A Third CRISPR Baby may Have Been Born

The Second International Summit on Human Genome Editing, held in Hong Kong last November, was meant to debate the pros and cons of genetically engineering humans. Instead, the proceedings were turned upside down by the revelation that He Jiankui, a Chinese biophysicist, had already done it.

He’d gone ahead and edited the DNA of twin girls with the powerful gene modification tool called CRISPR.

Then the Chinese scientist sprang a further surprise on the shocked gene-editing experts. A second Chinese woman, he said, was pregnant with yet another CRISPR baby. An early pregnancy test had confirmed it.

That third CRISPR baby is now due to be born at any moment—if he or she hasn’t come crying into the world already.

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Is an Obscure Member of the Herpes Virus Family Causing Infertility?

A new study has found that the little-known member of the human herpesvirus family called HHV-6A infects the lining of the uterus in 43% of women with unexplained infertility but cannot be found in uterine lining of fertile women. The study was conducted by investigators at the University of Ferrara, Italy.

The study also found that the response of the immune system to the virus may contribute to making the uterus less hospitable to a fertilized egg. The virus seems to activate immune cells called natural killer cells in the uterus, and lead those cells to produce chemicals called cytokines. Cytokines are tools the immune system uses to orchestrate an attack on a foreign invader, like a virus. However, the activated immune system cells and abnormal levels of certain cytokines may make it harder for a fertilized egg to lodge in the uterus, and grow into a baby.

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That Wasn't Autism.

The headlines read “New study suggests autism can be outgrown”, or “outgrowing autism: a doctor’s surprise and wonder.” The stories are based on studies reporting that 7-9% of children with a documented early autistic syndrome disorder (ASD) have no symptoms of the disorder on follow-up later in childhood or adolescence. That is good news. The question is how to account for it.

Is it possible to simply “outgrow” autism? Was the initial diagnosis wrong? Did some interventions work? Or might there be other explanations for this welcome news?

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Dementia, Other Geriatric Diseases to Present Health Care Crisis for China

In little more than half a century the average Chinese life span has almost doubled. Life expectancy in China is now 76 years, nearly on par with the U.S.’s 79 years. Yet this tremendous boon comes with a dark side: an aging population.

China’s one-child policy throttled population growth so successfully that the proportion of elderly Chinese is now soaring. A 2011 report from the Chinese Academy of Social Sciences predicts that the percentage of the population that is 65 or older will triple between 2000 and 2050. With an aging population comes a greater burden of diseases, chief among them neurodegeneration. Already China has more than nine million people with some form of dementia and more cases of Alzheimer’s disease than any other country, according to a 2013 paper in The Lancet. Its authors dubbed dementia “the single largest challenge to health and social care systems” in China.

The consequences of this trend are profound, and the country has only recently begun to prepare for them. In 2009 the government committed $124 billion to overhauling health care, with a goal of providing basic health insurance for 90 percent of its citizens. The plan also highlighted mental health services as a top priority for the first time. Last year China implemented its first mental health law, which expands psychiatric services throughout the country. Although the policy does not explicitly mention dementia, it underscores the urgent need for community mental health clinics, which could end up aiding families struggling to cope with a relative’s dementia.

To find out more about the implications of China’s demographic shift and the steps the country can take to buffer itself, Scientific American spoke with Michael Phillips, a psychiatrist who has lived in China for 30 years, during the annual meeting of the American Psychiatric Association last week. Phillips has dual appointments at Shanghai Jiao Tong University School of Medicine and the Collaborative Center for Global Mental Health at Emory University.

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Autism Strongly Correlated to Genes Related to Linguistic Impairment, OCD, etc

Lorenzo Miodus-Santini an 11-year-old sixth-grader from Princeton, who was classified as autistic at only 13 months old, was never a big talker. As an infant he didn't babble or coo. When he was a toddler beginning to speak, he would learn one word but forget another.

His older brother, Christian, a 15-year-old high school sophomore, shared some similar characteristics – difficulty with reading, processing words and speaking clearly. Doctors said he had language impairments but was not autistic.

New research published online today in the American Journal of Psychiatry, by scientists at Rutgers University and The Research Institute at Nationwide Children's Hospital in Ohio, reveals that there is a genetic link connecting family members with autism like Lorenzo Miodus-Santini to those like his brother, Christian, who have specific language impairment characterized by speech and language difficulties that can't be explained by cognitive or physical problems.

The research project leader Linda Brzustowicz, Rutgers professor and chair of the Department of Genetics, in the School of Arts and Sciences, says that genes in a narrow region of two chromosomes (15q23-26 and 16p12) responsible for oral and written language impairments can result in similar behavioral characteristics with one family member developing autism and the other having only language difficulties.

Specific language impairment is one of the most common learning disabilities, affecting an estimated 7 percent of children. It is not considered to be an autism spectrum disorder. Autism effects one in 88 children nationally – with nearly five times as many boys than girls diagnosed – about half of whom have some degree of language impairment.

"In this group of families we are trying to find genetic factors that might connect them," says Brzustowicz, who collaborated on the study with Christopher W. Bartell, principal investigator in the Battelle Center for Mathematical Medicine at Nationwide Children's Hospital. "This research is important because it is hard to understand autism until we find the genes that might be involved."

While scientists don't believe that there is one single gene that causes autism but rather a number of genes that increase the risk, Brzustowicz and her team of researchers are working to identify genetic patterns in these families in order to help gain a better understanding of the mechanisms that lead to autism, a developmental brain disorder that appears in the first three years of life.

In the Rutgers autism study, 79 families – mostly from New Jersey and Pennsylvania – with one child with autism and at least one with specific language impairment underwent extensive in-home testing. Besides taking blood samples for genetic testing, family members including parents, children, and grandparents and in some cases even uncles, aunts and cousins underwent a battery of tests to assess grammar, vocabulary and language processing.

"Our results indicate that there are shared patterns of DNA and visible behavioral characteristics across our group of study families," says Judy Flax, an associate research professor working on the study with Brzustowicz.

In addition to the language findings, researchers also found strong evidence of a genetic link in the areas of obsessive-compulsive, repetitive behaviors and social interaction skills, other symptoms associated with autism.

Brzustowicz says the next step will be to sequence the whole genome of those who participated in the study in order to compare the families to see if scientists can pinpoint any specific genes or mutations that are common to all.

link.

I think they ought to include parental ages of the children.  It would be MORE than illuminating.

This Would Explain Much: A Mutation That Allows Less Sleep

For most of us, setting the clock forward in the spring is a sad occasion, a sign that we're losing an hour of sleep.

Daylight saving time begins Sunday at 2 a.m. in most of the U.S. -- except for Hawaii and Arizona.

But for some genetically blessed people, a loss of one hour of sleep is not a problem. In fact, sleeping fewer than the recommended seven or eight hours is the norm. They naturally feel refreshed and ready to go -- at 4 a.m.

These "short sleepers" have a mutation on a gene known as hDEC2, that regulates their sleep-wake cycle. This mutation allows them to function on less sleep, researchers say.

Huh. My dad worked on almost zilch sleep or so it seemed to me when I was a kid -> teen. He'd be in bed late, if I woke up at 2 am he would often be still up, and get up relatively early.

Once I hit my 30s, I started doing this, too; I didn't used to though. In fact, last night I was up until 1:30 AM and got up at 5:30 AM. I'm a bit bleary at first, but I'm more than fully functional by 6 am: I had my family's lunches, breakfasts, and whatnot all done by then as well as having eaten. I've been doing this now for over 3 years as I have pursued the GLXP. I'm tired and sometimes irritable, but I am far more than merely functional, even without caffeine.

I'm also what I've termed an old campaigner to my wife as far as sleep goes. If I lay down and I want to, I go to sleep. This drives my wife nuts. I can get up and take care of something int he middle sleeping and I am back asleep in seconds after laying down.

There are a few times I can't sleep, but they are few and far between. Likewise, I don't start passing out until I've been up for 20 hours now. I can go to sleep earlier, but don't need to. Alnighters are tough though, but then, I am 37 now rather than 19. ;)

I do wonder if I'd test positive for the gene though.

I also wonder about the family's male longevity...despite its very poor lifestyle choices.

Autism Risk Linked to Mother's Age

Advanced maternal age is linked to a significantly elevated risk of having a child with autism, regardless of the father's age, according to an exhaustive study of all births in California during the 1990s by UC Davis Health System researchers. Advanced paternal age is associated with elevated autism risk only when the father is older and the mother is under 30, the study found.

Published online today in the February issue of the journal Autism Research, the study, "Independent and Dependent Contributions of Advanced Maternal and Paternal Ages to Autism Risk," is one of the largest population-based studies to quantify how each parent's age — separately and together — affects the risk of having a child with autism.

The study found that the incremental risk of having a child with autism increased by 18 percent — nearly one fifth — for every five-year increase in the mother's age. A 40-year-old woman's risk of having a child later diagnosed with autism was 50 percent greater than that of a woman between 25 and 29 years old.

Advanced parental age is a known risk factor for having a child with autism. However, previous research has shown contradictory results regarding whether it is the mother, the father or both who contribute most to the increased risk of autism. For example, one study reported that fathers over 40 were six times more likely than fathers under 30 to have a child with autism.

"This study challenges a current theory in autism epidemiology that identifies the father's age as a key factor in increasing the risk of having a child with autism," said Janie Shelton, the study's lead author and a doctoral student in the UC Davis Department of Public Health Sciences. "It shows that while maternal age consistently increases the risk of autism, the father's age only contributes an increased risk when the father is older and the mother is under 30 years old. Among mothers over 30, increases in the father's age do not appear to further increase the risk of autism."

Autism is a pervasive developmental disorder of deficits in social skills and communication, as well as repetitive and restricted behaviors, with onset occurring prior to age 3. Abnormal brain development, probably beginning in the womb, is known to be fundamental to the behaviors that characterize autism. Current estimates place the incidence of autism at between 1 in 100 and 1 in 110 children in the United States.

During the 1990s, the number of California women over 40 giving birth increased by more than 300 percent. But only about 5 percent of the 600-percent increase in the number of autism cases in the state can be attributed to women waiting longer to have children, the study suggests.

To conduct their investigation, the researchers obtained the electronic records for all births in California between Jan. 1, 1990 and Dec. 31, 1999. The records incorporated detailed demographic information, including the ages of both parents. To identify which children would develop autism, the researchers obtained electronic records identifying children born during the study period who later received an autism diagnosis from state Department of Developmental Services. In this study autism was defined as a diagnosis of full-syndrome autism at a California Regional Center.

The researchers also excluded a small number of births where demographic information about parents, such as their ages and levels of education, was not available. Instances of multiple births were analyzed separately. The exclusions brought the total size of the study sample to approximately 4.9 million births and 12,159 cases of autism.

For older mothers, the step-wise progression in the risk of having a child who later would be diagnosed with autism was apparent among every age group of fathers. When the father was older and the mother was younger — under 30 — the child's risk for developing autism also was elevated. For example, among births to mothers under 25, children fathered by a man over 40 were twice as likely to develop autism as those whose father was between 25 and 29. Among mothers over 30, the increased risk associated with older fathers dissipated, the study found.

Because of the large study size, the researchers were able to show how risk for autism was affected by each parent's age by holding one parent's age constant and then comparing autism incidence across the age of the other parent across five-year increments. The subtle interaction of how each parent's age affects the risk of autism then became quantifiable even when it was reliant on the other parent's age. This methodology is more efficacious and requires fewer assumptions than the mathematical modeling used by earlier studies, the researchers said.

The researchers note that understanding the relationship between increased parental age and autism risk is critical to understanding its biological causes. Earlier studies have observed that advanced maternal age is a risk factor for a variety of other birth-related conditions, including infertility, early fetal loss, low birth-weight, chromosomal aberrations and congenital anomalies.

I have to admit that when I first started reading about autism and getting a bit scared with the potential that one of my kids could end up with it, I came to the conclusion - or perhaps jumped to it! - that paternal age was linked to the problem. We already knew about the problems of having kids at age 35 for women (increased risk of Down's Syndrome, frex). The thought immediately crossed my mind that the primary difference between times prior and now was the increased age - fertility postponement - of parenthood. No proof then. This certainly adds credence to my hunch, that's for sure!

Why Adenovirus-Based Therapies Sometimes Fail

A new approach being developed to treat individuals with cancer that is resistant to standard therapy is the use of adenovirus-based therapies. Although promising clinical results have been obtained in some settings, in many cases the therapies have had little impact. One reason for this lack of efficacy has now been uncovered by a team of researchers, led by Nick Lemoine and Yahoe Wang, at Barts and The London School of Medicine and Dentistry, London.

In the study, they found that human pancreatic cancer cell lines expressing the protein CEACAM6 were not sensitive to being killed by adenoviruses. Further analysis revealed the molecular mechanism by which CEACAM6 mediates its effects and indicated that knocking down expression of CEACAM6 markedly increased the anticancer effects of an adenovirus in mice harboring human tumor cells. The authors therefore suggest that identifying whether or not a tumor expresses CEACAM6 and the downstream proteins required to block tumor cell killing by adenoviruses might provide a way to predict the response of patients to adenovirus-based therapies, and that these proteins might provide targets for the development of more effective adenovirus-based therapies.

I've been terribly curious why the virus based therapies for cancer haven't taken off. They were doing tries of tailored viruses back in the mid to late 90s. Now I know why. They had issues at different points and didn't understand why. Now, it seems, in one case, they do.

SWEEEET!

More Progress on the Zombie Drug

For the first time, researchers have demonstrated that the administration of minute amounts of inhaled or intravenous hydrogen sulfide, or H2S – the molecule that gives rotten eggs their sulfurous stench – significantly improves survival from extreme blood loss in rats.

Cell biologist Mark B. Roth, Ph.D., and colleagues in the Basic Sciences Division of Fred Hutchinson Cancer Research Center, in collaboration with surgeon Robert K. Winn, Ph.D., and colleagues at UW Medicine's Harborview Medical Center, report their findings online ahead of print in The Journal of Trauma Injury, Infection, and Critical Care. The article is slated for the July print issue, which comes out on July 10.

The researchers successfully used H2S to induce a state of reversible metabolic hibernation as a way to reduce death from insufficient blood supply to organs and tissues in a rat model of lethal hemorrhage. (Federal regulations mandate the use of such animal models in preclinical research to test the safety and effectiveness of various procedures and treatments before they can be tested in humans.)

They found that 75 percent of rats (18 of 24) given inhaled hydrogen sulfide and 67 percent of rats (eight of 12) given intravenous hydrogen sulfide survived at least two weeks – the duration of the monitoring period – after losing more than half of their blood for an extended period. In contrast, long-term survival rates for the untreated rats in the two control groups were 23 percent (three of 13) and 14 percent (one of seven), respectively.

"Our goal is to develop life-saving treatment for critically ill people suffering from acute, sustained blood loss, such as in a car accident or on the battlefield," said senior author Roth. "These findings have obvious implications for the military, but they also have tremendous implications for the civilian population."

OMG THEY"RE CLOSE TO THE ZOMBIE APOCALYPSE! AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAH! WE'RE ALL GOING TO DIE!

A bit more seriously, it's interesting to see if we finally do get teh much mumbled about in SFnal terms hibernation capability...because of stinky eggs.

IDK WTF to do

My wife's mouth hurts. We had some extensive work done some time ago when she came under my insurance. Since then, she's had issues with her mouth hurting. We keep going back to the dentist I've had for some time and they tinker a bit here and there, but generally throw up their hands saying either they don't know what's wrong or there's nothing wrong or its in her head.

I can see she's in pain. I can see she's hurting. Her dental hygiene is impeccable according to the dentist. In fact so clean that there's no point in the dentist cleaning or polishing her teeth. Yet Lyuda's still in pain.

We just got back from another appointment and it was pointless. Nada was figured out. It was a complete waste of an hour and a half. I needed to get stuff done for work - we thought they were going to open up the crown to take a look, always fun - and Lyuda needed to meet with a prof. I was unhappy, but Lyuda was even more than that to the nth degree.

It looks like we're going to change dentists. It's too bad. They've done some good work for me, but...geez this is ridiculous.

Canuckistani "Cure" for the Common Cold?

Researchers at McGill University have discovered a way to boost an organism’s natural anti-virus defences, effectively making its cells immune to influenza and other viruses.

The research was conducted by post-doctoral fellows Dr. Rodney Colina and Dr. Mauro Costa-Mattioli, working in collaboration with Dr. Nahum Sonenberg, a Howard Hughes Medical Institute International Scholar at McGill. They worked with colleagues at l'Institut de Recherches Cliniques de Montréal (IRCM) and the Ottawa Health Research Institute (OHRI). Their results are to be published February 13 in the journal Nature.

Their process – which could lead to the development of new anti-viral therapies in humans – involved knocking out two genes in mice that repress production of the protein interferon, the cell’s first line of defence against viruses. Without these repressor genes, the mouse cells produced much higher levels of interferon, which effectively blocked viruses from reproducing. The researchers tested the process on influenza virus, encephalomyocarditis virus, vesicular stomatitis virus and Sindbis virus.

“People have been worried for years about potential new viral pandemics, such as avian influenzas,” Dr. Sonenberg said. “If we might now have the means to develop a new therapy to fight flu, the potential is huge.”

I wonder if it will work on humans as well as it did on mice. Also I have to wonder what the problems of that much more interferon would be. Would this work on all viruses/virii? If so this could be a huge breakthrough.

I know nada to comment more. It just seems like I ought to try to get the attention of those that do know to see what they think.

Genetic Engineering People: A Friday Ramble

There was a discussion, which I am having a devil of a time finding, a while back on Brian's pre scienceblogs Laelaps about genetic engineering and people: that we should not be genengineering ourselves or our descendants because of the nasty possibilities that abuse of this could and probably would take place. Brian and Julia both came down on the side of being antigene-tinkers in a big way. At the time, I argued about genetic issues that my wife's and my own families have for genetically transmitted diseases ought to be wiped if at all possible, but they countered that this wasn't appropriate to do: they want to avoid the ubermensch or Sauron syndrome. At the time, it really bothered me: I respect their opinions, but I completely disagree with them. It would have just gone away, forgotten in the daily ups and downs had not James brought a usenet discussion into his livejournal. Then. I remembered. Then in returned to bother me.

My family tends to long lives at least on my father's side. Since we have arrived on these shores in 1683, the patrilineal line has had at least two centenarians and many that have made it into their late 80s. Last I checked my grandfather was still alive and kicking at his current mid to late 80s despite having been a career soldier, smoked, drank, and eaten all the nasty things that he ought not. He may reach his century. If this is really genetic, then my father and my siblings may reach such an age too. That means my daughter and any other children I have might too. Normally, this is a good thing. However, in other lines, dementia and Alzheimer's runs through them. Now mix a very long life with being a prisoner in your own failing mind. Wonderful, huh?

There are other genetic bits that could be cleaned up as well: horrible near sightedness? Check. problems with glaucoma? yep. Diabetes? oh yeah. etc. If we could tinker and fix those genes, if they are present, though my descendants would not need fear whatever genetic cruft may have been picked up by marrying and having feeling while only being human. For me, it feels like its a responsible act to fix this, not an act of hubris or desiring to create a superhuman. Yet, obviously others feel rather different. I am looking at this with hope and some others are looking at it with fear.

I view genetic engineering in this context as a medical procedure, de nada more. From my point of view, it's an improvement on the quality of life. It doesn't hurt that if this were wildly applied then we could see massive savings in medical expenses. My glasses have cost me with medical insurance $350 a pop and I've had many prescriptions. Yet that would pail compared to what a diabetic has to deal with. Or what a specialist home requires from a senior suffering from dementia.

I sat down and wondered about those fears. One of them is that The Rich will be able to afford fixes and the poor will not. That one is probably not a realistic worry, truthfully. With genome sequencing dropping in price - very soon it will cost around $1,000 per sequence! - and depending on how much the fixes cost, it might be that because of the savings in terms of chronic health issues that get wiped out that everyone will get at least that. The second thought is that people might pursue their own twisted ideals of perfection: supersoldiers, Saurons, ubermensch, or whatnot. Doesn't this happen anyways? People pick their own mates, right? It's another form of selection. Just cruder. Genetic engineering is just more advanced versions of that. Finally, others - not the two science oriented individuals above - have stated that its not our place to play God. *snorks*

I guess the point of this ramble is to try to spark a discussion among my readers - and I KNOW there are more of you than post comments! - about whether or not YOU feel gene tinkering with people is a net bad. I don't think it is, but I'd like to hear what others think. I'll write some possible follow-up comments myself if I get others to get the discussion amongst themselves going.

Here's hoping!