Becoming a critical reader in science

If you're a regular reader of my post, then you may have noticed I'm often critical of research papers or news stories I come across. I'm not doing that to be a smart-aleck, but rather to demonstrate a regular part of a scientist's job-to figure out if the ideas and data make sense as they are presented, otherwise known as critical reading. A recent article in Businessweek described a clinical trial slated to begin in September 2012. It was designed to determining whether infusing stem cells from umbilical cord blood into autistic children will improve behavioral functions. This study is the first of its kind in the US and I'm glad to learn somebody is actually doing a controlled experiment on the efficacy of stem cells on autism rather than relying on anecdotes. I also think we can use this article as a launching point to demonstrate how to critically read a science article.

The article paraphrased several possibilities that could explain how stem cells may change behavior in autistic brains. The first possibility is the stem cells may develop into brand new neurons to replace damaged ones. The second is the stem cells may help repair abnormal neural connections. The third is the stem cells may alleviate brain inflammation.

To begin narrowing down the possibilities, you will first need to know about the blood brain barrier (BBB). The BBB forms a physiological barrier that prevents direct contact between blood and the brain, and allows only certain small molecules to cross, like oxygen or hormones. It does a pretty good job of preventing bigger objects like viruses and bacteria from entering the brain. These facts weren't mentioned in the article and I thought of them only because I know a little about neuroanatomy. So, assuming stem cells are big and are delivered via the bloodstream, how are they supposed to get into the brain and work their magic? Like any nit-picky researcher might do, I started browsing the web for information that pertains to human cord blood cells crossing the BBB and affecting brain function (Note: it is indeed the reader's responsibility to research stuff if you encounter concepts you don't understand). The evidences from scientific literature are conflicted on this topic. For example, Chen et al.¹ claimed in 2001 that human cord blood infused into rats showed the cells were able to cross the BBB and could help heal brain injury. It was sort of confirmed by other similar studies^2-3, but if you look at the list of authors you'll notice the papers shared a few of the same names so I don't count that as independent verification. On the nay-sayer's side, there are at least two independent reports^4-5 that concluded cord blood infusions do not improve brain function. So, we may reasonably discount the notion that cord blood cells will enter the brain and develop into new neurons (at least not under the conditions described for this trial), or directly repair neural connections. For this idea to work, it will probably require an invasive surgery to insert the cells into the brain, and the risk of brain injury makes it an unattractive option. It may be possible to snort the cells into the brain⁶, but this method remains sketchy⁷. It's a really neat idea though!

If cord blood infusions have any observable effects, my best guess is the stem cells secrete molecules into the bloodstream that can cross the BBB and indirectly affect brain function. These molecules may very well contribute to neuron repair or reduce brain inflammation. We'll have to wait until the trial ends to have a more solid answer, but I hope I've helped to sieve through some possibilities and maybe showed you how to become a critical reader in science. Critical reading is not that hard, but it certainly is an acquired skill. The key is to be well-read enough so you can instantly compare your cache of random knowledge with what you're reading. Failing that, have a web browser open so you can research any concepts you don't understand (and thus build up your cache). You'll get better with practice and it'll soon be second nature.

Photo credit: © barn storming via Flickr (http://www.flickr.com/photos/wienerp/420626768/)

References:

1. Chen J, et al. Intravenous administration of human umbilical cord blood reduces behavioral deficits after stroke in rats. Stroke 32(11):2682-8 (2001).
2. Lu D, et al. Intravenous administration of human umbilical cord blood reduces neurological deficit in the rat after traumatic brain injury. Cell Transplant 11(3):275-81 (2002).
3. Vendrame M, et al. Infusion of human umbilical cord blood cells in a rat model of stroke dose-dependently rescues behavioral deficits and reduces infarct volume. Stroke 35(10):2390-5 (2004).
4. Mäkinen S, et al. Human umbilical cord blood cells do not improve sensorimotor or cognitive outcome following transient middle cerebral artery occlusion in rats. Brain Res 6;1123(1):207-15 (2006).
5. Zawadzka M, et al. Lack of migration and neurological benefits after infusion of umbilical cord blood cells in ischemic brain injury. Acta Neurobiol Exp (Wars) 69(1):46-51 (2009).
6. Danielyan L, et al. Intranasal delivery of cells to the brain. Eur J Cell Biol 88(6):315-24 (2009).
7. Chartoff EH, et al. Detection of intranasally delivered bone marrow-derived mesenchymal stromal cells in the lesioned mouse brain: a cautionary report. Stem Cells Int 2011:586586 (2011).