Children see, children do, but monkeys know better

I usually like to blog about recent articles, and I try to limit myself to papers published in the last 2-3 years. I’m going to make an exception this time and write about a publication from way back (2005). By scientific standards, 5 years ago is literally ancient (kind of like computer standards), but bear with me, this is going to be worth it (unlike a 5-year old computer).

Researchers from the UK were interested in finding out more about learning patterns, and about how our learning patterns differ from one of our close cousins, the chimpanzee. To test this, they subjected human children 2-4 years old and chimpanzees 2-6 years old to a simple task: retrieving a treat from a box.

In the first set of experiments, the researchers gave the chimps an opaque black box, and showed them how to open it to retrieve a treat inside. This wasn’t a simple pull-the-top-off kind of box, though. The box seemingly could only be opened following a series of specific steps: pulling a bolt, putting a stick in a hole, opening a door, etc. Chimps are quick-learners, though, and by imitating the researcher, they were soon able to retrieve the treat, no problem.

How well did the human children to at the same task? Quite well. They too were able to learn how to retrieve the treat from the black box by copying all the steps the researcher showed them. It would have been slightly worrying otherwise. I mean, we’ve taken over the world, right? Surely we can teach our young how to open a silly box, right?

The second set of experiments was almost exactly the same as the first one, except this time the box was made out of clear plastic instead of being opaque. The researchers went through the same process of teaching the chimps how to open the box. But there’s a catch: with a transparent box, it became very obvious that most of the steps supposedly needed to open the box were irrelevant. All you had to do was open the door. Chimpanzees, our closest living relative, are quite smart, and dropped all the unnecessary steps. They didn’t bother with the bolt and the stick and all those irrelevant actions: they went straight for the door and grabbed the treat.

When it was time for the children to be tested on the clear box, they too got shown how to open it by the researchers, including all the unnecessary steps. And when it was their turn to do it, they obviously…

Started pulling the bolt, putting the stick in the hole, etc.

Wait, what?

Did I get that wrong? I must have messed up the subjects… Wait… Nope. Those monkeys just fed us a piece of humble pie.

The researchers suggest that in the case of this study, the difference between how the chimps and how the children perform the task may have to do with a different focus of attention. Children pay more attention to the process of opening the box and the actions of the researcher, while chimps have their eyes on the prize, and focus more on the goal rather than the process. The researchers conclude by saying that imitation may be a human strategy that is often employed at the expense of efficiency.

The interesting thing about this article is that some news reports and descriptions of this experiment in magazines ended with a conclusion that more or less stipulated that our children imitated even the irrelevant steps of the task because that was the smarter thing to do, twisting the story around to make it sound like humans were superior to the chimpanzees in some way. Start your debate engines, but my opinion is that we should stop considering ourselves so superior. The results of this study are pretty straightforward. Do we really have to come up with a twisted interpretation of the results to make us sound like the winners? I would love it if we could just look at this experiment and say, hey, what do you know, we can learn something from the chimps.

Eyes on the prize, people. Eyes on the prize.

This monkey is laughing at you.

Reference: Causal knowledge and imitation/emulation switching in chimpanzees (Pan troglodytes) and children (Homo sapiens). (2005) Horner V., Whiten A. Anim Cogn 8(3):164-81.

Conquering cancer one virus at a time

Back in June, I participated in The Ride to Conquer Cancer, a 2-day bike ride between Vancouver and Seattle to raise money for BC Cancer. It was an extremely moving, positive and rewarding experience. It also gave me a chance to eat a piece of humble pie when 70 year-old cancer survivors (identified by flags on their bikes, adding to their wind resistance) would pass me going up the hill. The good news is that at the end of the 272 km, I was still smiling:

The bad news is that I didn’t conquer cancer.

Cancer research is well-funded, popular, and has been around for quite some time. So why can’t we get rid of this disease? The problem with cancer is that it’s tremendously difficult to target. Unlike cells infected by viruses and bacteria, cancer cells don’t display any obvious flags that something is wrong with them, which makes them challenging to distinguish from healthy cells. Therefore, most treatments for cancer involve killing a number of healthy cells, and that’s just not ideal.

Progress is being made, though, as a recent publication in the journal PNAS suggests. In this paper, a collaboration between researchers in California and in Japan lead to the discovery of a new way of identifying tumors for easier removal. They rely on an unlikely ally: viruses.

The researchers genetically engineered a special type of virus to carry a gene that codes for a fluorescent protein, GFP (for Green Fluorescent Protein - as simple as that!). If all the cells in your body were to be infected by that virus, you would glow (kind of like the famous puppy). While this would immediately up your popularity ranking at any science party, it doesn’t do much for treating cancer. So the researchers took it one step further and engineered the virus so that it would only express the fluorescent protein (make the cell glow) if the cell has an active telomerase. Telomerase in an enzyme involved in the replication of cells. If the telomerase enzyme is active when it shouldn’t be, it can cause cells to divide indefinitely, creating tumors. In fact, it is thought that over 90% of human tumors show telomerase activation. To sum it up, cells are infected with a virus that has a gene for a fluorescent protein, but only cancerous cells have an active telomerase, the switch that turns on the fluorescence. The result? Glowing tumors.

The benefits of these findings are two-fold. First, glowing tumors mean that surgeons can precisely remove the tumors without having to also remove a chunk of healthy tissue “just to make sure”. Second, tumors have a nasty habit of hitching a ride in your lymphatic system or your blood and disseminate throughout your body, making it very difficult to take out every little bit of sprouting tumor. With this innovation, all those little disseminated tumors can be identified and removed. Those two benefits together could greatly reduce the chance of a relapse, an important consideration when treating cancer. The researchers tested their mutant virus in two different types of animal models of cancer (colon and lung) with great success. While I’m usually worried at the prospect of glowing body parts, this research could have a big impact on cancer treatment.

If I want to give myself a chance to conquer cancer in 2010, I should probably spend less time on the computer and more time on the bike...

Glowing tumors

Reference: In vivo internal tumor illumination by telomerase-dependent adenoviral GFP for precise surgical navigation. (2009) Kishimotoa, H., Zhaoa, M., Hayashia, K., Uratad, Y., Tanakac, N., Fujiwarac, T., Penmanf, S., and Hoffmana, R.M. Proc Natl Acad Sci 106(34):14514-7.

Dating advice courtesy of your friendly neighborhood monkey

Dating advice websites abound with many different kinds of advice: good advice (don’t pick your nose), strange advice (date according to your blood type), not so good advice (Leos dating Leos need to hire domestic helpers). One suggestion that seems to pop up quite frequently is to mimic the body language of your date. He picks up his drink for a sip, you pick up yours. He strokes his hair, you stroke yours. He picks his nose, you pick your nose. You get the idea. As it turns out, in a social interaction context, we humans tend to unintentionally imitate what others are doing. Think of this as a team-building exercise: it’s a behavior that helps establish rapport, empathy and other fuzzy feelings toward each other.

A recent publication in the journal Science shows that behavior matching leading to increased rapport is not exclusive to humans, and it can also occur between different species.

The study looks at capuchin monkeys, a very social primate species. During the experiments, the monkey is given a ball to play with. On either side of the monkey’s cage stands an experimenter. One experimenter is mimicking what the monkey is doing with the ball (poking it, pounding it against the wall, trying to eat it… Mmmmm…), while the other experimenter is also playing with the ball, but not mimicking the monkey. The researchers show that not only do the monkeys look at the imitators more, they also spend more time hanging out close to the imitators and prefer to interact with the imitators in a food exchange game. The authors also did an important series of control experiments to show that these effects were not due to the monkeys perceiving more attention from the imitators.

So why are we subconsciously hard-wired to constantly be playing Simon Says? It is thought that the positive feelings resulting from behavior matching played an important role in human evolution by leading to higher levels of tolerance and by preventing aggressive behavior (to put it simply, by preventing us from beating each other up). The same principle probably applies to primates, and the empathic connection that results from imitation may explain the altruistic tendencies observed in the behavior of capuchin monkeys.

Next time you catch yourself winking back at someone who winked at you, or laughing at a joke you didn’t get because everyone else is laughing, keep in mind it’s for the greater good. After all, even monkeys know that imitation is the sincerest form of flattery.

Scientific Chick readers applying their new found knowledge
(Image from Loldogs)

Reference: Capuchin monkeys display affiliation toward humans who imitate them. (2009) Paukner, A., Suomi, S.J., Visalberghi, E., Ferrari, P.F. Science 325:880-882.

Need some real estate advice? Ask an ant.

What does it mean to be rational?

In a biological context, rationality means that when animals (including humans) are making a decision, they choose the option that maximizes their fitness benefit. For example: my cat, Mr. Minou, prefers to eat canned food rather than grass. Canned food provides him with more nutrients, more protein, and more energy than grass: it has a fitness benefit for Mr. Minou. Even if he is presented with a third option, say, dry cat kibbles, Mr. Minou stills prefers canned food, because it still has the highest fitness benefit (and, obviously, kibbles taste gross).

Pretty straightforward so far. So, being the advanced species we are, humans must be rational beings, right?

Wrong.

Here is another example. Let’s say you’re shopping for a new house. You have two equally important criteria for your new house: it must have big windows to get lots of natural light in, and it must have a big garage to store all your stuff. There are two houses on the market. House A has big windows but a small garage. House B has a big garage but small windows. Rationally, humans in this position have a 50% chance of picking either house.

Suddenly, a third house is made available on the market. House C has big windows, but NO garage. In a situation like this, humans overwhelmingly put rationality aside and shift their pick to house A with the large windows but the small garage, because the perceived value of house A increased when comparing it with other available houses. However, houses A and B have unchanged value!

The reason for this shift is that as decision-makers, we don’t assign absolute values to options, we assign relative values. We like to compare. And comparing can be misleading.

Recently, two American researchers wondered about the rationality of collective animals, such as ants. The researchers figured that just as choices we make result from the complex interactions of many brain cells, the decisions that an ant colony makes might similarly stem from a complex network of interacting insect. Ant societies act as unitary decision-makers, jointly deciding on things like a single travel direction, or a nest site. The researchers decided to take advantage of the ants’ nest-seeking strategies to test their rationality.

The ants in the study live in natural holes like hollow branches, and are able to emigrate to a new nest if their current nest is damaged. Colonies seeking a new nest reach consensus on the better site among the new options based on entrance size, cavity dimensions, interior light level, etc. The way a colony reaches consensus is fascinating: a few scout ants head out to assess the quality of potential homes. When a scout finds a potential new home, it leaves to recruit more scouts, who will then recruit more scouts, and so on. The strength of this technique lies in the key fact that the higher the quality of the nest an ant finds, the faster it will recruit other ants. Eventually, a threshold of recruiting is reached, and non-scout ants are recruited and eventually the entire ant colony is moved.

The researchers first established that ant colonies prefer nests that have small openings and low inside light levels. They then assessed the susceptibility of ant colonies to irrationality by comparing the colonies’ preference for new nests with different attributes in a very similar way to my house example: nest A has a dim interior but a large entrance size, and nest B had a brighter interior but a small entrance size. In this case, the ant colonies showed no preference for either site, which is very rational of them.

The researchers then added one of two decoy nests. Decoy nest A2 was just as dim as nest A, but had an even larger entrance diameter. Decoy nest B2 had the same entrance diameter as B but was even brighter than B. In summary, each decoy nest had a good feature equivalent to that of A or B, and the other feature was worse.

Well, the study suggests that we should turn to ants for real estate advice: the presence of either decoy did not affect the proportion of colonies choosing A or B. This means that even with the decoy, the ant colonies recognized that A and B had equal fitness values, and that the option of the decoy did not change the fitness values of the original nest sites.

So what is the ants’ secret for being so rational? The most plausible explanation is that for the most part, each scout ant only visits one site. If it’s good, it recruits, and if it’s crummy, it moves on. No comparing with the one next door. In this case, the fact that individuals in the decision-making strategy lack either the opportunity or the ability to compare all the options offers some protection against irrational, fitness-reducing errors.

Is this relevant for us, other than the piece of humble pie we must eat when realizing that ants can be more rational than we are? Well, when faced with a decision, it can be helpful to remember to evaluate each option for its absolute value, and not its relative value.

Mr. Minou himself occasionally forgoes rationality and chooses to eat grass. I suspect he only does it for the pleasure of watching me wash puke from the floor afterwards. Maybe in some twisted way, making sure I clean up after him confers him some kind of fitness benefit…

Mr. Minou being irrational

Reference: Rationality in collective decision-making by ant colonies. Edwards SC, Pratt SC. Proc Biol Sci (2009) Jul 22 [Epub ahead of print]

Aging is optional! Take two of these pills and call me in the morning.

We’re getting older.

Not exactly a surprise, I know, but I didn’t mean you and me are getting older. I meant we are getting older, as a population. In 2001, one Canadian in eight was aged 65 or older. By 2026, one in five will be 65 or older. So what should we do with an increasingly aged population? Well, this being a North American consumer culture, the sensible thing to do is try to sell them stuff. I mean, think of the size of the market!

Right now, a significant amount of research is being devoted to aging. The main focus is to try to slow down aging (partly by developing marketable supplements and such). As some of you might know, even my own PhD thesis project is on how to slow aging in the brain. Loyal readers of ScientificChick.com will also be aware of recent articles about caloric restriction, a potential way to keep old age at bay. Thankfully, a recent publication in Nature suggests a much easier way to live longer: forget starvation, all you have to do is pop a(nother) pill!

In this article, American researchers show that mice that eat rapamycin supplements starting at 600 days of age (senior citizens in mouse years) live longer, up to 14% longer for females and 9% longer for males. What’s more, rapamycin supplementation did not change the causes of death. The researchers propose that this drug could be acting by postponing death from cancer, by delaying mechanisms of aging, or both.

How does rapamycin work? Well, as you might expect with a miracle drug like this, we’re not really sure. Rapamycin is an inhibitor of a pathway called mTOR. The mTOR pathway has many functions in your cells, like coordinating the survival response arising when there are changes in nutrient and energy availability, and dealing with potentially deadly stresses, such as oxidative stress (the kind of stress fancy juices packed with antioxidants are supposed to battle). Since the mTOR pathway acts kind of like a central sensor of cell health, it makes sense that it would be implicated in regulating lifespan. Exactly how rapamycin is working its magic, though, is probably what the researchers are trying to figure out for their next article.

Could the increase in longevity following rapamycin supplementation be related to the effects seen with caloric restriction (the “eat less, live longer” paradigm)? Well, mice on rapamycin show no change in body weight, so we know the drug is not acting through a caloric restriction mechanism. The converse, however, may be true: it is thought that the beneficial effects of diet restriction may also be due to an inhibition of the mTOR pathway.

So don’t throw out the double-stuffed Oreos just yet, but don’t eat half the box either: rapamycin pills for humans won’t be on the shelves tomorrow. While mTOR inhibitors are currently being used to treat a few conditions (transplant rejection and some cancers, for example), there’s still a lot of work to do to tease out all the potential interactions and side effects.

Longevity in pill form? To me, it would feel like cheating the system. And if there’s one thing we keep learning over and over in the life sciences, it’s that trying to cheat Mother Nature always has some unintended consequences.

A great illustration of the aging mouse by TS Rogers

Reference: Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA. Nature 2009 16;460(7253):392-5.

The fountain of youth revisited

Not too long ago, I wrote about my love of brownies and an article on caloric restriction. I wasn’t really planning on bringing up this topic again so soon but a recent Science paper on caloric restriction in monkeys is getting so much media attention that I just had to throw in my two cents.

In the article, a group of American researchers study control and calorie-restricted (30%) monkeys over 20 years. What they show is that the calorie-restricted monkeys have a reduced incidence of age-associated death, diabetes, cancer, cardiovascular disease and brain atrophy compared to the control monkeys. From the sounds of it, we can stop looking for the fountain of youth (it’s in Florida, by the way). The media absolutely loves this story, and news reports and videos are quick to claim that caloric restriction increases longevity in our closest cousins, and it must be good for us as well.

First, a disclaimer from the friendly folks at ScientificChick.com: In the recent years, solid, convincing and well-controlled studies have shown some benefits of caloric restriction in various types of experimental subjects ranging from yeasts to humans. I won’t go back into the pros and cons of caloric restriction in this post. There is good evidence out there that it can be beneficial in some instances, and also good evidence that it’s not for everyone.That being said, I believe there are many problems with this particular Science paper on caloric restriction.

In my opinion, a major issue with the findings is that the control monkeys (the ones not on caloric restriction) are fed ad libitum (meaning they can eat as much as they want). You might be able to guess the problem already, but let me give you an example just in case: I have a cat, and if I were to offer him a constant supply of what seems to me like gross, bland cat food, he would keep eating it until he would slip in a food coma. I think this goes for most species, including us (ever heard of the candy jar experiment?). Therefore, it’s very hard to judge if monkeys who eat as much as they want are eating the amount of food they should naturally be eating. Chances are they are eating more (breakfast, lunch and dinner are not served at regular hours in the wild). And this is particularly relevant because eating too much (or obesity) happens to be an important risk factor for all the diseases the study looks at (diabetes, cardiovascular problems, cancer, etc.).

Another issue with the article is that few of the findings show a statistically significant difference between the control and the calorie restricted groups, even though the researchers are studying a reasonably large number of monkeys. When your results are statistically significant, it means that what you are observing is unlikely to have occurred by chance. This concept is a hallmark of solid and convincing science findings and the media should be very careful not to hype findings that aren’t statistically significant. In addition, almost every single news article on this publication claimed that caloric restriction had an effect on longevity. While the study looks at age-associated diseases, the longevity (or life expectancy) parameter is not assessed at all (though the researchers do mention they plan on assessing this in the future).

Lastly, and perhaps most disturbing from my scientist point of view, the lead researcher in this study happens to be co-founder and member of the board of LifeGen Technologies, a company focusing on the impact of dietary interventions on the aging process. A little research on this company made it very clear to me that the more people buy this whole caloric restriction business, the more money the company makes. If that’s not a conflict of interest, I don’t know what is.

Now if you’ll excuse me, a new cupcake store just opened across from my building, and I must significantly increase the quality of my life by going over and eating a cupcake.

My cat, Mr Minou, is not a fan of caloric restriction.

Reference: Caloric restriction delays disease onset and mortality in rhesus monkeys. Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R. Science. 2009 Jul 10;325(5937):201-4.

Who wants a memory booster?

One of my first posts was about erasing memories. That may be useful if you suffer from post-traumatic stress disorder or if you just sat through the last installment of the Transformers movies, however, I can think of more people who would benefit from memory enhancement rather than memory erasure. One recent publication in Science hints that this may be just around the corner.

First, how do we know what animals remember? One way to test memory in rats is by using object recognition. You present the rat with two identical objects and let the animal explore them for a few minutes. Then you replace one of the objects with a new object, and typically, the rat will spend more time exploring the new object than the old one (presumably because the rat remembers the old one). By testing rat visual memory performance using this simple paradigm, the researchers established that rats were able to retain information about an object for up to 45 minutes, but after 60 minutes the objects were forgotten and treated as new unknowns. The researchers then injected a special protein in a specific part of the rat’s visual cortex, a part of the brain that is important for processing visual information. Following the injection, the rats were tested again for object recognition, and low and behold, the rats were now able to remember object information for longer than 45 minutes. How much longer? 60 minutes? 100 minutes? 1000 minutes? Actually it was 14 months. The rats went from being able to remember an object for 45 minutes to being able to remember it for 14 months.

Now the relevance of this article mainly lies in the identification of the function of a part of the visual cortex. To confirm their findings, the researchers took control rats (that didn’t receive the special drug) and inactivated the brain cells in the section of interest of the visual cortex (ok, they destroyed them). Those rats couldn’t remember objects at all. Interestingly, the researchers also showed that if you inject the special drug, then introduce a new object, and then destroy the brain cells, the rats will still remember the object for a long time, meaning this specific region of the visual cortex is important for making new memories but not for storing those memories. These are all important findings that further our understanding of visual memory.

But 14 months?? Surely this kind of memory enhancement won’t go unnoticed. The researchers claim that “the role of the RGS-14 protein in the enhancement of visual memory makes this protein an important pharmaceutical target for the treatment of (...) memory defects as well as for boosting the memory capacity”. That being said, I don’t think this drug will hit the shelves anytime soon. First, in the article, the researchers have to inject it directly into a specific brain region, and I certainly wouldn’t volunteer for that. Second, the drug affects an important, ubiquitous protein with many functions, and it’ll be a while before we tease out all the potential pitfalls of toying with something like that.

Regardless, with the aging population and the ever-increasing need (or want?) for maximum brain performance, there is a huge market for memory enhancers and the race is on to develop the first one. Now is the time to ask and answer all the ethical questions that surround this issue. If you had access to memory enhancers, would you use them? What if they were really expensive? What if they had detrimental side effects? What if they had detrimental side effects and everyone in school or work used them to enhance their performance relative to people who don’t use them (Tour de France, anyone?)?

Memory enhancers: useful drugs or can of worms?

The object recognition task

Reference: Role of layer 6 of V2 visual cortex in object-recognition memory. Lopez-Aranda, M.F., Lopez-Tellez, J.F., Navarro-Lobato, I., Masmudi-Martin, M., Gutierrez, A., Khan, Z.U. Science 2009 325:87-89.