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From PBS NewsHour – Elephants and P53

By Jackie Judd

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February 22, 2016

Special correspondent Jackie Judd reports on researchers thinking outside the box.

MAN: The Ringling Bros. and Barnum & Bailey performing pachyderms!

JACKIE JUDD: This spring, all of these circus elephants will be permanently retired. But as they leave the center ring, they are taking center stage in another unlikely place, the Huntsman Cancer Institute in Salt Lake City.

DR. JOSHUA SCHIFFMAN, Huntsman Cancer Institute: Just about every person I met who heard about this would come up and ask, elephants, cancer, what’s the connection?

JACKIE JUDD: The possible connection is a work in progress, led by pediatric oncologist Dr. Joshua Schiffman.

WOMAN: Insert the needle into the vein.

JACKIE JUDD: He has enlisted the support of the Ringling Bros. Center for Elephant Conservation in Florida and the Hogle Zoo in Salt Lake to draw blood from these sturdy mammals for his experiments.

Logically, elephants should get cancer far more often than we do. They have 100 times the cells than humans, therefore, much more opportunity for those cells to mutate into cancer. But that’s not the case. Less than 5 percent of elephant deaths are attributed to cancer.

DR. JOSHUA SCHIFFMAN: Elephants have had 55 million years of evolution to figure out how to avoid cancer. Now it’s our turn to take a page out of nature’s playbook, and try to figure out, how do we help our patients and families with cancer?

JACKIE JUDD: Most humans have two copies of a gene called p53. When everything is working, the protein in p53 is a cancer-suppressor, repairing or killing mutant cells so they don’t multiply. Elephants have 40 copies of p53.

DR. JOSHUA SCHIFFMAN: This is our tissue culture room. This is where we actually do the experiments to try to understand, how does elephant p53 work? In here are the actual cells growing.

JACKIE JUDD: After bombarding elephant blood with radiation, Dr. Schiffman and his team stood back and observed how the elephant p53 responded to the damaged cells. The answer, recently published in “The Journal of the American Medical Association,” was that the multiple genes responded far more robustly than p53’s response in humans.

DR. JOSHUA SCHIFFMAN: Instead of trying to repair themselves, the elephant cells, many of them, all went on to cell death, to this cell suicide, or what we call apoptosis.

It’s as if these elephant cells have said, well, it’s much safer, much better strategy to just kill the cell and start over. If we do that, there’s no way that that cell can go on to become cancer, and that was an aha moment for us in the lab. We’re trying to learn how to get kids better with cancer without making them sick.

JACKIE JUDD: Now the research has turned to this question: How does elephant p53 respond in human cancer cells? And could it stop the disease cold? Could it be a treatment to prevent cancer or halt its growth?

DR. JOSHUA SCHIFFMAN: In here are three breast cancers from different individuals that have been growing in the labs. And we take the elephant p53 and transfect it. We put it into the breast cancer cell lines, and we wait and we see, will the elephant p53 kill these breast cancer cells?

JACKIE JUDD: The research, and where it may lead, would be especially meaningful for people like Tony Means. He and others with a genetic disorder called Li-Fraumeni Syndrome have only one p53 gene, instead of two, leaving them virtually defenseless against cancer.

In your family, your mother had Li-Fraumeni, died very young.

TONY MEANS, Cancer Patient: Yes, ma’am.

JACKIE JUDD: You have aunts and uncles who have cancer and have Li-Fraumeni.

TONY MEANS: Yes, a good chunk of our family. I would say a majority,

JACKIE JUDD: And they have all been tested? They have…

(CROSSTALK)

TONY MEANS: Well, every single one has been Li-Fraumeni.

JACKIE JUDD: Means is being treated for cancer and 6-year-old daughter Emma is being watched by Dr. Schiffman because of a small brain tumor. Two other children with Li-Fraumeni are frequently screened, and the family takes part in Dr. Schiffman’s research in any way they can.

TONY MEANS: I have kind of put hope in him by choosing to have children, knowing that there’s a chance they could have the gene.

JACKIE JUDD: But you understand this is years off, if ever.

TONY MEANS: Oh, yes, yes.

JACKIE JUDD: If ever.

TONY MEANS: Oh, yes, yes, yes, yes. Who knows?

JACKIE JUDD: And that is where Avi Schroeder comes in. Dr. Schroeder of Technion, the Israel Institute of Technology, joined the research several months ago, with the goal of developing a drug for humans that would mimic the elephant’s robust p53.

AVI SCHROEDER, Technion-Israel Institute of Technology: Now there’s a delivery issue. How can we get that protein to the disease site, into the cancer cells, to act and to perform the therapeutic activity on site? We’re going to wrap the proteins inside a nanoparticle, and they will release the protein inside the cancer cells.

JACKIE JUDD: And if everything works, the cancer cell will be killed?

AVI SCHROEDER: Yes, the cancer cell will go into a death cycle after that, yes.

MAN: We are excited to have Dr. Schroeder here.

JACKIE JUDD: The team of optimists believes clinical trials could begin in three years. Not surprisingly, there is skepticism in the medical community, and that is shared by Dr. Lee Helman, the head of clinical research at the National Cancer Institute.

DR. LEE HELMAN, National Cancer Institute: The whole idea of putting an elephant gene that’s regulated in a unique way into a human being, when we have had enough trouble putting human genes into human beings with all kinds of difficulty, I would say he has got a lot of hurdles to overcome.

JACKIE JUDD: But Dr. Helman does believe there is value to this deeper investigation into p53.

DR. LEE HELMAN: I think his finding only lends further evidence to support that hypothesis that p53 function, and understanding it and being able to regulate it, would be a major step forward in our ability to treat cancer.

JACKIE JUDD: Cancer touches almost every family, directly or indirectly. For families like the Means, it is a certainty.

So, what is happening in this lab, at this zoo, could be life- changing.

Have you taken the kids to the zoo to see the elephants?

TONY MEANS: Yes. Oh, man, that was awesome. The kids loved it, and it was kind of fun for me to sit there as a father and just look at them. This is the answer in their lifetime. That’s all I want is for my kids to have that. And this — this gives them hope.

DR. JOSHUA SCHIFFMAN: I don’t promise my patients it will happen, because I don’t want to have them disappointed. But if I didn’t believe this would work, I wouldn’t be trying it.

JACKIE JUDD: Dr. Schiffman concedes that turning to elephants for a cancer treatment is outside the box, but that, he says, is often where the best answers are found.

http://www.pbs.org/newshour/bb/elephant-genes-hold-big-hopes-for-cancer-researchers/#