Stumbling into Progress

The most exciting phrase to hear in science, the one that heralds new discoveries, is not 'Eureka!' but 'That's funny...'

That's a quote from Isaac Asimov, an author and biochemist at Boston University; and it's true. Most real scientific advances, not pedestrian steps forward but really important progress, do not come about from a linear progression from hypothesis to experiment to result. No, most great advances are stumbled upon somewhat by accident. I had a personal run-in with this myself just this morning. I'm not sure that my observation can be considered a great advance. It may very well be but you can never know that at the time, this is why Nobel Prizes are usually awarded for work that is 20 or 30 years old. So here's an insight into the process of science for you and it's stuff like this that makes me feel like I've got the coolest job in the world.

So you'll need a bit of background. You've got immune cells called macrophages and they're really important in the early fight against infection, including influenza viruses. Removing macrophages from mice and/or pigs will kill them if you then infect them with an influenza strain that typically wouldn't kill. Okay? Okay. Well, influenza viruses don't replicate in macrophages. They can enter the cell but they can't replicate in there and make the macrophage spit out lots more flu particles. Well, that's only half true because I have found that bird flu strains actually WILL replicate in macrophages. That's really important. I have gone on to figure out which gene allows bird flu to replicate in macrophages (it wasn't that hard, there are only 11 genes after all). Well, I took a non-bird flu strain and engineered it to express the bird flu version of that gene. Lo, and behold, that non-bird flu now replicates in macrophages and kills mice with a vengeance.

The next question was 'how does this happen?' The most obvious place to look first was cell death. It's possible that non-bird flu strains (we'll call them seasonal flu) kill the macrophages so quickly that replication never gets underway. The alternative, then, would be that bird flu viruses keep the macrophage alive long enough to make lots of new copies of itself. Well, that actually isn't the case. I was expecting to say 'Eureka!' I've got it! But I did the experiment and instead I noticed some other information lying underneath the surface. I had my 'hmmm, that's funny' moment. What I noticed (this just happened this morning so I'm pretty excited) was that after being infected for 18 hours the macrophages infected with seasonal influenza strains had stopped dividing. Cells normally divide of course and these macrophages had stopped. The macrophages infected with bird flu, however, were still dividing. Apparently, bird flu interacts differently with the macrophage and keeps the cell in its normal cycle of division and this is somehow necessary for the virus to replicate inside the cell. Now I'm excited to get back to work next week and test this hypothesis directly.

So this is how science happens most of the time. I was asking one question (concerning cell death) but I was observant enough to realize that my question was not the right question. Serendipitously, the experiment I ran was set up to provide me the information that has proven vital to moving forward, even without my intending to acquire that information. I love science and you should too because it's awesome and learning to think like a scientist makes you a cooler person. I should mention that the reason I'm so excited about this is that I am not a patient person and I probably miss this kind of information more often than not. So it's quite a rare occurrence that this time I took the time to notice it rather than get discouraged that there were no differences in cell death.