In re: Darwinian Medicine

Steven_Projan at INTERNETMAIL.PR.CYANAMID.COM Steven_Projan at INTERNETMAIL.PR.CYANAMID.COM
Tue Oct 10 07:51:01 EST 1995


While there is a metabolic cost to maintaining plasmids and transposons in a 
bacterial cell the view that these are readily dispensible genetic elements is a 
bit off the mark.

Many plasmids and transposons display remarkable stability even after hundreds 
of generations of non-selective growth in vitro.  In fact both plasmids and 
transposons have been sucecssfully used as markers in tracking epidemic strains 
of bacteria thus indicating that they are also realtively stable in vivo.

In the case of plasmids many have developed intricate systems which ensure 
stability.  Some plasmids (as well as transposons) encode production of 
bacteriocins which can kill closely related (e.g. plasmid-negative cells), the 
work of David Figurski on kil and kor genes reveals an amazingly complex group 
of plasmid encoded proteins designed to ensure the stability of certain types of 
plasmids.  Stanley Cohen, many years ago, described a locus on the tetracycline 
resistance plasmid pSC101 called par which enables the plasmid to be passed onto 
to both daughter cells after cell division.  There are many other such examples 
of strategies plasmids use ensure their stable inheritance.

It is perhaps best to think of the mobile genetic elements as organisms in and 
of themselves (see the 1980 article in Scientific American by Novick on 
"Plasmids").  These "organisms" have their own agenda (survival)  which in many 
cases result in their stable inheritance despite the metabolic burden imposed on 
the host cell.  

That being stated it makes good "Darwinian" sense to use antibiotics in a non-
abusive manner.  However we start running into interesting conflicts between 
what is best for the individual patient and the society at large.  For example:  
treating enteric diseases with antibiotics in developing countries where there 
is poor sanitation and hygiene results in a rapid spread of resistance rendering 
the antibiotic virtually useless in weeks, but is it ethical not to supply the 
antibiotics in the first place?  Do we insist that developing countries make 
proper sanitation a pre-requisite before they have access to antimicrobial 
agents?

As far as antimicrobial resistant bacteria are concerned:

Select for them and they will come.

Steve Projan
Wyeth-Ayerst Research
Pearl River, New York



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