DISCOVERYKGI is dedicated to education and research aimed at translating into practice, for the benefit of society, the power and potential of the life sciences.
Winter 2013
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insid
e KGI School of BioPharmacy Update
Meet KGI’s Post-Modern Medicine Man
Easing Rabies Burden in the Developing World
Continued on page 9
President Sheldon Schuster will soon
have a “powerhouse” new resource
at his disposal as he works with the
Board of Trustees to determine what
opportunities KGI should pursue in
the future. Last March, the Board of
Trustees approved the formation of
the institute’s first president’s council,
which is comprised of an elite group of
life science industry leaders. Although
not responsible for governance of the
institute or the implementation of plans,
council members will serve as confidential
advisors to the president and the board,
providing the institute with a vast wealth
of knowledge and industry expertise.
“KGI is experiencing significant
growth, while at the same time the health
care industry is undergoing dramatic
changes,” President Schuster said. “To
have this type of brain trust available to
me personally as an administrator and to
KGI as an organization during this period
of uncertainty, change and opportunity is
absolutely invaluable.”
Members of the inaugural council
will include James Cornelius; Michael
Friedman, MD; Robert Grubbs, PhD;
Freda Lewis-Hall, MD; Harlyne Norris;
Peter Salk, MD; and David Walt, PhD.
KGI Establishes President’s Council
In the spring of 2005, Robert Grubbs
received a call letting him know
that he had won the Nobel Prize in
Chemistry for his work on catalysis or
more specifically “for the development
of the metathesis method in organic
synthesis.”
He describes it as a “huge surprise.”
“There are always rumors going
around so you never know for certain,”
h e e x p l a i n s .
“There are many
people who do
incredible work
and who are
ment ioned as
being potential
recipients for
years, but they never win.”
Metathesis is a chemical reaction
in which an element or radical in one
compound exchanges places with another
element or radical in another compound.
Before the work of Grubbs and his fellow
Nobel recipients Yves Chauvin and
Richard Schrock, scientists had a very
limited understanding of metathesis
and little idea of the promise it held for
developing new materials. But Grubbs,
through his work in olefin metathesis in
particular, was able to develop highly
effective new catalysts that essentially
allowed for the creation of custom-built
molecules whose specialized properties
have a myriad of applications in industry
from the development of better drug
treatments to specialized plastics.
KGI welcomes Dr. Grubbs as an inaugural member of the President’s Council
An Interview with Nobel Laureate and Caltech Chemist Dr. Robert Grubbs
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By now you have probably heard from us through the mail, phone or email that we are in the midst of our 2012-2013 Annual Fund campaign. It’s a great time of year to give—you can sup-port KGI and get a tax benefit before the end of 2012. Thank you for your support.
Ways to give:• Please use the enclosed envelope to send a check or credit card number• Log on to support KGI.org to give online • Call (909) 607-8587 to donate over the phone
KGI to Pursue Independent School of BioPharmacy
For the past several years, KGI has been planning to launch
an innovative new School of BioPharmacy (SBP) that would
redefine the traditional Doctor of Pharmacy Degree. KGI’s
Board of Trustees determined that this ambitious undertaking
would introduce important innovations in pharmacy
education, enhance the institute’s standing as a leader in
bioscience graduate education and advance its mission to
develop the power and potential of the life sciences for the
benefit of society. Since the fall of 2011, Chapman University
has been a participant in this endeavor. The collaboration
held many potential benefits for both institutions. Chapman’s
programs in health informatics and health economics, as
well as a growing health sciences program, were a draw for
KGI, while Chapman’s leadership was intrigued with KGI’s
mission and concept for the school and valued the institute’s
expertise in niche education and its strong ties to industry.
Earlier this year, Chapman and KGI signed a memorandum
of understanding to establish the school, with a target date
to admit the first class on the KGI campus in the fall of 2014.
However, as the plans for the Chapman-KGI School
of BioPharmacy continued to take shape, it became clear
that, while the collaboration had been entered into with the
common goal of advancing healthcare education in our region
and furthering the missions of both schools, each institution
had a different vision for the SBP.
One of the major differences concerned the site of the new
school. It had originally been decided that classes would
be held on the KGI campus, recognizing that Chapman
would plan for a second SBP campus after accreditation
was achieved. Chapman University’s leadership concluded
this fall that the initial program should be moved to Irvine
in an industrial park facility it recently purchased for this
and other programs comprising its graduate health sciences.
KGI’s leadership believes equally strongly that it is vital for
the initial program to be held on KGI’s campus in order to
fully integrate the crucial KGI–related mission and services
with the SBP concept. Discussion to find common ground
around this fundamental issue was not productive.
“We are disappointed that, ultimately, this partnership
was not feasible,” said KGI President Sheldon Schuster.
“However, we have the full support of KGI’s Board of
Trustees’ Executive Committee to continue to pursue the
original School of BioPharmacy concept, which will be a
novel program among pharmacy schools in California and the
nation. We are energized by the return of control to KGI and
will pursue the concept for the school with our key strengths
at its core.”
KGI is continuing to work toward a January 2013
accreditation submission deadline for the new KGI School of
BioPharmacy. However, meeting this goal is strictly dependent
upon the funds being donated, pledged and/or loaned to give
the school a substantial financial footing. If substantial
funding is not acquired, submission of the application will
be delayed until January 2014 and admission of the first class
will be rescheduled to fall 2015.
“We believe that the SPB will greatly contribute to the
broadening of KGI’s recruiting base, building our faculty and
expanding our reputation,” President Schuster said. “With the
help of our strong supporters and generous donors, we have
no doubt that—just as 15 years ago we were able to launch
the bold undertaking to create the only graduate institution
in the country solely devoted to bioscience education and
discovery—the new KGI School of BioPharmacy will also
soon become a reality.”
ANNUAL FUND
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Since being elected to the KGI Board of Trustees
in 2009, Jim Widergren has brought invaluable
business expertise to the institute. In fact, his career
with its roots in both business and engineering embodies
the KGI professional model. “Jim’s knowledge base is
truly exceptional,” said KGI President Sheldon Schuster.
“His keen insight combined with his willingness to step
up and do whatever is necessary to help KGI grow and
thrive make him an outstanding board member and
supporter.”
Widergren, himself, credits much of his success
in business to his ability to understand the tech side
of industry. “I started in the automotive industry
designing turbochargers as an applications engineer,”
said Widergren, who retired in July of this year as the
senior vice president of Global Customer Operations for
Beckman Coulter. “At the beginning of my career, as an
applications engineer for Allied Signal Corp., I worked
directly with engineers at a major customer helping them
to design their engines using our turbochargers. I also
worked a lot with the service engineers who supported
end-user customers directly. This interaction with
customers made me interested in learning more about
the business side of technology.”
In order to learn more about the business side,
Widergren, who already held bachelors and master
degrees in engineering from Harvey Mudd College,
enrolled in UCLA’s Anderson School of Business. He
earned an MBA in finance and operations, which led to
positions on the business side of an engineering consulting
firm, Malcolm Lewis Associates, and a commercial real
estate development firm, Ferguson Partners. In 1992,
he joined the finance team at Beckman Instruments,
which later merged with Coulter Corporation to become
Beckman Coulter. “I have been on the business side ever
since, but the technical background was critical in my
success, as Beckman Coulter is a high-tech company
with technical customers. I could understand and solve
their problems.”
In fact, KGI’s unique educational program which
combines business with science and technology is what
initially intrigued him about the institute. “I think the
KGI MBS (Master of Bioscience) program is superb, and
I wish there had been such a program when I was in
college,” he said. “Rather than having to do two more
general master’s degrees, as I did, the MBS program
combines the best of both in a very industry-focused
way.”
Widergren also points specifically to the Team
Masters Project as one of the MBS program’s
distinguishing factors and representative of the type of
industry-focused experience that KGI offers its students.
“The TMP, which is modeled after the Harvey Mudd
Clinic Program, is a great way for students to learn to
interact with company deadlines, work with executives
and manage projects in a real-world setting, while still
having the support of the faculty and fellow students,”
he noted. “At Harvey Mudd, the Clinic Program was a
key to my education, and I am sure the TMP is having
the same effect on the KGI students.”
He also appreciates the institute’s large international
student population and believes that international
experience, which has been critical in his own career,
will be a key driver to future success in the life science
industries. “My international focus goes back to a
Thomas J. Watson Fellowship I was awarded while
at Harvey Mudd,” he explained. “I spent a year after
college in Asia studying energy development in rural
parts of Asia. By working at Beckman Coulter I was
able to combine my technical background, my business
experience and my international experience working on
the international side of the company for many years—
first in Finance, then in Operations. I have no doubt
that success in the future will require more international
interaction and understanding.”
KGI TRUSTEE PROFILE:
Jim WidergrenThis retired Beckman Coulter executive with vast business and international expertise is a firm believer in the KGI educational model
BOA
RD O
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UST
EES
Continued on page 7
President Sheldon Schuster hosted a luncheon at his new
home in Claremont on October 12 to honor the founding
trustees, donors and supporters of KGI. Among those in
attendance were original donors such as Harlyne Norris, KGI
trustee emerita, member of the President’s Council and of The
Kenneth T. and Eileen L. Norris Foundation, and Wendy Garen,
president and CEO of The Ralph M. Parsons Foundation. Allison
Keller, executive director and chief financial officer, and Maria
Pellegrini, PhD, executive director of programs, represented the
W. M. Keck Foundation. KGI was established in 1997 thanks
to a $50 million founding grant from the Keck Foundation.
Keller lauded KGI as one of the foundation’s best investments:
“From its beginning the W. M. Keck Foundation has put its
money into high-risk, high-impact projects, and I can’t think of a
better example of this than Keck Graduate Institute. Who knew
that you could pull it off and have a 22 percent year-over-year
growth rate? It’s about success, persistence and momentum,
and we can’t thank you enough for allowing us to share in this
success with you.”4
In today’s day and age, when insulin pumps are often
smaller and weigh less than cell phones, it’s hard to imagine
carrying around a backpack- style 18” by 18” insulin pump
weighing approximately 10 lbs. However, visitors to KGI’s
Science Heritage Center can now get an idea of exactly
how much the technology associated with these devices
has progressed by viewing a prototype of the first insulin
pump, which was created by Los Angeles pediatrician Dr.
Arnold Kadish in 1963. The device was donated by Kadish’s
son, John, who toured the Science Heritage Center over the
summer.
Dr. Kadish originally developed the pump for his
daughter, who had type 1 diabetes. The device delivered
both intravenous insulin and glucagon for improved glycemic
control. Through the efforts of the center’s curator, Robert
E. Finnigan Professor of Applied Life Sciences Dr. Jim
Osborne, and a close network of medical device professionals,
inventions such as Kadish’s insulin pump, which might be
otherwise lost, are now available for public display.
In fact, among the center’s recent visitors was Boy Scout
Troop #600. The California Inland Empire Council troop are
Webelos—a program that prepares 4th and 5th grade boys
to join a Boy Scout troop while learning outdoors skills and
participating in 20 different activity badges. “The items in
the Science Heritage Center are wonderful tools for getting
students of all ages interested in science and engineering
careers,” Osborne said.
Science Heritage Center Receives ‘Weighty’ Donation
A Great Day for Founders
Dr. Alan Rothfeld’s storytelling abilities
may be one of the reasons KGI students
consistently rate him as one of their favorite
professors—that and his impressive knowledge base
and wealth of experience. In addition to having spent
35 years as an academic and private practitioner
of pulmonary and critical care medicine, he’s also been
teaching medical students at the Keck School of Medicine
of the University of Southern California (USC) since 1979,
as a clinical professor of medicine.
After several years serving as an adjunct, Rothfeld
became a professor of practice at KGI this year. In many
ways, he says, teaching here is more fun in that it allows for
more flexibility. “Medical students have a pretty narrow
focus in that they are very concerned with what they have
to know to pass the test,” he said. “In my classes at KGI,
I get to show the whole spectrum of pharmacological
and medical science. It’s more about providing a broad
framework for (my students) to understand how to deal
with new situations, new drugs and new information—
and to be able to weigh benefits and risks.”
In fact, one of the consistent themes in Rothfeld’s classes
is that “unassailable truths” often have a shelf-life. As an
example, he points to the fact that conventional medical
wisdom used to hold that it was necessary to prescribe
drugs to suppress cardiac ventricular arrhythmias.
However, when outcomes were studied it was found
that, by and large, when you didn’t suppress arrhythmias
patients did much better.
Similarly, conventional medical wisdom used to hold
that it was necessary to raise the hemoglobin levels of
sick people. Actually, as Rothfeld points out, there is less
mortality in sick people with lower hemoglobin.
That’s why he stresses the importance of clinical trials.
“You don’t have to explain something for it to be true,
what works is what works,” he said. “The practice of
medicine is really about constantly translating findings
and putting them into practice.”
That’s why Rothfeld is such a strong proponent of
“rational medicine,” in which, as he describes it, you
have “some consideration of the
benefits and risks” associated
with a treatment, drug, or course
of action.
“You don’t seize on a small
benefit or potential benefit at the
cost of ignoring a huge risk. You
have to measure the overall benefit
to society and not be blinded by the idea of a miracle
treatment or miracle drug, which is, to some degree, the
paradigm of modern pharmacology.”
Often lost in the “miracle approach” to health care and
pharmacology is the fact that adverse drug reactions—
combined with errors and unnecessary therapies—cost
more lives than cancer and AIDS combined. “The truth
is we could cure cancer and not have as much impact on
the overall mortality rate as we would by cutting in half
deaths due to medical care. Why not put research into
how to decrease medical care-associated deaths and use
drugs more rationally?”
In addition to teaching KGI students about truly
modern medical practice, Rothfeld also serves as the
medical director and an adjunct professor of respiratory
therapy at Los Angeles Valley College, as well as the
director of translational research at COPE Health
Solutions, a leading healthcare corporation based in Los
Angeles. There, he is engaged, among other projects, in
research on the “Use of Behavioral Economics to Improve
Treatment of Acute Respiratory Infections.” The long-term
objective of which is to develop a set of applied behavioral
economic tools that are effective in promoting rational
choices among providers in infection treatment, a model
which could eventually be applied in other areas of health
care delivery and to other diseases and problems.
“We know that economic factors have a profound
effect on both patients and healthcare providers so
why not put effort into understanding them and then
incorporating them in to an applied model that will allow
you to improve patient outcomes?” he added.
Why not? It sounds pretty rational to us.
‘Post-modern’ Medicine ManAn advocate of rational medicine, Dr. Alan Rothfeld teaches his students how to deal with the unexpected
The practice of medicine is really about constantly translating findings and putting them into practice.
FAC
ULT
Y
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Advisory Council (AC) Chair Brenda Mann was
working as a post-doc in Houston when Larry
McIntire, then chair of the Bioengineering
Department at Rice University, first brought KGI to
her attention. He thought
that the brand new graduate
school taking shape in
California might be a good
fit given Mann’s postdoc
work in bioengineering and
biomaterials.
“It seemed l ike a
comple t e ly d i f f e r en t
environment. It wasn’t the
same as working in industry,
but it wasn’t the classical
academic track either,”
Mann said. “I was attracted by the idea of training
students to work in industry through innovative teaching
methods, including a cross-disciplinary approach that
would allow science and business faculty to work
together to a much greater degree and in a different
way than I’d seen.”
As one of the first faculty to be hired at KGI in 2000,
Mann jokes that VP of Academic Affairs and Dean of
Faculty Jim Sterling beat her to an actual start date, just
slightly, as least as far as bioengineering faculty was
concerned. “It wasn’t just a great teaching opportunity;
my time at KGI was also a great learning experience for
me. I learned so much about management, networking
and business development. Since the faculty was so small
and the school was so new, you were able to step outside
of your comfort zone.”
After three and half years as a member of the KGI
faculty, Mann moved to Salt Lake City with her husband
Jordan Gerton, who had been doing postdoc work at
Caltech and who was growing tired of the infamous
SoCal commutes. “I was happy at KGI, but sometimes
you have to make decisions based on what’s best for
both of you.”
Post-KGI, Mann had a choice between accepting a
traditional faculty position or working for a startup,
SentrX Surgical—a biotech company with an initial
market focus on therapeutic medical devices and
combination products to prevent post-surgical adhesions.
She decided to take a chance and work for the startup—a
bold move she would not have made, she says, if it were
not for her experience at KGI. “I was the third person
hired after the CEO and an administrative assistant. I
absolutely don’t think I would have done it if KGI hadn’t
made me comfortable with the business side,” she said.
“Before KGI, I had never seen a business plan; I didn’t
really know much about starting a company.”
In 2006, after serving as the director of pre-clinical
R&D for SentrX (now Carbylan BioSurgery), Mann
co-founded a spinoff company SentrX Animal Care,
which focuses on wound treatment products developed
specifically for horses and small animals. At first, as
the new company’s chief operating officer, she was
responsible for both manufacturing and research
and development, but as it grew she turned over her
manufacturing responsibilities to others and now
concentrates solely on R&D.
Yet, despite finding such success in industry, Mann
has never lost her connection with KGI. “I’ve served
on the AC since I left the faculty,” she said. Coming
from the animal health perspective, I think I provide
a different standpoint from other AC members, and,
in turn, have this incredible network of professionals
available to me from all areas of the life sciences. Most
importantly, I have the opportunity to get to know the
next-generation of industry professionals and stay on
top of how they think.”
In fact, Mann says the chance to interact with students
and colleagues face-to-face is why she particularly looks
forward to coming back to campus for biannual AC
meetings. “Occasionally, I think it may be time for
me to step off the AC but, since I’ve been here from
the beginning, I hope I provide a certain institutional
memory. It’s been very rewarding to watch and hopefully,
in some way, contribute to KGI’s growth over the years.
It’s fascinating to observe all the changes.”
ADV
ISO
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OU
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IL ‘Manning’ UpCurrent AC chair and former faculty member Dr. Brenda Mann talks about her long history with KGI, why she stays involved
Robert Baltera Jr., MS, MBA, was elected to the KGI Board of Trustees in September. A seasoned
pharmaceutical industry executive, Baltera acquired a wealth of business and product management
experience during 17 years with biotech pioneer Amgen and four years as CEO of Amira Pharmaceuticals,
which was acquired by Bristol-Meyers Squibb Company for $475M. While at Amira, Baltera was
instrumental in focusing Amira’s clinical development efforts and forging key collaborations with partners
such as GlaxoSmithKline. Before becoming Amira’s CEO, he held a number of senior management
positions at Amgen, the last being vice president of corporate and contract manufacturing. Baltera
also successfully used his collective experience to serve as team leader responsible for the approval
of Kineret™ in rheumatoid arthritis, a highlight of his many accomplishments while at Amgen. He
holds an MBA from UCLA Anderson School of Management and earned a Bachelor of Science in microbiology and a Master
of Science in genetics from The Pennsylvania State University.
Baltera Brings Experience, Insight to BOT
In September, the Board of Trustees
unanimously approved awarding a
Doctor of Applied Life Sciences honoris
causa to Marsh Cooper. In addition
to being one of the longest-serving
and most active members of the KGI
Board, Cooper is also a member of the
Board of Directors of the W. M. Keck
Foundation. Soon after the approval,
KGI President Sheldon Schuster and
Chair of the Board of Trustees Robert
Curry traveled to Toronto to present
Cooper with the degree and wish him
a Happy 100th Birthday!
Quite an Honor
In fact, business savvy, global thinking and an in-depth
understanding of science and technology are exactly what’s
needed in the industry leaders of tomorrow, and exactly why
he remains so committed to KGI’s mission: “We are entering
an exciting time for the life science and healthcare industries
with the emergence of personalized medicine and better
understanding of the human genome. But the best discoveries
are of little use to the world if they cannot be commercialized
and developed for people’s use. This requires both technical
and business expertise, which is a hallmark of KGI graduates.”
continued from page 3
STU
DEN
TS
For most people in the United
States, rabies is low on the
potential threat level. The number
of rabies-related human deaths averages
two or three each year and more than
90 percent of all animal cases reported
annually to the CDC occur in wildlife,
principally in wild carnivores and bats.
However, in areas of the developing
world, particularly in rural India, Asia
and Africa, rabies—an infectious disease
caused by a group of viruses from the
Lyssavirus genus — remains a pernicious
problem.
The World Health Organization (WHO) estimates that
more than 55,000 people die of rabies every year, with
roughly 36 percent of those deaths occurring in India.
Additionally, more than four million people are bitten
by dogs suspected to be rabid and thus should receive
treatment. A WHO report also stated that the paralytic
form of rabies is often misdiagnosed, contributing to the
underreporting of the disease.
If not treated after a bite from a rabid animal,
symptoms will usually develop between four to six weeks
and almost always lead to death. Current treatments
(cell culture vaccine plus antibodies from a previously
vaccinated human or horse) are effective but are often
unavailable, expensive, or inconveniently distant from
disease-burdened areas. More specifically, cell culture
vaccines may cost up to $40 to $50 for a full 4-5 shot
regimen delivered over the course of four weeks. The
cost of treatment along with the large number of shots
over time is not ideal for people living in rural areas who
must travel significant distances multiple times to receive
treatment.
That’s where KGI PhD candidate Ryan McComb
comes in. Working under Adjunct Professor Dr. Larry
Grill, McComb is conducting research that could lead to
the development of a more potent, less costly and locally
produced plant-made rabies vaccine. By increasing both
vaccine availability (through lowered production costs)
and reducing the number of times an exposed person
needs to receive a booster shot, the vaccine would have the
potential to greatly ease the rabies burden in developing
countries. Using cutting-edge bioscience research to help
develop (plant made) vaccines that can be produced locally
and cost-effectively is the focus of Dr. Grill’s work. In
addition to serving as an adjunct faculty member at KGI,
Grill is also a professor at Pitzer College, where he directs
The Ferre/Marquet Vaccine Research Center, which is
dedicated to developing cost-effective vaccine production
and addressing urgent health issues in southern Africa.
“With our goal of developing and providing
inexpensive vaccines that will be produced in developing
countries, the rabies vaccine could be the accomplishment
of the decade,” Grill said.
A modified plant virus vaccine is essentially a plant
virus that has been re-engineered to mimic the physical
structures and properties of a disease-causing pathogen,
such as virus, bacteria or parasite, McComb explains.
Plant-made rabies vaccines work by using plant virus
nanoparticles as antigen presentation scaffolds for eliciting
protective antibodies from the immune system.
PhD Candidate’s Research Could Help Ease Rabies Burden in Developing World
Ryan McComb gives his Thesis Scope presentation at KGI on Oct. 30.
With our goal of developing and providing inexpensive vaccines that will be produced in developing countries, the rabies vaccine could be the accomplishment of the decade.
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continued from page 1
Although his work has found broad-
based application in industry and Caltech
has one of the best university tech
transfer offices in the country, Grubbs
is well acquainted with the difficulties
and frustrations associated with moving
fundamental discovery into industry.
“I think traditionally there’s been
some frustration in academic labs
that when you license discovery to big
companies, it often tended to die on the
vine, and that transition into widespread
application just never happened, he
said.”
Such challenges are one of the reasons
that he’s particularly interested in the
KGI model.
“I have always liked the CUC
(Claremont University Consortium)
system,” Grubbs added. “And, I think
KGI’s model of collaborating closely
with industry to advance training and
education is a very interesting one. I
also think it’s important to give young
researchers and scientists a framework
for understanding how discovery
transitions into product in a commercial
environment.”
In order to facilitate that transition,
Grubbs helped to establish a company,
Materia, Inc., where many of the
commercial applications for metathesis-
based products have been developed.
Although not without a learning curve,
Grubb says the company has done
extremely well in acting as pipeline from
academics to commercial application.
In the meantime, Grubbs, who
spent his early life in rural Kentucky
and attributes much of his intellectual
curiosity to his grandmother’s influence,
is anxious to continuing following his
research path in olefin metathesis, where
he says there are “many problems of
catalysis yet to be solved.”
“I’ve been very fortunate to have been
able to follow my intellectual interests
and have it ultimately result in products
that have biomedical applications or
that can be found in products under the
hood of your car,” said Grubbs, adding
that potential new applications currently
under the company’s banner include three
drugs to treat Hepatitis C that are in
clinical trials.
Asked if things have changed for him
in the years since he won the Nobel Prize,
his reply is, “not really, I just have to say
no a little more often.”
Luckily, for KGI and President
Schuster, when asked to serve on the
newly formed President’s Council Dr.
Grubbs’ answer was yes.
“I can’t think of a better example of
a scientist whose work embodies KGI’s
mission to translate the power and
potential of science for the benefit of
society,” President Schuster said. “We
are very grateful that he has agreed to
take this active role in support of KGI.”
I think KGI’s model of collaborating closely with industry to advance training and education is a very interesting one. I also think it’s important to give young researchers and scientists a framework for understanding how discovery transitions into product in a commercial environment.
“Introducing what ‘looks like’ the dangerous pathogen
into the body gives the immune system the ability to prime the
body’s defenses for the real disease threat without causing the
disease,” he said. “Plant viruses are safe since they don’t infect
and replicate in animal cells but still act as a potent activator of
the body’s immune system.”
Furthermore, he adds, plant-made vaccines using modified
plant viruses are inexpensive to manufacture, compared to cell
culture vaccines, since they only require water, sunlight, and
fertilizer as opposed to cell culture media and large stainless steel
fermenting tanks. The infrastructure for producing plant-made
vaccines is much smaller and can be scaled up to meet demand
by simply increasing the number of acres of plant vaccine crops.
In addition, modified plant virus vaccines can be easily purified
by using alternative methods that are less costly than purifying
vaccine material produced in cell culture. And finally, modified
plant virus vaccines are very safe since they do not require the
use of animal products as found in cell culture media.
“I think these advantages provide a compelling case for
modified plant virus vaccines so long as they prove to be potent and
effective against the pathogen they are meant to protect against,”
McComb said.
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RESE
ARC
H Proprietary technology for manufacturing antibodies is an early KGI success story
Most of the KGI community is familiar with Dr. Jim
Cregg’s passion for Pichia pastoris (or Pichia p as it’s
known around here). The focus of his research has been
on developing the yeast as a system for the production
of recombinant proteins, and he is the lead inventor on
many of the seminal Pichia protein expression patents.
Several of those patents resulted from an interesting
collaboration between KGI and the Seattle-based biotech
company, Alder Biopharmaceuticals. And, the story of
how this particular patent came about speaks to the early
success of the KGI’s institutional model, which is built on
close collaboration with industry.
A crucial player in the story is former KGI Vice
President of Academic Affairs and Chief Scientific Officer
David Galas. Alder CEO Randy Schatzman happened to
mention to friend and former Celltech colleague, Galas,
how he and his partners (in what was then not even a
startup) were looking for an alternative way to produce
commercial antibodies for use in antibody therapeutics.
“Antibody manufacturing capacity is generally held
by a limited number of companies,” Cregg explained.
“They wanted to find a way to do it themselves and they
wanted an alternative to (typical) cell culture production.”
In other words, he says, they wanted a way to produce
them better, faster and cheaper.
And, that’s when Cregg and KGI Senior Research
Scientist (now Research Professor) Dr. Ilya Tolstorukov
entered the picture. Galas was familiar with the work
they had been doing with yeast and thought it might be
a good fit. While Cregg had been working with Pichia
since the ’80s, Tolstorukov’s PhD research project,
defended in 1973, was related to discovery of genes
involved in mating and “mating–type switching” in
classical yeast model Saccharomyces cerevisiae. In 1974,
he began working with methylotrophic yeast similar to
Pichia pastoris, particularly as it related to methods of
mating and genetic analysis. In fact, Cregg had studied
Tolstorukov’s publications when he first began working
with and learning how to manipulate Pichia P.
“When we first considered the idea of making
antibodies in the Pichia pastoris expression system, Ilya
spent several weeks analyzing the landscape and designing
the material to work with,” Cregg said, adding that
although he thought it was a possibility he still remained
somewhat skeptical that they could pull it off. “No one
had ever made full-length, multi-chain antibodies in Pichia
before, and I wasn’t sure we were going to be successful.
I had my doubts.”
And, the process of making them, which took about
a year, didn’t exactly go smoothly. “We had our lumps
and bumps along the way,” Cregg said. For example,
Tolstorukov had a “heck of a time” cloning the genes
that they needed to use in the R&D phase of the project
because commercial DNA libraries didn’t have anything
that would suit their purposes. “We basically had to design
and build our own,” Cregg noted.
Additionally, since Alder wanted to avoid having to
license technology (for the manufacturing of antibodies)
that was already patent-protected, the duo had to come
It was the first time I was involved to such a degree with a company making a product from yeast. It was a great experience for me to see a company come out of nothing using our ideas.
up with a novel approach to bringing together two cassettes
expressing heavy and light chains in one cell.
“The key element of our technology and what allowed us
to make it novel was an idea to mate (hybridize) haploid cells
expressing two different chains to create a diploid expressing
two chains capable of assembling into one tetrapeptide antibody
molecule,” Tolstorukov explained.
KGI, which had been fronting Alder the cost of this research
through use of its facilities and Cregg’s and Tolstorukov’s time
and talents, then licensed the technology to Alder. On its website,
Alder, which has grown from a startup company to one with more
than $100 million of investment in their antibody development
technology and portfolio of therapeutics, touts the Pichia system’s
ability to make “fully functional whole antibodies at a fraction
of the time and cost of other technologies.”
Its advantages, among others, include scalability (scales
reliably from 1 Liter to 50,000 Litersc); speed (each strain doubles
in 90 minutes) and cost-effectiveness (ramps to production with
minimal investment). Overall, it takes 12 months on average to
generate a commercial antibody strain using mammalian cell
cultures, while Alder’s Pichia-based “Mab Xpress® Antibody
Production System” takes about five weeks.
“The use of MabXpress has allowed us to progress our
therapeutics very rapidly from discovery into clinical studies,”
Schatzman said. “Another advantage of this technology is that
it has allowed us to consider entering disease markets where
antibodies have not previously played a role as therapeutics
and where pricing constraints have previously been a barrier
to therapeutic antibodies; an example of one such market is the
treatment of chronic migraine.”
Alder has long since repaid the research costs of developing
the Pichia system as well as an annual licensing fee. In addition,
KGI has stock in Alder which would yield a profit if the company
goes public. But, for Cregg and Tolstorukov, the benefits go
beyond the financial. “It was the first time I was involved to such
a degree with a company making a product from yeast. It was a
great experience for me to see a company come out of nothing
using our ideas,” Cregg said.
And while the circumstances that resulted in this proprietary
technology may have been unique, Cregg and Tolstorukov say
they are two of the strongest proponents of the KGI model of
collaboration with industry.
“I don’t think it would happen exactly same way today, with
one person (Galas) basically making the decision to fund the
research. Today, there would be committees to evaluate it,” Cregg
said. “That said, I do think it’s very exciting to see the work
going on here today—all the contributions that KGI is making in
rare diseases, in biomarkers, in medical devices, in many areas.”
Welcoming fellowship donors and student fellowship recipients
At the Sheraton Fairplex Hotel and Conference Center in Pomona
Wednesday, January 30, 2013
For An Italian Dinner – Buon Appetito!
KGI’s 5th Annual Fellowship DinnerSAVE THE DATE
This fall, KGI and the Jonas Salk Legacy Foundation hosted an exclusive screening of “The Shot Felt ’Round
the World” at the Huntington Library in San Marino. The documentary film about Dr. Jonas Salk and the nation’s
crusade to develop a polio vaccine includes interviews with Salk’s sons, Drs. Peter and Jonathan Salk, and those
who were part of his research team at the University of Pittsburgh. More than 150 people attended the event on
September 9, which included a panel discussion featuring Peter and Jonathan Salk, Tjardus Greidanus, the film’s
director-editor, and producer Laura Davis. KGI was able to grant complimentary admission to current students
thanks to the generosity of several anonymous donors.
The Shot Felt ’Round the World
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535 Watson Drive • Claremont, California 91711 www.kgi.edu