Inside Laboratory Management, Volume 6 (1) pp 6-7, 2002
Few analytical chemists get a chance to be featured in National Geographic, or to solve historical puzzles in the pages of Nature. Few start businesses in their garages, only to have them earn honors as “Small Business of the Year”.
Welcome to the world of Barry V. McCleary, who recently added the 2002 Harvey W. Wiley Award, AOAC’s top scientific honor, to his list of accomplishments. (The award is given annually for career achievements in analytical methodology). A soft-spoken Australian now living in his ancestral home of Ireland, McCleary is a cereal chemist whose work has centered around starches, grains, and their enzymes.
McCleary’s career path reveals a decade-long tension between two pairs of competing factors: government service and entrepreneurship, methods development and biochemistry.
Biochemistry, particularly the study of how plants build, use, and manage carbohydrates, was his first love, spurring a Ph.D. in Agricultural Chemistry in 1975 from the University of Sydney, Australia, followed by a 14-year career with the New South Wales Department of Agriculture.
That love of biochemistry indirectly led McCleary to his true calling: the development of analytical methods for carbohydrates and their enzymes – a career shift that was, ironically, propelled by the young Australian’s dislike of routine analysis, particularly with the time-consuming carbohydrate methods of the late 1970s.
“Nobody was updating the old standbys,” McCleary says, “and there had to be easier ways.” To reduce the drudgery, he took it on himself to develop simpler methods, intending this research as a sideline that would allow him to work more efficiently on the underlying biochemical problem.
That often led to two scientific papers: one on the method, the other on its application. Soon, McCleary noticed a trend: “I’d get more reprint requests for the method than the final paper,” he says. And unlike routine analysis, methods development was fun. “We all want to do something that makes a contribution,” he adds, “and [analytical chemistry] seemed to be where my strength was. I still like it.”
At the same time, McCleary’s practical mindset drew him to look for industrial applications. One early interest was the use of enzymes to modify guar gum into a commercially more valuable food thickener, similar to locust bean gum.
Chemically, this involved working with galacotmannans, the thickening agents found in both products, in an effort to make the guar variety mimic the higher value locust bean form.
In the early 1980’s McCleary published a series of papers proving that this was possible, and in 1982-3 he took a temporary post in the United Kingdom, with Unilever, working to scale up the process for tests in ice cream. Enzyme-modified guar gum has now been marketed for several years, made with gene-engineered yeast.
Another practical problem involved b-glucans, polysaccharides that, when found in excess quantities in barley, lead to viscosity related problems in beer manufacture. Brewers were pressuring plant breeders to develop better strains of barley, but the field was languishing due to lack of a good method for measuring the troublesome dietary fiber. In 1985, McCleary unveiled a method that is now the world standard, approved by AOAC and used industrywide.
Reading McCleary’s resume from these years is like watching a transoceanic Ping-Pong game, as he alternated between stints in New South Wales and visiting positions not only in the United Kingdom, but also in Switzerland, the United States, and Ireland. Partly, he traveled when his interests led him into product development research of the type that government agencies are loath to fund. Partly he traveled to seek out fellow experts and to “fertilize” his brain.
Analytical chemistry and entrepreneurship ultimately won out over government service. In 1988, McCleary shocked friends and colleagues by walking away from his secure government post to found his own company.
The company, called Megazyme, was anything but “mega-“ at the outset. The workforce was comprised of McCleary and his wife, Angela Kennedy, plus a half-time worker; its plant was a pair of auto garages. Getting rich wasn’t the goal. “ I did it because I wanted to continue working on methods development, and I could see a real need for enzyme/carbohydrate methods,” McCleary says. Furthermore, his government career had reached a point where the only advances left to him were into administration. “Lots of people younger than me haven’t seen a test tube in 10 years,” McCleary says. “I get to spend a day-and-a-half or 2 days a week in the lab. Had I stayed [in government], I’d probably be sitting behind a desk reading a boring report, wishing I was somewhere else”.
Megazyme succeeded quickly, thanks in part to good teamwork: McCleary developed the fledgling company’s product line, while Kennedy, with a background in business and marketing, looked after maintaining the cash flow.
Even before the company moved out of the garage, it began winning small-business awards, including a prize as the state’s top new small business, beating out other firms with up to 100 employees. Two months later, it was picked as manufacturer of the year in a nationwide competition, also for firms of up to 100 employees.
Now relocated to the Emerald Isle, Megazyme is still small, but still winning awards, most recently for its e-business, which draws half of its new customers and 45% of overall sales.
The company specializes in kits for measuring carbohydrate-related analytes. Its latest, currently undergoing an interlaboratory study for AOAC approval, measures resistant starches - the topic that McCleary has chosen for the symposium to be held in his honor at AOAC’s upcoming annual meeting.
Resistant starches are not digested by the small intestine. In other words, they are dietary fiber. But unlike conventional fiber, these are “invisible” fiber - they do not affect the food’s taste or texture. That means manufacturers can convert conventional products into good-tasting health foods by loading them with resistant starch. As McCleary puts it, “Consumers will be able to get more dietary fiber without having to eat bran”.
Unfortunately, resistant starches are also essentially invisible to conventional analytical methods. That makes them useless to manufacturers wanting to back up their label claims. Interest is so high in developing a standard method for them that when McCleary announced his interlaboratory study, he was swamped with labs wanting to participate.
McCleary’s other work at Megazyme has involved the development of kits for measuring enzyme activity, particularly for processing enzymes.
Many of these kits take the form of tablets that can be mixed in a test tube with the enzyme-containing matrix. The tablet is comprised of a specially tailored substrate, linked to a dye. When the enzyme acts on the substrate, it releases dyed fragments - which provide a simple indicator of the rate of enzyme activity.
One such kit measures alpha-amylase, an enzyme that breaks down starch. The enzyme is produced in moisture-damaged wheat, as part of the biochemical process that leads to sprouting. Even small amounts of it in wheat, however, yield a gummy bread that won’t slice.
McCleary’s method, which replaces a more time-consuming test used since 1967, reveals the amylase concentration of flour in 10 minutes. It has been adopted by the United Kingdom baking and flour milling industry and is undergoing an AOAC interlaboratory study.
What of McCleary’s unanticipated role as an historian? That involved an 1860-61 expedition across interior Australia. Intended as a scientific exploration the trek evolved into a race against another expedition for the prize of being the first European to make a south-to-north crossing of the Continent’s desert heartland. In the heat of competition, the explorers split off an advance party that abandoned any pretense at science and dashed across the continent as rapidly as possible. They won, but it was a Pyrric victory. In the haste to be first, the advance party outran its supply train and had to live off the land on its way back to civilization. Three of its four members perished, falling prey to a mysterious ailment that converted even the most minor activities into grueling workouts. The survivor would have died too, but was rescued in the nick of time by Aborigines.
History had judged the expedition harshly, painting it as a mismanaged affair run by glory seekers who took a big risk and paid the price. But the explorers should not have starved. They had met Aborigines who had taught them native cuisine, and nobody was hungry. Whatever killed them was not simple starvation.
McCleary found the vital clue in the late 1970s, when he was working with the Department of Agriculture. There, his first assignment was to track down the source of an ailment that in the previous 6 months had killed about 10% of the sheep in large areas of northern New South Wales. The ailment, never before researched, looked a bit like vitamin B1 deficiency, and a bit like poisoning cases reported in the United Kingdom from bracken fern. The culprit, McCleary discovered, was an Australian fern called nardoo, which contains the enzyme thiaminase, which destroys the vitamin thiamin, without which the body is unable to metabolize carbohydrates. “It’s pretty potent stuff,” McCleary says. “We figured that about 1 gram of the plant was enough to wipe out all the thiamin in a sheep’s body.”
Why the plant contains such an enzyme nobody knows, but the cure is simple: when farmers notice the first warning signs of nardoo poisoning, entire flocks are injected with large doses of thiamin.
A decade later, McCleary got to talking about this with another biochemist, JohnW. Earl. Earl was interested in history, and the conversation turned to the lost expedition of 1860-61. “ We spent some time thinking about it,” McCleary says “and it was obvious that they died from thiamin deficiency (beriberi) – something nobody had noticed before.”
Digging into the explorer’s diary entries revealed that the native food they had been preparing had been flour made by grounding spore pods of the nardoo fern. These pods contain less thiaminase than do the parts of the plant that McCleary’s sheep were eating, but they still contain substantial amounts. Aborigines could safely eat the flour because their recipe involved soaking the spores in water (removing the enzyme). The explorers appear to have treated it as wheat, skipping the all-important soaking stage. Given the biochemical effects of the enzyme, the result was the same as starving to death, only quicker: The more they ate, the less nourishment they could derive not only from the food, but also from their bodies’ own stored energy supplies.
Of all of McCleary’s many accomplishments, unraveling the mystery of nardoo is the one that has gotten him the most attention from the popular press. “It’s strange the things that come out of a barbecue with a friend,” he says.
Equally strange are the surprises that can grow out of a garage.
By Richard A. Lovett, Contributing Writer, AOAC INTERNATIONAL