Santanu Banerjee had a problem. Funders and medical journals weren’t all that interested in his research on a copycat version of HIV in mice because it didn’t apply to the way the real virus spreads in people.
“Your model is not good,” he was told, “unless it replicates the exact [human] pathology.”
So the University of Minnesota researcher made a decision in 2013 that could produce breakthroughs on HIV but also dropped him into an intense national controversy: He used tissue from aborted fetuses to create mice with human immune systems. “It comes closest to the actual infection situation,” he said.
Banerjee is one of six principal investigators at the university who have worked since 2014 with fetal tissue, which comes from elective abortions.
Most recall a similar controversy in the 1990s, when conservative lawmakers sought to ban fetal tissue research. But they watched it fade from state and federal politics — until last summer, when advocates against abortion claimed that abortion clinics in other states illegally profited from selling fetal tissue to researchers.
The claims are suspect, but they have prompted new calls to ban the research and new restrictions on how U researchers acquire and discard fetal tissue.
In their first public comments about the controversy, Banerjee and his colleagues expressed hope that their work in HIV, Parkinson’s disease, diabetes and spinal cord injury won’t be jeopardized by a debate they thought had been resolved long ago.
“It’s very surprising,” said Walter Low, the university’s associate head for neurosurgery research, who is working with fetal tissue. “It’s not as if we’re back in the 1990s. … We have guidelines here at the university, guidelines nationally, guidelines statewide.”
The university has been tepid in its public support since last summer, when it mistakenly denied that fetal tissue research takes place on campus and then acknowledged its error. Despite drafting new policies to preserve the research, university leaders declined last fall to join 53 institutions — including five Big Ten schools — in a statement endorsing the research.
And last week, the Board of Regents abruptly withdrew a resolution in favor of the research before its meeting.
When he first contemplated this line of research, Banerjee explored buying mice that a company already had engineered with fetal tissue to possess human immunity. But the mice cost $1,800 apiece. Instead, he acquired fetal tissue from a California donor bank, Advanced Bioscience Resources, and surgically implanted it in the kidneys of mice at one-ninth the cost.
Creating 200 such mice, Banerjee started studying lung inflammation and whether it leads to cognitive impairment in HIV patients.
Somehow, HIV slips through the brain’s protective barrier. Though he has suspended his work pending the U’s new policy on fetal tissue, Banerjee soon plans to test whether HIV drugs play a role, and whether treatment of inflammation reduces cognitive problems.
“These are toxic drugs,” he said. “They take care of the greater evil, but they also do things to you that you don’t necessarily want to happen.”
Low didn’t suspend his work. His focus is harnessing stem cells — the so-called master cells that generate other cells and tissues — so they can be transplanted and produce the dopamine that is lacking in Parkinson’s patients.
The stem cells come from a variety of sources, such as umbilical cord blood donated after childbirth, but not fetal tissue. However, Low said he needs fetal tissue as a model of normal human development against which to compare these differentiated stem cells.
“Our goal is to one day take a piece of your skin and make that into a pluripotent stem cell … that makes dopamine neurons for treating Parkinson’s patients,” he said.
U researcher Meri Firpo has similar goals to one day reprogram skin stem cells, which only make skin and heal flesh wounds, into “pluripotent” cells that can produce any cells or tissues in the body — and could be directed to produce insulin-producing islet cells.
Until that technique is proven, Low and Firpo work with stem cells from other sources — and use cells from fetal tissue for comparison.
Falling number of abortions
The utility of fetal cells today is different from the 1980s and 1990s, when researchers sought to use their regenerative qualities by transplanting fetal tissue directly into patients. Studies in Europe and the U.S. tested whether brain cells from fetal tissue could be implanted in Parkinson’s patients and produce the dopamine they need to slow their declines.
Fetal tissue research accelerated in 1993, when a ban on federal funding was lifted by President Bill Clinton — with ethics guidance from a white paper co-authored by Dorothy “Dorle” Vawter of the Minnesota Center for Health Care Ethics.
Over time, many researchers dropped the idea of using fetal tissue itself in transplants. Low said it would be impractical to rely on tissue donations from a limited and declining number of abortions.
“There isn’t enough tissue there for 1.5 million patients with Parkinson’s disease in the United States alone,” he said.
Instead, fetal tissue is commonly used as a “positive control” to confirm that experiments using stem cells from other sources are working. As a model of early human development, fetal tissue will likely help researchers understand why the new mosquito-borne Zika virus affects brain development in some babies of infected mothers, Low said.
Spinal cord repairs?
One study by Ann Parr, the university’s director for spinal neurosurgery, does involve an actual treatment derived from fetal tissue. California-based Stem Cell Inc. is funding a trial at the U and 11 other institutions to test whether a fetal stem cell line can repair chronic spinal cord damage.
The work involves a self-renewing cell line and doesn’t require new fetal tissue, Parr said. Patient recruitment at the U just started.
“There are lots and lots of people out there who have chronic spinal cord injury and there is nothing to offer them,” Parr said. “This is the first time this has been a possibility.”
Sabita Roy’s research is similar to Banerjee’s work — though she is buying mice from a company that has already used fetal tissue to humanize their immune systems. The director of the U’s division of infection, inflammation and vascular biology wants to understand HIV’s path to the brain and whether addiction to drugs such as morphine strips away the brain’s protection.
HIV now is manageable with antiretroviral drugs, but those drugs don’t reach into the central nervous system, where the virus can hide until patients think they are healthy, she said. “The moment they are off the antiretroviral treatment, the virus comes back with a vengeance.”
The researchers all considered the ethical implications of using fetal tissue, and took varying approaches to resolve any questions.
Some considered spiritual perspectives; the Hindu, Jewish and Muslim faiths generally permit the research — as long as a fetus isn’t conceived for that specific purpose — while Christian views separate by denomination. Banerjee and Roy came from Hindu homes in India and Malaysia, respectively. Parr was raised by Christian parents in Canada, where fetal tissue research hasn’t been as politicized.
All agreed with legal precautions, such as abortion clinics suggesting tissue donation only after women have abortions — to prevent coercion. They embrace the new U disposal policy, which equates tissue with donated human cadavers and requires that it be cremated or buried after its use in research.
“I will never induce somebody to abort a baby for research,” Banerjee said. “But having [tissue] go to my lab for research instead of the trash? My conscience is very clear.”