Can gold cure us?

No it can’t. But in a recent report (1) scientists show how using tiny gold particles they were able to deliver a therapeutic agent called siRNA to cells and tissues.

siRNA are two short stretches of ribonucleic acid (RNA), chemically very similar to DNA. siRNA molecules whose sequence is properly designed can be very powerful in reducing the level of a target gene’s activity, most commonly by stopping the production of the protein the gene encodes for. In their paper, the authors focused on a protein called endothelial growth factor receptor, or EGFR, which is known to be hyperactive in certain types of cancer. As you probably figured out by now, reducing the levels of EGFR protein by siRNA might therefore be a very powerful way of helping some cancer patients. This study did not involve any human patients, but it did show that gold nanoparticles coated with siRNA molecules designed to reduce EGFR levels were successful in doing so in cultured cells and even in the skin of mice.

The facts that EGFR is hyperactive in some malignancies as well as that siRNA can reduce levels of proteins have been known for decades. So why has it taken so long for the scientists to come up with an effective way of combining the two pieces of knowledge into something effective. The problem is, putting siRNA into cells, especially when they are a part of a living organism, is not a straightforward task. It’s a bit simpler when the cells grow in culture – we can mix siRNA with some chemicals or stick it into modified viruses, which have the natural ability to inject DNA or RNA into cells. But when it comes to patients, using these chemicals or viruses is not something you can get patients to agree to easily. The mentioned chemicals can be simply toxic and viruses are, well, viruses. These two methods can not only be harmful to cells or organisms, but they can also modify the so-called gene expression, i.e. set of genes that are active in given cells. For example, cells in our bodies usually know that they have been infected by a virus and they activate all sorts of genes to alert the body’s immune system, often resulting in phenomena such as inflammation. Scientists do have means of checking how the profile of active genes inside cells changes after they’ve been subject to a certain type of treatment, and one of the fascinating things about the gold nanoparticles was that they changed the activity of only seven genes in cultured cells. Is that a lot? Well, a chemical reagent used to deliver the same siRNA to the same cells affected 427 genes. On top of that, the siRNA delivered on gold nanoparticles was still about 50% active after 4 days, at which time the siRNA delivered by the compared chemical completely lost its activity. But most importantly, when tested in animals, the gold-delivered siRNA managed to get into the majority of cells, stayed active in there for a long time, exerted a prominent effect, and no obvious signs of toxicity were apparent in the skin (site of application) or any other tested organ.

This approach, obviously, has its limitations. In the mentioned study, the researchers applied the gold nanoparticles only to the skin. They did not mention or speculate about how the golden spheres could be delivered to another organ. After all, it’s not only skin that might require some siRNA. Direct injections might be effective, but this certainly requires testing. Additionally, it would be hard to imagine this technique being used systematically, say, to treat metastatic cancer. After all the authors point out just how localised the action of this method is. Nonetheless, this is a very promising discovery that seems to have a whole multitude of pros and limited number of cons. Hopefully, in the near future some of our conditions will get treated by rubbing some gold into our skin…

1. Topical delivery of siRNA-based spherical nucleic acid nanoparticle conjugates for gene regulation.

Evolution of music

OK, this isn’t really totally in line with the life science theme of this blog, but I personally found it really cool! And this is because on one hand I am interested in biology and its concepts in general, and that includes evolution, and on the other hand – I love music. Additionally, I have always wondered, what makes popular music… popular? How come “Poker face” by Lady Gaga was such a hit while “Dance in the dark” not so much? And this study that I stumbled upon combines these two phenomena – evolution under selective pressure and music.

So, evolution under pressure. Without going into too much detail, when some organisms, which can be as simple as bacteria or as complex as humans, start living in a new environment that is in some way different than the previous one, they evolve. For instance, a long time ago people from Africa – where it’s hot – migrated north, where it’s colder. Breathing in cold air through black people’s wide nostrils was probably not very healthy as it cooled downs their respiratory tracts easily and facilitated viral infections. But some people randomly developed more narrow noses. The air takes slightly longer to go through such a narrow passage and so gets warmed up before it reaches deeper parts of our air pipes. Warm air is something viruses don’t like, so they were less likely to cause respiratory infections in narrow-nosed people. Less infections equals less death equals longer life equals more time and opportunity to produce offspring who would also have the narrow nostrils. And so, in the European climate the narrow-nose trait took over the wide-nose one.

The study I’m going to talk about next (1), conducted at Imperial College London, subjected music to a similar process of evolution under pressure. It infused short pieces of music with genetic features and as the selective pressure – it used human taste. How did they make the evolution of music happen? Well, first they designed some programs that created pieces of music made of notes occurring at pretty much random pitches and timings, or in other words, made of random melody and rhythm. Then they had several thousands of people listen to those musical samples and rate them based on how pleasant they were to listen to. The half of the samples that was least pleasant was eliminated (died), while the other half was allowed to randomly pair. Within pairs, bits of musical samples were exchanged between one another to create a new “daughter” piece of music, the same way that we get the genes from each of our two parents randomly. At this stage, the authors allowed for rare random changes in the “daughter” music samples, i.e. bits of music or rhythm not present in either of the “parent” tunes. This was mirroring mutations, like the occurrence of the narrow nostrils in white people. Obviously these random changes in the daughter pieces could be either pleasant for the listener or unpleasant and contributed to either higher or lower score they received. And then, again, the highest-scoring 50% of samples was allowed to “survive” and “have sex” and produce the next generation of musical offspring. If you go to http://soundcloud.com/uncoolbob/sets/darwintunes/, you will be able to listen to the whole concept presented by Dr. MacCallum, the lead author of the whole project (the first track on the list), as well as music samples selected at certain “generations”. It is fascinating to hear how music in these samples gradually changes from random noise-like sequences of sounds to quite organised, structured and pleasant pieces of music.

Obviously, the study doesn’t exactly mirror how pop music is created. Firstly, music as we know it did not start as a random collection of sounds that sounded plain annoying. Secondly, new pieces of music do not arise as hybrids of existing songs (well, for the most). I mean, even if someone did put together “Bad romance” with “Like a prayer”, I can imagine this mix gaining some popularity but I struggle to see it staying at the top of pop lists as long as either of these two songs did.

Nonetheless, the whole concept is very interesting and the samples are just fun to listen to!

1. Evolution of music by public choice.