A while back I said I had “microbiomes on the brain”. I meant that metaphorically. But now, two surgeons at UC Davis are in big trouble for deliberately putting bacteria in their patients’ brains.
Thing is, they say the patients requested it. “If I come down with a glioblastoma, I will demand that it be done on myself,” one of the surgeons told the Sacramento Bee.
Glioblastoma is a nasty, nasty brain cancer. According to the SacBee article - I haven’t been able to track down any other information on this therapy - there are accounts of glioblastoma patients surviving years after contracting infections, leading to a hypothesis that introducing bacteria into head wounds might be an effective therapy. [UPDATE: lots and lots of info here, both on the UC Davis situation and on the idea of treating cancer with bacteria]
How did the UC Davis patients fare? One died of sepsis (infection), one died from the tumor but also had sepsis, and one lived for at least ten months after the treatment, with a reduction in the tumor but also suffering a wound infection. The surgeons then asked for permission from an ethics committee to infect five more patients.
The university said no way, launched an investigation, and ultimately told the surgeons not to do any more experimentation on humans. The surgeons say they weren’t experimenting, just applying an admittedly rare treatment.
Going rogue: DIY germ transfers
Bacterial transfers occupy a weird gray area in medicine They’re not exactly a drug, or a tissue, or a device (the categories the FDA considers for regulation). You can get bacteria from anywhere, especially if the source you’re looking for is the human microbiome: everyone you know is a potential donor.
Fecal transplants, which have a 90% success rate at curing debilitating C. diff infections, are so cheap, easy, and effective that they should be a first treatment, not a last resort; but few doctors offer them. One is working on a home enema protocol so sufferers can DIY the treatment with their donor (often a spouse or close relative).
Babies born by c-section miss out on their mothers’ vaginal microbiota, possibly leading to health problems. Probiotics and even fecal transplants have been tried, with mixed success, but the simple technique of smearing mom’s vaginal secretions onto the baby “has been proposed … but to date there are no published studies.”
Who knows what other bacterial “transplants” might be therapeutically important? For skin infections, vaginal infections, perhaps even transfer of mouth bacteria to prevent cavities? I’m not endorsing brain bacteria, but I bet there are some promising disease treatments growing in you, and on you, right now.
I had a fun time today on twitter #germchat discussing the human microbiome. Check out a Storify transcript here. Here are some of my favorite things I learned:
How do oral probiotics affect health in places other than the gut? According to @DrJamesVersalov, they provide molecules that circulate through the bloodstream and “act like hormones”: vitamins, amino acids, etc.
Is it bad to be sanitizing our hands all the time? @DrJamesVersalov says handwashing avoids spreading infections, but established skin microbiota survives washing. @JATetro adds that sanitizer (as tested in his lab) actually does kill all the bacteria.
Is our idea of beneficial probiotics skewed toward certain species? @JATetro says most are fermenters (as found in kimchee, kombucha, sauerkraut) and their byproducts, like sugars and amino acids, are “buffers” between bugs and our immune system. @peterdilaura agrees with my suspicion that there is “big potential impact from low abundant harder-to-culture bugs”. @JATetro says he found a microbe in the subway that he was asked to culture for probiotic potential.
Here’s an intriguing idea: @peterdilaura suggests we get “sub-therapeutic dosing” of antibiotics from food.
The concentration of probiotics matters, says @JATetro, and it may not be as simple as eating yogurt, as in the case of Danone’s health claims.
We are only 10% us: where did that count come from, that established bacterial cells outnumber our own cells 10-to-one? @bernat_olle says to check out Savage, 1977.
Some more quickies:
Healthy old people have healthy gut bacteria - Makes sense, right? But the logic behind it is very chicken-and-egg. The authors say that when somebody goes into a nursing home, they start eating institutional food, their diet affects their gut bacteria, and their gut bacteria affects their health. I find this theory appealing, especially if it convinces the institutions to provide better food: “Mashed potato and porridge were the only staples in this diet type that were consumed daily,” says one of the authors.
But it could be the other way around: they get sick, then enter the nursing home, where the diet changes their gut flora. Or, they get sick, which changes the gut flora, and also leads to their move to the home. The title of the actual paper sticks to the bare facts: Gut microbiota composition correlates with diet and health in the elderly - which is exactly what they found. Causation TBD.
Parents are resistant to cold and flu viruses - and the effect lasts even after their kids have long since left home. This seems only fair, since children are little disease vectors, ferrying germs to and from school (or, in my case, day care). The funny thing is, the study found that parents have the same levels of antibodies to the viruses as non-parents, but are still less likely to get sick when a researcher shoves viruses up their nose.
Their theory: parents are happier and less stressed (haha). My thought: there’s a lot more to the immune system than antibodies, so maybe one of those other aspects of immunity gets strengthened by frequent exposure.
Twitter chat about germs today (Thurs) at 1:00pm EST. Follow #germchat. It’ll be like sitting at the cool kids’ lunch table, except the table is, um, full of germs.
Ultraviolet light kills microbes - specifically UVC rays. Not surprising if you’ve ever laid a stinky blanket outside (or, you know, your roller derby kneepads). A new study tested UVC light on skin wounds in mice, and found that it kills germs without damaging skin cells or slowing healing. (Unanswered question: what about the good skin microbiota?) The researchers are excited about this as an alternative to antibiotics, since it’s hard to evolve resistance to radiation.
(Well, D. radiodurans has done it, but they say they can kill that off too, if they just crank up the voltage enough. That’s D. radiodurans in the picture - it lives in a tetrad so it has four copies of DNA segmented from each other. Its DNA is packed into toroids to limit damage, and it can use the four copies to fix each other. Pretty awesome bug, famously nicknamed “Conan the Bacterium.”)
Lab tests on pesticides have been missing something big: soil microbes. A recent study on RoundUp ready weeds (that is, they are resistant to the pesticide glyphosate, which is supposed to kill weeds but leave transgenic soybeans alone) found that the plants survive better in sterile lab soil than in “field soil” with its microbes intact. One possibility: the plants are weakened by glyphosate, and pathogenic microbes take advantage.
Quote of the day, from one of that study’s authors: “Dirt is a living organism”
You’ve heard of airborne infections. Try not to think about how many germs are a single breath of air - too late, I guess. It’s like when you see sunlight streaming through a window, illuminating all the dust in its path, and realize you’re breathing that stuff in all the time. Well, scientists in Korea have done the first metagenomic analysis of the “air virome” - all the viruses that are floating around. (It turns out the most common type is plant viruses.) Maybe the air is a living organism too?
Don’t we all? I thought. But the story was a good one: the belly button microbiome is now being studied, and Zimmer has some unusual species in his. The project comes from the lab of Rob Dunn; you may recall that Dunn and Zimmer were two of the three authors whose books I mini-reviewed last week.1
Dunn’s area is the ecology of species surrounding people, including but not limited to microbes, and the idea behind the belly button project was to find an area of skin that should be roughly comparable between people, and not washed too often. Preliminary results, reported by Jason “Germ Guy” Tetro, suggest that we accumulate belly-button bacteria from all the places we have lived, making it “a museum of lifetime experiences.”
My belly button pops inside-out when I’m pregnant. Have I just washed off all my lifetime experiences?
This is where you come in
Sixty volunteers had their navels swabbed and cultured for the project, which is now listed as “sampling complete,” but if you missed out, don’t worry - the next phase of research is about to begin: Armpit-pa-looza.
Dunn has plenty to say about armpit stink and why it’s valuable to humans, but perhaps the most astounding is that our bodies seem to deliberately cultivate stinky bacteria there (and in our crotches, sorry, genitoanal region) - feeding the critters with secretions from our apocrine sweat glands, and providing a hairy trellis for the resulting bacterial garden.
If armpits aren’t enough, you can also donate your poop to science - I mean, the website doesn’t mention poop, but what else could it be? - through the American Gut project. They are looking for diversity in their subjects, especially dietary diversity, which I think is an excellent question:
The government’s Human Microbiome Project effort sampled only healthy adults, mostly medical students! While it was an amazing project, did it really capture the American Gut? We are not sure, so we decided to find out. We are calling on athletes, couch potatoes, vegans, diabetics, Paleo dieters, centenarians etc – we need your help. If you have IBD, diabetes, autism or some other ailment – we need you too.
You know what to do. Go forth and swab thyself.
1 Obviously I foresaw this, rather than just choosing my library’s three least boring books on microbiology that weren’t checked out already. Expect Idan Ben-Barak to join the story in some further, bizarre way.
Imagine not knowing whether an animal is venomous.
I don’t mean some shadowy creature that bit you and then slithered off into the night before you could identify it. I mean a well-known species, represented in zoos worldwide, beloved of young zoology nerds (disclaimer: yes, I was one of those children). I mean the komodo dragon.
He’s planning on comparing the microbiomes of komodos in zoos and in the wild, looking at questions relating to the animals’ own survival - although I wonder if the work will confirm (or refute) any of the old factoids about deadly bacteria in komodo saliva.
The komodo’s saliva “teems with over 50 strains of bacteria,” says a typical fact sheet. It’s not that impressive a number - really, my or your mouth has more than that. Actually, the komodo’s probably does, too. The relevant study here is Aerobic salivary bacteria in wild and captive Komodo dragons (2002), which cultured 57 species; cultures don’t always give the full picture, as we know, and the researchers say their techniques disregarded any anaerobic species.
Those researchers injected komodo saliva into mice (and plain saline into controls) and waited a few days to see which mice died. Then they cultured blood from the dead or dying mice, and found a bug called Pasteurella multocida, which the komodo dragons happened to have antibodies to.
Case closed? Well, Pasteurella is found in a variety of animals, where it is sometimes a part of normal respiratory flora. And, as the authors of a human oral microbiome paper wrote, “the oral cavity is an open system where exogenous microorganisms from the environment are continually introduced by eating, drinking, and breathing.” Their point was that it’s hard to get a good count of species, but the same caveat can apply to the search for a single toxic bacterium. That’s what Fry thinks the deal was with Pasteurella - it was a bystander in the swampy water the komodo hunts in.
Tracking down the animal’s venom glands was a beautifully multifaceted approach, involving field observations like the one above, as well as anatomy studies (he put a komodo through an MRI machine to look for venom glands), modeling of the skull based on CT scans (to show that it doesn’t have a powerful enough bite to kill on its own - later confirmed by another researcher’s tests with live dragons) and tests of the contents of the venom glands (revealing two proteins that dilate the prey’s blood vessels and keep its blood from clotting). Phylogenetic studies also show that komodo dragons - plus a lot of other reptile species that you wouldn’t expect, like iguanas - come from venom-producing ancestors.
Here’s the latest study on short sprint intervals; study after study shows them to be better, or at least as good, as steady-state exercise. Better at what? In this case, the headline is about fat loss; the researchers say they saw no difference in insulin sensitivity, but did see some of your typical adaptations to exercise, including a 15% increase in VO2max.
I can’t take this study too seriously though, because the control group was not exercising. (Really, Heydari et al? Really??) They seemed to model their study after a previous one showing that women lost more fat on 20-minute sessions of sprints (8 seconds on, 12 seconds off) than on 40-minute sessions of steady state cycling.
Until a few years ago (as best I can tell), research on interval training was all about muscular and cardiovascular adaptations - in other words, measures of interest to athletes and their coaches. Then came a 2009 article (open access PDF) showing that 30-second sprints, with 4 minutes of recovery, can improve insulin action. The protocol required only 250 calories’ worth of work per week and was hailed as a way to manage or prevent Type 2 diabetes.
The 30-second sprint protocol is based on the Wingate test, devised in the 1970s to measure how hard your muscles can work anaerobically. Over time, researchers found that repeating the test - several times in a session and by doing multiple sessions - improves performance.
Another protocol, 60 seconds on, 60 seconds off, was shown in 2011 to improve insulin sensitivity among other measures. There are other variations, like the 8 seconds / 12 seconds in the first study above.
Everybody wants to improve the general public’s insulin sensitivity; we know this because you can’t read an article about insulin these days without seeing the words “obesity epidemic” and “metabolic syndrome” and an exhortation for everyone to exercise more. If you’re a public-health expert, or a doctor, or a researcher looking to justify your work, your main concern is getting people to exercise more. One way of doing that, paradoxically, is to have people exercise less - that is, to find the least amount of exercise that will do the job.
The authors of the 2009 paper wrote: “This novel time-efficient training paradigm can be used as a strategy to reduce metabolic risk factors in young and middle aged sedentary populations who otherwise would not adhere to time consuming traditional aerobic exercise regimes.” (By the way, I wonder if anyone surveyed the diabetic folks who are the target of this advice. What kind of exercise would they actually prefer?)
Even so, the American Diabetes Association makes no mention of intervals on their website, instead deferring to the Dietary Guidelines which recommend 30 minutes of “anything that increases your heart rate and causes you to break a light sweat.” Walking and gardening are among the suggestions.
Maybe the research just needs more time to trickle down? Or maybe the problem is the one identified in the ADA’s 2010 guidelines (which didn’t mention intervals, but did acknowledge that resistance training is at least as important as aerobic exercise) - not only are patients sometimes uninterested in exercise, their doctors may be afraid to prescribe it. “Many physicians appear unwilling or cautious about prescribing exercise to individuals with type 2 diabetes for a variety of reasons, such as excessive body weight or the presence of health-related complications. However, the majority of people with type 2 diabetes can exercise safely.”
Check out this 2011 review in the Journal of Obesity for the details on interval training research, especially as it relates to health (not performance) measures like insulin sensitivity and weight loss. Some interesting notes from that paper’s conclusion:
- Studies are typically done on cycle ergometers (exercise bikes), so while we assume that sprints in other sports must work the same way, we don’t actually have data on that. Oddly, people with Type 2 diabetes show more insulin resistance in their leg muscle than in their arms, so it may be important to work their leg muscles specifically.
- Diabetic subjects improve their insulin action more than non-diabetic subjects, on the same protocols.
- Insulin sensitivity may be an effect of the last session you did, rather than a permanent result of all the work you’ve done to date.
The Wild Life of Our Bodies by Rob Dunn
Basic idea: We evolved as part of an ecosystem that included not just microbes, but internal and external parasites, predators, and the many species of a hunted/gathered diet. Our bodies now have adaptations to organisms that aren’t there anymore - an immune system that goes haywire when parasites are missing, psychology that stems from a healthy fear of predators, etc.
Best part: the lady who, after careful research and exhausting her other options, goes to a clinic in Tijuana to get infected with parasitic worms. The worms are cultivated from the poop of the clinic owner, who is not a doctor. They would, ideally, live inside her for years. “The endeavor felt more like adopting a pet than modern medicine.”
Worst part: The book is long on stretched-out storytelling, light on actual facts. An air of gullibility from mentioning one or two simplistic theories about each complicated problem, and then moving on. The further you go into the book, the more unbridled speculation abounds. Nice ideas but needs more grounding in reality.
Microcosm by Carl Zimmer
Basic idea: We’ve learned a lot from E. coli in the lab (and in the wild). Zimmer takes us through major discoveries in genetics and cell biology, learned through the lens of E. coli but applicable to, in most cases, all the rest of life.
Best part: All the complicated, crazy stuff E. coli does in the wild that we don’t see in the lab. “To know E. coli by [lab strain] K-12 alone is a bit like knowing the family Canidae from a Pomeranian dozing on a silk pillow.” It finds friends, wages warfare against enemies, builds biofilms, executes a multi-stage plan for colonizing a gut, and hosts parasites of its own.
Worst part: Has been scrubbed of all terminology that would help you google anything, or recognize it if you read about it elsewhere; for example, the names of the genes or processes being (however skillfully) analogized. The Notes section provides no notes, just citations in the most minimal form possible.
The Invisible Kingdom by Idan Ben-Barak
Basic idea: Humorous tour of microbes in our lives.
Best part: Lots of little tidbits, like how D. radiodurans keeps its DNA radiation-resistant, the sidebar on tardigrades, the list of things around the house we could get rid of if there were no microbes. “Give [the dishes] a quick rinse in the sink, and that’s it. Food scraps will no longer make you ill or taste bad, so you can leave them on, if you like.”
Worst part: Whole chapters of apologizing for talking about science in a science book.