Tuesday, December 20, 2011

Are We 'Defining' Our Salmon To Death?

StopTheSemanticsAnd
GetOnWithTheTestingVille


Alexandra Morton has started her dissection of the Cohen hearings and it makes for compelling reading.

One of the things, amongst many, that she wrote about today that I found interesting was the following:

"...we now have biological definitions of disease and legal definitions of disease in conflict with each other and this is not going to work..."


****

Now.

I have to be very clear here right from the outset.

I know nothing about fish biology.

But I do know a little bit about 'expression profiling', the wee bit of hybridizational sleight-of-hand that allows you to identify genes that are either turned 'on' (= more expression) or turned 'off' (= less expression) in individual biological samples.

These samples could come from anything alive, be they cells in a culture dish, patients in a hospital, or animals in the wild.

Ond once the profiling has been done on lots of samples you can then subdivide them into groups or clusters based their 'on'/'off' patterns, which are sometimes called by their fancy-schmancy name of 'gene signatures'.

Are you still with me?

Because if you are, you can pretty much understand Kristy Miller's Science paper.

You know, the one that has caused all the kerfuffle.

****

Now, what Miller et al. did was collect tiny biopsy samples from the gills of a whole bunch of Fraser River sockeye salmon that were caught either in the ocean or in the river.

Then they did the expression profiling.

And then they did the clustering based on their gene signatures.

Then they did something very cool, which they could only do because the fish were radio-tagged before they were released after the biopsy was taken.

In short, they figured out which of the sampled fish made it to their spawning grounds and which ones did not, the latter being a measure of 'mortality'.

And guess what....

One genomic signature stood out because it was associated with higher mortality rates, regardless where the fish were originally sampled.

Thus, it would seem that this signature, especially if it points towards something that happened to the fish way out in the ocean before they even started spawning, could be pretty important, eh?

So.

Miller et al. had look at the individual genes themselves and tried to figure out what that certain 'something' might have been.

And this is where things got a little speculative.

In a good way.

Because that's the way things are supposed to work in science. First you make a series of observations and then you make a speculative prediction (ie. an hypothesis) based on those observations.


And this, from the very last line of the paper, was the Miller group's hypothesis:

"Our hypothesis is that the genomic signal associated with elevated mortality is in response to a virus infecting fish before river entry and that persists to the spawning areas."


Now.

With an hypothesis like that, what are scientists supposed to do?

Why, 'test' it of course.

And if it stands up to every rigourous test a gazillion scientists can think of, it will get to hang around for awhile.

And if it doesn't it will be thrown on the scrap heap where it belongs and, hopefully, all the observational data generated by all that additional testing will lead to even better and more accurate predictions/hypotheses.

And that's how we will move forward and figure out what is really going on with the Fraser River sockeye.

All of which is just another way of saying that we will never, ever figure out what is happening by mounting PR counter-spin offensives and/or engaging in lawyer-driven semantic battles about the legaleese of disease.

So....It would appear that the only sensible thing is to do now is to unleash ALL the scientists and:

Let the testing begin!


OK?

.

8 comments:

Rusty M said...

Here we go again ... splitters vs clumpers
:)

RossK said...

It's actually both....

Ha!

.

Rusty M said...

Gotta tell you, as a former "icthyologist" i really enjoyed this blog today, especially the genetics stuff!

Just don't get me started on the consquences of the use of colchisine in these experiments ...

Chris said...

Well, as someone who actually wanted to be a scientist but flunked out of every single course I took, I loved this post too.

If you could excuse a stupid question from someone who also doesn't quite follow the whole food chain of government science agencies/university labs/independent mad scientists, who should we be looking to for this testing then, Dr K? Is it DFO? Environment Canada? Is there someone whose mandate covers this stuff now? Who do we address the petition/plea/threat to, given the results to date and the parties who have produced them?
(And thanks, by the way, for making sense of the latest twist in this mess.)

RossK said...

Chris--

Your question is easily answered by having a look at the author list on the Miller paper by clicking the little author affiliation 'tab' here.

If you do so the following will pop-up.

1Molecular Genetics Section, Pacific Biological Station, 3190 Hammond Bay Road, Fisheries and Oceans Canada, Nanaimo, BC V9T 6N7, Canada.

2Department of Forest Sciences, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.

3Conservation Biology Section, Pacific Biological Station, 3190 Hammond Bay Road, Fisheries and Oceans Canada, Nanaimo, BC V9T 6N7, Canada.

4Fisheries and Oceans Canada, Cooperative Resource Management Institute, School of Resource and Environmental Management, Simon Fraser University, Burnaby, BC V5A 1S6, Canada.

5Department of Psychiatry, Centre for High-Throughput Biology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.

6Fish Ecology and Conservation Physiology Laboratory, Department of Biology, Carleton University, Ottawa, ON K1S 5B6, Canada.

7LGL Limited Environmental Research Associates, Sidney, BC V8L 3Y8, Canada.

8Department of Zoology and Faculty of Land and Food Systems, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.


A fantastic list of employers and associations, etc., eh?

So that is the answer - let them all do it!....And let them all freely associate and exchange data and compete for government-backed, arms-length, peer-reviewed operating grant funding to do so (ie. no targetted/sponsored junk, which is becoming a real issue in Canadian science - I'll write about that sometime as well)

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Rusty M said...

RossK,
Rather than squandering your energies trying to get politicians, scientists and special interest groups working hand-in-hand ... you'd probably have more success surviving an afternoon in the Yankee Stadium bleachers wearing your BoSox hat and BoSox jacket.

RossK said...

Mr. M.--

In many realms you would be correct....However, in this case you are, I would most humbly suggest, wronger than Chocolate Roy wandering through the desert with a fungo bat in hand....

Why?

Because the geeks have already shown they can work together - the pols just have to get out of the way.

_____
(and besides, the colchicine seems to have addled your hippocampus...because, it is EdK that owns all that BoSox junk, not me)

Chris said...

Cheers, Capt. K. I think this is the part that answers my badly thought-out question:

"let them all freely associate and exchange data and compete for government-backed, arms-length, peer-reviewed operating grant funding to do so (ie. no targetted/sponsored junk, which is becoming a real issue in Canadian science - I'll write about that sometime as well)"