BALTIMORE — Leaders from the stem-cell agencies of Maryland and California agreed Monday to collaborate on conducting research and pursuing grant funding from state and federal sources in hopes of increasing their ability to compete with other top-tier states for researchers and their grant money.
The agreement, signed at the 2009 World Stem Cell Summit here, is expected to be followed up by the formation of teams that pursue joint applications for funding from the NIH, as well as their respective states. The latter arrangement is designed to comply with laws in both states that forbid the spending of stem-cell funds outside their borders, and would replicate similar funding arrangements CIRM has worked out with partners in six nations.
The Maryland Technology Development Corp., known as TEDCO, is the first US state stem cell agency to reach such an agreement with CIRM. Maryland and California hope that the new accord will strengthen their stem cell efforts, and indirectly their broader life-sciences clusters, by drawing on combined strengths.
In addition to common strengths, however, both states face common competitors for research jobs and grant funding. Massachusetts usually places second to California in the amount of NIH dollars its researchers win every year, with about $2.3 billion in 4,932 grants, to California's roughly $3.2 billion in 7,228 grants during the federal fiscal year that ended Sept. 30, 2008. Maryland placed sixth, with $972.4 million in 2,140 grants, behind New York, Pennsylvania, and Texas, but just ahead of North Carolina, according to NIH data.
Maryland's NIH money dipped about 28 percent from the previous fiscal year, when it reported more than $1.3 billion in grants.
However, Maryland is home to the nation's top recipient of NIH money among academic research institutions, Johns Hopkins University, which received $581.9 million in FY '08, down from $618.7 million in FY '07. That is the last year for which data is available from the National Science Foundation on total obligations to research universities for science and engineering R&D to the top 100 schools from all federal agencies. As of FY '07, Johns Hopkins topped that list with nearly $1.2 billion, about double the funding won by second-ranked University of Washington with $612.5 million, and well above the $291.7 million recorded for the two University of Maryland campuses making that list, Baltimore and College Park.
As for research expenses, Johns Hopkins tops that list again with $1.55 billion spent during FY 2009, while University of Maryland spending was about $500 million.
O'Malley said Hopkins and the state-funded University of Maryland system — which saw its NIH grant funding for all campuses shrink to $186.3 million, from $187.95 million in FY '07 — constituted "the wishbone offense of Maryland's life sciences economy."
Top NIH grant winners like JHU and UM are just one reason why Maryland is an attractive collaboration partner, Robert Klein, chairman of CIRM's governing board, told BioRegion News. In addition to the extra NIH funding, Maryland offers top-tier research and the presence of a sizeable biocluster — more than 400 companies that employ a total 26,000 people.
"There are some areas where Maryland is ahead of California. There are areas where California is ahead. To bring that joint expertise together answers our moral obligation to patients to move therapies safely and effectively forward for them," Klein, chairman of the Independent Citizens Oversight Committee, said in an interview minutes after joining O'Malley in signing the collaboration agreement.
Maryland's strengths, according to Klein, include cancer, spinal cord, and central nervous system research, as well as biomedical engineering, and a history of medical innovation; the world's first heart surgery took place in the late 1940s at Johns Hopkins. "This is a state with a history of courage and commitment to new therapies. Our scientists have identified that there's great science, breakthrough science being done in Maryland that can complement the breakthrough science in California. Together, we can make remarkable contributions to the future of medicine.
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"Why would you create a state boundary, or a national boundary, in trying to bring the best minds of the world together to work to advance therapies?" Klein added.
Research teams in each state would decide when to collaborate with counterparts in the other; implementation details have yet to be worked out, but should be "hopefully in the next 90 days."
"Scientists have asked for this. They feel that progress can be accelerated by pulling these best minds together, regardless of geographic boundaries," CIRM spokesman Don Gibbons added.
As of Aug. 21, according to CIRM's funding summary, ICOC has approved a total $781.9 million in 307 grants to 39 recipients, seven of them businesses that won a combined nine grants totaling nearly $15.5 million.
Representatives from one of those companies, Fluidigm, attended the stem cell summit seeking potential partners. The company is developing a cell culture chip integrated fluidic circuit, and support system, designed to help scientists identify stem cell culture and differentiation conditions, as well as genes and molecules with an impact on the renewal and reprogramming of stem cells.
"We're lining up collaborators at early test sites in academia, in government labs, and in industry. Maryland happens to have a high concentration of folks who are really way up there in the field," Fluidigm CEO and co-founder Gajus Worthington said in an interview. "That's really the magnet for us. It isn't any specific geographic location as much as it is the high density of really high quality work, and Maryland happens to have that."
"The CIRM-Maryland agreement is so new. I don’t know if we know of any direct impact," Worthington added. "But clearly, we have systems in place at the University of Maryland and other places. We've met with many of [UM's] researchers there. They are very excited about the system, and I've got to believe they're going to be early adapters of the stem cell chip when it's available."
Looking ahead, he said, "I don't know, as we move on with our relationships with CIRM, if there are other opportunities where we're going to be able to do either the bicoastal work or something like that. We would hope that the chip gets adopted not just in these two states, but globally."
Based in South San Francisco, Calif., Fluidigm was the first business to win funding through CIRM when its governing board last December approved a $749,520 grant for the company, secured with stem cell reagent provider Stemgent of San Diego. The grant is being used toward developing a stem cell-specific microfluidic chip and support system designed to reprogram patients' differentiated cells, such as skin cells, into stem cells. "The end result may be the creation of a commercial product," Fluidigm said in its grant abstract.
Since December, work has progressed to create a prototype of the chip, and to develop a more experimental model, of the system hardware — a chip controller, an imager using a motorized microscope allowing for control of the chip and the surrounding environment, and a "hotel" mini-storage area for up to 16 chips.
"We're starting to get a reasonably clear idea of what the system will look like when we release it. We've demonstrated cell loading, the ability to deliver any one of 16 reagents to any one of 10 cell culture chambers. All the fluidics of the chip is working," Worthington told BRN.
1,000 Jobs for Maryland
TEDCO has awarded a combined more than $56 million in 141 grants to five institutions and three businesses since Maryland launched its stem cell program, part of the Maryland Stem Cell Research Act of 2006, enacted by then-governor Robert Ehrlich, a Republican who was unseated that year by O'Malley, a Democrat expected to seek re-election next year.
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Johns Hopkins alone accounts for 94, or two thirds, of the 141 grants, followed by 31 for runner-up University of Maryland, Baltimore; seven for University of Maryland, Biotechnology Institute; four for the Hugo W. Morse Research Institute at Kennedy Krieger Institute; two for University of Maryland, College Park; and one for each of three businesses, GlobalStem, Virxsys, and RetroTherapy.
TEDCO says the grants have employed more than 350 researchers, physicians, lab technicians, and others, and helped sustain another 700-plus indirect jobs at research institutions and companies receiving funding.
Maryland wants to add to that list this year. TEDCO administers the Maryland Stem Cell Research Fund, which plans to award $12.4 million for stem cell research during the current state fiscal year, which began July 1.
On Sept. 20, the MSCRF posted on its website links to formal requests for applications for grant funding under three programs:
• Investigator-Initiated Grants for investigators with preliminary data to support their grant applications, which may seek up to $300,000 of direct costs in any single year, for up to five years.
• Exploratory Research Grants for investigators who are new to the stem cell field, as well as for exploratory projects without preliminary data. Applicants can seek up to $100,000 of direct costs in any single year, for up to two years.
• Post-Doctoral Fellowship Grants for pre-doctoral students and post-doctoral fellows who wish to conduct research on human stem cells in Maryland. Fellowships can be up to $55,000 per year, for up to two years.
The RFAs set Nov. 12 deadlines for letters of intent, and Jan. 14, 2010, deadlines for applications, with the Maryland Stem Cell Research Commission set to decide who gets funding in April 2010.
Unlike the federal government, Maryland law permits funding the creation of new stem cell lines, even new lines of human embryonic stem cells.
Dan Gincel, director of the Maryland Stem Cell Research Foundation, said during a panel talk at the summit that the foundation will begin this year an ongoing focus in funding decisions on supporting collaborations between businesses and nonprofit institutions, from universities to research institutes.
The foundation has not set benchmarks for how much in funding, or how many grants, it will award to such collaborations, Gincel told BRN: "We thought that it's the best way, and the fastest way to the market. It offers the most translational research that we can get, and that's why we chose this."
New Fiscal Threat
TEDCO may finish this fiscal year awarding less money than it planned. O'Malley and other Maryland officials will scramble in coming days to plug a roughly $300 million budget shortfall announced last week by the state Board of Revenue Estimates. The shortfall reflects reduced tax revenues that the state blames on job losses due to the recession.
"The key is the governor, and the governor is very supportive. If the governor continues to put money in the budget … then it will continue to be funded," state Del. Samuel (Sandy) Rosenberg (D-Baltimore), a supporter of state stem cell funding, said at the panel talk.
Four times since April 2008, Maryland has plugged budget deficits by trimming spending for stem cell research. The state stem cell program has shriveled from the $24 million it enjoyed in the 2008 fiscal year – to $19 million at the start of FY 2009; then down to $18 million in October 2008, when the first shockwaves of the economic downturn surfaced; then up $400,000 to $18.4 million in the FY 2010 budget proposed by O'Malley; then down to $15.4 million in the budget hammered out by O'Malley and legislative leaders for the current fiscal year; then down again to the current $12.4 million in July.
"I chatted about it with the governor [Monday]. He remains very supportive and wants, if at all possible, to maintain if not expand what we're doing. But it's tough times," Rosenberg told BRN.
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More state money would be needed to fund the projects anticipated to emerge from the TEDCO-CIRM collaboration, Karen Rothenberg, chair of the Maryland Stem Cell Research Commission, told panel talk attendees: "We do not have from our existing fund the resources to move that forward, so there would need to be additional funds to continue to promote those sorts of collaborations."
"The hope is that with the interest of the scientists from both states working together, they will be able to partner not only in terms of reaching into state funds, but to collaborate, to do things with federal funding, private foundations, corporations, etc., sharing information," Rothenberg said. "Right now, there isn't money in the set-aside of existing funds for that."
The latest stem cell budget reduction was part of a $281.5 million wave of budget cuts agreed to over the summer by the Public Works Board, a panel of officials that oversee state spending, chaired by O'Malley and including Comptroller Peter Franchot and Treasurer Nancy Kopp [BRN, July 24].
Those cuts have not stopped the stem cell summit organizer, the nonprofit Genetics Policy Institute of Palm Beach Gardens, Fla., from honoring O'Malley as the winner of its Stem Cell Action Award for National Leadership [See BioRegion Newsmakers, this issue].
"While our current fiscal climate for the time being sometimes restrains our ability to do quite as much as we'd like to do, as quickly as we would like to do it, the investments we have made nonetheless are pretty significant," O'Malley said, addressing the stem cell summit on Monday. "Today it remains our goal and vision to make Maryland the most welcoming environment in our country for stem cell research and all the life sciences, and I should say not just in our country, but in the world."
To that end, O'Malley has announced plans for the state to spend $1.3 billion in state life-sci funding over 11 years through his BIO 2020 initiative, the first year's funding for which has been scaled back due to the state's fiscal condition. Continuing the stem cell program is part of that effort, as are the opening of two offices last week for the new state agency charged with attracting new life-sci jobs and retaining existing ones, the Maryland Biotechnology Center [BRN, Sept. 18].
Speaking with BRN minutes after his address, O'Malley said his administration would "do everything that we can to protect" the stem cell fund from further cuts.
One option, borrowing future funding for the stem cell fund, could emerge from the CIRM collaboration.
"California has a different structure to it, and that is bonding. Bob has given me some great ideas about bonding it," O'Malley said. "We're exploring all options. We'd like to maintain our leadership, and we're doing everything that we can to do so."
At a panel discussion the following morning, Klein defended California's decision to bond its stem cell funding over a decade, rather than rely on annual budget appropriations, as a model for other states to follow.
"It is very important to give long-term government support that's stable. The structure, term, and stability of the financial support is very critical to the scientific and financial leverage of the state, and economic impact you can create," Klein said.
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Among foundations and other donors, he said, "the annual appropriations process is really not looked at as a stable source of financial support, as demonstrated by state economies in the last couple of years."
Another advantage Klein cited: "In difficult economic years, we're not taking money from police service. We're not taking money from hospitals and clinics. We are making a capital investment in the future of California."
O'Malley said in his summit remarks that the collaboration agreement with CIRM emerged from more than a year of contacts between the two states that began in San Diego at last year's 2008 BIO International Convention, when the Maryland governor first spoke with Klein.
"We're stronger together. You look at the assets in California, the asset in Maryland, you look at the combining of those two in terms of the intellectual and financial wherewithal, and I think it's just a natural," O'Malley said. "I don’t think there's a better state on the East Coast that California could have chosen … because of the location of all those federal institutions, because of all the research that already goes on here."
The TEDCO-CIRM agreement could be the first of several multi-state agreements California and Maryland hammer out, Klein said. He and O'Malley told BRN they have not ruled out additional collaboration pacts with other states, even Massachusetts, before O'Malley quickly added: "but Massachusetts will follow Maryland."
The quasi-public Massachusetts Life Sciences Center has awarded $7.7 million to help support a stem-cell bank, and nearly $1.3 million for the International Stem Cell Registry. Both facilities were launched over the past year at the University of Massachusetts Medical School's Shrewsbury campus.
The stem cell bank provides stem-cell lines to in- and out-of-state researchers, while the registry details the properties and potential applications of about 500 specific hESC lines; includes information for researchers on obtaining the cells, with a catalog of references related to each hESC line; and includes information for doctors and patients about advances in stem-cell therapies.
The bank and registry are two of three anchors of Massachusetts' stem cell effort. The third anchor is the Harvard Stem Cell Institute, which focuses on basic research and clinical translation in five principal disease areas: cancer, diabetes, neurodegenerative diseases such as ALS and Parkinson's, blood disorders, and cardiovascular disease. The stem cell bank and registry received their funding through the $1 billion Massachusetts made available in its 10-year Massachusetts Life Sciences Act, enacted last year by Gov. Deval Patrick, a Democrat expected to seek re-election next year.
Massachusetts, Maryland, and California are three of eight states that have set aside one form or other of state funding toward human embryonic stem cell research. Indeed California has set aside the most public funding for stem cell research, since state voters in 2004 approved issuing $3 billion in bonds for the purpose through Proposition 71.
The other five stem cell funding states are Connecticut, Illinois, New Jersey, New York, and Wisconsin. New Jersey was blocked from issuing $450 million in bonds to create a stem cell institute and increase funding for research projects, after voters defeated a 2007 ballot question by 53 to 47 percent, though Gov. Jon Corzine, a Democrat seeking re-election in November, enacted a $270 million capital funding plan for stem-cell facilities in 2006 [BRN, Nov. 16, 2007].