[Moderator's note: This is an extra long post in what started out to be
a rather short FML, so posting it all at once and holding off on any
other Bob C posts for a few days.  And as I was editing this, another
large post came in, so forget that part about a short FML!  BIG]
 
writing.  I just figure I said what I wanted to say, I usually say a lot
of it, and there is not a need to argue endlessly on the subject.  This
time, I will respond because someone needs to address the statements, but
I will only do it once and will not engage in prolonged debate.  There is
no arguing with people who feel their personal beliefs are sacred, and I
will have nothing to do with a "religious debate" that involves stones.
My name may not be Stephen, but I like ferrets to rock my world.  So,
enjoy this response because *I* *won't* *make* *another* *one*!  This is
it.  That will let everyone else have the last word, and they are welcome
to it.  I have faith the FML membership can identify off-topic attacks
and a lack of argumentative coherence, when people evade questions or
ignore them, and I know Bill will bounce any post that attacks me in a
personal way.  In November, I'll write a series of cystine stone posts.
In the meantime, I have 4 chapters to write for yet-to-be-published
veterinary texts that take precedence, besides the skeletal and dental
analysis I'm getting published, traveling all over the country to discuss
ferret dental health and other topics, and formulating some new ferret
treats and foods.  I'll get back to this subject when I can.
 
Sukie said:
>Replace "decade" with "year" and it is more accurate recently for
>what is being seen in just one to two of the university urolith labs
>(depending on the figure used).  So, it makes sense as a possible
>typo (?)."
 
Bob: No, it is not a typo.  I could ask you prove your numbers with a
published paper, but I won't because I know how many papers on ferrets
with cystine stones have been published.  I only use numbers I know are
correct, which means if they aren't ones that *I* have generated, then
they need to have been published.  Anything else is anecdotal and
untested, which has no scientific bearing in a fair and unbiased
debate--which the members of this list deserve.  Nonetheless, Sukie's
statement is inflammatory rather than elucidative because I didn't hold
the "cystine side" to the same burden of proof I am typically held to (I
could delve into this subject at great length and provide documented
evidence from this and other lists.  Let's not go there, OK?  Some sewers
should never be entered, and the ferret community doesn't need that crap
spread on the internet.).  I gave away the benefit of the doubt on the
number of cystine stones with my statement, "Even if there were hundreds
of ferrets with cystine stones..." This statement more than concedes the
possibility that there may be more incidences than reported in the
literature, and concedes it well beyond the point to which Sukie can
provide any support or evidence.
 
The problem with Sukie's statement is that it makes it seem as if the
original argument is wrong.  I clearly said, "hundreds of ferrets," which
is a number greater than Sukie inferred to or can prove.  My point, "Even
if there were hundreds of ferrets with cystine stones during that period
of time, the chances of any one ferret having the disease is extremely
remote" has not been refuted by her inflammatory rebuttal.  We can
quibble about the exact numbers, but even if there were a THOUSAND
ferrets with the problem, compared to the millions of ferrets currently
living in the USA, "the chances of any one ferret having the disease is
extremely remote" remains a TRUE statement.  If anything, Sukie's
insistence that there are dozens per year only proves my point all the
more, since "hundred" is the larger number.
 
Besides, how correct IS her estimate?  Is it in fact dozens of ferrets
or dozens of stones?  How many ferrets are actually involved?  Has the
increasing number of ferrets in the USA been statistically accounted
for?  Are these stones from a single geographic region, or randomly
distributed?  Was the original sampling from the vets random?  Is this a
representative sample?  But even if it was dozens of ferrets per year,
randomly sampled over a large geographic area, what does that tell us?
Perhaps all we are seeing is a mistake caused by a couple of breeders,
and the blip in the number of cases doesn't apply to the rest of the
country.  See the problem with anecdotal evidence?  THAT is why I only
use my own, or documented and published numbers.
 
The rejection of anecdotal evidence has NOTHING to do with the
reliability of the people making the reports; they can be extremely
honest and true, but it is just that the statements cannot be
scientifically verified.  We cannot make ANY conclusion from them other
than noting they exist, including that the incidents are increasing in
number as Sukie consistently suggests.  But this is all a digression.
The debate point here is that I said the chances of a ferret getting a
cystine stone was extremely small, that sick animals should be treated
with due haste, and the remainder of the population should not be
punished with possible insulinomas and other diseases linked to a high
carbohydrate load diet because of an unfortunate few.  I didn't hold the
opposition to proving their numbers, and I have no desire to do so now.
I had already conceded the number could be higher, and Sukie's insistence
that the numbers could be dozens per years rather than decades was
rendered moot before she even made it.  Her objection does nothing to
disprove my point the problem is statistically minor, which makes her
rebuttal inflammatory and an appeal to emotion, NOT a scientific rebut.
 
Sukie said:
>Also, remember that most stones don't get tested; instead there is a
>tendency to assume that they are going to be the more common struvite
>stones.
 
Bob: This is a problem in sampling theory.  Archaeologists have to deal
with this problem all the time, which is why sampling theory is such an
important aspect of archaeology and has been for the last half century.
The crux of the problem is if the sampling is random or not.  If the
sampling is random, then the numbers are likely to be true.  The problem
is that vets are like doctors; they don't actually randomly sample.  For
example, how many vets would remove a mast cell growth off a ferret's
tail and send it in for microscopic testing?  Not many!  They know what
it is, they know it is harmless, and most are unwilling to charge a
client a bundle of money to prove what they already know.
 
The same is true for doctors; I have a small number of squamous cell
tumors burned off the side of my head every year; they aren't sampled,
but the single one that might have been a melanoma was.  Think about this
for a moment.  If over a period of time 100 squamous cell tumors were
removed, and out of that 10 were sampled to test for melanoma, out of
which 1 sample tested positive, what would the LAB see?  The lab sampled
ratio would be 1:10, which is a higher number than the true population
ratio of 1:100.  This could be interpreted as a tremendous increase of
disease, simply because the sample was not randomly collected.  Now, to
make matters worse, what if in that same period of time the population
doubled?  The lab might see it as a BIG increase in disease, even if it
isn't.  This happens ALL the time.
 
In the statistics for abnormal tail growths AS SEEN BY PATHOLOGY LABS,
mast cell growths on tails are underestimated because they are sent in
at a lower rate resulting in biased sampling.  The so-called increase in
numbers of cystine stones could be echoing nothing more than that vets
are noticing some stones don't look "normal," and so are sending them
in for analysis while discarding the "normal" looking stones.  If so,
this means the stones are not being randomly sampled.  That could mean
they are being sampled in numbers HIGHER than in the general population!
I've SEEN cystine stones, as well as dozens of other types, and I might
not know they are made of cystine, but I DO know they look different.  My
guess is most experienced vets would recognize that a cystine stone looks
different.  The reason is because MOST vets would see them in some breeds
of dogs (and some cats) and are acquainted with them.  There is not a
single fragment of evidence that suggests these stones are being randomly
sampled (that is, ALL stones from a single clinic during a specific
period of collection are analyzed), and THAT means ANYONE suggesting the
incidence is increasing in the general population is making a huge
assumption.  We were all taught what that means.
 
You can dislike this argument all you want, but it doesn't change the
need for a statistical study to determine if the samples are random or
not.  There has to be a reliable baseline in order to judge if an
increase in disease is real, or just a misunderstanding of numbers.  My
argument has NEVER been that cystine stones are not dangerous, but that
we should not let that particular problem influence how we feed the vast
majority of healthy ferrets.
 
Sukie said;
>To top it off a number that get tested never wind up in urolith labs --
>just with one of the very many pathologists used by vets."
 
Bob: This actually supports my observation that the sampling of cystine
stones is probably NOT random, but that is not why I am replying to the
statement.  Sukie's statement is EXTREMELY condescending towards
pathologists, even to the point of suggesting they are unqualified to
test the stones.  I think if I was a pathologist, I would be a bit upset
if I read a statement like this.  Having WORKED in a pathology lab, I can
say without a doubt the extreme majority of pathologists with access to a
polarizing microscope can easily distinguish between stone types.  Even
if one pathologist has a problem, which can be a possibility, they tend
to run in packs like wolves, and all the others aggressively lend a hand
in attacking the problem.  Hell, with a microscope and a few easily
obtained chemicals, I--or anyone on the FML shown what to look for--
can distinguish stone types with a bit of practice.  In my urinalysis
classes, I used a simple mnemonic to remind myself of what cystine
crystals in urine looked like: "Stop for Cystine!" That is because
cystine crystals look like transparent amber hexagonal stop signs, and
they look that way in ANY species -- it's a molecular thang.  Shape is
dependent on molecular composition.  Calcium oxalate crystals look like
tetrahedrons, triple phosphate crystals (struvite, or magnesium ammonium
phosphate) look like rectangular coffin lids, and uric acid crystals are
rhomboid shaped, and sometimes arranged in a floral pattern.  Tricalcium
phosphates can also form stop sign-shaped crystals, but they can be
identified because they are not birefringent while cystine crystals are
moderately so (no space to explain the term; they just look different
under polarized light).  Sometimes the crystals are amorphous, meaning
they have no definable shape.  They can still be identified; add acid and
if the crystal dissolves, it was probably triple phosphate.  Add base and
if the crystal dissolves, it was probably calcium oxalate.  If you add
acid and nothing happens, then add base and nothing happens, it is
probably some type of protein crystal, or perhaps some other unusual type
(drugs come to mind).  The presence of urinary crystals doesn't mean
there are stones, a degree of crystallization is normal in everyone and
every animal, but if you have stones, the chances are extremely good you
will see some of the crystals that built it.  You might have other stone
types as well, but here is a cool thing about cystinuria, the disease
that causes cystine stones.  Because cystine is ALWAYS present in
abnormal amounts, those with the disease almost always have cystine
crystals in their urine, even if they don't make stones.  Now, I am not
an urologist, but plop me in front of a microscope with a polarizing
stage, give me small bottles of acid and base, and I could do an adequate
job of identifying stones from any species, and I would know when to ask
for help.  A pathologist would easily out-perform my attempts.  So you
see, I take exception to the suppositional statement that any "one of the
very many pathologists used by vets" is incapable of identifying a
cystine stone.  I can do it, almost anyone on the FML with a photo of the
stones in front of them can do it, and I know most pathologists can do
it.  It isn't exactly rocket science, but I think it could be called
"rock science."
 
Sukie said,
>The change in rates is why there is concern among researchers about
>possible vulnerabilities been pushed; the figures changed suddenly and
>markedly."
 
Bob: You don't know this.  If you did, there would be evidence in print.
Where is the statistical analysis showing a sudden and marked change?
Or is this just an assumption?  This is an example of an inflammatory
statement that biases the reader without providing adequate supporting
evidence.  Use the dental analysis I have been presenting as an example.
Put 400 pet ferret skulls in front of you.  If dental tartar is present
on a tooth, you count it.  You don't worry if the tooth is completely
covered as opposed to half covered because skeletal rendering techniques
could have flaked some off.  Rather, you look at all the teeth to see a
pattern.  If tartar is on 1 tooth per side, call it minor, 2 teeth is
moderate, 3 is extensive, and 4 or more is severe.  Count both sides and
divide by half.  If I noted 98% of the ferret skulls had moderate or
worse dental tartar, what would that mean?  It really doesn't mean
anything because there is no comparison.  But, look at 400 black-footed
ferrets, polecats, and New Zealand feral ferrets, using the exact same
criteria, and see a 5% rate of dental tartar, and now, THAT is a
comparison!  Now you can say there is a sudden and marked increase in
dental tartar when moving from a natural diet to one primarily made of
kibble.  There is NO such comparison in the cystine stone controversy.
Maybe the increase is real, maybe it is an artifact of better
observation, or maybe it is an epiphenomenon of an increase in the number
of pet ferrets maintained in captivity.  Without a baseline, you simply
do not know, which is why that statement is inaccurate and inflammatory.
It is an opinion, not a fact.
 
Sukie said:
>Are cystine stones increasing?  [middle stuff edited for space] Sure.
>What can't be done is to draw conclusions before the data is in.
 
Bob: So what is Sukie doing?  There has been numerous times on the FML
that Sukie has stated outright that high-protein diets are a danger
because of the threat of cystine stones.  We have all read it.  Isn't
that a perfect example of drawing "conclusions before the data is in"?
Of course it is!!  However, the problem here goes beyond this petty
example.  The problem with cystine stones is one of the individual
ferret, while the problem of carbohydrates in kibble is one of the ferret
population as a whole.  Let me explain; EVERY ferret, even those with a
cystine problem, has a high protein, low carbohydrate requirement.
Suggesting otherwise would be like suggesting that because some humans
have IBD, their dietary requirements are likewise different.  IBD
sufferers have to adapt their individual diet to suit their particular
circumstances, but they still need a basic set of nutrients that are
unchanged because of their disease.  More importantly, just because they
have medical problems, it is no reason to make all humans change to a
similar diet.  My point, which is CONSISTENTLY missed or IGNORED, is that
ferrets with cystine stones, as tragic as those circumstances are and as
horrific as their health problems might be, should be treated as
individuals, and such treatment should not apply to the ferret population
as a whole.  Maybe I should restate this 3 or 4 times in a row.  Wait!
I have.  <sigh>  Sukie said: "Of course, there is a useful, cheap, fast,
and easy test which finds some (all?) of the ferrets with vulnerability
to cystine stones, so it's kind of a no-brainer to do it periodically for
any ferret on a high protein diet.  The question is more at what stage it
finds them since that it not well enough known.  Just check the urine pH.
If it too acidic then the ferret has a decent chance of being at risk for
struvite stones so protein will need to be reduced (BUT if it is too
alkaline that ferret is at risk for struvite stones and needs vegetable
intake reduced).
 
Bob: I had to read this one a few times...if the pH is too acidic the
ferret is at risk of struvite stones, but if it is too alkaline, they are
at risk for struvite stones?  I know this is some kind of a muddled typo
and you meant cystine stones in the first instance, so I will just
basically ignore it.  But it does beg for an explanation of urine pH, a
protein diet, and stones.
 
First of all, urine pH is NOT an adequate screening criterion for
discovering which individuals can have cystine stones.  It is like
saying the murderer was an angry woman, so all angry women are murderers.
I am white but not a racist, male but not sexist, patriotic but not
Republican, and an evolutionist but not an atheist.  Having acidic urine
in no way means your ferret has the autosomal recessive trait that causes
cystine problems.  IF your ferret has been diagnosed with cystine
problems, THEN pH is a somewhat adequate screening test to see if there
is an individual risk for developing stones, but if your ferret does not
have the cystine problem, a pH test does not mean the ferret will
suddenly contract the disease.  You can't catch the disease--you are born
with it.  Also, while cystinuric ferrets with acidic urine have a higher
risk of forming stones, hydration is also an important factor; pH neutral
urine with a lot of dissolved material is more risky than acidic urine
diluted with a lot of water.
 
Most crystals found in acidic urine are amorphous urates, calcium
oxalate, and uric acid; if there are stones present, they are probably of
these composition.  Crystals generally found in alkaline urine are
amorphous phosphates, triple phosphates (= struvite), calcium phosphates,
calcium carbonates, and ammonium biurates.  Cystine crystals are
generally found in acidic urine, however, they can be found in pH neutral
urine, and on rare occasions in alkaline urine (why hydration is so
critically important).
 
Cystine is an amino acid that is not as soluble in urine as most other
amino acids.  There are four such amino acids: Cystine, Ornithine,
Lysine, and Arginine (C-O-L-A).  The COLA amino acids have pH dependent
solubility.  For example, at pH 5.0 (moderately acidic), the saturation
point of cystine is 300 mg/L, while at a pH of 7.4 (slightly basic) it is
500 mg/L.  However, pH is only one factor involved in the precipitation
of the COLAs; the other is how much stuff is dissolved in the urine.
Urine concentration in ferrets with healthy kidneys is a factor of
hydration; dehydrated ferrets have more concentrated urine, and THAT is
not necessarily shown in a pH test.  There are four basic requirements to
making cystine stones:
a) the recessive genetic trait for poor COLA renal tubule transport,
b) a diet containing COLA amino acids,
c) acidic urine pH, and
d) poor hydration.
However, the only time factors b, c, and d are a problem is in the
presence of factor a.  Without the genetic predisposition for COLA
transportation problems in the renal yubules, cystine stones will
almost never occur.  Well, maybe if your diet is mostly COLA.
 
There is one aspect of all this that is rarely mentioned, which is the pH
of the urine inside the kidney.  Just because the urine in the bladder is
neutral or alkaline, it doesn't mean the urine in the proximal tubules is
as well.  The urine there tends to always have a low pH because of the
presence of short chain proteins.  This is why hydration seems be to a
better solution for preventing stones than the modification of diet.
However, it is hard to get a ferret to drink water in excess of needs,
so diet tends to be the only solution for the average pet owner.  You
can lead a ferret to water, but you can't make him use the litter box.
 
Because acidic, concentrated urine is not an adequate screen for cystine
stones (they probably have predictive value in a ferret with the
autosomal recessive trait, but cannot screen for the disease), what would
be a good, cheap screen?  Microscopic urinalysis of centrifuged urine
sediments comes to mind.  It is easy and relatively cheap and can be done
in a few minutes in the vet's office.  Observing hexagonal transparent
yellow cystine crystals in the urine sediment would be a fairly good
screen for the disease, and they would be seen even if the ferret never
forms a cystine stone.  Not enough urine?  A small amount of sodium
nitroprusside could be added; if it turns purple-red, it is a good
indication cystine is present in the urine in pathological amounts, and
you can do that to urine on a table.  Chemical analysis of the urine is
a good test; normal urine has less than 30 mg/d of cystine, while humans
and animals with cystinuria can have levels greater than 250 mg/d,
clearly abnormal.  Cystine stones, like the crystals, are amber in color,
and are radiopaque to x-rays.  Chemical analysis is diagnostic.  ALL are
good screens and easily available to a vet, and all are better than pH.
 
Having actually seen cystine stones, I can tell you they simply do not
LOOK like struvite stones, having a different color and form.  The grainy
stuff in mucous might be hard to identify, but the granules are amber
under the microscope.  I can't believe a vet, especially one that is
acquainted with what is a relatively common problem in some dog breeds,
would see an amber stone and assume it was struvite.  I would think the
opposite would be true; they would see something that seems unusual, so
would tend to send it in for analysis.  Unfortunately, this is NOT random
sampling, so the numbers of reported cystine stones have a very good
chance of being over-estimated.  It is like apples and oranges.  It is
easy to spot the odd apple in a bushel of oranges; they just stand out
and tend to get picked first, so are sampled at a higher rate than seen
in the population as a whole (the bushel).
 
Sukie said:
>Otherwise, don't draw conclusions until the study is done.  That is
>always wise.
 
Bob: Again, Sukie's entire post is a drawn conclusion, as has been her
past ones where the assumption is made that a high protein diet causes
cystine stones and is a danger to the general ferret population.  Making
statements suggesting a high protein diet is dangerous to the overall
population of healthy ferrets IS drawing a conclusion.
 
Sukie said:
>Are cystine stones and cystine slush very inclined to prove fatal when
>they occur?  Yes, uncomfortably so, and those who are saved (especially
>males who are more inclined to block) have a tendency toward kidney
>damage and often to needing a penile amputation and urethra rerouting.
 
Bob: Besides being graphically inflammatory, this is a very misleading
statement.  In small mammals like ferrets, the risk of kidney damage and
death is correlated to size.  The smaller the mammal, the easier it is to
block stuff up AND the faster it is to cause organ damage.  Also, males
have 2 to 3 times more risk of stones because of the length and kinks of
the urethra.  ANY stone in ferrets is a high risk, and Sukie--or anyone--
cannot show the risk of any one stone to the organs is less or more
dangerous than another.  It is not the composition of the stone that
makes it dangerous, but the size--the bigger the stone, the better its
ability to block things up.  Struvite stones tend to be very big and they
can grow very fast, so I would tend to argue they are MORE dangerous
because of those factors, as well as being far more commonly encountered.
 
As for the graphic imagery of an amputated penis, in this case all it
does is mislead the reader into assuming cystine stones are the major
culprit, but in fact that honor goes to struvite.  That makes the image
inflammatory and unnecessary--a clear appeal to emotion rather than to
reason.  It would be likewise unfair of me to graphically describe the
prolonged, agonizing death of a ferret, screaming, drool dripping down
their chins, and all because they developed insulinoma from eating kibble
containing a high load of refined and processed carbohydrates.  Or, I
could be more blatant as some people do (Sukie excepted), screaming at
anyone that suggests I am wrong, that I have held these screaming ferrets
in my hands while they bit through their tongues during a low-blood sugar
induced seizure, watching them slowly die in agony, and how dare you
suggest I am wrong when the lives of ferrets are at stake, dammit!
Hummm, that's not fair in a discussion, either.  I have an idea.  How
about a simple discussion of the facts, and let's leave the inflammatory
imagery off the table, ok?
 
There is another factor involved here, which is the size of the bacula
(os penis) in the male.  The bacula has a urethral groove on the top that
prevents the urethra from collapsing during prolonged sex, especially
with a squirming partner.  Ferrets like to engage in particularly
prolonged, squirming sex, so that little bone has some importance.  The
trouble is, early neutering has a significant impact on the normal
development of the bacula.  They are smaller, the urethral groove is not
as well developed, and the hooked tip is not always formed correctly.  I
suspect this is a factor in the blockages seen in male adrenal ferrets,
and I wouldn't be surprised to see the problem in ferrets with
cystinuria.  Sukie's example may be more of a symptom of early neutering
than of cystinuria.
 
Sukie said:
>It may be that centuries of milk and bread, and many decades of kibble
>use on farms has had its impact of vulnerable individuals not dying off,
>which increases rate of vulnerability once a higher protein diet is
>tried again.
 
Bob: Well, it wasn't exactly "centuries of milk and bread." The bread
and milk diet was never very popular, and when it was given, it was
always part of a diet that included a fairly nice amount of raw and
cooked meats.  I have investigated this diet to a degree that surpasses
the category "anal-retentive."  There are some aspects of this diet that
many people are not aware, such as it was never very popular until the
Victorian era, when the advent of transportation and mechanization
decreased the costs of milk and bread.  Ferrets, like any other working
animal, have ALWAYS been fed foods considered economically cheap.  Before
milk and bread was made cheap during the industrial revolution, they were
too precious to be fed to ferrets, who usually dined on rats and rabbits.
So the only real places the diet was popular was in relatively rich
urbanized countries--the same people who printed the books.  Even so,
a careful reading of the veterinary literature of the era, as well as
advice offered in farm newspapers, advertising circulars, and the diet
recommendations published in the ferreting books, are almost universal
in condemning the diet as a main fare.  Your supposition fails based on
a lack of historic evidence that the bread and milk diet was as popular
as you indicate.
 
The supposition also fails because "bread" as defined in these early
diets was not made of the type of flours typically used today.  Most of
these breads were very coarsely ground grains, NOT the finely ground and
sifted stuff that we see in our kitchens today.  Most modern flours lack
the percentage of bran the early flours contained, making a considerable
amount of historic bread indigestible to ferrets.  Nor were they cooked
in a heated and pressurized food extruder that denatures the
carbohydrates, allowing them to be absorbed better.  Much of these breads
would have been in the intestines for too short of a time to allow
efficient digestion, and they would have acted more in the realm of
"fiber" than carbohydrates.  That means the milk proteins and fats would
have been the foods most easily and first digested.  And guess what?
That means this early diet is higher in protein and fat than a cursory
look might indicate.  Most of the bread and milk diets would have had
less digestible carbohydrates than found in modern kibbles, which means
they would supply higher proportions of protein than in typical kibbled
diets.  Just in case you missed it, yes, the milk and bread diet had a
lot of carbohydrates which make it seem as if it is a low-protein diet,
but because the digestibility of a lot of those carbohydrates was low in
the ferret, the diet wasn't as low in protein as one might assume.
 
It fails at another level as well.  While a low protein diet might have
helped to mask cystinuria, it wouldn't have prevented it.  Plenty of
ferrets with the disease would have been noted, simply because they would
have been dehydrated and formed stones, REGARDLESS of diet.  Cystinuria
is a fairly common problem in dogs, and their diet compared to ferrets
is considered too low in protein, yet they have cystine stones, as do
humans.  Sukie assumes stones won't occur because of a milk and bread
diet, when in practice it absolutely would occur.  Besides, can you
imagine how acidic the urine would be on such a diet?  A ferret with low
pH urine from a milk diet, dehydrated from the diarrhea it invariably
causes, and THAT is the makings of some hum-dinger stones.  This is not
the diet to mask cystinuria.
 
We can argue the above points all day long, but there is one fatal flaw
in Sukie's supposition.  It fails to account for the common practice of
hybridization of ferrets to polecats.  This happened ALL the time (still
does), which is why recent genetic studies still cannot identify the
progenitor.  The subject of hybridization of ferrets to polecats is
mentioned in more than 90% of all the historic ferret literature.  For
Sukie's supposition to be true, it would mean the genetics of every
system EXCEPT those for cystinuria would be normalized back to the
polecat.  There are a few geneticists on the FML who would argue that
would be somewhat difficult.  Even now, ferret-polecat crosses have been
imported into the USA for color and build, so hybridization CONTINUES to
this day!  There HAS to be some type of evidence for Sukie's supposition
to have ANY bearing on this issue, and there is none.  Perhaps Sukie
knows this and is offering the argument as a Strawman for me to
systematically shred.  I've got to find that wizard.
 
I've heard this same argument before when some people were suggesting
adrenal disease was due to breeding practices.  I argued against it then
for the same reasons I am arguing against this now.  The argument then
was that most ferrets came from an initial small population, and adrenal
disease was bred into the ferrets at that point.  We now know the disease
is linked to neutering, especially early neutering.  It is easy to blame
things on poor genetics, but all you have to do is look at the numbers
and know it is wrong.  The numbers are simply not there for Sukie's
supposition to be true.
 
Sukie said:
>The CAUSE of cystine stones in ferrets remains unknown, and is part of
>what is being studied so it is premature to assume a genetic cause must
>be at the base of it, let alone a shared genetic cause, though that is
>certainly a strong possibility."
 
Bob: Is there realistically ANOTHER possibility?  This is one of those
statements that is technically true, yet results in an erroneous message.
Is the cause of cystine stones in ferrets proved?  No, not yet.  But come
on; it has been proved in dozens of animals, and since the mechanism at
fault is in the renal tubular transport system, and the problem is the
same in dozens of species, how many alternatives are there?  Cystine is
not being efficiently transported from the urine in the renal tubules
back to the bloodstream.  That means there is too much cystine in the
urine, and since it is not very soluble, it precipitates out and forms
cystine crystals, which may or may not form stones.  However, the basic
problem is that the cystine is not being transported from the urine back
to the bloodstream.  How many things can cause that?  So many different
mammals have the problem, and in the ones that have been proved, it is
caused by an autosomal recessive genetic trait.  Are you suggesting some
scientist is implying the problem in ferrets is something else, because
that would be big news, as in really BIG news.  Me, I'm going to use
Occam's razor to cut to the truth.  The simplest solution is nearly
always the correct one, and that means cystinuria in ferrets is caused by
the same thing that causes it in all the other species.  Call me a slave
to patterns, but I'd rather investigate the obvious than concentrate on
something that has a higher percentage of being wrong.  I guess you can
call a duck a dog if you want, but how do you stop it from quacking?
 
Sukie said:
>There is also investigation into certain food types -- for instance,
>the vets on at least two of these cases have noticed that the
>individuals had dried peas in part of their high protein diet.
 
Bob: Ferrets have no business consuming vegetable foods.  Their teeth
are not designed to render them, their stomach is not designed to digest
them, and their bowel is not designed to absorb them.  Ferrets are
designed to eat prey, the whole prey, and nothing but the prey, so help
me carnivore.  It is not just the carbohydrates, which in ferrets are
very bad, but also the phytochemicals found in most plants.  I don't want
to get into a prolonged discussion on this topic, but I do want to say
that ferrets may not react to this disease in the same way as some other
animals, more specifically the dog.
 
I am under ethical constraints NOT to discuss this at length for the
moment, and those that know and understand me will tell you my principles
mean more to me than money, success, or friends, so don't expect me to
say exactly why I know this.  Nonetheless, I think I can give you an
idea to part of this new thinking that ferrets with cystinuria might
have to be treated differently compared to dogs or humans.
 
Ferrets have NO, as in ZERO carbohydrate requirements.  That means they
have evolved the mechanisms to met their energy needs using protein
(roughly 60% of energy needs) and fat (roughly 40% of energy needs).
Protein is converted into glucose via gluconeogenesis; about 85-89%
occurs in the liver, about 1-5% in the bowel (which is used up there),
and about 10% in the kidneys.  The kidneys and liver specialize in
different types of amino acids that they convert into sugar.  All mammals
can do this, but most mammals cannot convert enough protein into sugar
because that reaction is oxygen dependent, and in humans, the oxygen
levels in the liver are too low.  However, ferrets have a huge liver and
kidneys for their body mass, and since they are small animals, they get
around the oxygen hump and are able to break the rule.
 
Carbohydrates in diet throw off this beautiful mechanism because they
are preferentially used compared to protein or fat.  In other words, if
a ferret eats carbohydrates and protein, the carbohydrates are used for
sugar BEFORE the liver starts converting protein to energy.  I am sure
there are already people who have had that little light over their heads
switch on.
 
If a ferret is consuming a diet of carbohydrates and proteins, the
carbohydrates are use to supply energy, which means the protein levels
in the blood remain higher, so there is a greater protein load for the
ferret to transport across their renal tubules.  If that same ferret has
their carbohydrates removed, the use of the proteins for energy reduces
the overall protein titer in their bloodstream.  That means there are
LESS proteins to transport, and a lower chance that the ferret could form
cystine crystals.  I've actually seen the data on this and it gave me
goose bumps.
 
There is more.  Prey animals are up to 70% moisture, but kibble is less
than 10%.  If you need a comparison, a hardwood floor is about 10 to15%
moisture and drywall is about 4 to 8%.  It takes a lot of moisture to
process dry kibble, which means that soon after a dry kibble diet, the
ferret becomes slightly to moderately dehydrated.  That means the
proteins and other substances in the urine are more concentrated, so
the chance of forming a cystine stone is higher.
 
I wish I could tell you more.  The subject has enthralled me to such a
degree that it is almost all I think about.  The point here is that the
treatment of cystinuria in ferrets may not be the same as in some other
species.  That means a ferret is NOT a cat or a dog.  I *WILL* tell you
more later, once my ethical constraints have expired.
 
Sukie said:
>Again, don't draw conclusions until the study is done.
 
Bob: Again, Sukie has already made her conclusions know to everyone on
the FML, and have for sometime.  She repeatedly pushes her agenda while
admonishing the rest of us to remain open minded.
 
Sukie said :
>Also everyone who is interested in diet should definitely ask your vets
>to let you read a copy of the Dec 2004 "Journal of Exotic Mammal
>Medicine and Surgery" article by Dr. Mark Finkler on the carbohydrate-
>insulinoma hypothesis which he originated.
 
Bob: I would hardly suggest Finker originated the hypothesis; a detailed
search of the literature would show he was not first in line on that one,
and I don't think he would suggest he was either.  However, I have a
tremendous amount of respect for his abilities, and think his paper--
actually a review--is an important one that others will build on, and I
do believe it is the first in the veterinary literature.  I think it
would have had greater impact in a journal with a broader appeal, but
I think it will be read and cited for many years.
 
Finkler's review was well balanced, giving both sides of the argument a
fair representation.  That is extremely important in a good discussion,
which is the reason why I have used my Sunday evening to reply to Sukie's
posts.  Personally, it matters little to me if you find my argument is
persuasive or not--at least both sides have been presented.  That is
unfortunately not always the case.  I'm not sure dietary bias is always
recognized by well meaning people; I think the IFC made a grave error by
only allowing one side of the carbohydrate question to be presented at
their upcoming forum.  Don't get me wrong, I really, honestly like Tom
Willard a lot; I have supported him and his product for a long time (for
years it was the only food I would recommend), and if the guy wasn't
snoozing, I would have went to work for him.  But the guy simply can't
discuss ferret nutrition without turning it into a Totally Ferret
commercial.  Recall everything he has posted here.  I mean he means well,
and he certainly has a great deal of confidence in his product, and loves
ferrets and all that, but "Totally Ferret" tends to permeate his message.
My best guess, based on historic precedent, is that people at that forum
are not going to hear a balanced view of the carbohydrate problem; they
will hear his side only, he will object to a high protein diet, and he
will be able to argue it without risk of refutation.  The IFC should have
allowed an opportunity for the opposite point of view to be presented,
and Finkler would have been a perfect choice.
 
This has been a long discussion, in part because Sukie's original posts
were long, and in part because you simply cannot refute a complex
question with just a few sentences.  I suppose I could have not addressed
the issues and just repeated ad infinitum (and ad nausium) "Prove it,
prove it, prove it, prove it," but that would have hardly helped
explaining the reasoning behind the demand for proof.  Many of Sukie's
points are not points at all, just emotional diatribe and inflammatory
statements.  Most of her suppositions are unsubstantiated, but that is
ok; this is a subject with little ferret-centered publication, so the
presentation of supposition is to be expected.  I admit I am tired of
reading Sukie's continuous decrying of a high protein diet, while at
the same time telling people not to make up their minds, or warning the
opposing point of view against drawing a conclusion before the facts are
in.  I would suggest she follow her own advise, but I don't think anyone
has to do that.  I have already come to some conclusions that I might
change later if refuted.  I have NEVER been frightened of admitting I
was wrong.  I apologize to people all the time and I might end up doing
it over this.  But I *am* going to draw a conclusion, and I think most
people will as well, just like Sukie has done.
 
My primary concern is not if I am right or wrong.  All I care about is a
ferret's quality of life.  That is all I care about.  THAT is why this
question is so damned important, why I gave up my Sunday evening to pen
this response, and why I made it so long.  I think Sukie has gone too far
on this question.  I think her ideas are somewhat beneficial to a ferret
with cystine stones, but it certainly isn't beneficial to the ferret
population as a whole.  Sukie's basic argument, as she has presented it,
is that it is important to not move to a high protein diet because a few
ferrets may, might, could have cystinuria.  My basic argument is, yeah,
they might, but the greater good is to feed a better diet to EVERY
ferret, while at the same time identifying the sick ones and treating
them individually.  I don't want ANY ferret to suffer.  I just can't
accept that it is somehow better for a ferret to die of low blood sugar
while in the midst of a hypoglycemic seizure, caused by an insulinoma
triggered by a diet of highly refined and processed carbohydrates, than
it is to suffer from cystine stones.  The symptoms of a blockage caused
by cystine stones are no different than from any other stone; we CAN
watch for it.  Vets can do a simple screening, either of a microscope
exam of urine sediments, by adding a dye to the urine, or even by
chemical analysis to check cystine levels in the urine.  Sick ferrets can
be treated with diet and hydration, and the breeding of the line can be
halted.  In the meantime, we can provide a better diet for our ferret
that will go a long way in preventing insulinomas and other diseases.
 
Ok, I've said what I wanted to say.  Anyone else can say anything
they like, and they are more than welcome to do so.  As far as my
participation is concerned, this debate is finished; I've already said
this stuff 3 or 4 times in the last few months, and I really don't want
to continue to make the same points to people who are prejudiced against
a particular viewpoint.  I'm going to work on a new formulation for a
softer ferret diet I have thought up that may not hurt teeth, I've got
to finish some book chapters, and for Godsake, I have to play with my
ferrets.
 
Bob C
talktobobc
[Posted in FML issue 4977]