It was here in San Francisco that scientists were given the freedom to discover the last great breakthrough in medicine, recombinant DNA, while religious ideologues were forcing Recombinant DNA labs to be shut down in Boston, Massachusetts. Had San Francisco not maintained its support of science and medical research, we would not have had the discovery at the University of California, San Francisco of artificial human insulin, which was the first therapeutic product of recombinant DNA [1].  Recombinant DNA research has subsequently led to more than one hundred critical heart and cancer therapies, as well as given us critical knowledge necessary to decode the human genome.

The legacy even extends to when the initial cases of HIV/AIDS were being diagnosed; it was San Francisco, not the federal government, which responded to the emergence of the disease. In 1981, San Francisco and then-Mayor Dianne Feinstein pledged the first public funds in the entire United States to the fight against HIV/AIDS [2].  San Francisco’s early charge helped the entire nation better understand the disease and led to subsequent federal funding programs.

Stem Cell Research Is the Next Frontier of Medicine

On November 2nd, 2004, California voters approved Proposition 71, a $3 billion bond initiative to establish the California Institute for Regenerative Medicine (CIRM). Over the next 10-12 years, CIRM will provide a steady stream of stem cell research funding to scientists in California. As a result of this forward-thinking, California has become the leading funding agency for embryonic stem cell research in the world, funding $157 million in grants by March 2007.

California’s stem cell program has created a new model for how to fund medical research in this country. Scientific and medical research is effectively the most important intellectual capital investment and asset of this society and must be funded with long term capital debt instruments. By making long term investments in today’s intellectual property, CIRM is investing in our society’s health in the future.

In support of this effort, San Francisco has created an environment to energize and facilitate the growth of California’s investment in this research. San Francisco offered the CIRM an unparalleled package of benefits and incentives to have the Institute locate in Mission Bay. The partnership between the city and the Institute has given the CIRM an opportunity to flourish and has converted the Bay Area into the epicenter of stem cell science in California, in the nation, and the world

Proposition 71: California’s Response to Lack of Federal Funding

On August 9, 2001, President George W. Bush decreed that no further human embryonic stem cell lines could be derived using federal funds, limiting federally funded research to cell lines already in existence. His decision was rooted in his ideological opposition to using excess microscopic cell clusters – “blastocysts” – that would otherwise be discarded for medical research, an opinion he shares with his ideologically conservative political supporters.

This decree was widely perceived as a crippling blow to the progress of pluripotent stem cell research because there were too few embryonic stem cell lines available for study and all of the President’s approved lines are corrupted by mouse feeder layers resulting in chromosomal abnormalities in the human cells and raising the possibility of viral infections in human clinical application. President Bush’s decree immediately created a major funding gap for this field of science.

On behalf of the patient advocates – from the 70 plus areas of chronic disease and injury – who could potentially be treated or cured of degenerative diseases by using embryonic stem cells, Proposition 71 was California’s solution to address this funding gap. Funding restrictions, political uncertainty, and the fears that the United States would no longer be globally competitive in this field, only added to the urgency of passing this Initiative to ensure that this biomedical research of extraordinary potential had a future.

The State and City as Patrons of Science

In passing Proposition 71, 59% of the electorate, seven million California voters – more votes than for any U.S. Senator in the prior history of this country – made a commitment to this potentially life-saving research. It was clear that Californians would not let religious ideology and federal inaction threaten to bury science.

This commitment marked a departure from the traditional thinking of how basic scientific research should be funded in the United States. California voters decided that supporting embryonic stem cell research was so important to the future of this nation that the state of California should fund embryonic stem cell research at levels equivalent to that of a national program. The passage of Proposition 71 effectively made California a surrogate national embryonic stem cell program.

San Francisco’s unique vision, led by Mayor Newsom, was essential to California realizing its ambitious goal of becoming a world leader in this field. In competing for CIRM’s headquarters, Mayor Newsom’s team (with financial support/contributions of civic leaders and the chamber of commerce) put together an aggressive proposal to create an environment that would help CIRM grow and strengthen its mission.

The proposal included incentives such as 10 years of 20,000 square feet of rent-free office space in Mission Bay, the center of San Francisco’s up-and-coming biomedical research community [3].  The proposal, also, included provisions that would give CIRM the opportunity to host major conferences in the city’s convention centers and provide room and board to conference attendees at no cost and/or at a substantially reduced cost to CIRM [4].

These incentives and many others allowed CIRM to immediately establish itself as an international focal point for stem cell research. Furthermore, by granting the Agency use of facilities and conference centers at little or no cost, San Francisco’s proposal allowed for more of CIRM’s funds to go directly to scientific research.

A central component of San Francisco’s visionary plan was the development of Mission Bay into a center for bio-tech and medical research. With the University of California – San Francisco (UCSF) at its center, Mission Bay has become a cluster for biotech and medical research innovation. In forming a partnership with CIRM, San Francisco accelerated and confirmed its position as a preeminent hub for the biomedical and life-sciences research community globally.

This vision and commitment by San Francisco to make the city an optimal center for scientists generally and stem cell research, specifically, has encouraged many biomedical and life sciences companies to relocate to the Bay Area. The environment that the city has produced is certainly a contributing factor to the Bay Area hosting the nation’s largest concentration of biotech research capacity. Approximately one-third of the State’s total bio-medical and life sciences industry, including all biotech companies, research institutions and universities engaged in biomedical research, development, and manufacturing, is located in the Bay Area [5].

In June 2005, the International Society for Stem Cell Research (ISSCR) held its 3rd Annual Meeting in San Francisco. The Annual Meeting is the world’s premier stem cell research event. Generally, it is attended by approximately 2,500 scientists, physicians and medical professionals from every continent [6].  The fact that the ISSCR held its 3rd Annual Meeting in San Francisco less than a year after the passage of Proposition 71 and CIRM’s residence in the city is a testament to how CIRM and San Francisco’s symbiotic partnership have propelled them both to critical status in the world of stem cell research. Additionally, California was distinctly recognized by the international community when CIRM was asked to become a member of the International Stem Cell Forum, an organization composed of 17 medical research nations from around the world who are committed to advancing stem cell research. California’s stem cell agency is only one of two members not representing entire nations [7].  CIRM was admitted concurrently with China and France.

Historical Precedent of Scientific Patronage

Californian voters and the “city-state” of San Francisco have “stepped up to the plate” in order to become patrons for science while religious ideology threatens scientific progress nationally. San Francisco is the benevolent host to California’s surrogate national stem cell program; it stands in sharp contrast to the inactivity (and intolerance) of the federal government. It is reminiscent the role of Florence (a city-state in Italy) in launching the Scientific Revolution, despite extreme religious suppression of experimental science by religious ideology that dictated precise rules for the physical and biological world.

During the Inquisition of the 16th and 17th century, the Catholic Church prosecuted individuals, including Galileo and other scientists, by accusing them of crimes related to heresy and banned their works. In response, the powerful and wealthy Florentine Medici family in Italy was compelled to act as patrons to the persecuted scientific community. In 1657, Grand Duke Ferdinando II de’ Medici of Florence established Accademia del Cimento (the Academy of Experiment) as Europe’s first scientific society where scientists could freely work on their studies [8].  The Academy’s mission was the development and diffusion of Galileo’s experimental method in the natural sciences [9].

The Academy enabled scientists to progress with their scientific experiments using the experimental method instead of their results needing to be validated and determined by religious ideology. Over a period of just ten years the Academy of Experiment helped incubate the ideas of these scientists and produced the “Notebook of Experimentation”, a manual that was a precursor to the formalized Scientific Method [10].   The Academy of Experiment closed in 1667 but it was a prototype for more permanent scientific academies, such as the Royal Society of London (established in 1660) and the Royal French Academy of Sciences (est. 1666) [11].

The beginnings of the Scientific Revolution can be traced back to the early work on the Scientific Method in the Academy of Experiment as well as the personal patronage of the Medici dynasty. This was a scenario where a patron that protected science for only a decade launched an entirely new scientific method which propelled society forward without the constraints of the Inquisition and religious ideology.

The struggle between science and religious ideology will never disappear and requires lasting vigilance. California is just one step along the long road, like the battle for Science in Florence; but, it is an important step for this country to take at this time.

Changing Paradigm for How Medical Research Should Be Funded

San Francisco’s supportive environment of California’s stem cell program is vital to the future of medical research funding. In its commitment to CIRM’s success, San Francisco has helped promote a new long term state model for our nation investing in our intellectual capital to reduce human suffering and a critical new field of medical science.

In 2004, California voters agreed that Proposition 71’s funding needed to be long-term and stable. Proposition 71 was designed to have CIRM’s funding come from General Obligation bonds that will be paid off in the 35 years, after they are issued. By using this capital structure CIRM would not be subject to controversial and unpredictable Washington politics or volatile annual state budgets.

The commitment of Californians to this new capital structuring model marks an important paradigm shift in funding medical research in the United States because it provides 10 to 12 years of long and stable funding for stem cell research. Historically, state legislatures, funding at very low levels, and Congress, which funds the National Institutes of Health, have funded medical research for one or two year cycles. In this current government funding format, scientific and medical research is forced to compete with operational budgetary costs like road-paving decisions, harbor maintenance decisions and crop subsidies. Medical research funding has been grouped with the annual operating costs of government, as it were an annual maintenance cost. This is not an operating cost; scientific and medical research is the most important intellectual capital of our society.

The Salk vaccine, which protects us all against polio, represents a case study that illustrates the kinds of benefits that society can receive, over the long term, with an investment in medical research.

In the 1940’s and 1950’s polio was one of the world’s most widespread and damaging diseases [12].  In 1952 and 1953 the U.S. experienced an aggregate total outbreak of 93,000 polio cases, up from a typical number of around 20,000 cases a year [13].  The physical, financial (specifically expensive iron lung equipment and long term care) and mental costs of the disease were devastating and, as prevalence increased, cost projections into the future could have proven to be economically disastrous for the nation.

In the early 1950s, the Salk vaccine was discovered and then subsequently disseminated widely. The vaccine has benefited generations of individuals over the last 50 years. A new study by researchers at the Harvard School of Public Health (HSPH) found that polio vaccination in the United States has resulted in a net present value savings of over $180 billion, even without including the large, intangible benefits associated with avoidance of disabling fear and suffering [14].  As a society we have avoided that cost because of our investment in the intellectual property generated by the Salk vaccine research. The same study found “these historical and future investments translate into over 1.7 billion vaccinations that prevent approximately 1.1 million cases of paralytic polio and over 160,000 deaths, thus saving Americans hundreds of billions of dollars in treatment costs” [15].

Proposition 71 Had Funded $157 million in Embryonic Stem Cell Research

CIRM has successfully begun to make the first disbursements of funds for stem cell research grants. In just the past year, CIRM has successfully disbursed a total of $157 million in research fellowships, seed grants and comprehensive research grants. The grants awarded to date, in combination with $48.5 million in grants for building shared lab facilities that are expected to be awarded in June, make California the world leader in the funding of human embryonic stem cell research.

One of the comprehensive research grants is a study that will be conducted by principal investigator, Dr. Jerome Zack, the associate director of the University of California Los Angeles AIDS Institute. Dr. Zack will study genetic modification of proteins to inhibit HIV as well as using human embryonic stem cells to develop into genetically modified adult blood cells for future potential treatment of HIV/AIDs patients. Also, Dr. Susan Fisher of the University of California San Francisco received a grant to study effective strategies for prompting embryonic stem cells to generate all the types of cells in the body. These studies are some of many that offer promise to the patient community of potential therapies and cures for chronic disease and injury.  San Francisco’s support of CIRM continues the legacy of the city encouraging and promoting medical science and innovation.

A long-term investment in society’s medical intellectual capital creates a return on investment. When rate of return is averaged over the medical research portfolio of the society, it substantially exceeds the initial cost of the investment. This cost should be financed over the long term benefit period of the therapy, vaccination, or cure. The future well-being of this nation will be best served by a commitment that embraces this new paradigm. San Francisco citizens and the city’s civic leaders have embraced this new paradigm for medical science funding. San Francisco has lifted and enhanced the mandate of 7,018,059 California voters and the hopes of families everywhere suffering from the tragic human toll of chronic disease and injury.

ACTION ITEMS

1. Support and Contribute to the University of California San Francisco (UCSF) and its affiliate, the Gladstone Institutes for their stem cell research programs. UCSF’s Human Embryonic Stem Cell Program and the Gladstone Institutes have launched a CIRM Scholars Training Program for stem cell researchers. These two programs are important for San Francisco to maintain its status as a premier biomedical research center in California, the nation and the world.

2. Support and Contribute to the new stem cell research facilities at UCSF and the Gladstone Institutes. UCSF’s Institute for Regenerative Medicine will be a keystone of the University’s stem cell program; the Dolby Family has already contributed to launching facilities development programs with a major gift. The facility will house a new stem cell registry and bank for distribution of human cell lines to researchers at UCSF, throughout the state, and beyond. The facility will also be used to train stem cell researchers and a separate research area within the facility will be devoted entirely to stem cell research to comply with the federal restrictions on stem cell activities. The Gladstone Institutes’ Embryonic Stem Cell Laboratory (ESCL) houses the Institutes’ studies on the great potential of embryonic stem cells. The Gladstone Institutes’ have been an important contributor to the development of therapies for chronic diseases in California.

3. Support and Contribute to the City College of San Francisco’s Stem Cell Certificate training program. The Governor’s office has given the City College of San Francisco a $780,000 grant to create a Stem Cell Certificate training program. This program, which is the first technical Certificate to equip students with the latest in stem cell research techniques, will provide students the scientific background and laboratory experience needed to find jobs in this emerging field.