Got Your Goat

Raising goats

Nexia Biotechnologies CEO Jeffrey Turner, PhD is working on something big

BY PATRICIA NICHOLSON

Raising goats in Quebec may not sound like a wildly ambitious plan — unless it’s Jeffrey Turner’s plan. Turner, PhD, is president and CEO of Nexia Biotechnologies Inc. (Vaudreuil-Dorion, QC), and his goats do some impressive tricks.

Nexia Biotechnologies is best known for its lead product, BioSteel® — a manmade spider silk spun out of proteins from the golden silk spider expressed in the milk of transgenic goats. Its applications include body armour and surgical sutures, as well as technical sports gear and potentially replacing many plastics and nylons. The company’s second product in development is a recombinant version of butyrylcholinesterase (BChE) called Protexia™. BChE is a bioscavenger, found in very small quantities in blood, that absorbs and neutralizes nerve agents. By expressing BChE in the milk of transgenic goats, Nexia Biotechnologies hopes to produce commercial quantities of the bioscavenger, which has military and civilian applications.

“It’s really what we consider to be the next wave in biotechnology — creating these materials,” Turner says. They aren’t exactly disease treatments, he says, but they do address life-threatening situations. “Be it a bullet for BioSteel or be it a nerve gas for Protexia. The world’s a dangerous place and if we could solve some of those things with innovation and science, so much the better. That’s really the story of Nexia.”

Turner’s interest in proteins began in Antarctica. After completing a master’s degree in animal physiology at McMaster University (Hamilton, ON), Turner was a visiting scientist with the United States Antarctic Research Program at McMurdo Station, Antarctica, where he studied proteins in fish.

“I’d done a lot of work in the past on fish, but none on proteins, so I got really interested in these wonderful little molecules called proteins,” Turner says. He then began studies at the University of Illinois at Urbana (Urbana, IL), where he earned a second master’s degree in protein chemistry and a PhD in molecular biology. He returned to Canada in 1987 to join the animal science department at McGill University in Montreal, Que.

Something Big

“It was great — what a wonderful community and a super bunch of people. I really dug into it and built up a lab,” Turner says of his years at McGill, where he researched lactation in farm animals. “Then I found myself seven years later sitting there saying, ‘is this it?’”

As a 34-year-old tenured professor at a major university, Turner was hardly dissatisfied with his position. But nor was he complacent about the future.

“That’s when I met a couple of venture capitalists. I’d never met these types of people before. People like Bernard Coupal in Montreal. Bernard was really the godfather of biotechnology in Canada,” Turner says. “He’d say, ‘Why don’t you do something big with your life?’ So I said, ‘I’m doing something big with my life. I’ve got this great position, I’ve got lifelong tenure.’ And he said, ‘No, I mean really do something big.’ So we started talking, and I told him my views of the future, and he said, ‘Well, if I gave you a few million dollars of research money, would you leave the university and start a company?’”

Turner resigned from McGill and went into business in September 1993 with $2.5 million and the MAC-T (mammary alveolar cells with large-T antigen) cells he’d patented at the university.

Got Your Goat

“I was trained as a scientist. I had no business background whatsoever,” he says. “So I built a good team and surrounded myself with business people who knew about things, and some fabulous scientists who are still here today. And we set about building Nexia.”

The MAC-T cell line made it possible to evaluate in vitro the performance of foreign genes in a mammary environment.

“We call it the world’s smallest dairy,” Turner says. “Epithelial cells are the only cells in the udder that make milk. We took those out of the cow and we immortalized them . . . The MAC-T cell technology was really the foundation on which we could evaluate genes for production, be they spider silk genes, be they Protexia genes and bioscavenger genes and things like this. So we had that good technology but we didn’t really have a system for producing the proteins.”

Turner says the BioSteel technology took about five years to develop. The spider silk genes and the promoter, or switch, that controls the genes were licensed in from separate sources. Together, these make a DNA construct.

Using the method by which Nexia Biotechnologies produced its first transgenically modified animals, that construct is then introduced into a goat egg using a very fine glass tube. About five per cent of the time, the introduced DNA is successfully integrated into a goat chromosome.

“Today we use a different technology called nuclear transfer — popularly called cloning,” Turner says. “We take the same gene, put it into a cell, make sure that it works, make sure it’s part of the chromosomes and everything, and then we take that cell and we put that into a single-celled goat egg. And that way you know the gene is in there and you have greater than 95 per cent chance that you will have a transgenic animal being born.”

A couple of transgenic males — Webster and Peter, in the case of BioSteel — can pass the modification on to enough offspring to build a herd.

“It’s a front-end-loaded technology. Once you’ve got the gene into the genome of an animal, you just disseminate it in the truest sense of the word through the male line,” he says. The genes are transmitted faithfully from one generation to the next, so once the founder animals are produced, Turner laughs, “You’re a bunch of goat farmers. So you milk the goats and then you purify the proteins and then you make your products. But all the genetic modification for these things has been done long ago.”

Nexia Biotechnologies chose to work with goats because it required an animal that bred quickly and matured quickly.

“All animals make milk, so you could use mice. Mice are genetically modified very easily, but they don’t make a lot of milk. As I’ve often quipped, there are no commercial mouse cheeses,” Turner says. “Dairy cattle, on the other hand, make a lot of milk, but it takes years to modify them genetically. It takes 12 months before they are even mature. So we wanted an animal that was easy to modify and produced a lot of milk using conventional milking machines. And that was a goat.”

But not just any goat. Nexia Biotechnologies’ BELE® (breed early, lactate early) goats were developed from Nigerian dwarf goats, which, unlike most goats, breed throughout the year. These were bred with larger North American female goats that produce more milk.

“The BELE goat was an innovation that we brought to this sector and has allowed us to move very quickly and produce the materials on a much more compressed timeline as opposed to cows. We’d still be working on the first silk gene if we were working with cows.”

Fame and Fortune

BioSteel captured the public imagination as few other biotech products have done.

“The promise of BioSteel was enough to do the largest IPO in biotech history in Canada,” Turner says of the company’s initial public offering in 2000. “We raised $42.5 million to produce BioSteel and to get the transgenic platform working.”

But the real attention was to come later. In January 2002, Nexia Biotechnologies and the U.S. Army published a paper in Science describing BioSteel, and Nexia found itself under a very bright spotlight.

“It was incredible . . . Pictures of cartoon goats in Esquire magazine rappelling down Madison Avenue in New York,” Turner says. “Trying to live up to that type of hype has been a challenge for us.”

Turner points out that prior to the publication of that paper, Nexia Biotechnologies’ goal was widely considered impossible.

“You have to remember that the DuPonts of the world, the U.S. Armies of the world, had spent literally millions and millions of dollars to try to create manmade spider silk and failed miserably,” he says. “So for a little startup company to think that it could do something was, to say it mildly, a little bit audacious.”

Publications ranging from The Economist to the New York Times reported on the Canadian startup with the amazing goats.

“When you have such a — I daren’t use the word ‘sexy’ technology — but let’s say very exciting technology, the real challenge is maintaining an even strain and letting people know where the technological hurdles are,” Turner says. “But when you read something in the Wall Street Journal or Time magazine that says, Small Canadian Company is Taking on the World, or This Goat Could Save Your Life, it’s pretty hard to manage that public relations- and IR-wise.”

The challenge, he says, was not getting people excited about BioSteel, but getting them to be realistic. Turner says there is much work yet to be done. “We can mimic the spider on toughness and flexibility and modulus. On strength we’re about 30 per cent there,” he says. “We’re still learning from the spider and hoping to get that stronger. But in the meantime we continue to get more goats. More goats mean more silk.”

Role of a Lifetime

Turner is a rarity in Canadian biotech companies: a founding scientist who has remained in the CEO position for a decade, long after many founders prefer to become CFOs. But Turner says his role is no longer in the lab.

“I’m very much involved with the intellectual property development and taking the technology and making a product. Saying, ‘What can you make out of spider silk? What uses of Protexia can you get?’ That’s my level. But not at the bench. I haven’t been at the bench now in a few years,” he says. “We’ve got lots of talented scientists, but we need to have someone to communicate that science to the investment community; communicate that science to our clients that need things done. So that’s my job: to translate what we do in the lab into solutions for people that have these problems — many of them life-threatening.”

After 10 years at the helm of a high-profile biotech company, he says the biggest challenge is converting science into technology.

“The thoughts and the concepts and the early experiments are science,” he says. “You know — is it possible? What does the mountain look like? Can we get to the top of the mountain? And there’s an enormous amount of time, effort and excitement around getting to the top of the mountain for the first time. That’s science, and it’s hard and it’s tough and it takes time, but it’s really exhilarating.

“The challenge is, once you’ve climbed the mountain, you have to go back and cut steps for everybody else. Build a road so everyone else can do it,” Turner says. “That’s been a huge challenge, doing that, at least for me and for our company. We’ve been brilliant at the science, and we’re working very diligently to turn the science into technology and products.”

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