A Brave New World here we come! Chinese scientists find out embryo design not working so well

Aliasgharson, Wikimedia Commons. 

Aliasgharson, Wikimedia Commons. 

Well it was bound to happen sooner or later: Chinese scientists reported the first attempt to modify (design) the genome of human embryos. The group of Junjiu Huang at Sun Yat-sen University in Guangzhou published in Protein & Cell that they alter the human genome using CRISPR/Cas9 technology. This is the first step to being able to correct disease (which is what they were trying to do) or make designer babies.

This is obviously kind of a bit very controversial which the Huang attempted to address by using non-viable embryos. Specifically, they used "tripronuclear zygotes": eggs that were fertilized by two sperm simultaneously, which apparently happens in around 7% - 8% of IVF embryos. Such embryos have three nuclei total (two sperm pronuclei and one oocyte nucleus) and, while it's true they won't normally develop, it seems it's also possible to suck out the extra one and have a normal human birth. (Note the sucking process unfortunately kills most of the embryos though.)

The ethical dimensions of genome editing are, shall we say, broad and the concerns many. Most significantly, these are germline modifications, which means the changes will be passed to any children of those who were modified.

Dolly, the world's first cloned sheep, now stuffed at  the National Museums of Scotland. Mike Pennington, Wikimedia Commons.

Dolly, the world's first cloned sheep, now stuffed at  the National Museums of Scotland. Mike Pennington, Wikimedia Commons.

All that said, editing isn't exactly working very well right now: of 86 embryos injected using various experimental conditions, only 4 lived and were edited as intended. Now a 4.65% success rate isn't exactly a super good bet but maybe there's some situation where people would do that. Except, the research also revealed "notable off-target effects" or editing where it's not supposed to be edited. In addition, the study "likely underestimated the off-target effects" because it sequenced a portion of the genome, the exome. [One can kind of think of the exome as a TV show with segments you'd ignore, maybe ads, removed with the rest spliced together. That's a pretty bad analogy but suffice it to say the information of our genes has "extra pieces" interspersed with the "real pieces." This study looked only at the "real pieces" and thus underestimated the occurrence of unintended editing.] As Huang commented,  “If we did the whole genome sequence, we would get many more.”

They summarize: "Further investigation of the molecular mechanisms of CRISPR/Cas9-mediated gene editing in human model is sorely needed. In particular, off-target effect of CRISPR/Cas9 should be investigated thoroughly before any clinical application." Indeed.

Remember Dolly, the cloned sheep who developed severe arthritis and progressive lung disease? Cloning is arguably way easier than editing and I'd hate to be the person who got editing 1.0. All of the above said, we've already opened Pandora's box; this will I think inevitably be applied to people, be for good or bad.

As for cloning, China is now "cloning on an 'industrial scale'." As the Chief Executive of the industrial cloning company said, "if it tastes good you should sequence it... you should know what's in the genes of that species" apparently so we can soon just edit all pigs to taste perfect. Of note, my parents traveled to China. The thing that stood out to my father? "I've never had bacon that tasted as good."

Want your ADHD child to learn? Let them squirm!

I remember talking with the mother of a child with ADHD. She recounted interaction after interaction with his school, many not exactly turning out as desired. My response was simple: "Run him." At least in my experience, physical activity is the easiest way to get, say, a puppy or my kids, or for that matter myself, to be calm in both body and mind.

As it turns out, research at the University of Central Florida (UCF) verified that off the cusp reply: kids with ADHD in particular learn better when they're squirming. More specifically, physical activity like fidgeting and moving hands, feet and legs helps in learning, reasoning and comprehension [article].

Physical movement was actually most pronounced when kids with ADHD needed to use their brains' executive brain functions including working memory (which they measured). “What we’ve found is that when they’re moving the most, the majority of them perform better. They have to move to maintain alertness.” explains Mark Rapport, an author in the study and head of the UCF Children’s Learning Clinic.

According to Rapport, "facilitate their movement so they can maintain the level of alertness necessary for cognitive activities.” If you can make it work for your family, I suggest that this is superior to (much more expensive) pharmacological intervention.

The mom I was talking with? She got an exercise bike for her son, and it worked.

 
 

New research verifies old: excessive vitamins give you cancer. Historical paper and notes.

Ah how the wheel turns round... Just announced at the American Association for Cancer Research Annual Meeting, dietary supplements increase the risk of heart disease and cancer. "Evidence shows that people who take more dietary supplements than needed tend to have a higher risk of developing cancer." Great.

So basically, too much of a good thing can indeed be bad. If you're eating a healthy diet, at best mega vitamins doses just waste money. At worst, they help your cancer grow. Take away: save money and just eat a well balanced diet. Maybe copy Ray Kurzweil's breakfast (paywall; without paywall) as he aims to live forever.

Linus Pauling.

Linus Pauling.

This vitamin story has a long, very human history to it that I actually got to touch. As a freshman undergraduate, I had the amazing opportunity to work as an intern archivist in the Linus Pauling Papers collection. Pauling is one of only four people to have been awarded two Nobel prizes, one of two who were awarded Nobels in different fields, the only person to have been awarded a Nobel in both Science and Peace and the only person to be awarded two unshared Nobel Prizes. The guy was brilliant: "one of the most influential chemists in history and ranks among the most important scientists of the 20th century." I'll never forget pursuing his documents, notebooks and papers, let alone organizing, cataloging and, in some extremely small way, "discovering" them. [He sent regular letters to his wife and in one, wrote that he wanted to win a Nobel. After he did, he went back, found that letter and in the margin wrote something like "I did it!".]

Pauling is also a classic example of how people get stuck in belief, in this case about vitamin C. He firmly believed that vitamin C would prevent cancer. Note you can also firmly believe that you can jump off a cliff and fly. [Really, don't try it.] Unfortunately for that belief, according to research done in Pauling's own institute, vitamin C helped cancer in everything but near lethal doses [Pubmed ref]. The study was published in 1994, 11 years after a serious falling out with Dr. Arthur Robinson, the study's first author and a colorful scientist who was fired from his tenured position as President at the Pauling Institute at the time of the research. [Incidentally Robinson was awarded a $575,000 lawsuit settlement against Pauling. Online sources say $425,000 was for "slander and libel" and I'm unable to find a primary source on that; if you know one, please post a comment below. More in the June 11, 1979 issue of Baron's: Of Mice and Men - The Linus Pauling Institute is plunged into controversy.] Since then, other studies have shown that supplements "seem to increase overall mortality" (great Atlantic article)  and that vitamin C doesn't seem to do anything [good] for cancer. Poor Pauling must be rolling in his grave. Be very wary of anyone, scientist or otherwise, who substitutes "belief" for "reproducible results"!

With the rather current nature of its questions, I read the Robinson paper a bit more in depth. The study itself is straight-forward: they irradiated hairless mice with UV while feeding them 38 diets with different nutrition and vitamins. They then quantified the number and severity of cancerous skin lesions and looked at those as a function of, say, how much vitamin C they ate. A few things stood out to me.

Note the significantly reduced number of lesions for mice on the "Black mixture" diet. Table 1 from Robinson AB, Hunsberger A, Westall FC. Suppression of squamous cell carcinoma in hairless mice by dietary nutrient variation.&nbs…

Note the significantly reduced number of lesions for mice on the "Black mixture" diet. Table 1 from Robinson AB, Hunsberger A, Westall FC. Suppression of squamous cell carcinoma in hairless mice by dietary nutrient variation. Mech Ageing Dev. 1994 Oct 20;76(2-3):201-14.

First, because the number of diets they tested was pretty big, the number of mice was what I'd call exploratory, in the 40-50  range. That's actually not so bad (it is in fact 1846 mice all together) except that second, there's no error bar anywhere in the paper, only averages. Error bars are a measure of the scatter of data and directly affect the chances that two groups are statistically "the same." Pretty intuitively, when scatter is high, you need a really big difference to say "they're different." From what's published, we really just can't do that. (I also couldn't find supplemental data listing individual mice to calculate scatter.)

Skin cancer in mice eating a control diet (top row) was significantly worse than those on a diet supplemented with antioxidants (bottom row). This was later found to be due to a sunscreen effect of BHT, which accumulates in skin, not antioxidan…

Skin cancer in mice eating a control diet (top row) was significantly worse than those on a diet supplemented with antioxidants (bottom row). This was later found to be due to a sunscreen effect of BHT, which accumulates in skin, not antioxidant activity. Figure 2 from Black HS, Chan JT. Suppression of ultraviolet light-induced tumor formation by dietary antioxidants. J Invest Dermatol. 1975 Oct;65(4):412-4.

Third, speculating on the meaning of their data, the authors the conclude that "perhaps nutrition during cancer therapy should be viewed as the provision of fuel for a race between rapidly growing young tissues and mature older tissues wherein nutrient restriction or malnutrition may favor the older tissues." Cancerous cells are indeed fast growing with unique metabolic needs and this idea that something which is good when you don't have cancer might not be so good if you have it has recently been proposed in the context of antioxidants by Jim Watson. We might paraphrase Jim's thoughts as "take antioxidant as long as you don't have cancer and stop as soon as you've got it." Actually, this makes a lot of sense: the immune system is constantly surveilling (including for cancer) and it uses oxidative bursts to kill things. Lots of antioxidants hanging around? Harder to kill stuff. As it turns out, I've also worked on cancer studies that revealed aspects of the same phenomenon. With the caveat that biology is complex, it seems antioxidants are likely to help cancerous cells more than normal ones.

Fourth and finally, despite the lack of error bars, one thing really did stand out: one diet, the "Black mixture," had around 5-fold less severe lesions and about half the number of lesions in total as any other (see table above). That mixture contained a standard mouse chow supplemented with a bunch of antioxidants: 0.5 g vitamin E, 12 g vitamin C, 5 g butylated hydroxytoluene (BHT, which is in cereal boxes as an antioxidant preservative), and 1 g glutathione per kg of food. The mix was replicated from another study by Black that previously obtained similarly striking results (see mice picture). Robinson et al. broke down that mixture and tested the vitamins independently: vitamins alone didn't show the protective effect. Black later found a mechanism for the (reproducible) observation: BHT accumulates in the skin and acts as a sunscreen, reducing the amount of UV that reaches the lower layers of skin where cancer forms.

In summary: 1) antioxidants are probably not the best thing to take when cancer happens; 2) supplements at best don't do much if you've good nutrition and at worst increase the risk of death; and 3) as so often happens in science, the reproducible anti-cancer activity of a synthetic antioxidant BHT in mice wasn't (as hypothesized) due to its antioxidant properties at all but rater, because it formed a sort of internal sunscreen in skin.

Despite daily multi-gram quantities of vitamin C, Linus Pauling died of prostate cancer in 1994. His wife Ava Helen died 13 years earlier of stomach cancer.

Be careful, biology is complex.

Antibiotic resistant bacteria go airborne and people wonder if it's a health risk

From science fiction to zombies to rather realistic scenarios, we've got movies galore saying yes, contagious outbreaks are bad and airborne outbreaks are really bad (this is all true by the way). Yet even with that backdrop, the title of a Medical Daily article wonders aloud: "Antibiotic-Resistant Bacteria From American Cattle Become Airborne, But Is It Life-Threatening?"

Now, I normally try to be pretty nonjudgmental about most everything and to be fair the article itself is accurate and well written. That said, headlines change the way we think and how we read articles. When things are literally "if you get this, you or your family can die," I feel like genuine bluntness is called for. Antibiotic resistance jumps between bacteria and it's when they "learn" to be resistant to many antibiotics that you end up in the "untreatable" category. There's no faster way to get around than by air so yes people, airborne antibiotic resistance is absolutely life-threatening. I just don't understand why there's any doubt here...

As the authors of the study conclude, “there is significant potential for widespread distribution of antibiotics, bacteria, and genetic material that encodes antibiotic resistance via airborne PM [particulate matter = stuff blown by the wind]." And "feedlot-derived microbes, including those possessing antibiotic resistance, can be transported to new locations where they may occupy new niches" like maybe in you or your family.

According to the CDC (watch the video), 2 million people get antibiotic resistant infections per year and 23,000 of them die; that's really a whole bunch of people... For comparison, there were 32,719 deaths from car accidents in 2013 and that number has been going down for years. Antibiotic resistant infection deaths? They're predicted to rise to 10 million deaths per year at a cost of $100 trillion by 2050. $100 trillion???

Surely there's a gazillion ways people come to believe what they do and those beliefs are formed from good information, bad information, garbled unintelligible information, everything... That's a big reason for doing this website: to bring people good, reliable, understandable information that you can act on, usually with a bunch of links and references. I suggest that anyone putting stuff out there must be really careful to not incite doubt especially with such serious (not to mention extremely straight forward) issues. You've my word I'll give you the best information I've got in everything here.

So just to be clear, airborne antibiotic resistance is absolutely life-threatening. If it doesn't hit us today, it unfortunately will tomorrow and that applies as much to people as it does to cattle.

MIT study: lower income kids end up with smaller brains

MIT researchers found that lower-income students have thinner brain cortexes compared to those from higher-income families (Washington Post version). This difference correlated with performance on standardized tests.

While the study didn't examine possible causes, previous research shows that children in lower-income families experience greater stress during childhood development. They also are exposed to less language and educational resources. All these are likely causes for reduced brain development.

The study was based on MRI brain imaging (a technique that's both slow and expensive) and consequently had a relatively low n, or number of subjects: 23 from lower-income families and 35 from higher-income families (all 12 - 13 years old). Given that number, verifying studies will be good but I'm pretty confident this trend will be reproducible. As Dr. John Gabrieli, an author of the study and professor of brain and cognitive sciences at MIT summarized: “Just as you would expect, there’s a real cost to not living in a supportive environment. We can see it not only in test scores, in educational attainment, but within the brains of these children.” None of this is surprising.

My gut says this is less a function of income and more about time, which lower-income workers have less of, at least measured by sleep.

With the pace of life today, it's hard but my take-away on this is to make time for your kids, explain things to them (actually just talking to them all the time is really good), do stuff with them and try to answer their questions. Even if you don't know the activity or question, they learn from our approaches. Making your kids smarter is worth the time.

Wanna not get sick? Wash your hands. Without antibacterial soap.

Everyone knows they're supposed to wash their hands but guess how less often you'll get sick if you do it? A major meta analysis (an analysis that puts together the results from many studies) of 30 different studies from 1960 to 2007 shows you'll reduce gastrointestinal illness by 31% and respiratory illness by 21%. A dataset this huge (and repeated by many different groups), means we can really trust the results.

Practically, if you don't washing your hands and had "stomach flu" three times over the past year, then you start washing your hands, you'll get it only twice

Of note, antibacterial soap and ethanol hand sanitizers were not effective. The best method? Good old soap and water! Considering that antibacterials disrupt hormones (might even make your kids fat?) and that young kids can get drunk off hand sanitizer, I think this is a case of simpler is better.

Artificial intelligence (AI) software now replacing humans

People have worried for a long time that robots would take jobs from humans and now it's really happening: 150 former workers for the UK telecom firm O2 have been replaced by artificial intelligence (AI) software that does cell phone unlocking and number porting, sim swaps and contract migration. Once the AI learned its job by watching humans, AI replaced the workers.

Blue Prism developed the AI and, as their chairman Jason Kingdon explained: "They mimic a human. They do exactly what a human does. If you watch one of these things working it looks a bit mad. You see it typing. Screens pop-up, you see it cutting and pasting." Hm.

Although some people are predicting more robots won’t mean fewer jobs, I'm not so sure. What happens when jobs in the food industry, nurses and truck drivers -- three of the most common jobs in America -- are gone? Not only that but what happens when our AI creations wake up? Somehow we've got to figure out how to give them morals but then again, look at how we humans screw things up...

Oh and yes, remember Cyberdyne from Terminator? It's a real company that makes robotic exoskeletons. And Skynet? Britain Launches Final Real-Life Skynet Satellite, Dubs it Skynet with No Sense of Irony (that's the title of Gizmodo's article).

Thinking about our kids, I'm wondering where this all is going to end up...