"Let
me show you something," Hsueh-Chia Chang says, like a kid with
a new toy. With that, he hunches over his laptop, taps the keys
a few times and produces the image of a tornado. A funnel cloud
forms at the top of the screen swirling debris ever faster, drawing
it in and concentrating it down. The 10-second video brings a
smile to the face of the Notre Dame chemical engineering professor
nearly every time he views it because he knows how truly amazing
it is. That, and how valuable it might be.
What makes the twister astounding is its size. The funnel cloud
has the diameter of .0008 of a meter, and each piece of debris
floating inside is half as thick as a human hair. What makes it
valuable is its potential use. Chang, the director of Notre Dame's
Center for Microfluidics and Medical Diagnostics, and his colleagues
have developed and patented the means to quickly mix, pump and
separate incredibly minute amounts of liquid.
That ability overcomes a major technical roadblock in the development
of a whole new generation of advanced diagnostic and sensing devices,
ones similar to the new glucose meters for diabetics. The new
meters have the potential to replace many costly and time-consuming
lab tests.
Among other things, Chang's inventions, which employ electric
fields to move fluid through a silicon chip, could be used to
separate blood cells from plasma or concentrate bacteria or viruses.
Best of all, they can accomplish in seconds what current
technology takes hours to do. Precisely how valuable the inventions
may be remains to be seen, but representatives of a major pharmaceutical
firm and an agricultural chemical company have demonstrated interest
in the technology as well as a local Granger, Indiana, company
specializing in water quality testing.
Chang's micropump technology is just one of a spate of inventions
that Notre Dame research labs have generated recently. Within
the last several years, there has been a growing sensitivity at
the University to what is known as "technology transfer," marked
by more faculty members applying for patents and more being issued.
Some are even beginning to pay off, albeit modestly.
None, however, has come close to generating the royalties of
Notre Dame's first and most famous effort in technology transfer,
Father Julius Nieuwland's groundbreaking work with polymerized-2-chloro-1,3-butadiene,
which led to two patents and the development of the first synthetic
rubber, Neoprene, in 1931 by the E.I. DuPont de Nemours chemical
company. That particular bit of "intellectual property" was very
good fortune for the University -- some $2 million when the royalty
payments ceased in 1948.
Now 53 active patents are on the books for Notre Dame faculty
inventions, ranging from technology to make freeze-resistant plants
to potential anticancer drugs. All of these have been entered
since 1972, and the bulk, 35, since 1980 when the Bayh-Dole Act
came into effect. The act mandated that institutions pursue the
commercialization of technologies developed with federal funds.
Prior to 1980, the U.S. government owned any invention created
with federal money. But few made it to the marketplace because
of bureaucratic red tape and lack of incentives, explains Richard
Jensen, Notre Dame professor of economics and econometrics. Nationwide,
patents from university research were rare, and so the fact that
Notre Dame had few before 1980 is not unusual. In an effort to
spur development, the federal legislation gave back patent rights
to universities and other institutions, requiring them to make
"diligent efforts" to commercialize the inventions and give the
faculty inventor a share of any subsequent income.
To a fair extent, the Bayh-Dole Act has had its intended effect,
says Jensen, who has written extensively on university technology
transfer. As evidence, he cites a survey of the Association of
University Technology Managers that shows a 176 percent increase
in patents and 131 percent increase in licenses from 1991 to 1998
among the 86 responding schools. Further, the economist notes
that university technology transfer has generated more than 2,000
new firms in the last decade and is estimated to support 180,000
jobs each year. Not only that, some of the most famous recent
inventions have come from university labs, including the anticancer
drug Taxol, the Google search engine, the MRI diagnostic machine
and the famous Cohen-Boyer process for splicing genes, not to
mention Gatorade.
Currently nine licenses have been granted to companies to use
Notre Dame technology, and options are out on another four. Additionally,
there are seven pending license agreements, four of which are
with Notre Dame faculty "start up" companies. License revenue
has taken an amazing jump at the University, from a paltry $250
in 1999 when the Office of Technology Transfer was established
to $624,250 since then. All of this comes from a few licensed
patents issued from 1997 on.
To put that in some perspective, the 10-campus University of
California system, which ranks number one in technology transfer,
earned $261 million in the year 2000 and had 324 patents. "Of
the 220 member institutions in the Association of University Technology
Management, there are about 10 'big dogs' in university technology
transfer, such as the University of California system, Stanford,
MIT, Johns Hopkins, Wisconsin and the like," says Mike Edwards,
who heads up Notre Dame's two-person tech transfer office. "Most
are more at Notre Dame's level. Very few universities actually
make money on technology transfer. Most lose money. The majority
of offices are only two- or three-person offices, which provide
service to faculty, market some intellectual property and generally
don't recover enough to pay salaries."
* * *
With earnings of more than $300,000, a modest sum by national
standards, the most valuable Notre Dame invention in recent years
has the oddly intriguing name of "piggyBac." The invention emanates
from a virus that can turn a cotton boll worm into a puddle of
goo within hours of infection. As amazing as that feat may be,
however, it has nothing to do with the patent.
PiggyBac is a little snippet of renegade DNA that ND Biology
Professor Malcolm Fraser found while studying how baculoviruses
mutate. The chunk of DNA, called a transposon, has the ability
to copy and insert itself into a new position within the same
or a different chromosome. Using the transposon, the virus mutates
by picking up bits of transposon DNA from the infected caterpillar.
The transposon's commercial value became apparent after Fraser
demonstrated its ability to move not only itself but also any
genes that are placed inside it from one DNA molecule to another
in cell culture systems. Subsequently a colleague at the U.S.
Department of Agriculture showed this transposon could move genes
into the chromosomes of Mediterranean fruit fly tissue. "That
turned out to be a significant observation because it proved that
it could move genes across orders of insects," Fraser says.
Up until then researchers thought the transposon worked only
with caterpillars. Since then, piggyBac, whimsically named by
Fraser to reflect its transport ability and origin in the baculovirus,
has been shown to work with a wide variety of insect species as
well as vertebrate cells. It has become the most widely used tool
for manipulating genes in insects, especially Drosophila, the
fruit fly.
The pharmaceutical industry, in particular, has found piggyBac
useful. "All these companies are looking for gene targets for
their new drugs, and they need a nice system to screen those targets
and their functions," Fraser explains. "Ethically, of course,
you can't manipulate genes in the human genome, but Drosophila
is a nice system that gives insight into a lot of fundamental
processes that carry over to humans, and piggyBac, it so happens,
offers the best way to manipulate Drosophila genes."
Meanwhile, using piggyBac, Fraser and his collaborators have
produced the first transgenically engineered silkworm, inserting
a fluorescent green protein into its skin. The achievement is
significant because it demonstrates the feasibility of harnessing
the silkworm to produce a useful protein product such as human
growth hormone. Fraser explains, "Since silk is a protein product,
if you can genetically modify a silkworm to produce another protein
of importance, you will get a large amount of that product along
with silk.
Pharmaceutical companies are keenly interested in transgenically
producing proteins of medicinal value. Most schemes, however,
involve more complicated systems such as goats and their milk.
The simplicity of the silkworm offers a distinct advantage, Fraser
says. "You can transgenically engineer a silkworm much easier
than a mouse or goat system," he points out. "So in a matter of
months you can get it to produce the protein of interest and in
a few more months you can amplify that to production levels. In
contrast, it's much harder to engineer a goat, and to amplify
that into a herd could take years."
* * *
Some of the spike in patent activity at Notre Dame is directly
attributable to the College of Engineering's Center for Microfluidics
and Diagnostics. The center was established with seed money from
the Graduate School and the College of Engineering specifically
to develop fundamental research that also may have commercial
potential.
And the seeds have borne fruit. Another recent Microfluidics
Center invention currently in license negotiations is for something
technically known as "binary solitary cross field electrophoresis,"
developed by the center's associate director, David Leighton.
Mercifully, in the patenting process, the professor of chemical
engineering decided to rename the technology simply "Zeta Filtration."
The Zeta filter is a clever device that uses an AC electric field
to quickly separate out "biological nanoparticles," things like
bacteria, viruses or cellular components, an ability important
to the development of medical analytic and diagnostic devices.
While Chang and his colleagues have concentrated their work
on the microplumbing needed for biological sensing devices, Professor
of Chemical Engineering Al Miller's lab has generated a patented
electrochemical technique to fabricate a minuscule grid that can
be configured in a number of useful ways, as an extremely sensitive
detector of E. coli bacteria, for instance, or as an
infrared energy detector.
Essentially, Miller's team discovered how to make a tray of
tiny containers and place them on a silicon chip. The closely
packed wells are about 15 to 30 atoms in diameter. When filled
with cadmium sulfide crystals, which are sensitive to infrared
energy, the chip might be used to detect minute amounts of heat.
To make an E. coli detector, the wells are filled with
gold, then the surrounding structure is dissolved away to form
gold "nanonwires." Then antigen molecules sensitive to E.
coli antibody are added to the tip of the gold wire. If E.
coli bacteria are present, the electrical resistance of the
system changes, Miller explains. A startup company owned by one
of Miller's former Ph.D. students who helped to develop the technology
is negotiating with the University to license it.
* * *
Unlike most other research institutions, which established offices
of technology transfer in the 1980s, the University didn't open
its own office to coordinate the management of intellectual property
until 1999.
"In the old days," says the chemical engineer Leighton, "what
used to happen is that a faculty member would develop something
and then send a patent disclosure to the University's patent committee.
They'd look it over, send it to a company in Arizona who would
evaluate it. Then they'd look it over, send you a coffee-mug souvenir
and decide whether to option it. If they optioned it for six months,
they'd send you a check for $1,000. After that they'd say there's
no market and that would be that. Or they might refer it back
to the University, which would release it to the inventor who
would say, 'Now what?' So nothing happened."
In years gone by, Al Miller says, faculty were sometimes discouraged
by a perceived lack of support for the patent process and often
didn't pursue ideas because of that. "When I joined the faculty
in the late '60s, the attitude toward intellectual property was
that it was a 'trade school' kind of thing. It was beneath our
intellectual dignity, because at a university, you see, we publish
scholarly papers or monographs."
With the establishment of the Office of Technology Transfer
the University affirmed with a tangible symbol that monographs
and patents are not mutually exclusive. For the first time a centralized
office was given the mandate of managing the University's intellectual
property from the patenting process through overseeing the licensing
of technology to commercial ventures.
Also signaling more openness, when Jeffrey Kantor became dean
of the graduate school in 2001 one of the first things he did
was to meet personally with as many faculty researchers as possible
to make them aware of the University's patent policy and encourage
them to file disclosure forms when they discover anything of potential
commercial value. In fact, since then there has been such a steady
increase in the number of disclosures filed -- with 43 last year
alone -- that tough decisions must be made on which ideas to follow
through on since the patent process is expensive. It runs around
$25,000 for a domestic patent and twice that to protect the rights
internationally.
Another tangible sign this May was when the University hosted
the inaugural symposium of the Indiana Innovation Network, a new
consortium bringing together business leaders and the academic
research community to foster collaboration in the development
of new technologies. In announcing the symposium, Kantor noted,
"Research being conducted here has much potential for stimulating
economic development in Indiana. Notre Dame is both committed
and enthusiastic about ensuring that all steps are taken to get
important discoveries into the marketplace where they can find
value."
The University and the city of South Bend also are working to
develop a "technology park" in the area of the old Notre Dame
Woods, south of campus. Similar to such developments at other
universities, the technology park would offer research and development
space to commercial interests collaborating with Notre Dame scientists
and engineers.
One more change in the culture has been a new openness to faculty
involvement in startup companies based on technology they have
developed. For instance, Chang and his colleagues Mark McCready
and Dave Leighton along with a recent MBA/engineering graduate,
Andy Downard '02, formed a company called Microfluidics Applications
to commercialize their technology. The fledgling company, which
at the moment is little more than a business plan, has been aided
by Notre Dame's Gigot Center for Entrepreneurship through its
IrishAngels program, which matches Notre Dame alumni entrepreneurs
with fledgling businesses to help them reach their goals.
Another faculty startup company is Emu Solutions, formed by
Professor of Computer Science Peter Kogge and Associate Professor
of Computer Science Jay Brockman to commercialize technologies
that mix memory and logic capabilities on the same silicone chip.
Jensen, whose academic specialty is the economics of University
technology transfer, gives high marks to Notre Dame for an incentive
system that encourages faculty to file disclosures. "Our survey
of 65 leading universities showed that, on average, leading universities
give 40 percent of the income from patent licenses to the inventors,"
he says. "Notre Dame provides 50 percent of the first $100,000
generated by the patent to the inventor in income, 25 percent
of the next $100,000 to $1 million and another 25 percent in funding
for research support, and 25 percent of anything over $1 million
in income.
"So Notre Dame is more generous than average for inventions
that are successful but less generous for any that are enormous
successes." The tactic is a good one, Jensen says "because giant
successes are quite rare, [and] providing a greater incentive
for modestly successful inventions seems like a wise policy for
inducing disclosures." Moreover, he notes, "providing part of
the payment to inventors in the form of funds for research support
is very important and is not that widespread in practice. In fact,
our survey found that faculty considered obtaining sponsored research
funds as the most important objective of technology, even over
cash payments."
Of course that shouldn't come as a surprise, since faculty are
primarily interested in publishing cutting-edge scientific papers
and training students. Anything that helps them do that is welcome.
At Notre Dame there are numerous beneficial examples of corporate
collaboration and support involving University researchers. For
many years, for instance, Professor of Chemistry Marvin Miller
has had a relationship with the Eli Lilly pharmaceutical firm
that has resulted in eight patents. Those include compounds that
combat resistant strains of staphylococcus and inhibit
tuberculosis.
One notable example of beneficial ND research cooperation with
commercial interests has been the collaboration between Norbert
Wiech '60 and several Notre Dame chemists and biochemists, notably
professors Paul Helquist and Olaf Wiest.
Wiech, who owns a small pharmaceutical firm in Baltimore specializing
in treatments for rare diseases, several years ago enlisted the
aid of Helquist and Wiest to help him further his development
of a novel compound called CG1521. That compound inhibits the
enzyme HDAC, which can sometimes cause DNA strands to coil too
tightly, thus inhibiting their ability to transmit the genetic
code and produce the proper proteins. Such genetic code errors
are implicated in genetic-based diseases as well as cancer. Helquist
is a synthetic chemist whose specialty is making new compounds,
while Wiest's expertise is in chemical computer modeling, which
is invaluable in making novel compounds unseen in nature.
Recently, Helquist, Wiest, Wiech and their collaborators reported
a significant breakthrough in the Journal of Medicinal Chemistry.
They had discovered a formerly unknown binding site on the HDAC
molecule that offers a new target for modified forms of Wiech's
compound, CG1521. This offers the hope of new therapies for such
diseases as thalassemia, which is an inherited illness marked
by anemia caused by faulty synthesis of hemoglobin.
* * *
Faculty generally give the University an "A" for effort for the
improved patent climate, but wish for even more technical support.
"I think the University has improved, but it has been at the low
end of the learning curve and has needed to get up to speed quickly,"
the biologist Fraser says. "Part of the problem is that with only
a two-man office there isn't much of an infrastructure for pursuing
patents, and because of that there is a tremendous amount of extra
work for the researcher. For instance, on my last patent the lawyers
said they needed a copy of every citation of this patent, so I
had to spend hours pulling together all these articles. And that
means I have to take valuable time out of my work to do that."
High on the wish list of faculty researchers for the Office
of Technology Transfer is an on-staff patent agent, someone with
a science or engineering background who speaks the language of
technology and who could help faculty with the technical preparation
of their patent applications. "It's unrealistic for a lawyer to
write the patent," Leighton says.
The patent process starts with the faculty member filing a disclosure
form outlining the idea and the reasons why it might be valuable.
Next the Office of Technology Transfer has the idea evaluated
to determine how marketable it is. "After that we generally file
a provisional patent for one year," says Edwards. "It's important
to protect the idea before the faculty member presents any scientific
papers on it. If an idea seems extraordinary, we may file for
a full patent right away. After 12 months a decision must be made
whether to file a full patent, otherwise the idea goes into public
domain. In the meantime, with the help of the researcher we attempt
to find a corporate sponsor or someone to absorb the cost of the
full patent in exchange for a favorable license agreement."
"The faculty member is intimately involved in the whole process,"
Kantor says. "Especially since it is usually the researcher's
reputation and exposure that generates the licensing opportunities.
This is not something where the faculty member merely files a
disclosure statement and walks away."
Notre Dame's reliance on faculty to provide marketing leads
for their technology is the norm for university technology transfer
efforts, Jensen notes. Traditionally, licensing university-generated
patents is a tough sell, the economist says, because the technology
is so raw and basic that companies fear the cost of development
might outweigh the projected profits.
"Our survey of 65 leading universities indicated that 45 percent
of all inventions disclosed to technology transfer offices involved
technologies with merely a proof of concept, and 37 percent involved
technologies with only a lab-scale prototype. . . . Such inventions
are so embryonic that respondents to our survey reported that
71 percent of all inventions disclosed to technology transfer
offices required inventor involvement in further development for
any chance of commercial success."
"In an academic environment you tend to develop things to a
certain level," Leighton observes. "That's where the primary intellectual
content has been extracted. You figure out how things work, publish
your paper and that's that. Whereas companies developing a product
must figure out all the issues to make it work reliably and produce
it in an economical means. It's another level of development.
Polishing up an idea."
* * *
As Jensen points out, few University technology-transfer efforts
are profitable, so there must be other reasons to engage in it.
Kantor says, "The reasons we're involved in technology-transfer
efforts go beyond merely revenue generation. The key thing is
that it allows what's going on in our laboratories to have an
impact on people's lives."
"Frankly, even if it is not a financial success for the University,
it is a success," the Center for Medical Diagnostics associate
director David Leighton insists. "Technology transfer, giving
useful ideas back to the community, is as much a part of the academic
enterprise as is education.
"It would be very nice if one of these ideas hit it big and
vast amounts of money come into the University's coffers. But
the probability of that happening is like winning the lottery.
The probability of anybody getting rich is low, but the probability
of everyone being enriched in an academic sense is very high."
John Monczunski is an associate editor of this magazine.
(July 2005)
