Re: genome research project on oldest people for cancer clues

Archimedes Plutonium wrote:

> I understand that human bodies have cancers all the time and
> constantly throughout life but these cancers never develop because the
> body immune system
> destroys the cancer before it becomes out of control. I do not know
> how true that picture is. But let us say there is some truth to the
> idea.
This theory, called the "Immune Surveillance Theory" was a popular idea 
until recently.  Unfortunately studies using mice lacking all T-cells 
and B-cells (T-cells appear to be the main anti-cancer cell in our 
bodies) found that these mice didn't have higher incidences of cancer 
then did "normal mice".  Since that experiment several other experiments 
have confirmed these results.  As such most immunologists no longer 
believe this theory.  This came as a big disappointment to many of us, 
as there is no question in the scientific literature that you can 
generate successful immune responses against tumours, but these seem to 
be rare outside of the laboratory.

> Since we have genome project with the ability to map the entire genome
> of an individual. Then it would make much sense to map the genome of
> the oldest humans alive because their genetic coding is more resistant
> to disease especially cancer than the majority of other genomes.
Not necessarily.  Most age-related disease (cancer, heart disease, 
diabetes, etc., etc., etc.) have both genetic and environmental factors 
associated with them.  To make things worse most of these diseases 
involve many genes, none of which guarantee disease, but each of which 
increase your risk of getting the disease.  So if you find a very old 
healthy person there is no guaranteed a genetic sequence will tell you 
anything - they may have "risk" genes but have never been exposed to 
environmental factors, and thus didn't develop the disease.  Likewise, a 
person with a disease (i.e. lung cancer) may have none of the genetic 
factors associated with that disease, but were heavily exposed to an 
environmental factor (i.e. smoking) which caused the disease.

There are a variety of techniques which allow us to find disease genes.  
Basically, they involve looking at a group of people with the same 
disease, and you look for a genetic marker which is found in most of the 
people.  Usually you will find several markers, with more investigation 
you can usually find specific genes.  The hard part is showing those 
genes are involved in the disease process.  Sometimes we do the reverse 
- start with a gene and look to see if people with a disease have a 
mutation in the gene.  Either way you start with a diseased population, 
as it is easier to identify things they have in common then things that 
are different to "normal" people.

> So, it would make sense to contact the oldest humans around for DNA
> and to map their entire genome and then compare those genomes for
> answers as to why they can live so long without contracting cancer or
> many other diseases.
But how do you identify what is different from the rest of us?  Today we 
only have 1 "complete" human genome, so we don't exactly have a lot to 
compare to.  Even with modern genome sequencing equipment it still will 
take at least one year to sequence a human genome (likely longer), so 
this would be a very inefficient approach.  And if you had a large 
enough data base you would still be looking for the same things we look 
for today - common markers within the genome which are associated with a 
disease.  The traditional techniques of looking for disease-linked 
markers has been very successful to date, and will remain far more 
effective then your idea for many years to come.  Until we can sequence 
the entire genome of a person in a resonable amount of time your 
technique will be much slower then what we currently use.

Bryan Heit