A chance to lead

On August 9, 2001, Milton Wallack listened on the radio as then-President George W. Bush announced plans to halt federal funding for certain areas of stem cell research. “I remember it all too well. I’ll never forget that date,” the co-founder of Connecticut Stem Cell Coalition said. A close relative had just been diagnosed with type 1 diabetes, a chronic condition in which the body’s immune system mistakenly attacks and destroys insulin-producing cells. Researchers thought stem cells could one day replace these lost cells.

Bush’s mandate—which forced scientists to rely on just a few existing human embryonic stem (ES) cell lines—threatened scientific progress. Researchers prize human ES cells because they are easy to grow in the lab, and have the potential to become almost any cell in the body. Wallack, now a retired dentist in Branford, but always an activist, felt something had to be done.

He met with Yale’s Diane Krause, M.D., Ph.D., professor of laboratory medicine, cell biology, and pathology, and Wesleyan University’s Laura Grabel, Ph.D., the Lauren B. Dachs Professor of Science and Society, two researchers thinking of working with human ES cells in the state at the time. Gradually, Wallack’s coalition expanded to include academics, lawyers, and politicians. In 2005, Wallack asked Paul Pescatello, J.D., Ph.D., then president and CEO of Connecticut United for Research Excellence, an organization formed to promote bioscience in the state, to become co-chair of the Connecticut Stem Cell Coalition. Their goal? Convince the state to provide funding for human embryonic stem cell research. Pescatello, who now leads the Connecticut Business & Industry Association’s (CBIA) Connecticut Bioscience Growth Council (as well as the New England Biotech Association), agreed. “We wanted to make it clear that Connecticut would be a safe haven for stem cell research,” said Pescatello, a lawyer who became a lobbyist for the biopharmaceutical industry after he lost his brother to glioblastoma.

Despite the controversy surrounding embryonic stem cell research, Pescatello believed that a bipartisan legislative coalition would support it. Working with business and economic development advocates, especially the lobbying team at the CBIA, Pescatello drafted the blueprint for what became Connecticut’s stem cell statute. At the time, only California and New Jersey had plans to provide state funding for human ES cell research. Massachusetts’ policymakers were debating the issue, but they faced pushback from the Roman Catholic Church, whose influence was decidedly less in Connecticut, Pescatello said. By 2005, Wallack and Pescatello along with their team were ready to take their legislation to the state capitol in Hartford. The proposed bill permitted human embryonic stem cell research and set aside state funding for it, but banned any activity related to human cloning.

Perfect timing

Around the same time that Wallack and Pescatello’s team of lobbyists were meeting with state lawmakers, newly appointed Dean Robert J. Alpern, M.D., Ensign Professor of Medicine, and Carolyn W. Slayman, Ph.D., Sterling Professor of Genetics, professor of cellular and molecular physiology, and deputy dean for academic and scientific affairs, asked a strategic planning committee where the School of Medicine should strengthen its research focus. “The medical school had faculty members—some of whom knew each other, some who didn’t—who worked with stem cells,” Slayman said. “But nobody would have looked from the outside and said, ‘Yale is a powerhouse of stem cell research.’ It just wasn’t true at the time,” she said. The committee recommended creating a stem cell center. In 2005, a search began for the new center’s director.

Haifan Lin, Ph.D., then a professor at Duke University, stood out among potential candidates, Slayman recalled. While other medical schools had focused on disease-specific research, Lin suggested that the field had far more to learn about the basic biology of stem cells. “How can it be that at cell division (in stem cells), one daughter cell keeps all of its potential, while the other starts off on a process of differentiation?” Slayman said, her eyes widening at the memory of the tantalizing, yet incredibly basic science question that faced the burgeoning field at the time. Lin accepted the position.

By late spring 2005, the Connecticut legislature’s public health committee began reviewing the proposed stem cell legislation. That committee’s co-chair, state senator and now U.S. Sen. Chris Murphy, became the bill’s key champion, Pescatello said. Former Gov. M. Jodi Rell remembered very little resistance among lawmakers. “The bill was written and drafted about 20 times, then scientific leaders came in to make their case, and we decided this was the course we wanted to take,” she said. “It was time to step out front.” On June 15, 2005, Rell signed the act into law. The law earmarked $100 million in state funding for stem cell research, at a rate of $10 million per year through 2015. Gov. Dannel P. Malloy recently extended stem cell research funding for $10 million a year through 2018.

Lasting impact

In 2015, researchers at the Georgia Institute of Technology looked at how state funding had affected stem cell research in the few states that had set aside a large chunk of money in the mid-2000s. The team compared California, Connecticut, Maryland, and New York. “In both California and Connecticut, state funding programs appear to have contributed to over-performance in the field,” they wrote in Cell Stem Cell. Connecticut especially seemed to reap benefits. Approximately 67 percent of human ES cell-related articles published by researchers in the state acknowledged state funding, according to the study.

Essentially no scientists were studying human embryonic stem cells in Connecticut in 2001, and now more than 150 researchers are working on such projects with state funding, Wallack said. At Yale, more than 30 labs work on human ES cell research today.

Both the medical school’s stem cell core labs and the University of Connecticut-Wesleyan University Stem Cell Core have relied on state funding. While Yale’s core labs provide embryonic stem cell culture, genomic analysis, and imaging services, the UConn core focuses on induced pluripotent stem (iPS) cell technology, said Marc Lalande, Ph.D., who has directed UConn’s Stem Cell Institute in Farmington since its opening in 2007. The result has been close collaboration among the three universities in ways that complement one another, Lalande said. “Since this is a state fund, we have had a great collaboration. We have retreats once each semester,” he said. “Diane and Haifan are good friends.”

In March 2009, President Barack Obama, by executive order, lifted some of the restrictions on federal funding for human ES cells. One year later, UConn scientists contributed four brand-new human ES cell lines to the National Stem Cell Registry maintained by the National Institutes of Health for use by all stem cell researchers. Lalande pointed to the creation of ImStem, a stem cell therapy biotech company founded at UConn, and continued collaborations with Alexion, a biotech that was started by a Yale professor that moved its headquarters back to New Haven earlier this year.

Two years ago, the legislature approved a measure that moved the responsibility of distributing state stem cell research grants from the public health department to Connecticut Innovations, a quasi-public organization that serves as a state venture capital fund and lender. The Connecticut Stem Cell Program has been renamed the Regenerative Medicine Research Fund. This change reflects a broader trend in science, and does not take away the focus from stem cell research, Wallack said.

“When we started this in 2004, people thought I was crazy and they said, ‘You’ll never get this done,’ ” Wallack recalled. A self-described optimist who “always sees the glass 110 percent full,” Wallack has already set his sights on a concern that weighs on all stem cell researchers who rely on state funding in Connecticut: how to secure the next round of funding after 2018.