Sam Ogden

Jonathan Tilly likes to gauge the significance of his work by the hair on the backs of his arms. Look at it standing up, he says, thrusting out his forearm on a mid-August afternoon. A reproductive biologist at Massachusetts General Hospital in Boston, Tilly was explaining a procedure to retrieve stem cells from the ovaries of a sterile woman. This experiment, he hopes, will help to quell criticism of his most controversial claim: that ovaries have the potential to make eggs indefinitely. This defies the long-held dogma that female mammals are born with all the oocytes (precursors to eggs) they will ever produce, a population that dwindles with age and is exhausted at menopause.

Tilly first challenged that doctrine in 2004, in a paper1 suggesting that the oocytes in mouse ovaries are being replenished by stem cells. If properly understood, such cells could be harnessed to generate fresh eggs for women with fertility problems, or even achieve a goal Tilly has been pursuing for 25 years: delaying or halting menopause. The hairs are still up, Tilly says. It happens every time I think about that experiment.

He has since published a parade of headline-grabbing papers, culminating this year in a report2 that he had isolated the elusive stem cells from human ovaries and coaxed them to develop into bona fide oocytes. But his work has been dogged by doubt. Some researchers question his methods and reasoning. Others have tried, and failed, to repeat his experiments. Tilly always makes what I call big satellites, something tremendous in the sky, says molecular biologist Kui Liu at the University of Gothenburg in Sweden. He exaggerates, Liu says, and produces a big press release. A few years later, people realize, Oh, not right.

Tilly says he has weathered a lot of attacks. When I made the decision to pursue this, it was out of pure excitement that we found something that could revolutionize the field. It never even crossed my mind that it would be so negative and so nasty. And it really is negative and nasty.

Trisha Gura discusses Jonathan Tillys controversial work.

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But now the stand-off of mistrust, and sometimes open contempt, has taken a strange twist. Two of Tillys most vociferous critics have become his collaborators: one serving on the board of advisers at his start-up company, OvaScience in Cambridge, Massachusetts; the other working directly with the stem cells that Tilly had isolated. These cells are doing things in vitro that can really start to address scientific problems, says Evelyn Telfer, a reproductive biologist at the University of Edinburgh,UK, who was doubtful of Tillys work in the past. If we are really interested in the science...then this is a great tool.

The no new eggs doctrine has a long history. In 1951, the influential anatomist Solly Zuckerman, at the University of Birmingham, UK, performed an in-depth analysis of evidence available at the time. He concluded that none of it effectively countered a proposal from the 1870s stating that female mammals stop producing oocytes after birth3.

For the first 15 years of his career, Tilly focused mainly on programmed cell death, or apoptosis, and he was struck by the fact that no one had ever quantified the loss of eggs due to ovulation and natural oocyte death over time. So beginning around 1999, Tilly commandeered a microscope and mouse ovarian tissue in order to count the follicles, the cellular compartments in which oocytes develop, in mice at different ages. He found a mathematical imbalance: the number of degenerated follicles was three times higher than expected on the basis of the starting pool. If the mice were losing oocytes at this rate, their eggs should be depleted far sooner than they actually were. Something had to be replacing them, he concluded: stem cells were the likely culprit.

Original post:
Reproductive biology : Fertile mind