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November | December 2012

Canadian Chemical News | L’Actualité chimique canadienne

Living Factories Lessons from nature Keeping pace in the biotech business Special issue: How the future of biotechnology depends­on the chemical sciences and engineering



Chemical Institute of Canada www.accn.ca


www.uwaterloo.ca


Table of Contents

November | December 2012 Vol.64, No.10

Features Simon Fraser University

chemistry

business

Much of the m ­ omentum in biotechnology has been provided by ­progress in chemistry, which has ­informed our ability to piece apart the intricacies of biological reactions.

16

Cues from the living world

Biotechnology is an extension of the human instinct to learn from the natural­ world. By Tim Lougheed

John Hryniuk

CHEMICAL ENGINEERING

24

Nature’s industrialists

Ushering in a future where commodity chemicals are not made, but grown. By Tyler Irving

20

Managing mindsets

Faster isn’t always better when it comes to running a biotech business. By Tyler Irving

Departments 5

From the Editor

7

Letters to the Editor

9

Guest Column By Tim Clark

10

 hemical News C By Tyler Irving

29

Society News

30

ChemFusion By Joe Schwarcz

november | December 2012 CAnadian Chemical News   3


www.amgen.ca


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

Editorial Office 130 Slater Street, Suite 550 Ottawa, ON K1P 6E2 T. 613-232-6252 | F. 613-232-5862 magazine@accn.ca | www.accn.ca

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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. 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

W

hen our news editor, Tyler Irving, told me he wanted to interview some chemical engineers at the University of Toronto who were analyzing beaver poop and moose guts I thought “Great! A wildlife story!” But of course, Tyler’s article “Nature’s Industrialists” on page 24 is hardly a fuzzy-animal tale; it’s a story about how chemical engineers are probing nature for ways to revolutionize huge industrial sectors like commodity chemicals, forestry and oil and gas. The story — along with an introductory essay by Tim Lougheed and a Q and A on the ups and downs of managing a biotech business — showcases how the future of biotech depends on the chemical sciences and engineering, the thesis for this special issue on biotechnology. This is also the last issue of 2012, and the editorial team is now gearing up for 2013 which promises to be a transformational year for ACCN, the Canadian Chemical News. We aim to be “Your Information Nucleus” — the source to which you turn to stay involved and in touch with the Canadian chemical sciences and engineering community. So we asked ourselves “How can we deliver more content to our readers in a more timely, more accessible and more interactive way?” The answer, we know from our readership survey, from your letters and from meeting you at conferences, is clear: we need to grow our online content. To do this, we’ll be delivering the same great magazine content in six 48-page hard-copy magazines, rather than our current 32-page issues 10 times each year. The new, larger magazine will include two new editorial columns, expanded Chemical News and Society News sections, longer, more in-depth feature stories, and more. This shift will also accommodate an upgrade to our electronic content, such as the new electronic newsletter that delivers career advice and some of the latest happenings of the CSC, CSChE and CSCT every week. 2013 will also see the launch of our new blog where we will bring you the latest developments in a more timely, more interactive venue. And that’s just the beginning. We invite you to visit www.cheminst.ca throughout the months of November and December as we unveil what we’ve got in store for you in 2013. Hope you enjoy the read!

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Write to the editor at magazine@accn.ca

Visit us at www.accn.ca november | December 2012 CAnadian Chemical News   5


www.lanxess.com


letters to the editor

I

n late September, the Council of Canadian Academies (CCA) released a report that stated that Canadian science is healthy, growing and internationally respected, but found that chemistry as a discipline was “falling behind” by some expert rankings. CSC President Cathleen Crudden pointed out in her response to the report that the performance of chemistry is at risk of being skewed since many highly active, emerging fields such as nanotechnology, materials and energy were given their own classification outside of chemistry. We asked for your feedback. Here’s what you had to say:

Meaningful measurements a must

The CCA report states that Canadians accounted for only 2.6 per cent of chemistry articles in refereed journals and that this is a “relatively low concentration of activity in chemistry.” However, this research was found to be of high quality. It was also reported that “Canada’s share of the world’s scientific publications is particularly high in some other fields,” which included earth and environmental sciences; a survey of international researchers ranked them fourth in the world. The report also states that “Scientific output and impact in these fields were either static or declined in 2005–2010 compared to 1994–2004.” Having for many years published physical chemistry applied to environmental problems, I offer some longstanding observations that are relevant to these parts of the report. In the first place, environmental science could not even exist without chemistry. Without analytical chemistry it couldn’t start, and without physical chemistry it couldn’t go anywhere. Organic and inorganic chemistry back them up. The report’s classification of scientific fields is therefore misleading. It incorrectly implies that environmental science is not part of chemistry. As a result, not all of the chemical research publications are being accounted for. For environmental chemistry, the quality issue raised by the report is an international one, not just a Canadian problem. Two serious limitations are still found in the literature of soil and water contaminants. Chemical stoichiometry for reactants and products is universally ignored. Related to that, the descriptions of kinetics and equilibria do not properly account for the fact that the real environment has physically and chemically irregular mixtures. Instead, chemically meaningless parameters are

still substituted for realistic descriptions of reactions, kinetics and equilibria. For environmental science, a note can be added to the information in the report: six Canadian laboratories have contributed to improved descriptions of physical chemical reaction mechanisms in the soil-water part of the environment. Conventional chemical kinetics can replace the chemically meaningless parameters. A seventh laboratory at York University in Toronto has started experiments with which to connect the soil-water part to the atmospheric part. All of this is a Canadian initiative. Donald Gamble Department of Chemistry Saint Mary’s University, Halifax

Lost lustre

I sometimes feel that I was educated in “the Golden Era” of chemistry in Canada (the 1960s). Deryck Ross Ottawa

Doing more with less will catch up

It is gratifying to see the impact and world-wide recognition of the Canadian Science enterprise. However, as the CSC President notes, “Canada is the only OECD country with a net decline (of over six per cent) in research and development expenditures between 2005 and 2010.” Thus, Canadian scientists became very good at doing more with less and less. Unfortunately, the continued funding decrease, especially for research equipment and infrastructure, will eventually catch up in the scientific output metrics in years to come. This will be particularly evident in experiment-heavy sub-fields of chemistry, physics, biomedical sciences and engineering. Elod Gyenge Department of Chemical and Biological Engineering The University of British Columbia

Write to the editor at magazine@accn.ca. Letters are edited for length and clarity.

november | december 2012 CAnadian Chemical News   7


www.melochemonnex.com/cic


guest column

This is not your grandpa’s cutting edge

I

t’s common knowledge in academic circles that most undergraduate students in general and organic chemistry classes have no intention of staying in chemistry. Most of them either want to go to medical school or into ­biochemistry, biology or medical sciences. Why do so few science students actively choose to go into chemistry? Many academics believe that it is because students don’t see the relevance of chemistry anymore — to them it’s archaic and staid — at a time when ­chemistry has never been a more dynamic, diverse and critical field! I was one of those students who saw chemistry as a course-hurdle in the same vein as calculus and social science options. I started off majoring in biology which I felt was a more fascinating and relevant field. But the more chemistry classes I took, the more intuitive it seemed and because of some really insightful, passionate instructors, I began to realize that chemistry isn’t confined to bubbling coloured potions in the lab, dry Lewis diagrams and mass balances, but that it is universal and is absolutely everywhere — in our medicines, batteries, detergents, electronics and in biological systems. The discrete worlds of biology, ­chemistry and physics started melding together with chemistry at the heart of it and that’s when I knew I wanted to be a chemist. During my graduate studies I was able to work with a professor whose research program resides at the interface of

organometallic and polymer chemistry, materials science and engineering. This exposure to a wide range of fields helped me to become a much more versatile scientist, a critical skill these days in the job market. It emphasized for me the breadth of chemistry in emerging fields such as nanotechnology and biotechnology. I was conducting research with hydrogen storage materials as well as photonic crystals for biometrics: chemistry for me was far from stale and archaic. The field encompasses so many areas within science, established and cutting edge, even if they do not have “chemistry” in the name or don’t have dedicated chapters in undergraduate textbooks. An increasingly acute awareness of our sensitive environment led me to postdoctoral work in “green” chemistry with a polymer chemist studying fuel cell membrane assemblies. Now at GreenCentre Canada, I develop numerous early-stage green technologies from academic labs across the country. These innovations can be a more sustainable replacement for products or processes currently manufactured or used in industry. The field of green chemistry is the ultimate example of how pertinent chemistry is today. Alongside green chemistry are fields like nanotechnology, energy, materials, and the theme of this special magazine issue, biotechnology. Each of the burgeoning fields is firmly rooted in chemistry.

By Tim Clark

Unfortunately, chemists have our work cut out for us to reverse the notion that our field has fallen off the leading edge. The recent State of Science Report by the Council of Canadian Academies (CCA) confirmed that science in Canada is continuing to flourish and be recognized around the world, but in the same stroke pigeon-holed chemistry by defining it by classic (dare I say archaic) divisions such as inorganic, organic and analytical. The classification system used for the report exacerbates the idea that chemistry is antiquated and bumped chemistry from among the top six performing fields in Canada, leaving it lagging behind emerging areas such as nanotechnology, materials, and energy, all of which are borne of chemistry. In fact there are entire sub-disciplines in chemistry departments across the country dedicated to these topperforming fields. You wouldn’t know it from the CCA report, but there has never been a better time to become a chemist and actively contribute to these critical disciplines which will enhance the world in which we live. Tim Clark is a Senior Product Development Scientist with GreenCentre Canada in Kingston, Ont.

november | December 2012 CAnadian Chemical News   9


Chemical News Health

Epicatechin, a flavonoid chemical found in dark chocolate, has been shown to have significant effects on the memory of the great pond snail.

How good is a snail’s memory? It may depend on what it has eaten. A new study shows that a molecule found in dark chocolate can have positive effects on the long-term memory of these slow-moving mollusks. Previous studies in rodents have suggested that flavonoids — plant metabolites often found in tea, wine and dark chocolate — are associated with improvements in learning and memory. However, the mechanism

Environment

­ aturally N ­deposited ­hydrocarbons dominate in Athabasca ­sediment The load of organic contaminants introduced into the ecosystem via natural erosion of exposed bitumen from the banks of Alberta’s Athabasca River far exceeds that from oil sands development, a new study of ­sediments suggests. There have been concerns about polycyclic aromatic compounds (PAC) - some of which are carcinogenic - in the Athabasca River system for some time. A 2009 paper in Proceedings of the National Academy of Sciences (PNAS) by University of Alberta ecologist David Schindler and others examined dissolved PAC concentrations in the

10  CAnadian Chemical News

waters of the Athabasca near oil sands development. These concentrations showed a slight increase, from around 0.025 µg/L upstream to as high as 0.135 µg/L near industrial operations. But as Roland Hall, University of Waterloo ecologist and author of the recent study, points out, this increase could include contribution from natural processes. “The industry is located in exactly the same place where the natural deposits come out into the riverbank,” says Hall. “You can’t really conclude that the difference is only due to industry.” Since PACs are hydrophobic, most of them would partition into sediments rather than the water. For this reason, Hall and his colleagues decided to study sediments collected from lakes in the Peace-Athabasca river delta - located 200 kilometres downstream from the oil sands operations - to assess the baseline load of PAC delivered there over the past few centuries. Although such studies had been called for by government-appointed expert panels, NSERC declined funding on the grounds that the research was in industry’s interest and should be funded privately. In the end, Suncor Energy Ltd. stepped forward to provide money for the study. “We knew that with industry funding, the optics would not be in our favour,” says Hall. “But we’ve been up front about this and conducted the research in exactly the same way that we would have if we had been funded by NSERC.” In a paper recently published in the open-access journal PLoS ONE, Hall and his team reported concentrations of PAC in lake sediments ranging from about 0.1 to 3 milligrams of PAC per kilogram of sediment. Lakes that did not receive floodwaters had levels of PAC three times lower than those that did, indicating that air deposition is small compared to that from waterborne sediment. Significantly, all peaks in PAC concentrations corresponded to known flood events, both before and after 1967. “We could not detect a change since the onset of oil sands development [in 1967] compared to the natural levels that came in previously,” says Hall. The localized increases in dissolved PAC near oil sands development may well be compatible with undetectable changes in sediments further downstream. “The distance and amount of dilution involved is such that I don’t see a conflict [between our findings and Hall’s],” says Peter Hodson, an ecologist at Queen’s University who was a co-author on the 2009 PNAS paper. However, both Hodson and Hall point out that the overall flow of the Athabasca is decreasing as the glaciers that feed it continue to shrink. This in turn will affect its ability to dilute PAC, regardless of the source.

November | December 2012

Ken Lukowiak

Chocolate ingredient ­improves memory in snails


Canada's top stories in the chemical sciences and engineering

has been unclear: they might facilitate the growth of new cells and blood vessels in the brain, act as anti-oxidants preventing the death of existing neurons, or act independently. To find out, Ken Lukowiak, professor in the Hotchkiss Brain Institute at the University of Calgary, turned to a unique model organism: the great pond snail (Lymnaea stagnalis). Because the snails absorb drugs through their skin, have an open circulatory system and can be trained in only 30 minutes, the effects of growing or dying blood vessels and neurons on memory can be eliminated. The team lowered the oxygen content of the water the snails live in by bubbling nitrogen through it. This caused the snails to open up their pneumostome (breathing tube) to get oxygen from the air. By gently tapping them with a stick, the researchers

| Chemical News

trained the snails to keep their tubes closed. Most snails remember this lesson for only about three hours, but in a paper published in the Journal of Experimental Biology, the team showed that snails exposed to 15 mg/L of the flavonoid (-)epicatechin through the water remembered the task even after 24 hours. “To get a 24-hour memory, you have to have altered gene activity, implying a significant change to the neuron,” says Lukowiak. The team is now testing neurons isolated from snails to figure out what those biochemical changes might be. As for ­effects in humans, Lukowiak is circumspect. “As far as I know, no one has actually looked at this in humans, but if I had to bet money, I’d say it probably helps. If tea, wine or dark ­chocolate makes you happier and less stressed, your memory will probably improve as well.”

Business

Great Lakes Biodiesel Inc.

Canada’s biodiesel ­production to double this fall

The largest biodiesel plant built in Canada to date is set to open this month in Welland, Ont. In a stroke, the 170 million litres per annum operation will almost double this country’s current biodiesel production of about 200 million litres per year. The plant cost approximately $25 million and will produce biodiesel primarily from soya oil, as well as some canola oil. “Ontario is a large grower of soybeans, so we have a good source in our close proximity,” says Barry Kramble, CEO of Great Lakes Biodiesel, the company founded in 2007 to build the facility. Kramble cites other advantages of the Welland site such as its links to road, rail and water transportation and its strategic location for both the primary Canadian markets in Ontario and Quebec and American markets to the south. In July 2011, Canada’s government mandated that all diesel and home heating fuel must contain an average of 2 per cent biodiesel over the next reporting period. In addition to this, the federal government’s ecoENERGY program pays incentives for each litre of biofuel produced. Great Lakes Biodiesel expects to collect $63.5 million dollars from this program over the next five years. Still, there’s room for even more production in the future. “The mandate created an inherent demand of approximately 600 million litres of biodiesel per year,” says Kramble. “So there’s still a fair way to go in order for Canada to produce enough to support its own mandate.”

An artist’s conception of Canada’s largest biodiesel plant, set to open in ­November in Welland, Ont. The plant will almost double nationwide capacity.

november | December 2012 CAnadian Chemical News   11


Canada

Where Science Meets Business

The business forum of the

Mark your Calendars! April 4, 2013 | Toronto The 3rd CIC “Green, Clean and Sustainable” Seminar This business-focused seminar features leaders from industry (associations, companies) and highlights current developments along with forecasts for the future of green chemistry and engineering in Canada. The speakers will focus on small and large scale successes in the chemical industry. The third annual seminar will provide stimulating panel discussions along with valuable networking opportunities.

CIC/SCI Canada Awards Banquet SCI Canada*, the business forum of the Chemical Institute of Canada, will host its annual awards dinner in recognition of those who have made outstanding contributions to the chemical industry. SCI Canada rewards excellence in the field of chemistry and the chemical industry by presenting awards to industry and academic leaders for outstanding achievements they have made in business development. Join us at this influential event to celebrate the accomplishments of your colleagues.

www.cheminst.ca/AwardsDinner *in 2012, SCI Canada became a forum of the Chemical Institute of Canada and as such merged with the CIC’s Economics and Business Management subject division.


Canada's top stories in the chemical sciences and engineering

| Chemical News

Alternative Energy

World’s first 100 per cent bio-fuelled jet soars over Ottawa On October 29 the world’s first 100 per cent bio-fuelled jet hit the skies above Ottawa. The flight was powered by fuel derived from a variety of mustardseed that contains a higher proportion of long-chain C22 fatty acids than other oil crops such as canola. “Essentially, this gives manufacturers 20 per cent more carbon to convert into fuel,” says Steven Fabijanski, President and CEO of Agrisoma, the Canadian company that developed the mustardseed crop. Because jet fuel is composed of slightly smaller molecules ranging from C9 to C15, the seed oil must be cracked, as well as isomerized to produce cycloparaffins and aromatics which improve properties of the fuel such as density and viscosity at low temperatures. This is accomplished via a catalytic ­hydrothermolysis (CH)

process developed by the American company Applied Research Associates, Inc. (ARA), which uses water at elevated ­temperature and pressure to crack the plant oils. “Compared to traditional hydrocracking processes, the CH process is less expensive, requires less hydrogen and does not require hydrocracking catalysts,” says Ed Coppola, ARA Principal Engineer. The finished fuel is being tested in the National Research Council’s (NRC) Falcon 20 twin-engine jet. This unique aircraft contains two fuel tanks and is able to alter the mix between petroleum-based and bio-based fuel on the fly. A second aircraft - the fighter trainer T-33 - is capable of flying within the wake of the Falcon 20 and chemically analysing its emissions using a specialized sensor slung under the wings. “There’s really only a handful of aircraft around the world that can do anything like this,” says Dave Marcotte, manager of Airborne Research at NRC. Flights conducted over the summer which used up to 60 per cent biofuel found that blending petroleum and bio-based fuels can reduce emissions of aerosols by 30 to 50 per cent. The results from 100 per cent biofuel flight are still being analysed.

Biochemistry

Richard Rothery

Form follows function in molybdenum enzymes New insight into the organic chemical ‘cages’ that hold reactive metal centres within molybdenum-containing enzymes could help cure genetic diseases and improve industrial catalysis. Molybdenum-containing enzymes have many roles in ­bacteria, from catalysing atmospheric nitrogen fixation to facilitating the sulphur chemistry used to survive in hydrothermal vents. In higher organisms, they fall into only two categories: xanthine ­dehydrogenases are involved in metabolic pathways; sulfite ­oxidases ­catalyse a small but important set of reactions involved in brain development. Unlike other metal-containing enzymes where the metal atom is held in place by amino acid residues, ­molybdenum is contained within a cofactor: a large organic ­molecule called a pyranopterin. Joel Weiner’s team in the biochemistry department at the ­University of Alberta examined the structure of 319 pyranopterins in 102 protein structures from bacteria, yeast, algae and animals. “When you look at the three-dimensional protein structure, you find that the pyranopterin shape changes based on what the ­enzyme is doing,” says Weiner. “In the sulfite oxidases, the pyranopterin was always very flat, whereas in the xanthine dehydrogenases, it’s skewed.” In bacterial enzymes, molybdenum is contained using two pyranopterins; one flat and one skewed. In a paper published in Proceedings of the National Academy of Sciences, the team theorized that skewed pyranopterins act only as a conduit for electrons during reactions. In contrast, flat ­pyranopterins work with the surrounding amino acids to tune the electrochemical potential of the molybdenum. Human enzymes

can only do one or the other, but bacterial enzymes can do both, which explains their ability to catalyse a wider range of reactions. Understanding this form/function relationship could help medical researchers create pyranopterin analogues for people with genetic diseases where molybdenum-containing enzymes are malformed or not functional. It could also help chemists design artificial cofactor molecules and enzymes to catalyse reactions which are currently difficult or impossible. 1 dihydro pyranopterin

Sulfite oxidase family

1 tetrahydro pyranopterin

Xanthine dehydrogenase family

Enzymes containing molybdenum use organic molecules called pyranopterins to hold the metal ion in place. The pyranopterin found in sulfite oxidases (left) is relatively flat, while those in xanthine dehydrogenases (right) are skewed. Understanding the form-function relationship between these molecules in enzymes could help cure genetic diseases and improve artificial enzymes for industrial catalysis. november | December 2012 CAnadian Chemical News   13


 Canadian Society for Chemistry

96th Canadian Chemistry Conference and Exhibition

Call for papers Opens: December 5, 2012 Closes: February 15, 2013 May 26–30, 2013 Chemistry without borders

QUéBEC Québec, Canada

www.csc2013.ca


Canada's top stories in the chemical sciences and engineering

| Chemical News

Mathieu Coinçon

Pharmaceuticals

Researchers identify molecular anti-virulence mechanism A team at Université de Montréal has identified a compound that neutralizes a pathogen, not by killing it, but by disabling the ­molecular machinery it uses to infect host cells. The approach could provide an alternative to conventional antibiotics. Biochemist Christian Baron and his team have been studying an enzyme called VirB8 which is produced by certain bacteria, including Brucella. “This is a pathogen that affects farm animals and workers, but there are concerns that it could be used in bio-terror attacks,” says Baron. VirB8 enables bugs like Brucella to secrete the toxins and other molecules they need to infiltrate host cells and multiply inside them. If the function of VirB8 is blocked, the bacterium loses its infectiousness. Since VirB8 must pair up into dimers in order to function, Baron’s team looked for molecules that could disrupt dimerization. Using a high-throughput screening apparatus at McMaster University, the group tested over 30,000 compounds. The most effective was a member of the salicylidene acylhydrazide class called B8I-2. In

Researchers at ­Université de ­Montréal have shown that the salicylidene ­acylhydrazide derivative B8I-2 (above) binds to the bacterial protein VirB8. Inhibiting this protein causes ­bacteria to lose their virulence, and could provide an alternative to traditional antimicrobial drugs.

their latest paper published in Chemistry & Biology, the team used x-ray crystallography to identify the exact binding site on VirB8 that is affected by this inhibitor. They also collaborated with Université de Montréal chemist Pierre Lavallée to develop analogues of B8I-2. “When you make small changes that cause the molecule to lose activity, it tells you what parts of it are really important,” says Baron. “That will inform how we design better molecules.” Still, studies with live bacteria show that B8I-2 already works well enough to render strains of Brucella non-virulent. Baron is currently looking for partners to perform the structure-activity relationship and animal studies that would be required to move B8I-2 and its analogues down the path to becoming commercial drugs.

www.wiley.ca/chemistry

www.wiley.ca/chemistry

november | December 2012 CAnadian Chemical News   15


Cues from the

LivinG

World By Tim Lougheed

A

stronomy is often touted as the first science pursued by human beings, but perhaps biotechnology actually deserves that title. For while the earliest human minds were undoubtedly pondering the spectacle of the night sky and the mysteries of the universe, they must have been no less engaged in trying to understand and manipulate the natural world closer to hand. The term “biotechnology” today conjures up all manner of microscopic and genetically modified marvels, but its origins point to our survival and success on this planet. It undoubtedly began with the quest for the next meal, perhaps given the observation that some foodstuffs became more palatable after soaking in water or scorching in fire. Such insights would have broadened our diet, along with the range of environments we could inhabit. At some point an anonymous genius discovered zymurgy, the magic of fermentation that allows staples like beer, wine, and bread to be created from ingredients that might otherwise seem to be unpromising. Enterprising farmers subsequently learned how to cross-breed edible plants for desirable traits like drought-tolerance. We now associate this kind of manipulation with our newfound ability to analyse and alter the genetic structure of organisms, but our efforts actually preceded the very notion of a gene by thousands of years. Contrast a modern wheat field with the uninspiring middle eastern grass that was the original precursor of this crop and you will witness one of our civilization’s most ambitious — and longest running — biotechnology initiatives.

16  CAnadian Chemical News

November | December 2012

By the 20th century, these initiatives were proceeding at a furious pace. Much of the momentum has been provided by progress in chemistry, which has informed our ability to piece apart the intricacies of biological reactions. Biotechnology blurs the lines that might once have distinguished these two disciplines, yielding results that are not easily classified as either biological or chemical discoveries. Among the most dramatic milestones was the initial unravelling of DNA in the 1950s, a triumph of chemical analysis that in turn opened up entirely new ways of regarding the biological world. While we have always known that living things pass on characteristics to succeeding generations, investigators now had access to the chemical structures governing this transfer. We are still coming to grips with the implications of such progress, which lays bare the chemical underpinnings of all that we regard as life. And as much as we worry about the damage this knowledge will allow us to wreak on the environment and ourselves, the natural world is teaching us more than we have ever known. According to Adrian Tsang, Director of Concordia University’s Centre for Structural and Functional Genomics, some of the most humble inhabitants of that world promise to dazzle us with major discoveries. Tsang’s team is focussing on fungi, which have traditionally served as the source for many widely used commercial enzymes. Now fungal genomes are being analysed as part of a systematic search for enzymes to tackle specific problems, such as how to


Chemistry | Biotechnology

Humans have always drawn lessons from the natural world to improve­their standard of life. Biotechnology­is the logical progression­of this instinct­.

break down and recycle materials like plastic or petrochemicals. “These organisms are the major decomposers of terrestrial biomass,” he explains. “We’re basically learning from them. They have had a billion years of evolution to handle this. They have developed all kinds of strategies to break down the toughest materials. We’re asking ‘how do they do it?’ and then, ‘can we mimic it in a factory-type of situation?’ ” In this way, 21st-century alchemists are not interested in transmuting lead into gold, but garbage into fuel, and they are recruiting the help of organisms with the requisite chemical experience. Enzymes derived from fungi may become integral to turning municipal or agricultural waste products into energy sources, presenting a viable alternative to established sources such as oil or coal. Tsang adds that the environmental footprint of this alternative would be much smaller, since it eliminates the very waste it employs. “Quite clearly, we are transitioning to a biomass-based economy,” he concludes.

“Down the road, we can have a reasonable standard of living without the massive use of chemicals [from] petroleum.” The case of Bacillus thuringiensis (Bt) illustrates the types of products populating this new economy. Since the 1980s, this bacterium has displaced traditional pesticides as a way of ­combatting the insect infestation in Canada’s forests. In contrast to a “scorched earth” agent like DDT, which does tremendous damage to plants and soils in an effort to control insect populations, when Bt is consumed by insects, it releases proteins that kill them without any attendant environmental impact. Researchers at Natural Resources Canada’s Great Lakes Forestry Centre in Sault Ste. Marie, Ont. have spent the past two decades tailoring dozens of varieties of Bt targeted to specific species like spruce budworm, so that these pests can be all but eliminated

The report listed the high expectations that are attached to biotechnology, from crop varieties that resist cold or particular diseases, to medicines capable of waging molecular warfare with diseases that are currently difficult to treat. What is perhaps even more interesting about biotechnology is the new tools that it supplies, not just for answering scientific questions, but for applications such as monitoring the quality of foods or the presence of pollution in an environment. “The next decade will see an increasing economic impact from biotechnology and its applications,” states the report. “Just think of what has happened in the few short years since the current strategy was instituted. In that brief interval, we have seen the mapping of the genomes of humans, plants, animals and microbes and the emergence or rapid expansion of new

Much of the momentum in biotechnology has been provided by progress in chemistry, which has informed our ability to piece apart the intricacies of biological reactions. with widespread spraying that poses no hazard to other species. Such innovations, and the economic promise that accompanies them, prompted the federal government to draft a formal biotechnology strategy in the late 1990s. A report by the Canadian Biotechnology Advisory Committee revisited this strategy some 10 years later, estimating the global market value of biotechnology products to be on the order of tens of billions of dollars, and increasing rapidly. As of 2006, the Canadian government was already investing some $750 million annually in this field, most of that amount going to academic and industry research projects like that at Concordia.

fields of biotechnology (genomics, ­pharmacogenomics, proteomics, stem cell biology, bioinformatics etc.).” Looking back, it is relatively easy to characterize the course of the 20th century by our growing ability to harness the insights of chemistry to muster technological change that defines what we eat, what we wear, the materials in the buildings we inhabit, and the vehicles that take us from one place to another. It already appears likely that the character of the 21st century will build on this chemical foundation to introduce even more fundamental change, creating a standard of living for us with technology adapted from the most rudimentary mechanisms of life itself.

November | december 2012 CAnadian Chemical News   17


Illimar Altosaar, a professor in the University of Ottawa’s Department of Biochemistry, Microbiology and Immunology, has witnessed such progress during the course of his own career. “The semantics and lingua franca of the catch phrase ‘biotechnology’ has also transformed throughout the three decades of the gene transformation revolution,” he says, referring to an article he co-authored on this subject in 1982. Writing in this very magazine two years before it was renamed from Chemistry in

should be strictly identified in much the same way that the name of regional wines like champagne are controlled, making the nature of the genetic modification apparent to everyone with an interest in these products. Other branches of science have embraced the principles of biotechnology in comparable ways. Taxonomy, the practice of identifying and distinguishing species, has traditionally classified specimens of plants or animals based on macroscopic physical char-

It is likely that the character of the 21st ­century will build on a chemical foundation to ­introduce even more fundamental change, creating a standard of living for us with technology adapted from the most rudimentary mechanisms of life itself. Canada, Altosaar described impending changes that would affect all facets of biological science. “Considerable progress has been achieved in the development of methods for introducing and maintaining genetic information in mammalian cells,” he wrote. “The use of this technology in conjunction with methods for in vitro manipulation of DNA has begun to answer some very fundamental questions at the molecular level concerning gene regulation.” Altosaar contrasts this somewhat tentative observation with his most recent publications, which simply treat biotechnology as a given aspect of contemporary research projects. In a 2012 article for the Journal of Plant Biochemistry & Biotechnology, he and his colleagues review the way in which genetically modified crops are developed for specific circumstances, such as promoting resistance to particular pesticides. They go so far as to recommend that key genes employed for this purpose

acteristics, such as the colour of leaves or number of legs, this new approach looks exclusively at distinctions in common strands of DNA. Paul Hebert, a professor at the University of Guelph’s Department of Integrative Biology, has spearheaded a movement dubbed the barcode of life, which applies the principles of molecular biology to the classification of species. “Now, all of a sudden, being able to read DNA sequences has turned this into a digital game,” he says, describing the basis for the International Barcode of Life Database, a digital archive that has grown up from Hebert’s work. This resource, which is expected to provide DNA identifiers for upward of 500,000 species within a few years, is already being consulted by scientists tracking the fate of threatened habitats, law enforcement officials tracking the distribution of poached lumber, and food agencies tracking the quality of products on the market. In each case the task at hand would have been much more daunting

without a straightforward reference service made possible by biotechnology. Hebert envisions hand-held equipment that can immediately identify species from tiny samples of material, capable of monitoring changes in environments that range from remote wilderness settings to polluted industrial landscapes. More specifically, this method could accelerate the pace of bio-prospecting and the cataloguing of information about organisms that could play an important part in biotechnology. It was just this kind of information that came to the attention of the Cetus Corporation, a California-based company that was among the first of the world’s biotechnology ventures. In 1985, researchers there were struggling with ways of reproducing large samples of a single type of DNA, so its biochemical pattern could be studied in detail. Their work was stymied until they learned about Thermus aquaticus, a bacterium first identified in the hot springs of Yellowstone National Park almost two decades earlier, then sent to a private, non-profit repository called the American Type Culture Collection. This organism secreted an enzyme that made possible the polymerase chain reaction (PCR), which has since become the workhorse method of handling genetic materials. Hebert argues that equally dramatic discoveries should emerge from the barcoding of the world’s organisms, which will provide essential data in a digitized form that PCR eventually made possible. “For people in chemistry, who have had machines to read concentrations of metals and organic compounds for decades,” he says, “they may think it’s a bit antediluvian to be only now bringing instrumentation to bear on the business of telling life forms apart.” Tim Lougheed is a freelance writer based in Ottawa.

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The Canadian Society for Chemistry is a co-owner society of PCCP.


Managing Mindsets Ian McCarthy explains why faster isn’t always better when it comes to managing a biotech business.

By Tyler Irving

ACCN Why does biotechnology need its own centre for

management? IM Ultimately, all industries are different, but biotechnology

in particular deals with high levels of uncertainty and innovation. At the same time, it’s a very controlled industry; the regulatory framework means that products are only approved for one use or market segment. That’s in contrast to other industries, where the use of an innovation gets shaped and changed by consumers. Finally, the level of capital investment required is much higher than many other industries. So there are a lot of factors which make it unique from a management perspective. That said, I’m a big believer in learning from other sectors. A lot of what we do involves understanding relevant practices in those sectors and applying them to biotech.

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Simon Fraser University

As challenging as it is, scientific discovery is really only the first step in a biotechnology breakthrough. Building a strong, well-managed business that can nurture the innovation through to market is crucial. Yet, for those most comfortable in the lab, the idea of running a business is often a foreign concept. Ian McCarthy is the director of the Centre for Biotechnology Management at Simon Fraser University’s Beedie School of Business. His research focuses on the strategies and management practices by which biotechnology and other high-tech industries can grow, adapt and keep up with the competition. ACCN spoke with McCarthy to learn more about how to manage the business of biotech.

Managing the ups and downs of starting and growing a ­biotechnology business is Ian McCarthy’s ­specialty. He is the director of the Centre for Biotechnology ­Management at Simon Fraser University’s Beedie School of Business.

ACCN Canada is often touted as an ideal place for

biotech, due to our natural resources and scientific expertise. Do you agree? IM I think Canada is really well endowed with top scientists

who have the ability to generate world-class intellectual property. The challenge lies in having the right sort of investment environment, in providing the capital needed to take ideas from the laboratory to the market. This is a challenge for many countries, but I think it’s particularly acute in Canada. Most of the investment money is beyond our borders, and when it comes to funding, proximity matters. Canada has certainly had success in terms of getting money from foreign venture capitalists, but I would say it’s probably the number one issue limiting the growth of biotech in Canada. ACCN What is Canada’s biotech scene currently like? IM There are hundreds of biotech companies across the country, largely located in the major metropolitan regions, such as Toronto, Vancouver and Montréal. That’s where the


Business | Biotechnology largest concentrations of universities and medical schools are; these are also very liveable cities which makes it easier for entrepreneurs to attract talent to work in their new ventures. ACCN Is that clustering of talent a good thing? IM Many of the people associated with the Centre for

Biotechnology Management have done work on the phenomenon of industry clusters, and we know they are important to the competitive health of an industry. First of all, assembling a concentration of biotech firms and talent drives a healthy competitive dynamic between the firms and talent. It raises the management game of companies and their employees. You have to be good at managing and motivating your employees, because if you aren’t they’ll walk across the road to another company. There are also economies of scale. Everyone wants a Silicon Valley, or Boston’s Route 128, because in addition to having a cluster of high-tech companies, you’re more likely to also have peripheral support companies, such as a regional office of a venture capital firm, or appropriate law firms specializing in intellectual property. In sum, clusters matter, as they provide a critical mass of companies which drives productivity and innovation, which help both the region and the industry as a whole. ACCN Are we nurturing the kind of clusters we need in

Canada? IM All of the big cities have been doing so for many years.

Often these revolve around research parks: in Vancouver we have Discovery Parks, which works with LifeSciences BC on biotech, but also in other sectors. In Toronto you have the MaRS Institute, which is well connected to the hospitals and universities, and which provides knowledge, training and infrastructure that feeds into the cluster. Some of this uses industry money; a lot of it uses government money. Of course, there are only so many resources to go around, but these are the sort of competitive dynamics which exist for all industry clusters around the world. ACCN Describe some of the projects in which you study good management strategies for biotech. IM My colleague Karen Ruckman and I have a project in

progress that is looking at the speed of licensing. Whether you choose to license a technology and how fast you do it is a very significant factor, because patents are only protected for a limited period of time. The reasonable assumption is that if

you have intellectual property, you want to license it and get revenues as soon as possible. We measured the time it takes from filing a patent to actual licensing, and matched that with the relative sizes of firms, previous licensing experience and other factors. You might imagine that the larger and more experienced the company, the faster it would be at licensing. We actually find the opposite trend: experience at licensing seems to make companies slower at it, probably because they become more diligent, taking their time to find the right partner. Also, bigger companies are less desperate for income, so that also tends to make them slower to license. In essence our research reveals some of the organizational and ­technological factors of biotech companies that affect their propensity to license with each other, which in turn impacts the resulting speed of a licensing deal. ACCN You’ve also written about how the concept of velocity applies to industry; can you explain that? IM In the 1980s, Stanford University professor Kathy Eisenhardt

studied the speed and process of strategic decision-making in the minicomputer industry. Because many aspects of the industry were changing so rapidly and in different directions, she characterized it as a ‘high-velocity’ industry. She proved that firms led by managers who made faster decisions will outperform those that don’t. As her work was eventually replicated for many different industries, I noticed that just about every industry was being called ‘high-velocity,’ including biotech. I thought to myself, “how can biotech be a high-velocity industry when it takes 10 to 15 years to develop a product?” Going back to Eisenhardt’s original definition of industry velocity, you find that what she talked about was rapid and discontinuous change in five things: regulations, technology, products, customer demand and competitors. What I saw in the biotech world was a mix of different speeds and directions: the science is changing very rapidly and often discontinuously in terms of new discoveries, but the products change slowly and more continuously. When it comes to regulatory change, it is slow, but the direction can change, as when [U.S. president Barack Obama] undid the restrictions that inhibited and indeed almost killed stem cell research in the U.S. So biotech isn’t really a high velocity industry, and the key to success is not necessarily being uniformly fast. Rather, it’s in synchronizing the decision-making schedules of different

november | december 2012 CAnadian Chemical News   21


Demand

Products

Competitive

Direction of change

Technological Continuous

Regulatory Low

Rate of change

High

Loose coupling Tight coupling

functional areas: research, product development, legal and in the case of large firms, manufacturing. All of these functional areas are operating on different temporal clocks, and effective leadership is all about coordination and synchronization. In our work we talk about two temporal mindsets: monochronic and polychronic. Monochronic people like to do things in a linear, one-at-a-time fashion. Polychronic people are multitaskers, and think of time as being intangible, so they are less concerned with deadlines. What we argued in our paper was that if you’re in a world like biotech, where everything is changing at very different rates, managers with polychronic temporal orientations will outperform the monochronic ones. ACCN How can chemists and chemical engineers

­interested in biotech benefit from your research? IM Entrepreneurship, management and leadership are like

music, medicine, sports or any other arena. Some people are born gifted entrepreneurs, and there would be very little a business school could add, but that’s a very small percentage of the population. What we do is study what makes a great entrepreneur and their road to success. We then distill and convert this understanding into knowledge, training and education which helps people raise their entrepreneurial game. A classic example is networking. We know entrepreneurs are good at it, and we know that the network of a first-time entrepreneur is different to that of an experienced serial entrepreneur. We can study their techniques

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Industries are not uniformly fast or slow, according to business ­professor Ian  ­McCarthy. Rather, they can be ­characterized by both the rate and direction of change in five main functional areas: regulations, technology, products, ­customer demand and competitors.

ACCN What about researchers who

don’t want to start new ventures, but instead prefer to partner with existing firms for research and development? IM Biotech is a bit of an outlier in this

regard compared to other industries. In a way, it’s precisely because it’s so innovative in terms of science that it often feels less inclined to be innovative in terms of its business models and management ideas. Part of it is also the regulatory framework behind biotech, which slows the pace of its development and makes it difficult to experiment with the process of business innovation. But I think this is a key area where biotech could learn from other industries. It’s very difficult for one firm, even a big one, to possess all the knowledge and resources necessary to do business. Certainly it’s good in terms of job creation, but if the long-run outcome is that it makes you uncompetitive, then it’s not viable. Thus, open innovation, user innovation and crowd-sourcing are hot topics these days. More and more, firms are asking their industrial customers, their suppliers and even their consumers, to innovate on their behalf. I don’t see any reason why this “open source” trend should not apply to the biotechnology industry, whether it’s pure outsourcing arrangements for things like field trials or testing services, or outsourcing to take advantage of problem-solving talent you don’t have. For example, two employees of Eli Lilly established a spin-out company called InnoCentive, which posts scientific and engineering problems for the public to view and solve. It then rewards the individuals who come up with the best solutions. ACCN Does all this apply to small firms as much as to

the big ones? IM I would say it applies equally, if not more. I recently read a

report that stated only a third of Canada’s biotech companies actually make profits, and of those, about half were making only a few million dollars a year. These companies suffer from liabilities of smallness and newness. They’re fragile, and they need stronger management and leadership to ensure that they survive than a larger, more established company which is sitting on billions of dollars of cash reserves.

from a diagram by Ian McCarthy ( REF. McCarthy et al. 2010. A multidimensional conceptualization of environmental velocity. Academy of Management Review, 35(4): 604-626)

Discontinuous

for making connections and gathering knowledge, capital and talent, and translate this into lessons.


Ichikizaki Fund for Young Chemists The Ichikizaki Fund for Young Chemists provides financial­assistance to young chemists who show unique achievements­in basic research by facilitating their participation­in international conferences or symposia.

Eligibility: • be a member of the Canadian Society for Chemistry or the Chemical Society of Japan; • not have passed his/her 34th birthday as of December 31 of the year in which the application is submitted; • have a research specialty in synthetic organic chemistry; • be scheduled to attend, within one year, an international conference or symposium directly related to synthetic organic­ chemistry. Conferences taking place in J­ anuary to March of each year should be applied for a year in advance­in order to receive funding in time for the ­conference.

Deadline: December 31, 2012 For more details:

www.cheminst.ca/awards

CIC Award for High School / Cégep Chemistry Teachers Sponsored by the Beaumier Churcott Foundation Presented in recognition of excellence in teaching chemistry at the high school or Cégep level and to encourage and promote chemistry at the high school and Cégep level in Canada. The full Terms of Reference for this award are available at

www.cheminst.ca/awards

Deadline: December 15, 2012 for the 2013 award

Submit your nomination to: awards@cheminst.ca

www.oleotek.org


Sara Collaton

Nature’s Industrialists

By blending biotechnology and engineering, Canadian researchers­are ushering in a future where commodity chemicals­ are not made, but grown.

R

adhakrishnan Mahadevan’s desk is piled high with scientific papers, and the walls of his office present whiteboards covered in complex differential equations. Such an environment is entirely appropriate to the convoluted task that Mahadevan, an associate professor in the Department of Chemical Engineering and Applied Chemistry at the University of Toronto, has set for himself: to model the metabolic pathways of microorganisms, and to determine how they can be manipulated to optimize the production of valuable chemicals. Every day, nature simply and efficiently performs chemical transformations — some on a truly immense scale — that would confound even the most talented chemical engineer. Of course, nature has a secret weapon: enzymes. Over millennia, these protein-based biochemical catalysts have evolved to facilitate reactions that would otherwise seem impossible. In the last decade, the plummeting costs of techniques like DNA/RNA sequencing and protein mass spectrometry have greatly accelerated research into understanding how enzymes work. Now, the time is ripe to see if these lessons from nature can be used to solve human problems such as breaking our addiction to crude oil or making more

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By Tyler Irving

efficient use of forest resources. In these endeavours, chemical engineers like Mahadevan are leading the way. “In many ways, a biological system is no different than a chemical factory: they both take raw materials and process them into products,” says Mahadevan. A process control engineer by training, Mahadevan became interested in microbes about ten years ago, when he attended one of the first ever conferences in what’s now called systems biology. “That term means different things to different people, but from an engineering point of view, we try to break a biological system down


Chemical Engineering | Biotechnology

Radhakrishnan Mahadevan’s computer models of metabolic­processes describe how to tweak the genetics of microorganisms to maximize the production of valuable chemicals­.

algorithms have been proposed for this, but ours can solve really large-scale problems in a fraction of the time,” he says. “We’re going from days and weeks to sixty seconds.” While such detailed models may be new, the idea of producing a valuable chemical from a microbial process is not; the yeast Saccharomyces cerevisiae has been used to ferment sugar into ethanol for thousands of years. But in most cases, biologically-produced chemicals currently cost more than their oil-based equivalents. That may change as oil reserves diminish or if carbon pricing becomes widespread, but for now turning valuable sugar cane or corn into a low-value biofuel makes questionable economic sense, and researchers are focusing their efforts elsewhere. “A lot of chemical engineers working in biotechnology are focused on commodity chemicals rather than fuels,” says Pratish Gawand, a PhD candidate in Mahadevan’s lab group whose passion for biotechnology shows through in his rapid-fire speech and encyclopedic knowledge of key papers. “Commodity chemicals still have a relatively large market, but are sold at a higher price than ethanol, so it’s easier to justify the cost of production.” Gawand cites a 2004 U.S. Department of Energy report that identifies 12 classes

into parts, see how the parts link up together, and then reconstruct a model of the overall system,” he says. He points to a poster on his wall which depicts the rough outline of a cell, thickly covered with a spider’s web of arrows and "A lot of chemical engineers working in biotechnology boxes containing the names are ­focused on commodity chemicals rather than fuels. of enzymes and chemical It's easier to justify the cost of production." intermediates. It’s a metabolic map, describing all of the reactions by which the bacte- of non-fuel chemicals that could be produced from biomass sugars using known rium E. coli converts one molecule into metabolic pathways. At the top of the list was succinic acid. This four-carbon another in order to extract energy or molecule can be used as a building block in everything from polymers to pharmabuild cell components. In Mahadevan’s ceuticals. It’s also part of the citric acid cycle, the series of biochemical reactions computer models, this network of that provides energy in all aerobic organisms. Since microbes like E. coli already enzymes, metabolites and reactions is produce succinic acid as part of their metabolism, getting them to produce lots represented by sets of equations and of it should be a matter of tweaking only a few genes. Predicting which genes to variables. Changing the parameters of tweak is exactly what Mahadevan’s models are designed to do. the model can predict the effect of overBut there’s another problem: if you force a bug to spend all of its energy producing expressing, down-regulating, or even succinic acid, it tends not to grow very quickly. Luckily, that problem is being deleting the gene that encodes for a tackled by Nik Anesiadis, a student just finishing his PhD in Mahadevan’s lab whose specific enzyme. easygoing manner belies his knack for detail. Anesiadis’ solution takes advantage of Last year, Mahadevan and his graduate a phenomenon called quorum sensing. Many bacteria produce signalling molecules student Laurence Yang published a paper that are sensed by their neighbours; the concentration tells the cells how crowded in Metabolic Engineering in which they they are. When things get too cosy for comfort, the cells turn certain processes off describe a new computer algorithm called or on, almost like a genetic switch. Using molecular biology techniques, Anesiadis EMILiO: Enhancing Metabolism with has managed to incorporate his genetic changes into this switch. The result is a Iterative Linear Optimization. EMILiO line of E. coli cells that grow normally until their vessel is full, then start producing searches through existing metabolic succinic acid like crazy. That system is still being refined, but bio-based succinic models and identifies which modifications acid is already moving ahead in industry. BioAmber, an American company with are most likely to increase production a patented process for producing succinic acid using yeast, is currently building a of a given chemical target. “Previous 34,000 tonne per annum plant in Sarnia, Ont.

november | December 2012 CAnadian Chemical News   25


Ultimately the idea would be to create a ‘forest biorefinery’ where each fraction of wood - c­ ellulose, hemicellulose and l­­ ignin ­provides its own set of valueadded­ p ­ roducts. *** Where Mahadevan is a chemical engineer working with biological systems, Emma Master is the opposite: an environmental microbiologist who has found her niche in chemical engineering. Her office, one floor up in the same department as Mahadevan’s, is neatly organized and the diagrams she needs to explain her work are filed away in drawers. This is ironic, as the wood-derived molecules she works with are some of the messiest around, both in terms of where they come from — think of rotting tree trunks — and in terms of the chaotic chemical structure they posses. “Softwood remains one of the more difficult, biologically recalcitrant biomass sources to work with,” says Master. That’s because wood is actually a mix of three biopolymers: cellulose, hemicellulose, and lignin. Cellulose is the most straightforward: a long chain of glucose molecules joined up with a repeating beta 1,4 linkage. But hemicellulose, while sporting the same basic backbone, contains other sugar groups that branch off randomly in all directions, giving it unpredictable properties that vary wildly from one species to another. These branching groups interact with lignin (an even more complex polymer) and cellulose, binding the tree together. Although they are among the most common chemicals on the planet, making use of these three polymers requires their efficient separation. Traditionally, the North American pulp and paper industry has focused exclusively on cellulose, using harsh chemicals to isolate it from its less-valuable cousins and refining it into newspaper, cereal boxes and hundreds of other products. But competition from developing countries and the rise of paperless communication has meant hard times, and the industry is now searching for ways to extract more value from trees. Hemicellulose and lignin offer many possibilities: they could increase the structural strength of plastic in everything from car door impact panels to lawn furniture, or act as non-toxic scaffolds in medical implants. They could even be broken

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down into their basic sugars and fermented into ethanol, saving corn and sugar cane for more valuable applications. Ultimately the idea would be to create a ‘forest biorefinery’ where each fraction of wood — cellulose, hemicellulose and lignin — provides its own set of value-added products. But before any of that can happen, Master and other researchers like her have to conquer the inherent messiness of hemicellulose and lignin. Unsurprisingly, she’s relying on enzymes to do so, and she’s looking for them in some of the most unusual places. For the last two years, one of her students has been carefully raising cultures of bacteria originally isolated from beaver droppings and the stomach contents of moose. “The moose can consume pine needles, which are quite difficult to digest, and the beaver can eat bark,” explains Master. “We thought that if we looked at their gut flora, we might find some organisms with interesting catalytic activity.” Some of the bacterial cultures are fed with cellulose, while others are grown in the presence of lignin or other inhibitory compounds. The bugs are happily producing biogas (methane), so something in there must have the right enzymes to break down these recalcitrant chemicals. Eventually, Master hopes to use RNA sequencing to identify these enzymes in the most successful cultures. Another place to look for hemicelluloses and lignindegrading enzymes is in fungi, which are known for their ability to grow on rotting wood. Two months ago, Master’s group published the genome of Phanerochaete carnosa, a fungus that is particularly good at degrading softwoods. “Of course the genome just gives you the blueprint; it doesn’t tell you which genes are expressed in different conditions, or which enzymes are secreted into the culture medium,” says Master. For that she needs techniques like proteomics. This involves extracting fungal proteins/enzymes from


Chemical Engineering | Biotechnology

her cultures and using other enzymes to digest them into smaller chunks. These chunks are then run through a mass spectrometer, the readout of which is a biochemical fingerprint for the protein of interest. Using techniques like these, Master’s group has already achieved some success. They’ve identified enzymes that act as glycoside hydrolases, meaning they can break off the branching sugars that make hemicellulose so tough to deal with. Using these enzymes in industrial processes could make it easier to achieve clean separation of wood’s three biopolymers (current chemical methods tend to contaminate the hemicellulose and lignin streams). Enzymes may also provide a way of standardizing the quality and properties of hemicelluloses between species. The group has even managed to introduce the gene for one of these enzymes into the model plant Arabidopsis thaliana, causing it to partially separate its own hemicellulose and lignin as it grows. Of course, a plant that digests its own structural materials doesn’t grow very robustly, but Master already has a solution in mind. “One way to control any negative consequences is by using a genetic promoter that is only induced during later stages of

It’s clear that both biotechnology and chemical engineering need each other if either is to fulfill its promise of solving society’s problems.

John Hryniuk

plant development.” The approach is similar to Anesdias’s method of late expression in E. coli, although it uses a completely different genetic switch. Master hopes that experiments like these will help researchers identify genetic markers in trees that lead to fibre characteristics which are optimized for separation in the forest biorefinery.

Emma Master studies the enzymes that fungus and other organisms use to break wood down into its constitutent biopolymers - cellulose, hemicellulose and ­lignin - which can then be used in plastics, adhesives, medical products and more. Recently, her group introduced genes from fungus into this Arabidopsis plant, a common­model organism for genetic studies.

*** It’s clear that both biotechnology and chemical engineering need each other if either is to fulfill its promise of solving society’s problems: Mahadevan’s models apply chemical engineering techniques to biological systems, while Master’s work on biorefineries applies biotechnology techniques to industrial chemistry. As Pratish Gawand wryly observes, blending the two is not without its challenges. “With engineering processes, you can be sure of what’s going on,” he says. “Biological processes are not like that; the bugs are finicky and things don’t always work the way you think they will. It’s really an art. But when your strategy works and you’re able to make something that could actually be useful to industry, that is very exciting.” Exciting indeed, for the ultimate goal is nothing short of transformational change to some of the world’s most staid industries, from petrochemicals to pulp and paper. “It’s about being able to do more with what nature has given us,” says Emma Master. “That’s very motivating.”

november | December 2012 CAnadian Chemical News   27


www.bio.org/worldcongress


News from the Chemical Institute of Canada and its three Constituent Societies | Society news

Things to know

Save the date

It’s time to renew your CIC and Constituent Society membership for 2013. Be sure to maintain your Canadian Society for Chemistry, Canadian Society for Chemical ­Engineering or Canadian Society for Chemical Technology membership to continue to access CIC member benefits like ACCN, the Canadian Chemical News, reduced registration rates for conferences and professional development courses and access to our career service initiatives. Renew now at https://secure.cheminst. ca/default.asp, where you can also sign up for our convenient automatic renewal service to save you time next year! The Call for Papers for the 96th Canadian Chemistry Conference and ­Exhibition, to be held May 26-30, 2013 in Québec city, Que. is scheduled to open December 5. Visit www.csc2013.ca to submit your abstract. The first round Call for Symposium Submissions for the Pacifichem Congress, scheduled to run December 15-20, 2015, opens January 1, 2013. Find out more at www.pacifichem.org.

April 4, 2013 CIC “Green, Clean, and Sustainable” Seminar & SCI Canada Awards Dinner Toronto, Ont. cheminst.ca/awardsdinner May 26-30, 2013 96th Canadian Chemistry Conference and Exhibition Québec, Que. csc2013.ca June 6-8, 2013 College Chemistry Canada Corner Brook, Nfld. collegechemistrycanada.ca

Conferences

CIC announces EnviroAnalysis partnership Beginning in 2013, the CIC will partner with the EnviroAnalysis Corporation to run the EnviroAnalysis Conference in Toronto. The focus of the meeting since it began in 1996 has been the science of measuring and monitoring contaminants in the environment, the cornerstone of environmental investigation and regulation enforcement. “We’re very pleased to be partnering with this important event,” says Roland Andersson, CIC’s Executive Director. “The CIC has the experience and know-how to host tremendously successful conferences, as demonstrated by our annual chemistry and chemical engineering conferences, the two largest conferences in their subject areas in Canada. At the same time, this new connection with the analytical and environmental chemistry community will help the CIC to expand our industrial and government network and programming activities.” The 2013 EnviroAnalysis Conference is scheduled for September 15-18 at the Toronto airport strip. Watch cheminst.ca for more details. Subject Divisions

CIC industry programming boosted by merger The CIC Economics and Business Management (E&BM) Subject Division officially merged with the Society of Chemical Industry (SCI) – Canada Section in October. In 2013 SCI Canada will become a Forum of the CIC. The merger will immediately provide the dormant E&BM Division with a governance body, a set industrial program, which includes the long-running SCI seminar and awards dinner, and an infusion of funds.

June 15-19, 2013 World Congress on Industrial ­Biotechnology & Bioprocessing Montreal, Que. bio.org/events August 11-16, 2013 44th World Chemistry Congress Istanbul, Turkey iupac2013istanbul.org August 18-23, 2013 9th World Congress of Chemical ­Engineering (WCCE9) Coex, Seoul, Korea wcce9.org September 15-18, 2013 EnviroAnalysis 2013 Toronto, Ont. enviroanalysis2013.ca October 20-23, 2013 63rd Canadian Chemical Engineering Conference Fredericton, N.B. csche2013.ca

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


Chemfusion

Anti-antifreeze makes little sense

W

hy do they put antifreeze into shampoo?” That’s what my somewhat indignant caller wanted to know. She had been doing some shampoo label reading and discovered propylene glycol. Recognizing it as an ingredient in a recently purchased antifreeze product, she was mystified as to why it should be in her shampoo. Actually, she was more than mystified. She was disturbed. The notion of washing her hair with antifreeze was not appealing. As we in the chemical community realize, the inclusion of a chemical in a product that is not meant to be consumed or applied to the skin does not mean that it is not safe for consumption or skin application. But for others that seems to be a tough concept to swallow. A chemical used in antifreeze, they maintain, has no place in personal care products. Propylene glycol is indeed used in antifreeze products and increasingly so because it is far, far safer than ethylene glycol, the classic antifreeze component. Some anti-chemical activists don’t see it that way. They relish in pointing out that propylene glycol is just one carbon atom away from the “highly toxic” ethylene glycol and absurdly infer that it is close to being just as dangerous. In personal care products propylene glycol is not used because of its ability to lower the freezing point of water. Here it is its ability to form hydrogen bonds with water that makes it useful. Incorporated into a cream or shampoo, propylene glycol acts as a “humectant,”

30  CAnadian Chemical News

meaning it reduces moisture loss and prevents the hair or skin from drying out readily. For the same reason, it is used as an additive in pipe tobacco. But affinity for water is not the only reason propylene glycol finds a use in personal care products. It is also an effective emulsifier, meaning it prevents water and oil from separating. Since most cosmetic products are mixtures of water and a variety of oily materials, emulsifiers are critical for the achievement of an acceptable texture. Indeed, the production of suitable emulsions is the most critical aspect of cosmetic manufacture and the production of emulsifiers is a whole world in itself. Propylene glycol is remarkably nontoxic. It is almost impossible to achieve toxic levels through ingestion; it is approved for use in human food as a solvent for colours and flavours. It’s also approved for inhalation; it is the solvent used in electronic cigarettes to dissolve nicotine. According to the World Health Organization, an average-weight person would have to ingest about three pounds of propylene glycol to produce a toxic effect. One alarmist website features the following wisdom: “For starters it alters the structure of the skin by allowing chemicals to penetrate deep beneath it while increasing their ability to reach the blood stream. Sounds lovely, right? So even if propylene glycol was good for you, its main job is to help any other chemicals you come in contact with reach your bloodstream.” That isn’t lovely, it’s

november | December 2012

By Joe Schwarcz

nonsense. The main job of propylene glycol is to act as a humectant, not to help chemicals reach the bloodstream. If there is a concern about this chemical, it would be its role as an environmental pollutant. Not from cosmetics, but from extensive use as an airplane de-icer. Several thousand gallons may be used to de-ice a single airplane. If propylene glycol then ends up in lakes and rivers it can significantly increase the biological oxygen demand meaning that aquatic organisms including fish that also require oxygen can suffer. Of course, if airplanes are not de-iced when needed, humans will suffer. Interestingly, propylene glycol is also used as a solvent for boric acid in the battle against wood-boring insects such as termites, beetles and ants. It helps to convey the toxic boric acid into the wood where it dispatches the bugs. I’m surprised that nobody has yet tried to frighten people about propylene glycol in their cosmetics by saying that it is an ingredient in insecticides. Of course, so is water. Joe Schwarcz is the director of McGill University’s Office for Science and Society. Read his blog at chemicallyspeaking.com.


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ACCN, the Canadian Chemical News: November | December 2012