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Cover Story

November 19, 2007
Volume 85, Number 47
pp. 15-20

Suits and Lab Coats

Industry draws on academic know-how to help develop specialty chemicals and other new materials

Marc S. Reisch

Photo Gallery

Chemical companies, such as BASF, are forging new relationships with academic partners to further research with technological and commercial promise. Some of the research support that BASF will be funneling into Harvard University in the coming years could help move some fundamental work in those more practical directions. Examples from the lab of David A. Weitz, a professor of physics and applied physics, are illustrated in the images here. In other cases, universities are aiding commercialization of fundamental research and helping along start-up firms such as Liquidia Technologies, whose nanoparticle replication technology is also shown here.

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Universities obtain funding from a variety of sources to support scientific research. Government is the largest benefactor, but endowments, foundation grants, gifts from wealthy individuals, and alumni donations all can influence research projects. And then there is the matter of support from private industry.

Harvard University/Liang-Yin Chu/Weitz Lab Group
Captivating research Multiple emulsions formed with microfluidic devices can be used to create drops within drops for ingredient encapsulation and controlled release.

Chemical and life sciences companies have long had an interest in university research that could lead, for instance, to electronic chemicals that make computers run faster or reagents that quickly diagnose disease. Support from industry can be a welcome supplement to a school's research budget; it can also raise fears of more insidious consequences, such as inappropriate enrichment of a corporate donor or faculty member or an inclination to influence government policies that are more favorable to the interests of a corporate sponsor.

Industry contributes a growing piece of the overall research-funding pie. According to a recent survey of universities conducted by the National Science Foundation, corporations supported academic science and engineering research to the tune of $2.4 billion in 2006. Industry expenditures rose for the second year following a three-year decline from 2002 to 2004.

Still, industry support accounted for only 5% of university R&D budgets in 2006, below the most recent peak of 7% in 2001. By contrast, federal, state, and local government funds accounted for about 69% of total science research spending in 2006.

The renewed growth in industry support for academic research comes on the heels of a tumultuous period in which businesses and universities tangled over the ownership and value of intellectual property developed with industry funds (C&EN, March 19, page 25). Some chemical firms have complained that university licensing officials focus too heavily on generating licensing fees. University representatives have grumbled that corporations undervalue academic contributions to the development of products.

Against this background, the world's two largest chemical firms, Dow Chemical and BASF, have established new high-profile research programs at universities that raise questions about the nature of an industrial enterprise's involvement in academic pursuits.

Keystone Nano
Hot Flashes Suspended in the vials are fluorescent imaging agents imbedded in nanocomposite materials.

Last month, Dow said it would make a gift of $10 million over five years to launch the Sustainable Products & Solutions Program within the Haas School of Business at the University of California, Berkeley. Dow and UC Berkeley say the program will operate in partnership with the school's College of Chemistry. It will also tap faculty across the campus to fund basic research in chemistry, environmental policy, and the interface between the two disciplines.

As soon as it was announced, however, the program raised red flags over the degree of influence Dow could exercise over projects chosen. One critic was Michael P. Wilson, a research scientist at the university's Center for Occupational & Environmental Health in the School of Public Health. When C&EN initially spoke with Wilson, he was concerned that unless the program had a clear organizational structure, Dow might influence the scientific questions being posed by the university's researchers. While not opposed to university-industry partnerships to address technical challenges, such as those in green chemistry, he asked if such partnerships might compromise researchers' independence and commitment to the public interest.

Wilson, who also serves on the California Environmental Protection Agency's green chemistry advisory panel, added, "Those of us working in the technical and policy aspects of green chemistry at Berkeley are unlikely to become involved in this program until the lines of authority are delineated."

Following discussions with Haas faculty and Tony Kingsbury, a Dow executive on temporary assignment at UC Berkeley, Wilson and his colleagues have tempered their criticism. Wilson says that the recasting of Kingsbury's title from executive director of the sustainable products program to executive in residence indicates that Dow does not intend to influence public policy; rather, Dow wants to participate in developing technical and policy changes within the company to advance its own sustainability goals.

Wilson expects that he and his colleagues at the occupational and environmental health center will now explore how best to engage with the Dow-funded program, particularly if it can address some of the technical problems California will confront as it forms a new statewide chemical management policy.

"Policy issues are a minor part of the program Dow envisions at Berkeley," Kingsbury tells C&EN. He hopes to fund research into ways to deal with global water, energy, and housing issues. He expects that the program will encompass everything from research into new chemical syntheses to funding for business school students who are studying environmental sustainability.

Kingsbury also points out that Dow's gift comes with no strings attached. Dow will play no role in deciding which projects the center will fund; university faculty will make those decisions. All research results will be the property of the university. Kingsbury notes that he will have an observer role on the program steering panel.

He points out also that Dow hopes to be just one of many corporate supporters of the program. He plans to recruit companies in sectors such as retail, consumer products, mining, and semiconductors to contribute to the program.

BASF's agreement is with Harvard University, with which it will set up the BASF Advanced Research Initiative to support cooperative research intended to yield new products. The $20 million, five-year program will initially support 10 postdoctoral students and other Harvard researchers, primarily in the School of Engineering & Applied Sciences.

Although it involves two high-profile names, the announcement of this program set off no obvious alarms, perhaps because it has many of the hallmarks of traditional university-industry research initiatives and involves no debate over public policy. Its focus is on research leading to new products.

David Weitz, a professor of physics and applied physics at Harvard who will have a hand in directing the initiative, says Harvard has many cooperative agreements in place with industry. BASF will decide on the projects it will fund and has pledged to work with Harvard on applying fundamental research to new product development.

Target research areas include polymer systems for improved delivery of active ingredient molecules in pharmaceuticals, agrochemicals, cosmetics, and other areas. Another research program is an investigation of biofilm formation with the goal of discovering new ways to inhibit microbial growth. A third area, the details of which are still being worked out, is exploring the use of carbon dioxide as a raw material.

Jens Rieger, polymer research director for BASF, notes that his company has 1,400 cooperative agreements in place with universities and industrial research partners worldwide. Rieger, who will direct the work with Harvard for the German company, says there is a strong interdisciplinary component to the initiative. "It will give students a good feel of what industrial research is all about," he says.

That's not necessarily a bad thing, according to Venkatesh Narayanamurti, dean of Harvard's engineering school and a former researcher at Bell Laboratories. "It is important for engineering schools to be connected to the real world," Narayanamurti says. "Students need to know how to work with industry." Information should flow in both directions between the school and industry, he adds.

Narayanamurti sees industry funding as a stopgap to make up for shortfalls in support from government sources. He says a comfortable level of funding from industry would be 10-20% of the engineering school's research budget, which was $38 million in 2006. Excluding the BASF program, about 5% of the engineering school's budget now comes from industry and that figure will only go up. In fact, he points out, government agencies often encourage universities to work with industry as a way to commercialize technology for the greater public good.

Though many Harvard scientists have close ties to industrial companies, including advisory positions and commercial interests, Narayanamurti says a combination of faculty integrity and oversight committees keeps universities centered on their primary mission of educating students.

Indeed, a 2005 survey of 1,800 U.S. life scientists conducted by agricultural and applied economic professors Brad Barham and Jeremy Foltz at the University of Wisconsin, Madison, found that commercial interests are not turning universities from their mission of serving the public good. More than 50% of scientists at the nation's top 125 universities for biological research had no commercial ties, while 90% held only one or no patents, and just 8% received patent revenues. "The findings," they wrote, "should reassure those concerned with preserving the country's long-standing model of basic publicly supported and openly shared research."

View Enlarged Image Keystone Nano
Dressed to kill NanoJackets, developed at Penn State, can carry cancer-killing drugs.

German chemical firms have historically had very close ties to academia, points out Michael Droescher, head of chemicals innovation management at Evonik Industries, the German company formerly known as Degussa. Government money plays a sizable role in support of academic research in Germany, he says, but industry has always been a supporter.

Evonik now spends about $15 million, or 3% of its annual R&D budget, on cooperative agreements with universities, mostly in Germany. The firm does not conduct basic research, Droescher says, but uses support of university research as a window onto fundamental scientific advances. In some cases, university researchers work in Evonik's labs. Such cooperation has helped Evonik develop, for instance, metal oxide nanoparticles used to polish silicon wafers and to modify polymer surfaces.

Another firm benefiting from ties with university researchers is Sigma-Aldrich's SAFC Hitech business. Earlier this year, Sigma-Aldrich acquired Epichem, a British maker of high-purity chemicals for electronics and photovoltaic markets. Stephen Robinson, vice president of global sales for the former Epichem, says the business could not have succeeded in the fast-changing electronic chemicals business without access to "leading-edge, front-end technology" from university researchers.

By outsourcing R&D to universities, the small company gained access to advanced chemistry at a modest price. "It costs less to help professors and postdoctoral students than to take on the equivalent science research in-house," Robinson says.

Anthony C. Jones joined Epichem when he was a postdoctoral researcher at the University of Liverpool, England. Now a consultant and part-time chemistry professor at the university, Jones worked for 12 years at Epichem, where, as he says, he "bridged the gap between customer needs and university researchers" using a network of schools including Imperial College London and the University of Bath.

The company and its university partners had a mutually beneficial relationship on the cutting edge of technology, Jones recalls. As an academician, he sees alliances with industrial partners as a way to help students learn and get jobs.

Joseph M. DeSimone, professor of chemistry and chemical engineering at the University of North Carolina, Chapel Hill, also sees university-industrial research as an effective way to get scientific advances to the public. While potential conflicts of interest abound, "you have to shine a light on such conflicts and manage them appropriately without exploiting one party or the other," he says.

When DeSimone arrived at UNC 17 years ago, he found a $25,000 check from DuPont waiting for him. Although he had chosen a faculty position at UNC, he had interviewed for a research job at DuPont "and they had gotten to know me pretty well." The check, DeSimone says, came with a note encouraging him to use it for whatever research he chose to conduct.

In 1996, DuPont licensed supercritical CO2 polymerization technology developed in DeSimone's lab. The technology produces Teflon and other fluoropolymers without the use of the processing aid perfluorooctanoic acid, a bioaccumulating chemical that is suspected of causing health problems, including cancer.

One of DeSimone's graduate students, Jason Rolland, cofounded a firm called Liquidia Technologies based on dissertation work for a Ph.D. completed at UNC. The relationship between Liquidia, of which DeSimone is also a cofounder, and UNC remains very close, Rolland says. The firm is developing replication technology that Rolland worked out in his research using imprint lithography methods to make fluoropolymer-based molds and templates to fabricate polymeric organic nanoparticles and patterned films. Potential applications range from drug-carrying particles to fuel-cell membranes.

When the National Cancer Institute made UNC one of seven centers of cancer nanotechnology research in 2005, the imprint lithography method was at the heart of the initiative. DeSimone, one of the principal investigators in the $25 million program, will be using the replication technology to produce particles designed to carry therapeutic, detection, and imaging agents into the body.

Liquidia supplies the nanoparticle templates to the cancer research effort, allowing students to devote more of their time to research and less to the mechanics of producing templates. "We're joined at the hip," says Luke Roush, Liquidia's vice president of business development.

Universities have an obligation to commercialize research for the public good, says Jeff Davidson, chief executive officer of Keystone Nano. Two-year-old Keystone has lab space in a Pennsylvania State University business incubator and is "getting on" with cash from a state-funded group, the water treatment firm Nalco, and a mix of angel investors, Davidson says. He sees university efforts to foster start-ups based on faculty research as a way to make sure they transfer "robust and scalable" technology to industry.

Liquidia
Boomerangs Templates for precisely controlled drug-carrying nanoparticles were developed as part of a University of North Carolina grad student's doctoral dissertation.

Keystone is developing composite particles, with diameters ranging from 5 to 50 nm and based on calcium and phosphate. The firm calls them NanoJackets. "When we started the company, our lead employee started working in the Penn State labs of James Adair," Davidson recalls. The NanoJacket particles are based on the work of Adair, director of Penn State's Particulate Materials Center. Adair and Mark Kester, a Penn State professor of pharmacology, hold equity positions in the company and serve as chief science and medical officers, respectively.

Keystone is developing the NanoJackets to encapsulate drugs and fluorescent molecules. "They are tiny FedEx trucks," Davidson says, with applications in cancer treatment and diagnostic imaging. A venture with Nalco is developing the NanoJackets to hold water treatment and other specialty chemicals that the partners hope will improve time release and stability of ingredients and also help to target ingredients at the molecular level.

University researchers regularly come up with any number of unusual specialty chemicals, composite materials, and technologies. Left alone as academic curiosities, these scientific advances might be filed away to gather dust instead of dollars. As Harvard's Narayanamurti says, "We must be as innovative in funding and translating research as we are in conducting it."

He and his academic colleagues realize that conflicts with industrial partners will be inevitable. However, by "staying connected to the real world," as Narayanamurti puts it, and cultivating healthy relationships, academics and students not only have an opportunity to learn but also to come up with innovations that make a world of difference.

Chemical companies, such as BASF, are forging new relationships with academic partners to further research with technological and commercial promise. Some of the research support that BASF will be funneling into Harvard University in the coming years could help move some fundamental work in those more practical directions. Examples from the lab of David A. Weitz, a professor of physics and applied physics, are illustrated in the images here. In other cases, universities are aiding commercialization of fundamental research and helping along start-up firms such as Liquidia Technologies, whose nanoparticle replication technology is also shown here.

View Enlarged Image David Weitz
Captivating clusters Scanning electron microscope image of a colloidosome that can encapsulate many different materials. Permeability of the shell of solid particles can be controlled for ingredient delivery by adjusting the size of the interstices between spherical particles on the surface. The diameter of each sphere is less then 1 µm.
View Enlarged Image David Weitz
Microgel Master Scanning electron microscope images of colloidosomes formed with the help of thermoresponsive microgel cores as templates. When the cores are cooled, they shrink, forcing the colloidal particles to buckle and jam together into a robust coating.
View Enlarged Image David Weitz
Up close and personal Providing a somewhat planetary appearance, this confocal microscope image reveals the surface of an emulsion drop covered with colloidal particles. This is a precursor to the formation of a colloidosome.
View Enlarged Image David Weitz
Drop Engineering When flowed through a microfluidic device like the branched one shown here, large droplets (top) break successively into ever smaller and more uniform droplets. The droplets' monodispersity shows up clearly in the image on the right.
View Enlarged Image David Weitz
Crystallized Binary-alloy colloidal crystal consisting of particles of two different sizes, crystallized into an AB6 structure, as viewed by confocal microscopy (left and center) and in a computer rendering (right).
View Enlarged Image Liquidia
Ah, Nuts! Liquidia can control nanoparticle size, shape, and chemical composition to enable design of, for instance, hex-nut-shaped inhalable therapeutic agents. The technology making this possible was developed at the University of North Carolina, Chapel Hill.
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