Day 6 stem cells: Researcher 2
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By DON WALTON / Lincoln Journal Star
What is it?
The challenge, the mystery, the lure of discovery?
Is it venturing deep into the unknown, with the exhilarating prospect of going where no one has been before?
Age: 57
Hometown: Omaha
Education: Harvard University; MD at Columbia University
University of Nebraska Medical Center position: Charles W. McLaughlin professor of surgery and senior associate dean for research in the College of Medicine
Major research focus: Cellular therapy in treatment of liver disease
UNMC tenure: 15 years
Along the way: Immunology research fellow at Harvard Medical School; transplant surgery fellow at the University of Pittsburgh; started liver transplant programs at the University of Pennsylvania and Columbia.
Quote: "Be creative and test yourself. Dostoevsky didn’t invent novels, but the characters in 'Crime and Punishment' are his."
Factoids: Two sons; majored in physics and chemistry in college.
A question: After living in Boston and New York, is it Yankees or Red Sox?: Yankees.
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BY MARK ANDERSEN / Lincoln Journal Star
The cells of every major organ fall into two broad classifications, the stroma and the parenchyma.
The stroma form the ducts, the vessels, the connecting and supporting stuff. The parenchyma provide the function. In the heart, the parenchyma contract. In the pancreas, there are several parenchyma, making insulin, hormones, digestive enzymes.
The goal of embryonic stem cell research is replacing dead parenchyma.
Let's say there's a heart attack cutting blood flow to the heart. Without oxygen the muscle cells, the parenchyma, quickly die.
The stroma, it's tough.
"It's gristle," said Dr. David Crouse, associate vice chancellor for academic affairs at the University of Nebraska Medical Center.
It remains as a skeletal structure that could be induced to accept new parenchyma.
Actually, the stroma may influence the final stages of the parenchyma.
"It may well be that the stroma is what makes up that microenvironment of signals," Crouse said. There is a unique relationship of each stroma to each parenchyma in every tissue, controlling the way those cells grow.
With Parkinson's, the goal would be to force embryonic stem cells into becoming dopamine-producing cells, and then to inject those. It would be crucial that none of the original stem cells remain to cause cancer.
Research appears to be overcoming this hurdle, Crouse said. "In an increasing numbers of animal studies, that's being overcome."
But there’s another big hurdle.
The new parenchyma would have different DNA, would be seen by the body's immune system as invaders. Patients would have to be treated with the drugs organ transplant recipients take to stave off rejection.
A solution to this might be therapeutic cloning.
Instead of starting with embryonic stem cells, scientists hope to create an artificial blastocyst using DNA from the patient. They would begin with an egg from a woman but extract its native DNA. Into the egg cytoplasm they would insert DNA extracted from skin cells from the patient.
Theoretically, stem cells developed from this manner also could be used to create a twin of the original person. No responsible scientist would attempt such an abomination, said James Turpen, another UNMC researcher.
"That's an ethical line that should not be crossed," he said.
Instead, the knowledge gained from embryonic stem cell research would be used to push these cells into becoming therapeutic parenchyma. Because the implanted cells would have the same DNA as their host, the body wouldn't reject them.
Reach Mark Andersen at 473-7238 or mandersen@journalstar.com.
***
Related stories
Yes, all of that, and more.
Sure, there is ego. But there’s also altruism.
Sure, there’s brainpower and experience and talent and dedication and testing. But also serendipity.
“A lot of that,” Dr. Ira Fox says.
He’s the voyager on this journey of discovery.
“Eureka moments are unmatched,” Fox says. “And they are rare.”
Sometimes, he says, you’re like a running back probing the line when “unexpectedly you find a break that may result in a short run or a long run.”
But 70 percent of the time medical research experiments don’t work. That is, not the way you anticipated.
“An idea you had may come out differently than you expected,” Fox says. That may be frustrating, but it doesn’t mean there hasn’t been discovery.
“A lot of phenomena could pass you by, but, if you are prepared, you will recognize it. That’s a special moment.”
The mystery “unfolds itself, layers and layers,” Fox says.
“You are standing on the shoulders of others. But it is yours.”
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Ira Fox is a medical research scientist. And more.
A surgeon actively engaged in liver transplantation until four years ago.
Professor at the University of Nebraska Medical Center.
Senior associate dean for research.
A physics and chemistry major at Harvard, he earned his medical degree at Columbia and started liver transplant programs at the University of Pennsylvania and Columbia.
Fox has been at the Medical Center for 15 years, lured back to his hometown from the East by the opportunity to work at “one of the premier liver transplant programs in the world.”
A brilliant and engaging man, he lets you into his world on his terms. But, during a couple of one-hour interviews in his cramped office down a labyrinth of hallways, he offers coffee and lets you in farther than expected.
Into the mind and work of doctor and scientist, but not so deep the reporter will drown.
Even into who he is and what drives him.
Hesitant to talk about his belief system, he does.
Hesitant to let you into his lab, he doesn’t. Actually, hesitant is not the accurate word. It is no.
That is his space, his ship, where the voyage takes place.
n n n
“I tell my students: ‘If you don’t get up in the morning and love it, you won’t do it.’”
When he was performing liver transplants, Fox got up at 2 a.m. And loved it.
“If you don’t show up,” he says, “everybody cares. Patients, families, colleagues, nurses. You’re their lifeline.
“But, in research, nobody cares if you show up,” Fox says.
“It’s your project. Only 10 people know what you’re working on. The mice certainly are happier if you don’t show up. Patients may send you a Christmas card, but your mice never will.
“So, if it’s not in your heart, in your gut, don’t start,” he says.
It’s in Fox’s heart. And deep in his gut.
“I can’t believe people pay me to do this,” he says.
Fox figures he’s got the best of all worlds in medicine.
Surgery. Clinical care. Teaching. Research.
“What a great thing!” Fox says. “It gives me a much broader view of medicine.
“I became fascinated with clinical medicine, but I felt something was missing. I found myself leaning toward doing surgery because I enjoyed instant gratification. I liked taking somebody who was sick and making them better.
“I found medical research to be the best combination of science and interacting with people.
“My life goes through waves,” he says. “Variations and combinations.
“Even now, I’m being pulled back” into patient care, Fox says. “I took a stint last year. I love it.
“One of the best things about my life is I get to do all these things, and there is benefit in all of them.
“But my intentions are mostly research now.”
n n n
Infusing human liver cells into a diseased liver in 1997, Fox was the first to get transplanted individual liver cells to partially correct a rare metabolic liver disease in a 10-year-old child.
The patient was able to avoid undergoing a liver transplant for many years.
That landmark research was reported in the New England Journal of Medicine in 1998.
“To this day,” Fox says, “no one has learned more” in this particular area.
Recently, there was another breakthrough.
Fox and other researchers were able to turn mouse embryonic stem cells into liver cells, an advance reported in Hepatology magazine.
Significant?
“Very significant,” he says.
What’s next?
“Try to do the same thing with human embryonic stem cells. Basically, we now have a road map of where we need to go.
“I’m confident we will be able to do that. We’re pretty far along. But there’s a long way to go.”
The promise of that research is the prospect of treating some liver disease with cellular therapy rather than the trauma of transplantation surgery and its accompanying regimen of immunosuppression.
“I’m not known for embryonic stem cell research,” Fox says. “I’m known for cell therapy in treatment of liver disease. I’ve been at this for 20 years.
“Embryonic stem cell research is a natural consequence of what I want to accomplish.”
It’s also the eye of the storm.
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Fox is one of two researchers at the med center using dated human embryonic stem cell lines approved by President Bush in 2001 for federal research funding support.
That, he says, represents perhaps one-fifth of his research activity.
“My goal is to cultivate ways to treat patients with liver disease. I try to transplant isolated cells,” Fox says. “My research is focused in that direction.”
No somatic cell nuclear transfer, or so-called therapeutic cloning.
No fetal cells, “not an area I’m interested in pursuing.”
The vast majority of his work involves adult stem cells, Fox says.
“But there are some problems with adult liver cells,” he says, including a limited supply, their “incredible ability to expand,” and their age.
At some point, current federal limits on embryonic stem cell research funding and Nebraska’s own research limits, imposed and proposed, could place a roadblock in Fox’s path.
“Life is filled with struggle,” Fox says.
“I don’t worry about those things. I’m willing to let the work speak for itself.”
What matters is progress, he says.
“If you had liver disease and this was a therapy,” Fox asks, “would you want to wait?”
n n n
The moment of decision is approaching.
“Once you’ve proven you can do it, if society chooses not to move forward, that’s society’s business,” Fox says. “Just as long as all the facts are known.”
Fox distinguishes between society and the organized opponents of expanded embryonic stem cell research, whose leading voices have come from pro-life, or anti-abortion, organizations.
“There are political forces in this state that would like me not to do this work at all,” he says.
“But the decision is not up to those people; it’s up to the public.”
And if the public says go no further, stop where you are, would Fox consider leaving Nebraska so he could pursue his research elsewhere?
“If the people of Nebraska choose to follow that path, I’ll make my own decision,” he says.
n n n
Life.
“I don’t know if any cell line in my lab has the potential to be a human,” Fox says.
“Potential doesn’t define reality. Every egg doesn’t become a person; every sperm doesn’t; every combined egg and sperm doesn’t. In my opinion, only God controls whether a bunch of embryonic cells becomes a person.”
And that, Fox suggests, is “the amazing part of creation. If all it took was (automatic), where’s the mystery and wonder in that?”
When does human life begin?
“I’m not smart enough to figure that out,” Fox says.
“But is this (a collection of embryonic cells) a human being? To me, the answer is no.”
Opponents of embryonic stem cell research are “interested in making a political point,” Fox says.
“They’d have a lot more credibility (if they talked about) shutting down in vitro fertility clinics.”
Pro-life opponents are “internally inconsistent,” he says. “It’s all selective because it’s political.
“No embryos are being destroyed over here.”
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Labels are misleading, Fox says.
Many religious-right leaders who profess to be pro-life argue against universal health care, he says.
“How can you not want to provide relief from misery and ill health?
“If you go to church and screw people at work,” Fox asks, “does that make you more or less faithful?
“I’m pilloried, and told I have no moral or ethical foundation. I do what I do because I think it’s the right thing to do.
“I get up in the morning and I believe in God, a being out there more powerful than me who helps divine our lives. The rest to me is cultural.”
Fox is Jewish. His Polish parents were imprisoned at separate concentration camps during the Holocaust. His father was at Buchenwald and spoke of it only twice — when his wife died and when interviewed for Steven Spielberg’s depiction of the Holocaust in “Schindler’s List.”
Fox had watched the tape with one of his two sons just the night before an interview for this story.
That piece of his biography emerges when Fox is asked whether his research is motivated in part by altruism.
“That’s an innate part of who I am,” he says. “My parents were Holocaust survivors. That’s part of me.”
As a liver transplant surgeon, beginning in 1983, and a doctor and researcher engaged in using and discovering cellular therapy to treat liver disease, Fox has been focused all his adult life on healing.
“Liver transplantation was not very successful when I started, but I wanted to be involved at the ground floor in saving people’s lives.
“It feels really good to take someone who is really ill and carrying them through a liver transplant.
“I’m in medicine to help heal.
“What makes you think I’m not interested in protecting life?”
Reach Don Walton at 473-7248 or at dwalton@journalstar.com.
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