Frozen Eggs Perks as Policy

Posted on March 3, 2016 by Roger Gosden

Ashton Carter announced the Pentagon will make a bigger commitment to family-building for people serving in the military. The package includes new benefits for maternity leave and child care, and even a pilot scheme for egg and sperm freezing. The news is less surprising since Facebook and Apple rolled out a policy of offering $20,000 perks to young employees for defraying the costs of egg banking, which amount to >$10,000 per cycle + annual storage fees.

The aim is to retain highly-trained staff from leaving early to start a family. Most women are aware that their biological clock starts to wind down from around age 30, long before the average age of menopause. Egg banking is portrayed as fertility insurance, but is it just a lottery?

egg freezing

Eggs come in from the cold

The first freezing trials with human eggs were far less successful than with embryos. Since they are delicate single cells, their survival is all-or-nothing, whereas embryos afford to lose one or two cells from the bunch. Fewer than half were surviving in the 1980s, and very few of them made babies with IVF. Even more alarming was the evidence that chilling damages apparatus in eggs on which the chromosomes “dance” during cell division, putting babies at risk of birth defects from the wrong number of chromosomes. Many labs besides our own tried to improve results, but the breakthrough came with vitrification, which turns cells into a glassy solid instead of ice. Masashige Kuwayama at the Kato Clinic in Japan perfected the method. It involves ultra-rapid cooling in a highly concentrated solution, similar in some respects and different in other ways to making smooth ice cream. Like home-made ice cream, vitrification is not a technically sophisticated process, but it demands expertise of the technician who, working under a microscope, mounts each egg in a minute droplet for plunging into liquid nitrogen. I wonder if a technique that depends so heavily on operator skill in an unregulated environment can produce consistent results across clinics.

Egg banking emancipates fertility preservation for women, whereas men have had sperm freezing since the 1950s. The original rationale for banking was to help young women preserve their fertility from the sterilizing effects of high-dose chemotherapy and radiation. It also helps women to have genetic children after a hysterectomy, although a surrogate must then be commissioned to carry the baby. Before egg banking there was embryo freezing, but that requires IVF and therefore a male partner, or ovarian tissue freezing, which we developed as an alternative technology and is still used for child patients. One of the great advantages of freezing eggs versus embryos is that there are fewer issues surrounding the disposal of surplus eggs because they carry less moral gravity.

Although egg banking has been a bright hope on the dark road through cancer treatment, it is now embraced by far greater numbers of healthy women. This is being encouraged by perks from employers and lauded by media reports and TV. As if that publicity was not enough, clinical providers are heavily invested in advertising. I am told that business is booming, and more and more fertility clinics want some of the action.

But pause to consider the “customer.” I think that word is more apt than either patient or client, because these women are seeking treatment for a non-medical condition (aging) and from for-profit clinics. More and more fertility clinics that started as private medical practices are becoming absorbed into big business. I suspect these entities are now looking less and less like a familiar medical environment and more and more like normal commercial operations.

And who is the typical customer? She is a professional or businesswoman in her 20s or early 30s who dares not step off the career ladder during her most fertile years, or perhaps she hasn’t found a Mr. Right yet. There are other reasons, but a common conflict is between biological imperatives and social pressures. Employers are slowly recognizing this dilemma, but the answer they provide (if any) is technology instead of a better deal for women’s careers. Consequently, the average age of motherhood is rising, and already passes 30 at the birth of the first child in several countries. Men are luckier, although fresh mutations are more common in older sperm.

What price would you pay for a child of your own? There’s the nub of it. Fertility treatment involving IVF is unaffordable by most couples on low incomes, and those who can afford egg banking to delay family-building are investing in uncertainty. As this is a new technology there are very few centers with enough data to provide a reliable estimate of the chances of pregnancy with banked eggs. A British authority (HFEA) reported that up to 2012 there were only 20 babies born from 160 treatment cycles, and the US registry (SART) announced 162 live births in 2014, a success rate of 1 in 5 cycles. We await updates.

Success can never be assured. Since the chances with one batch of eggs are unlikely to be high, multiple rounds of treatment (i.e., more eggs) are required, and preferably collected at very young adult ages. Can you think of another product costing as much with so little security? Would you buy a new car or boat from a dealer without a guarantee? Would you dare commit thousands of dollars to a lottery? The reason that people will spend so much on fertility services, even taking out large loans or remortgaging their home, is because having a baby is a life event. Nothing compares with it.

This cautious post may seem surprising from someone who spent his whole career in reproductive technology and biology. Egg freezing is, of course, a wonderful breakthrough which I welcome unreservedly for patients needing emergency fertility preservation, but to others I say let the buyer beware.

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No Sex Please, We’re Bananas

Posted on February 14, 2016 by Roger Gosden

That’s a problem for our banana-munching republic. Sex was suspended for banana cultivation long ago, and the price we will pay is a Bananageddon. Here’s why.

The plant is propagated vegetatively and cannot produce seeds because it is genetically triploid. Two sets of chromosomes in a diploid plant are company, but three is a crowd because the threads of DNA get tangled and can’t segregate into equal halves to make haploid germ cells in male and female flowers. The vast banana plantations in the tropics are genetically identical clones, and the lack of diversity in these monocultures renders them vulnerable to pests that can evade their natural defenses.

There is only one kind of banana in the marketplace today, and its existence is threatened by the fungus Tropical Race Four whose hyphae kill after growing into the plant and cannot be eradicated from the soil. It has devastated crops in Asia and Australia because farming practices are so intensive, providing no physical or genetic barriers to the spread of disease. When it begins to rampage across the growing regions of Latin America bananas at 60 cents a pound will be a memory.

We have bananas

We have bananas

The fruit we love dangles on the thread of a single variety, whereas the many kinds of apples-Granny Smiths, Golden Delicious, McIntosh Red, etc- are begotten from sexual unions and seed dispersal. Until sixty years ago the Gros Michel was the big banana, with a less attractive name than the Cavendish which is currently the reigning monarch of the bunch. I am told that the Gros was the more tasty of the two, although I can’t remember because I was too young, being born around the year 10 BCE (Before Cavendish Era). When Gros plantations came under attack by an earlier disease, the Cavendish was planted as a substitute because of its greater resistance, but now it too is under a threat.

The Cavendish is an aristocratic banana. Sometime in the 1830s it was grown on the estate of the Duke of Devonshire of the Cavendish family, whose stately home is the famous Chatsworth House in Derbyshire.  The 6th Duke recognized an outstanding talent in his boy gardener, Joseph Paxton, who designed the greatest greenhouse in the world for his master, and which became the inspiration for his plan of the Crystal Palace at the Great Exhibition of 1851. Sir Joseph, as he later became, was one of the most ingenious men of the Victorian Age, and all because of the Duke’s trust and confidence.

One of his claims to fame was to grow in his greenhouse the variety of banana that now adorns our fruit bowl; as a young man, Joseph never asked what bananas could do for him, but asked what he could do for bananas. The Cavendish is his gift to the world, and it is a shame that the Devonshire family motto can’t be changed from Cavendo tutus to Deus nisi quod fixa (meaning God save the banana). But I digress…

In the past few weeks, banana biologists have announced the genome sequence of their fruit. The Bananome will enable them to peel open the fruit for genetic engineering to confer resistance to specific diseases and boost its nutritional bounty, perhaps by augmenting vitamin A whose deficiency still causes blindness in children. We will then have to choose GMO bananas or have no bananas, but genetic engineering will be fruitless unless vegetative propagation is bypassed for making new cultivars. To straighten our banana troubles we need to suspend cloning in this Brave New World long enough for a bunch of native plants to have wild sex.

Next Post: The Dark Side of Physics and Biology

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If Snow be Black

Posted on January 29, 2016 by Roger Gosden

After last week’s monster storm that left Eastern USA snow white, the snowbanks slowly melted into pools and streams. But what if snow were black? The Bard liked nature the way he saw it, but he loved to mock our conventional sense of color.Sonnet #130, ver#2

Casting back to Physics 101, I remember learning how experience tidily lines up alongside theory. Dark surfaces feel hotter than light ones as they don’t release energy so efficiently, and dark roofs and asphalt are heat sinks making urban centers several degrees warmer than outlying countryside. There is little advantage in a black roof for absorbing heat when it is snow-covered, but a white roof in summer can significantly reduce AC bills by reflecting the sun’s rays.

Standard white paint reflects 80% of solar radiation, whereas standard black has only 5% reflectivity. The thermal emissivity of asphalt and snow are similar, but the solar reflectance index from combining reflectivity and emissivity is theoretically 100 for white versus 0 for black. Some difference!

Snow be black

Snow be black

Instead of sprinkling salt to lower the freezing point of your icy path, test whether powdered black carbon (soot) melts ice faster by absorbing heat than leaving it untreated. Almost unnoticeable traces of black carbon can have noticeable effects. Consider the melting of glaciers, which started accelerating in the Alps in the second half of the 19th Century. This was originally blamed on climate change (temperature and precipitation), but a recent model from measuring ice cores predicts a better fit to the fallout of black carbon in the Industrial Age. The Alps are encircled by cities that industrialized early and depended on burning dirty coal.

Weathermen who speak of ‘black ice’ know that it is, strictly speaking, science fiction. It’s very hard to imagine how atomic bonds would be bent to abolish the reflective properties of ice, at least in the universe we know. But who knows? Nature looks stranger every day we look closer. Black holes look black because gravity captures light from escaping. Both black coal and transparent diamonds are from carbon, not paradoxical but a discovery that would have humored Shakespeare.

If snow was not white, our world would be hotter, have higher sea levels, different fauna and flora, and no snowmen on Christmas cards. According to that incurable optimist, Dr. Pangloss, “It is demonstrable that things cannot be otherwise than as they are; for as all things have been created for some end, they must necessarily be created for the best end (Trans. Candide). But Tom Torrance, a theologian famous for embracing Carl Barth and Niels Bohr, once reminded me that we live a contingent universe, and ought to be thankful for this one and not to be born somewhere much stranger in the multiverse. Yes, let snow be white.

Next Post: Dees Bones Gonna Walka Round

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Are Bats So Scary?

Posted on January 23, 2016 by Roger Gosden

Some animals have few human friends, like bats. We had a little brown bat tucked inside folded wings, like dead leaves, hanging over a rocker in our porch. It was a welcome guest. But ask the public about the most despised animals and bats come near the top of the list, whether in myth or fact—they give people creeps at Halloween, they hang out with witches, they are revenants haunting graveyards, they drink blood, and the latest accusation is they gave us the Ebola virus. So this week I’m defending bats but mostly writing about zoonoses (What?). I’ll try to explain…bat

There’s no smoking gun that would convict bats in a fair court of law. It’s true that maps for bat density and infectious diseases are closely matched, and fruit bats can be found roasting on charcoal fires in Guinea where the first cases of Ebola were reported. Circumstantial evidence is usually sufficient for prejudice when a creature is ugly, loathsome, and gets tangled in your hair (sic)! It matters not that “nice” animals like antelopes and chimpanzees harbor the same virus, and likely many other mammals too when the research is done. At one time, rabies was believed to be confined to canids, but we now know that every mammal can transmit the virus. It seems that every species that was crowded onto the Ark is a potential vector for a zoonosis that Noah’s family might have caught. Yes, there’s a microbial zoo in furry animals, the ones we think are cute and the others we loathe. All this said, I admit we can’t let bats off the hook, but we should agree the culprit for Ebola is still unknown.

Bats carry a menagerie of over thirty viruses, probably not a record load and certainly not all harmful to us, but alien to human hosts. Bats tolerate most of them without harm to themselves (they succumb to rabies) because microbes have piggy-backed their hosts for eons, time enough for host and pathogen to adapt through mutation and natural selection for virulence to taper off. This biology is a brilliant challenge for evolution deniers to deny. It’s not in the interest of a piggy-backer to break the back of the one carrying them, because when that one dies so does the other. And that is why new host-pathogen associations are so much more dangerous than old ones.

There are historical precedents where the introduction of a pathogen to an immunologically naïve population was devastating. Take the story of measles and smallpox brought by Europeans to the Americas, or Americans building the Panama Canal in the jungle who brought yellow fever home, or when raccoons deliberately moved across state lines in the 1970s transferred rabies to local wildlife. The history of HIV crossing to humans is still unsettled, although the retrovirus evidently has progenitors in healthy chimpanzees today. I published a speculation that it jumped species in the 1920s during human surgery involving grafted organs from chimpanzees, although that theory is dangling. The likelihood of hosting a foreign microbe is much greater between closely related species like mammals and to a lesser extent birds, than, say, reptiles or amphibians. Certainly, the reservoir of potential pathogens in animals will never run dry, but their abundance is not as alarming as the opportunities for exposure.

Some two decades ago, Laurie Garrett wrote The Coming Plague as a reaction to the complacent belief that infectious diseases had been largely overcome (smallpox, etc.), and the redirection of research endeavor to degenerative diseases. She was running with the tide because while drafting her book the HIV-AIDS epidemic kicked in, TB became resurgent, Legionnaire’s disease grabbed headlines, Lyme was discovered, and Ebola, etc. Tellingly, she chose as her subtitle, Newly Emerging Diseases in a World out of Balance.

There was a time when our distant ancestors were “in balance with nature” in the sense that their relationship with nature hardly changed over eons, except for the strains of climate. When microbes jumped on hunter-gatherers from another species (perhaps their prey food), the infection probably fizzled out without triggering an epidemic, either because their immune system quenched the invaders or the microbes slew them. The new diseases were unlikely to be transmitted between the small bands of thinly dispersed people, and large parts of the world were uninhabited until recent millennia. How different today! Our species has grown enormously in number and now extends its reach into every corner of the world, except the depths of the ocean which are much safer from pathogens. We are climbing a gradient of risk as rural populations move into crowded cities, as tropical rainforest destruction brings new exposures, as climate changes encourage migration of tropical diseases, as air circulating in airplanes efficiently spreads airborne infections, and in so many other ways. A perfect storm.

Well over 300 new infectious diseases have been recorded in my lifetime—SARS, HIV-AIDS, West Nile, MRSA, Ebola, Nipah, Hanta, and you name them—as well as countless others that are not yet attributed to a specific pathogen or go unnoticed in rural obscurity or poverty stricken regions.

Optimists look forward to the conquest of heart disease and cancer, but the tide of infectious diseases will continue to run over the feet of scientific Canutes for ages to come. They will wash up on the shores of human communities so long as we share habitats and have farm animals. To adapt a famous quotation, the price of biosecurity is eternal vigilance. New infections need to be nipped in the bud before they become runaway epidemics. As new diseases steal up on us, it is hard for public health bodies like the WHO and CDC to prepare for new threats, and to strike a tolerable balance between public risk and individual liberty. I have a personal example of how overreaction follows a feeble response to a threat.

Courtesy of HSE, UK

Courtesy of HSE, UK

In the 1990s, a few dozen unlucky people in the UK and one in France received the awful news that they had contracted “mad cow disease,” which is caused by a prion protein. This new variant of Creutzfeldt-Jakob disease was introduced to the human food chain when up to a million cows were fed rendered products of dead cows. I remember when the then Minister of Agriculture, John Gummer, declared on TV, “There is nothing wrong with British beef!” between nibbles of hamburger with his daughter. What a bummer! The burger didn’t kill him, but public ridicule destroyed his political career. The lesson learned, American authorities were far more cautious, as I discovered after moving to the States. I had lived in the UK in the years when egregious farm practices still existed. In consequence, I am officially deemed to be an unsafe blood donor, which is a pity for someone with the universal donor blood group. I am still waiting for my mad cow diagnosis.

I find cycles of public anxiety about Ebola rather ironic while our attitudes towards the otherwise beneficial and marvelous bat family are consistently grim. Rather, they should be reversed. We ought to worry whenever we hear news of a bat species in trouble, and be constantly alert for ill news of a new zoonosis of whatever origin. New pathogens are far more threatening to national security than terrorism which is currently gripping the public imagination, or at least until a sophisticated bioterrorist has the know-how to manipulate a pathogen for causing a pandemic. Perhaps then the word zoonosis will emerge from its obscurity at the back of the dictionary.

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Mastodon in Our Town

Posted on January 16, 2016 by Roger Gosden

Not Mastodon the heavy metal band from Atlanta, but a heavy, leathery mastodon from Virginia. It is the first found east of the Blue Ridge. A local bricklayer was hunting on private land one day in 1983 when he found a strange object near a muddy creek. As he couldn’t identify it, he asked the geologist Jerre Johnson who realized it was the tooth of an elephant. An elephant in America—had Barnum & Bailey’s Circus been in town? But this animal was quite different to African and Indian elephants today, from a line that became extinct about 11,000 years ago. They are related species, but mastodons split early from a common Proboscidea ancestor, presumably trekking across a land bridge between Asia and Alaska ahead of mammoths that came later.

The private owners of the land forbad excavation, but when they sold it the new owners gave permission for excavation by Dr. Johnson, now Emeritus Professor at the College of William & Mary. He led a dig involving dozens of volunteers, including archeologists, Eagle Scouts, and many members of our chapter of the Virginia Master Naturalist program. It became a triumph for citizen science.

A breakthrough came after ten days of fruitless digging when the dirt started to yield its fossil treasure, including more teeth, ribs, limb bones, and broken tusks seven feet long and six inches wide at the base. The beast was old judging by its molars which were worn down by a rough diet. This was not a grazing species like modern elephants, but a browser of tree branches and leaves.

Mastodon fossil

A tusk in protective plaster

Fossils in the coastal plain are not living matter turned to rock, they are the real thing. In eroded outcrops of this region, you can find strata of mussel shells inches thick. They look as fresh as if they were washed up from the rivers or Chesapeake Bay by recent storms, but may be a few million years old. Likewise, we had real mammoth bones, not rocks, although they no longer had the gleaming white freshness of shells. Dr. Johnson distributed them for his volunteers to wash and dry, and I was given a hefty chunk of what I guessed was the head of a humerus. The tusks were coated in plaster to protect them on their journey for display at the Virginia Living Museum (humorists take note), but unfortunately not enough of them were preserved for assembling a skeleton.

Mastodon tooth

See the nipples on the molar

I was curious how mastodons got their name. Was it from the huge muscles needed for mastication? When the first fossils were discovered two centuries ago they mystified geologists who called the new species, ‘Incognitum.’ It was the French geologist George Cuvier who coined the name mastodon, although this was later dropped by taxonomists for the more ponderous, Mammut americanum. I previously blogged about the curious names chosen for new animals to science, sometimes they are more whimsical than biologically meaningful. Cuvier chose mastodon, which means ‘milk tooth,’ because the crowns of the molar teeth looked like nipples. You can see on this picture why he chose a quirky name. The teeth don’t resemble those of any other kind of elephant, extant or extinct, which is why they can tell a mastodon from a mammoth.

The discovery was so unusual that it interested the Smithsonian Institution and the Washington Post. One day soon, carbon dating will reveal the fossil’s age, and perhaps museum conservators will deduce whether score marks on the ribs were made by the claws of a saber-toothed cat or a dire wolf.

We know that mastodons died out at the end of the last Ice Age with other megafauna, but was their extinction caused by climate change or Clovis hunters? I guess it was an irresistible convergence of the two, which are the same threats facing elephants today and so many other species of animals and plants. Central Africa has lost 100,000 (64%) to poachers and habitat loss in the past decade alone. I missed live mastodons in our town by a whisker of geological time, and dearly hope that future generations will have more than elephant bones to marvel at.

Next Post: Why bats  scare us

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