It’s been 40 years since Louise Brown, the world’s first test tube baby was born. Since then millions of babies conceived via in vitro fertilization have entered the world and gone on to live normal, healthy lives.

In fact Brown’s recently born baby boy was conceived the old fashioned way.

But IVF involves growing embryos in a petri dish for days before implantation. Can that really be risk free?

No it turns out, but the risks-while still not completely understood-are small.

Last fall the CDC reported that IVF babies have a slightly higher risk of birth defects including atrial septal defect, cleft palate and digestive system abnormalities. About 1.1% of the mothers of normal babies had used IVF, whereas 2.4% of mothers that had babies with birth defects had used IVF.

And a few hereditary syndromes are more common among IVF babies. Beckwith-Wiedemann syndrome, which is characterized by tissue hyperplasia and multiple childhood cancers, occurs in less than 1 in 13,000 normal births, but it’s 10 times more frequent in IVF babies.

Angelman syndrome, which is characterized by mental retardation and motor defects, is also linked to IVF.

 “There is a growing consensus…that there are risks,” said Richard Schultz, the associate dean for the natural sciences at the University of Pennsylvania told the New York Times. “It is now incumbent on us to figure out what…we can do…to minimize (them).”

Scientists believe the culture medium used during incubation affects gene expression but as of now there is no standard medium and little data linking specific media to outcomes.

In fact, according to Elizabeth Ginsburg, director of IVF at Brigham and Women’s hospital, “programs use multiple media, and (frequently) switch from one media to another.”

Reykjavik-based Decode Genetics, which is a lot better at personal genomics than selecting investment advisors, is back in the news now that its scientists have determined that 57% of all thyroid cancer is attributable to 2 genetic variations.

Julius Gudmundsson and colleagues report in Nature Genetics that the variants are simple base-pair substitutions occurring in genes residing near those controlling thyroid gland development, one on Chromosome 9 and the other on Chromosome 14.

Compared with those having neither variant, “the risk associated with these variants was almost six-fold, which is quite extraordinary,” Erich Sturgis, a head and neck surgeon at Houston’s MD Anderson Cancer told the New York Times.

Each year in the US, about 35,000 cases of thyroid cancer are diagnosed. Treatment generally includes surgical resection of the gland followed by lifelong thyroid replacement. It’s quite effective and only 1,500 people die from thyroid cancer each year.

The Decode breakthroughs are thus not going to trigger interest in population-wide screening programs, but the information would be useful in the assessment of people at high risk, such as those with a positive family history of the disease. 

Gudmundsson’s group reached its conclusions by performing a genome-wide association study involving 192 positive cases and a large control group.

They showed that people having both genetic variants had low levels of thyroid-stimulating hormone, which is produced normally by the pituitary gland.

TSH helps thyroid cells mature, so the authors postulate that chronically low TSH levels might impede their differentiation and thus increase the risk of malignant transformation.

If this theory proves correct, TSH supplementation might reduce the risk of developing thyroid cancer in affected individuals.

Christakis and Fowler are at it again!

Two months ago they caused a stir by publishing research in BMJ which seemed to show that happiness is contagious, a conclusion that some chalked up to an inexcusably naïve failure to recognize the effects of epiphenomena in social networks.

Now these crowd pleasers have put a piece in PNAS which concludes that a person’s popularity is genetically determined. 

Or as Christakis, a medical sociologist at Harvard told Medical News Today, “We were able to show that our particular location in vast social networks has a genetic basis.”

“In fact, the beautiful and complicated pattern of human connection depends on our genes to a significant measure,” he waxed.

Does this guy think he’s Ram Dass or what?

To reach this data-mining epiphany, Christakis and Fowler characterized the social networks of 1,110 identical and non-identical teen-aged twins from the National Longitudinal Study of Adolescent Health.

They measured popularity by the number of times an individual was named as a friend and the likelihood those friends knew each other.

Does this work for everybody?

Whatever, the scientists observed a higher concordance among the networks of identical twins than their non-identical counterparts.

They also concluded that whether a person was central to, or at the periphery of her social network was genetically determined, which inspired them to raise Charles Darwin from the dead, all in the same article.

Maybe it’s good to be on the periphery of a social group, they mused, like when there’s Ebola virus floating around. Then again, those hub-of-the-network types have access to more information like which Starbucks still has Christmas Blend in stock.
 
Please people.

Twenty-five years after tamoxifen was introduced for the treatment of breast cancer, David Flockhart and his team at Indiana University determined that the body coverts the drug into a different substance known as endoxifen, and the latter is actually the cancer-figher.

Flockhart’s group discovered that the body uses an enzyme known as 2D6 to engineer the conversion, and that there is considerable variation in 2D6 gene expression.

In fact 7% of the general population possess a wholly inactive enzyme and another 20-40% have a weakly active variation.

Flockhart told the New York Times that was “scary” because it meant tens of thousands of women had received a drug that did not protect them against recurrent breast cancer as they had thought.

It’s scary for Big Pharma too. Tamoxifen had fallen out of favor ever since clinical trials showed that aromatase inhibitor drugs performed better.

But the studies were done before we knew about 2D6 and as an aside, the aromatase inhibitors net up to 36 times more revenue per patient than the now-generic tamoxifen.

Suppose the trials had assessed only women with a fully active 2D6 enzyme. Could tamoxifen have performed as well or better than the aromatase inhibitors? 

Matthew Goetz and colleagues from the Mayo clinic went back and checked tumor samples from a previous trial for 2D6 gene status and reported that 32% of women with the inactive variant had relapsed or died in 2 years. Only 2% percent of women with a fully active enzyme relapsed or died.

But other studies reached contradictory conclusions and it turns out there are dozens of 2D6 variants which can confound results in clinical labs.

Two years ago, an FDA advisory panel recommended that the 2D6 test be discussed on the label for tamoxifen. Just recently, the agency got around to accepting the recommendation.

Influenza is a viral infection of the nose and throat that typically causes fever, headache, muscle aches and weakness. Sometimes pneumonia complicates the flu. The cause can be bacterial or the virus itself. In a typical season, flu mortality is well below 1%.

In 1918, an extraordinary number of flu victims developed pneumonia. Mortality ran 400% higher than usual.

In fact, “The 1918 influenza pandemic was the most devastating outbreak of infectious disease in human history, accounting for about 50 million deaths worldwide,” according Yoshihiro Kawaoka and colleagues from the University of Wisconsin and the Universities of Kobe and Tokyo.

Now these scientists think they’ve discovered what triggered the pandemic.

The team isolated genes one-by-one from the 1918 strain, substituted them into the modern flu virus and then infected ferrets, which develop flu a lot like humans do.

Time after time the ferrets developed normal flu until the scientists used a 3-gene combination called PA, PB1, and PB2 (along with a 1918 version of the nucleoprotein or NP gene).

This combination enabled the flu virus to invade the lungs, causing pneumonia and death. The team has published its findings in the Proceedings of the National Academy of Sciences.

Most experts believe there will be another flu pandemic someday. No one knows when or which strain will cause it, but the H5N1 avian influenza virus that currently circulates among birds and domestic poultry in Asia, Africa and Europe remains a likely suspect.

The current strain of Avian flu rarely infects humans but when it does, it kills. More than 60% of the 391 people infected so far have died. 

A few mutations that increase its attack rate in humans would transform H5N1 into a monster that could kill millions in months.

Genetic mutations can cause or prevent disease and scientists at the University of Maryland recently came across an interesting case of the latter.

The scientists asked folks from an Amish community near Lancaster, Pennsylvania to swill down a creamy milkshake and then tracked what happened to fat levels in their blood.

In nearly all participants, triglyceride levels rose for several hours then slowly declined to baseline as would be expected. But in about 5%, the levels started out low and jumped no more than a smidge.

Tori Pollin and colleagues traced the favorable phenotype back to a gene mutation that had already received the inauspicious name apoC-III. The gene codes for APOC3, a protein that normally slows down triglyceride metabolism.

According to Pollin’s report in Science, the cohort with the gene mutation also had higher levels of HDL (good)-cholesterol and lower levels of LDL (bad) –cholesterol. And they had fewer coronary artery calcifications on CT scanning. In short, the mutation was cardio-protective.

The isolated nature of the Amish population enabled the scientists to trace the apoC-III mutation to a man born more than 200 years ago.

In commenting on the study, Daniel Rader told the New York Times, “this is among the strongest human evidence we have that APOC3 is quote, unquote, bad.”

We love it when University of Pennsylvania cardiac researchers talk like that. He added, “if you had a drug to turn off the gene to prevent as much APOC3 being made, this study suggests that that would be beneficial to do.”

We’re on it.

Scientists from Columbia University are reporting that osteoporosis, a chronic bone-wasting condition that affects 10 million elderly Americans, may be mediated by serotonin, a compound previously known for its role in brain functioning.

The astonishing conclusion appears in the journal Cell.

Scientists had known for years that a rare, inherited brittle bone disease was caused by a mutation of a gene known as LRP5. More recently, a second mutation of LRP5 was reported to cause just the opposite—bones so dense that tooth extractions became nearly impossible.

So something was up with LRP5, and the tempting assumption was that the gene directly impacted bone formation.

Not so, according to Gerard Karsenty and colleagues. They proved that LRP5 blocks production of serotonin in the gut.

Then they proved that while gut serotonin has no impact on brain functioning, it does impair bone formation after travelling there through the blood stream.

“We made mice with the inactivated gene,” Dr. Karsenty told the New York Times. These mice had 4 times the normal levels of circulating gut serotonin, and in their bodies “the bone-forming cells are on strike,” he added.

The mice developed marked osteoporosis.

Karsenty’s team then harvested bone cells from the brittle boned mice and proved in the laboratory that the cells were perfectly capable of normal development and functioning, so long as they were not bathed in serotonin.

Karsenty’s team hopes its work might prompt development of a drug that suppresses gut serotonin synthesis and thus stimulate bone growth in osteoporosis patients.

Atlas Sports Genetics claims to have a test that predicts which kinds of sports match your child’s innate abilities. You can buy it right now for $149.

The test determines ACTN3 gene expression. ACTN3 is one of 20,000 human genes.

The so-called R variant of ACTN3 instructs the body to produce alpha-actinin-3. This protein component of fast-twitch muscles provides forceful, quick contractions required to excel in power and speed sports like football and sprinting. The X variant suppresses the production of alpha-actinin-3.

Children inherit one copy of the ACTN3 gene from each parent, so they can be “RR,” “RX,” or “XX.”

Atlas Sports claims that power and speed sports are best suited to RR offspring, whereas endurance sports like marathons and distance swimming are best suited for XX offspring. Apparently RX offspring can do anything.

If this sounds dicey to you, you’re not alone.

Dr. Theodore Friedmann, the director of the gene therapy program at UCSD for example, told the New York Times the test amounted to “an opportunity to sell new versions of snake oil.” He elaborated, “I don’t deny that these genes have a role in athletic success, but it’s not that black and white.”

There is no doubt the science being commercialized here is compelling, if not ready for prime time.

In 2003, Australian scientists studied 429 world class athletes including 50 Olympians. They found that 50% of the 107 sprint athletes were RR. That’s twice the frequency of RR in the general population. And not one female sprinter was XX. What is more, every male Olympian involved in power sports had inherited an R variant from at least one parent.

So where does the XX Spanish long jumper fit in?

It’s hard to know but Carl Foster, a co-author of the study and director of the human performance laboratory at the University of Wisconsin-La Crosse has devised another way to see whether your 6th grader will excel at power and sprint sports:

“Just line them up with their classmates for a race and see which ones are the fastest,” he said.

Suppose you had two groups of 70 year olds, one whose parents had lived to be 100 years old and the other whose parents died at a younger age. Which group would you expect to live longer?

This isn’t a trick question and the answer is no surprise but the question is why. Why do the offspring of centenarian parents live longer?

Dellara F. Terry and colleagues from Boston University make a persuasive case that the benefit is conferred through reductions in cardiovascular risk.

They report in the Journal of the American Geriatrics Society that septuagenarian children of centenarian parents were 81% less likely to die during a 3.5-year follow-up than age-matched controls, and same group was 78% less likely to have a heart attack, 83% less likely to have a stroke, and 86% less likely to develop diabetes.

And yet the children of centenarians were just as likely as the second group to develop cancer, depression, glaucoma, bone fractures, thyroid disease, hypertension, macular degeneration and dementia.

“The most dramatic difference we’ve seen among centenarian offspring, one that’s been consistent throughout the period we’ve been following them, is the decreased prevalence of heart disease and its risk factors,” Dr. Terry told the New York Times.

OK so is it nature or nurture?

“Just because something is familial doesn’t mean it’s all genetic,” Terry explained to the Times. “It could be there are health-related behaviors they have learned from their parents. It’s also possible it’s genes, or the absence of bad genes, they inherited from their parents.”

Which is another way of saying we don’t know right now but if we can figure it out we’ll let you know.

Scientists in St. Louis have decoded the entire genome of a woman who died of leukemia and in the process, they identified several mutations that probably caused the disease, accelerated its progression or rendered it resistant to chemotherapeutic agents.

The researchers sequenced DNA from the woman’s leukemia cells and her non-cancerous skin cells, and then compared them side-by-side. The comparison revealed 10 mutations that were present only in the cancer cells.

“This is the first of many of these whole cancer genomes to be sequenced,” Richard K. Wilson told the New York Times. Wilson is Director of the Genome Sequencing Center at Washington University and a senior author on the paper published in Nature. “They’ll give us a whole bunch of clues about what’s going on in the DNA when cancer starts to bloom,” he added.

The scientists’ strategy to sequence the entire genome of a human cancer cell represents a break from previous approaches that had focused on a few hundred “likely suspect” genes. The strategy has been enabled by recent advances that make it far cheaper and quicker to sequence large amounts of DNA. The advantage of the new strategy is that it eliminates the possibility that the genes actually associated with cancer are not among the “likely suspects.”

Indeed Wilson’s group found that 8 of the 10 mutations in their study were not considered likely suspect genes.

The woman’s sequenced DNA will be made available for other research projects. Before her donation, the only fully sequenced human genomes had come from Craig Venter, the founder of the Institute for Genomic Research, and Nobel Prize winning molecular biologist James Watson.