In 20 years, will anyone roll the dice on a naturally conceived child?

A human parent’s biggest fear is having a child with a genetic disorder (though the most commonly expressed fear on Facebook is of Donald Trump winning a second term!).

Technology is bringing us pretty close to eliminating this fear and giving us a bewildering array of options.

She Has Her Mother’s Laugh: The Powers, Perversions, and Potential of Heredity by Carl Zimmer reminds the reader of the diversity in sperm and egg cells due to meiosis:

In men, meiosis takes place within a labyrinth of tubes coiled within the testicles. The tube walls are lined with sperm precursor cells, each carrying two copies of each chromosome—one from the man’s mother, the other from his father. When these cells divide, they copy all their DNA, so that now they have four copies of each chromosome. Rather than drawing apart from each other, however, the chromosomes stay together. A maternal and paternal copy of each chromosome line up alongside each other. Proteins descend on them and slice the chromosomes, making cuts at precisely the same spots. As the cell repairs these self-inflicted wounds, a remarkable exchange can take place. A piece of DNA from one chromosome may get moved to the same position in the other, its own place taken by its counterpart. This molecular surgery cannot be rushed. All told, a cell may need three weeks to finish meiosis. Once it’s done, its chromosomes pull away from each other. The cell then divides twice, to make four new sperm cells. Each of the four cells inherits a single copy of all twenty-three chromosomes. But each sperm cell contains a different assembly of DNA. One source of this difference comes from how the pairs of chromosomes get separated. A sperm might contain the version of chromosome 1 that a man inherited from his father, chromosome 2 from his mother, and so on. Another sperm might have a different combination. At the same time, some chromosomes in a sperm are hybrids. Thanks to meiosis, a sperm cell’s copy of chromosome 1 might be a combination of DNA from both his mother and father.

A particular child of two parents, therefore, is just one choice from a near-infinite array of genetic possibilities assembled from the four grandparents. That’s what comes out when a baby is conceived naturally. What if parents were given the opportunity to choose from hundreds of possible outcomes?

In 2012, the Japanese biologist Katsuhiko Hayashi managed to coax induced pluripotent stem cells to develop into the progenitors of eggs. If he implanted them in the ovaries of female mice, they could finish maturing. Over the next few years, Hayashi perfected the procedure, transforming mouse skin cells into eggs entirely in a dish. When he fertilized the eggs, some of them developed into healthy mouse pups. Other researchers have figured out how to make sperm from skin cells taken from adult mice.

Nevertheless, the success that Yamanaka and other researchers have had with animals is grounds for optimism—or worry, depending on what you think about how we might make use of this technology. It’s entirely possible that, before long, scientists will learn how to swab the inside of people’s cheeks and transform their cells into sperm or eggs, ready for in vitro fertilization. If scientists can perfect this process—called in vitro gametogenesis—it will probably be snapped up by fertility doctors. Harvesting mature eggs from women remains a difficult, painful undertaking. It would be far easier for women to reprogram one of their skin cells into an egg. It would also mean that both women and men who can’t make any sex cells at all wouldn’t need a donor to have a child.

Today, parents who use in vitro fertilization can choose from about half a dozen embryos. In vitro gametogenesis might offer them a hundred or more. Shuffling combinations of genes together so many times could produce a much bigger range of possibilities.

But the implications of in vitro gametogenesis go far beyond these familiar scenarios—to ones that Hermann Muller never would have thought of. Induced pluripotent stem cells have depths of possibilities that scientists have just started to investigate. Men, for instance, might be able to produce eggs. A homosexual couple might someday be able to combine gametes, producing children who inherited DNA from both of them. One man might produce both eggs and sperm, combining them to produce a family—not a family of clones, but one in which each child draws a different combination of alleles. It would give the term single-parent family a whole new meaning.

Here’s a yet more science fiction-y possibility… The highest fertility among Americans is in the lowest income mothers, i.e., those who are on welfare. The government will be paying for 100 percent of the costs of any children produced by these mothers: housing, health care, food, education, etc. Once grown up, these children are likely to be low earners and therefore on welfare themselves (see The Son Also Rises). What if the government begins to run out of borrowing capacity and decides that it needs to fund future taxpayers, not future welfare recipients? The tendency to work and pay taxes is as heritable as anything else. So the government offers financial inducements to mothers who agree to abort children conceived with low-income men and instead incubate embryos provided by the government. Said embryos to be carefully screened such that the moms are almost guaranteed to have a physically and mentally healthy child and the government is almost guaranteed to get an adult that enjoys working and paying taxes.

Readers: What do you think? In 2040 or 2050 will there be anyone willing to roll the genetic dice by having sex and seeing what kind of baby comes out?

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Adventures in the U.S. health care system

In case of crazy weather on our Greenland-to-Alaska cruise (through what used to be called the “Northwest Passage” and is now the “Trump Global Warming (TM) Passage”), I decided to fortify myself with some scopolamine patches. A physician friend wrote me a prescription for 8 patches, each of which can last for three days, but sometimes they come off in the shower, etc.

Wikipedia dates the medication to 1881. The brand name patches were about $340. Thanks to the patent (presumably on the delivery mechanism) having expired, the generics are available for only… $275.

We pay the big $$ for Blue Cross/Blue Shield coverage, so I had the pharmacy run my card. Coverage was denied due to a mismatch in name/gender/relationship that could not be further explained. It was a Saturday, so calling Member Services was unsuccessful.

On Monday, I invested some time in calling Blue Cross, which invested some money in paying a woman to deal with me. She explained that the pharmacy had “rung me in” with two Ls in my first name and with a gender of “female” (of course I asked how many additional gender options there were and she was familiar with only “male” and “female”; where is the LGBTQIA enthusiasm?) It should be a $10 co-pay for a 30-day supply.

After visiting four different pharmacies, I found one that had two packages of the patches in stock. They said that the insurance company would pay them $154, which means that the total price would be $165 (a 40% discount off the $275 that would have been charged to the struggling uninsured person!).

To me this is a great example of how the 18 percent of GDP that is purportedly for “health care” is illusory in terms of benefits to Americans. Absent FDA regulation, the generic patches would have cost $20-40 (8 cost about $60 in the Canadian regulatory environment). It took a week and the efforts of multiple people to get this organized. As soon as the doc wrote the prescription, why didn’t the patches show up a few days later via a standard ecommerce retail process?

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Knee replacement in Mexico

It has long amazed me that the typical non-emergency medical intervention for an American does not start with a plane flight to a country in which medicine can be done efficiently.

“A Mexican Hospital, an American Surgeon, and a $5,000 Check (Yes, a Check)” (nytimes) is a story about a knee replacement that happens in the way that Econ 101 would suggest:

The hospital costs of the American medical system are so high that it made financial sense for both a highly trained orthopedist from Milwaukee and a patient from Mississippi to leave the country and meet at an upscale private Mexican hospital for the surgery.

Ms. Ferguson gets her health coverage through her husband’s employer, Ashley Furniture Industries. The cost to Ashley was less than half of what a knee replacement in the United States would have been. That’s why its employees and dependents who use this option have no out-of-pocket co-pays or deductibles for the procedure; in fact, they receive a $5,000 payment from the company, and all their travel costs are covered.

Dr. Parisi, who spent less than 24 hours in Cancún, was paid $2,700, or three times what he would have received from Medicare, the largest single payer of hospital costs in the United States. Private insurers often base their reimbursement rates on what Medicare pays.

Interesting, but it raises more questions than it answers, e.g., why aren’t all knee replacements done in a country where knee replacements can be done efficiently?

[Separately, note that the NYT informs us that Mexico is too dangerous for a caravan of Hondurans to dwell, which is why they need to continue across the southern border of the U.S. and claim asylum. But, on the other hand, the same newspaper tells us that Mexico is sufficiently safe and organized to serve as a meeting place for American surgeons and privately insured patients.]

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Another reason to abandon the suburbs in favor of the city?

If you’ve been on the fence regarding whether to give up the car-dependent lifestyle and move back to the city… “Lyme Disease Cases Are Exploding. And It’s Only Going to Get Worse.”:

Since 1992, the Cary Institute [Millbrook, NY] has been compiling a record of tick ecology that they believe to be the longest continuous study of this kind in the U.S. and possibly the world. … The process for counting ticks not affixed to hosts is called a drag — the researchers pull a one-square-meter sheet of fabric along the ground for 30 meters then tally the number of ticks affixed to it. Oggenfuss holds the Cary Institute record for ticks collected in a single drag: 1,700. As horrifying as that haul was — and it would, by extrapolation, put the tick population on the Cary Institute’s 2,000-acre campus at 2 billion — Oggenfuss is quick to note it was exceptional, and tick density is irregular. Her more conservative calculations of average tick populations, based on drags done during the same time of year (August, the larval peak), are only reassuring by comparison: upward of 20,000 ticks per acre, more than 100,000 on the Henry Control grid, and more than 40 million on the Cary Institute grounds.

Here’s the bottom line for American humans: “It’s estimated that 300,000 people contract Lyme every year in the U.S., with victims found not just in traditionally tick-heavy areas like upstate New York and Maine, but also in all 50 states and Washington, D.C.”

We dug our own Lyme-infested graves by burning fossil fuels:

Human-driven climate change is making tick season longer and tick country larger. As winters get warmer and shorter, ticks become dormant later in the year (if at all should it fail to fall below freezing) and active earlier.

But the disease started in Connecticut, which is much cooler than the southern U.S. Climate change is so powerful that it is spreading ticks and Lyme disease both north and south:

When Aucott joined Johns Hopkins in 1996, Lyme disease had been a mounting concern for a number of years, but conventional wisdom held that the illness would not spread south of the Potomac River. However, he soon began seeing case referrals from first northern then southern Virginia. Lyme is now endemic in North Carolina and has moved westward to Tennessee, Kentucky, and Ohio.

How about escaping both state income tax and Lyme disease by moving to Las Vegas (check Nevada family law first; the state takes a completely different approach to custody and child support compared to the typical winner-take-all U.S. state)?

That very scenario is playing out on the U.S.-Mexico border in Mexicali, where a particular clade of brown dog tick has caused a massive outbreak of Rocky Mountain spotted fever, which can be fatal in up to 30% of cases and causes more deaths than any other tick-borne disease in North America. … While ticks need moisture to survive, the common brown dog tick requires far less than most. This particular clade takes that to the extreme, suggesting its spread could be hastened by climate change. “This tick needs it hot and it needs it dry. This tick is rooting for global warming and drought,” Foley says. As places like California and Arizona become hotter and drier, the tick’s reach will expand, she says. To compound matters, research has shown that the hotter the temperature, the more aggressive this tick becomes. “You can actually do experiments and bring the temperature up and increase the bite rate of that tick,” Foley says.

How about simply live in the city? It would be tough to get bitten by a tick in Midtown Manhattan.

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Mothers acquiring cells from babies

She Has Her Mother’s Laugh: The Powers, Perversions, and Potential of Heredity by Carl Zimmer:

In 1996, Lee Nelson proposed that microchimerism might make some mothers sick. With half their genetic material coming from their father, fetal cells might be a confusing mix of the foreign and the familiar. Nelson speculated that being exposed to fetal cells for years on end could lead a woman’s immune system to attack her own tissues. That confusion might be the reason that women are more vulnerable to autoimmune diseases such as arthritis and scleroderma. To test this possibility, Nelson and Bianchi collaborated on an experiment. They picked out thrity-three mothers of sons, sixteen of whom were healthy and seventeen of whom suffered from scleroderma. Nelson and Bianchi found that the women with scleroderma had far more fetal cells from their sons than did the healthy women.

But maybe this can be good?

It’s also possible that being a chimera can be good for your health. Bianchi’s first clue that chimerism might have an upside came in the late 1990s, when she was searching for fetal cells in various organs. She discovered a mother’s thyroid gland packed with fetal cells carrying Y chromosomes. Her gland was badly damaged by goiter, and yet it still managed to secrete normal levels of thyroid hormones. The evidence pointed to a startling conclusion: A fetal cell from her son had wended its way through her body to her diseased thyroid gland. It had sensed the damage there and responded by multiplying into new thyroid cells, regenerating the gland.

What about getting genes from a baby that is not genetically one’s own?

As chimerism rises out of the freak category, it also raises unexpected ethical questions. Somewhere around a thousand children a year are born to surrogate mothers in the United States alone. As Ruth Fischbach and John Loike, two bioethicists at Columbia University, have observed, the rules for surrogacy are based on an old-fashioned notion of pregnancy. They treat people as bundles of genes. As a society, we are comfortable with a woman nourishing another couple’s embryo and then parting ways with it, because she does not share the hereditary bond that a biological mother would. If the pregnancy goes smoothly, the surrogate mother is supposed to leave the experience no different than before the procedure. But Fischbach and Loike observed that a surrogate mother and a baby may end up connected in the most profound way possible. Cells from the fetus may embed themselves throughout her body, perhaps for life. And she may bequeath some of her cells to the child. This is not merely a thought experiment. In 2009, researchers at Harvard did a study on eleven surrogate mothers who carried boys but who never had sons of their own. After the women gave birth, the scientists found Y chromosomes in the bloodstreams of five of them.

More: Read She Has Her Mother’s Laugh: The Powers, Perversions, and Potential of Heredity

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Human Chimeras

Some more interesting stuff from She Has Her Mother’s Laugh: The Powers, Perversions, and Potential of Heredity by Carl Zimmer… It turns out that Biology 101 contains a lot of simplifications (lies!).

Wikipedia: “A genetic chimerism or chimera … is a single organism composed of cells with distinct genotypes. In animals, this means an individual derived from two or more zygotes, …

How can this happen to a human and how does that interact with our “science is settled” attitude regarding DNA tests? Zimmer gives some examples:

In 2001, a thirty-year-old woman in Germany discovered she was a chimera while she was trying to get pregnant. For the previous five years, she and her husband had been trying to have a baby. They were fairly certain the problem didn’t lie with her biology, because she had gotten pregnant when she was seventeen and had had regular menstrual cycles ever since. A fertility test revealed that her husband had a low level of viable sperm, and so they made plans for IVF. As a routine check, the woman’s doctors took blood samples from her and her husband. They looked at the chromosomes in the couple’s cells, to make sure neither would-be parent had an abnormality that would torpedo the IVF procedure. The woman’s chromosomes looked normal—if she were a man. In every white blood cell they inspected, they found a Y chromosome. Given that she had given birth, this was a weird result. And a careful exam revealed that all her reproductive organs were normal. To get a broader picture of the woman’s cellular makeup, her doctors took samples of her muscle, ovaries, and skin. Unlike her immune cells, none of the cells from these other tissues had a Y chromosome in them. The researchers then carried out a DNA fingerprinting test on the different tissues, looking at the women’s microsatellites—the repeating sequences that can distinguish people from one another. They found that her immune cells belonged to a different person than her other tissues. It turned out that the woman had had a twin brother who died only four days after birth. Although he was unable to survive on his own, his cells took over his sister’s blood and lived on within her.

In 2003, a woman in Washington State named Lydia Fairchild had to get a DNA test. Fairchild, who was then twenty-seven, was pregnant with her fourth child, unemployed, and single. To get welfare benefits, state law required that she prove that her children were genetically related both to herself and to their father, Jamie. One day, Fairchild got a call from the Department of Social Services to come in immediately. A DNA test had confirmed that Jamie was the father of the three children. But Fairchild was not their mother.

When Fairchild was rushed to a hospital to deliver her fourth child, a court officer was there to witness the birth. The officer also oversaw a blood draw for a DNA test. The results came back two weeks later. Once again, Fairchild’s DNA didn’t match her child’s. Even though the court officer had witnessed the child’s birth, the court still refused to consider any evidence beyond DNA.

In Boston, a woman named Karen Keegan had developed kidney disease and needed a transplant. To see if her husband or three sons were a match, her doctors drew blood from the whole family in order to examine a set of immune-system genes called HLA. A nurse called Keegan with the results. Not only were her sons not suitable as organ donors, but the HLA genes from two of them didn’t match hers at all. It was impossible for them to be her children. The hospital went so far as to raise the possibility she had stolen her two sons as babies. Since Keegan’s children were now grown men, she didn’t have to face the terrifying prospect of losing her children as Fairchild did. But Keegan’s doctors were determined to figure out what was going on. Tests on her husband confirmed he was the father of the boys. Her doctors took blood samples from Keegan’s mother and brothers, and collected samples from Keegan’s other tissues, including hair and skin. Years earlier, Keegan had had a nodule removed from her thyroid gland, and it turned out that the hospital had saved it ever since. Her doctors also got hold of a bladder biopsy. Examining all these tissues, Keegan’s doctors found that she was made up of two distinct groups of cells. They could trace her body’s origins along a pair of pedigrees—not to a single ancestral cell but to a pair. They realized Keegan was a tetragametic chimera, the product of two female fraternal twins. The cells of one twin gave rise to all her blood. They also helped give rise to other tissues, as well as to some of her eggs. One of her sons developed from an egg that belonged to the same cell lineage as her blood. Her other two children developed from eggs belonging to the lineage that arose from the other twin. When Lydia Fairchild’s lawyer heard about the Keegan case, he immediately demanded that his client get the same test. At first, it looked as if things were going to go against Fairchild yet again. The DNA in her skin, hair, and saliva failed to match her children’s. But then researchers looked at a sample taken from a cervical smear she had gotten years before. It matched, proving she was a chimera after all.

More: Read She Has Her Mother’s Laugh: The Powers, Perversions, and Potential of Heredity

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Why is Roundup still for sale?

The California legal system has determined that Roundup causes cancer. See, for example, “$2 Billion Verdict Against Monsanto Is Third to Find Roundup Caused Cancer” (nytimes):

The jury, in state court in Alameda County, reached its verdict two months after a federal jury in San Francisco awarded $80 million to a man who claimed that Roundup had caused his non-Hodgkin’s lymphoma. In August, a state court in San Francisco found that Roundup had caused the cancer of a school groundskeeper, awarding him $289 million. A judge reduced that figure to $78 million.

Yet the German owners of Monsanto (safe to assume they wish they’d spent their hard-earned dollars in some other country?) still make the stuff and Amazon still sells it (example). Glyphosate from a variety of manufacturers is available at Home Depot.

How are the retailers immune from liability? If we have faith in our legal system to come up with correct answers to scientific questions, such as “Does glyphosate cause cancer?” then why are millions of Americans apparently still buying and using it?

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Minimal number of approved drugs; fewer approved each year

Some numbers that I heard at Harvard Medical School:

  • About 1500 compounds that are currently approved as patented or generic drugs.
  • About 500 in clinical trials.
  • About 10 approved every year and declining.

Declining? With half of the new glass towers in Boston and Cambridge packed with biologists and chemists? “It’s getting tougher to approve new drugs because they have to be safe, be effective, and be somehow better for an average population of patients than current drugs,” said my source. “Don’t get me started on the FDA. These criteria are probably too strict. A compound that has bad side effects for one person might affect another person very differently. So it would be good to have more options, especially for those with unusual genetics.”

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Men are not bigger than women; richer Americans are not thinner

Playing around with R (bleah) and NHANES data (a comprehensive survey of American health and socioeconomic situation; see also this exploration tool at Harvard Medical School), I got a few surprises…

American women actually have a slightly higher average BMI than men. Muscles are supposedly heavier than fat and men are supposedly more muscular, right? This theory is not supported by data. Given two random adults of the same height, the woman will actually be heavier.

One of our fellow residents (might not be a citizen) rang up a BMI of 120(!). Plenty of company in the 50-60 range…

There is almost no correlation between income and BMI. However, the correlation is in an unexpected direction. An increase in income of 6X seems to result in an increase in BMI of about 1. The rich are not thinner. (NHANES may not be a good sample for the truly rich).

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