute of Canada www.accn.ca


Table of Contents

September 2012 Vol.64, No.8

Features chemistry

David Corkum (left)

business

16

Small Time

The venom of a small rodent sparked a small drug company in a small New Brunswick town. Expectations for ­success are big. By Anita Lahey

owen egan

CHEMICAL ENGINEERING

24

Burning Questions

Finding the next incarnation of the combustion­engine in the age of biofuels­. By Sylviane Duval

20

Waning of the Wonder Drugs With bacterial resistance on the rise, where will we get the drugs of the ­future? By Tyler Irving

Departments 5

From the Editor

6

Letters to the Editor

9

Guest Column By Cathleen Crudden

10

 hemical News C By Tyler Irving

29

Society News

30

ChemFusion By Joe Schwarcz

September 2012 CAnadian Chemical News   3


 Canadian Society for Chemical technology | Professional Development

advance your professional knowledge and Further your Career

laboratory safety Course september, 17–18, 2012 toronto, ont. For chemists and chemical technologists whose responsibilities include managing, conducting safety audits or improving the operational safety of chemical laboratories, chemical plants and research facilities.

Course outline and registration at

www.cheminst.ca/profdev Continuing professional Development presented by the Chemical institute of Canada (CiC) and the Canadian Society for Chemical  technology (CSCt).

Outreach

national Chemistry week! october 13-21, 2012 NCW is an annual, week-long, celebration of the chemical sciences in Canada. it presents a great opportunity for youth to get connected with the wonders of the chemical sciences. get your children, classrooms and/or colleagues involved. visit www.cheminst.ca/outreach highlighted activities of 2012: Canadian Water experiment, “It's Chemistry, Eh!? ” youtube Contest, National Crystal growing Competition golD SpoNSorS

Silver SpoNSorS

disCounT memBers FOR CIC/CSCT


FRom the editor

Executive Director

Roland Andersson, MCIC

Editor

Jodi Di Menna

news editor

Tyler Irving, MCIC

art direction & Graphic Design

Krista Leroux Kelly Turner

contributing editors

Peter Calamai Tyler Hamilton Tim Lougheed

Society NEws

Bobbijo Sawchyn, MCIC Gale Thirlwall

Marketing Manager

Bernadette Dacey, MCIC

Marketing Coordinator

Luke Andersson, MCIC

Circulation

Michelle Moulton

Finance and Administration Director

Joan Kingston

Membership Services Coordinator

Angie Moulton

Editorial Board

Joe Schwarcz, MCIC, chair Milena Sejnoha, MCIC Bernard West, MCIC

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Subscription Rates Go to www.accn.ca to subscribe or to purchase single ­issues. The individual non-CIC member ­subscription price for 2012 is $100 CDN. The institutional subscription price for 2012 is $150 CDN. Single copies can be ­purchased for $10. ACCN (Canadian Chemical News/ L’Actualité chimique canadienne) is published 10 times a year by the ­Chemical Institute of Canada, www.cheminst.ca.

T

he fundamental purpose of any good magazine, in my view, is to make people think. To relay information? Sure. To entertain with good storytelling? Certainly. To report on important developments? Absolutely. But ultimately, if we can engage a community of readers in a dialogue on a relevant and topical subject, we’ve been successful. That’s why our “Letters to the Editor” pages are so important. This is where we can publish your points of view. Your comments help us to keep the discussion alive with the rest of our readership, who, we know from experience, very much want to read what their peers have to say in response to the stories we publish or about something happening in the subjects we cover. Lately, we’ve been getting several letters: insightful, thought-provoking, articulate letters. We couldn’t be more thrilled. You can read three of the most recent letters we’ve received on pages six and seven of this issue. Keep the e-mails to the editor coming! We’ll print your ideas and in this way help connect you to your fellow readers. In this issue we attempt to provoke your thoughts with a report by expert story teller Anita Lahey. She writes about a company in New Brunswick that illustrates how small enterprises are increasingly taking on the high-risk early stages of pharmaceutical research. In our Q and A, we talk to Gerry Wright about how our approaches to creating antibiotics are shifting in the face of resistant strains of bacteria. We then move on to the question of how combustion engine designs are evolving in the age of biofuels. Hope you enjoy the read!

Recommended by the Chemical Institute of Canada (CIC), the Canadian Society for Chemistry (CSC), the Canadian Society for Chemical Engineering (CSChE), and the Canadian Society for Chemical Technology (CSCT). Views expressed do not necessarily represent the official position of the Institute or of the Societies that recommend the magazine.

Change of Address

circulation@cheminst.ca Printed in Canada by Delta Printing and postage paid in Ottawa, Ont. Publications Mail Agreement Number: 40021620. (USPS# 0007–718) Indexed in the Canadian Business Index and available online in the Canadian Business and Current Affairs database.

Write to the editor at magazine@accn.ca

ISSN 0823-5228

Visit us at www.accn.ca September 2012 CAnadian Chemical News   5


letters to the editor

Wither are you going, DFO?

The media has recently reported that Fisheries and Oceans Canada (DFO) is closing its environmental chemistry and toxicology programs. This action is short-sighted. I worked almost 33 years at DFO’s St. Andrews Biological Station (SABS) in St. Andrews, N.B. In 1988 DFO decided to separate chemistry and biology and to place them in different organizational structures and sometime in the 2000s, went a step further and organized two specialized chemistry centres, one on each coast. These centres now appear to be closing. Instead of in-house expertise and laboratories, DFO will rely on contracts for environmental chemistry and toxicology work. State-of-the-art analytical chemistry equipment is very expensive and cannot be duplicated in several locations; maintaining it in just one or two laboratories is a good decision. On the other hand, chemical expertise and routinely-equipped laboratories should be present in all DFO’s research establishments. Contracts cannot replace them. Contracts are suitable for well-defined tasks with precise endpoints, provided the results are checked by in-house knowledge. Contracts are useless for exploratory projects. When I began work with the water pollution section (WPS) of SABS in the late 1960s, my first project was to participate in a study of salmon movement in the Miramichi estuary. I concentrated on organic chemicals whose major sources were two pulp mills and a wood-preserving plant, which used, as it was common knowledge, creosote. I soon detected a high concentration of pentachlorophenol in the effluent. At the same time, WPS was also studying acidification of a river receiving a tailings pond effluent in northeastern New Brunswick. The investigation was carried out by a contract awarded to a university and by in-house measurement of heavy metals and pH in water samples. No cause of the acidification was found, but when I added hydrochloric acid to a sample, release of colloidal sulfur showed that the acidification was caused by thiosalts formed by oxidation of pyrite in the mine’s concentrator, and the rest is history. Shortly afterwards, SABS was called on to investigate massive herring kills in Long Harbour, Nfld. suspected to be caused by yellow (elemental) phosphorus. Our tests demonstrated its high toxicity to herring. Since it’s also highly toxic

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september 2012

to humans, this was dangerous work and could not have been carried out without an in-house lab and chemical expertise. As a result of our work, a company accepted responsibility for the fish kills. In another example from my time with DFO, a survey of DDT in freshwater and marine fish was performed by a contract, without in-house quality control. The contractor’s report did not mention PCBs, or even the presence of unidentified peaks in the gas chromatograms, although PCBs must have been present. This again is an example of a failed contract, since, among other things, PCBs interfere with the measurement of DDT. These examples illustrate the importance of on-site labs and chemical expertise, and the impossibility of replacing such studies by contracts. There is a need to maintain chemical and toxicological expertise in all DFO research establishments. In response to the decision to eliminate it, I wonder “Quo vadis DFO?” [Whither are you going, DFO?] Vladimir Zitko St.Andrews, N.B.

Budding business

Alanna Mitchell’s article “Water Works” (July/August 2012) bemoans the fact that good ideas developed in the science halls of our universities do not make it “out of the lab.” (One ­exception pointed out was, sadly, picked up by a French company, not a Canadian company.) Most universities have a faculty dedicated to entrepreneurial pursuits. It seems obvious that the science folks should partner with these budding business people to bring the former’s ideas to fruition. Indeed, within a university, there should be a requirement for these two disciplines to cooperate by assigning a potential “good idea” to a senior or graduate business student as a bachelor’s or master’s project with the object of developing the idea into a viable business model. I see a place for the engineering department to become involved as well. Gordon A. Boyce Dartmouth, N.S.


letters to the editor

Ethics radar pinging

In response to the latest Canadian science budget (Letters , June 2012), I am feeling increasto the editor, ingly torn. I am so fortunate to have a dynamic, wonderful research group of motivated and ambitious students, post-docs, ­u ndergraduates and others (our highly qualified personnel!), and the most important thing I can do, as their supervisor, is to repay their effort and loyalty by supporting them for the rest of their careers as best I can. I am torn because, in the past, I did everything in my power to help them find their first “real” jobs in Canadian academia, government and industry, and I will of course continue to do so if that is their wish. However, these days, with respect to academia, my ethics radar is pinging loudly because I am concerned about the future of young researchers in this country. I sense a moral dilemma. Can we continue to promote academia to our young people when they are faced with substantial cuts that potentially undermine their ability to do their job, if they can even get one? Scholarships and equipment grants are under attack, and these cuts hurt young people far more than older, established people like me. Even the number of new professorial jobs that I could see this year in Canada was very low as universities grapple with budget challenges. Minor top-ups to “starting” Discovery Grants do little to help these new professors get their programs kick-started. We are competing now with aggressive and highly funded universities in the Middle East, Asia and Europe that are wooing our best and brightest with an increasingly loud siren call; I've now personally witnessed top young Canadian-trained highly qualified personnel move to assistant professor positions in Saudi Arabia, Germany, Korea and China in the past two years thanks to funding packages that will allow them a fair chance. To lose a generation of researchers will be devastating to Canadian science. We have little time to act to prevent this enormous loss of talent.

Correction: The Kingston, Ont. company, PARTEQ Innovations, does not receive paid industry sponsors as stated on page 25 of the July/August 2012 issue (“Water Works” by Alanna Mitchell). The sponsors mentioned are associated with PARTEQ’s spinoff, GreenCentre Canada. Write to the editor at magazine@accn.ca. Letters are edited for length and clarity.

Jillian Buriak Professor of Chemistry University of Alberta

September 2012 CAnadian Chemical News   7


guest column

Making molecules matter

L

ast May, I left the 95th Canadian Chemistry Conference and Exhibition in Calgary full of enthusiasm for my coming year as CSC president. In particular, I was invigorated by the enthusiasm for the Canadian Society for Chemistry’s increasing role as an advocate for science. Advocacy is a complicated subject. We were lucky in Calgary to have Howard Alper, the current chair of the Government of Canada’s Science, Technology and Innovation Council, NSERC president Suzanne Fortier and University of California, San Diego chancellor Marye Anne Fox, provide advice on how best to advocate for science. In my role as president of the CSC, increasing our efforts at advocacy is at the top of the list of things I plan to accomplish. So when I finally boarded the plane home from the conference, I was energized for the coming year, but also a touch tired after a week of activities. When Rebecca — a talkative 40-something waitress — sat down beside me, I saw my chances of catching up on sleep evaporating. Eventually Rebecca asked me what I did. When I told her I was a chemist, she asked what I “actually” did. So I told her I was an organic chemist, and worked on a class of molecules that have rightand left-handed forms. I talked about how these molecules have a big impact on a variety of industries, including the pharmaceutical industry, but how most people don’t appreciate the impact that handedness has on the properties of a molecule. Before I got further, she asked: “What’s a molecule?” Switching gears, I talked about atoms and how they’re

arranged in groups to make molecules, and how chemists can actually control this, including even how atoms are arranged in space. A great example is CH3CH2OH (ethanol, which we both agreed is a very respectable and tasty molecule) and its isomer CH3OCH3, which has exactly the same number and type of atoms, just arranged differently. Rebecca was surprised to hear that this new molecule had completely different properties and was not at all something you would want in a drink, even if it wasn’t a gas at room temperature. From there, we moved into the discussion of research funding, and I used the example of green energy. Undoubtedly part of our energy future will involve solar, wind and other alternative energy choices, Rebecca agreed. However, if we don’t invest now to support early stages of research in these areas, Canada will be buying such technologies in the future, rather than selling them. Surely that’s not where we want to be as an advanced nation. Of course it gets more complicated when one realizes that predicting tomorrow’s great discoveries is not a trivial matter. Take NMR (Nuclear Magnetic Resonance) spectroscopy for example. When this technique was first invented, it was thought to be a toy for physicists. But now, this is one of the most important tools in chemistry that allows us to look at molecular structure. Perhaps more importantly, NMR forms the basis of Magnetic Resonance Imaging (MRI), something that changes the lives of multitudes of Canadians every day. The laser, the telephone, digital cameras: these are all

By Cathleen Crudden

examples of incredibly useful inventions that came out of basic research. Funding science is tricky business. Yes, it’s very important to fund research that will make an impact on people’s lives in the near term. We can all understand the value of things like energy, health, information technology and green chemistry. But equally important is funding research for which the objectives may not be immediately obvious, because predicting the future is also a difficult task. Luckily investing in the future isn’t. NSERC and the other granting councils have a great track record of funding research excellence in all its iterations from basic to applied, and money given to them to fund Canadian research goes extremely far. So continued investment in NSERC, CIHR and the Social Sciences and Humanities Research Council of Canada (SSHRC) is a great way to support the future of science and the future of Canada. Most importantly, scientists must take the time to advocate for science. What I learned on my plane ride from Calgary is that being an advocate doesn’t just mean talking to politicians and policy makers. It also means talking to people like Rebecca, and taking the time to convince Canadians who don’t necessarily work in the sciences of the importance of what we do with their tax dollars. If we’re successful, research funding can be a priority for all of us. Cathleen Crudden is the 2012-2013 President of the Canadian Society for Chemistry and a professor in the Department of Chemistry at Queen’s University. To find out more about the CSC’s advocacy initiatives go to www.cheminst.ca.

September 2012 CAnadian Chemical News   9


Chemical News Earth Chemistry

­ anadian C ­research ­disproves ­arsenic-based DNA The discovery of a bacterium that can use arsenic instead of phosphorus to construct its DNA is ‘flim-flam.’ That’s according to University of British Columbia ­micro­­bio­logist Rosie Redfield, who this summer published what she says is the final word on the controversy that has come to be known by its Twitter hashtag, #arseniclife. In December 2010, Felisa Wolfe-Simon and her colleagues at the NASA Astrobi-

ology Institute and the U.S. Geological Survey published a paper in Science reporting on a new organism isolated from arsenic-rich Mono Lake in California. Called GFAJ-1, it grew on artificial media that contained high levels of arsenic and very low levels of phosphorus. Secondary ion mass spectrometry (SIMS) appeared to show arsenic associated with its DNA. Days after the publication, Redfield posted a rebuttal on her blog. Among her many objections was the claim that there wasn’t enough phosphate for growth. “If you starve bacteria for phosphate, they can be very economical with it,” says Redfield. “My calculations suggested there was just enough phosphate to explain the amount of growth they saw.” Others joined in the fray, pointing out that the arsenate ester bonds that would be required to make arsenic-based DNA are unstable in water, with an estimated half-life of less than one second. Despite these concerns, the original authors continued to insist that their results were valid and did not retract the paper. Redfield then decided to solicit help in trying to replicate the findings herself. In her latest paper, also published in Science, her team used stringent DNA purification protocols that weren’t followed by the original authors. The arsenic disappeared, indicating it wasn’t covalently bound to DNA. Moreover, the purified DNA was stable in water for months, something that wouldn’t be true of an arsenic-based molecule. For Redfield, the latest publication marks the end of the story. Still, she would have preferred to see a retraction of the original paper. “When researchers publish things that are not true, they should be apologising for them,” she says. “I don’t think anybody has apologised.”

Health

Neutralizer assay improves biological sensing

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September 2012

Alya Bhimji

DNA probes designed to detect specific biomolecules coat the tips of gold electrodes, like these ones embedded in a silicon chip. A new assay developed at the University of Toronto pairs each DNA probe with a neutralizer made of peptide nucleic acid (PNA). The technique increases the sensitivity of the probes, and allows for a single chip that can detect hundreds of analytes at once, from adenosine triphosphate (ATP) to cocaine.

Imagine a portable electronic device that could analyse­ blood for up to 180 different components at once: sequences­ of DNA and RNA, proteins and even small molecules like adenosine triphosphate (ATP). It sounds like science fiction, but a discovery at the University of Toronto is bringing such a device closer to reality. Electrostatic sensor systems use probes composed of short DNA sequences attached to an electrode. Since DNA is negatively charged, binding of the probe with a complementary strand results in a higher magnitude of charge. This change triggers the reduction of reporter ions electrostatically associated with the DNA strands, creating an electric current that can be measured. However, there are drawbacks. “Traditional assays can only detect molecules with significant negative charges like DNA and RNA,” says Jagotamoy Das, who works under the supervision of Shana Kelley in the Department of Pharmaceutical Sciences at U of T. Additionally, because


Canada's top stories in the chemical sciences and engineering

| ChemiCAl news

TEChnIQuES

keviN DaZe

Calixarene tool kit can read epigenetic codes A group of researchers at the University of Victoria has demonstrated that calixarene molecules can be used to read information encoded on DNA-packaging proteins called histones. The discovery provides a new tool for the emerging field of epigenetics, the study of heritable information stored in molecules other than DNA and RNA. In the past, histones were thought of as spools around which DNA was wound. More recently, post-translational modifications to the histones — for example, acetylation or methylation of certain amino acids — have been shown to play a role in determining which genes get expressed at which times. This epigenetic ‘histone code’ can be probed by antibodies in enzyme-linked immunosorbent assays (ELISAs). But such assays have shortcomings. “Some code elements are really similar and difficult to distinguish,” says Fraser Hof, professor of chemistry at the University of Victoria, noting that the failure rate with antibodies is over 20 per cent. Hof’s group has been working on an alternative approach based on calixarenes. These cup-shaped macromolecules bind preferentially to certain histone code elements. In a paper recently published in the Journal of the American Chemical Society, Hof’s group described a new assay in which various calixarenes, each paired with a fluorescent dye, were exposed to peptides bearing the modifications of the histone code. The dyes were quenched by binding to the calixarenes, but histone code elements compete for the binding site. Since each calixarene has a different affinity for a given code element, a pattern of fluorescent responses results. Taken together, the signals lead to a unique ‘fingerprint’ for each code element.

Cup-shaped calixarene molecules can bind to the post-translational modifications that are added to the amino acids of proteins called histones. here, a monobrominated p-sulfonatocalix[4]arene (spheres) binds to a trimethyl group (stick figures) which is attached to a lysine residue. Such a system could assist researchers probing the epigenetic code, which regulates how genes are turned on and off in complex organisms.

A set of only three calixarenes was sufficient to distinguish histone code elements with a high degree of reproducibility. “We really didn't expect this to work so well; I thought we were going to need up to 10 different sensors,” says Hof. Even better, the system works in real time, unlike ELISA. The team hopes it can be used to study the activity of the enzymes that add and remove histone code elements.

the change in charge is often small compared with the background, such sensors are not sensitive enough to detect analytes at low — but still physiologically relevant — concentrations. The new assay developed by Das and his colleagues relies on a neutralizer made of peptide nucleic acid (PNA). The charge of this synthetic DNA analogue can be tuned by adding cationic amino acids to the end, while its affinity for the DNA probe can be controlled by introducing mismatches to its sequence. A properly designed PNA sequence will neutralize the probe but will be dislodged when the molecule of interest binds to the probe instead. This results in a bigger charge difference than with DNA alone and allows for the detection of neutral molecules, even at low concentrations. In a paper published in Nature Chemistry, the team shows that the new system works effectively with probes designed for DNA, RNA, ATP and even cocaine. Best of all, the electrodes can be miniaturized and embedded on chips, allowing for fast and portable systems capable of detecting hundreds of analytes simultaneously. A spin-off company founded by Kelley, Xagenic Inc., is working toward developing commercial systems. The technology could have applications in medicine, forensics and many other fields.

September 2012 CAnAdiAn ChemiCAl news

11


Canada's top stories in the chemical sciences and engineering

| Chemical News

Peter Alan, University of California – Santa Barbara

Biochemistry

Tryptophan technique illuminates protein folding Misfolded proteins are implicated in diseases from Alzheimer’s to Parkinson’s, but tracking the process by which they occur remains one of biochemistry’s greatest challenges. Now, a team at Université de Montréal has shown that a technique based on the fluorescence of tryptophan might be a better tool to probe protein folding than anyone previously thought. The transitions involved in protein folding are notoriously difficult to study as the half-folded intermediates don’t usually last long enough for their unique signatures to be unambiguously detected by traditional methods such as crystallography or nuclear magnetic resonance (NMR) spectroscopy. An alternate method is based on the fluorescence of tryptophan (while several amino acids exhibit fluorescence, tryptophan’s is the strongest). By measuring changes in the light emitted by excited tryptophan molecules, researchers can glean information about the local environment in a specific part of the protein. “It has become dogma that tryptophan has to be at least partially buried in the folded structure in order to see a strong change in fluorescence between unfolded and folded states,” says Stephen Michnick, a biochemist at Université de Montréal. In a technical report published in Nature Structural and Molecular Biology Michnick and Alexis Vallée-Bélisle disproved that theory. They created mutant versions of the protein ubiquitin with tryptophan substituted in sites that were exposed on the surface of the protein. Fluorescence spectroscopy showed that even on these sites, the electronic differences between folded and unfolded states was still enough to cause detectable changes in fluorescence. The team went on to create mutant versions of ubiquitin with up to 27 of its 76 amino acids

In this artist’s impression, yellow tryptophan fluoresces ­between two assembly states of the protein ubiquitin, which are drawn at a different scale. A team at Université de Montréal has shown how tryptophan can be used as an effective probe to monitor conformational changes in protein folding.

replaced with tryptophan. The larger number of probes allows researchers to study many areas of the protein at once. The technique is surprisingly simple, which Michnick says is precisely the point. “I hope this gives the protein community a license to try something that they probably wanted to try but didn’t have the nerve to, because they thought it was crazy,” he says. He adds that the technique could be applied not only to protein folding intermediates, but any conformational change in proteins including allosteric transitions and macromolecular assembly.

Pharmaceuticals

Pateamine A could combat muscle wasting Cachexia - chronic and irreversible muscle wasting - is a common cause of death in patients with cancer or AIDS. New research shows that a molecule called pateamine A can interfere with the biochemical pathways that cause cachexia, and may point the way toward a therapy. Pateamine A is part of a family of cytotoxins first isolated in the early 1990s from marine sponges in New Zealand. It has since been shown that pateamine A is a general inhibitor of enzymes involved in the translation of genes into proteins. At high doses, this leads to cell death. However, at lower doses, pateamine A has been shown to have anti-tumour and anti-inflammatory effects, although it’s not yet clear how these effects occur. Imed Gallouzi is an associate professor in the Department of Biochemistry at McGill University. His group has been studying the molecular mechanisms behind muscle wasting. Since cachexia is often triggered by inflammation, Gallouzi theorized that the

anti-inflammatory properties of pateamine A might protect against muscle wasting. In research published in Nature Communications, the team demonstrated that cultures of muscle cells grown in petri dishes and treated with low doses of pateamine A (less than 0.125 μM) were protected from muscle wasting induced by inflammation-causin g enzymes IFNγ and TNFα. Those same low doses were also able to prevent muscle wasting in mice exposed to the same inflammation-causing enzymes and in mice injected with cachexiacausing tumours. Why it is that low doses of pateamine A inhibit cachexiainducing enzymes but leave others alone is still a mystery that Gallouzi and his team are working to nail down. They are motivated by the fact that no cachexia therapeutic currently exists. “So far it’s an irreversible condition,” says Gallouzi. “If we are successful, we would dramatically improve the quality of life for these patients.”

September 2012 CAnadian Chemical News   13


Chemical News Polymers

Indium catalysts improve biopolymer synthesis

For years, starch-derived, biodegradable poly(lactic acid) has been a popular bioplastic, but its market penetration has been limited by undesirable mechanical properties and low heat tolerance. A series of indium catalysts developed at the University of British Columbia could provide a solution. Poly(lactic acid) (PLA) is made by ring-opening polymerization of lactide, which itself is a condensed dimer of lactic acid. Because lactic acid is chiral, there are several forms of PLA. Both the left-handed L form (PLLA) and the right-handed D form (PDLA) have relatively low melting points, as do random (atactic) mixtures or alternating (heterotactic) mixtures of the two. However, if the polymer is made as a stereoblock - a chunk of PLLA followed by a chunk of PDLA - its heat tolerance increases significantly. UBC chemist Parisa Mehrkhodavandi has been studying the chiral catalysts needed to make stereoblock PLA. While certain tin and aluminum complexes have been shown to selectively form PLLA over PDLA, they have their drawbacks. “Lactide derived from biological sources will always have some water in it, but most known catalysts are decomposed by water,” says Mehrkhodavandi. They can also take days to react, and can be thrown off by any functional groups that might be added to the monomers to improve their properties. In contrast, Mehrkhodavandi’s group has developed unique catalysts based on ­indium. Not only are they more tolerant of water and functional groups, they are also much

more active. “The aluminum system takes 12 days to do what we can do with indium in 30 minutes,” says Mehrkhodavandi. The key to this reactivity, as confirmed in a recent paper published in the Journal of the American Chemical Society, is that the indium complexes have two metal centres as opposed to one. Despite these advantages, there is still work to be done; for example, the ­enantioselectivity is still not quite as high as with the slower-acting aluminum complexes. Nevertheless, the technology has been licensed by the commercialization organization GreenCentre Canada, which is working with Mehrkhodavandi and unnamed partners toward industrial application.

Environment

No trend in Athabasca fish mercury levels: government study Among the many concerns arising from increased oil sands development is the potential for rising levels of mercury in Athabasca River fish. However, a study released this summer by Environment Canada (EC) found no significant trend in these levels since the 1970s. The study is a response to one published in 2009 by Kevin Timoney of Treeline Ecological Research and Peter Lee of Global Forest Watch. Based on publicly available data from three fish sampling events — from 1976, 1992 and 2005 — that study concluded that mercury levels in Athabasca fish had risen significantly. The more recent study, published in the Journal of Environmental Monitoring, included a much broader range of data. It also attempted to account for inconsistencies in previous data gathering. For example, mercury concentrations are higher in older, larger fish as a result of bioaccumulation, so studies must be adjusted for body size. As well, mercury accumulates in some organs more

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than others, so concentrations in fillet (muscle) tissue can’t be directly compared with whole body measurements. “After we corrected for many of these things, we found no specific, discernible trend in mercury levels in the Athabasca River,” says Andre Talbot, one of the co-authors of the EC study. In response, Kevin Timoney says he welcomes the new study, but that “it is dangerous to confuse failure to find an effect with lack of an effect.” Both researchers agreed that inconsistent data gathering in the past has made it difficult to attribute mercury levels in fish to any one source, anthropogenic or otherwise. In response to criticisms such as these, both the federal and Alberta governments are implementing what they claim will be a “world-class” monitoring program for potential pollution of the Athabasca. Talbot says that the current study should be viewed as a baseline for this new program.

Parisa Mehrkhodavandi

The chirality or “handedness” of its monomer strongly influences the properties of poly(lactic acid) (PLA), one of the world’s most popular renewable polymers. Both the random (atactic, top) and alternating (heterotactic, middle) patterns result in polymers that are amorphous, with relatively low melting points. In contrast, an isotactic stereoblock (bottom) polymer has a higher melting point. A new class of indium catalysts developed at the University of British Columbia could allow for faster synthesis of stereoblock PLA that is more tolerant to impurities like water.


small

Time J

The big risks and big e ­ xpectations of a small drug company in small-town New Brunswick. By Anita Lahey

ack Stewart, a biochemist, jokes that normally he would not be caught dead cavorting with a biologist. But 12 years ago, an Australian biologist visiting his labs at Mount Allison University in Sackville, New Brunswick, beckoned him to look under a microscope. As Stewart peered at the tooth of a northern, short-tailed shrew, the Australian said, “See that little groove? That’s where the venom is delivered.” “No, no,” Stewart protested. “This is just a local shrew!” But his colleague knew his stuff: the diminutive shrew, which might be mistaken for a mouse and is the most common small mammal in eastern North America, possesses a secret weapon. As it bites its prey (often an insect), a poison in its saliva causes profound paralysis. When Stewart asked how it worked, the biologist replied, “You’re the biochemist, you figure it out.” That unexpected encounter diverted Stewart from a 25-year research focus on biochemical adaptations and ultimately led to the creation, in the unlikely locale of small-town New Brunswick, of Soricimed Biopharma Inc., one of the tiny startups that are increasingly taking on the high-stakes, early stages of drug research and development. Named after the taxonomic family to which the shrew belongs (Soricidae) and founded in 1995 by Stewart and Moncton businessman Paul Gunn, the company employs five researchers in a 2,000-square-foot, state-of-theart laboratory in what was once a car dealership and a pub: a low-rise, ex-strip mall on the outskirts of Sackville, a town with a single traffic light about a half hour’s drive from Moncton. “We see the morning sun rising over the Tantramar Marsh and Chignecto Bay at the top of the Bay of Fundy,” says Stewart.

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It’s in this idyll that Stewart awaits the results of Phase 1 clinical trials that began in July for SOR-C13, a peptide designed, based on the properties in the shrew’s saliva, to treat ovarian cancer. [As ACCN went to press on August 14, Soricimed announced that the first patient had begun treatment with SOR-C13 at the Juravinski Cancer Centre in Hamilton, Ont.] Should the study yield promising results, Soricimed’s plan, typical of the micropharma model that is transforming the drug industry, is to partner with a large American pharmaceutical company for Phase 2 trials and beyond, in what is known as a “co-development deal.” “Large pharma has really cut out early stage discovery and research,” says Gunn. “They rely on companies like us to bring research to a certain stage.” The partners then divide clinical development and market approval


Business | Pharmaceuticals

of a drug, with the larger company taking on the bulk of later-stage development plus marketing and distribution. The smaller partner receives an upfront payment, “development milestone payments” and, when (or if) the product gets to market, a royalty. “It’s much more capital-efficient than if we tried to do everything ourselves,” says Gunn. “The risks get shared.” Gunn has his eye on risk for good reason. Poised to spend a quarter of its $10.5 million in capital on its Phase 1 trials, and in need of far more cash to carry on to Phases 2 and 3 — up to $130 million expected to be covered through a partnership with a large pharmaceutical company — Soricimed is in sore need of investors and public funds, both of which its home province is short on. As a recent Toronto Star article on Soricimed’s plight reports, New Brunswick logs the lowest cash injection from the Canadian

Institutes of Health Research of any other province by a long shot: $1.46 per capita, compared to $26.03 for Ontario and Nova Scotia. Add to that the dim prospects faced by your average biopharma start-up, even those situated in more flush locations. Donald Weaver, Canada Research Chair in Clinical Neuroscience at Dalhousie University in Halifax, who has co-founded seven biotechnology companies and documented the rise of the micropharma phenomenon, asserts that more than 90 per cent of small biopharma ventures fail. “Drug discovery in general is high-risk,” says Weaver. “It takes about 15 years to push a drug out, and this has only been going on about 15 years, so it’s a bit early in the game to say how micropharma is really performing.” That said, having reached Phase 1 trials — which establish a safe dosage for Phase 2 trials involving 50 to 100 patients — gives Soricimed a favourable outlook. “Most fail long before Phase 1,” says Weaver. “And if you can get through Phase 1 successfully, that is a major accomplishment, it’s a ‘pop the champagne cork’ time.” Like most scientific research, early-stage drug development often involves following hunches that lead nowhere. The road to SOR-C13 was different: the hunch led to two potentially promising discoveries. What happened next shows why small and nimble, when it comes to companies building new drugs, can work so well. Shortly after his encounter with the biologist, Stewart learned that research into the shrew’s poison begun in the early 20th century “fell off the map” by the 1960s. “Nobody had discovered what the compound was.” Stewart got down to business. Step one: trapping shrews, which he did in his own backyard, using live Sherman traps baited with No Name pepperoni. “None of this highfalutin fancy stuff,” he says. “Shrews go after the fattier food.” Step two: with the help of student researchers in his lab, Stewart separated the components in the shrew’s saliva then conducted a series of bio-assays, injecting each component into mealworms (flour beetle larvae). “Anything that wasn’t paralytic was eliminated,” he says. “Eventually there is only one thing left.” The process took two years. Another year, and they’d isolated enough of the compound to decode its amino acid sequence (a peptide is a sequence of bonded amino acids), which meant they could have the peptide replicated. “We could essentially order it, and start looking at its properties in the laboratory.” They quickly learned the peptide stops nerve transmission. There was a burgeoning field of research into toxic peptides being adapted for pain treatment, so Stewart steered his investigations in this direction. Then came the twist. “A couple of the cell cultures we were using started dying,” he says. “That is never a good thing, until you realize they’re cancer cells.” The peptide, lo and behold, had two functions: one end of the molecule blocked nerve transmission by hitting sodium channels. The other end blocked calcium uptake by cells, which had a profound impact on some cancer cells. Stewart realized he was onto something and pitched his project at an investor forum in Moncton. Paul Gunn, working in finance for a software company and “looking for something to invest in on the side,” was intrigued. He and Stewart met and hit it off. Gunn convinced the National Research Council (NRC), the Atlantic Canada Opportunities Agency (ACOA) and several private investors to join him in backing

September 2012 CAnadian Chemical News   17


Stewart’s research. “We had the happy problem of two very interesting potential drugs,” says Stewart. “But we were very tiny and poor. We couldn’t afford to run two development programs. We decided we’d start both, pain and cancer, and determine which direction the science would take.” Cancer won. Epithelial cancers such as breast, ovarian and prostate contain a calcium “channel” known as TRPV6 (transient receptor potential vanilloid family number 6) that, for reasons as-yet unknown, brings an abnormal amount of calcium into cancer cells. This contributes to tumour growth in two significant ways: it increases the rate at which the cells divide, and it inhibits apoptosis (the usual cycle of self-destruction when cells are under stress). Here’s where the shrew comes in: one half of the saliva peptide Stewart and his team had isolated — the non-paralytic half — automatically binds to the TRPV6 channel, which stops calcium from flowing into the cell. The stressed cell is thus able to begin its normal “suicide circuit,” ultimately shrinking the tumour. Further research with SOR-C13 — the synthetic peptide modelled after the shrew’s — on cell cultures, animal models and, finally, human tumours grown in ice, have consistently shown a deadly effect on tumours, without causing stress to other cells. This lack of toxicity is a holy grail in cancer treatment — as, it turns out, was the TRPV6 channel. “People have been calling TRPV6 an excellent potential drug target for almost as long as we’ve been doing this work,” says Stewart. “It’s a common refrain in scientific papers. Our drug is its only known inhibitor. The whole pain aspect is still sitting here waiting for development, but the cancer swept us away.”

*** Soricimed has grown modestly in tandem with its promising discoveries. In 2006, one year after incorporating, Gunn left his job at Whitehall Technology to focus wholly on the start-up. In 2007, Stewart took a leave of absence from the university. The following year the Sackville lab was set up, and by 2009 Stewart had retired from academia. The company now has more than 100 shareholders and has raised

18  CAnadian Chemical News

September 2012

$6.5 million in equity, plus $4 million from the NRC and ACOA. It wasn’t easy, says Gunn. The Atlantic provinces are not a hotbed of seed money such as the $150-million venture capital fund recently set up by Eli Lilly & Co., which is largely focusing its attention on the research of Quebecbased micropharma firms. “You have to work a lot more to get national and international exposure because people don’t come looking to Sackville for the next cancer drug, the next diagnostic drug, the next scientific breakthrough.” Gunn has countered this disadvantage in part by recruiting two former big pharma executives to his board, whose experience and connections have proven instrumental as Soricimed embarks on partnership talks with big pharma representatives. And although Sackville is not swarming with biochemists, Stewart’s connection to the university — plus the fact that Soricimed is the only game in town — allows him to handpick and recruit top-notch scientists. By pharmaceutical standards, Soricimed remains miniscule, what Gunn calls a “semi-virtual” company. New ideas are investigated in-house, then farmed out to third-party, contract research organizations. “One will look at toxicology,” says Gunn, “another at analytical processes. At any one time there could be a hundred to a hundred and fifty people working on our stuff from Vancouver to Newfoundland, as well as in the U.S. and Europe.” This approach has saved the purchase of a quarter of a million dollars worth of


joel sartore / david corkum

Senior research technician, Chris Rice (above, left) consults with chief scientific officer Jack ­Stewart in the lab at Soricimed ­Biopharma in Sacksville, New ­Brunswick. The company is in Phase 1 clinical trials for a cancer drug that is based on a peptide found in the saliva of the northern short-tailed shrew (below).

lab equipment, says Gunn, as well as the need for researchers with specialties Soricimed might only require occasionally. The company can reign in or ramp up research projects according to cash flow and other factors. “We can turn on or off work as we choose,” says Gunn. “We’re not stuck with huge overheads.” Weaver says that’s exactly why more and more drug development is coming out of universities and small biotechs: “They have the capacity to be flexible. If you start off in pain and all of a sudden go, ‘Woah, it works better in cancer,’ you can do that shift overnight. Try doing that in a huge corporation.” Though small pharmaceutical ventures have been popping up in Canada since the 1990s, in the early days of the micropharma trend, Soricimed remains unique in its backyard. “When we went through our application with Health Canada and the U.S. Food and Drug Administration, they told us ‘We can’t find any other company in New Brunswick that’s done this before. You should be in Montreal or Toronto or Boston, or anywhere but here.’ But we have a very small footprint. We can be where we want.” For the foreseeable future, that “where” is Sackville, despite the challenges that presents for the company’s investment prospects. Should its Phase 1 trials for SOR-C13 fail, Soricimed has more than pain treatment in its back pocket. Its peptide’s habit of travelling straight to a tumour makes it a great candidate for a diagnostic tool — an application the company is pursuing simultaneously. A study involving 6700 provincial blood samples in New Brunswick is underway, which will test SOR-C13’s ability to diagnose early-stage ovarian cancer, which typically shows no symptoms before its progression to later, untreatable stages. And that’s not all. The peptide might also be used to ferry traditional treatments through the body — again, because it beelines right for the cancer hot-spots. “You could attach a chemo drug and deliver it right to the cancer site, with less toxicity and using a lower dose,” says Stewart. “We have a number of products — not as many as large pharma, but we’d have to strike out a lot of times before we had nothing left.” Anita Lahey is a freelance writer formerly based in New Brunswick.

September 2012 CAnadian Chemical News   19


Waning of the Wonder Drugs With bacterial resistance on the rise, where will we get the drugs of the future? By Tyler Irving

In the face of reports of drug resistant strains of bacteria, like Staphylococcus aureus and Clostridium difficile, finding out exactly why the ‘wonder drugs’ of yesteryear appear to have lost their punch — and more importantly, what can be done about it — is critical. Gerry Wright, professor in the Department of Biochemistry and Biomedical Sciences at McMaster University, aims to answer these questions. Using tools like environmental genome sampling and highthroughput screening, he has gained new perspectives on how bacteria evolve resistance and has identified strategies that could lead to new drugs. ACCN spoke with Wright to find out how we will create the antibiotics of the future. ACCN You've said that the current situation with regard

to antibiotic resistance “approaches perfect storm characterization.” How so? GW For over 70 years, we’ve benefitted from an ample supply

of antibiotics. Today, that’s being eroded by an upsurge in antibiotic resistant strains of bacteria. At the very same time the pharmaceutical industry is looking elsewhere; they no longer see antibiotics as a profitable area of research. The end result is this ever-growing disconnect between clinical need and potential solutions, hence the ‘perfect storm.’ ACCN How have antibiotics been developed in the past? GW Probably the grandfather of antibiotic discovery is Paul

Ehrlich, who in 1909 systematically tested a series of chemicals — primarily dyes and arsenic-based compounds — for their activity against Treponema pallidum, the organism that causes syphilis. The result of this first high-throughput screen was Arsphenamine (also known as Salvarsan), a drug whose effectiveness was nothing short of stunning for its time. In the 1930s sulfonamides (sulfa drugs) were identified by Bayer AG and used to treat a wide variety of bacterial infections.

20  CAnadian Chemical News

September 2012

However, then as now, the most effective drugs came from natural products, which have consistently been of low toxicity and highly effective as drug molecules. The classic example is penicillin: Alexander Fleming identified the organism that produces it in the late 1920s, and by the early 1940s scientists had been able to purify and manufacture it. The time between 1940 and 1960 was really the golden era of antibiotic discovery. Small molecules produced by microbes, in particular fungi and soil-dwelling bacteria, were the source of the chemical scaffolds for almost all antibiotics in use today. Synthetic chemistry played a huge role in the elaboration of these natural scaffolds to create new drug molecules. The only significant antibiotic compounds that were completely synthetic were the quinolones and fluoroquinolones, identified in the 1960s and early 1970s. ACCN Much of your work focuses on studying how bacteria develop resistance to antibiotics. What have we learned about this over the years? GW Bacteria produce chemicals for almost every purpose,

from signalling molecules to antibiotics that keep the competition down. If microorganisms produce antibiotics, they have to have a way of protecting themselves, so the evolution of antibiotic resistance goes hand in hand with the evolution of antibiotics. Now that we can sequence the genomes of these organisms, we can trace these resistance genes. And because bacteria can share genes between species, these resistance genes show up even in bacteria that don’t produce antibiotics. In 2006 we had a paper in Science where we sampled the collection of all the antibiotic resistance genes in the genomes of non-pathogenic soil bacteria; we call this the antibiotic resistome. What we found is that these bacteria are resistant to many different antibiotics, on average somewhere between seven or eight of the 20 that we screened. Of course, there is the possibility that these microbes may


Chemistry | Antibiotics

have somehow been exposed to man-made versions of the antibiotics we were looking at. So last year some of the same people did a similar screen of the genomes of organisms that had been frozen in permafrost 30,000 years ago. And a few months later, we did the same for bacteria isolated from Lechuguilla Cave in New Mexico, where the bacteria had been cut off from the surface for at least 4 million years. In all cases, the result was exactly the same; they are all intrinsically multi-drug resistant. What this shows is that we have failed to understand the chemical ecology of antibiotics. We are lucky that the bacteria that cause disease have, by and large, been highly drug-sensitive, at least for the last 70 years or so. But our work shows that the resistance genes are out there in the genomes of non-pathogenic bacteria. On top of that, we’ve created a massive selection pressure to move those genes around. ACCN You’re referring to the use of antibiotics in everyday­products? GW Absolutely. The organisms that produce antibiotics have

been doing so on a microgram scale, in very confined environments. Even so, resistance has spread around the world among bacteria that live in those environments. But a situation like we’ve had over the last 70 years, where compounds like penicillin get applied on gram or kilogram scales, is

unprecedented in the history of this planet. Human use of antibiotics has provided an evolutionary pressure to move resistance genes from organisms that don’t cause disease into those that do. The fact that we have this problem of antibiotic resistance in what were almost universally sensitive organisms 70 years ago is the proof of this. ACCN Why haven’t drug companies kept up with the problem of resistance? GW Let me use an example: The first penicillin-resistant organisms were actually discovered before penicillin was made into a drug. These organisms produce enzymes called beta-lactamases that destroy penicillin. They were never really that much of a problem until the 1950s, when those beta-lactamase producing genes started to spread around. So medicinal chemists began tinkering with the structure of penicillin to render it impervious to these enzymes. The bacteria responded by evolving point mutations in those enzymes, and the cycle continued; it’s been a real arms race. By the 1990s, we ended up in a situation where we had basically exhausted our ability to tinker with existing scaffolds. There are only so many ways that you can differentiate drug molecules before they start becoming lousy drugs, with issues of toxicity, bioavailability and so on. What we need at this point is new scaffolds, and that’s really what’s been

Gerry Wright, shown here in his lab at the Michael G. DeGroote Institute for ­Infectious Disease Research, suggests that previously discarded chemical ­scaffolds might be one potential source of new antibiotics. An example is ­daptomycin, shown above. Originally discovered in the mid-1980s but rejected due to toxicity issues, the compound was finally commercialized in the 2000s, when new experiments showed that toxicity could be controlled with careful ­dosing.

September 2012 CAnadian Chemical News   21


lacking. The last really new scaffold was a lipo-peptide called daptomycin, discovered in the early- to mid-1980s. So we’ve exhausted our ability to make new derivatives and at the same time we haven’t discovered any new scaffolds. ACCN If that’s true, where are the antibiotics of the

future going to come from? GW There are scaffolds that have been looked at but were

discarded because we already had better drugs around. Daptomycin is a good example; when it was first discovered by Eli Lilly in the 1980s, early studies found that it was associated with toxicity, so it was dropped. Later, a new company called Cubist felt that they could deal with the toxicity by changing the dosing. They bought the rights and showed that, using appropriate dosing, it was perfectly viable; it’s now making something on the order of $700 million to $900 million a year. So that’s one possibility. I also think there’s always a great opportunity to keep looking to natural products. During the 1990s, a lot of drug companies worked very hard on using computer models to make synthetic antibiotics and that unfortunately has not worked. We haven’t yet figured out the rules for making molecules that will get into bacteria and kill them. So I’m biased toward natural products, and here we can really benefit from our ability to sequence genomes. Today we can sequence a bacterial genome in an afternoon for a thousand dollars, and that price keeps dropping. We’re no longer even limited to the species we can grow in the lab, which we know make up less than 10 per cent of the organisms that live in a gram of soil. Instead you can extract all of the DNA and sequence it directly, so you know everything that’s produced in there. Of course, you don’t necessarily know which genes will produce antibiotics, but you might find an interesting chemical scaffold worthy of investigation. I think there are tremendous opportunities there. Finally, another route we’ve taken in my lab with my colleagues Eric Brown and Mike Tyers is combining molecules. That takes advantage of what we’re now beginning to understand from systems biology, which is that a single molecule usually can’t completely shut down an organism’s ability to grow; in other words, true antibiotics are rare. There’s a lot of redundancy in microbial metabolism, with

22  CAnadian Chemical News

September 2012

biochemical pathways having all sorts of backups. It’s kind of like the internet; it’s very hard to shut down by unplugging one computer, but if you unplug two, three or four, you can at least start to affect the local networks. We can now do high-throughput screens for combinations of molecules, and we’ve been very successful in identifying some that can kill bacteria and fungi too. ACCN What will these changes mean for the way ­chemists work? GW I think chemists are going to have to get more comfort-

able dealing with natural products, since this is really where we’re going to find the new antibiotics. It’s tough because they are complex and challenging, with multiple stereocentres — not the kind of thing that is easy to work with. But more broadly I think this is going to really be an era of partnership. It has already been to some extent in the past, but the antibiotic field has not seen the level of co-operation between biologists and chemists that anti-hypertension or anti-cholesterol drugs have, for example. It will be medicinal chemists, analytical chemists and biological chemists working with geneticists who will help us find the new scaffolds. Another aspect is making sure these things get from the lab to the clinic. I think it’s evident that if we wait for the pharmaceutical industry to do this, we’re going to be waiting for a long time. On the other hand, history has shown us that the large pharmaceutical companies are very receptive to acquiring bright technologies and moving them down the clinical pathway. I think a lot of this research is going to get done in academic labs and in small biotech companies. The critical element is to make sure that we get sufficient interest by funders, whether those are venture capitalists, angel investors, government or private sector. There are lots of reasons to be hopeful, but the pump needs to be primed. ACCN Is this a war we can win? GW I don’t like the war mentality much, and in fact it has been

part of the problem. We’re not at war with these organisms, we’re just trying to control their growth. If we think of them as agents of evolution, as opposed to something we need to eradicate, we will have much better success in the future.


Perfecting the process of making biofuels is not enough. We need machines that can efficiently burn them. Researchers in McGill’s Alternative Fuels Lab are figuring out what the next incarnation of the combustion engine will look like in the age of biofuels.

Questions

By Sylviane Duval

T

24  CAnadian Chemical News

September 2012

Owen Egan

PhD student Sean Salusbury (left) and Jeffrey Bergthorson use an impinging-jet apparatus to produce a flat, stagnant flame, ideal for taking measurements at McGill’s Alternative Fuels Lab where they study the combustion and emissions from alternative and traditional fuels.

he Macdonald Engineering Building infamously burned to the ground in 1907. But now, over a century later, nobody minds that Jeffrey Bergthorson and his team like to play with fire in the safe confines of their newly renovated lab on the building’s first floor. The researchers carefully blend the right mix of fuel and air to create small, flat flames about three centimetres in diameter. Then they use laser diagnostics to probe the combustion chemistry of different fuels. These flames are the Number One apparatus of the Alternative Fuels Lab. The Number Two apparatus is no less unexpected: a tube containing a mix of fuel and oxidizer through which they blast a shock wave that raises the temperature of the fuel so it catches light. With this, they measure the time it takes for the mixture to ignite. “Nothing in here looks like a jet engine,” smiles Bergthorson, who is an assistant professor in the Department of Mechanical Engineering. “But these apparatus allow us to study the fundamental principles that precede engine design.” Bergthorson is part of a cross-Canada team, led by McGill plant science professor and Green Crop Network director Don Smith, that’s working on developing new kinds of fuel and the engines that can burn them. The network, called BiofuelNet, was one of the winners of the Government of Canada’s 2012 Networks of Centres of Excellence competition, announced in May, which supports promising collaboration between


Chemical Engineering | biofuels

researchers and industry. Instead of processing crops that could be used for food, they’re developing ways to turn waste, such as wheat straw, corn stover (leaves and stalks) or even wood salvaged from demolished buildings, into fuel. (Growing crops isn’t out of the picture entirely though: BiofuelNet is also looking at the energy potential of “purpose-grown biomass” — things such as willow trees or fast-growing grasses that aren’t edible and don’t require prime agricultural land.) Bergthorson’s expertise, however, is in the combustion, not the creation, end of things: Once you’ve created a biofuel, how does it burn? And how can engine design be tweaked to get a bigger waste-intoenergy bang for the buck? When Bergthorson was completing his PhD at Caltech during the early 2000s, the “burning” questions in aerospace technology related to advanced high-speed propulsion and, therefore, combustion. Before turning his attention to how alternative fuels might benefit the commercial aviation industry, he studied supersonic combustion for hypersonic aircraft. Jet fuel is strictly regulated. It must meet strict standards for energy content per litre, composition, viscosity, surface tension and other physical and chemical properties — tough criteria that make it impossible to use oxygencontaining biofuels such as ethanol or first generation biodiesel in aircraft. As well, the industry has put its foot down on the stratospheric cost of retooling

the fuel supply system at airports and upgrading the global airline fleet for non-compatible fuels. The combustion engine isn’t going away. “Renewable source or otherwise, jet fuel has got to be a hydrocarbon similar to petrofuel,” says Bergthorson. “There aren’t any disruptive technologies because nothing else has the high power-to-weight ratio or the necessary energy density. Hydrogen takes up too much space, and the power density of batteries is too low. There isn’t going to be an electric jumbo jet.” The question is not whether alternative fuels burn — we already know that any hydrocarbon burns in the heat and pressure of an engine. It is how they burn — the way their physical and chemical properties affect the performance of the engine — and what comes out of the proverbial tailpipe. One issue is materials compatibility. Alcohol- or vegetable-oil-based biofuels, for example, are corrosive and can wreck rubber seals by changing the way they swell. (It’s serious business: the space shuttle Challenger tragedy was caused by rubber seal failure.) Another issue is physical properties. A biofuel with a different viscosity than petrofuel will spray into the engine differently, change how the fuel and air mix and, therefore, affect combustion. Both are problems for Bergthorson’s collaborators at other universities. Bergthorson himself is experimenting with different blends of alternative fuels to see what happens to the sequence

of chemical reactions that converts fuel and air into carbon dioxide and water. This includes extinction behaviour (how easy it is to blow out the flame), flame speed and stability; type and quantity of emissions; fuel droplet evaporation; and reignition at low temperatures. The last point is crucially important for restarting the engine after a flameout incident at 30,000 feet. However, lighting a small flame in a lab and kickstarting a jet engine on a runway are worlds apart. Between the two lie gas-turbine combustor experiments and the inherent complexities added by the fuel spray and evaporation processes. Instead of this, Bergthorson has adopted an experimental and modeling approach that allows him to assess the effect of industrially relevant turbulence levels on the flame without using an actual combustor — and without cramming a jet engine into his lab. The results will inform other research work to integrate alternative fuels into transportation and power generation systems and help develop new engine designs that improve efficiency and reduce emissions. Soaring petroleum prices, concerns over climate change, European cap-andtrade schemes that affect airlines and the International Air Transport Association’s goal to reduce its carbon footprint by 50 per cent by 2050 — it all adds up to very keen interest in research that explores bio-derived fuels that will keep costs and emissions down. Bergthorson is involved in several large scale collaborative efforts

September 2012 CAnadian Chemical News   25


Particles within a flat, stagnation flame are illuminated by a laser sheet in order to study reaction­ rates. In this way, researchers­can compare the performance of standard and alternative­fuels.

Sean Salusbury

with industry. Pratt & Whitney Canada, for one, has called on him — as well as experts at Université Laval, Ryerson University, the National Research Council’s Gas Turbine Research Laboratory, the Indian Oil Company and other partner organizations and universities in India — to investigate the performance of different biofuel and petrofuel blends. “Synthetic kerosene has been approved for use in jet engines. It meets the fuel standards but because it is made from gasified coal, its environmental footprint is worse than petrofuel,” says Bergthorson. “Bio-derived fuels are now being shown to be engine-compatible and carbon friendly. The industry is already certifying hydro-treated vegetable oils, thereby opening the doors for widespread adoption.” Could we also see these blends at the neighbourhood gas station in the future? Bergthorson shakes his head. “True, we could obtain fuels similar to gas or diesel from these processes,” he says. “But because they have to meet the standards for jet fuel, they need more processing and that leads to higher costs. There will be cheaper solutions for the gas tank than bio jet fuel.” In another collaboration, Bergthorson is working with Rolls Royce Canada, five Canadian universities and the National Research Council on novel fuels for gas-turbine engines. Rolls Royce’s Energy Division converts aviation gas turbine engines into power-generation systems suitable for remote or off -shore uses or for peak power generation by replacing the combustor and other key parts.

26  CAnadian Chemical News

September 2012

“The first two things a customer cares about when buying an engine are cost and reliability,” says Bergthorson. “But increasingly, they are asking if they can burn this, that and the other fuel depending on what is available and what is cheapest.” The research on gaseous fuels (syngas or biogas blended with natural gas) and liquid fuels (biodiesel, alcohols and upgraded pyrolysis oils blended with petrodiesel) will provide data that will help Rolls Royce meet ever-tightening emissions standards for these engines. As a result, Rolls Royce will be in a better position to evaluate what alternative fuel mixtures will work in existing engines and what design changes can be made to next-generation engine combustors to allow further fuel flexibility. This story first appeared in the winter 2012 issue of McGill University’s Headway magazine.


The Department of Chemistry invites applications for a probationary (tenure-track) faculty position at the rank of 足Assistant Professor in Inorganic Chemistry with an anticipated start date of July 1, 2013. The successful candidate will be expected to establish an independent, externally funded research program, and to develop and teach innovative courses in chemistry at the undergraduate and graduate levels. The Department of Chemistry (www.uwo.ca/chem) is a large research-intensive department with strong programs in many areas of chemistry and with several interdisciplinary links to research groups in other departments in the Faculties of Science and Engineering and the Schulich School of Medicine & Dentistry. The Department of Chemistry is home to world class research facilities and has strong 足affiliations with Surface Science Western (www.surfacesciencewestern.com), the Western Nanofabrication Facility (nanofab.uwo.ca) and the Integrated Microscopy Unit (www.thebiotron.ca). Interested candidates should send two hard copies of their application package which includes an up-to-date curriculum vitae, a teaching philosophy and a statement of teaching interests, a description of research accomplishments, and a 5 page research proposal, together with the names, mailing and e-mail addresses and telephone numbers of three referees to: Dr. K. M. Baines, Chair | Department of Chemistry, Western University Chemistry Building, Room 003 Dock 11 1151 Richmond Street N, London, Ontario, N6A 5B7, Canada The deadline for receipt of two printed copies of the full application is 足September 30, 2012. Applications sent by e-mail will not be considered. Positions are subject to budgetary approval. Applicants should have fluent written and oral communication skills in English. All qualified candidates are encouraged to apply; however, Canadians and permanent residents will be given priority. Western University is committed to employment equity and welcomes applications from all qualified women and men, including visible minorities, aboriginal people and persons with disabilities.


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which time the CSC nominating com-

­Biotechnology & Bioprocessing

University of Toronto were all named

mittee will review the submissions.

Montreal, Que.

fellows of the Canadian Academy of

www.bio.org/events

Engineering­in June.

with their CV to cscboard@cheminst.

­University of Alberta, Robert Legros

Registration for the 62nd Canadian Chemical Engineering Conference

July 13–18, 2014

In Memoriam

being held in Vancouver, B.C., October

International Conference on Chemistry

14-17, 2012 is now open. Register by

Education, 2014

September 10 to take advantage of

Toronto, Ont.

early registration fees. Information can

www.ICCE2014.org

The CIC wishes to extend its condolences to the families of John Breau, MCIC, Robert Jenkins, MCIC, Frank Martens, MCIC and J.E. (Ted) Newall, HFCIC.

be found on the conference website at www.csche2012.ca.

Find more news from the CIC at accn.ca/societynews. Is there something going on that you think we should write about in this section? Write to us at magazine@accn.ca and use the subject heading “Society News.” September 2012 CAnadian Chemical News   29


Chemfusion

How sweet it is

B

osco chocolate syrup — notable for its cameo as fake blood in Alfred Hitchcock’s 1960 Psycho shower scene — is still around, though it has undergone a significant transformation over the years. First introduced in 1928, the sweet sauce’s main ingredients were corn syrup and cocoa with sugar and malt extract added for taste and xanthan gum as a thickener. The main difference from the 1960s is that high fructose corn syrup is now one of the ingredients because it achieves the same degree of sweetness with less sugar, a more expensive ingredient. The substitution of high-fructose corn syrup for cane sugar is a pattern that became common in the food industry in the decades that followed Hitchcock’s landmark film. Sugar tariffs and large subsidies introduced in the 1970s for corn growers in the U.S. made the technology for producing high fructose corn syrup popular as a cheaper way to add sweetness to foods and beverages. Since high fructose corn syrup is a liquid, it is easier to transport and blend than granulated sugar, particularly when it comes to formulating beverages. Its popularity is waning today as its ubiquity in things like carbonated beverages has been pointed to as a contributor to obesity, cardiovascular disease, diabetes and non-alcoholic fatty liver disease. Corn syrup and high fructose corn syrup are not identical products. Corn starch, which is used to make both products, is a white powder, chemically

30  CAnadian Chemical News

By Joe Schwarcz

composed of polymers of glucose. This means it consists of hundreds of glucose molecules joined together either in a straight chain known as amylose or in a branched chain version called amylopectin. Treating the starch with dilute hydrochloric acid breaks down the chains, yielding a mix of individual glucose molecules along with maltose, which is two glucose units joined together, and various short glucose chains known as oligosaccharides. To make corn syrup commercially, instead of using an acid, a mixture of corn starch and water is treated first with alpha amylase, a bacterial enzyme that breaks the starch down into oligosaccharides, followed by the addition of gammaamylase, an enzyme isolated from the Aspergillus fungus that converts some of the oligosaccharides to glucose. In the case of high fructose corn syrup, another bacterial enzyme, D-xylose isomerase, is used to convert some of the glucose into fructose. Fructose is sweeter than glucose, so an equivalent amount of high fructose corn syrup is sweeter than regular corn syrup. While corn syrup is made of corn starch, the two substances are different in more ways than you may think. You can’t walk on corn syrup, but you can walk on a liquidy mix of water and corn starch. Well, maybe not walk, but you can run. That’s because a mixture of water and corn starch is a non-Newtonian fluid. Isaac Newton did more than watch apples fall. He was also interested in the

September 2012

viscosity of liquids and determined that the viscosity can be changed by altering the temperature. Try warming up some honey in the microwave and see how easily it then flows. Non-Newtonian fluids can changed their viscosity not only in response to temperature change but also in response to pressure. When pressure is applied to a viscous waterstarch mixture, it momentarily becomes a solid but quickly reverts to a liquid. That’s why you can run across a basin filled with water and corn starch. Your weight provides enough pressure to solidify the corn starch. But you can’t dilly-dally. You have to take the next step before the mixture reverts to a liquid state. If making a pool of corn starch is too big a challenge, which it probably is, you can impress your friends by making a small batch in a bowl. (For a Hitchcockian twist, add some food dye and it looks like blood.) Then slap it hard with your hand. Everyone will expect the guck to fly all over the place, but if done right, the fluid’s non-Newtonian nature guarantees that nothing happens. (But if your slap is too timid, you’ll end up with a bloody mess!) Joe Schwarcz is the director of McGill University’s Office for Science and Society. Read his blog at chemicallyspeaking.com.


62nd Canadian Chemical Engineering Conference

VAncouver British Columbia, Canada

October 14–17, 2012 Energy, Environment and Sustainability

www.csche2012.ca


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ACCN, the Canadian Chemical News: September 2012