San Diego’s Cancer Warrior

The Race to the $1,000 GenomeAtomic Gardens

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LSF News

History in the MakingThe Race to the $1,000 Genome

Ivor RoystonSan Diego’s Cancer Warrior

LSF Oral History ProgramGenex CEO J. Leslie Glick

Atomic Gardens

In ReviewBiotech Bookshelf

Experiments in radiation induced-mutagenesis have been taking place for over eighty years, but we generally do not recognize how commonplace mutation-derived crops and ornamental plants have become.

From a young age, he wanted to cure cancer. As an adult, it became his life’s work. Despite his single-minded focus, Royston’s career took a series of unexpected detours.

EventsBiotech Pioneers Convene

Editor:Production Manager:

Staff Writers:

Design/Layout:

Mark JonesDonna LockBrian DickHeather NelsonSusan RogersZachary Rais-Norman

LSF Magazine

Spring 2012 1

Welcome to the inaugural issue of LSF Magazine.

The Life Sciences Foundation (LSF) tells the story of biotechnology. It pre-serves the historical record of the in-dustry, commemorates its remarkable achievements, registers its failures and disappointments, and recognizes the contributions of participating individu-als, teams, and organizations. We have established LSF to serve as the custo-

dian and caretaker of the field’s collective memory. Biotech ventures are prospective, oriented toward the

future, toward plans and actions that hold the greatest prom-ise for success. There is little time in the biotech industry for reflection. Yet the factors that determine success (knowledge,

capital, perseverance, and luck, for example) remain constant. There is much to be learned by revisiting the past – history offers lessons on how to adapt, survive, and prosper. LSF col-lects and shares these lessons with students, teachers, scholars, journalists, policymakers, and the general public, as well as scientists and businesspeople in the biotech industry.

LSF Magazine is a conduit for the Foundation’s message: history is an asset, an instrument, a force. It can be deployed to engender public understandings of science and technology, and to foster public support for innovation. Please enjoy, and please spread the word.

G. Steven BurrillExecutive ChairmanThe Life Sciences Foundation

from the executive chairman

The mission of the Life Sciences Foundation (LSF) is public under-

standing. What do public constituencies need to know about the biosciences and biotechnology?

Publics need to know, first of all, that life scientists are foolhardy. Biore-searchers attempt to cure dread, refrac-tory diseases, the causes of which are not fully understood. They attempt to

secure food supplies for a global population that now exceeds seven billion people. They attempt to develop new sources of energy for a world that has become thoroughly dependent on abundant, inexpensive fossil fuels. In these undertakings, the complexities of biology and the chaotic winds of social, political, and economic change create impossible obstacles. Contemporary life scientists tilt at windmills. The public needs to know.

The public also needs to know how important these efforts are, and what is required to sustain them. The public needs to have realistic expectations regarding the potential benefits of biotech research and development, and sober, reasoned understandings of associated risks.

Above all, the public needs to be reminded that the life sciences are human pursuits. They unfold in processes of

cooperation and competition, often in unexpected and very human ways. For all of the extraordinary discoveries, insights, and inventions they produce, they are populated by ordinary people with strengths and weaknesses, virtues and vices, talents and limitations – temperaments and personalities of every sort. Like all of us, these people are committed to families, friends, and communities; they hold values, opinions, and beliefs; they are motivated by passions, interests, aspirations, ambitions, hopes, dreams, even obsessions.

If highlighting the personal dimension of science and technology reveals imperfections, it also encourages sympa-thies that outsiders can hardly muster for faceless institutions. It depicts science as a familiar place, a comfortable place for people (and for you, too, young person, should you feel called to a career in it!).

Featured articles in LSF Magazine will discuss various aspects of the biotech trade – scientific, technical, organiza-tional, commercial, financial, legal, and so on – all of which are important. But they will also tell about lives in the industry. We will feature stories about people, the real sources of innovation.

Mark JonesDirector of ResearchThe Life Sciences Foundation

from the editor

Bay Area Biotech Pioneers

Pitch Johnson, Bill Bowes, Steve Burrill, Bill Rutter

Roberto Rosenkranz, Arnold Thackray, Alex Zaffaroni, Jr.Moshe Alafi

Bill Rutter and Hollings Renton David Morgenthaler and Bill Bowes

2 Spring 2012

Susan Desmond-Hellmann

Stanley CohenLeroy Hood

Bill Bowes and Sam Eletr

Judy Swanson and Pitch Johnson

Spring 2012 3

LSF San Francisco Bay Area Biotechnology History Dinner

LSF held a special early February dinner in San Francisco to unite pioneers from the Bay Area biotech community’s earliest days. The event was co-hosted by Bill Bowes, G. Steven Burrill, Brook Byers, and Bill Rutter. Featured speakers included Pitch Johnson, Susan Desmond-Hellmann, and LSF President & CEO Arnold Thackray. Over eighty leaders in science and industry attended, including an honor roll of trailblazers involved in such firms as Cetus, Genentech, Chiron, and Applied Biosystems.

4 Spring 2012

San Diego CONNECT Entrepreneur Hall of Fame AwardLSF visited San Diego on March 1 to attend CONNECT’s prestigious Hall of Fame Luncheon at La Estancia Hotel. CONNECT President Duane Roth pre-sented the organization’s highest honor, its Entrepreneur Hall of Fame Award. This year’s honoree was San Diego bio-tech inventor, CEO, director, and venture financier Howard E. ‘Ted’ Greene.

Greene served as CEO and Chairman of Hybritech and Amylin Pharmaceuti-cals, and was involved, in various capaci-ties, in the formation of many other San Diego biotech companies. Mr. Greene is currently a director of several early-stage biotech and internet startups. LSF was pleased to join leaders of the San Diego biotech community in recognizing his achievements.

Boston/Cambridge Events: LSF and CHF at BIO 2012LSF and sister organization the Chemical Heritage Foundation (CHF) will kick off the summer by co-sponsoring functions in Boston. The events will coincide with the 2012 BIO International Convention in Boston, on June 18-21. Stay tuned for details as the dates approach. For information on the BIO meeting, visit: convention.bio.org

Palo Alto Conversation: LSF-CHF ‘History Live’ – HIV/AIDSLater this year, LSF will partner once more with CHF, and with the National Institutes of Health (NIH), to host an AIDS-focused ‘History Live’ session. The conversation, to be moderated by Ed Penhoet, will take place at the Gordon

and Betty Moore Foundation in Palo Alto. It will consider the crucial roles played Chiron Corporation and Gilead Sciences in HIV/AIDS research and dis-covery. These two companies developed products that have increased life expec-tancies, improved quality of life, and transformed treatment regimens for AIDS patients around the world. Look for further details in the coming months.

LSF is now on Facebook

The Life Sciences Foundation is now on Facebook. Each week, we’ll post news stories, trivia, and video clips about the past, present, and future of biotechnol-ogy. Find us at www.facebook.com/life-sciencesfoundation. ‘Like’ us, and spread the word!

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advisory board spotlightBill Bowes is the senior member of LSF’s distinguished Advisory Board. After a twenty-five year career as an investment banker with the San Francisco office of Blyth & Co., he went into venture capital in 1978. He co-founded U.S. Venture Partners in 1981.

Bowes first became involved in biotechnology as a director of Cetus in the early seventies. In 1980 and 1981, he co-founded two companies that would dramatically alter the historical course of the life sciences, medicine, and the biotech industry – Applied Molecular Genetics (better known as Amgen) and Applied Biosystems. Around the same time, he also started the tech firm, Applied Micro Circuits – “It was my applied phase,” he says.

Bowes once calculated the price per ounce of Epogen®, Amgen’s recombinant version of the red-blood cell stimulating hormone, erythropoietin. Approved for sale by the FDA in 1989, Epogen® was the biotech industry’s first blockbuster drug. For years, the Thousand Oaks production facility for the entire supply of the product was a single small room. The price per ounce? Bowes figured it at $6 million. “An ounce of the stuff,” he explains, “is 100,000 therapeutic doses. It’s an amazing little drug.”

J. Craig Venter

Spring 2012 5

Rivalries are often productive. In the life sciences, the competition involving Jim Watson, Francis Crick, Maurice Wilkins, Rosalind Franklin, and Linus Pauling accelerated the discovery of the

molecular structure of DNA. The cloning of the insulin gene was driven by competition among teams at Harvard, UCSF, Genentech, and the City of Hope Medical Center. In recent memory, the competition between Celera Genomics and the public consortium of sequencing centers brought the Human Genome Project to completion ahead of schedule and under budget.

Another contest is now heating up in genomics – the race to produce the first human genome for $1,000 or less. In pursuit of this goal, several private firms are developing ‘next generation’ instruments to increase the speed and reduce the cost of whole genome sequencing. ‘Next genera-tion’ refers to technologies that rely on new chemistries and high-performance computational tools to accelerate the reading, alignment, and genomic assembly of nucleotide sequences by orders of magnitude.

Participants in the field recognize the importance of competition to progress. In 2003, the J. Craig Venter Sci-ence Foundation established a $500,000 prize for the team making the greatest contribu-tions to the realization of the $1,000 goal. Three years later, the Venter award was folded into the $10 million Archon X Prize in Genomics offered by Canadian philanthropist Stew-art Blusson’s X Prize Founda-tion. The prize will go to the

first group that can sequence 100 human genomes in 10 days, with no more than one error per 100,000 sequenced bases.

$10 million is no paltry sum, but in this race, com-mercial opportunities are far greater material incentives. According to healthcare marketing experts, $1,000 is the price point at which whole genome sequencing will be broadly adopted in clinical medical laboratories. When the analysis of personalized genomic information becomes a routine element of standard medical practice, substantial shares of the sequencing market could be worth billions.

The race to the $1,000 genome could conclude in a matter of months. The horses have rounded the clubhouse turn and are thundering down the backstretch. Illumina and Life Technologies, both located in San Diego County, lead a field that includes 454 Life Sciences (now a subsid-iary of Roche), Complete Genomics, and Knome, among others. The front-runners are neck-and-neck, sprinting for the finish line. The stakes are potentially enormous. It’s history in the making. It’s exciting!

A Brief History of DNA Sequencing

The arrival of the $1,000 genome is thrilling because it promises to be revolutionary. ‘Next generation’ technolo-gies are innovative, the sequencing speeds are phenomenal, and the coming milestone points toward transformative changes on the horizon in medicine and many other fields. Still, a review of the history of DNA sequencing suggests that the $1,000 genome is perhaps better understood as a relay station than a destination.

The first partial DNA sequence was determined by Stanford biochemist Dale Kaiser and Cornell molecular bi-ologist Ray Wu in 1968, following the discovery of restrict-ing and polymerizing enzymes. In 1975, British biochemist

The Race to the $1,000 Genome

History in the Making

Fred Sanger Leroy Hood

6 Spring 2012

Date Organization Cost Genome2003 The Human Genome Project $300 million haploid composite2007 J. Craig Venter Institute $70 million J. Craig Venter2008 454 Life Sciences $1.5 million Jim Watson2009 Complete Genomics $3,700 George Church

The federal government estimates that the Human Genome Project (HGP) spent $300 million on DNA sequencing (not including expenditures for technological innovation). It took thirteen years to generate the final sequence (1990-2003). ‘Next generation’ sequencing technologies will soon read the 6 billion nucleotide bases that make up a diploid human genome in a single day.

Plummeting Costs

Fred Sanger invented ‘plus-minus’ sequencing, a protocol notable for the introduction of gel electropho-resis as a method of separating DNA fragments. The same year, Harvard University’s Allan Maxam and Walter Gilbert introduced an alternative chemistry that was complex, but became popular be-cause it could be performed with purified double-stranded DNA.

In 1977, Sanger published the first fully sequenced DNA-based

genome, the 5,386 nucleotide base code belonging to phage-bacterium Φ-X174. He also invented the ‘chain termination’ method which provided the basic enzymatic chemistry em-ployed in ‘first generation’ sequencing for the next twenty-five years. The Sanger method effectively rendered Maxam-Gilbert sequencing obsolete because it was more efficient and required fewer toxic chemicals.

In 1986, Applied Biosystems (ABI) produced the first automated DNA sequencer. The invention was enabled, in part, by a fluorescence-based detection system developed in Leroy Hood’s laboratory at Cal Tech. With this breakthrough technology, reading the entire human genome became a vi-able notion. As a direct result, the Human Genome Project (HGP) was organized and commenced just four years later, in 1990. Over the thirteen-year course of the HGP, commercial and academic contributors produced innovations in ‘first generation’ instrument designs and continuous improve-ments in sequencing speed and efficiency.

As the HGP made its start, and ‘first generation’ tech-nologies continued to leap ahead, foundational ideas for ‘next generation’ sequencing methods were coalescing. In 1992, original ABI founder Sam Eletr and famed molecu-

lar biologist Sydney Brenner developed massively parallel signature sequencing (MPSS), the first alternative to Sanger’s ‘chain termination’ approach, at Lynx Therapeutics, an ABI spin-off. Following a series of acquisitions, work on MPSS was folded into the development of ‘sequencing by synthesis’ (SBS), the method utilized by Illumi-na’s current machines. A diverse array of competing approaches appeared on the scene over the course of the 1990s.

As soon as the Human Genome Project was complete in 2003, the field was off to tackle the next challenge. The ‘Book of Life,’ the focal point of public hopes for over a decade, was a grand scientific and technical achievement, but it disappointed those awaiting medical miracles. It was less an answer to fundamental questions than a source of new puzzles. It was not a terminus, but a point of departure.

History suggests that the $1,000 genome will be remem-bered in much the same way – not as a paradigm-buster (despite the remarkable technological advances the race has generated), but rather as a link in a long chain of innovations made possible by prior developments in molecular biology and information technology.

History and Hype

If history tempers ‘next generation’ bravado in this instance, it also serves as an antidote to technological pessimism. Many skeptics remain leery of genomics hype. They point out that the size of the market for whole genome sequencing is a matter of speculation and debate. Genomics will be in-

Greg Lucier

Jay Flatley

Spring 2012 7

Battle in San Diego: Illumina vs. Life Technologies

corporated into medical practice as biomedical research-ers and pharmaceutical companies identify diagnostic biomarkers and develop targeted drugs. Personalized medicine will not be realized by the $1,000 genome, but rather by biomedical and biopharmaceutical research informed by analyses of whole genome sequences – and it may take some time.

All of this is true, but the history of DNA sequencing is not a chronicle of unkept promises, and the immediate impact of whole genome data is not the end of the story. It is a chapter in the middle of an epic saga about techno-logical innovation propelled by scientific and commercial competition. For over forty years, progress in DNA se-quencing has been consistent and sometimes spectacular. The field has moved from the laborious production of a few kilobytes of sequence data in a week to automated operations that generate gigabytes of data in hours. Whole genome sequencing may not deliver an instant medical revolution, but it could well provide a steadily accelerating stream of data to biomedical research – information that may be used to develop innovative approaches to health maintenance and the treatment of disease.

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San Diego competitors Illumina and Life Technologies unveiled new whole genome sequencers in January at the 2012 J.P. Morgan Healthcare Conference in San Francisco. Both machines will enter the market later in the year.

Life Technology’s Ion Proton ma-chine is fast and small, the size of a laser printer. It can sequence an entire human genome in a little over 24 hours, for a little over $1,000. The price tag for the machine is $149,000. Most sequencers em-

ploy optical technologies to read genetic code; the Ion Proton uses semiconductor technology developed by former 454 wizard Jonathan Rothberg. Last year, Rothberg used a similar device to sequence the genome of Intel co-founder Gordon Moore.

Illumina’s offering is called the HiSeq 2500. It employs se-quencing by synthesis (SBS) technology. The HiSeq 2500 is more accurate than the Ion Pro-ton, but also considerably more expensive: $740,000. Illumina

machines have lately dominated clinical and bioscience research markets due to their superior accuracy and output, but prospective buy-ers of ‘next generation’ sequencers must now weigh tempting trade-offs. Illumina CEO Jay Flatley is not concerned: “I don’t think the market will be commoditized in my lifetime.”

Reliable clinical diagnosis requires a high degree of ac-curacy and ‘next generation’ technologies have struggled to deliver ‘medical grade’ reads at low prices. If customers remain willing to pay premiums for qual-ity, the eventual victor in the race for the $1,000 genome may not reap commercial rewards. Laggards may fail in the sprint, but win in contests for market share. Still, Life Technologies CEO Greg Lucier is op-timistic about the prospects of the Ion Proton: “We have the enviable technology position.”

8 Spring 2012

From a young age, Ivor Royston wanted to cure cancer. As an adult, it became his life’s work. Trained as a physician and immunologist, he conducted pioneering studies in the diagnosis

and treatment of blood and lymph cancers. Despite his single-minded focus, Royston’s career took a series of unexpected detours.

Royston co-founded two successful biotechnology companies, established a non-profit cancer research institute, became a venture capitalist, and played a pivotal role in establishing San Diego as one the world’s leading centers of biotech research and devel-

opment. Along the way, he found himself immersed in ethical controversies, legal actions, policy scrums, a professional misconduct investigation, and large-scale institutional shifts associated with the emergence of the biotech industry.

Ivor Royston has played numerous roles in and around biomedicine and biotechnology: physician, professor of medicine, technological innovator, en-trepreneur, scientific consultant, company director, financier, philanthropist, and show business impre-sario. His story is a window on an important episode in the history of American science and industry.

" C a n c e r wa s a b l a c k b o x . N o b o d y k n e w w h at i t wa s . I f e lt i t w o u l d b e t h e n e x t f r o n t i e r i n m e d i c i n e . I wa n t e d t o w o r k o n i t . "

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The boy who wanted to cure cancerIvor Royston was born in Retford, England, in Nottinghamshire, as World War II drew to a close in the spring of 1945. His parents were refugees from Eastern Europe. His Polish father was a roofer and sheet metal worker; his Czech mother, a homemaker. Ivor was the eldest of three sons. He describes his family as “lower middle class.” When Royston was nine years of age, an uncle in America convinced his parents to move to the United States, a land “paved with gold” and ripe with “tremendous opportunity.” The family crossed the Atlantic, first to Plainfield, New Jersey, and soon after to Washington, D.C.

As a student, Ivor excelled in math and science. In middle school, he began participating in science fairs, and often found himself in the library, reading medical texts. The more he read

about human biology, viruses, and cancer, the more enthralled he became: “That’s how I developed an interest in cancer research. I was fascinated. People were dying of cancer, but no one knew what it was or what caused it.” During the summer of his senior year in high school, Royston took a job as a medical research as-sistant at the Walter Reed Army Medical Center. “The experience propelled me forward,” he says. “I really enjoyed interacting with the doctors and scientists.” By the end of the summer, Ivor knew he wanted a career in medical research.

Ivor embarked on an ambitious, single-minded journey to a career in medicine and biomedical research. He matriculated at George Washington University in 1963, and graduated from Johns Hopkins University four years later with a bachelor’s degree in biology. In 1970, at the age of twenty-five, he was awarded an M.D. from the Johns Hopkins School of Medicine.

By that time, he had compiled an impressive record of research for one so young – he had participated in studies in virology at the Agricultural Research Center in Beltsville, Maryland and the National Cancer Institute in Bethesda, and had conducted an epidemiological investigation of cancer mortality in Israel dur-ing the summer of 1967, immediately after the Six Day War. That work turned into Royston’s first scientific publication, in Cancer, the official journal of the American Cancer Society.

To complete his internship and residency, Ivor traveled across the country to Stanford University in Palo Alto, California: “I had never been west before,” he explains. He was also attracted by Stanford’s top-notch reputation in oncology. He spent two years working at the Stanford University Medical Center – a complex of light sandstone buildings that featured architect Edward Dur-rell Stone’s signature courtyards, pools, and decorative screens. Royston, who was used to the gritty, inner-city character of the Johns Hopkins’ facility in Baltimore, says: “It didn’t really look like a hospital to me.”

The biomedical researcherAfterwards, Ivor moved back to Washington. As a physician, he was eligible for a draft deferment if he served at least two years with the Public Health Service. In a stroke of luck, he was selected for a post, and for three years worked in the Bureau of Biologics at the National Institutes of Health (NIH), first as a Staff Associ-ate, and then as Chief of Viral Oncology: “I had my own lab and technicians. I started doing my own independent research on mononucleosis. It was quite productive. We were able to elucidate what was going on in infectious mono. That led to my first major New England Journal publication.”

While at the NIH, the focus of Royston’s research shifted from virology to immunology. His work on mono had focused on interactions between the Epstein-Barr virus and T and B cells: “I became fascinated with how the body reacts against viruses, and that’s immunology.” Royston started thinking hard about the immunology of cancer – and about leukemias and lymphomas, in particular. Today, thousands of investigators in academic and industrial settings are attempting to stimulate cellular or humoral responses to cancerous cells that elude or overwhelm the body’s defenses. In the mid-1970s, work in this area was just taking off. Advances in the field had opened up new lines of inquiry, and Royston followed them toward vaguely-shaped opportunities on the horizon.

Ivor decided the he needed to become board certified in on-cology and internal medicine – the double specialty would allow

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From his youth, Ivor Royston felt a calling to medicine, but also an affinity for business. As a freshman at Calvin Coolidge High School in Washington, D.C., Ivor joined an investment club with fifteen classmates. The group was called ‘The Chessmen,’ after the sixteen pieces on a side in the game of chess. The members pooled their savings to purchase second trust mortgages at a discount.

They evaluated opportunities, earned interest as notes matured, and eventually made money. Ivor was intrigued by the strategy and the assessment process: “It was a positive experience.” He credits his involvement in the club with sparking his interest in finance and business.

Below, Royston is at the head of the table.

Teen Age Businessmen

10 Spring 2012

him to pursue career goals in both cancer research and clinical medicine. As a researcher, he was intrigued by the intellectual puzzle of cancer; as a physician, he felt compelled to solve the daunting challenges that cancerous cells present to doctors, and to counter the horrible insults they inflict on patients and fami-lies. A post-doctoral fellowship in a department of oncology at a top-flight medical school seemed like the ticket to his destination. Once again, Royston decided that Stanford was the place to be, due to its prominence in cancer research. He returned to Palo Alto.

The technological innovatorBy virtue of his talent, experience, and vaulting ambition, Royston had moved onto the cutting-edge of biomedical science. He began collaborating with new Stanford faculty member Ron Levy, who was using antibodies to probe receptors on the surfaces of B and T cells. Levy hoped to locate clues to the causes and molecular character of lymphomas and other tumors of the immune system.

The work was right up Royston’s alley, and he had appeared on the scene at precisely the right moment to catch an enormous wave of change.

As Royston was making his way west to the Bay Area, momen-tous events were taking place inside a British Medical Research Council laboratory in Cambridge, England. Argentine biochemist and lab chief César Milstein and German cell biologist Georges Köhler, a visiting post-doc, were inventing hybridoma technol-ogy, a method of cell hybridization (fusion) that enabled, for the first time, the high-volume production of monoclonal antibodies.

Hybridoma cells are products of fusions in which the genetic material of a B-lymphocyte that produces a specific, desired anti-body is transferred to a cancerous lymphocyte (Köhler and Milstein used murine myeloma cells) that can be maintained indefinitely in culture. The ‘immortality’ of the resulting hybrid cell permits the continuous harvesting of identical (monoclonal), highly specific antibody proteins that have multiple uses in biological

Left: Royston with post-doc Robert Dillman, inspecting a cell sorter at UCSD in 1981

Right: Royston (second from right) with peers at Stanford University in 1976

Spring 2012 11

and biomedical research. The invention provided researchers with reliable sup-plies of standardized reagents, and earned Köhler and Milstein the 1984 Nobel Prize in Physiology or Medicine.

Royston remembers reading about the invention in the August 1975 issue of Nature. He immediately recognized its significance for the immunological study of cancer: “It was obviously the answer.” Prior progress in the field had come in piecemeal fashion, haphazardly, in fits and starts. Inexhaustible supplies of specific antibodies held out the promise of genu-inely cumulative advances toward com-prehensive understandings of cancer cells. Before Royston could employ hybridoma technology, however, he had first to obtain Milstein’s myelomas: “I needed that cell line.” It was indispensable at that time, as it was the only source of fusion partners that would yield viable hybridomas. It didn’t be-come available for another year and a half.

In 1976, as Köhler and Milstein ironed out kinks in their cell hybridization proce-dures, immunologist, geneticist, and cell biologist Leonard Herzenberg arrived in Cambridge as a visitor to Milstein’s lab. He was on sabbatical leave from the Stanford University School of Medicine. Herzenberg learned how to perform fusions and tend to hybridoma clones. When he returned to Stanford at the end of a year, he car-ried some of Milstein’s myeloma cells with him. He passed them out to interested col-leagues, and gave instruction in the art of hybridoma technology. In the late spring of 1977, the Stanford University Medical Center became one of the few places in the world in which monoclonal antibodies could be manufactured.

Ron Levy was a recipi-ent of some of the cells, and he passed them on to Royston. Royston then suggested to a friend, lab technician Howard Birndorf, that they tackle hybridoma technology as a team: “I said, ‘Howard, we ought to figure out how to do this.’” From then on, Birn-dorf was Royston’s designated hybridoma maker. Birndorf says, “I was the technical guy. Ivor knew how to think about mono-clonals. I knew how to make them.” The two friends didn’t know it yet, but they had lucked into a gold mine.

The tenure-track professor of medicineWhen Royston finally received the cov-eted myelomas, his two-year postdoc-toral fellowship was drawing to a close. He had been on the job market through the 1976-1977 academic year, looking for a permanent academic post. He received offers from several elite institutions, and ultimately selected the School of Medicine at the University of California, San Diego (UCSD). Birndorf moved with him.

Royston found the UCSD opportunity particularly appealing because the duties included both research and clinical prac-tice, and the university was planning to open a new cancer center. He was assigned laboratory space at the Veteran’s Adminis-tration Hospital near the main university campus in La Jolla. It was tiny: 250 square feet on the sixth floor in the ‘hemoc,’ the hematology and oncology unit. Lab bench-es lined both sides of the room. There was a single bench top tissue culture hood. “That was it,” says Birndorf. “Ivor had to take the

l e a s t attractive space because he was the new kid.” The lab was funded by government grants that Royston had secured. “I received funding,” he says, “because monoclonal antibodies were a brand new, hot area.”

When the lab was adequately tooled, Royston and Birndorf began making an-tibodies to lymphoma antigens. It was groundbreaking work. Says Royston: “No one in San Diego had ever worked with monoclonal antibodies. I was the first. Ron Levy was doing it up at Stanford. Oth-ers were doing it at the Wistar Institute in Philadelphia and the Fred Hutchison Cancer Center in Seattle. I can count the places on one hand. It was a brand new technology.”

Royston’s studies generated a lot of information about the characteristics of lymphoma cells: “It worked out quite well. It was very easy for us to do.” He also began to think broadly about other applications of monoclonals: “I began to realize how powerful these antibodies were about six months after arriving at UCSD. I had a ‘Eureka!’ moment. It dawned on me that a whole new generation of therapeutics could be developed for treating cancers.”

The entrepreneurThe idea of commercializing hybridoma technology grew out of the need to gener-ate more antibodies for clinical research

La Jolla Veteran’s Administration Hospital

Howard Birndorf Royston in the lab

to be continued...12 Spring 2012

than the tiny VA Hospital lab was equipped to produce. Royston wanted to inject an-tibodies into patients with lymphoma and leukemia: “I remember thinking, ‘How am I ever going to be able to treat patients?’ That’s where the idea of the company came from. We couldn’t manufacture these anti-bodies at the university. I realized we were going to be encumbered by that.” It wasn’t long before Royston and Birndorf were struck by the idea of going into business. It was early in 1978.

Birndorf recalls, “Our initial business plan was, ‘Let’s make and sell antibodies for research pur-poses.’” Royston and Birndorf saw that hybridoma technology could be used to produce standardized reagents. Antibody supplies could be vastly improved and continu-ously replenished without hav-ing to purify blood, and without having to immunize and bleed animals repeatedly. Royston talked to suppliers of conventional products, and realized how far out on the curve he had landed: “They had farms with goats and sheep and horses. You don’t need goats and sheep and horses to make monoclonal antibodies. I realized this was a major shift in thinking.”

Ivor wasn’t sure how to proceed. “In my typically compulsive way,” he recalls, “I went to the library and checked out a book called How to Start Your Own Business.” It was rare at that time for life scientists to be involved in business, but while at Stanford, Royston had heard all about Paul Berg, Stanley Cohen, and recombinant DNA. He had heard about Herb Boyer, too: “I was familiar with Genentech. I knew it was doable.” He hadn’t inquired about financ-ing details, however, and had never heard of venture capital. In 1978, venture capital was not yet a commonplace term.

What Ivor and Howard knew for cer-tain was that they couldn’t afford a startup on their own. Birndorf was soon on a plane back to his hometown of Detroit search-ing for ‘angels’ within his constellation of acquaintances: “I went back and pitched this to several wealthy friends of my par-

ents. I had a friend in Chicago who knew commodities brokers. I asked if they would be interested.” He found no takers: “It was all so technical, so wild, that nobody un-derstood it.”

Birndorf returned empty-handed and frustrated, but while he was away, Royston had discussed the idea with his wife, Co-lette, an oncology nurse whom he had re-cently wed. The conversation led to a ser-endipitous connection. It turned out that Colette knew a venture capitalist – Brook Byers, of Kleiner, Perkins, Caufield & Byers, the San Francisco and Menlo Park firm that had seeded Genentech and Tandem Com-puters, and had, since its inception in 1972, established a reputation as one of Silicon Valley’s premier venture capital outfits. Colette put Royston in touch with Byers, who agreed to meet the young physician in San Francisco. Looking back, Royston says, “I’m sure Brook was just doing her a favor,” but the coincidental link turned out to be a marvelous stroke of good fortune.

On May 1, 1978, Royston and Byers met for lunch. Royston elected to highlight ‘cloning’ in his explanation of hybridoma technology: “I sat down with Brook and said the magic words. I knew his firm was involved with Genentech. I said, ‘You guys know how to clone genes. We’re cloning antibodies.” He sketched the basics of hy-bridoma technology on a napkin and ex-plained that it could be used to generate unlimited amounts of specific antibodies

with uses in biological research, clinical diagnostics, and therapeutics. Byers was intrigued. Royston believes that his expe-rience with Genentech had primed him for a similar opportunity in immunology.

A few days later, Byers sent word that his partners would visit San Diego to meet

Royston in person and see his lab-oratory. Royston and Birndorf pre-pared to “put on a show.” In early June, Kleiner, Perkins, Caufield, and Byers flew down from the Bay Area. “It was the only time,” Royston says, “I ever saw all four of them together.” The venture capitalists spent the day taking in a hybridoma-making demonstra-tion and talking about Royston’s work at the UCSD School of Medi-cine.

Late in the afternoon, Royston and Birndorf drove the visitors to the airport. The group went into the terminal and sat in a small

lounge to conduct business. Tom Perkins was the principal spokesman for the investors. Royston remembers him asking: “‘What is it going to take, Ivor, to make monoclonal antibodies outside of your laboratory?” I said, ‘We need a couple of hundred thousand dollars.’ Perkins said, ‘I’ll give you three. Now show us you can

make antibodies outside the lab.’” Birndorf says it was “the first and last time anybody offered us more than we were asking for.”

And so it was that Ivor Royston em-barked on adventures in commercial bio-technology. Up until this point, his career had followed a conventional path through well-ordered institutions. Beyond it, he moved into uncharted territory on an un-tamed frontier. We’ll tell more in Part II of Ivor Royston’s story – see the next issue of LSF Magazine.

images courtesy M

entus, Inc.

J. Leslie Glick at the opening of Genex’s first research facility in 1980

Spring 2012 13

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, recol-

lections, and testimonies of history-makers.LSF is assembling a virtual oral history archive. We are record-

ing, transcribing, and publishing interviews with leading figures in the biosciences and the biotech industry. These documents contain stories about the history of biotechnology that have yet to be heard by scholars, journalists, and the general public. This month, we are adding to the collection an interview with biotech pioneer J. Leslie Glick.

Les Glick received undergraduate and Ph.D. degrees in biology from Columbia University and performed postdoctoral studies at Princeton. He subsequently became a faculty member at SUNY-Buffalo with a joint appointment at the Roswell Park Memorial Institute. In 1970, after five years as an academic, he was “bitten by the entrepreneurial bug,” and co-founded a cell-culture manu-facturing company called Associated Biomedic Systems (ABS). He became Chairman and CEO three years later.

In 1977, Glick came across an ad in Science: “Wanted: CEO for a genetic engineering firm.” He knew of Genentech and Cetus, and was intrigued. He answered the ad, and learned that there was not yet a company, but that a Princeton, New Jersey entrepreneur named Bob Johnston was eager to start one.

Glick called on David Jackson, a University of Michigan biochemist whom he had met at a scientific conference in 1975, for an opinion on the prospects for such a business. Jackson was well-positioned to make an assessment. As a postdoc in Paul Berg’s Stanford laboratory in 1972, he had helped create the world’s first recombinant DNA molecule. Jackson suggested an unexploited niche: employing genetically-engineered bacteria to improve

the manufacture of specialty chemicals, amino acids, vitamins, enzymes, and hormones for industrial uses.

Glick conducted further research on fermentation techniques and identified opportunities across a variety of fields – chemical processing, food processing, animal health, waste treatment, and the production of cleaning agents, for example. Glick decided to proceed. Bob Johnston secured funding, Glick established the company in Rockville, Maryland, and Genex went on to become one of the largest and most successful biotech operations of the early 1980s.

Dr. Glick’s oral history tells the full story. To read the transcript in its entirety, visit LSF’s online oral history archive at biotechhis-tory.org. Below is an excerpt in which Glick discusses his decision to leave academia and go into business at ABS:

The LSF Oral History Program

This was something I knew absolutely nothing about. I told my father about it. I was doing pretty well as an academic, so he said to me, ‘What do you know about business? How can you go into business?’ I said, ‘I know nothing about business. We’ll do it for six months, we’ll go bankrupt, and I’ll go back to academia.’ He must have scratched his head on that. It was an experiment. You try things and if they don’t turn out right, you pick yourself up and you do it all over again. At the end of three years, my partners went back to academia, but I was like a duck in water at that point.

Genex CEO J. Leslie Glick

14 Spring 2012

In 2007, restaurants in Shanghai, China began offering patrons a purple potato called Purple Orchid Three. It was bred

from seeds exposed to mutation-inducing cosmic radiation during a trip into outer space. The unusual color resulted from overexpression of the flavonoid anthocy-anin. Grown by the Haikou Purple Orchid Co. on Hainan Island, China’s southern-most province, Purple Orchid Three en-joyed a faddish popularity. But it wasn’t a novelty. Since 1987, China’s space breeding program has produced dozens of mutant crop varieties.

Radiation-induced mutagenesis has a long history. The United States and the Soviet Union began sending seeds and plants into space in the 1960s, and earth-bound mutation breeding experiments date back to the beginning of the 20th century. Environmental conditions in space (mi-crogravity, weak geomagnetic fields, and an ultra-clean vacuum) are especially con-ducive to genetic alteration, but terrestrial applications of X-rays and gamma rays are also effective means of crop modification

and improvement. The aim of mutation breeding is to

introduce genetic variation. As rates of genetic change increase, so do chances to select desirable traits for propagation. Most mutations caused by exposure to radiation or chemical mutagens prove useless, but some increase crop yields, confer resistance to diseases or pests, or enhance fitness in stressful environmental conditions, such as drought, frost, or poor soils (with depleted nutrients, extremes in salinity, acidity, or alkalinity, etc).

Over 2,700 mutant plant varieties have been developed by irradiation. Many are ornamentals (the familiar chrysanthemum, for example), but 65% are food crops bred for human consumption. Best-selling mutants include the red-fleshed Rio Star® grapefruit (see sidebar), the disease-resis-tant Gold Nijisseiki pear, and high-yield Creso durum wheat, along with varieties of alfalfa, barley, chickpeas, pepper, rice, sesame, tomato, and many more.

Today, mutant plant varieties are wide-ly distributed. Consuming them is practi-

cally impossible to avoid, but relatively few people are aware of their ubiquity. There is irony in this circumstance. Scientific assess-ments of risks associated with agricultural biotechnologies show no appreciable dif-ference between plants modified by tradi-tional selection, hybridization, radiation, or the tools of molecular genetics, yet public fears have prompted governments to impose strict forms of regulation on experimentation and industrial production involving recombinant DNA. Policy debates on genetically modified organisms can be gainfully informed by an historical review of radiation mutation breeding.

The Origins of Radiation Induced-Mutations in PlantsX-rays and radioactivity were discovered at the end of the 19th century, and biolo-gists as well as physicists soon began to investigate their effects. Testing the hy-pothesis that radiation induces genetic changes, Dutch botanist Hugo de Vries began exposing plants to radium. Others,

AtomicGardensPublic Perceptionsand Public Policy

Spring 2012 15

such as Charles Stuart Gager, Director of the Brooklyn Botanic Garden, built on de Vries’ work and subjected a wide variety of plants to X-rays. But solid evidence of artificially produced mutations was not marshaled until the late 1920s.

In 1927, while working at the Univer-sity of Texas in Austin, Herman Joseph Muller (see sidebar), a student of famed Columbia University geneticist Thomas Hunt Morgan, established that X-rays did indeed cause genetic mutations in fruit flies. The following year, geneticist Lewis J. Stadler published three papers reporting X-ray induced mutations in barley.

Stadler was an assistant professor at the University of Missouri and a consultant to the U.S. Department of Agriculture. He

had taken up the study of maize genetics in 1920 after reading Morgan’s classic text, The Physical Basis of Heredity. Following his 1928 success, Stadler continued experi-ments on numerous food crops, including barley, oats, and wheat.

Geneticists of the era concluded, per-haps over-optimistically, that mutations could be artificially induced at rates exceed-ing those of spontaneous change. Stadler remained skeptical, and continued to pursue the question experimentally. Nev-ertheless, his discovery motivated many researchers to set up X-ray machines in their laboratories.

Scientists in the late 1920s and the 1930s explored the effects of radiation on a wide variety of plants. Investigations continued during the Second World War, although scientific communications were often stymied by wartime secrecy.

Gamma Fields And Peaceful Applications Of Atomic EnergyAfter the war, interest grew in peaceful ap-plications of atomic energy. In 1946, Presi-dent Harry Truman signed the Atomic En-ergy Act, which established the U.S. Atomic Energy Commission (AEC) and placed the development of nuclear weapons and power under civilian control. Radiobiologi-cal research programs were assembled at nuclear energy development sites.

National laboratories in the United States, Europe, and the Soviet Union began using gamma rays to induce mutagenesis in plants. Many prepared plots that came to be called ‘gamma fields’ or ‘atomic gardens.’ The first gamma field was established in 1948 at the Brookhaven National Labora-tory on Long Island. By 1964 the lab had installed a number of different ‘gamma’ facilities to study plant irradiation—a field, a forest, a greenhouse, a cell, and a pool. In a 1967 issue of Radiation Botany, a jour-nal first published in 1961 for specialists in radiation mutation breeding research, Brookhaven radiobiologist Arnold H. Spar-row provided a complete survey of the Laboratory’s radiation facilities.

The gamma field encompassed 12.8 acres of land that Brookhaven scientists used to experiment on more than 300 plant species. In 1959, the researchers observed that radiation from the gamma field had injured nearby trees. The finding prompted them to create a ‘gamma forest,’ which ex-amined the effects of gamma rays on an entire ecosystem. The gamma greenhouse

was a concrete structure with a lead cap surrounded by earthen embankments. Cobalt-60 was raised from a shielded re-ceptacle in the floor. The ‘hot cell’ was a small (2 meter) shielded chamber. A radia-tion source was lowered from the ceiling. Plants were placed on removable shelves that could be accessed through a set of slid-ing doors coated with lead. In the gamma pool, radioactive materials were lowered into the water to shower plant specimens placed at the bottom.

The world’s largest gamma field (100 meters in radius) opened in April 1962 at

The Rio Star® Grapefruit, a product of radiation-induced mutations, now accounts for three quarters of all grape-fruit trees grown in Texas. The mutant strain was developed by Richard A. Hensz, a Texas horticulturalist and director of the Texas A&I University Citrus Center in Weslaco, Texas. Work-ing at the Brookhaven National Laboratory in Long Island, Hensz began irradiating seeds from the famous Ruby Red grapefruit using X-rays in 1963. In 1976, he produced a new strain that was resistant to cold tempera-tures. Grapefruit crops had been devastated by severe freezes in the past; when another hit in December of 1983, the Rio Star® trees were spared. The Citrus Center began giving away Rio Star® seeds to farmers in 1984. The sweet, dark-red fruit quickly became popular among growers and consumers.

Herman Joseph Muller (1890-1967) is best known for his work on the genetic effects of ion-izing radiation, and the devel-opment of X-ray mutagenesis. After graduating from Columbia University, he began to take an interest in the genetics work being done in Thomas Hunt Morgan’s famous Drosophila Fly Room and joined Morgan’s group in 1912. Muller subse-quently became Professor of Zo-ology at the University of Texas in Austin where he announced his discovery of the mutagenic effects of X-rays in 1926. His pioneering contributions were honored with a Nobel Prize in Physiology or Medicine in 1946. Muller was also active politically – after World War II, he encour-aged public awareness of the long-term effects of radioactive fallout.

Gamma Field at the Institute of Radiation Breeding in Japan

Gamma Greenhouse at the Brookhaven National Laboratory

16 Spring 2012

the Institute of Radiation Breeding (IRB) in Ohmiya, Japan. Plants were arranged into concentric circles sur-rounding a radiation source (Cobalt-60). A shielding dike eight meters tall surrounded the field to prevent gamma rays from escaping. The radi-ation source was raised on a tower up to six meters above the ground. The plants were exposed to different levels of radiation to produce varying rates of mutation depending on proximity to the source—from 300,000 times the nor-mal background radiation level at the closest point to 2,000 times at the furthest. The IRB has officially released 470 mutant cultivars, including Reimei rice, Raiden and Raikou soybeans, and the Golden Nijisseiki pear.

A number of international meetings and conferences were held in the 1960s with the goal of multiplying mutation breeding programs and expanding practi-cal applications. The most important were organized by the UN’s Food and Agricul-tural Organization (FAO) and the Vienna-based International Atomic Energy Agency (IAEA). An international symposium spon-sored jointly by the FAO and IAEA was held in 1969, and led to the publication of the first Manual on Mutation Breeding. This decisive meeting marked a fundamental shift in the field away from basic research towards practical applications. Eleven years later, another joint symposium, entitled “Induced Mutations—A Tool in Plant Re-search,” elaborated ways in which induced mutations could serve instrumental purposes in a number of fields, including molecular genetics.

Some twenty gamma fields were eventually con-structed worldwide. Only a few remain operational, most in Europe and Asia. U.S. scientists have largely abandoned radiation breed-ing research, but American programs produced notable results in their time. In his 1967 review in Radiation Botany, Sparrow identified eight widely-cultivated mu-tants registered by American

laboratories between 1953 and 1963. On the list were food industry staples, including early maturing Sanilac beans, disease resis-tant Alamo X oats, the tough-hulled NC4X peanut, and winter-hardy Pennrad barley.

By the mid-1980s, American and West-ern European plant researchers had turned to gene splicing, and mutation breeding had migrated to other parts of the world. Radiation-induced mutagenesis produces random mutations; recombinant DNA enables precision interventions. Where know-how and skill in molecular biology accumulated, mutation breeding came to be seen as a relatively blunt instrument, an inferior tool. Paige Johnson, a nanotech-nologist who also writes on garden history, provides apt analogies: “If you think of genetic modification today as slicing the genome with a scalpel, in the 1960s they were hitting it with a hammer.”

Despite its lack of specificity, radiation

breeding remains an impor-tant tool for crop research. It was embraced in the de-veloping world because of low adoption costs. Today, interest in Asia remains par-ticularly strong. In 2008, a gamma greenhouse twice the size of the IRB gamma field was constructed in Malaysia. The extraterrestrial creation of Purple Orchid Three is merely one among many late developments in mutation breeding.

Atomic Advertisements and Atomic Enthusiasts

Experimentation with irradiated seeds was not confined to the hallowed halls of science. From the 1940s through the early 1960s, enterprising businesspersons marketed mutants to the general public. In the 1940s, David Burpee, head of the W. Atlee Burpee Seed Company, foresaw limitless opportunities: “Yesterday we were using the old established catch-as-catch-can methods. Tomorrow we will work in a laboratory as scientifically equipped as that of a chemist or physicist, and our ex-periments will be systematically planned in advance…through the use of X rays, light rays, aging, mutilation, and chemicals we may induce mutations almost at will.”

Burpee hawked seeds modified by chemical mutagens, but ‘atomic seeds’ were sold in the late 1950s and early 1960s by dentist-turned-entrepreneur, Clarence J. Speas. Speas began experimenting with X-

rays in 1937, as an instructor in oral surgery at the Univer-sity of Vermont. In 1957, he received approval from the Atomic Energy Commis-sion to obtain a quantity of Colbalt-60, which he used to irradiate seeds in a backyard cinderblock bunker on his farm in Tennessee. A series of photos from the May 1, 1958 issue of Life magazine show Speas giving a tour of his fa-cility to high school students and showing off his tray of irradiated seedlings. In 1960, he founded Oak Ridge Atom Industries, Inc. to sell ‘atom-ic’ products.

On May 24, 1961, the

Spring 2012 17

company hosted a conference in Knoxville, Tennessee on ways to improve tobacco by irradiating seeds, seedlings, and flowers. Speas appealed to the tobacco industry for support and explained the science of radiation-induced mutagenesis. Charles M. Sprinkle, Coordinator of Agricultural Research at the R.J. Reynolds Tobacco Co., wrote back to the home office:

Dr. Speas discussed in detail the work he and his associ-ates have been doing in the field of irradiation. He gave each person present a bound report containing a general outline of a proposed re-search program for altering or improving tobacco. He pointed out that his orga-nization has close personal contacts with around 6,000 scientists at Oak Ridge who are available to do consult-ing work. In addition, he can engage people in vari-ous agricultural fields at state experiment stations. He said that research could be conducted much faster by private enterprise than by traditional experiment sta-tion methods. Experiment station personnel and facili-ties would be engaged for certain phases of the work.

Sprinkle also listened to K. Wayne Graybeal, a Director at Oak Ridge, who addressed “the removal of carcinogens by irradiating finished cigarettes or by alter-ing the tobacco plant.” Graybeal assured his audience that “if the tobacco industry desires it, a program can be oriented in this direction.”

Oak Ridge Atom Industries failed to develop a non-carcinogenic cigarette, but it did produce a string of successes including

early prolific straight neck squash, Califor-nia Wonder peppers, and New Hampshire midget watermelons. Newspapers occa-sionally reported on Speas’ more fantastic creations. A 1962 article in the Lodi News-Sentinel told of “200 tomatoes produced on one plant, which grew to a height of more than ten feet in a five-gallon bucket.” Other miraculous results included roses of four

different colors on one rose bush, a seven foot-tall petunia, tomatoes shaped like sau-sages, and corn with eight ears on a stalk.

The first public showing of an ‘atomic garden’ took place on March 4, 1961 at the Home and Flower Show in Cleveland, Ohio. Life magazine published a photo spread on the event. The images drew attention to altered or enhanced traits, such as un-usual colorings or bloom sizes. Housewives

were shown marveling at atomic plants and seeds. Eventually, ads for atomic gardens appeared in many leading dailies – the New York Times, the Los Angeles Times, and the Chicago Daily Tribune. Common themes were public participation in science, the enjoyment of conducting one’s own ex-periments, and pecuniary opportunities. An advertisement for Oak Ridge Atom In-

dustries promised a $3,000 cash prize to the winner of a contest for “the most unusual plant.” It also agreed to “purchase or pay royalties on new varieties deemed to have commercial value.”

The atomic gardening fad was brief, but it portrayed radiation-induced mutagenesis in wholly positive terms. Consumers were assured that irradiated seeds were not radioactive, and that mutant plants embodied improvements, not hazards. An Oak Ridge ad in the Chicago Daily Tribune encour-aged the public to join in “100% safe scientific experiments. The seeds are safe to handle; the veg-etables are safe to eat.” Another ad proclaimed that “Atomic gar-dening is no longer restricted to the laboratory! Now every ‘green-thumb’ gardener in Chicago can share in this exciting develop-ment!”

Public Perceptions and Scientific Understanding

Mutation breeding was popularized during a time of great technological optimism. The dangers of radioactivity were widely-publicized and broadly understood, yet the products of radiation breeding were incorporated into the food supply without generating fear or controversy. Not so for new agricultural biotechnologies employ-ing the methods of molecular biology.

When crops containing genetically-

Muriel Howorth was a middle-class British housewife and atom-ic enthusiast who championed the benefits of nuclear power. In 1959, Howorth founded the Atomic Gardening Society. She gathered irradiated seeds from American breeders, and received X-rayed peanuts from Walton C. Gregory, Professor of Agronomy

at North Carolina State College. Media attention garnered by the ‘atomic peanut’ helped Howorth generate interest in the Atomic Garden Society. She encour-aged members to document the changes that took place in their plants, providing guidance in her manual entitled Atomic Gardening.

Radiation Tower at the Institute of Radiation Breeding in Japan

18 Spring 2012

modified organisms (GMOs) first appeared in the 1990s, protests were organized by environmental groups such as Greenpeace, Friends of the Earth, and the Earth Lib-eration Front. ‘Frankenfood’ horror stories were promulgated by activists: ‘GMOs pose risks of ecological contamination;’ ‘GMOs threaten populations of Monarch butter-flies;’ ‘GMOs are potentially allergenic and dangerous to consume.’ The claims were false, dubious, or grossly exaggerated, but, as sociologists Sheldon Krimsky and Roger P. Wrubel have observed, once “techno-myths” become established, they are dif-ficult to dislodge.

Media publicity fed skepticism and hostility toward recombinant crops, and public opposition prompted the European Union to place a moratorium on the impor-tation and sale of GMOs in 1998. The ban was lifted only after the U.S. protested to the World Trade Organization and stricter labeling practices were implemented in 2004. Vague fears of biotech-related haz-ards became so acute and so widespread during this period that food supplies in humanitarian aid shipments to Zambia and Zimbabwe—where some 2.5 million people were at risk of starvation—were rejected at African ports because they contained GMOs.

Gross incongruities obtain between public perceptions of GMOs and the scien-tific consensus on the issue. Critics describe the production of GMOs as unnatural, but human beings have been performing genetic manipulations in plants and ani-mals for thousands of years. Agriculture originated with plant domestication via

seed selection as early as 10,000 years ago. Plant hybridization and radiation-induced mutagenesis later permitted the artificial introduction of genetic variation. Forms of hybridization – grafting and fusing plants in order to transfer and combine dispa-rate traits in the same organism – were refined in the late 19th century, and allowed semi-directed genetic modification. The principal advantage afforded by radiation-induced mutagenesis was acceleration of random mutation rates. Nearly all foods consumed by human populations are prod-ucts of one or more of these techniques of intentional genetic manipulation.

Contemporary molecular-scale inter-ventions do not represent a break from prior breeding methods. Recombinant DNA has enabled directed genetic altera-tions and the design of transgenic species, but there is no scientific basis for distin-guishing organisms engineered by recom-binant means from organisms produced by spontaneous mutations, selective breeding, hybridization, or irradiation.

Scientific assessments have consistent-ly found that the introduction of recom-binant DNA into food supplies does not pose a unique risk. That is, a recombinant organism poses the same kind of risk as a non-recombinant organism. What mat-ters is how an organism interacts with its environment, not how the organism was produced.

Research, Risk, and RegulationIn the United States, the regulatory ap-paratus for agricultural biotechnologies was sketched in a 1986 statement issued by the Office of Science and Technology Policy (OSTP), called the “Coordinated Framework for Regulation of Biotechnol-ogy.” Regulations have been established and enforced by three agencies: the Food and Drug Administration (FDA) evaluates new food products, the Environmental Protection Agency (EPA) determines the safety of microbial pesticides and other microorganisms, and the Department of Agriculture (USDA) considers the status of new plants and weeds.

In 1992, the FDA declared that food products derived from transgenic plants are “not inherently dangerous” and do not re-quire special regulation. The agency could find no rationale for holding recombinant genes, proteins, or organisms to different standards in composition and processing than conventional crops. However, while the FDA determined that recombinant products were identical in form to conven-tional products, the EPA and USDA – citing ecological concerns – vastly increased the scope of regulation, requiring case-by-case reviews and lengthy field tests. Crops al-tered by radiation-induced mutagenesis had never provoked such a reaction, and

Spring 2012 19

were not bundled into the new classifica-tion created for recombinant products.

The policies adopted by the EPA and USDA were more responsive to public con-cerns and wishes, and placed less emphasis on expert testimonies. They also gener-ated unintended consequences that have since become systemic, bureaucratically-sustained facts of commercial and scien-tific life: public and private investment in agricultural biotechnology has dried up, technical progress has been retarded, tight regulations have reinforced consumer wariness, and opponents of biotechnol-ogy have had more opportunities to delay the development and release of GMOs via litigation in the courts.

In January of 2001, the White House Council on Environmental Quality (CEQ) and the Office of Science and Technology Policy (OSTP) released the results of an

exhaustive review: “No significant negative environmental impacts have been associat-ed with the use of any previously approved biotechnology product.” Proponents of agricultural biotechnologies find it ironic that poorly-informed environmental activ-ists have protested and effectively arrested the development of tools that could reduce pesticide use, require less land for farming, and leave more room for natural habitats that promote biodiversity. Yet, it would be counterproductive for those promoting scientific approaches simply to reiterate misunderstood facts and figures.

In a 2000 commentary in Nature Bio-technology, policy analysts Ambuj Sagar, Arthur Daemmrich and Mona Ashiya noted that when confronted by new technological risks, such as those posed by recombinant DNA, public constituencies tend to form opinions not only by evaluating technical

facts and expert competence, but also by assessing the ways in which the social ties, economic interests, and political allegianc-es of policymakers and scientific authorities bear on grounds for trust. “Biotechnol-ogy’s future,” they concluded, “ultimately relies on governing institutions listening and responding to the public, rather than discounting key stakeholders as irrational, scientifically illiterate, or technophobic.”

If the potential of agricultural biotech-nology to improve crops and solve urgent environmental problems is to be realized, public fears cannot be blithely dismissed and ignored. Fears will dissipate when pub-lic understandings of science are enhanced and transformed. As the tale of radiation-induced mutagenesis illustrates, history can serve as a tool of enlightenment.

A. M. van Harten. (1998). Mutation Breeding: Theory and Practical Ap-plications. Cambridge: Cambridge University Press.

Q. Y. Shu. (2009). Induced Plant Mutations in the Genomic Era. Ed. Rome: Food and Agricultural Organi-zation of the United Nations.

B. S. Ahloowalia, M. Maluszynski, and K. Nichterlein. (2004). “Global impact of mutation-derived varieties.” Eu-phytica. 135: 187-204.

Suggestions for further reading...

20 Spring 2012

Klaus Buchholz and John Collins. Concepts in Biotechnology: History, Science, and Business. Weinheim, Germany: Wiley-VCH, 2011. 490 pp. $75.00Klaus Buchholz and John Collins have combined a technical history of industrial applications of biological tools, with discussions of law, economics, business, manufacturing, and government regula-tion. The text traces the development of scientific tributaries – disciplines, discoveries, and techniques – over time, from 1850 to the emergence of recombinant DNA and the ‘new’ biotechnology in the 1970s, through the present state-of-the-art in bioprocess engineering, industrial biotechnology, plant biotechnology, and biopharmaceuticals. Sections on biomedicine include coverage of DNA sequencing, genomics, personalized medicine, stem cells, and regenerative medicine. The authors, Buchholz, a German chemist, and Collins, an English microbiologist, have been active participants in the biological sciences and the life sciences industry for over forty years.

Elizabeth Popp Berman. Creating the Market University: How an Academic Science Became an Economic Engine. Princeton, NJ: Princeton University Press, 2011. 278 pp. $35In the U.S. in the late 1970s and early 1980s, ties deepened considerably between academic institutions and market-based economic actors. Universities became closely attuned to the needs of industry and to the economic value of research conducted on their premises. Elizabeth Popp Berman describes the change as a shift in institutional logics – academic institutions once embodied scientific purity, but began increasingly to respond to economic imperatives. Why, Berman asks, did ‘market logic’ become influential in academic settings? Rather than attributing the change to the ‘animal spirits’ of capitalism, or technological breakthroughs that imbued research with practical utility and market value, Berman credits the government with effecting the transformation. She contends that that entrepreneurial ingenuity and innovative processes of technological development were conjured up by administrative incentives to commercialize research. The burst of high-tech innovation that emerged from academic institutions in the 1970s and 1980s resulted, so the argument goes, from a series of government policies implemented to transform universities into engines of economic growth.

Jennie Popp, Marty Matlock, Nathan Kemper, Molly Jahn, eds. The Role of Biotechnology in a Sustain-able Food Supply. Cambridge, UK: Cambridge University Press, March 2012. 300 pp. $55. This edited volume poses a weighty question: how can the nations of the world simultaneously feed growing populations and preserve fragile ecosystems? Contributors consider the possible role of agricultural biotechnology. They represent a wide range of academic disciplines, including agricultural economics, agronomy, animal science, bioengineering, biostatistics, communications, entomology, environmental science, food science, plant breeding and genetics, plant pathology, public health, and soil science. The benefits, costs, risks, and ethics of recombinant DNA, transgenic plants and animals, and GM foods have been roundly debated since the early 1980s. This book offers a fresh perspective. Chapters on technical, ecological, economic, and political issues are linked by the theme of sustainability and a focus on long term outcomes. The authors do not restrict their analyses to problems and solutions articulated by present stakeholders; they inquire into actions that can be taken now to ensure an economically viable and healthy food future for generations in perpetuity. The book offers no simple answers, but the editors endorse cooperation and collaboration across multiple disciplines as a key to future food security.

Biotech Bookshelf

G. Steven Burrill, ChairBurrill & Company

Dennis GillingsQuintiles Transnational

John LechleiterEli Lilly & Company

Phillip SharpMIT (Academic Advisor)

Henri TermeerGenzyme Corporation

Arnold ThackrayChemical Heritage Foundation

Joshua Boger, Co-ChairVertex Pharmaceuticals

Carl Feldbaum, Co-ChairBiotechnology Industry Organization

Daniel AdamsProtein Sciences

Sol BarerCelgene

James BlairDomain Associates

William BowesU.S. Venture Partners

Brook ByersKleiner Perkins Caufield & Byers

Ronald CapeCetus Corporation

Robert CarpenterHydra Biosciences

Frederick FrankPeter J. Solomon Company

Jay FlatleyIllumina

Martin GerstelCompugen

Joseph GoldsteinUT Southwestern

James Greenwood Biotechnology Industry Organization

Harry GruberTocagen

David HaleHale BioPharma Ventures

William HaseltineAccess Health International

Paul HastingsOncoMed Pharmaceuticals

Susan Desmond-HellmannUniversity of California

Perry KarsenCelgene

Arthur LevinsonGenentech

Greg LucierLife Technologies

Joel MarcusAlexandria Real Estate Equities

John MartinGilead Sciences

Alan MendelsonLatham & Watkins

Tina NovaGenoptix

Stelios PapadopoulosExelixis

Richard PopsAlkermes

George PosteArizona State University

William RastetterReceptos

Roberto RosenkranzRoxro Pharma

Ivor RoystonForward Ventures

William RutterSynergenics

George ScangosBiogen Idec

Steven ShapinHarvard University

Stephen SherwinCeregene

Jay SiegelJohnson & Johnson

Vincent SimmonGenex Corporation

Mark SkaletskyFenway Pharmaceuticals

Thomas TuriCovance

J. Craig VenterJ. Craig Venter Institute

Advisory Board (in formation)*

Founding Board of Directors*

*One affiliation past or present

The Life Sciences Foundation (LSF) has been established to record, preserve, and make known the story of biotechnology — that complex mixture of brilliant science, daring entrepreneur-ship, and socio-political realities that has become central to hu-man hope in the new millennium.

Looking back is a means of understanding the present

and acquiring wisdom with which to move forward. LSF dis-seminates the lessons of the past by acting as a clearinghouse for materials and information. The Foundation aims to collect and curate the historical record, enrich it through research and publication, and share it with institutions and organizations en-gaged in complementary heritage projects.

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