tag:blogger.com,1999:blog-4062334622304514923.post7534114219995138608..comments2024-02-23T03:15:18.221-08:00Comments on Rule of 6ix: Certain strains put a strain on virus researchConnor Bhttp://www.blogger.com/profile/08132413724023944783noreply@blogger.comBlogger6125tag:blogger.com,1999:blog-4062334622304514923.post-62053418775257775162012-01-25T01:15:46.348-08:002012-01-25T01:15:46.348-08:00Sure, but I think that any work on pathogenesis in...Sure, but I think that any work on pathogenesis in vivo needs to be as close as possible to what you actually observe. Especially if this is being used for the likes of antibiotics/vaccine trials. You could waste a lot of money on something that is not real. But of course for other subjects I don't think it's necessarily so important. Although, if you can develop a more wild-type model, why not?<br /><br />I agree with the lab strains being clinical ones at some point in time. That's something you will just have to keep updating. As long as people are using a clinical one with low passage history then it should ultimately be fine. I think. It's just it seems some people are OK using a 50+ passaged microbe and they think what they see is real.Connor Bhttps://www.blogger.com/profile/08132413724023944783noreply@blogger.comtag:blogger.com,1999:blog-4062334622304514923.post-59248253356606739062012-01-24T13:30:19.612-08:002012-01-24T13:30:19.612-08:00The utility of clinical strains needs to be weighe...The utility of clinical strains needs to be weighed up depending on what you need from the model. In some cases it could well be worth it to bang your head against a brick wall of failure for 3 years until finally cracking the problem. In others, wasting time developing a new model when there are perfectly relevant ones already available may not be worth it. <br />To be fair, most common lab strains did start out as clinical isolates. But then the world moves on, and the strains circulating in the community change, and they become irrelevant. Or they get passaged into impotence.<br /> Equally, today's hot new clinical strain could be tomorrow's lab adapted strain. Working with clinical strains shortens the distance between the bench and the bedside. But it doesn't eradicate it. <br />There will still be biases based on what gets sent from the wards or the community, and what can grow in the lab. To some extent, there will always be a need to play catch up with microbes evolving in the community.The Defective Brainhttps://www.blogger.com/profile/04753079302510607981noreply@blogger.comtag:blogger.com,1999:blog-4062334622304514923.post-56388757954391466952012-01-24T02:07:21.048-08:002012-01-24T02:07:21.048-08:00Defective Brain - it is a very important topic and...Defective Brain - it is a very important topic and sadly it isn't really talked about, officially at least. If you are doing tissue culture work with mammalian cells for example, quite recently people have begun to focus on primary cells but the same cannot be said about true 'wild-type' pathogens. <br /><br />The DH5alpha thing is hilarious but quite worrying how that can be done. <br /><br />I agree whole-heartedly with your last two points, but sometimes when you have funding for three years it's not that easy. But maybe with all the sequencing advances etc this might become a non-problem in the next couple of years.Connor Bhttps://www.blogger.com/profile/08132413724023944783noreply@blogger.comtag:blogger.com,1999:blog-4062334622304514923.post-61545129181431432822012-01-23T07:24:55.436-08:002012-01-23T07:24:55.436-08:00Great post on a really important topic that no-one...Great post on a really important topic that no-one likes to talk about.<br />I would like to think that most scientists give some thought to what bacterial strains they use as their models, but I have been at a prize winning conference presentation where someone used DH5alpha e.coli for a mouse model of EHEC. For those of you who didn't immediately facepalm upon reading that, it's like using a toothless blind chihuahua to model a bear attack. <br />But there are a few arguments for using "lab adapted" strains of bacteria. Often lab adapted strains have publicly available genomes, and are more amenable to genetic manipulation. So they can be used to analyse specific metabolic or pathogenic processes. <br />There are some who I've worked with who take the view that "lab -adapted" strains are an excuse to not develop better techniques for working with clinical strains. <br />Working with strains that no-one else has worked on increases your chance of finding something no-one else has spotted before, and isn't that why we went into science in the first place ?The Defective Brainhttps://www.blogger.com/profile/04753079302510607981noreply@blogger.comtag:blogger.com,1999:blog-4062334622304514923.post-29815265377260377792012-01-23T03:13:57.230-08:002012-01-23T03:13:57.230-08:00Joe, thanks for your comments - I had in particula...Joe, thanks for your comments - I had in particular thought of the HCV situation. <br /><br />But I think this example is different from the others where groups do - as you say - stick their head in the sand and fail to discuss that their results are based on a lab adapted strain. <br /><br />Maybe they don't realise that they are doing but I think it would be hard for any PI not to know what they are working with. <br /><br />I think compromise is important but if you are a group leader wanting to work on a certain aspect of a virus, why not go and develop the proper tools to do so correctly? Without backing your work up with wild-type/clinical isolates I find it extremely difficult to interpret the work. More so with pathogenesis work that relies on every aspect of the viral life cycle.Connor Bhttps://www.blogger.com/profile/08132413724023944783noreply@blogger.comtag:blogger.com,1999:blog-4062334622304514923.post-54770242717724676282012-01-23T02:14:33.772-08:002012-01-23T02:14:33.772-08:00Some very good points raised.
Lab adapted virus s...Some very good points raised.<br /><br />Lab adapted virus strains often lead to misleading data that poorly reflect the situation in vivo. This is particularly a problem when scientists don't realise the virus is adapted, or in some cases stick their head in the sand and ignore the fact.<br /><br />However, almost all biological research involves compromise. For instance, primary isolates of hepatitis C virus (HCV) will not grow sufficiently well in tissue culture to allow robust study of the virus life cycle. This held back HCV research for years. But in ~2005 a virus taken from a patient in Japan with raging acute hepatitis turned out to replicate just fine in the lab. <br /><br />By virtue of its ability to grow in vitro this virus cannot be considered normal. However, it opened the door to thousands of fantastic studies in to HCV and could eventually lead to new therapies. <br /><br />Compromises will always be necessary. But by acknowledging the caveats and interpreting the data with care, valuable work can be done. Although, problems will continue to arise when scientists unwittingly or willingly ignore the intrinsic flaws in experimental systems.Anonymoushttps://www.blogger.com/profile/13492460803118161030noreply@blogger.com