Stem-cell scientists find right chemistry


The day – Valentine’s Day, as it happened – began in a whirl of coffee cups, bustling dogs and homework, then a brisk walk around the block – in other words, business as usual for a UC Irvine couple who are a high-profile science team engaged in cutting-edge stem-cell research.

Brian Cummings and Aileen Anderson, whose stem-cell treatment for spinal cord injury is being tested on patients in Switzerland, say their office – only a short walk from their home on the UCI campus – has a family feel as well.

At UCI’s recently constructed Stem Cell Research Center, they supervise a crew of young students and technicians whose bond with their mentors is so close that they call themselves the “Andermings.”

“I suppose it’s like having an orphanage,” Cummings joked as he prepared for the day ahead.

It would include a lengthy meeting with the Andermings on how best to grow human embryonic stem cells without animal-cell contamination, a critique of a doctoral candidate’s presentation of potentially significant new findings and a session with Alzheimer’s researchers at an institute called UCI MIND.

But first, Cummings, Anderson and their two dogs – Chesapeake and Indiana – had to get the couple’s 6-year-old daughter, Camryn, to school.

After Camryn finished her homework (completed strategically a day in advance, leaving more time for afternoon play), they took the long way round to the Montessori school, also easy walking distance from their home.

Along the way, they encountered another faculty couple, from the German department, and their dog. They stopped with Camryn, giggling as the dogs rolled and tumbled on a neighbor’s lawn.

•••

Cummings, 47, and Anderson, 45, together since they were both undergrads at the University of Illinois, say living and working with each other comes naturally.

“People say, ‘Do I need a break from her?’ ” Cummings said as he wrangled the dogs.

“More people say, ‘Do you need a break from him?’ ” Anderson replied.

Later, the conversation transitions into a science meeting as the two take the 20-minute walk past UCI’s Ecological Preserve and into the Sue and Bill Gross Stem Cell Research Center. The energy-efficient building, with an open design to encourage chance meetings among scientists, houses a roster of high-powered researchers as well as their experimental subjects: rodents.

The center was seeded by $27 million in state stem-cell funding and $10 million from donors Bill and Sue Gross. The building was completed in 2010.

Now, researchers working there cultivate lines of human embryonic stem cells that can grow into a variety of cell types, from brain cells to liver and heart cells.

The ability to coax stem cells into many forms – and with it the potential to treat Alzheimer’s, paralysis and a long list of diseases – is fueling an explosion of research around the nation and across the state.

Anderson and Cummings showed that their stem-cell treatment, using cells derived from aborted fetuses, allowed partially paralyzed rats to walk again. The rat’s recovery was revealed in a dramatic before-and-after video.

So far, the human trial of the treatment in Switzerland is showing no ill effects on patients, Cummings said.

But stem-cell research is buffeted by political controversy, funding uncertainties and, sometimes, attacks by stem-cell research opponents.

The trial of the treatment developed by Cummings and Anderson with their collaborators, StemCells Inc., was the first of its kind in the world when it was announced in 2010.

In some ways, that made the family – and their team – a target.

Concerns about possible intruders prompted the couple to place a camera at their front door. Cummings’ tires have been slashed, he said, though he doesn’t know if that was the work of people who oppose the harvesting of human embryonic stem cells, animal-rights activists (angered by experiments on rodents) or perhaps a disgruntled student.

At the moment, Cummings and Anderson are running five research programs and leading 17 researchers. All of it is funded by $2.2 million in grants, much of it from California Institute for Regenerative Medicine, or CIRM.

Created by voter initiative – Proposition 71 in 2004 – CIRM is California’s $3 billion answer to federal restrictions on funding for stem-cell research. Those restrictions were started by the Bush administration and eased, but not eliminated, under President Obama.

Cummings said opposition to their research is based, in part, on incorrect assumptions.

A big one is that the research involves the destruction of embryos. In reality, they work with balls of cells created at an earlier stage of human development, called blastocysts – a distinction many opponents do not draw.

“Embryonic stem cells don’t come from embryos,” he said. “And they never have.”

The raw material comes from fertility clinics and otherwise would be discarded.

Cummings says those who say that such research is immoral have it wrong.

“The argument is backward,” he said. “It’s immoral to throw away this stuff and not use it to help someone.”

••

During their meeting with the Andermings, project leader Hal Nguyen described the group’s plan to grow a series of stem-cell cultures and check a compelling question: Is some of a stem cell’s transformation guided by the microscopic environment in which it dwells, or is it entirely dictated by the cell’s internal workings?

“The plan is in the email,” Nguyen told Anderson.

“Dude, I have 400 emails,” Anderson said.

The group’s task was meant to answer a classic nature-nurture question, Anderson said. In this case, “nature” is the DNA coding in the stem cell itself, while “nurture” is the cellular environment, with all its floating nutrients and chemical signals.

“Will that environment, the extrinsic factor, trump anything the cell can do?” Anderson had wondered earlier. “Or is the intrinsic programming of the cell the principal determinant? Is that the main driving factor?”

Cummings stood by in the tiny meeting room while the researchers batted around their questions and answers. He said Anderson, a spinal cord specialist, was the expert in this arena, though he couldn’t help piping in during a discussion of the medium in which the cells would be grown.

“You’re comparing two different medias, too?” Cummings asked.

“We all know what we’re talking about,” Anderson told him. “Don’t interrupt.”

Then it was on to a larger, mostly empty meeting room where Sheri Peterson, a doctoral candidate, wanted to test her presentation on Cummings and Anderson.

Her eventual target is an advancement committee that will determine her future. The presentation will be crucial in her quest for a Ph.D.

Peterson ran through an array of slides projected on a large screen to reveal her findings. Inflammation of damaged tissue being regenerated in rats, she said, might be eased or worsened simply by manipulating proteins surrounding the regenerating cells.

Again, the topic was in Anderson’s wheelhouse.

“My notes said, ‘Nicely done,’ ” Cummings told Peterson.

“He’s not an aficionado,” Anderson said.

The husband-and-wife researchers then provided her with a detailed, slide-by-slide critique.

•••

Cummings’ expertise centers on traumatic brain injury. But he also is an expert at the complex task of marshaling grant funding. On his office wall, a whiteboard densely covered with writing tells the story: Cummings must police incoming and outgoing grants like an air traffic controller, timing the grants and the work they fund to match years of employment for graduate students and staff members.

The grants come and go over months and years, and so do the students and staff. Get the timing wrong, and you might have funding with no researchers, or researchers with nothing to do.

“At UCI, I’m like a small-business owner,” Cummings said.

Over a hasty lunch in his office (cold sandwiches grabbed during a trip, with Anderson, to a nearby campus snack shop), Cummings spoke of the merging of home and office life.

Writing up grant requests takes up both researchers’ time. Often, as they write, Camryn is playing in the background, whether at home or at the office. And research collaborators can show up wanting to conduct interviews at any time, holidays included.

“I did draw a line in the sand at Christmas Eve,” Anderson said.

Cummings knows such stress has driven other husband-and-wife teams into open conflict. But that just isn’t his and Anderson’s style. In fact, he said, keeping a scientific perspective, even at home, might help keep things calm.

“There’s no need to be yelling and shouting at each other because we don’t think that way,” he said. “You’re supposed to believe nothing until you prove it.”

That doesn’t mean they don’t differ, sometimes strongly, over scientific details.

“They don’t always agree with each other, and that’s good,” said Brittany Greer, an intern in their lab and an Anderming.

Nurturing the students and young scientists is part of the pleasure of doing science for both halves of the research couple, Anderson said.

“You start to look at this crowd of people as your second family,” she said. “They’re your kids. That is fun and rewarding for sure.”

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Stem-cell scientists find right chemistry

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