Passion, perseverance, and a multidisciplinary team: That’s what the American Chemical Society’s 2017 Heroes of Chemistry awardees say are the key components of developing successful commercial products that benefit humanity.
Six teams of industrial chemical scientists, from Bristol-Myers Squibb, Corning, the Dow Chemical Company, DuPont Crop Protection, Genentech, and Merck & Co., received ACS’s most prestigious industry award during the ACS national meeting in Washington, D.C., in August.
Industrial chemical scientists represent more than half of ACS’s membership, and the Heroes of Chemistry Award is one way that the society celebrates their achievements.
The following are snapshots of the winning teams and their life-changing products.
Bristol-Myers Squibb: Daklinza (daclatasvir) and Sunvepra (asunaprevir)
“To be cured of a disease as significant as hepatitis is really remarkable,” says Percy Carter, head of discovery chemistry and molecular technologies at Bristol-Myers Squibb, who nominated the team for the award. “The team not only found drugs that had therapeutic utility, but they also really made some very fundamental observations and contributions to understanding the biology of the virus.”
Awardee Nicholas Meanwell says one of the most significant milestones during the project was the presentation of the Phase 2 clinical study of daclatasvir and asunaprevir against the hepatitis C virus (HCV). “This Phase 2 clinical study demonstrated for the first time that the combination of two small-molecule HCV inhibitors in the absence of immune stimulation was sufficient to cure a chronic HCV infection,” he says, adding that the clinical trial changed the focus of HCV drug development from add-on therapies to the then-standard interferon and ribavirin combination to direct-acting antiviral combinations, which have become the modern standard of care.
Meanwell credits the “teamwork, innovation, tenacity, intensity, and persistence” that each member of the team brought to the project, “all motivated by their desire to bring forward a new option for patients with HCV.”
Serendipity played a role in the development of Corning’s ClearCurve optical fiber, which can be bent with virtually no signal loss. Bendability is especially important, for example, when installing optical fibers that deliver high-speed internet in apartment buildings, where the fibers need to be routed through multiple units and around tight corners.
Awardee Dana Bookbinder recalls the momentous day when the team realized they were on to something. “We were in Ming-Jun Li’s lab, and we were just having fun. We were not thinking about bend performance at all.” Li wrapped the fiber they had developed around a cylindrical rod. To their surprise, there was no loss of optical signal. “We were like, ‘Huh, that’s weird,’ ” Bookbinder recalls. So they tried the same thing with a thinner rod—a pen. “Ming wrapped the fiber around the pen, and still there was no loss of optical signal. We were like, ‘What the heck is going on?’ ” Bookbinder says. “Then, ‘Aha!’ We couldn’t sleep. We’ve made many modifications since that time.”
“As industrial scientists, we want to make products that can change people’s everyday lives,” Li says. “We invented something that enables people to get more bandwidth at home, and it has enabled the growth of the whole industry. We’re really proud of that.” Team member Pushkar Tandon says the discovery of ClearCurve is just one more accomplishment in Corning’s rich history of life-changing innovations.
Dow: Avanse and Evoque polymers
“The chemistry that goes into a can of paint is amazing,” says awardee James Bohling of the Dow team, which developed Avanse acrylic resins and Evoque precomposite polymers. Dow says its Avanse and Evoque technologies helps make architectural paints more economical and environmentally friendly.
“In a typical paint, the opacifying pigment titanium dioxide is used inefficiently. When the TiO2 particles get close to each other, they scatter less light, and in something as thin as a paint film, these materials will naturally crowd each other,” Bohling says.
In developing Avanse and Evoque, the Dow team hoped to enable paint manufacturers to reduce the amount of titanium dioxide pigment required to produce paint. Not only is TiO2 expensive, but it is also energy intensive to produce. Bohling and his many colleagues developed a technology that allows binder polymer particles to controllably self-assemble with the TiO2. The polymer surrounds the individual TiO2 particles, thereby improving the spacing of the TiO2 and forming a more ordered film.
This means that less TiO2 is needed for the production of paint and that “when you space out the TiO2 particles, you get better barrier properties. Because the pigment is completely covered with polymer, it prevents the formation of channels where stains can penetrate into the film,” Bohling says. “In my house, when I look at the walls that were painted with this technology, I see nicely painted walls. I smile to myself when I spill something on those walls because I can wipe it off.”
Bohling points out that the work is based on Dow’s acrylic emulsion technology, which earned an ACS National Historic Chemical Landmark in 2008.
DuPont Crop Protection: Zorvec (oxathiapiprolin)
DuPont’s Zorvec (oxathiapiprolin) is a new class of fungicides that treats plant diseases caused by oomycete pathogens. The compound, which inhibits the oxysterol-binding protein in fungi, can be used to control diseases such as late blight, downy mildew, and crown rot—which affect potatoes, grapes, and vegetables—without harming other crops and animals.
“Talk about a compound hitting that sweet spot,” says awardee Lisa Hoffman. “Zorvec really hit that sweet spot of everything that it needed to do to be successful. It stood out from the over 1,700 analogues that were tested during the discovery process.” Through this investigation, the team was able to improve the activity of their initial hit 10,000 fold. “We had gone from a compound barely detectable in our early screens to the most effective oomycete fungicide ever developed,” says awardee Bob Pasteris. “It is different from other disease control products in that it can stop an active lesion from expanding; no other oomycete control compound can do this.”
As is often the case in research, the journey to commercial project was filled with uncertainties. Pasteris notes that “the project was almost canceled three times after hitting an activity plateau that the team struggled to break through.”
Even after the team discovered their lead compound candidate, they needed to figure out how it worked on a molecular level. “It was really a black box,” awardee James Sweigard says. But “in a very short time, we went from essentially knowing nothing to being 100% sure that we had the right answer. That was pretty neat,” Sweigard says.
“We knew from the beginning that Zorvec had to be different,” Hoffman says. “It had to be able to differentiate itself in the marketplace.” Ultimately, she says the team was able to “give growers the thing they didn’t even know they wanted.”
Genentech: Erivedge (vismodegib)
When lesions began showing up on Shelley Baker’s face 12 years ago, doctors initially told her she had the scaly skin condition called psoriasis. Eventually, doctors diagnosed Baker with a common form of skin cancer called basal cell carcinoma. She had two large spots on her face, and because of their location, doctors said it would be difficult to surgically remove them.
In 2013, Baker put her faith in a newly approved treatment for advanced basal cell carcinoma from Genentech called Erivedge (vismodegib). She took one pill a day and “within three weeks, Erivedge started closing up those spots on my face,” Baker says. “I was always very self-conscious of what my face looked like, and Erivedge made me realize that I didn’t have to spend the rest of my life living the way that I was.” Baker has been off the medication for the past two years and is in remission.
Awardee Jim Marsters says the collaboration to develop Erivedge began in 2003, and the drug was approved by the U.S. Food & Drug Administration in 2012. “We set out to design a molecule that targeted the Smoothened receptor in the hedgehog signaling pathway. Our expectation was that treating patients with this agent would cause a reduction in their basal cell lesions and we’d see both a decrease in the lesions as well as generation of normal skin.” The team’s hunch proved right.
“It’s gratifying to hear patients’ success stories,” Marsters says. “Every chemist that’s worked on an active molecule like this shares the sentiment that you’ve been given this opportunity to work in a field where you have a chance to help patients, and that’s a really great feeling.”
Merck & Co.: Zepatier (elbasvir and grazoprevir)
Denise Butler learned in graduate school in 1996 that she had been infected with hepatitis C. But because she felt okay, she went for years without treatment, which at the time would have been interferon and ribavirin.
After she had her second child, she began to feel severe fatigue, brain fog, and other symptoms related to her disease. Her doctor enrolled her in a clinical trial for Merck’s Zepatier, a drug for treating hepatitis C. After two weeks, there was no detectable virus in her blood. “I just started bawling,” Butler says of hearing the news from her doctor. “The disease almost becomes part of you, and when somebody tells you that you don’t have it anymore, you’re like, ‘Are you kidding me? I’m cured?’ ”
K. Rajender Reddy, medical director of Penn Medicine’s Liver Transplant Program and a consultant for Merck, says that Zepatier has the added benefit of treating hepatitis C in people with kidney transplants. “Previously, hepatitis C-positive kidneys were only given to hepatitis C-infected individuals,” Reddy says. With Zepatier, patients who receive a hepatitis C-infected kidney, which has a much shorter waiting list than a noninfected kidney, have an option for treating the hepatitis C. The once-standard therapies, interferon and ribavirin, cannot be given to people with a transplant because of the risk of organ rejection.
Zepatier is a combination of two compounds, elbasvir and grazoprevir. Both target enzymes required for viral replication. “One key feature of these molecules is their extraordinary potency against a wide variety of mutant enzymes because HCV is a very diverse disease with many different potential mutant proteins,” says awardee John McCauley.
He adds that he’s proud to be an industrial scientist: “I get to work on interesting chemistry, be very creative, and work with a great team of people that have a wide variety of expertise. To be able to do all of that and have a chance to affect people’s health and to affect their lives, that’s the combination that makes me love what I do.”
Know chemistry heroes that ACS missed? Nominations for 2018 open in late November. Visit www.acs.org/heroes for more information.
Makonen Belema, Min Gao, Andrew Good, Lawrence Hamann, Fiona McPhee, Nicholas Meanwell, Van Nguyen, Paul Scola, Lawrence Snyder, Li-Qiang Sun, and Alan Wang.
Dana Bookbinder, Ming-Jun Li, and Pushkar Tandon.
The Dow Chemical Company
Linda Adamson, James Bardman, Kebede Beshah, Marie Bleuzen, James Bohling, Ward Brown, Stan Brownell, Michael Clark, Beth Cooper, Steven Edwards, David Fa- sano, Catherine Finegan, John Hook, Melinda Keefe, Alvin Maurice, Ozzie Pressley, William Rohrbach, and Wei Zhang.
DuPont Crop Protection
John Andreassi, Mary Ann Hanagan, Lisa Hoffman, Robert Pasteris, and James Sweigard.
Remy Angelaud, Georgette Castanedo, Janet Gunzner-Toste, Mike Koehler, Jim Marst- ers, Kirk Robarge, Scott Savage, Dan Sutherlin, Vickie Tsui, and Shumei Wang.
Merck & Co.
Craig Coburn, Steven Harper, Daria Hazuda, Kate Holloway, Bin Hu, Nigel Liverton, John McCauley, Craig McKelvey, Mark McLaughlin, Peter Meinke, Michael Rudd, Vincenzo Summa, Feng Xu, Bin Zhong, and Ping Zhuang.