Healing our Brains, Changing our Selves?

In using stem cells to treat brain disorders, scientists might be tampering unwittingly with the deepest reaches of human experience: our personality, our mood and behavior, perhaps even our sense of self. While nobody knows how likely such side effects are, a group of scientists and philosophers at Johns Hopkins University in Baltimore, Md., says they are a cause for concern and need to be addressed.

Until now, the public debate about stem cells has centered on the moral problems of harvesting the most potent cell type—embryonic stem cells—from human embryos. But the science has already moved ahead. Earlier this year, California biotech company Geron received approval to use embryonic stem cells in an attempt to treat spinal cord injuries; and on June 8, StemCells Inc., another California biotech, completed the first clinical trial using neural stem cells to treat Batten disease, a rare and fatal disorder that gradually breaks down brain tissue. Stem cell trials are also lined up or ongoing for stroke, Parkinson’s disease and Huntington’s disease.

In any clinical trial, safety is the first issue scientists study. But as they race to develop treatments for devastating neurological disorders, they might miss the philosophical fine print that changing the brain involves.

“Scientists certainly don’t always think through all of the implications of their work,” says Debra Mathews, the geneticist-turned-bioethicist who convened the working group at Hopkins. In their latest paper, published in the May issue of The American Journal of Bioethics, Mathews and her colleagues suggested that grafting stem cells into a person’s brain might lead to forgetting important memories and facts, to a more subdued or aggressive personality, or to altered sexual desire.

Although the risk of such changes may appear low, Mathews says, “there aren’t any data. We can extrapolate from preclinical trials, but I don’t think that’s particularly useful, because, you know, we can’t ask a mouse how he’s feeling today.”

Before having the idea for the working group, Mathews had been intrigued by the faulty rewiring that sometimes bungles brain function after a stroke. “You end up with very odd psychological effects like someone meaning to laugh but they cry,” she says.

Existing therapeutic technologies, such as deep brain stimulation, have also caused widespread personality changes in some cases, Mathews adds. “We know that it happens, and it’s not something that has been looked at, although deep brain stimulation has been around for a decade.”

How grafts will affect brain function depends on the number and injection site of the transplanted cells—both variables that doctors can control. But once the newcomers are in place, it is difficult to predict exactly how they will interact with the cells already present. Will they upset local brain circuitry or integrate smoothly?

In any case, explains Mathews, it is more than unlikely that a person would wake up from a transplant feeling like, in a sense being, the donor of the stem cells. “It’s not going to happen, because the way that our brains hold or represent our personalities or our thoughts or our memories are in complex networks of cells, not in individual cells, and certainly not in the DNA of individual cells.”

Other researchers add that the Hopkins group’s speculations should not cause undue alarm among patients. “Everything that involves interfering with the brain tends to feel scary to people,” says Dr. Maartje Schermer, a physician and ethicist at Erasmus University Rotterdam in the Netherlands. “I’m not worried that something terrible might happen, but we should look at it of course.”

Schermer says that many of the concerns raised by the group apply equally well to treatments that are common today, such as psychiatric medication. In a recent project, she interviewed a group of people who were taking drugs for Attention Deficit Hyperactivity Disorder, a common psychiatric diagnosis. “They really seemed to wrestle with their sense of identity: ‘Who am I? Am I me on the medication or off the medication?’” Schermer recalls. “Maybe we have neglected these kinds of changes too long.”