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From Eureka to Useful

From Eureka to Useful

Developing an idea into a productive tool demands experience, foresight and a persistent champion



For decades, a combination of politics and peer pressure pushed Eve Ntseoane away from farming in her native South Africa. Although her parents both grew up on farms, they couldn’t stay there as adults. “Black people were moved to townships, because of remnants of the Land Native Act of 1913,” she explains. During school vacations, though, Ntseoane’s mother would take her and her brother to a farm where her uncle worked. “As a child I hated every first few days of the visit, but with chickens and puppies around, I would start enjoying it,” she remembers. “One morning my cousin and I climbed on the wagon carrying farmworkers to the corn fields. It was fascinating to help out, though we played most of the time.”

Ntseoane studied agriculture during her first three years of high school, but she says, “It came with a stigma that farming was for the not-so-clever.” Eventually, she succumbed to the peer pressure and her parents’ wishes, and became a teacher. She only taught for three years before moving to the corporate world, where she worked in communications.
Nonetheless, her past and changing social circumstances eventually lured Ntseoane back to the corn fields. Through the South African government’s Land Reform Strategy, she obtained a 539-hectare farm south of Johannesburg. The plot is situated “near a little town called Vanderbijlpark, which is popular for the Vaal Dam that supplies water to most South African provinces,” she says.

She began farming corn, working with traditional varieties. But in 2011, she says, “AfricaBio, an organization in South Africa, introduced me to Bt maize.” This corn gains insect resistance through a bacterial gene derived from Bacillus thuringiensis (Bt) that encodes a toxin. When Ntseoane planted these seeds on two hectares, they produced 7 tons of corn per hectare. That was more than double her previous harvest of conventional corn, which, at 2 to 3 tons, was kept at a low yield by stalk borers. The next year, the Bt corn again produced 7 tons per hectare for Ntseoane. Even in the following draught year, every hectare of the Bt corn yielded 5.5 tons. As Ntseoane says, “Had I not used the new technology, I wouldn’t have harvested much.”

Ntseoane’s story illustrates a fundamental truth in the field of biotechnology: getting the most out of a technical innovation requires vision, courage and commitment—plus the ability to take advantage of available resources.

Accelerating Innovation’s Application

“Innovation is the creative lifeblood of every country,” wrote The Honorable Birch Bayh in the forward to Michael A. Gollin’s Driving Innovation. Many would argue that the same could be said for the complex and promising field of biotechnology.

The question is: How can scientists turn “eureka moments” into useful products and services more quickly, more effectively? In Think Like a Freak, Steven D. Levitt and Stephen J. Dubner write: “The modern world demands that we all think a bit more productively, more creatively, more rationally; that we think from a different angle, with a different set of muscles, with a different set of expectations; that we think with neither fear nor favor, with neither blind optimism or sour skepticism.”

In addition to that new kind of thinking, would-be innovators must also learn from experience. As Levitt and Dubner point out, “The key to learning is feedback. It is nearly impossible to learn anything without it.” And when gathering feedback, it never hurts to turn to the best and the brightest, like Robert Langer, the David H. Koch Institute Professor at MIT and the author of over 1,000 patents, which have been licensed to more than 300 companies.

Langer explains that determining which innovations will lead to great products “depends a lot on your goal, because lots of things can be useful. I like it to be based on breakthrough science that could be really game-changing.” And when assessing the way forward—from the discovery in the lab to working toward commercialization—he warns against a common mistake: underestimating the task. “The major thing people do is underestimate how long it takes, how expensive it is and how many difficulties you’ll run into.” In order to combat these issues, he encourages biotech entrepreneurs to be prepared. “Surround yourself with great people,” he says, “and have more capital rather than less.”

Also, Langer firmly believes that any innovation with a good chance of successful commercialization requires a dedicated, unyielding campaigner. He watches many of his students take their own work down this road, and he says, “They are real champions of the ideas, and having a champion is very important.” In fact, Langer gains empowering feedback for himself by watching his students advocate for their own ideas. “Having students do things that make them happy is very important to me,” he says.

Without a champion, even an amazing idea can fall flat. Langer often cites the Apple corporation as an example. With Steve Jobs and Steve Wozniak, Apple excelled. When the board decided to replace Jobs with a “professional” CEO, the organization stumbled through five of them while its business faltered. But when Jobs took over again, it rose to become the world’s most valuable company. The lesson, Langer stresses, is that even the most astoundingly innovative ideas need the leadership of a champion to succeed.

Make the Right Measures

The excitement of a eureka moment in the lab, however, can get some scientists moving too fast. “If the ambition is to commercialize an idea,” says Anders Nordström, a senior advisor at Sweden’s Uppsala Innovation Centre, “many scientists focus too much on the technical science. They need to define what it means, the benefit, for the customer.” Which is not to say that potential buyers can always articulate their precise needs. “The market need might be there, but the customers might not know it yet,” he says.

Just because someone creates a technical solution of some sort, however, doesn’t mean that a market exists for it or can even be created. To determine this, says Nordström, you “need to define the market and who will be the customer.”

For instance, Nordström describes an experience that he had with Sweden’s Mentor4Research program, which was designed to help academic researchers commercialize their ideas. Olle Ericsson, then a researcher at Uppsala University, had a concept for a more efficient sample-preparation kit to be used in next generation sequencing (NGS). “Olle had no experience whatsoever in business, but was extremely eager to learn,” says Nordström, who was Ericsson’s Mentor4Research advisor. “Still, we understood that the NGS market was growing tremendously.” Nordström helped Ericsson structure the approach, make important contacts and build a company called Halo Genomics—which Agilent Technologies soon acquired—that eventually turned the innovation into a product called HaloPlex. As Nordström recalls, “We knew we were in a very hot market.”

For most innovators, however, the road ahead is rarely that clear. Typically, says Nordström, “You have to start with assumptions, and then try to validate them through a network of experts. From that, you can see if the assumptions sound reasonable or not.” Building a community of advisors helps scientists test these assumptions (see “Room to Grow,” page 26).

Start-up expert Steve Blank, architect of the U.S. National Institutes of Health’s I-Corps @NIH program, which teaches scientists and clinicians how to take their biotech ideas from lab bench to bedside, agrees. “We now understand that innovation in life sciences requires two parallel paths,” he says. “First, making the science better and useful. But second, we need to understand how to commercialize the science. We never had a formal process to test whether the science could turn into a commercially successful product. We do now.”

The I-Corps/Lean LaunchPad methodology, which Blank developed, allows for rapid testing and learning. “People hypothesize in the lab but rarely think of things like ‘Who do you think will pay for this?’” he explains. To find out, Blank makes scientists in the program go out and talk to at least 100 potential customers. “The principal investigators must get out and see the people,” he says. “For one thing, you might find that the market wants something that you have but that you thought no one would want.”

What are the most common mistakes made in turning an innovative idea into something commercial? “The biggest mistake is thinking that your faith is fact,” says Blank. The I-Corps @NIH addresses that problem when it makes an innovator take an idea to the real world. “You start with faith in your idea and then replace as much of that with fact as soon as possible,” he says.

Making the right assumptions about the market, however, solves nothing without the right science. Sean Ainsworth—now CEO of Retro-Sense Therapeutics in Ann Arbor, Michigan—learned that the hard way. “In a previous company,” he says, “we were working on a science that hadn’t been as fully validated as it needed to be.” And unfortunately, the company was already raising capital and lining up customers when obstacles in its research turned up. “We returned the money to the investors,” Ainsworth says, “and we took the science back to the lab.”

That experience made Ainsworth extra cautious with RetroSense—a company with a gene therapy that repairs vision in people with retinitis pigmentosa or age-related macular degeneration. “We ensured that it wasn’t just one individual who had developed and published something,” he says. “In this case, it had been done with people around the world.” With solid research in place, RetroSense has continued to thrive. In fact, it recently raised US$6 million to file an investigational new drug (IND) application with the U.S. Food and Drug Administration (FDA).

Spread the Capabilities
Indeed, developing an innovative product and finding a market for it is a challenging feat under the best of circumstances. But, not surprisingly, in some areas of the world it is far easier than in others. As the founder and CEO of Seeding Labs in Boston, Massachusetts, Nina Dudnik sees this disparity firsthand. Her organization works to bring advanced scientific instruments and training to developing countries. When asked if scientists in developing nations suffer more from a lack of the tools needed to innovate or from a need for the means to commercialize their innovations, Dudnik points out that the two are inextricable linked. “There are obstacles at every point along the way,” she says. “For the scientists we serve, the first barrier is usually related to a lack of access, not potential. Without access to the tools and infrastructure needed to make discoveries, the potential to innovate based on that research is severely diminished.” Which is exactly why Seeding Labs is committed to providing that access. For the moment, the dearth of equipment seems to be the dominant concern in developing countries. As Dudnik says, “From my observation, the difficulty in obtaining resources for research itself overshadows the focus on taking the discoveries out of the lab and into the market.”

Helping these nations become biotech innovators who can get their ideas or products to market also requires a highly-skilled workforce. “Being in an innovation hub like Boston,” Dudnik says, “it’s very clear that building human capability is absolutely critical to making the whole pipeline work.” (See “Biotechnology’s Crucial Question,” page 28.)
Many groups work together to build human capacity in the Nordic countries, which consistently rank high on the Scientific American Worldview Scorecard. On this year’s list, for example, Denmark, Finland and Sweden placed second, sixth and eighth, respectively.

Scandinavian Success
To power innovation, the Scandinavian countries collaborate on many levels. For example, Sweden’s nonprofit Uppsala BIO works to promote regional and national growth in the life sciences. Uppsala BIO’s CEO, Erik Forsberg, says, “We try to identify gaps in the system. What could make the life science sector grow more efficiently?” He answers part of his own question, saying, “It mostly comes down to innovation.”

Also, in terms of getting an innovation onto the market, projects must cross the so-called “Valley of Death”—that no man’s land where a concept is not far enough along to attract financial support but desperately needs it to move ahead. To increase the odds of crossing that divide, Uppsala BIO created the BIO-X program. “Here,” says Forsberg, “we can provide support through a network of competence—from users, such as clinicians, and from people with significant industrial experience. In addition, BIO-X can provide participants with a couple hundred thousand dollars for a couple years.” After that, says Forsberg, “You’ll need other funders.”

The “other funders” in Sweden, and most other countries, provide venture capital (VC). To gain a better understanding of how biotechnology VC works in Sweden, Scientific American Worldview talked with Eugen Steiner, CEO of Glionova Therapeutics in Stockholm and a venture partner for HealthCap, a family of VC funds investing in international life science research. In addition, Steiner has served as the CEO for several small start-ups.

Although he admits his bias as a partner in a VC firm, Steiner says, “There would be no biotech industry if there were no VCs.” Biased or not, few in the field would disagree with Steiner’s blunt assessment, because it takes money—often lots of it—to commercialize an innovation.

How VCs invest in biotechnology, though, depends on the overall economic environment, says Steiner. When the general economy is in decline, as in 2008, financing for biotech firms tends to dry up. This is a huge stumbling block for fledgling innovators. “However, even when no one wants to invest in biotech,” he says, “there are always some companies seen as the best ones.” Those businesses tend to be further along, and in troubled economic times, they’re the ones that get the VC. Such is the law of the VC jungle.

And while being backed by exceptional science greatly improves the odds of getting funding to turn an innovation into a product, investors need to be convinced. “Bring as much data to the table as possible,” Steiner says.

Impressive data, however, won’t always be enough to ensure that one particular eureka moment leads to a groundbreaking product that’s used around the globe, or anywhere, for that matter. Many other factors—from Ntseoane’s hard work on her farm in South Africa to Langer helping a student commercialize a research result—come into play in moving biotechnology forward. The best results emerge when great science is championed by an experienced team that lives and breathes persistence. Only then can biotechnology innovations change the world.

 

Illustration by Keith Negelly

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