delaying marriage even longer
Study Casts Doubt on Limits to Fertility

By Rick Weiss
Washington Post Staff Writer
Thursday, March 11, 2004; Page A01

For more than half a century textbooks have taught that female mammals -- be they mice, cows or women -- are born with all the eggs they will ever have.

The result is one of the great sexual disparities: Males, who make fresh sperm daily, can sire children at virtually any age, whereas females gradually deplete their limited supply of eggs to the ticking of the biological clock.

Now Harvard researchers have come to the radical conclusion that female mice produce a constant stream of new egg cells as adults -- challenging a central dogma of reproductive biology and raising the heretical possibility that women, too, clandestinely produce fresh eggs for at least the first half of life.

The findings suggest the possibility of extending fertility much longer than was thought possible and even restoring fertility in women whose ovaries have shut down.

"I'd regard this as one of the most significant discoveries in the reproductive field in the past several decades," said Duke University developmental biologist Haifan Lin, who studies egg development. "It provides a new potential opportunity for prolonging the reproductive span of females."

After all, Lin and others said, if women are busily making eggs for their first 40 or 50 years -- rather than simply spending down a nonrenewable endowment -- then it may be possible to tweak that egg-production machinery in ways that can keep it going a decade or two longer.

It may even be possible to transplant into older or chemotherapy-damaged ovaries some egg-producing cells that have been frozen since youth, restoring a woman's lost fertility.

Those options could have profound social impact by granting women more freedom with regard to the timing of careers and parenthood. Even if women chose not to have children later in life, an extended period of fertility could have significant health implications -- perhaps delaying the onset of heart disease, osteoporosis and other ailments that become more prevalent after menopause but also possibly increasing the risk of other diseases, such as breast cancer, that have been linked to years of exposure to the hormones the ovaries churn out.

Experts warned that the study, led by Harvard developmental biologist Jonathan Tilly and published in today's issue of the journal Nature, will have to be confirmed by others.

"At this point I'm agnostic," said John Eppig, a reproductive biologist at the Jackson Laboratory in Bar Harbor, Maine. "My mind is racing."

But Tilly said his group already has completed an added study that supports the idea that women, too, are still making eggs as young adults.

If doctors can learn how to tap that egg-making capacity to delay menopause, said Marian Damewood, president of the American Society for Reproductive Medicine, "that could be the most significant advance in reproductive medicine since the advent of in vitro fertilization more than 25 years ago."

Scientists in the early part of the 20th century went back and forth on the question of whether mammals could make fresh eggs after birth, but a 1951 journal article seemed to settle the issue in the negative, and few revisited the question after that. By examining ovaries retrieved from experimental animals -- or from cadavers and surgical patients of various ages -- scientists documented a declining number of egg cells with age.

In humans that decline starts just five months into fetal life, when the number of eggs -- each nestled in a hormone-secreting niche called a follicle -- peaks at about 7 million. The vast majority are gone by birth, and the last typically disappears in a woman's 40s or 50s, prompting menopause.

Tilly's work shows that the daily rate of egg loss is actually much higher than scientists knew -- at least in mice -- but the loss is largely masked by simultaneous production of new eggs.

"As much as we still ourselves are in disbelief that the dogma is wrong, it's very real," said Tilly, director of the Vincent Center for Reproductive Biology at Massachusetts General Hospital in Boston. "The dogma is wrong."

The new view that eggs are being made every day even as a somewhat larger number of them shrivel and die could resolve some seeming contradictions.

For one thing, Tilly said, "it makes no sense to have a fixed population of eggs that have to sit around for decades until they are used," accumulating mutations and other problems along the way. In less complex animals, including insects, females as well as males make sex cells into adulthood. It is gratifying, Tilly said, to see mice following that sensible pattern.

In one set of tests, Tilly's group showed that on a single day as many as 1,200 egg-encasing follicles were dying in the ovaries of young adult mice -- far too many for the initial supply to last a reproductive lifetime. The group also identified a population of what appear to be egg stem cells -- the self-replenishing kind of cell that makes egg cells -- in one region of the ovary. Each ovary seems to have about 63 such cells -- few enough to have been missed by early ovary gazers.

Another experiment showed that meiosis, a process unique to the production of sperm and eggs, was occurring in the ovaries of adult mice. The team also used molecular markers to show that some stem cells in adult mouse ovaries seemed to be growing into new eggs.

For one strain of mouse, the team calculated that about 77 new eggs are produced every day -- not a huge number, but infinitely bigger than zero.

"Seventy seven eggs a day! That's just unbelievable," said Hans Scholer, a University of Pennsylvania mouse stem cell expert. "That's really a major finding."

To get a sense of whether women may also be making eggs, Tilly looked at the incidence of premature menopause in cancer patients treated with various cancer drugs. In results not published in the Nature paper, he found that 106 of 107 women treated with busulphan, which specifically knocks out cells making eggs or sperm, went into premature menopause, compared with only 69 of 140 treated with different drugs. That difference suggests that egg production was indeed going on in the women's ovaries, Tilly said.

The new thinking has quickly raised new questions, including why egg stem cells die or shut down in middle age and whether drugs or other stimuli might keep them going. Scientists already know some of the hormones that insects use to maintain egg production in adulthood, and similar hormones have been identified in mice and humans. Scientists said they were now eager to test the effects of those hormones on mammals.

Extended fertility would have its ups and downs, said Judith Houck, a historian of medicine at the University of Wisconsin at Madison. "Historically, in the 20th century, menopause has been seen as the moment when women finally get to live for themselves . . . a time when women could look more carefully at intellectual interests, take up painting, go back to school," Houck said. Delaying of menopause could mean delaying that transition, she warned.

"On the other hand," Houck said, "more and more women are choosing to have careers, and the most convenient way to do that is to leave childbearing until at least their 30s. So it may help them replicate the male model of success."

dream come true

I HIKED ON A REAL GLACIER YESTERDAY!!! AND I EVEN GOT TO "SWIM" (i.e. JUMP IN AND GET THE ROCK OUT AS QUICKLY AS MY NEARLY FROZEN BODY WOULD LET ME) IN A "POOL" (i.e. A GIANT CUP OF GLACIAL ICE WATER).

i have had this dream the last several months of walking on a glacier and i did it. i feel somewhat fulfilled. as for the swimming, when my guide asked us if we wanted a swim, and no one responded, he then started singling us out. so as i approached this pool -- essentially water filling a crevasse in this glacier -- he asked me, how 'bout a swim? i assessed the situation and said, only if you go. because no one else was game, he said bloody hell i'm going. and i had to live up to my word (americans are not well respected in international circles and i feel it's important to act as a sort of good-will ambassador in my travels :) ) and i went in too. BLOODY HELL IT WAS COLD! let me describe this to you.

See, franz josef glacier is a "mild" glacier as it reaches down to pretty temperate zones. i doubt the elevation was much above 1000 feet, so we're not talking about leaving the troposphere. well, with the sun baking this thing, the top of it melts and runs off, creating these braided rivers downstream. but on the glacier, the water can accumulate in crevasses, as water will go where it wants to go and gather where it wants to gather. so here we have melted glacier accumulating in a giant cup made of ice, and into this we jumped.

brr.

back to the north island tomorrow. i do and i don't want to come home. can i put myself into debt just to avoid living with my parents?! sigh.

detour
rafting yesterday was awesome! i'm quite glad i got to do it, and the people were friendly, the guide was competent and nice, and not sleazy at all, as river guides are known to be. i even jumped off a 30-foot ledge! go me! of course, i would have felt horrible if i didn't; this 40-something year old lady, who'd never gone rafting much less done heaps of adrenaline type activities, went first and jumped nearly without hesitation. but ooh those nasty sandflies!

today i've taken a detour to franz josef glacier. as of late i've had a dream to stand on a glacier. i didn't think i'd get it in this time, but then with global warming, who knows if the glaciers would be here the next time I'm here. so when i showed up in greymouth and found out it was only two hours more to franz josef, off i went. and here i am. tomorrow morning is the big date. i'm so excited!

so ... let's just say, there are certain aspects of my vacations that truly define my vacations. WHY AM I SO PREDICTABLE? WHEN WILL I EVER STOP BEING A COMPLETE IDIOT? crikey.

thus with my heart mildly scathed, i am quite looking forward to coming home in 9 days.

not too late for a career change ... back
i have just done one of the most amazing things ever ... i went on a three-day sea kayaking trip in the Abel Tasman National Park, in the northern tip of the South Island of NZ. the combination of the scenery, the mode of transport, the company and the weather and the lifestyle just created one of the most pleasant times ever. we got to play with 3-month old seal pups, lunched and lounged on lonesome beaches, and sailed using a tarp, whilst drinking wine. it's funny because it was a small group -- just four of us and a guide -- and it made me feel like i was so unique that i got to do this, but i know thousands and tens of thousands even have also done this, and will do so after me.

now i'm in murchison, and at the spur of the moment, when i walked into the information stand, the guy asked if i wanted to go rafting and i just said yes. i don't know why. i don't think i could top the sea kayaking experience, but hey, it can't hurt to try.

after being with the same four people for the last three days, getting to know them fairly well, i feel lonely again. i guess it's good that i'm heading to hanmer springs and a familiar face.

augh! i've lost my camera! i highly suspect someone stole it, but i keep hoping that i've just misplaced it, even though i've been through all my stuff! it's not the camera that i'm so worried about; that's fairly easy to replace, altho' it's a great camera. IT'S THE FILM! why god why?!

ps
oh, and, i think i'm getting sick...

see what you get from some indecision?
i popped into the local STA TRAVEL branch today and found out that only one seat was available on 3/28, and then the only other day was 4/4, if i wanted to move my flight back. if i didn't change it, i'd be leaving 4/7. i decided to think about it before making the decision, and before i knew it, it was 5pm, the office was closed, and i can't see them until monday. (it's saturday here.) so i decided to bite the bullet and head to the south island, via a NZ$150 ferry, with my car, and take a tiki tour of the s. island. i hope to sea kayak a few days in the national park, and walk on a glacier, maybe visit a friend and some other cool locales. but this isn't what i originally wanted to do. it's probably what's best as i did fork over a lot of money to fly here, who knows when i'll do it again, and do i REALLY want to go and live with my parents again? grass is greener, always, in my head.

currently i'm in wellington, the lord of the rings capital of the world. the world premiere was here and for NZ$195 i can take a tour of the film sites around this city. uhh...no thanks. i think i could manage it by myself.

it is the weekend, and i'm so jaded about going out and drinking alcohol, any amount. i figure, i've spent the last six months essentially staying out late every friday and saturday night. so as this is my vacation, i'm going to relish sitting around, watching tv, reading and writing. it's OK. i'm not 18 and looking to get pissed (drunk) and hook up. not that i really was into it at 18, either.

so in short, here i am stuck on the other side of the world, doing nothing but having several lazy days in a row.

back in the familiar place
i'm in the internet cafe in tauranga that was the center of so much poor judgment. it's weird being back here, where i feel everyone i know hates me. though that's not true because i've been able to catch up with old friends. it's like i never left. and it feels like i never will because of my damn car. it hasn't passed its warrant, or inspection, and i've had to stick around for a few days so i can fix the things that need to be fixed and then get it retested. stupid jackass who did the inspection was so picky! and then today when i went back he wouldn't see my straightaway. oh well. at least i get to check my email.

so after the car gets sorted out, i'm down to napier, art deco capital of new zealand, and hawke's bay, one of the major wine-producing regions. i'm excited to finally GO somewhere, but i'm also really homesick. well, not missing living with my parents and my endless work obligations. i just miss being around people i know. i haven't had much of that in the last several months, what with working all the time and retreating into this solitary existence. so i'm thinking the remedy might be to cut my vacation short and just visit PEOPLE. oh people, how i love people. actually, that's not true. i hate people. i love my friends.

ps i've gotten into boston university and new england school of law. i'm still waiting on my top two choices.

if this is paradise, why does it rain so much?
i forgot about you, dear blog. for better or worse. i am here in rarotonga, the edge of the world, the last time zone of the day, the middle of nowhere, a rainy paradise. this is my second fully day on the island and my third rainstorm. it was quaint yesterday when i was on my push bike, touring the island. (it's about 20 miles and my bum hurts a lot.) today, not so cute. but still, it's amazing here.

i'm in avarua, the main town in rarotonga, though if you were on a highway in kentucky, this place would be a blink-of-an-eye village. the mosquitoes are fierce, as is the sun. i'm quite burned even tho' it was thoroughly overcast yesterday. monday, i'm off to aitutaki, what i suspect from pictures to be an even more idyllic place. i love swimming in warm, clear waters, though it's a little freaky to do it by myself. it's not hard to find a lonesome swimming place, and then i worry about sharks and random spiky poisonous creatures. in reality, i don't have much to worry about, but sometimes standing on the beach, thinking about how vast the pacific is and then how small this blot of land is ... well, it's just a little scary.

my voyage to rarotonga was a long one. from newark airport to LA for five days or so, then a 13 hour flight to auckland. then the next day, a four hour flight BACK EAST and over the dateline to the Cook Islands. It was Wednesday then it was Thursday, then I woke up and it was Friday and I hopped back on a plane to Thursday and woke up on Friday again. There really isn't much jet-lag because the hours are so close, but it's just plain weird, damn it.

So ta ta for now.