LSF
MAGAZINE
Winter 2015
Telling the Story of Biotechnology
special issue:
Global Biotech
Departments
04 LSF News
06 LSF Events
12 Educators’ Corner
Bio-Rad’s Gift
14 Biotech Bookshelf
Biotechnology in Africa and Swiss Made
16 LSF Oral History Program
Dennis Gillings, “Calculated Risk and Reward”
28
George Poste, “Embracing Complexity”
20 Gems from the Archive
The first Hambrecht & Quist Healthcare
Conference, January 1983
22Obituary
Robert Schimke (1932-2014)
24 In Conversation
Florence Wambugu, Kenyan scientist
and technology advocate
24
22
52 Photo Finish
The Art of Robert Schimke
Features
28 Global Biotech Centers
Singapore, Cambridge, Dubai,
38
Shenzhen, and Santiago
38 Vital Tools
A Brief History of CHO Cells
48 Global Biotech Philanthropy
Diagnostics for All
14
2 LSF Magazine Winter 2015
20
Erbitux and the Manzanar Project
From the editor
This issue of LSF Magazine contains stories
on global developments in biotechnology.
Here’s a brief history lesson:
At the end of the nineteenth century,
Germany led the world in science and industry. Over the next three decades, the world’s
technoscientific center of gravity migrated west,
to North America. Public and private institutions in the United States expanded support for
scientific research and the nation’s technological capabilities grew.
In the 1920s, the American economy began
exercising innovative capabilities across a wide
range of industries. Even through the Great Depression, with much of the country’s labor force
idled, US corporations built industrial laboratories and testing facilities, made inventions, and
stoked the nation’s economic furnace.
In the 1940s, the war effort ignited further
rounds of innovation. Scientists and engineers
employed by universities, federal agencies, and
private contractors were pressed into research
duty. In the postwar period, scientific and technological progress became a national security
matter of the highest priority.
In the 1950s and 1960s, venture capital,
skimmed from the wealth of the most productive economy in human history, generated a
wild blossoming of high technologies. Science
and capital combined to transform California’s
Santa Clara Valley and Boston suburbs along
Route 128 into vibrant technopoles.
When molecular biology came to practical
fruition in the 1970s with the invention of
recombinant DNA and hybridoma technologies, conditions conducive to life science
enterprise were already set in place in America.
The emergence of the biotechnology industry
can be attributed to powerful economic forces
unleashed in the United States in previous
decades.
At the end of the twentieth century, America
led the world in bioscience and industry. In
2015, it still does, but the future is uncertain.
The world economy has become globalized. It is
characterized by new developmental logics.
International trade has intensified and
accelerated. Information technologies permit
knowledge and capital to circulate and settle
virtually anywhere on the planet. Time and
space have been compressed, and many problems once posed by distances and borders have
been dissolved. National, regional, and local
economies that used to operate provincially
have been connected, integrated, and made
interdependent.
The biotech industry has been enmeshed
in this process for at least two decades. The
spectacular rise of the industry’s contract
research and manufacturing sectors, and the
formation of foreign subsidiaries by biotech
operations large and small, reflect opportunities
and needs to access emerging markets. At
the same time, cities and states all over the
global map have reconfigured policies to attract
biotech enterprises and spur the creation of
new regional industries.
So far, self-sustaining centers of biotech
innovation have been established only in places
endowed with strong science, entrepreneurial
cultures, business-friendly policies, sturdy
support infrastructures, and skilled workers.
Many developed countries in Europe and Asia
possess these attributes and are racing to catch
up with the United States.
Other nations are making substantial investments in education and research in hopes of
getting into the game (Brazil, India, and South
Korea are prime examples). They are developing manufacturing capabilities and positioning
themselves, through a host of inducements,
as outsourcing destinations and gateways to
emerging markets.
In the near term, poor countries in Africa,
Asia, Latin America, and the Middle East have
virtually no chance to participate in the global
biotech economy as producers, but with further
economic development, they may generate
enough wealth to become purchasers. Until
then, they will remain largely dependent on
charity.
History matters in this evolutionary process.
Head starts and deficits matter, but the future
hasn’t been written. The twentieth century was
the “American century.” The twenty-first is a
question mark.
Executive Editor
Mark Jones
Editor
Marie Daghlian
Production Manager
Gavin Rynne
Design/Layout
Carol Collier
Zachary Rais-Norman
Contributors
Brian Dick
Michael Hammerschmidt
Victor McElheny
Eddie Patterson
Gavin Rynne
Ramya Rajagopalan
Barri Segal
Ian Signer
Hallam Stevens
Kevin Vickery
© Copyright 2015
Life Sciences Foundation
All rights reserved
Mark Jones
Winter 2015
LSF Magazine 3
giving
Supporting LSF
A message from Board Chair Carl Feldbaum
Dear Friends,
The Life Sciences Foundation (LSF) is a unique institution. Its mission
is to record, preserve, and share the history of biotechnology. No other
organization is dedicated to carrying out this work.
The history is compelling. Late advances in the life sciences are
profoundly transforming the human condition. The technologies are
epoch-making, but few in society at large understand the processes of
innovation that created them.
LSF is now working to inform the curious public—students, teachers,
future innovators, your kids and grandkids, for example—and others with
professional interests in the industry, such as journalists, policymakers,
and scholars in academic institutions.
The foundation is telling the story in various ways – through events,
publications, the Internet, and social media—not for the sake of nostalgia
(although there is nothing wrong with that) but for understanding and
inspiration. When the past is shared, it becomes a resource for education.
If stories aren’t told, experience is squandered.
The LSF staff consists of a small group of historians, archivists,
educators, and web designers who are steeped in the history, skilled in
heritage preservation, and adept at public outreach. To extend its reach,
the foundation has partnered with leading institutions of higher education and scientific research, including Cold Spring Harbor Laboratory,
the National Institutes of Health, the Smithsonian Institution, and the
University of California.
I ask you to join me in supporting the Life Sciences Foundation. Please
make a gift, or better yet, a three-year pledge. Your donation will help us
build a sustainable organization. With your support, we will ensure that
the story is told, and told well.
Sincerely,
Carl Feldbaum
4 LSF Magazine Winter 2015
Ways to Give to the Life Sciences Foundation
Donate Online
Matching Gifts
Donate by Mail
Corporate and Foundation Grants
LSF is now able to accept gifts through our website. Giving
online is a safe, simple, efficient way to support LSF. Your secure
tax-deductible donation will help LSF conduct interviews, collect
archival materials, engage key audiences, and tell biotechnology’s
story. Go to biotechhistory.org/donate-now to make your gift.
If you wish to make a contribution by mail, you can send your
check to:
Life Sciences Foundation
P.O. Box 2130
San Francisco, CA 94126
Gifts of Stock
Donating stock directly to LSF may be advantageous to you,
especially if the stock has increased in value. You will receive
an immediate income tax deduction at full value and avoid tax
on the gain. LSF will benefit immediately. Contact LSF’s VP for
development, Michael Hammerschmidt, by email at michael@
biotechhistory.org or call 415.798.2104 for more information.
Honor/Memorial Gifts
Recognize the accomplishments of a friend or family member
with an honor gift.
Make your charitable gift go twice as far—it’s easy. Many
companies match their employees’ charitable contributions.
Some match gifts of spouses or retirees, as well. You can double,
and sometimes even triple your impact. Does your firm have a
matching gift program?
Each year, LSF proudly receives support from corporations large
and small. Many of the foundation’s programs are sustained by
corporate grants. If you make decisions on corporate giving,
please consider support for LSF. Many of our supporters direct
the giving of individualized funds within national, private, and
community foundations, or their own family foundation. This is
another way to support LSF.
Planned Gifts
Planned gifts are a very personal way for you to help LSF
share the biotech story and achieve your retirement and estate
planning goals at the same time. Make LSF a part of your legacy
by including a gift of any size in your will or living trust. Supplement your retirement income and save taxes while helping
LSF with a life income gift. Your gift plan can be tailored to meet
your financial situation, now and for years to come. For further
information on planned gifts, contact:
Michael Hammerschmidt
VP for Development
michael@biotechhistory.org
415.798.2104.
Winter 2015
LSF Magazine 5
LSF news
Foundation & Event Updates
Foundation Advisors in the News
LSF advisor and Harvard University Franklin L. Ford Research Professor in the History
of Science, Steven Shapin,
was awarded the History of
Science Society’s 2014 Sarton
Medal for Lifetime Scholarly
Achievement. Shapin is one of
the world’s most distinguished
scholars in the history and
sociology of science. He is
widely lauded for influential
studies of scientific inquiry in
historical, cultural, institutional, and political context,
including Leviathan & The
Air Pump, A Social History
of Truth, and The Scientific
Life: A Moral History of a Late
Modern Vocation. The Sarton
Medal has been presented
annually since 1955 in honor
of Harvard’s George Sarton,
founder of the journal Isis.
LSF advisor Alan Mendelson
was honored with the 2014
Life Sciences Leadership
DiNA Award at BayBio’s
11th Annual Pantheon
Ceremony held on December
11, 2014. Mendelson served
as legal counsel to Amgen
for twenty-six years, from
1980 to 2006. Andrea Brown,
vice president and corporate
counsel at Grifols USA, made
the presentation. Lou Lange,
founder and CEO of CV
Therapeutics from 1992 until
the company’s sale to Gilead
Sciences in 2009, was also
honored. Karen Bernstein,
co-founder, chairman, and
editor-in-chief of Biocentury
Publications, presented Lange’s
award. The Pantheon Awards
Ceremony celebrates stellar
achievements in the Bay Area’s
life sciences industry.
6 LSF Magazine Winter 2015
Marie Daghlian
Joins LSF
LSF welcomes Marie
Daghlian to the position
of developmental editor.
For the past ten years she
served as a writer, editor,
and researcher for the Burrill
Media Group. She helped to
produce the Burrill Report
and Burrill & Company’s
annual industry compendium.
Marie brings a wealth of
valuable experience to LSF,
and will help the foundation’s
research, communications,
and education teams share
the history of biotechnology
with multiple audiences, in
print and online formats,
through multiple outlets. In
a former life, Marie designed
and manufactured women’s
clothing. Her merchandise was
sold in boutiques throughout
the United States for thirty
years.
LSF Staff in the News
LSF Research Associate
Ramya Rajagopalan
published an article in the
September 2014 issue of
Sociological Theory on the
implications of genomics
research for understandings of
race and ethnicity. The paper
was co-authored with leading
scholars in biology and the
social sciences, including
Troy Duster of the University
of California, Berkeley and
Richard Lewontin of Harvard University. In October,
Rajagopalan was featured on
Perpetual Notion Machine, a
public radio show produced
by WORT-FM in Madison,
Wisconsin. The installment,
entitled The Genome—Promise and Peril, examined legal
and ethical issues created by
advances in genomics and
personalized medicine. Listen
to the podcast at wortfm.org/
the-genome-promise-andperil/
“The Interferon
Tournament”
In November, LSF sponsored
a special history colloquium
hosted by the University of
California, San Francisco’s
Department of Anthropology,
History, and Social Medicine
at the university’s Mission Bay
campus. Nicholas Rasmussen,
professor of history at the
University of New South
Wales in Sydney, Australia,
gave a presentation entitled
The Interferon Tournament:
Economies of Honor and
Credit. The talk reviewed the
early 1980s race to clone the
interferon gene. Rasmussen is
the author of Gene Jockeys: Life
Science and the Rise of Biotech
Enterprise (Johns Hopkins
University Press, 2014).
UCSF Professor of Medicine
Emeritus Henry Bourne added
commentary and led an open
discussion.
Changing the
Face of Biotech
Leadership
What does it take to build
winning teams over time?
Please join us in San Diego
on February 12, 2015 for
“Changing the Face of Biotech
Leadership,” an evening
with accomplished industry
leaders, women executives
who will explore rarely
discussed facets of the biotech
industry: diversity and the
significance of gender in the
formation of effective teams
and organizational cultures.
In the third event of this
series, panelists will offer
personal insights and recount
how they navigated shifting
professional landscapes to rise
to positions of responsibility.
A reception with the speakers
will follow. To register, please
visit: changethefacesandiego.
eventbrite.com.
LSF Docent Training
LSF has new look
After a successful run at the
Reuben H. Fleet Science
Center in San Diego, Genome:
Unlocking Life’s Code, a traveling museum exhibit created
by the National Institutes of
Health and the Smithsonian
Institution continues its fiveyear tour of North America.
The exhibit will arrive at the
Tech Museum in San Jose,
California on January 22. LSF
is training volunteer docents
to introduce museum visitors
to the history of genomics
and DNA sequencing. If you
are interested in sharing the
biotech story with people of all
ages and wish to volunteer as
a docent, please visit Genome:
Unlocking Life’s Code at
www.biotechhistory.org/
genome. After the run in San
Jose through April 27, the
show will move to St. Louis,
Missouri in May and Portland,
Oregon in October.
The Life Sciences Foundation
has relaunched its website
with a new look and new features. The website is optimized
for multiple platforms so you
can now explore everything
that LSF has to offer on your
smartphone just as easily as
you would on your desktop.
An updated timeline interface
allows you to delve deeply
into biotech’s rich history and
enhanced audio-video capabilities help bring that history to
life. You can also read the oral
histories of biotech pioneers,
watch a video of an LSF event
on your tablet, or download
the latest edition of LSF
Magazine. See for yourself by
visiting LSF online at
biotechhistory.org.
Winter 2015
LSF Magazine 7
LSF news
LSF Event Recaps
Changing the Face of Biotech Leadership
The Life Sciences Foundation hosted two events this fall that
addressed the circumstances of women in the higher circles of
the biotech industry. Changing the Face of Biotech Leadership,
was held at the Genzyme Center in Cambridge, Massachusetts on
October 20, and at Genentech Hall on the Mission Bay campus of
the University of California, San Francisco on November 17.
In Cambridge, Genzyme CEO David Meeker welcomed
attendees and introduced panel moderator Caren Arnstein,
Genzyme’s senior vice president for corporate affairs. The panel
featured Deborah Dunsire, CEO of FORUM Pharmaceuticals,
Becky Levin, founder and chairman of the executive search firm
Levin & Company, Vicki Sato, a professor of management practice
at the Harvard Business School and an associate faculty member
in the Harvard Department of Molecular and Cell Biology, and
Alison Taunton-Rigby, director and trustee of several healthcare,
life sciences and financial services organizations.
In San Francisco, Science Futures founder Nola Masterson
greeted the audience and introduced panel moderator Simone
Fishburn, executive editor of SciBX for BioCentury Publications.
The panelists were Gail Maderis, president and CEO of BayBio,
Susan Molineaux, president and CEO of Calithera Biosciences,
and Kathy Stafford, senior vice president of human resources and
organizational development at Solazyme.
In lively discussions, the speakers shared their personal experiences as women moving through the industry ranks into positions
Nola Masterson of Science Futures (second from right) in San Francisco
of leadership. They dispensed advice on professional development
and considered opportunities for women currently entering the
field. MassBio was the presenting partner on the East Coast; BayBio was the presenting partner in the West. BioMed Realty Trust,
LSF’s national event sponsor, provided generous support for both
events. Science Futures was the event sponsor in San Francisco.
A third Changing the Face of Biotech Leadership event will take
place in San Diego, in February 2015.
The Cambridge panelists: Vicki Sato, Becky Levin, Alison Taunton-Rigby, Caren Arnstein, and Deborah Dunsire
8 LSF Magazine Winter 2015
A question for the
panel in Cambridge
Deborah Dunsire greets an
audience member
Clockwise from bottom left: Kathy Stafford, Gail Maderis, moderator Simone Fishburn
and Susan Molineaux
Winter 2015
LSF Magazine 9
LSF news
Other Event Recaps
Cold Spring Harbor Laboratory
History Conference:
Plasmid Biology
In late September, the Genentech Center at Cold Spring
Harbor Laboratory hosted Plasmids: History & Biology, the
latest in a series of conferences on the history of molecular
biology and biotechnology. The three-day meeting was organized by Jan Witkowski of Cold Spring Harbor Laboratory
and leading figures in plasmid research over the past fifty years:
Dhruba Chattoraj of the National Cancer Institute, Stan Cohen
and Stan Falkow of the Stanford University School of Medicine,
Richard Novick of New York University, and Chris Thomas of
the University of Birmingham.
The program featured presentations from an illustrious
group of geneticists, molecular biologists, microbiologists,
and pathologists. Speakers reflected on the development of the
field from the discovery of horizontal gene transfer by Joshua
Lederberg and Edward Tatum in 1946 to contemporary
research with implications for biomedicine, public health,
agriculture, ecology, pharmaceutical R&D, synthetic biology,
and evolutionary theory. A roundtable on history featured
commentary by science historians Roy Curtiss III, of Arizona
State University, Matthias Grote, of the Technische Universitat
in Berlin, and LSF Director of Research Mark Jones.
Julian Davies (left) from the University of British Columbia and Richard Novick, New York University
10 LSF Magazine Winter 2015
Above:
Chris Thomas (left)
of the University of
Birmingham with
Bruce Levin from
Emory University
Left: Ananda
Chakrabarty of
the University of
Illinois, Chicago
Chris Thomas
Left: Stan Cohen and
Jim Watson
Below: The traditional
group portrait, at the
Hershey Laboratory
Winter 2015
LSF Magazine 11
education
Bio-Rad’s Gift
The Life Sciences Foundation has teamed with the National
Institutes of Health and the Smithsonian Institution to present
Genome: Unlocking Life’s Code. Recently, the foundation received
a generous donation of educational kits from Bio-Rad Laboratories in Hercules, California for use in LSF’s museum docent
training program.
The kits provide LSF-trained docents with hands-on activities
they can use to engage the interested public as they share the
wonders of the human genome.
With the Genes in a Bottle kit, for example, museum visitors
learn about the double helix as they make necklaces containing
samples of their own unique DNA. The Candy Caper and STEM
Electrophoresis kits help visitors to understand DNA sequencing
as they solve a mystery using the laboratory technique of gel
electrophoresis.
Genome: Unlocking Life’s Code was designed by the National
Institutes of Health and the Smithsonian Institution to increase
public awareness of the ways in which advances in genomics
are profoundly reshaping the human experience. The traveling
exhibit is currently at the Reuben H. Fleet Science Center in San
Diego. It will move to the Tech Museum of Innovation in San
Jose for a three-month run beginning on January 22 and closing
on April 27, 2015.
BioRad’s DNA Model from
the Biotechnology Explorer
educational series
12 LSF Magazine Winter 2015
LSF trained docents demonstrate BioRad’s Candy Caper
kit to visitors at the Reuben H. Fleet Science Center
Winter 2015
LSF Magazine 13
biotech bookshelf
Winter Reading
It all started with milk. Then came cheese, chocolate, cuckoo
clocks, skiing, and a secretive banking system that launders
money for corrupt dictators, drug lords, and tax cheats. Author
R. James Breiding considers this view of Swiss economic history
grievously uninformed and lamentably common. Swiss Made:
The Untold Story Behind Switzerland’s Success dispels its misconceptions and aspersions.
Breiding explains that while Switzerland’s dairy products,
confections, timepieces, and resorts are world-class, they are not
the country’s main outputs, and although fraud is a problem in
the Swiss banking industry, it is not a standard business practice.
Explanations for Switzerland’s economic success lie elsewhere.
Switzerland is roughly the size of Maryland, landlocked and
mountainous, with few natural resources. Its population is just
eight million. There are more people in New York City. Because
of the nation’s geographic and demographic limitations, Swiss
industries are heavily dependent on foreign trade.
Yet, in 2013, the country’s gross domestic product (GDP) per
capita was fourth highest in the world: US$74,277. The comparable figure in the United States was US$48,377. Switzerland’s great
prosperity results from its ability to wring value from cross-border transactions. The banking industry is a prime example. Swiss
banks manage an estimated US$7.7 trillion in private wealth
from other countries, and generate 11 percent of Switzerland’s
gross domestic product.
Breiding speculates that Switzerland’s dependence on
outsiders has produced a cosmopolitan culture of openness—to
communication, diversity, and free exchange. He sees the
attitude reflected in federal law, which protects local autonomy,
individual liberty, and economic freedom with light regulation
and low tax and tariff rates. The political philosophy is conducive
to entrepreneurship and competitiveness.
The book discusses many Swiss industries. Chapter nine is
devoted to pharmaceuticals, which in 2012 accounted for 32
percent of the country’s total exports. As a research intensive, innovation-based sector, the pharmaceutical industry is especially
important for Switzerland’s economic future, because it bolsters
the nation’s position in the global knowledge economy.
It began in Basel at end of the 19th century when three family-owned dye and chemical companies, Ciba, Geigy, and Sandoz,
began manufacturing medicinal products. F. Hoffman-LaRoche
was founded as a dedicated pharmaceutical firm during the same
period. Brieding’s narrative follows the origins and growth of
these venerable companies through the twentieth century until
an unlikely series of events made tiny Switzerland a major player
in biotechnology.
In 1990, Roche purchased 60 percent of Genentech for
14 LSF Magazine Winter 2015
R. James Breiding, Swiss
Made: The Untold Story
Behind Switzerland’s
Success (London: Profile
Books, 2013).
US$2.1 billion. The following year, it purchased exclusive rights
to PCR, Kary Mullis’ revolutionary DNA amplification technology, for US$300 million. In 1994, Ciba-Geigy purchased
a 49.9 percent share of the Chiron Corporation for US$2.1
billion, and in 1996, Ares-Serono of Geneva introduced the
first of several new recombinant therapeutic products, which
enabled it to grow into the world’s third largest biotechnology
company.
In 2005, Novartis (formed in the 1996 merger of Ciba-Geigy
and Sandoz) acquired all outstanding shares of Chiron for
US$5.1 billion. At that moment, three of the world’s ten largest
biotechnology companies had Swiss owners. And by 2005, more
than seventy new biotech startups had appeared around Basel,
Geneva, and Zurich, including Actelion, a company that was
founded in 1997, and within seven years had attained a market
capitalization in excess of US$2 billion.
The nascent Swiss biotech industry is well positioned for
further growth. It is taking shape in the vicinity of large, watchful biopharmaceutical and biochemical companies, including
Novartis, Roche, Syngenta, and Lonza, and Switzerland’s seven
world-class universities—two Swiss Federal Institutes of Technology and the Universities of Basel, Bern, Geneva, Lausanne,
and Zurich. Its orientation is global, of necessity. Swiss markets
are far too small to permit companies to recoup the massive outlays required for biopharmaceutical research and development.
Swiss Made is handsomely bound and superbly written. The
research base is impressive. Throughout, the survey of Swiss
industries is embedded in a rich, contextualizing narrative that
describes evolving social, cultural, and political conditions in
Switzerland and beyond, over hundreds of years.
Breiding was born in the United States, the son of a Swiss
immigrant. He studied in Lausanne, at the International Institute
for Management Development. He is not merely an observer of
Swiss industry. He is an investor with skin in the game. In 1999,
he co-founded Naissance Capital in Zurich.
In 2001, in the midst of a famine, the late Zambian President Levy Patrick Mwanawasa rejected food aid from Western
countries because it contained genetically modified organisms
(GMOs). In 2005, Ghana’s parliament approved biosafety
regulations to protect the country’s flora and fauna from harmful
GMOs. In 2012, Kenya instituted a ban on GM crops in reaction
to a study (soon discredited) that reported tumors in rats fed a diet
of GM maize.
Most of Africa’s governments have adopted similar precautionary rules. The continent has become a vast battleground on
which rival political factions are struggling to decide the future of
agricultural biotechnology.
On one side, international organizations including the United
Nations’ Food and Agriculture Organization, the United States
Agency for International Development, the World Bank, and the
Alliance for a Green Revolution in Africa, a partnership between
the Rockefeller and Gates Foundations, are seeking to increase
food security, eradicate hunger, and reduce poverty through technology investment and development, food aid, and the promotion
of science-based regulatory policies.
They have been joined by numerous African stakeholder
groups including AfricaBio, Africa Harvest Biotechnology
Foundation International, the Economic Union of West African
States, and the West and Central African Council for Agricultural
Research and Development.
On the other side, environmental groups such as Greenpeace
and Friends of the Earth maintain that the introduction of GMOs
will lead to environmental degradation, loss of biodiversity, the
disappearance of indigenous cultural practices, and the debt
subjugation of African farmers to First World governments and
corporations.
Their message resonates with African anti-GMO activists and
dozens of continental and regional citizens’ groups, including
the African Centre for Biosafety, Biowatch, the Coalition for the
Protection of African Genetic Heritage, the Malian National Coordination of Peasant Organizations, Nyéléni, the Forum for Food
Sovereignty, and the South African Freeze Alliance on Genetic
Engineering. Some of these groups oppose food aid; some support
non-GMO food shipments from the European Union.
Conflicted governments are caught in the middle. To date,
GM crops have been introduced for regular use in just four of
the continent’s fifty-three countries: Burkina Faso, Egypt, South
Africa, and the Sudan.
Biotechnology in Africa is an edited volume that presents arguments from the pro-technology side. It was assembled by Kenyan
plant pathologist and virologist Florence Wambugu, founder and
CEO of Africa Harvest, and Daniel Kamanga, the organization’s
director of communications. It includes contributions from leading African authorities—biologists, agriculturalists, economists,
policymakers, lawyers, and lobbyists.
The book chronicles the tumultuous history of GM crops on the
Florence Wambugu and
Daniel Kamanga, eds.,
Biotechnology in Africa:
Emergence, Initiatives,
and Future (New York:
Springer, 2014).
continent and reviews technologies currently in development, case
studies of successful commercialization, arguments for regulatory
reform, and proposals for harmonizing regional biosafety guidelines.
In the opening chapter, Wambugu addresses regional food
security and biosafety issues in the context of global political
economy. She argues that opposition to GMOs is a greater
economic threat to Africa’s smallholder farmers than engineered
seeds because under present conditions, only multinational
corporations can afford to make technological innovations and
improvements in agriculture.
The book then moves to overviews of contemporary biotech
research in Africa, including efforts to improve major staple crops
such as cassava, potatoes, and bananas.
Later chapters discuss efforts by governments, research
institutions, and aid organizations to build infrastructures, train
scientists and technicians, and establish trust with citizens and
stakeholders.
A key chapter highlights the interrelated technical, economic,
political, and cultural dimensions of efforts by African researchers
to develop GM sorghum. Sorghum is a primary food source for
300 million people in Africa’s arid and semi-arid regions, but it
lacks essential micronutrients, such as vitamin A, and its iron and
zinc content is not in a bioavailable form. Because sorghum is a
dietary staple, these deficiencies can have serious health consequences, such as xerophthalmia, which causes blindness, anemia,
and diarrheal disease.
The African Biofortified Sorghum Project, a consortium of
fourteen public, private, and non-profit organizations, is working
to increase the nutritional value of varieties preferred by African
farmers while ensuring biosafety and environmental protections.
Field trials have taken place in Kenya and Nigeria, but resistance
to the technology and a lack of sustained funding has put the
project at risk.
Biotechnology in Africa has certain stylistic and structural
faults (non-specialists will find the material informative but dry;
specialists will be disappointed by the lack of an index), but the
book’s message is plain: without substantial investment, effective
community outreach, and consistent governmental support,
potentially beneficial technologies will continue to languish.
Winter 2015
LSF Magazine 15
oral history spotlights
Oral histories are narrative accounts of events and historical processes as
told from the point of view of eyewitnesses and participants. They preserve the experiences, recollections, and testimonies of history-makers.
Dennis Gillings
Calculated Risk and Reward
Dennis Gillings has always been a risk taker. In 1982, he gave up
a secure career as a professor at a top university to build Quintiles,
the biostatistical consulting company he had cofounded with a
university colleague. The company was born from the idea that
drug development is, in essence, an information science, and that
patients benefit when all stakeholders are properly informed.
Having grown Quintiles from a tiny startup to a publicly traded
transnational corporation, an industry leader with operations
in fifty countries, Gillings risked it all once more by taking the
company back into private ownership...
Dennis Gillings was good at math—always at the top of his
class. He earned a bachelor’s degree in mathematics at Exeter,
a diploma in mathematical statistics at Cambridge, and then a
PhD in mathematics at Exeter in 1972. His advisor, John Ashford, steered him into biostatistics and health services modeling.
“Ashford made a tour of the United States,” Gillings says. “He
came back and told me biostatistics was a big thing, and there
was a shortage of people trained in the field.”
Ashford encouraged his protégé to consider a faculty position
in biostatistics in the School of Public Health at the University of
North Carolina (UNC). Gillings traveled to a biometrics meeting
in Germany to meet the chair of the department, Bernard
Greenberg. Greenberg wanted someone to run the unit’s health
services program, and to start right away. He offered Gillings the
job on the spot.
But Gillings had made plans for extensive travel in Africa,
and didn’t want to give them up. He took one of his first risks
when he asked for a one-year deferment. He got six months.
“A typical business negotiation,” he says. With little more than
a suitcase and sense of adventure, he drove from Morocco
to South Africa. Gillings calls the journey “an extraordinary,
character-forming experience.”
He immediately embarked on another life-changing experience when he flew to North Carolina. Gillings had grown up in
London imagining that America was a dynamic and progressive
place. Chapel Hill didn’t fit his mental picture: “I had assumed
that because of the country’s material wealth, it would be more
sophisticated, but it wasn’t. In North Carolina, there were “blue
laws” that restricted liquor sales, a hangover from Prohibition, I
suppose. Wine was almost unheard of and a lot of the gourmet
foods I was accustomed to were unobtainable.”
Gillings began his appointment in a small trailer in the woods
16 LSF Magazine Winter 2015
adjacent to the university, Trailer 39. At first he was put off by the
arrangement, but he soon found that separation from the main
campus had advantages: “My colleague, Gary Koch, an outstanding statistician, had decided to relocate there. We built our own
little empire with our own students. We had a good time there,
professionally and socially.”
As associate director of the Center for Health Services Research
at UNC, Gillings provided statistical consulting services for the
entire health sciences campus, which included the schools of medicine, pharmacy, nursing, dentistry, and public health. At the time,
graduate students provided labor, but weren’t compensated. One
of Gillings’ first acts was to change this plan: “It had a huge impact
because we used to get a large number of what I called ‘rubbish
questions.’ People clearly hadn’t thought through what they wanted. As soon as they had to pay $25 an hour, their ability to describe
and think through what they wanted improved enormously.”
Gary Koch soon recommended Gillings’ services to Ken
Falter, the chief clinical statistician at the large drug maker,
Hoechst-Roussel. Falter wanted help interpreting adverse
effects of a diabetes drug called Glyburide. The problems had
been reported in Germany. Gillings had all of the charts and
reports translated from German by colleagues in the languages
department, and then determined that the drug was being
prescribed, in some cases, to the wrong patients. The finding
prompted Hoechst-Roussel to change the drug’s label, which
led to regulatory approval of an important new treatment in the
United States.
The problem was solved in a month, and the good result
snowballed into many more industry assignments. Gillings
and Koch’s statistical services were soon in high demand.
Gillings proposed the creation of a non-profit institute within
the University through which revenues from contract research
would be funneled back to the school. The UNC administration
rejected the idea. Gillings decided to start his own firm. It was
permissible—university rules allowed faculty members to devote
one day per week to outside consulting.
The new enterprise was called Quintiles. It was housed
originally in Trailer 39, “and that worked very well,” Gillings
says. “I would feed a lot of the work into projects for students.
Papers would get published, and the students generated consulting income.” The business grew. In February 1982, Gillings
incorporated and moved the firm off campus with five full-time
employees.
As Quintiles continued to expand, Gillings felt pulled to
devote more time to the company. He was by now a full professor at the university, but in certain respects the achievement
felt limiting. He started to entertain the notion of leaving: “I
thought, ‘If I stay here for the rest of my life, there’s too much
more of the same.’” Seeing business as “the best of both worlds,”
he took a two-year leave of absence in 1986 to focus full-time
on Quintiles. It was another calculated risk. He reckoned that he
could go back to higher education if things didn’t work out.
It was a perfect time to grow the business. Drug makers had
begun outsourcing clinical development work in the 1980s in
order to rein in skyrocketing R&D costs. Quintiles started with
statistical analysis, added data management, and soon offered a
comprehensive clinical services package. “By about the late 1980s,
I’d really built that model very successfully and built it internationally,” Gillings says. He had moved the company into England, with
clinical trial management operations in London and Reading.
By 1990, it was clear that the way forward was to address the
full range of drug makers’ clinical needs, and to do it efficiently
by standardizing clinical research. Gillings moved to reorder the
field through the introduction of new information technologies,
but struggled against regulatory and industrial inertia. Computer systems couldn’t be changed in the middle of clinical studies
without the approval of the FDA, and clients dragged their heels.
Earnings demands from Wall Street soon tempered much of
the resistance. Quintiles prospered and extended its reach into
Europe, Asia, and Australia through acquisitions and new investments in infrastructure. In 1994, in order to fuel further growth,
Gillings sought to raise money in public markets.
During the grueling roadshow in advance of the IPO, he told
prospective investors that the pharmaceutical industry didn’t
have the internal resources to move all of its products to market,
and that helping them represented an enormous opportunity.
“There were a lot of drugs in the pipeline,” he says. “It was a
once-in-a-lifetime growth spurt for the pharmaceutical industry.” Quintiles successfully completed the IPO.
The company became a global full-service contract research
organization (CRO), handling not only clinical trial management, but also marketing and sales functions, and health
economics policy analysis. In 1998, the company’s revenues
exceeded $1 billion.
Gillings realized that although the opportunity was global,
success depended on local performance. When opening new
branches, he made visits, met with regulators, scientists, and
customers, and evaluated each opportunity on the ground. He
also took quarterly worldwide tours of company facilities to
meet face-to-face with employees at every site.
Having no formal training in business, Gillings credits his
success to his evaluation skills and his intuitive understanding
of statistics: “I have been quite good at taking difficult problems
and transforming them into something manageable.” His ability
to derive useful information from confounding data sets has
enabled him to make sound calculations of risks and rewards.
It wasn’t always easy. In 2003, Gillings decided to take Quintiles back to private ownership—he didn’t want the organization
to be driven by short-term expectations as it retooled for the
future. At risk was his entire stake in the company he had started
in Trailer 39 and grown into a thriving transnational corporation
operating in fifty countries.
Once again, the gamble paid off. Gillings was able to improve
Quintiles’ infrastructure, processes, and strategic flexibility. The
retrofitting drove accelerated growth over the next ten years. In
May 2013, Quintiles went public again on the New York Stock
Exchange, under the symbol Q.
Gillings has observed the CRO sector evolve from a consulting resource in the 1980s, to an outsourcing resource in the
1990s, to an indispensable strategic infrastructure in the 2000s.
“Now that we serve a strategic function,” says Gillings, “we are
changing the way things are done. This is as it should be, because
we have become highly skilled in the logistics of drug development. If you took CROs out of the current system, nothing much
would get done.”
With promising scientific, therapeutic and analytical advances on the horizon, Gillings now anticipates the richest reward of
all flowing from his calculated risks—better health for patients
around the world.
Winter 2015
LSF Magazine 17
oral history spotlights
George Poste
Embracing Complexity
George Poste is a big picture guy. He believes that progress in science and medicine requires understandings of complex wholes, and
that reductionism is foolhardy. “With reductionism,” he says, “you
delude yourself into thinking that you can understand a complex
system by analyzing its parts, but you can’t.” Poste’s appreciation
for big picture thinking has been reinforced by adventures in cancer
research, drug discovery, genomics, and biosecurity, but it first
came to him through exposure to the traditional practices of an
older world.
George Poste grew up in rural Sussex, in the south of England,
during the postwar period, a time of austerity and reconstruction. The life of the local community was ordered by the natural
rhythms of farming. His father was a mechanic, “a keen practical
intellect” who made his living servicing farm machinery and
vehicles.
Poste observed that veterinarians also played critically
important roles in the farm economy, and in the course of
their work confronted “a diverse set of intellectual challenges.”
Veterinarians are trained to diagnose and treat ailments of many
different kinds—equine, bovine, porcine, ovine, caprine, and so
on. It seemed to the boy that their practice was far more demanding than that of the village physician.
In 1954, Poste came to a branching point—the Eleven Plus
exam that stratified primary school students on the basis of
intellectual ability. He took the exam a year early, but still scored
in the top 5 percent, which put him on the university track. Some
time later, he began accompanying local veterinarians on their
rounds. He wanted to acquire their big picture perspective on
health and illness.
At the age of eighteen, he went off to the University of Bristol
with a plan to study clinical veterinary medicine. He was not surprised to find that “veterinary students had the highest entrance
qualifications, and the medics, dentists, and vets all went to the
same classes.”
At the time, biomedicine was being rebuilt on molecular
foundations. Poste feels “fortunate to have been there at the
beginning, to get training in molecular biology.” He became
particularly interested in cancer—studies of retroviruses and
oncogenes had begun to reveal the complexities of tumor
biology.
Poste completed his veterinary training in 1966, but rather
than going into clinical practice, he went on to earn a PhD in
18 LSF Magazine Winter 2015
virology at Bristol in 1969. He then accepted a position as a
lecturer in the field at the University of London’s Royal Postgraduate Medical School.
Two years later, he took a sabbatical at the Roswell Park
Cancer Institute in Buffalo, New York. “I’m the only guy who
ever went to Buffalo not knowing that it snows there,” he laughs.
The institute had recruited a stellar multidisciplinary group
composed of molecular geneticists, cell biologists, immunologists, and pharmacologists. Poste found it a uniquely stimulating
environment: “There was a great intellectual nucleus and I was
trying to absorb everything like a sponge.” The sabbatical visit
turned into a permanent tenured appointment at the State
University of New York.
Then, out of the blue in 1981, Poste received a call from a
headhunter representing a “major research firm.” It turned out
to be the Philadelphia pharmaceutical house, Smith, Kline &
French. “I had never thought about going into industry,” says
Poste. “I had a typically insular, academic view of the world, and
by this time I was a full professor. But I went through the interviews, and only an idiot would come away unimpressed by what I
saw and the ambitious plans that the company had to participate
in the then emerging new domain of biotechnology.”
SmithKline had recently introduced the world’s first
blockbuster drug, the anti-ulcer histamine blocker cimetidine
(Tagamet), one of the inventive payoffs of James Black’s pioneering work in “rational drug design.” Bryce Douglas, the company’s
senior vice president of R&D, recognized the potential of
molecular biology to advance this novel mode of drug discovery
and development. He encouraged Chairman Henry Wendt and
CEO Bob Dee to invest heavily.
Douglas recruited Stanley Crooke, who had built BristolMyers Squibb’s oncology program, as president of R&D, and
Poste as vice president of research—two people he believed had
the background and the will to innovate. “This was sophisticated
strategic planning,” says Poste. “The molecular revolution was
underway, and Bryce wanted SmithKline to be part of it.”
Still, it was a struggle to bring molecular biology into an organization steeped in pharmaceutical chemistry. Poste remembers:
“It was a pretty traumatic time. Stan Crooke and I literally tore
the place apart. We imposed radical change.” And, he admits, “It
wasn’t always done optimally or with adequate consideration.” It
was a difficult time for the company’s powerful marketing group,
too. “Sales people understand existing markets,” says Poste, “but
they have a harder time with disruptive technologies.”
Battles ensued. Poste was convinced, for example, that
recombinant DNA technology would revitalize SmithKline’s
vaccine business, but on three separate occasions, factions in
the company’s executive suite pushed to sell it off. “I laid down
in front of it each time,” says Poste, “and I’ve got the scars on
my back to prove it. But I was right—vaccines now have profit
margins that equal pharmaceuticals.”
Crooke left in 1988 to start his own company, Isis Pharmaceuticals, and Poste took over as president of the R&D division. In
the 1990s, as part of a forward-looking executive cadre, he helped
to devise a “grand plan” for the company. It was an early vision of
“personalized medicine.” Poste anticipated an integrated program
of genomics-based drug discovery, companion diagnostics, and
healthcare informatics.
In 1993, he spearheaded SmithKline’s landmark $125 million
deal for rights to develop drugs, vaccines, and diagnostics from
gene sequences identified by the pioneering genomics company,
Human Genome Sciences. It was a bold move. The company
recouped its investment by subleasing access to the sequence
data, but the integrated healthcare framework wasn’t realized. “It
was premature,” says Poste, “and the company reverted back to
the standard pharma model.”
In retrospect, Poste sees the episode as a lesson in biological
complexity and big picture pharmacology: “You need to work
from the bottom up, you need the genes, but you also need a topdown understanding of the system. So, we missed a lot of things.”
Two decades later, molecular medicine is still moving into terra
incognita. The “personalization” of medicine is still in its infancy.
In 2000, SmithKline merged with Glaxo Wellcome, and Poste
was ready to step out. He had by this time received high honors
from his country of origin—he had been elected a Fellow of the
Royal Society and received the Order of Commander of the British Empire from Queen Elizabeth—and he had helped shepherd
more than thirty new drugs to market.
In his “retirement,” Poste planned to shuttle between his
three favorite cities—San Francisco, San Diego, and Scottsdale,
Arizona—serving biotech enterprises as a director and consultant. After 9/11, however, his expertise became vital to the US
Department of Defense. For two years, he traveled regularly to
Washington, DC to chair the agency’s Defense Science Board
Bioterrorism Task Force (and he continues to advise on matters
of national security).
In 2003, Michael Crow, president of Arizona State University,
asked Poste to help the school set up a life sciences innovation
center, the Biodesign Institute, that would merge the best of
university and industry research styles. Some on campus felt the
two approaches were antithetical. Poste didn’t. He accepted the
invitation.
He implemented what he calls a “3M” approach as the core
organizing principle in the Biodesign Institute’s multi-investigator, multi-institution, multi-million dollar research projects. “Just
as in industry,” Poste explains, “projects are led by teams and the
matrices of ever-fluid, ever-shifting assemblies of skills needed at
any given time to tackle specific problems.”
In 2009, Crow asked Poste to lead another new program, the
Complex Adaptive Systems Initiative (CASI), to drive 3M projects on a larger scale across the university’s research units. CASI
seeks multidisciplinary solutions to pressing problems as they
emerge from within complex sociotechnical systems—financial
crises, food and water shortages, pandemics, bioterrorism, cyber
warfare, and the complex potential effects of climate change, for
example. For a big picture guy, CASI is an ideal environment.
Poste chalks up much of his professional success to luck, and
the fact that he never worked for anyone who viewed him as a
competitor: “Every single person I‘ve worked for has been gifted.
None felt threatened by my talents.” He also acknowledges the
stimulating influence of creative and insightful colleagues at
Bristol, Roswell Park, SmithKline, and Arizona State.
Beyond good fortune and good friends, he recognizes the
importance of three fateful personal decisions: “To go to university, to come to the United States, and to go into industry. Those
choices led me to a very enjoyable and successful life.” Finally,
Poste cites his natural inquisitiveness, inherited from both of his
parents. “I still have a voracious appetite for knowledge,” he says.
“My kids joke that when they try to nail the coffin shut, my hand
will shoot out and they’ll hear, ‘Wait a minute, there’s one more
thing I want to know.”
Winter 2015
LSF Magazine 19
gems from the archive
The First Hambrecht & Quist
Healthcare Conference
Monday, January 10, 1983. High temperature: 54° F.
It seemed positively balmy to those who had traveled from the
East Coast for the first Hambrecht & Quist (H&Q) Healthcare Conference, a three-day meeting of investors, stock analysts, bankers,
and company executives at the St. Francis Hotel, pictured above, on
San Francisco’s Union Square. Two hundred and twenty registered
attendees were on hand to take the measure of the healthcare industry in the West and learn about new opportunities in biotechnology.
Presenting companies included hospital operators, medical
device manufacturers, a medical information services provider, and
five biotechnology startup firms: Centocor, Collagen, Genentech,
Monoclonal Antibodies, Inc., and Xoma. The biotech industry was
still very small. By 1983, it had put just a handful of products on the
market, a few diagnostic kits and one therapeutic—recombinant
human insulin, invented by Genentech and manufactured and
marketed by Eli Lilly and Company.
The meeting was organized by Annette Campbell-White, H&Q’s
healthcare specialist. As new biotech and medical device companies
proliferated in the Bay Area and became increasingly visible on Wall
Street, she had the notion that H&Q could host a West Coast event
to complement the annual East Coast healthcare conference held by
Alex. Brown & Sons in Baltimore, Maryland.
Monday’s discussions focused on trends in healthcare delivery,
20 LSF Magazine Winter 2015
regulation, and pricing. On the second morning, a ninety-minute
session posed a question, “Medical Genetics – the Next Revolution
in Medical Therapeutics?” Panelists Mr. Michael A. Wall, president
of Centocor, Inc., Dr. Patrick J. Scannon, president of Xoma, Inc.,
and Mr. R. Swanson, president of Genentech, Inc., talked about
new opportunities in pharmaceuticals and diagnostics created by
the invention and application of recombinant DNA and hybridoma
technologies.
The conference was roundly deemed a success. A second was
held the following year, and it turned into an annual event. In 1999,
Hambrecht & Quist was acquired by Chase Manhattan. The event
was renamed the Chase H&Q Healthcare Conference. Chase merged
with J.P. Morgan in 2000, and from 2003 on, the meeting became
known by its current name, the J.P. Morgan Healthcare Conference.
The event has grown tremendously over the years. Last year, more
than 430 public and private companies presented to more than 9,000
invited guests. J.P. Morgan hosts many investor events every year. The
January Healthcare Conference in San Francisco is the largest.
Campbell-White attributes the popularity of the conference to
scheduling and the weather: “I believe to this day that the key to the
success of the conference is timing. People have new budgets and
new ideas and the weather’s bad on the East Coast.”
Winter 2015
LSF Magazine 21
obituary
Robert Tod Schimke (1932-2014)
Robert Schimke enjoyed an illustrious thirty-five year career
in science at the National Institutes of Health and Stanford
University. He established the field of protein turnover, advanced
understandings of the ways in which hormones control gene
expression, elucidated the phenomenon of gene amplification, and
showed how apoptosis (programmed cell death) prevents genomic
instabilities associated with cancer. Schimke mentored many students who later made important contributions to the life sciences,
biomedicine, and the biotechnology industry, and he played a brief
but consequential role in the formation of Amgen. After a serious
injury in 1995 made it impossible for him to run his laboratory, he
devoted his energies to another creative pursuit—painting.
Robert Schimke was born and raised in Spokane, Washington
in the years spanning the Great Depression and World War II.
His father was a dentist, his mother a piano teacher. Schimke
didn’t remember his youth with fondness. He was a gifted student, but also, in his words, “a holy terror” with a penchant for
finding trouble. Still, he managed to earn a full scholarship for
early admission to Stanford University, which made him exempt
from military conscription.
He majored in biology, graduated in 1954, a year early, and
entered the Stanford School of Medicine. There, he benefitted
from a new program designed by Dean Robert Alway and
Henry Kaplan, chair of the radiology department, to modernize
the curriculum and introduce medical students to laboratory
research. Schimke joined the laboratory of pharmacologist
Avram Goldstein, and worked on the biochemistry of addiction.
He further developed his research skills as a postdoc in the
laboratory of noted biochemist Oliver Lowry at the University of
Washington, St. Louis.
After an internship at Massachusetts General Hospital,
Schimke joined the NIH in 1960. He worked in biochemical
pharmacology at the National Institute of Arthritis and Metabolic Diseases and studied the cellular regulation of enzymes under
the direction of Herbert Tabor. Researchers knew that substrates
stimulate enzymatic activity; Schimke investigated the role of
substrates in enzyme degradation.
He coauthored a 1964 paper on the topic that received hundreds of citations and established enzyme stabilization as a new
field in biochemistry. He discovered that enzymes are protected
from degradation when bound to their substrates, the molecules
on which they act.
22 LSF Magazine Winter 2015
Schimke’s work on gene amplification was
critical to the production of recombinant
erythropoietin (EPO), an important turning point
in the history of the biotechnology industry.
In 1966, Schimke returned to Stanford to teach in the School
of Medicine’s Department of Pharmacology. He served as
chair from 1970 to 1973, and then moved into the university’s
Division of Biological Sciences. He built on his protein turnover discoveries and focused on the hormonal control of gene
regulation. He demonstrated, first in rat livers and then in chick
oviducts, that specific gene functions could be influenced by
steroid hormones.
In 1978, Schimke and graduate student Fred Alt showed
how murine sarcoma cells developed resistance to the cancer
drug methotrexate. Methotrexate works by inhibiting
an essential enzyme. Schimke and Alt found that cells
responded by increasing, or “amplifying,” the number
of copies and expression level of the gene that codes for
the enzyme. Beyond explaining a mechanism of drug
resistance, the work revealed a high degree of genomic
instability in cancer cells.
In the fall of 1979, Schimke happened to sit next
to venture capitalist Sam Wohlstadter on an airplane.
Wohlstadter was then working with colleague Bill Bowes
to identify opportunities for starting new biotechnology
companies. Schimke and Wohlstadter discussed gene
splicing. Wohlstadter told Bowes about his new Stanford
connection, and the pair approached Schimke about
forming a new venture.
Schimke declined the invitation to become a founder,
but agreed to serve as a scientific consultant. He was
soon forced to bow out of the project, however, when
his father became gravely ill. He suggested that Bowes
and Wohlstadter contact UCLA biologist Winston
Salser, whom he knew to be highly entrepreneurial.
Salser became a cofounder, recruited an all-star scientific
advisory board, and, with Bowes, gave the company a
name, Applied Molecular Genetics—Amgen, for short.
Schimke eventually joined the company’s scientific
advisory board and his work on gene amplification
became the basis for techniques that Amgen employed
to scale up production of its first product, recombinant
erythropoietin (EPO). Around the same time, Chris
Simonsen left a postdoctoral position in Schimke’s Stanford lab and found employment at Genentech, where
he helped Art Levinson develop a similar method for
amplifying the expression of the gene for tissue plasminogen activator (tPA). The development and introduction
of EPO and tPA were important turning points in the
early history of the biotechnology industry.
Schimke continued to investigate the underlying
mechanisms of gene amplification through the mid1980s, and then turned his attention to cell-cycle
events and apoptosis. Schimke showed that selective
pressures on cells when cell-cycle events were interrupted were important factors in inducing the genomic
instability that had already been shown at work in gene
Robert Schimke painted in a variety of styles and media, but all
of his works were kinetic. “They are all moving,” he said. “There is
nothing static about them.”
amplification.
Tragedy struck in 1995. Schimke, an avid cyclist, was
severely injured in a collision with a car while cycling
home from his lab. He was partially paralyzed from the
neck down. With determination and years of physical
therapy, he regained some mobility, but remained mostly
wheelchair bound for the rest of his life.
The accident effectively ended Schimke’s scientific
career at age sixty-two, but he had already considered
retiring to spend more time painting and gardening.
For a time, he kept abreast of scientific progress as an
associate editor for the Journal of Biological Chemistry,
but by 2002, his time was wholly devoted to painting.
He experimented prolifically with different styles and
media. Unable to enjoy his previously active lifestyle,
he told an interviewer that he invested his energy in his
paintings: “They are all moving. There’s nothing static
about them.”
In nearly thirty years at Stanford, Schimke mentored
more than one hundred students, many of whom went
on to have distinguished research careers in academia
and industry. Many have expressed admiration and
appreciation for his direct style of communication, his
passion for teaching, and his ability to anticipate movements in scientific research. Fred Alt, now a professor
of genetics at Harvard Medical School and a Howard
Hughes Medical Institute investigator, says, “He was
incredibly honest. He would say exactly what he thought
about your work, and he was usually right. As a mentor,
he was tough, but never impatient.”
Robert Schimke died on September 6, 2014 in Palo
Alto, at the age of eighty-one. He is survived by his wife
Patricia Jones, a professor of biology at Stanford, three
daughters, and five grandchildren.
Winter 2015
LSF Magazine 23
in conversation
Florence Wambugu
On Agriculture and Food Security in Africa
Florence Wambugu grew up in the foothills of
Mount Kenya in the 1950s and 1960s. Food was
scarce. The local staple crop, the sweet potato,
was frequently ravaged by blight. Wambugu
resolved to do something about it. She became a
plant pathologist. She studied at the University of
Nairobi and went to work for the Kenyan Agricultural Research Institute. She concurrently obtained
a master’s degree at North Dakota State University,
and earned a PhD at the University of Bath, in
England. In 2002, she founded Africa Harvest
Biotech Foundation International, an organization
devoted to technological and economic progress in
all of the continent’s diverse regions. Here Wambugu talks with LSF’s Brian Dick about opportunities
and challenges related to the adoption of agricultural biotechnologies in Africa.
BD: Dr. Wambugu, you are an advocate for the
use of agricultural biotechnologies to increase
food production in Africa. What led you to this
pursuit?
FW: Food security is a serious problem in Africa.
The genetic modification of plants can help to
solve it. As a PhD student, my thesis research
focused on controlling the sweet potato virus that
was limiting yields. Viral diseases often devastate
African crops. There’s no winter to break the
disease cycle so the incidence of infection is
very high. Plant diseases are also spread by
cultural practices that farmers are reluctant
to give up, such as sharing seeds and cuttings.
Genetic modification (GM) technology could
potentially confer resistance to viral infection
and increase yields, allowing farmers to continue
sharing seeds. That’s what originally attracted
me to genetic engineering. After a brief period
of postdoctoral work in the United States, I came
back to Africa.
BD: Please tell us about Africa Harvest. What are
the organization’s goals and current projects?
FW: Our mission is to improve food security
and the welfare of African populations by
using the tools of agronomy and agricultural
biotechnology. We are working to build
healthy communities and help smallholder
farmers produce plentiful, nutritious food
supplies. We must support producers. We are
not disseminating information and deploying
technologies simply to get better field results.
We are working to create sustainable agricultural
systems.
We bring a comprehensive value-chain
approach that provides farmers with access to
high quality seed, information, and material
resources—through microcredit programs, for
example. We must fight poverty as well as insects,
plant blight, and environmental problems. It is
absolutely crucial that smallholder farmers have
access to functional markets. They have to be
able to sell their goods. Toward this end, Africa
Harvest conducts economic research, lobbies
for constructive policy change, and identifies
opportunities for establishing produce market
centers. We know that technology uptake is high
when there are robust markets in place.
Dr. Florence Wambugu at a meeting
sponsored by the World Agroforestry Centre
24 LSF Magazine Winter 2015
Winter 2015
LSF Magazine 25
Africa Harvest uses tissue culture technologies to improve banana yields
BD: You’re describing a holistic approach.
FW: Yes, we work on natural resource management, for instance.
Africa is dealing with many different kinds of environmental
problems—desertification, water pollution, loss of biodiversity,
and the effects of climate change, for example. All present major
challenges, especially to poor rural people who depend on
natural resources for their livelihoods. Africa Harvest engages
with communities to improve the quality of water and soils,
conserve forests and biodiversity, and implement climate change
mitigation strategies.
Incidentally, Africa Harvest has yet to deploy GM technology.
So far, the products are cultivars improved by conventional means,
such as disease-free, high-yielding tissue-culture banana plantlets.
Sixty percent of Africa Harvest’s work is doing the legwork to
increase farmers’ access to hybrid seeds and plants. There is still
significant resistance in Africa to the introduction of GM crops.
Our communications programs are focused on disseminating
accurate, reliable information about GM technologies in order to
counter the influence of anti-GM scare campaigns, and to dispel
public confusion. At the same time, we are working to develop
partnerships with farmers’ associations, governments, and food
aid organizations. Africa is a big continent. If we can effectively
share with others what we’ve learned, we will make an impact.
BD: In what specific areas can biotechnologies be brought to
bear on economic and food supply problems?
FW: There are many. GM cotton represents a big economic
opportunity for Africa. Kenya’s once-flourishing cotton industry
has been decimated by the high cost of pesticides, most of which
are imported. Farmers ended up spending most of their income
on chemicals. In India and South Africa where GM cotton is
approved for planting, small-scale farmers are benefitting much
more than large-scale farmers because the new technology allows
them to use much less pesticide on their cotton crops.
26 LSF Magazine Winter 2015
The introduction of GM seeds could dramatically improve
maize production in Africa. The average yield of maize in
Africa is about two tons per hectare, one-fifth the average yield
in North America. Many African farmers keep their seeds for
replanting rather than buying them anew every season. This
practice spreads disease, and accounts for a large percentage of
yield loss. Insects are a major problem, too. They are vectors for
transmitting diseases to plants. We could double yields by planting maize genetically modified to express the Bt trait for insect
resistance. In addition, incorporating the technology into the
seed simplifies the diffusion process. Farmers already know how
to handle seeds, so they can readily benefit from the technology
without radically altering their way of life.
BD: The development of a genetically modified sweet potato was
your first project, but it failed in field trials in 2004. What are
the prospects for reviving it?
FW: As I said, I focused on the sweet potato because it was
heavily infected and because warm winters provided no way to
break the infection cycle. We explored vaccinating against aphidborne viruses so farmers could continue to share seeds. The first
field trial failed to confer durable resistance because the virus
infecting sweet potato plants in Africa was more virulent than
the strain we used to modify the plant, which came from a clone
being tested at the University of North Carolina. Unfortunately,
we couldn’t continue the research because funding dried up.
Research to develop an effective vaccine against the sweet potato
virus continues in Uganda. It is related to my earlier work,
but I’m not personally involved in the follow-up. In any case,
the history of the sweet potato project illustrates some of the
obstacles confronting African researchers.
BD: Are there points of light? Current projects with promise?
FW: There are. Africa Harvest is currently working with Pioneer,
Sorghum is an important African staple. Africa Harvest is developing a biofortified variety.
a DuPont company, on the biofortification of sorghum. It is
similar to the Golden Rice project. We are trying to enhance
nutritional value. We have genetically modified the plant
to increase its vitamin A content. This is important because
communities in the driest parts of Africa rely on sorghum as a
staple crop since it is drought-resistant. But because sorghum
lacks essential micronutrients, people in these communities can
suffer from blindness caused by vitamin A deficiency, or anemia
due to a lack of iron. There is a dedicated website for the Africa
Biofortified Sorghum Project: biosorghum.org. The project was
started with funding from the Bill and Melinda Gates Foundation. Further funding from the Howard G. Buffett Foundation
supported advanced technology development.
BD: Your book, Biotechnology in Africa, discusses the response
of African governments to the potential uses of GM technology.
What are some of the challenges and prospects?
FW: A lot of money is being poured into research in Africa, but
disseminating that research to farmers is very poorly funded.
African farming is small-scale. Growers need to be educated
and nurtured. They need guidance. Without addressing these
needs, it will be very hard to make improvements in African
agriculture, no matter how much money is spent on research.
This has been my main punch line for some time: we need to
expand financial support for technology diffusion. We need to
reach out effectively to farmers and local communities. From
a distance it may seem otherwise, but most African countries
have publicly funded biotechnology laboratories. The science
is not the problem. Rather, it is a lack of investment, and more
importantly, a lack of understanding regarding the complexity of
getting GM products to market, mainly due to the high cost of
the regulatory process. African universities are doing good work,
but they are constrained by the great expense of compliance with
national and international regulatory requirements.
Overcoming the pervasive influence of anti-GM activism is
another big challenge. Anti-GM groups are hampering progress
by propagating fear. They claim that GM seeds are instruments
of imperialism and corporate control. They say that big multinational companies want to control the seed because it enables
them to dominate Africa by economic and technological means.
They also continue to recycle discredited studies that purport
to show evidence of harm caused by genetically modified
products—severe allergic reactions, cancers, and autoimmune
disorders. Many politicians are captive to this kind of fear
mongering. It is true here in Kenya. GM food imports have been
banned in this country. This is unfortunate because government
support is critical if the continent is to benefit from GM technology. Without political will, you can’t commercialize a product
in Africa. GMOs are so highly politicized that the science or
technology alone is not sufficient.
BD: You mentioned the high costs of regulatory approvals.
Have they effectively barred public institutions from introducing beneficial technologies?
FW: Yes, but the door is not entirely closed. Four African
countries have approved GM crops: Burkina Faso, Sudan, South
Africa, and Egypt. Many others are putting reasonable regulatory frameworks in place. The Sudan, for instance, has gotten
up to speed very quickly with GM technology from China. In
addition, young Africans are gaining knowledge through the
Internet. They are becoming more sophisticated. A critical
mass is forming. I believe that the next generation of politicians
assuming power in Africa will be more open to new technologies. So there’s hope for the future. African biotechnologies are
coming of age. We’ve made a big investment, and I believe it will
come to fruition.
BD: Thank you, Dr. Wambugu.
FW: My pleasure, Brian, thank you.
Winter 2015
LSF Magazine 27
Global Biotech Centers
Biopolis:
Singapore’s Scientific Tiger
An ambitious plan to foster public-private R&D collaboration
S
ingapore became a sovereign democratic state when
it withdrew from the Republic of Malaysia in 1965.
Over the next two decades, free trade policies, a low
debt burden, and export-oriented industries transformed the national economy into a dynamic high
growth Asian “tiger.”
The city-state’s prosperity has been sustained into the twenty-first century, thanks in part to public and private commitments
to participation in the emerging global knowledge economy.
Philip Yeo can take some credit for it. A PhD systems engineer
with a Harvard MBA, Yeo was appointed chairman of Singapore’s
Economic Development Board in 1986. He became one of the
chief architects of national economic policy.
Yeo pressed the government to dedicate human, intellectual,
and material resources to high tech innovation. In 2000, he
became the founding chairman of Singapore’s Agency for Science,
Technology, and Research (A*STAR), and adopted projects in the
life sciences and biotechnology to showcase Singapore’s innovative
capacities.
With a budget of US$1.15 billion, Yeo implemented the
Biomedical Sciences Initiative (BMSI), an ambitious plan to foster
academic-industry collaborations. The mission was to establish
Singapore as a global leader in healthcare delivery, biomedical
innovation, and biopharmaceutical outsourcing services. The
initiative gave rise to Biopolis, a science park designed to help
Singaporean scientists and industrial partners meet or exceed
global standards of excellence in research, product development,
manufacturing, and clinical testing.
Nobel laureate Sydney Brenner coined the name. He was
impressed with Singapore’s commitment to science, and taken by
Yeo’s notion of a bio-city. He was eager to serve as a consultant:
“This was to be an experiment in developing state-of the-art
biomedical research at a national level in what was a third world
country not too many years before. I viewed it as an exciting
venture and an exciting opportunity.”
Yeo located Biopolis near the National University of Singapore.
28 LSF Magazine Winter 2015
Left: Philip Yeo
was the founding
chairman of
Singapore’s Agency
for Science,
Technology, and
Research (A*STAR)
He explained that “the close proximity of talent from corporate
laboratories, startups, and public research institutes will create a
vibrant R&D environment to spur new discoveries and speed their
translation into applications.” He made a concerted effort to attract
world-class scientific talent. Edison Liu, former head of clinical
sciences at the US National Cancer Institute, was his first five-star
recruit. Others followed.
The Biopolis research ecosystem fosters academic-government-industry collaborations
The first phase of construction at Biopolis raised seven
buildings at a cost of US$290 million. The 600,000 square foot
complex was completed in 2003. Five of the structures housed
A*STAR research institutes—the Bioinformatics Institute, the
Bioprocessing Technology Institute, the Genome Institute, the
Institute of Bioengineering and Nanotechnology, and the Institute
of Molecular and Cell Biology. The institutes employed more than
2,000 state science workers. The two other buildings provided
laboratory and office space to private companies.
Multinational pharmaceutical corporations arrived to lease
space and set up operations. Eli Lilly and Company was the first.
GlaxoSmithKline (GSK) and Novartis soon followed. Lilly opened
a systems biology laboratory, GSK established a center for research
on cognitive and neurodegenerative disorders, and Novartis
created an institute for research on tropical diseases. Each addition
was an important validation of Yeo’s vision.
Investments in Biopolis returned early dividends when an outbreak of severe acute respiratory syndrome (SARS), a potentially
deadly viral illness, originated in China and spread into Southeast
Asia. In March of 2003, the virus arrived in Singapore and tested
the city-state’s public health system. Two hundred eighty-three
persons were infected. Thirty-three died.
It could have been much worse had not teams of scientists at
Biopolis’ Genome Institute worked in collaboration with private
firms, Roche and Genelabs, to develop a rapid immunodiagnostic
test. Singaporean authorities used the product to identify and
isolate infected patients, and slow the spread of the virus.
Biopolis continued to expand. Many new facilities have been
added to the park over the past ten years, including four major
structures to house institutes for research in immunology, medical
biology, molecular engineering, and neurology, commercial offices
and laboratories, and retail businesses. Still on the drawing board
are twin towers that will provide additional lab space to meet
swelling demand.
Today, Biopolis is an important part of Singapore’s US$30
billion biomedical economy. During its eleven years in operation,
it has created jobs, improved Singaporeans’ quality of life, and
carved out a spot for the city-state on the world’s scientific map.
More than fifty life science companies are involved in translational
and clinical research in and around Biopolis, in collaboration with
A*STAR institutes and life scientists and biomedical researchers at
the National University.
“Biopolis was conceived as a key pillar of Singapore’s economy,” says Lim Chuan Poh, A*STAR’s current chairman. “That
conception has become a reality. Today, it is a thriving eco-system
of public research institutions and corporate labs and a vibrant
community of local and international biomedical scientists
carrying out world-class research.” Winter 2015
LSF Magazine 29
Global Biotech Centers
The “Cambridge Phenomenon”
Cottages, Colleges, and Science Parks
Biotechnology in England’s green and pleasant land
B
ritain got off to a slow start in commercial biotechnology, especially considering
the importance of British scientists and
research institutions in the brilliant rise
of molecular biology. But the country has
made a comeback.
One of the great technical pillars of the life
sciences industry, hybridoma technology, was
invented in 1975 at the British Medical Research
Council’s famed Laboratory of Molecular Biology
(LMB) in Cambridge. It was a method for producing
monoclonal antibodies. The inventors, Swiss cell
biologist Georges Köhler and Argentine biochemist
César Milstein, reported the breakthrough in a 1975
paper in Nature. They concluded the article by stating
that the technique “could be valuable for medical and
industrial use.”
That turned out to be true. Today, monoclonal
antibody products generate annual revenues in excess
of $80 billion worldwide. Although he was personally
ambivalent about privatizing academic research,
Milstein approached the Medical Research Council
(MRC) to recommend that a patent application be
filed. After a cursory investigation, an MRC reviewer
judged that the invention did not merit the filing
expense. Americans rushed in to commercialize the
technology.
A sympathetic stateside observer, Harvard
immunologist Fred S. Rosen, wrote: “Anonymous
administrators responsible for such decisions should
be publicly exposed for their bad judgment and incompetence. Perhaps the time has come to restore the
stockades and gallows at Tyburn as a way of reintroducing accountability.” The history of biotechnology
might look very different today had it begun with the
British in control of monoclonal antibodies.
30 LSF Magazine Winter 2015
In any event, Britain is back in the biotech race,
and Cambridge is its swiftest runner. It’s a medieval
town—William of Normandy built a castle there
in 1068 and Cambridge University was founded
in 1209—but in twenty-first century biology, it is
state-of-the-art.
The university’s life science departments vie
with Harvard, MIT, and Stanford for top rankings,
and many other world-class academic institutions,
including Addenbrooke’s Hospital, the Babraham
Institute, the European Bioinformatics Institute, the
LMB, and the Sanger Institute (formerly the Sanger
St. John’s Chapel,
Cambridge University.
The university was
founded more than
800 years ago.
The British Medical Research Council’s Laboratory of Molecular Biology opened a new facility in 2013. It was paid for, in part, by royalties from sales of
the institution’s antibodies.
Centre), make Cambridge a vital center of basic biological
research.
In the late 1960s, technology spillovers from university
laboratories created the “Cambridge Phenomenon,” an efflorescence of entrepreneurship and innovation across the Fens.
The Cambridge Science Park was built in 1970 to accommodate
university spinoff companies and corporations engaged in
university-industry research partnerships.
Initially, most of the action was in electronics and computing—the area became known as “Silicon Fen”—but life science
startups began to appear in the 1980s. Today, the park serves as
an outpost for big biotech and big pharma companies, including
Amgen, AstraZeneca, Bayer, Genzyme, and Sigma-Aldrich.
In addition, Granta Park, established in 1997 in nearby
Great Abington, lists Gilead Sciences, MedImmune, and Pfizer
Regenerative Medicine as tenants, and the Babraham Research
Campus serves as an incubator for more than thirty small
biomedical, biotechnological, pharmaceutical, and healthcare
services companies. Biotechnology has become an important
part of the “Cambridge Phenomenon.”
And fittingly, the town has acquired all the accoutrements of
a thriving high tech cluster and innovation ecosystem. Leading
British, European, and American venture capital firms have
opened offices in Cambridge, and a strong base of angel investors
has emerged to support local business development. Some have
organized. The Cambridge Angels, for example, are a group of
high net worth investors with experience as successful entrepreneurs in internet, software, infotech, and biotech ventures.
The university offers a wide range of specialized educational
offerings in the life sciences and the business of biotechnology,
and local nonprofit organizations such as the Cambridge
Network and Biology in Business have generated training
and networking programs for students, scientists, and biotech
professionals.
One Nucleus, a Cambridge-based trade association with
more than 500 member organizations, is working to integrate
British companies into global life sciences, biotech, and healthcare networks. The group was formed in 2010 by the merger
of the London Biotechnology Network (LBN) and the Cambridge-based East of England Biotechnology Initiative (ERBI).
CEO Harriet Fear has established relationships with sister
organizations in the United States, Europe, Asia, and Australia.
So, the Cambridge cluster of biotech firms has become fully
networked and globally connected. It has talent, infrastructure,
and access to capital. Local leaders now want to avoid repeating
past mistakes—they don’t want to let big fish technologies swim
away down the River Cam.
Last year, Cambridge Innovation Capital (CIC), a partnership
between Cambridge University, several London investment
banks, and ARM, a Cambridge-headquartered semiconductor
and software multinational corporation, was established for this
express purpose.
The firm intends to distribute £50 million over three years
to discovery stage life science startups built around Cambridge
University technologies. According to CIC chairman Edward
Benthall, the objective is to encourage Cambridge University
spinoff companies “not to flip technologies to US corporations,
but rather to build big businesses.”
Winter 2015
LSF Magazine 31
Global Biotech Centers
DuBiotech:
Watering a Desert Flower
Dubai invests in infrastructure and offers incentives for foreign investment
D
uBiotech (the Dubai
Biotechnology & Research
Park) is part of an effort to
attract foreign investment,
diversify the oil-dependent
economy of the United Arab Emirates
(UAE), and establish Dubai, the country’s
most populous city and emirate, as a
key node in global healthcare and high
technology networks.
Dubai has been a hub of Persian Gulf
commerce since the late nineteenth
century. If the hopes of the emirate’s
economic planners are realized, it will
soon become a preferred location for
foreign producers of goods and services
targeting emerging markets in the Middle
East, Asia, and Africa.
DuBiotech is the brainchild of His
Highness Sheikh Mohammed Bin Rashid
Al Maktoum, vice president and prime
minister of the UAE and ruler of Dubai.
“We have been working very hard to
bring our country and society into the
knowledge age,” he said at a launch event
for the park in February 2005. “It is a
historic transformation. It entails reconsidering all our activities, regulations,
and rules for work and education, as well
as the structure of our government and
economy.”
The Sheikh’s objective is to make DuBiotech the largest center of life sciences
research and development in the Middle
East. Foreign companies have many
incentives to become part of it. The park
32 LSF Magazine Winter 2015
is one of Dubai’s twenty-two free trade
zones. The emirate allows 100 percent
foreign ownership and full repatriation of
profits and capital to firms that establish
a presence in the zone. Firms are also
exempt from customs duties on imported
goods and services and from all corporate
income taxes for fifty years.
DuBiotech offers attractive leasing
options and a host of client services,
including expedited registration and
licensing of products for distribution and
sale in the UAE, guidance on environmental, public health, and safety regulations, and matchmaking help to facilitate
partnerships with local and regional
companies and organizations.
The project came together quickly
when the details of the incentive package were announced and Germany’s
Frankfurt Biotechnology Innovation
Centre agreed to assist in infrastructure
development. The park has been designed
to accommodate a variety of businesses,
from startups to multinational corporations. Its office and laboratory spaces can
be tailored to meet virtually any set of
needs.
The key ingredients that Dubai and
DuBiotech lack are a critical mass of
scientific talent and an appropriately
trained workforce. As Mohammed Yahia,
editor of the Abu Dhabi periodical,
Nature Middle East, points out, the nature
of these shortcomings is such that it may
take an extended period, many years,
“We have been
working very hard
to bring our country
and society into the
knowledge age.”
Sheikh Mohammed Bin Rashid
Al Maktoum
Vice president and prime minister of
the UAE and ruler of Dubai
before the success of DuBiotech’s efforts to become a gateway to
eastern markets can be assured. “To create such a hub and make
sure it is sustainable,” he says, “you need to build up Dubai’s
science community. You need to have a robust scientific culture
in place, and that is not created overnight.”
Marwan Abdulaziz Janahi, DuBiotech’s director of business
development acknowledges the challenge. “We are trying to
bridge this gap,” he says. In 2006, the University of Sharjah, one
of the UAE’s leading academic institutions, joined the project
and pledged to foster university-industry collaborations. At the
press conference announcing the agreement, which included
plans to expand and improve academic programs for biotech
workforce development, DuBiotech’s executive director, Abdulqader Al Khayat, said, “Research done at universities has been
one of the key drivers of the biotech industry and we are keen to
develop this here.”
Regional science and education may or may not become a
competitive advantage, but DuBiotech has continued to grow.
In 2007, it broke ground for the construction of a state-ofthe-art laboratory and office complex, and the municipal
government, in partnership with Mubadala Development, a
diversified investment company controlled by the government
of Abu Dhabi, and LabCorp, an American clinical laboratory
operator, established a branch of Dubai’s National Reference
Laboratory in the park. Light manufacturing, packaging, and
warehouse and shipping facilities were added in 2010.
More than 150 life sciences companies currently reside
in DuBiotech, including leading American and European
biopharmaceutical corporations such as Amgen, Bayer, Bristol-Myers Squibb, Sanofi’s Genzyme, Merck Serono, and Pfizer.
Many have set up regional headquarters in DuBiotech, and
partnered with local contract manufacturers and regional
distributors.
The park’s new headquarters are slated to open in 2015. Like
all of DuBiotech’s buildings, the 500,000 square foot, twenty-two
story structure will be green—LEED-certified for energy
efficiency. Looking ahead, DuBiotech’s planners have drawn up
blueprints for a self-contained biotech city with residential housing, schools, a hospital, retail sales and entertainment centers,
and a nature preserve.
The science park already has an impressive roster of companies in residence, and with 30 million square feet of space in
which to grow, DuBiotech may succeed in turning Sheikh Al
Maktoum’s dream into a reality.
An artist’s rendering of Dubiotech headquarters, currently under
construction, slated to open in 2015
below: Dubai, population 2.1 million
Winter 2015
LSF Magazine 33
Global Biotech Centers
BGI:
“Experience a Brilliant Life”
Startup culture in Shenzhen’s “biology factory”
I
f you’ve heard of Shenzhen – a city of fifteen million people
in Guangdong province in southern China – you’ve probably heard of its electronics industry. In 1979, Shenzhen
became China’s first Special Economic Zone: a city designated for entrepreneurial capitalism and trade with Europe and
North America.
With three hundred skyscrapers built in the 1980s alone,
Shenzhen was transformed from a small fishing town on the
Pearl River delta into a sprawling city. In 2014, Shenzhen’s boom
continues apace. Its location helps. Only the Shenzhen River
separates the city from Hong Kong’s prosperous New Territories.
Cross-border traffic on rail, motor vehicle, and pedestrian
bridges is heavy.
Shenzhen’s economic explosion has been powered by
electronics manufacturing. Foxconn – the Taiwanese company
that assembles Apple’s iPhones and iPads – owns Shenzhen’s best
known factory complex, but many other electronics, computing,
and telecommunications firms, Chinese and foreign, have operations in Shenzhen, including Dingoo, Hasee, Huawei, Netac,
Skyworth, Coolpad, and ZTE.
The prospect of well-paid work has attracted young people
from all over China. The streets of downtown Shenzhen have the
feel of an oversized university campus—everyone seems under
thirty.
Recently, Shenzhen has also begun to attract international
attention for its biotechnologies. In 2007, BGI (formerly the
Beijing Genomics Institute) relocated its headquarters from the
capital to Shenzhen. The city government offered the company
tax incentives and three years of free rent on a building in its
Beishan Industrial Park.
BGI has expanded rapidly since then, under the leadership
of cofounder and Chairman Henry Yang. It now employs 3,000
people in a wide variety of ambitious, large-scale initiatives,
including the International Cancer Genome Project, the 1,000
Mendelian Disorders Project, the 1,000 Plants and Animals
Genome Project, the 10,000 Microbial Genomes Project, as well
34 LSF Magazine Winter 2015
Hong Kong’s next-door neighbor, Shenzhen, is known as China’s Silicon
Valley. More than 300 skyscrapers were built in the city in the 1980s.
as efforts to sequence the genomes of the SARS virus, the giant
panda, the silkworm, and plants, including rice, cucumber, and
soybean.
BGI is also employing its high-throughput sequencing and
bioinformatics tools to ramp up capabilities in transcriptomics,
proteomics, and metabolomics. According to its leaders, the
organization’s primary goals are to contribute to better understandings of human health and to reduce the costs of health care,
both in China and overseas.
Some observers are skeptical of the rhetoric, but the firm
has begun to deliver. For example, BGI and Shenzhen health
Francis Collins (center), director of the US National Institutes of Health, with BGI employees during a 2010 visit to Shenzhen
authorities have worked together to provide non-invasive prenatal genetic tests to local residents at prices that ensure coverage
under public health insurance schemes.
BGI’s employees are inspired and motivated by the mission.
Several of the company’s arms (such as BGI Tech, BGI Health,
and BGI Agriculture) are operated as for-profit companies, but
the enterprise as a whole remains not-for-profit, and much of
its work is funded by government grants. At present, profits
generated by BGI’s commercial operations are reinvested to fund
research and development.
The nature of BGI’s work invites comparisons with Shenzhen’s electronics industry. BGI is often called a “biology
factory,” which does for genome sequencing what Foxconn and
others have done for consumer electronics. Many of its projects
are notable for their size and their scaling trajectories—more
and more people and machines are being deployed to sequence
genomes at accelerating rates with increasing efficiency.
But the Shenzhen labs feel more like a start-up than a factory.
There is little structured discipline. Staffers are free to come,
go, and work as they please, working late into the night and
sleeping through the mornings, or napping at their desks in the
afternoon.
The hierarchy is minimal. Business attire is not required and
rarely glimpsed. Individuals are judged on their demonstrated
abilities to work in teams that generate high quality publications
and innovative technologies.
Shenzhen has become China’s Silicon Valley, and BGI aspires
to be its Google. Google’s mantra is “Do No Evil.” BGI urges
employees to “Build a Magnificent Industry” and “Experience a
Brilliant Life.”
The opening scene of a recent documentary film, Bregtje
van der Haak’s DNA Dreams (2013), shows BGI Chairman
Yang delivering a rousing “I have a dream” speech at the 2011
International Conference on Genomics. His is a technohumanist dream of solving the world’s health problems through
biomedicine.
Illumina Hiseq 2000 sequencers at BGI
BGI’s employees believe in Yang’s vision. They are highly
educated, driven by a desire to have an impact on the world, and
deeply devoted to their jobs. Their social lives revolve around the
organization’s community-building efforts: social clubs, sports
and fitness teams, extracurricular hobby and activity groups.
Many have brought their families (including parents and siblings) to live with them in BGI housing. This all-encompassing
environment breeds devotion to the organization’s goals.
At the moment, BGI seems enriched in possibilities. It is
producing a quarter of the world’s genomics data, and the future
may be wrapped inside its youthful and ambitious gene dreams.
Winter 2015
LSF Magazine 35
Global Biotech Centers
La Fundación Ciencia & Vida:
Bioscience and Industry in the Andes
A unique organization moves Chile into the global knowledge economy
C
hilean biochemist Pablo Valenzuela is an original
biotech pioneer. With scientific colleagues Bill
Rutter and Ed Penhoet, he cofounded the Chiron
Corporation in the San Francisco Bay Area in 1981.
Rutter served as the company’s chairman. Penhoet
was appointed president and CEO.
As vice president of research and development, Valenzuela directed a remarkable series of scientific breakthroughs,
including the invention of the first recombinant vaccine for
hepatitis B, the first complete sequence of the HIV genome, and
the discovery of the hepatitis C virus.
Throughout his tenure at Chiron, Valenzuela harbored a
desire to spark scientific, biomedical, and industrial innovation
in his homeland. In 1986, he established BiosChile in Santiago,
a commercial manufacturer of scientific tools—reagents, laboratory equipment, instrumentation, and medical diagnostics. It
was Chile’s first molecular biology company.
Five years later, BiosChile created a San Francisco Bay Area
subsidiary called Austral Biologicals to manufacture a wide range
of proteins used in biological and biomedical research—antibodies,
antigens, growth factors, and transcription factors. In 2001, the
company spun out its clinical diagnostics business to form a new
company in partnership with Grupo CH Werfen SA, a Spanish
firm. Together, the three units are called Grupo Bios.
In 1997, Valenzuela founded a nonprofit research institute
in Santiago, the Fundación Ciencia y Vida (FCV), with his
wife, Dr. Bernardita Méndez, who also served Chiron as vice
president of regulatory and quality affairs. They formed the
organization to conduct world-class biological research to spur
the development of a national biotechnology industry, and to
help Chile move into full participation in the global knowledge
economy.
The FCV has assembled a wide range of programs to
advance Chilean science, facilitate academic-industry
Santiago, Chile; population 6.3 million
36 LSF Magazine Winter 2015
Pablo Valenzuela
and Bernardita
Méndez, founders
of La Fundación
Ciencia y Vida
partnerships, foster scientific entrepreneurship, and enrich
Chilean science education. Valenzuela, Méndez, and committed colleagues in Santiago are true believers: they are confident
that scientific progress will drive growth in the Chilean
economy, and contribute to the vitality and welfare of Chilean
society and culture.
FCV researchers conduct basic scientific investigations,
but they also seek innovative solutions to practical problems
confronting Chilean industries. The Chilean economy is based
largely on natural resource extraction. Its largest industrial
sectors are agriculture, aquaculture, mining, and forestry.
The FCV has established research programs designed to shift
the basis of growth in these areas from intensified resource
exploitation to advances in knowledge and technology.
The goal is to reduce environmental degradation and
introduce sustainable resource management systems while
improving the quality and quantity of industrial outputs and
enhancing Chile’s ability to compete in global markets.
The FCV’s industrial research projects have included efforts
to engineer trees for improved cellulose and wood production,
microbes for “bioleaching” in the industrial recovery of copper
and other metals, and vaccines to fight bacterial and viral infections that reduce yields in fruit cultivation and salmon farming.
The development of Chile’s human and intellectual capital
is another important part of the organization’s mission. In
many different ways, the Fundación works to create environments conducive to excellence in scientific discovery and
technological innovation.
The FCV’s long-term strategy for strengthening Chile’s
scientific culture entails investments in grassroots science education. Several programs are underway. To achieve near-term
results, the Fundación has established international exchange
and training programs for PhD students in the sciences at
Chilean universities.
These programs include opportunities for learning not just
about science, but about the business of biotechnology as well.
At the FCV, students can take courses in entrepreneurship,
management, finance, regulatory affairs, technology transfer
policy and practice, and intellectual property law.
And in order to stimulate public and private investment
in basic and applied science, technology development, and
entrepreneurial ventures, the FCV is working to educate
Chile’s political and business leaders about the importance of
the life sciences for the nation’s economic future. The message
has been received. In 2006, the Chilean government allocated
funds to open a science and business park at the FCV to attract
and support entrepreneurial biotech ventures, both foreign and
domestic.
The park currently provides laboratory and office space for
several companies headquartered in the United States, new
Chilean companies affiliated with Start-Up Chile, a government program established to assist technology ventures, and
spinoffs from the FCV, such as Andes Biotechnologies, which
Valenzuela founded in 2008 with long-time colleagues, biochemists Luis Burzio and Arturo Yudelevich, to pursue novel
anticancer therapeutics.
The FCV’s programs in education, basic science, applied
science, and business creation are helping Chile build a scientific infrastructure and a self-sustaining innovation ecosystem
that—despite being geographically remote—is integrated into
the global knowledge economy.
When Pablo Valenzuela and Bernardita Méndez created the
Fundación Ciencia y Vida, they envisioned a thriving Chilean
biotech industry. It may be taking shape.
Winter 2015
LSF Magazine 37
Hamsters were instrumental in the development of
molecular biology during the second half of the twentieth
century, literally. Females imported from China donated
ovary cells that enabled academic scientists to overcome
technical obstacles and make early progress in the study
of mammalian genetics. Later, the cells enabled industrial
scientists to overcome technical obstacles and make early
progress in the production of recombinant proteins. Today,
Chinese hamster ovary (CHO) cells remain indispensable
tools in both science and industry, and they may help
translational scientists, pharmaceutical developers, and
bioprocess engineers solve intractable problems in twentyfirst century biomedicine and healthcare economics.
38 LSF Magazine Winter 2015
Robert Briggs Watson in the 1920s
In the late fall of 1948, the Chinese civil war was approaching
its climactic final scenes. As Mao Tse-Tung’s communist forces
marched across the country’s northern provinces, a truck
carrying a nondescript crate made its way from Peking to the
republican capital of Nanking. The crate contained twenty
compartments lined with wood shavings; each housed a Chinese
hamster. There were ten males and ten females.
The hamsters were a gift from Dr. H.C. Hu of the Peking
Union Medical College to Dr. Robert Briggs Watson, an
American physician studying malaria in Asia for the Rockefeller Foundation’s International Health Division. Watson was
retrieving the animals for Victor Schwentker, a skilled rodent
breeder in upstate New York. Schwentker had learned that the
hamsters were valuable in biological and biomedical research.
He also knew that it would be impossible to procure them after
the Communists came to power.
On December 6, the hamsters were delivered to Watson’s
doorstep. Nanking was being evacuated. Only the Yangtze River
separated the city from the Maoists. Watson was preparing to
flee, while suffering from dysentery and a respiratory infection.
On December 10, he packed his laboratory equipment into a
station wagon. He packed the hamsters as well.
Against the advice of Chinese friends and the American
Embassy, he braved an eleven-hour drive through blinding rain,
first to Wuxi and then on to Shanghai, narrowly avoiding mudslides and roving bands of Communist troops, as the hamsters
chattered away in their compartments.
The hamsters escaped China on December 12, 1948, on one
of the last Pan-Am flights out of Shanghai. After the Maoists
claimed victory and established the new People’s Republic, Watson was accused of “war crimes” by the Chinese Germ Warfare
Commission and tried in absentia for conspiring with Chinese
nationalists on behalf of the US government to carry out a
biological attack. H.C. Hu was also charged. He was convicted
and sent to a detention camp for six months of “reeducation.”
The hamsters landed in San Francisco, and were shipped to
Schwentker’s farm in New York. More than six decades later,
cell lines originating from Hu’s hamsters continue to serve as
important tools in biomedical research and living factories for
the manufacture of life-saving drugs.
A reluctant lab animal
In 1919, Dr. E.T. Hsieh of the Peking Union Medical College
became the first researcher to bring Chinese hamsters into the
laboratory. He needed animals to inoculate, in order to distinguish strains of disease-causing pneumococcal bacteria. Mice
were scarce, but hamsters were abundant in the fields surrounding Peking.
Five years later, Jocelyn Smyly, an Irish doctor working at
the college, and American colleague Charles Young showed
that Chinese hamsters were easily infected with the protozoan
parasites that cause leishmaniasis (black fever). Soon, researchers throughout China were using captured Chinese hamsters
to study a range of infectious diseases including tuberculosis,
influenza, diphtheria, and rabies.
Unfortunately, the rodents couldn’t be bred in captivity. Dr.
Marshall Hertig made several attempts at Peking Union beginning in 1928, while he worked with Smyly and Young on leishmaniasis. When he left, he shipped 150 hamsters to the United
States to establish a colony at the Harvard Medical School.
The attempt was an abysmal failure. The animals survived the
bitter New England winter, but did not reproduce. Hertig built
natural mating burrows in the basement of Harvard’s Comparative Pathology building, and later in the grassy yard outside, but
to no avail.
Scientists did not give up trying to domesticate and breed
Chinese hamsters. They recognized that the hamster was an
exceptionally useful animal model for genetic research. They
become sexually active at two months, and their gestation period
is only three weeks. Several generations could be studied in a
single year.
In 1943, Italian geneticist Guido Pontecorvo came up with
another good reason for using them. He spread metaphase hamster cell nuclei on microscope slides and—with the low-resolution instruments available to him at the University of Glasgow’s
Department of Zoology—counted fourteen large chromosomes.
Pan-Am routes in the Americas and across the Pacific in 1947
Winter 2015
LSF Magazine 39
Watson’s Diary
December 1948,
Nanking to Shanghai
40 LSF Magazine Winter 2015
Mice have forty. Rats have forty-two.
The size and low number of the hamster chromosomes facilitated cytogenetic research. Given the methods of the day, they
were the easiest rodent chromosomes to identify, characterize,
and map. Geneticists came to covet the animals, and persisted in
breeding experiments.
Hamster whisperers
Victor Schwentker decided to try his hand, too. He had
a thriving animal supply business in Brant Lake, New York,
seventy miles north of Albany. He bred mice, rats, voles, moles,
rabbits, hamsters and guinea pigs. By 1948, he had become
the largest supplier of animals to biological laboratories in the
northeastern United States.
Schwentker knew that demand for Chinese hamsters would
be high. He found Robert Briggs Watson in China, through contacts among his biomedical research customers, and arranged to
have some of the animals shipped to the United States.
Where others had failed, Schwentker managed to domesticate
and breed the creatures in captivity. The process entailed a great
deal of labor intensive taming. Within two years, Schwentker
had a thriving colony, the first established outside of China.
Word spread, and researchers started placing orders.
George Yerganian, a graduate student at Harvard, was one of
them. He was conducting doctoral research on plant genetics,
but in 1948, he found Pontecorvo’s paper in a Harvard Library,
and realized that the hamsters’ low chromosome count would
make the species a preferred experimental model. He purchased
several animals in order to study their estrous cycles and mating
habits.
In 1951, Yerganian began working on a postdoctoral fellowship in radiation biology at the Brookhaven National Laboratory
on Long Island. He gained access to microscopes more powerful
than those used by Pontecorvo and determined the correct
number of chromosomes in Chinese hamsters: twenty-two. Two
other cytogeneticists reached the same conclusion independently, Robert Matthey at the Université de Lausanne in Switzerland,
and Leo Sachs at the John Innes Institute in Norwich, England.
Schwentker discontinued sales of Chinese hamsters in 1954.
They were popular with researchers, but the animals are naturally solitary, and females became aggressive in captivity. Raising
and breeding them was difficult and laborious. Schwentker
Diabetic Hamsters
In the late 1950s, George Yerganian noticed that repeated inbreeding produced lines in which the hamsters
uniformly developed symptoms of adult-onset diabetes,
including periodontal, pancreatic, and retinal problems.
For the next decade, he published papers on these and
other pathologies with collaborators from Boston area
hospitals and universities, and widely distributed diabetic hamsters to research laboratories and pharmaceutical
companies in Europe and North America. Teams at the
Upjohn Company of Kalamazoo, Michigan and the
Charles H. Best Institute in Toronto bred the animals
and established new colonies. Eventually, biomedical researchers around the world adopted the Chinese hamster
as a standard animal model in which to study the appearance and progression of spontaneous diabetes. Yerganian’s Boston University vivarium was the point of origin.
never published or shared his breeding techniques, but by 1954,
Yerganian had devised his own hamster-taming methods.
Yerganian had accepted a joint appointment the year before
at Boston University and the Children’s Cancer Research
Foundation (which later became the Dana-Farber Cancer
Institute). With funds granted by the National Cancer Institute,
he established a breeding center and began distributing hamsters
to scientific colleagues. For the next decade, he was the sole
supplier of Chinese hamsters to biomedical research institutions
in the United States.
In 1983, Yerganian launched a private company, Cytogen
Research and Development, Inc., to supply Chinese hamsters to
public, non-profit, and commercial research laboratories. For
many years, the company’s facilities were located on the Brandeis
University campus in Waltham, Massachusetts.
“The mammalian E. Coli”
In the 1950s, studies in human and animal genetics were
hindered by a lack of mammalian cell lines. Researchers had
tried for decades to grow ex vivo animal cell cultures, but cells
typically survived for just a few division cycles. Efforts to generate and maintain continuously growing mammalian cell lines
ended routinely in failure and frustration. Contamination by
bacteria and molds was common, but even when this problem
was solved in the 1940s by the introduction of antibiotics, the
long-term viability of animal cell cultures did not improve.
There were exceptions. In 1943, Wilton Earle and colleagues
propagated the first continuously growing mammalian cell
line, mouse L, at the National Cancer Institute, and in 1951, Dr.
George Gey grew the first immortal human cells, the famous
HeLa line, at the Johns Hopkins University School of Medicine.
But these cultures were mixtures of heterogeneous cells, many
of which contained chromosomal abnormalities. For many
inquiries, Mouse L and HeLa cells had limited utility.
Important advances were made in 1948 when
A Chinese hamster
Winter 2015
LSF Magazine 41
Dr. Theodore Puck
Earle’s lab established a clonal (genetically homogenous) mouse
L culture, called mouse L929, and in 1955, when geneticist
Theodore Puck managed to isolate and propagate single clones
and establish clonal HeLa cultures at the University of Colorado
School of Medicine in Denver.
Researchers in Puck’s laboratory went on to develop novel in
vitro culturing techniques, special growth media for mammalian
cells, a large collection of useful human and animal cell lines,
and methods for mutagenesis and gene mapping that enabled—
for the first time—studies of molecular genetics in mammalian
cells.
In 1957, Puck learned of the Chinese hamster and its
compact genome. He contacted George Yerganian and asked
for specimens. Yerganian sent a single adult female, housed in a
handmade box with a mesh top. She arrived by railway courier,
after riding trains for several days. No one could have predicted
how important this single hamster would become in the history
of the life sciences, biomedicine, and the biopharmaceutical
industry.
Puck removed an ovary, extracted a cell, and gently coaxed
it into expansion in a petri dish. It was the first culture derived
from a Chinese hamster. Puck found that with proper treatment,
CHO cell cultures grew quickly. The cells were hardy and could
be maintained indefinitely. By subcloning, Puck and a junior
colleague, Fa-Ten Kao, generated the CHO-K1 cell line, which
became a standard research tool in molecular and cell biology.
Labs from around the world requested cells from Denver,
and Puck distributed them freely. His CHO cell lines became the
gold standard for in vitro studies of mammalian biology. He took
to calling them “the mammalian E. coli.” Molecular genetics had
previously advanced mainly through studies of microbes—viruses, bacteria, and fungi. After 1957, thanks largely to Puck and the
unique properties of CHO cells, geneticists had new opportunities to study higher organisms.
Add sugar
In 1973 and 1974, University of California, San Francisco
biochemist Herbert Boyer and Stanford University geneticist
Stanley Cohen conducted a series of experiments that demonstrated the utility and power of recombinant DNA technology as
42 LSF Magazine Winter 2015
an instrument of genetic engineering. The invention set the stage
for the birth of the biotechnology industry.
Genentech, the first company established to commercialize
the technology, made headlines in 1978 and 1979 when it
reported the manufacture of medically useful peptide hormones,
first insulin and then human growth hormone, in bacteria, in
E. coli—naturally, because molecular biologists knew far more
about E. coli cells than other any kind. They had been studying E.
coli for decades. Researchers had developed an intuitive feel for
its behaviors, proclivities, moods, and reactions.
Genentech’s accomplishments were impressive, and they
stirred competition. Many molecular biologists were encouraged to reproduce the company’s success with other genes and
molecules of commercial value. A host of biotech startups sprang
up, endowed with sufficient capital to explore the potentially
lucrative new field.
After insulin and growth hormone, Genentech selected the
gene for tissue plasminogen activator (tPA) as a cloning priority.
So did several competitors. tPA is a blood clot dissolving protein.
It was considered a promising treatment for heart attacks. The
size of the potential market made it an enticing target.
Genentech scientists isolated the gene and plugged it into the
E. coli expression system that had produced insulin and human
growth hormone. This time, the result was different. Dennis
Kleid, one of the company’s early cloners, reports that the
bacteria made only half-hearted efforts to express the molecule.
“Just tiny amounts were detected,” he says, “and the protein
wasn’t folded properly.”
The failure was a reality check. Researchers at Genentech and
competing firms had hoped that simple prokaryotic cells would
be suitable for the commercial production of a wide range of
large, complex human proteins. The tPA experience gave them
pause.
The post-mortem drew attention to the many post-translational modifications that cells make to turn amino acid
chains into functional proteins. In human beings, the process
is complex; prokaryotic bacterial cells don’t possess the same
modification repertoires. In the tPA experiment, the molecule
hadn’t folded properly because E. coli isn’t fully equipped for
mammalian glycosylation.
Glycosylation is an enzymatic process in which sugar groups
are linked covalently to newly synthesized proteins. The sugars
cause the proteins to fold into stable, soluble forms. Early experiments with E. coli and other microbes taught gene cloners that
prokaryotic cells would not turn some heterologous (foreign)
gene products into biologically active molecules. tPA was one of
them.
The use of E. coli as a recombinant protein factory gave rise
to other sorts of problems. In 1980, for example, Genentech
came to a dead end in its quest to make a recombinant hepatitis
B vaccine. When company scientists inserted the gene for a viral
antigen into E. coli, the bacterium’s cellular machinery lurched
to a halt. Dennis Kleid remembers the mishap: “E. coli hated that
protein. The bacteria stopped growing. They just quit.”
The “Axel Patents”
On February 25, 1980, Columbia University inventors,
molecular biologist Richard Axel, microbiologist Saul
J. Silverstein, and geneticist Michael H. Wigler, filed an
application with the United States Patent and Trademark
Office (USPTO) for a patent on the “Wigler method” of
“co-transformation,” techniques for cloning and expressing heterologous genes in nucleated eukaryotic cells. The
Cohen and Boyer invention had described the re-engineering of non-nucleated prokaryotes, such as bacteria.
The Wigler method became a standard tool in mammalian biology and genetics, biomedical research, and commercial biotech manufacturing. The USPTO issued the
initial patent to Columbia University in 1983. The claims
were broad. They covered many different vectors and cell
types in the production of many different recombinant
proteins, and the university made nine additional filings
to extend, refine, and manage the patent estate. Ten firms,
including Amgen, Biogen, Genentech, and Genetics Institute, purchased licenses at low “early bird” prices. After
June 1, 1984, the university granted twenty-four additional licenses at a higher rate. By the time the patents
expired in August 2000, they had generated more than
$790 million in royalties.
The problem stemmed from the fact that E. coli does not
secrete proteins in large quantities. E. coli is a gram-negative
bacterium. Its envelope has two membranes, each with different
properties and functions. Genentech found that recombinant
proteins generally don’t cross both of these barriers without
assistance.
Consequently, recovery of proteins from E. coli entailed
lysing the cells, which complicated the purification process
and added to production costs. And in the case of the hepatitis
B project, the presence of hepatitis antigen in the cytoplasm
evidently caused enough discomfort that the cells stopped
dividing.
The problems with E. coli prompted Genentech to hire
Arthur Levinson, a postdoc at the University of California,
San Francisco, to investigate eukaryotic expression systems.
Levinson worked first to express the hepatitis antigen in yeast,
and then he turned to mammalian cells. By August 1981, he
had developed an experimental expression system in monkey
kidney fibroblasts.
Amping up
Mammalian cell expression was a wide-open field, but
Levinson wasn’t the first entrant. By the time he began experimenting with monkey kidney cells, Michael Wigler, Richard
Axel, Saul Silverstein, and colleagues at Columbia University
had already been putting recombinant DNA into mouse cells
for nearly three years. In 1979, they showed how to clone and
express genes coding for desired proteins along with selectable
markers. They filed a patent on the invention in February 1980.
But protein yields in early mammalian cell expression
systems were disappointing. Research conducted several years
before in the laboratory of Stanford biologist Robert Schimke
provided means of improvement. In 1976, as Schimke was
studying how cancer cells develop resistance to chemotherapeutic agents, one of his graduate students, Fred Alt, discovered
a phenomenon called gene amplification.
Alt observed that when mouse sarcoma cells were exposed
to methotrexate, a highly toxic cancer drug, most died but some
became resistant and survived. He and Schimke investigated
and found that methotrexate inhibits a vital enzyme called
dihydrofolate reductase (DHFR). Somehow, resistant cells
made tens or even hundreds of copies of the DHFR gene, which
produced enough excess DHFR to overcome the methotrexate
in the medium.
In their patent application and related papers, Axel and colleagues at Columbia proposed that DHFR amplification could
significantly increase gene expression in mammalian cells. A
test of the idea became feasible in 1980, when Columbia cell
biologists Lawrence Chasin and Gail Urlaub isolated mutant
CHO cells that lacked the enzyme.
In 1982, a postdoc working in Phil Sharp’s MIT laboratory
had the idea of engineering these DHFR-deficient cells for the
production of recombinant proteins. Randy Kaufman had been
a graduate student in Schimke’s lab at Stanford. He spliced the
Winter 2015
LSF Magazine 43
Blockbuster drugs
made in CHO cells
Product
Sales
(USD B)
Year
of first
Approval
Patent
Expiry
(US)
Company
Humira (anti-TNF)
11.00
2002
2016
AbbVie; Eisai
Enbrel (anti-TNF)
8.76
1998
2028
Amgen; Pfizer; Takeda
Rituxan/MabThera (anti CD20)
7.91
1997
2016
Biogen Idec; Roche
Avastin (anti-VEGF)
6.97
2004
2017
Roche/Genentech
Herceptin (anti-HER2)
6.91
1998
2019
Roche/Genentech
Epogen (epoetin alfa)
3.35
1989
2013
Amgen; Johnson & Johnson
Avonex (IFN-ß-1a)
3.00
1996
2015
Biogen Idec
Rebif (IFN-ß-1a)
2.59
1998
2013
Merck Serono
Aranesp/Nesp (darbepoetin α)
2.42
2001
2024
Amgen
Advate/Recombinate (Octocog α)
2.37
1992
Eylea (anti-VEGF)
1.88
2011
Total Sales in 2013
57.16
DHFR gene into an engineered plasmid (a circular ring of DNA)
adjacent to a gene that codes for a monkey virus (SV40) protein,
and then introduced the plasmid into the DHFR-deficient CHO
cell mutants.
He anticipated being able to select for cells that both survived
exposure to methotrexate and produced the SV40 protein in
large quantities—if, as he hoped, the cells generated copies of
both linked genes. It worked. In fact, the genes from the plasmid
were incorporated and amplified as part of the hamster genome.
It was possible to increase yields.
On March 23, 1982, Kaufman and Sharp submitted an article
on the work to the Journal of Molecular Biology. Kaufman subsequently constructed a vector for amplified expression of alpha
interferon in CHO cells. He recalls encouraging Sharp to file for
a patent on the invention, but the lab chief declined.
As a co-founder of Biogen—which was at the time working
to develop alpha interferon as a pharmaceutical product—Sharp
recognized the value of amplified gene expression in cells
that could fold human proteins into proper shape, but he was
satisfied that the Axel patent had wrapped up the territory. As it
happened, Biogen didn’t use Kaufman’s system. The company’s
manufacturing and marketing partner, Schering-Plough, made
interferon in E. coli.
By the beginning of 1983, Genentech’s Levinson had also
devised a DHFR expression system with help from Chris Simonsen, another alumnus of Schimke’s lab. The pair filed a patent
application on January 19. Later in the year, Kaufman took his
CHO cell expertise to Genetics Institute in Boston, where he
worked on the production of tPA, erythropoietin (EPO), a red
blood cell growth-stimulating hormone, and Factor VIII, a blood
clotting factor.
44 LSF Magazine Winter 2015
Baxter
2021
Regeneron; Bayer Healthcare
Scaling up
Success in boosting CHO cell expression created a new set
of problems. Once companies learned how to make proteins in
CHO cells, they had to install manufacturing processes. Mammalian cell cultures had never been grown on industrial scales.
In the early 1980s, it was generally assumed that they were not
well suited to growth in suspension in fermentation tanks. CHO
cell manufacturing became a technological adventure.
Growth media in high volume bioreactors are stirred in order
to maintain optimal or at least workable environmental conditions—temperatures, pH levels, oxygen transfer rates, broth
consistencies, and cell densities, for example. Precision control
is necessary to achieve efficiency and quality in production, but
stirring creates turbulence in growth media and shear forces
greater than fragile mammalian cells can withstand.
In the early 1980s, all good cell biologists knew that mammalian cell cultures grew best in roller bottles. Roller bottles are
small vessels that contain liquid cell growth media. Cell cultures
coat the interior surfaces in a thin monolayer, and the bottles
are slowly rotated. The action alternately washes the cells in the
growth medium and exposes them to air.
Genentech and other early biotech companies used roller
bottles to grow mammalian cells that expressed and secreted
functional recombinant human proteins, but when it came time
to scale up, they had no blueprints to follow. No one had ever
assembled an industrial scale mammalian cell culture production system. Company scientists had no idea how adaptable
or scalable their processes would be, if at all. Everything was
experimental.
Genentech ventured first into this uncharted territory as it
prepared to introduce CHO cell-derived tPA. The initial task
was to produce enough of the drug to supply clinical trials. Bill
Recombinant DNA
Expression Systems
Young was Genentech’s head of manufacturing.
He remembers that it was difficult to project
demand—no one knew how much of the drug to
4% Human
administer to patients.
The trials began with very low doses, but the
35.5% CHO cells
8.5% Misc.
clinicians kept bucking them up. Young worked
with calculations that started at 5 milligrams
per dose and rose to 150 milligrams. Soon, he
says, “It was almost impossible to make enough
product in roller bottles. I could envision these
16.5% Yeast
bottles taking off over the entire building. It
was the Rube Goldberg approach to biotech
manufacturing. We just kept adding more and
more bottles.” Genentech had a problem.
Young credits Jim Swartz with casually
16.5% Misc. mammalian
ushering in a new era of bioprocess engineering.
29% E. coli
Swartz was a chemical engineer who had come
Biopharmaceutical applications (1982 to 2014)
into the company from Eli Lilly and Company.
According to Young, he asked, as the manufacturing group mulled over its predicament,
became, and they remain, preferred hosts for the production
“’Why don’t we try growing these cells in a fermenter? We’ve got
of recombinant protein therapeutics. Of the twenty top-selling
a 10,000-liter fermenter that we bought for bacterial work. How
biopharmaceuticals on the market in 2013, eleven were manudo we know that the cells won’t grow in it?’”
factured in CHO cells. Combined annual sales of these protein
The cell biologists on staff repeated the conventional wisdom
products exceeded $57 billion.
that mammalian cells are too delicate, but Dennis Kleid remembers a timely and influential suggestion from a contrarian, Rob
Arathoon: “He suggested that we change the gear ratio on the
Bioprocess optimization
impeller and stir the tank very, very slowly.” Some calculations
On May 2, 2014, Biogen CEO George Scangos delivered the
indicated that gentle agitation could work for CHO cells, which
annual Michaels Lecture to the MIT Department of Chemical
grow relatively slowly and need less oxygen than E. coli. The idea Engineering. He spoke about challenges and opportunities in
gained traction.
bioprocessing and observed that since the 1980s, yields and
Levinson worked with the company’s manufacturing group to costs in protein drug manufacturing have followed a biological
design a bioprocessing system that would facilitate the growth of analogue of Moore’s Law.
genetically engineered CHO cells in suspension in the 10,000-liIn 1965, Intel co-founder Gordon Moore predicted that
ter bioreactor. Young hired three industrial microbiologists from transistor counts in integrated circuits and computing capacities
Burroughs Wellcome with experience in large-scale cultures for
and speeds would double every two years, and so they have.
animal vaccines, and the project team worked through a host of
This year, Scangos explained to his MIT audience that outputs
technical and regulatory issues—purification, validation, risks of
in biotech manufacturing have also increased exponentially. Cell
viral contamination, and so on—to deliver clinical grade tPA.
biologists and bioprocess engineers have boosted cell culture
Young calls the scale up process “horrendous,” but somehow
yields from 100 milligrams per liter in the early 1980s (at a cost
it all came together. In fact, the company discovered that CHO
of $10,000 per gram) to 5 grams per liter today (at $100 per
cells in suspension made a more potent product. When the big
gram).
bioreactor went online, the medical staff had to back down recAdvances in computing are now approaching physical
ommended doses from 150 to 100 milligrams. It was a mystery.
barriers. Soon, it will be impossible to go smaller. According to
“The molecule was different chemically,” says Young, “but we
Scangos, advances in bioprocess manufacturing are also pushing
never found out exactly why.”
up against limits—not physical, but economic. Biogen currently
On November 13, 1987, Genentech’s tPA became the first
controls 10 percent of the world’s mammalian cell culture capacFDA-approved pharmaceutical product manufactured in CHO
ity (Roche, Amgen, and Biogen together account for 55 percent
cells. The commercial performance of the product was underof the total). Scangos believes that it has become infeasible
whelming, but the design and construction of the manufacturing for biotech manufacturing operations to continue leveraging
system was genuinely innovative. “Nobody had ever done
classical economies of scale.
anything like this,” says Young. “It was a completely new way of
There are some further parallels. Physicists and electrical
making a pharmaceutical product.”
engineers contend that after the end of Moore’s Law, advances
In the mid-to-late 1980s, many companies followed Gein computing power will result from greater energy efficiency
nentech’s lead and turned to eukaryotic cells as E. coli systems
and the emulation of materials and architectures in biological
proved inadequate or inferior to viable alternatives. CHO cells
information processing systems—DNA, cells, and brains, for
Winter 2015
LSF Magazine 45
example. Similarly, Scangos maintains that future advances in
bioprocessing will be realized through improved utilization
of existing assets and the installation of flexible, networked
communication, supply, and production processes.
On the technical side, cell biologists and bioprocess engineers
continue to improve the utilization of the industry’s vital tools.
They are learning how to make better bioreactors and growth
media, and how to make cells healthier, happier, and more
sociable—i.e., tolerant of increasing cell densities—in order
to improve protein yields. Drug companies have developed a
wide variety of CHO cell lines with genotypes, phenotypes, and
behaviors adapted for expression of different kinds of recombinant proteins.
Hamster cell genomes
In the age of genomics and bioinformatics, these conventional efforts are swimming in great pools of new data. Researchers
have gained access to the astoundingly complex universe of
molecules and pathways that constitute mammalian cell drug
factories. Nate Lewis, a systems biologist and assistant professor
at UC San Diego School of Medicine who studies CHO cells,
says, “In the past, researchers tweaked environmental conditions, or the vector with the inserted gene, but they never really
knew what was going on inside the CHO cell itself. The cell was
a black box.”
To open the black box, several big biotech and pharmaceutical companies launched a private consortium to sequence the
genome of several CHO cell lines in 2006. In a former life as an
industrial scientist, Lewis became part of a second sequencing effort initiated by GT Life Sciences, because, he says, “The lack of a
genome had really stalled CHO research. After the E. coli genome
was sequenced, researchers were able to do metabolic engineering
in bacteria. We wanted to be able to do it in CHO cells.”
Scientists are now using CHO genome sequences to provide
detailed portraits of transcription, translation, protein synthesis,
and post-translational modification in altered hamster cells.
They are uncovering biomarkers that distinguish high-yield
lines, and others that point to rate-limiting cellular processes.
They have shed light on hamster glycosylation pathways.
Vanishingly small variances in glycosylation can have dramatic
impacts on drug efficacy, stability, and safety. The biochemical
toolkit utilized by CHO cells resembles that found in human
cells, but hamsters lack a few key enzymes, and they possess
others that add non-human sugar modifications, which may
diminish therapeutic efficacy or induce immune responses. All
of this is grist for the molecular pharmacologist’s mill.
Drug makers are now combining their expanded knowledge
base with precision tools for knocking genes down and out. In
2009, Alnylam of Cambridge, Massachusetts began applying
RNA interference (RNAi) technology to silence select CHO cell
genes. In May 2014, researchers at the Technical University of
Denmark made the first demonstration of CHO genome editing
with CRISPR/Cas9 technology. The targets included genes that
diminish the efficacy of therapeutic antibodies.
Others researchers are attempting to create humanized CHO
cell lines by knocking out CHO genes that code for enzymes
involved in non-human modifications. Such an approach could
enable CHO cells to mimic human glycosylation, and drug
makers to produce safer, more efficacious medicines.​​
At UCSD, Lewis is taking a global “systems biology” view of
CHO cell protein factories. He is using computational methods
to build models of metabolic pathways involved in recombinant
protein secretion. He has two goals. He wants first to generate
predictive rules that researchers can use to determine optimal
cell lines, media, and growth conditions for the high volume
manufacture of specific proteins.
Secondly, he wants to develop predictive algorithms for
engineering cell lines, biological systems that will produce
high quality biotherapeutics displaying a wide range of desired
characteristics, properties, and specificities. “With the genome
sequence and these models in hand,” he says, “we will be able to
control in a very specific manner the attributes of proteins.”
CHO cells, drug prices, and
biosimilars
The metabolic engineering of mammalian cells can enhance
the safety and efficacy of new biological drugs. It may also
further improve biomanufacturing processes, reduce production
Sequencing the CHO Genome
When plans for the CHO cell genome project were announced, many researchers hoped that it would lead to
deeper understandings of CHO biology. They envisioned
the creation of “designer” cells lines and vaulting advances
in biopharmaceutical development. This promise has not yet
been fully realized, but the field is moving rapidly from the
manipulation of single genes to multiple gene orchestration.
In 2006, leading biotech and pharmaceutical companies
joined forces with the Society for Biological Engineers to
establish the CHO Consortium. Member organizations
worked cooperatively to map and sequence the genomes of
several different CHO cell lines, and agreed to share resulting
46 LSF Magazine Winter 2015
intellectual properties. Members had full access to the consortium’s extensive database. Participating companies included Bayer Healthcare, Boehringer Ingelheim, Bristol-Myers
Squibb, SAFC Biosciences, and Schering Plough.
GT Life Sciences, a privately held San Diego firm,
launched a second effort to sequence CHO cell line genomes,
in partnership with the Beijing Genomics Institute (now
BGI). In August 2011, the partners published the first open
access CHO genome sequence, for the CHO-K1 cell line.
Two months later, GT Life Sciences was acquired by Intrexon
Corporation, a synthetic biology company located in the San
Francisco Bay Area.
costs, and perhaps help to lower drug prices—at a time when
healthcare expenditures are spiraling upwards and payers are
exerting intensified pressure on drug companies to engage in
deep discounting.
The biotech sector is at the center of the imbroglio because it
has focused largely on the development of innovative specialty
drugs and treatments for unmet medical needs. Branded biopharmaceuticals are often the best and sometimes the only treatment
options available to doctors and patients, and in the age of genomics and precision medicine, these high value products frequently
serve small patient populations. The prices are very high.
The economic pain has led payers—patients, providers,
insurance carriers, pharmacy benefits managers, governments,
taxpayers, employers, and labor unions—to question the value of
the products. Are the benefits worth the great expense? When the
question was put to Severin Schwan, CEO of the Swiss pharmaceutical company, F. Hoffman-LaRoche, he said, “There is no objective
answer. At the end, you are discussing, what is the price of life?”
Schwan implies that the issue is for society to decide, not
CEOs, accountants, or scientists. How much should we pay
to take care of people? How much can we afford to pay? Who
should decide, and on what basis? Schwan also implies that the
prices are fair: the drugs give “life” and society at large must
decide whether to pay for it.
Finally, he assumes relations of trust between corporations
and communities, but these seem to have broken down. In
public debates on pricing, drug companies are portrayed, in
turn, as ethical firms doing their best to balance obligations to
customers and shareholders, and as price gougers motivated by
unbridled greed.
Industrialists maintain that the high prices reflect the realities
of drug development: it is immensely difficult, enormously
expensive, intensely competitive, and highly regulated. The
vast majority of projects miscarry. Revenues from successful
products must subsidize a host of failures. Innovation is a risky,
costly business.
In November 2014, The Tufts University Center for the Study
of Drug Development (CSDD) released an estimate of total development costs for a new FDA-approved pharmaceutical product in the United States: $2.6 billion. Critics are loath to accept
the figure. Rohit Malpani, policy director of Doctors Without
Borders told The Economist, “If you believe that, you probably
also believe the earth is flat.” Skeptics complain that Tufts relied
on information supplied by pharmaceutical companies.
The debate is heating up, but process improvements are
unlikely to have substantial impacts on prices for patented
biopharmaceuticals, because manufacturing costs represent only
a small fraction of total expenditures. But even slight savings
could make a difference in markets for generic products, where
producers compete on the basis of price.
In the United States, biopharmaceutical manufacturers have
not yet faced competition from off-brand products, but many
first generation protein drugs will soon lose patent protection. A
host of companies are gearing up to develop facsimiles.
The products are called “biosimilars” or “biological
Cell-Free Gene
Expression and
Protein Synthesis
Genetically engineered CHO cells may represent the
future of biopharmaceutical production. Or they may
have no future at all. Sutro Biopharma would prefer the
latter outcome. The company is developing a cell-free
gene expression platform as an alternative to in vivo cell
culture and transgenic modes of production. The idea
is to transcend limitations imposed by adapted biological systems. Sutro’s alternative separates all cellular
components required for transcription, translation, and
protein synthesis into an extract. Users simply add DNA
encoding desired proteins. The company claims that
its technology optimizes biochemical processing and
affords grams per liter yields in just eight to ten hours
even at commercial production scales.
follow-ons” rather than generics because they resemble the
original products, but are not identical. The complexity of biological molecules precludes the design of exact replicas. Protein
products can vary from factory to factory even if the same host
cells and manufacturing process are used.
Market penetration of biosimilars could be rapid in the
United States if the products offer significant savings. A report
published last year by the RAND Corporation estimated price
cuts between 10 and 35 percent. Competition among small
molecule generics typically cuts prices in half, but the biologicals
will have higher production costs. They may also be required to
clear significant regulatory hurdles.
The regulatory environment is unsettled. The 2010 Patient
Protection and Affordable Care Act created an abbreviated
licensing pathway for biological products that are “interchangeable” with licensed drugs, but the FDA is still finalizing regulations. If the rules favor developers, healthcare payers will surely
gravitate to the cheaper alternatives.
Elsewhere around the world, the picture is clearer. The
European Union established an approval process in 2004, and
the first wave of products appeared two years later. As of May
2014, twenty products had been approved for sale. Investment in
biosimilars production is also growing rapidly in China and India, where high-cost branded biologics strain national healthcare
systems. Demand is high for alternatives, and regulatory barriers
are relatively low.
CHO cells have served as vital tools in the development of
innovative protein therapeutics for more than thirty years. Now,
they are helping drug makers deliver follow-ons at affordable
prices to doctors and patients in more than fifty countries. If molecular biologists can engineer CHO cells for more efficient cell
culture production, the result will be better medicines at lower
costs for millions of people around the world. n
Winter 2015
LSF Magazine 47
Global Biotech Philanthropy
DFA’s diagnostic tests
are embedded in
paper panels about
the size of a quarter.
Fluid samples are
placed on dots.
Results are indicated
by changing colors.
Diagnostics for All
Miniature diagnostics, global impact
D
iagnostics for All (DFA) is a nonprofit organization located in Cambridge, Massachusetts with one mission: to revolutionize public health on a global scale. Sixty
percent of people in the developing world
lack access to adequate medical care. DFA is working to
change that. The organization is developing inexpensive
point-of-care diagnostic devices that can quickly read a
patient’s health status without the use of power or water
and without professional medical personnel.
DFA’s diagnostic tests employ a technology invented
in the lab of Harvard University chemist George Whitesides in 2007. Reagents are printed in liquid-wicking
grooves on paper to make a tiny microfluidic device,
a “lab-on-a-postage stamp.” A single drop of blood
from a finger-prick changes the color of the device to
indicate the test result. The tests are fast, easy to use, and
48 LSF Magazine Winter 2015
biological waste disposal is simple. The paper can be
incinerated after use.
Whitesides and cofounder Carmichael Roberts, a
Massachusetts venture capitalist and former biotech
executive, established Diagnostics for All in 2008.
The startup attracted a group of young scientists and
social entrepreneurs committed to improving access to
healthcare in developing countries. Harvard University
granted DFA an exclusive royalty-free license to the
technology for not-for-profit applications.
DFA offers sublicenses to private ventures interested
in commercializing the technology in resource-rich
countries, but the organization relies primarily on charitable donations, grants, and pro-bono contributions to
support its operations and research.
The Bill and Melinda Gates Foundation has been a
consistent backer. In May 2011, the Foundation awarded
a two-year grant of $2.9 million for the development
of animal health diagnostics that will enable smallholder farmers in Sub-Saharan Africa to improve
livestock care.
In December 2012, DFA received an additional
$2.6 million to develop rapid tests that identify
immune markers of successful vaccination against
tetanus and measles, and in May 2014, another $1.2
million for a bovine estrus diagnostic that indicates
when cows are ready for artificial insemination.
The organization’s medical tests diagnose a
range of treatable conditions including tuberculosis,
malaria, HIV, diabetes, and liver failure, a common
side effect of drugs prescribed for tuberculosis and
HIV/AIDS. In resource-rich areas, expensive medical
equipment is used to monitor patients for early signs
of liver complications. In developing countries, such
monitoring costs are prohibitive. DFA’s finger-prick
test to assess liver health in fifteen minutes is currently in field trials.
Innovations in the pipeline include quantitative
devices developed jointly with University of Illinois
chemist John Rogers and MC10, a Boston area
consumer electronics company. They incorporate
flexible electronic sensors, transistors, and batteries
to provide digital readouts of biomarker levels. Prototypes detect micronutrient and vitamin deficiencies
in children.
Conventional microfluidic diagnostic devices
are designed for use with external readers in
clinical laboratories—equipment that is unsuitable
for field use in developing countries because it is
expensive, fragile, and easily broken or stolen. DFA’s
quantitative technologies do not require additional
instrumentation.
The electronics work with the image processing
Harvard University
chemist George
Whitesides,
co-founder of
Diagnostics for All
capabilities of mobile phones, which are now prevalent in even the world’s most remote regions. Current
DFA president and CEO Marcus Lovell Smith
announced a successful trial in December 2013:
“We were able to demonstrate a simple and reliable
method for analyzing results and transmitting them
by mobile phone.”
Many of DFA’s products are in final trials. Field
use of the tests requires only minimal training and
sample preparation. At a cost of just pennies per unit,
paper diagnostics are poised to become foundational
technologies for sustainable regional healthcare networks that will reach the world’s most underserved
and disadvantaged populations.
Winter 2015
LSF Magazine 49
Global Biotech Philanthropy
The Manzanar detention camp in California’s Owens Valley. More than 100,000 Japanese-Americans were held there during World War II.
Erbitux
and the
Manzanar
Project
Drug royalties for coastal
desert aquaculture
50 LSF Magazine Winter 2015
I
n a March 2004 press release, the US Food and Drug
Administration announced that it had approved sales
of Erbitux, a new biopharmaceutical from ImClone
Systems, Inc., of New York, New York, for the treatment
of advanced colorectal cancer.
Three years earlier, the agency’s refusal to consider the
company’s application for review of the product precipitated an insider trading scandal that landed CEO Sam
Waksal, Merrill Lynch broker Peter Bacanovic, and media
personality Martha Stewart in prison. The episode was a
public relations fiasco for the biotech industry, but there
are other stories to tell about Erbitux and the people
involved in its development.
Erbitux was invented by cell biologist Gordon Sato,
in collaboration with two colleagues at the University of
California, San Diego (UCSD): his son, Denry, who was
working in his lab as postdoc, and John Mendelsohn, the
founding director of the UCSD Cancer Center.
Sato (right) with research assistant Abraham Fesahe and newly planted Mangroves
along Eritrea’s desert coast
Sato trained for a PhD in biophysics at Caltech under Max
Delbrück, and did postdoctoral work at the University of
California, Berkeley with Gunther Stent, and the University
of Colorado, Denver with Theodore Puck. He enjoyed a long,
successful career, and was elected to the National Academy of
Sciences in 1984, the same year Erbitux was invented.
Erbitux is the trade name for a chimeric (part murine, part
human) anti-EGFR monoclonal antibody known generically as
cetuximab. EFGR stands for epidermal growth factor receptor. It
is overexpressed in a variety of solid tumors, including squamous cell cancers, carcinomas, melanomas, glioblastomas, and
meningiomas.
Levels of EFGR overexpression correlate with rates of growth
and metastasis, and prognoses for patients. Erbitux works by
binding and blocking growth factor receptor sites on cancer cell
surfaces. This prevents the downstream molecular signaling that
initiates uncontrolled tumor cell division.
Sato retired from science in 1992 to work full-time on a
humanitarian cause he had taken up a few years before—the development of sustainable aquaculture systems in coastal deserts
subject to famine. He went to the drought-stricken East African
country of Eritrea to construct fish farms and plant salt-tolerant
mangrove trees in tidal areas on the Red Sea, to supply food for
livestock and people.
Gordon Sato, fifteen years old, at Manzanar in 1943
The idea came from Sato’s experience as a teenager. He was
born in Los Angeles and raised on Terminal Island, a Japanese
community near the port of Long Beach. On February 9, 1942,
the FBI incarcerated all of Terminal Island’s adult male Japanese
immigrants, including Sato’s father. The families were given
forty-eight hours to evacuate their homes, which were razed, and
then sent to an internment camp in Manzanar, California, in the
Owens Valley, the desert area beneath the eastern face of the Sierra
Nevada.
Sato was fifteen at the time. It was at the camp that he first
began thinking about self-sufficient desert communities: “Since I
was a child,” he told a reporter in 2008, “I loved science and I envisioned science would help poor people, and it can. In Manzanar, I
thought about the desert, and when I was in Africa I thought about
the desert. It came from my experiences at Manzanar.” He named
his coastal desert aquaculture program the Manzanar Project.
As Erbitux neared approval in 2004, Sato was in Eritrea. The
New York Times reported that, as a co-inventor of the drug, he
stood to receive several hundred thousand dollars a year in royalties from sales. When informed that he might be receiving some
checks, Sato said, “I hope so, because I’m running out of money
here.” By that time, Sato had reportedly spent half a million dollars
on his personal African crusade.
Winter 2015
LSF Magazine 51
photo finish
The Art of Robert Schimke
Stanford physician and cell biologist Robert T. Schimke took up art
in 1976, at the age of forty-four. He turned to the pursuit at difficult
times in his life, and experimented with various media and subject
matters. His scientific career was ended and his artistic vocation interrupted when he suffered devastating injuries in a 1995 bicycling
accident on a mountain road in Woodside, California. He experienced nearly complete paralysis, but by 2002 he had regained sufficient movement to return to painting. He subsequently worked with
acrylics, temperas, and oils, and layered brush and drip techniques, to
create vivid landscapes, floral designs, and abstract patterns. With the
help of an assistant, he created more than 400 original works, many of
which now hang in scientific workplaces including the headquarters
of the American Society for Biochemisty and Biophysics, Amgen, the
Caruthers Biotechnology Building at the University of Colorado in
Boulder, Genentech, Google, the National Institutes of Health, and
the Stanford University Center for Integrated Systems.
String Theory
52 LSF Magazine Winter 2015
Colored Triangles
Fusion
Winter 2015
LSF Magazine 53
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54 LSF Magazine Winter 2015
Board of Directors
Brook Byers
Kleiner Perkins Caufield &
Byers
Carl Feldbaum, Chair
Biotechnology Industry
Organization
Heather Erickson
Life Sciences Foundation
Frederick Frank
EVOLUTION Life Science
Partners
Dennis Gillings
Quintiles Transnational
Ivor Royston
Forward Ventures
John Lechleiter
Eli Lilly and Company
Phillip Sharp
MIT (Academic Advisor)
Scott Morrison
EY
Henri Termeer
Genzyme Corporation
Board of Advisors
Daniel Adams
Protein Sciences
Alan Gold
BioMed Realty
Arthur Levinson
Calico
Josef von Rickenbach
PAREXEL
Sol Barer
Celgene
Joseph Goldstein
UT Southwestern
Greg Lucier
Life Technologies
Roberto Rosenkranz
Roxro Pharma
James Blair
Domain Associates
James Greenwood
Biotechnology Industry
Organization
Magda Marquet
Ajinomoto Althea
William Rutter
Synergenics
David Meeker
Genzyme Corporation
George Scangos
Biogen Idec
Alan Mendelson
Latham & Watkins
Steven Shapin
Harvard University
Fred Middleton
Sanderling Ventures
Stephen Sherwin
Ceregene
Tina Nova
Illumina
Jay Siegel
Johnson & Johnson
Stelios Papadopoulos
Exelixis
Vincent Simmon
Genex Corporation
Richard Pops
Alkermes
Mark Skaletsky
Fenway Pharmaceuticals
George Poste
Arizona State University
Thomas Turi
Covance
Dennis Purcell
Aisling Capital
J. Craig Venter
J. Craig Venter Institute
Joshua Boger
Vertex Pharmaceuticals
William Bowes
U.S. Venture Partners
Robert Carpenter
Hydra Biosciences
Marc Casper
Thermo Fisher Scientific
Nancy Chang
Orbimed
Susan Desmond-Hellmann
Gates Foundation
Jay Flatley
Illumina
Chris Garabedian
Sarepta Therapeutics
Harry Gruber
Tocagen
David Hale
Hale BioPharma Ventures
William Haseltine
Access Health International
Paul Hastings
OncoMed Pharmaceuticals
Sally Smith Hughes
University of California,
Berkeley
Perry Karsen
Celgene
Rachel King
Glycomimetics
Affiliations for identification purposes
P.O. Box 2130
San Francisco, CA 94126
biotechhistory.org