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Brigham doctor turns to animals for ideas

When faced with a thorny medical problem, Dr. Jeffrey Karp and his students sometimes head to Franklin Park Zoo or the New England Aquarium. But they're not goofing off.

Animal life is a big source of inspiration for Karp and his colleagues at the center on regenerative therapeutics he runs at Brigham and Women's Hospital. The group has a knack for developing clever pieces of medical engineering based on how animals have adapted to their environment.

A case in point: waterproof bandages inspired by the sticky feet of the Tokay­ gecko, a native of Southeast Asia.

"Evolution," Karp said, "is really the best problem-solver."


Now Karp has two more creature-inspired inventions: a cancer detector sparked by jellyfish tentacles and a painless needle designed after the quills of a porcupine.

"He's been very innovative about taking nature's lessons and applying them in interesting ways that might lead to different useful medical products," said MIT scientist Robert S. Langer, who collaborated with Karp on the gecko and porcupine work.

Quills from porcupines have backward-facing barbs in a precise pattern, which makes them good at penetrating skin — and hard to remove, as any dog with a mess of quills in its nose could attest.

Riffing off this idea, Karp and his colleagues developed needles that take less energy to insert — "and may thus reduce pain upon insertion" — and arrayed the barbs to make them 30 times harder to remove.

These needles could be used in place of surgical staples — imagine a quickly placed patch that works like stitches to close a wound — that degrade when no longer needed. They could also be used as injection needles that require less pressure to insert, allowing a doctor or nurse to more accurately and sensitively place a needle or a probe, without overshooting.


"These could have multiple applications," said Karp, who published a paper on the new needles in early December in the Proceedings of the National Academy of Sciences.

The needles are still being tested in Karp's lab and are several years away from being used on patients.

Karp published a second paper in the same journal in November in which he posited that cancer cells can be plucked out of the bloodstream, much the same way a jellyfish uses its tentacles to grab tiny prey out of a vast ocean. "It really doesn't matter where the food or prey land, they can be captured," Karp said.

Modeled on the jellyfish, he developed a thumbnail-size device that mimics the actions of tentacles to pluck cancer cells out of the bloodstream. Karp hopes to use it to test for cancer cells in human blood, and to see which drugs work best against those cancer cells. His lab is applying for Brigham and Women's permission to review blood samples in this way.

Scientists have wanted to grab malignant cells out of blood since the 1800s, when cancer cells were first found in the bloodstream, said Dr. Howard Scher, chief of the Genitourinary Oncology Service at New York's Memorial Sloan-Kettering Cancer Center.

Most cancers kill not at the site where they began growing, but after they have spread elsewhere in the body. If cancer cells can be found in the blood before they establish a foothold at a secondary site, that could be tremendously helpful in stopping their spread.


"Finding these cells is a big deal," said Mehmet Toner, a professor of bioengineering at Massachusetts General Hospital and Harvard Medical School.

Tracking the number of cancer cells could also help doctors monitor the effectiveness of drugs — for example, whether tumor cells in the blood rise or fall after treatment.

"Every single pharmaceutical company is interested in circulating tumor cells," said Toner, who is working on a tracking device that is closer to market than Karp's. "Billions of dollars are going into this field."

So far, only one such device, from Johnson & Johnson, has received approval from the Food and Drug Administration. Karp said his approach, which will take several years to refine, will screen more blood faster and separate out captured cells for analysis.

The small device that Karp and his colleagues designed consists of tiny tentacles made of long chains of DNA that are studded with smaller DNA segments that act like hands. As blood flows over the device, the arms wave around like sticky jellyfish tentacles in the sea, with the hands grabbing cancer cells.

The lab's main technological innovation, Karp said, was to attach these arms to a herringbone-shaped platform, which disrupts the blood flow. This directs the cancer cells toward the waving arms and allows the device to process more blood, more quickly.

Because the hands are DNA, they can be made to easily release the fragile cancer cells without harming them, Karp said.

Those cells can then be used to test drugs, to see which one will be most effective against the patient's own cancer cells.


"There's a significant opportunity here to enable a more personalized approach," Karp said. "Instead of guessing, this could provide an opportunity to fine-tune and select the best possible chemotherapy for a patient."

The device might even be usable to detect rare fetal cells in a mother's blood, Karp said, avoiding the need for amniocentesis to judge the health of the baby.

With amniocentesis, a large needle is used to withdraw fluid from the amniotic sac; in rare cases, this can cause a miscarriage.

"The beauty of the platform is how flexible it is," said Scher, who has not been involved in the work, but traveled to Boston this month to talk with Karp about it. "I just like the way he thinks. Totally out of the box, but totally logical."