[Am-info] Re: What is teratology?

[Glenn T. Livezey, Ph.D.]

"John J. Urbaniak" <jjurban@attglobal.net> wrote;
> I give up.  What's "Teratology?"
"Erick Andrews" <eandrews@star.net> wrote;
>The study of turf wars?  Nope, I don't think so.  See...
>http://www.teratology.org
>"The Teratology Society is a multidisciplinary scientific society
>founded in 1960, the members of which study the causes and
>biological processes leading to abnormal development and birth
>defects at the fundamental and clinical level, and appropriate
>measures for prevention."
>I guess what I don't understand is...what relationship, if any...
>do they have to the March Of Dimes.  (http://www.modimes.org)
>Maybe Dr. Livezey can better explain?
>Anyways, I hope we're not getting too OT.

I will give you the short reply to both to both, then the lengthy
version after, so you can skip on to soemthing mor "on topic" if
you like.
(relatively) SHORT VERSIONS:
As I wrote to John offlist;
>> Teratology is the study of the causes of "birth defects".
>>From the root word 'terat', greek for 'monster', a layman's appraisal
>>of the appearance of the most unfortunate developmental outcomes that
>>display a distorted morphology (physical structure/appearance). This
>>is the kind of 'birth defect' most people are familiar with and mean
>>when they discuss potential "teratogenicity" of a substance present
>>during prenatal development (drugs - legal/illegal, or environmental
>>toxins, ingested/absorbed by Mom during her pregnancy). Same thing
>>for exposure to radiation of one source or another (radioactive
>>substances, electromagnetic fields - powerlines, microwaves - cell
>>phones/towers, etc). For most folks, if the baby looks 'normal',
>>and has the right number and placement of the easily recognizable
>>parts and peices, its all good.
To which he replied with questions regarding the long version 
(see below).
As to Erik's questions, The Teratology Society (the URL you cite)
is an association of physicians, scientists, industry representatives
(chemical, pharmaceutical) and government regulators whose jobs 
focus on the study and prevention of birth defects in the classical
sense - ie, morphological or physical defects in fetal development.
The March of Dimes is a charitable foundation that raises funds for
research into the causes and prevention of birth defects. MOD also 
provides information services for professionals and the public, as
well as support services for families who have members affected by
some form of developmental disorder. Their focus, historically, has
also been on the physical malformations most people think of as a
"birth defect".

THE REST: LENGTHY VERSION:  
The society to which I belong (used to belong to Teratology as well)
is a sister organization of the same array of members whose focus is
on "Birth defects of the mind". We concern ourselves with functional
deficits. Rather than study overt physical deficits or changes in 
appearance of tissues, that sometimes involve organ function as well,
our studies are related to behavior and learning and so are confined
to changes in the nervous system that most often have no outward
'signs' or expression in the physical appearance of a being. 
as I wrote to John............
>> IF YOU REALLY WANT TO KNOW....:
>> However, my interest is in 'Neurobehavioral Teratology', limited to
>> "birth defects of the mind", which are purely functional deficits,
>> often in the absence of a physical malformation. Learning disorders,
>> behavioral disorders, which I find are abundant after therapeutic
>> levels of prescription medications taken throughout fetal brain
>> development, may even be observed after exposure to "safe", even
>> 'recommended' levels of prescription medications, vitamins, and a
>> variety of 'natural/herbal' remedies, if very specific "windows of
>> vulnerability" are targeted. Aren't you glad you asked?

see http://nbts.bsbe.umn.edu or http://www.nbts.org

>"John J. Urbaniak" returned the volley with;:
>Sure - never hurts to learn something.
>Power lines, microwaves, cell phones - are there certified verified links
>to birth defects?
>But it seems that quantification of "purely functional defcts" would be
>pretty difficult.  I imagine that Einstein would have been considered a
>child with such defects. John

to which I now reply and amplify........................

Glenn again. I am happiest knowing I shall never stop learning, even
if it is just what I fail to remember ;-)
If you really want to know, please let me apologize for producing a
rather lengthy 'answer'. In my field, the answers are seldom short or
simple. And we are always looking to improve our 'answers'.
The study of the effects of such things as powerlines, microwaves (not
your oven, but the communications towers) and cell phones are indeed
controversial, but there exists at least sufficent evidence to warrant
further study. Most people think of studies trying to link proximity to
power lines or cell phone use with the incidence of focal cancers.
There is little that I am aware of to support a finding of risk in most
studies to date. But there is still room for more and better studies.

And indeed, quantification of "purely functional defects" is 'pretty
difficult'. That's why it is 'the lessor known quantity'. But there are
ways. My own research, and that of others, relies on quantification
of brainwave patterns - using PCs to collect and analyze spontaneous
and evoked neural activity patterns using many of the same methods
developed by electrical and mechanical engineers to evaluate any
recorded signal produced by circuits or machines via transducers.
That's how I came to spend so much time brooding over efficient
uses for computer resources, and the landmines some people's
business models placed in my path. - there, a nod to 'on topic'.

As to "Einstein ... considered a child with such defects", you are
right in that I would expect data collected from a young Einstein
to perhaps deviate from the norm in some measurable and quantifiable
way or another, but I can't imagine someone labeling his accelerated 
development and capacities as 'defective'. But it does happen, and
we continue to try and educate the public and public schools to avoid
this. "Genius" is not what I have tried to quantify. Nor even
"intelligence", too many variables, too many definitions, no agreed
upon 'standard'. No, what I have tried to do is study measurable and
quantifiable electrophysiological 'correlates' of some measurable 
and quantifiable behavioral parameter. For instance, there
is a kind of alpha (8-13Hz in humans) wave spindle pattern, 
that appears during quiet wakefulness and sleep onset, that 
correlates with reduced arousal level, but can also be detected during
full arousal as a measure of perceived reward when an animal is 
learning to press a lever for food reward. Under these circumstances
it is called "Post-reinforcement Synchronization" or PRS, and it
can be quantified as to magnitude and latency from the rewarded 
behavior (pressing the lever). The magnitude of this brainwave
response correlates in a positive manner with learning rate in this
simple associative learning task in cats. as I said, it occurs in 
response to the perception of reward, as in - when the cat presses 
the lever and a small quantity of milk is delivered to a cup along
side of the lever. Through a tedious series of experiments it
has been demonstrated that this 'signal' is not an artifact of
the cats licking the cup, its not an indication of drowsiness
under the learning or performing circumstances, it is
dependent upon the recognition of an 'expected' and valued
reward, and its diminished magnitude and/or delayed onset
is correlated with a greater training time to learn the task of
lever pressing for milk reward - in a quantifiable and
statistically significant manner. This isn't to say we can
show you the "autism pattern" in a child so diagnosed, not yet
anyway. But it is my goal to develop an noninvasive diagnostic
test of the EEG (electroencephalogram) of newborns, that will 
identify and measure subtle brain damage at birth, that will
predict the appearance of specific learning or behavioral 
disorders later in life. So that the right children are attended
to in the right way so that they may take full advantage of their
early school years - instead of going unrecognized until they are
years behind their peers in education and social development.

I will try to finish up this answer by tying this exact measure and
experiment into "functional defects" and "neurobehavioral
teratology". You see, I studied that 'alpha burst' in cats
for my Ph.D. thesis project. First I demonstrated the
positive correlation between the magnitude of that response
to reward and the rate at which the animals learned to press
the lever (and only the lever) for milk reward. Then I wanted
to prove (read 'test') the hypothesis that this was not merely
coincidence, but was a genuine causal relationship. To do
this I theorized that prenatal exposure to Valium (diazepam)
would result in a diminished number of receptors for that
drug in the brains of the offspring - a permanent deficit. I
further theorized that that receptor deficit would produce a
functional deficit - in the capacity to produce that 'alpha wave'.
And I raised sufficient numbers of litters of cats to adulthood,
to measure only the lingering effects of that long past exposure
to the drug in utero. I used a dose in the middle of the
therapeutic range to produce - I thought - a subtle but still
measureable deficit. It worked too well. The animals were
incapable of learning the task, even after a period of training
time 6 times longer than the average for untreated animals.
The animals exibited greatly diminished and delayed alpha
spindles in response to reward. And after all the behavioral
tests were finished, we examined their brain tissue and did
demonstrtate that the receptors for that drug were reduced
by as much as 50% in some brain regions. But the most
frightening aspect of those early experiments was this - the
behavioral disorder/learning deficit that those animals most
closely resembled was attention-deficit hyperactivity disorder
ADHD, a diagnosis that has been growing in our children
for the last 30 years - echoing the popularity of that drug
in terms of millions of prescriptions/thousands of tons of
pills consumed per year. We treat our ADHD children with drugs
like Ritilan, that are derivatives of amphetamines - speed.
And in ADHD its effect is a paradoxical calming. My cats
could be "normalized" - that is their behavior and brainwaves
would approximate the untreated controls - by one of two
treatments; I could give them back the exact dose of Valium
they experienced before they were born, or amphetamines.
Remember I said that brainwave pattern was also a part of
sleep onset? Valium and its chemical cousins are prescribed
for sleep disorders, especially the type that appears in the
elderly as a result of "stress" known commonly as aging. My
later studies showed I could produce chronic stress and a
model of  "insomnia" with identical measures to the changes
in sleep patterns with advanced age, and treatable by the
same drug. In followup studies of rats, I could follow the
offspring well into "middleage". The chronic stress they
exhibited eventually weakened their immune systems,
producing a braod array of cancers and infections at 10
times the rate and much earlier onset than in the controls.

The general rule for all subsequent studies has been, whatever
symptom a drug might be used to treat, I can create that
symptom in an animal model by prenatal exposure to the drug.
Prenatal anti-anxiety drug, permanent anxiety.
Prenatal anti-convulsant, increased seizure activity.
My most recent study was with Prozac. Most people know
it as an antidepressant, but it is also used for anxiety/panic
disorders and for many psychological disfunctions that fit under
the broad term 'obsessive-compulsive' disorders - everything
from bursts of rage to drug dependency.

I wish I had good news, but I can't find anyone to fund my
studies into the effects of prenatal Prozac. Not since I showed
the initial results which indicate that the effects on simple
behaviors and brainwave patterns vary from increases to
decreases, and everything in between, depending on the exact
dose given. This one is simply too complex to get a simple
answer from two simple tests. But then, there are 17 known
receptors for the brain transmitter that Prozac acts upon.
With Valium there were only 2. But think of all the things
they use Prozac for, and think of the tons of pills sold in ever
increasing waves since the late 80s. Now we have lots of
pharmacological cousins (they are all selective serotonin uptake
inhibitors - SSRIs), but their structural chemistry varies 
- Prozac, Luvox, Celexa, Zoloft, Paxil - and guess what seems to be 
the greatest threat from Paxil? Drug dependence. The idea that at 
least some patients who are treated with Paxil may never be able to 
quit without a lengthy and perhaps only partially successful 
weaning program - this from a drug used to treat drug addiction.

Prozac, the original SSRI, has brought in 24 BILLION dollars to
the Eli Lilly company to date. Do you think they might want to 
know if their drug was causing harm to our children? I did.
Silly me. No one wants to admit there might be a problem, because
no one has a solution - except for litigation.
You see, we also know that not treating a pregnant woman for her
convulsions, or her depression, or whatever can result in harm to
the developing fetal brain. So we are damned if we do and damned
if we don't UNTIL we do enough research to determine the safest
approach, possible postnatal treatments, or a whole new treatment
approach for the mother that will not affect the child. That also
means years and piles of money.

So, I have to get back to my professional ranting and begging for
support, so I can get back to my research and development of more
diagnostic tools for the physicians who work in this field.

I hope the answers you wanted are in there somewhere.

Glenn
-- 

Glenn T. Livezey, Ph.D.
Treasurer and webmaster
The Neurobehavioral Teratology Society

University of Minnesota
Neuroscience Department
Room 6-145 Jackson Hall
321 Church St. S.E.
Minneapolis, MN 55455

(612) 624-2991 FAX 6-5009 
glivezey@lenti.med.umn.edu
webmaster@nbts.org