Why a Physiologist Chose to Study Traditional Human Populations'

1
Why a Physiologist Chose to Study Traditional
Human Populations.
Kenneth L. Campbell
Department of Biology University of
Massachusetts at Boston
2
(No Transcript)
3
As an analytical chemist and biochemist, I seek
to make visible, and quantifiable, processes that
are normally invisible.

• A challenge for static chemicals
• Moreso for dynamic physiological processes
• Doing so greatly enlarges the number of
  explanatory variables that can be applied to
  solve questions
• about observable processes interactions
• about behaviors ecological associations

I also seek to occupy a unique niche in science
that allows me to optimize all the potential
impacts of my efforts.
4
What Are My Big Questions?
How does the body function reproduce?
What ecological variables have the most
impact? What are the limits of normality? What
happens when it malfunctions? What environmental
factors limit normalcy?
Environmental interactions are often chemical
exchanges how does endocrinology play a role?
What are the roles of binding proteins other
molecules? What is the impact of dietary
variation on steroid metabolism? Does diet alter
total hormones, binding proteins,
regulators? How does immune function alter
endocrinology reproduction?
How can we best evaluate physiological systems
interacting with the environment?
Can I develop approaches tools that optimize
minimally invasive, real-time, generation of
physiological data in the field? How do we create
the interdisciplinary bridges needed to explain
fertility its dependence on ecological
variables?
5
The Gainj Project
6
1. Was the uniform physiological potential for
human reproduction, then assumed by many social
scientists, correct?
2. Could the proximate determinants of human
fertility be estimated in this natural fertility
group?
3. Could modern clinical diagnostic laboratory
methods be successfully applied in field settings?
7
How could it be assumed that humans had a uniform
potential for reproduction and reproductive
physiology? Dizygotic (two-egg) twinning rates
varied by over 16-fold across populations!
8
Where were the Gainj?
9
Gainj Project 1982
10
What was new or striking about New Guinea for a
lab scientist?
Just about everything!
11
What did we find among the Gainj?

• Late age at maturation in men women
• Late age at marriage first birth
• Long interbirth intervals
• Prolonged lactation
• Long intermenstrual intervals
• Hormonal evidence of male subfecundity
• Indications of a unique physiological
  accommodation to diet allowing euthyroidism
• A model for human reproductive ecology

12

• Field interviews including reproductive life
  histories menstrual diaries
• Time studies direct observations
• Anthropometry
• Cross-sectional blood sampling bi-weekly saliva
  collections
• Immunoassays for steroid, thyroid, protein
  hormones, serum binding globulins
• Protein screening of many alleles later PCR
  sequencing of isolated DNA
• Extensive data analysis mathematical models

13
Physiology demography were synergistic in
explaining fertility.
14
Prolonged intensive nursing keeps prolactin high
ovulation suppressed.
15
Long intermenstrual periods also occur,
independent of age probably due to chronically
high PRL, early fetal losses, subfecundity.
16
Role of Gainj men in TFR Make no assumptions.
17
Even two assays for the same molecule sometimes
disagree.
18
Believe the data. Many Gainj men are subfecund.
19
(No Transcript)
20
Lessons from the Gainj Project

• Needed a better way to rapidly get endocrine
  information
• Needed a more optimal source material to measure
  hormones than saliva or blood
• Needed better ways to evaluate lactation
  nursing
• Needed a means to evaluate timing adequacy of
  insemination
• Needed means to make field studies more efficient
  of time resources

21

• Study of a group with seasonal reproduction
  high fertility does fecundity vary seasonally?

• Natural contrast with nomadic sedentary
  subpopulations do they differ reproductively?

• Used hormonal assays in the field

• Dried quasi-longitudinal samples on paper for
  later analysis of blood and urine

• Interviews, anthropometry, hormone protein
  assays combined with mathematical modeling

22
(No Transcript)
23
Kenya also had striking images.
24
What did we find among the Turkana?

• Late age at maturation in men women
• Little evidence of accelerated endocrine aging
  patterns compared to the Gainj
• Some seasonality of reproductive status in women
• Suggestion of dietary impacts on male hormone
  binding proteins
• Major subpopulation differences in early
  pregnancy loss (malaria rates?)
• Indications that immune function is faulty

25
The typical late adolescent nadir of SHBG occurs
after 20 in Turkana males.
26
DHEAS declines early in the Gainj but normally in
the Turkana.
27
Turkana births cluster in the late dry early
wet season so conceptions must take place in the
late wet and early dry seasons. Right?
28
Turkana women show some evidence of seasonality
consistent with births clustered in the early dry
season.
29
Given TBG data in New Guinea, we suspected SHBG
would rise if albumin levels fell with seasonal
food shortage it would be most pronounced in
nomads. Its more complex.
30
Turkana pregnancy losses are high but might be
expected for nonclinical populations in medically
underserved areas.
31
Dramatic differences between sedentary nomadic
women suggest very early, undetected losses in
nomads /or differing disease (malaria?) rates in
the subpopulations.
32

• Dynamic population, shifts between subpopulations
  areas common

• Mobile population compromises longitudinal studies

• Politically unstable area, intertribal raiding
  common

• Still no ready way to evaluate if timing of
  coitus or adequacy of insemination contribute to
  fertility patterns

33
1. Each population demonstrates unique, invisible
elements of physiological adaptation.
2. Key determinants of fertility, e.g., timing of
adolescence senescence, can be determined more
precisely with hormones in field studies.
3. Lab assays on urine work in the field can
improve project efficiencies.
4. Men, as well as women, can constrain natural
population level fertility.
5. Physiology is highly elastic can allow
normal function under marginal conditions.
6. Interdisciplinary studies are, indeed,
necessary to explain behaviors ecological
interactions single parameter studies are often
misleading.
34
Human reproductive ecology is an important branch
of human biological studies. Because it is
interdisciplinary, it will be synergistic. We
will learn more about the impacts of
environmental variables on human reproduction
working as a team than we would ever learn
separately. Moreover, we may act on what we
learn more readily as a group than we ever could
working alone.
35
Support from NSF, Umass/Boston, Sandia National
Labs, Hybritech, Quidel, Monoclonal Antibodies
Inc.
(in the lab at UMB)
36
(No Transcript)
37
Anthropology B Campbell
W Lukas Anthropology
38
A Brief History of the Gainj Project

• Originated from JW Wood dissertation
• Endocrinology added after first field season,
  genetics consultation with UM Reproductive
  Endocrinology Program KL Campbell
• Socioeconomic dimensions greatly enhanced
  reproductive histories added by PL Johnson
  dissertation work
• Reproductive Ecology stems from mutual
  reinforcement of demography physiology data
• NSF supported second field season following lab
  computational work along with Mellon Fdn

39
Dr. Wood had a rough start!
40
Things did get better.
41
Female Reproductive Life History Interchild
Spacingafter J. W. Wood, 1994, Dynamics of
Human Reproduction Biology, Biometry,
Demography. Aldine, De Gruyter Hawthorne, NY.

• Premenarchealgtreproductive maturitygtreproductive
  senescence

-follicular phase-midcycle-luteal
phase-menses-follicular phase/cessation
-fertilization-nidation-gestation-parturition-foll
icular phase/cessation
-lactation-follicular phase/cessation
42
Gainj birth intervals from reproductive histories
were long independent of parity.
43
Development of noninvasive method to evaluate
simultaneously ovarian status, insemination
status ( adequacy), urogenital microbial
status using DNA from serial urine sediments

• Can we do it in humans?

• Can we do it in animals?

44
The ovarian cycle yields estrogen fluctuations
that drive the endometrial vaginal cell cycle.
The vagina urethra arise from interdigitated
developmental anlage both are estrogen sensitive
proliferating, differentiating dying by
programmed cell death (apoptosis). Apoptosis
includes ordered decay of DNA that gives ladder
patterns on gel electrophoresis. PCR allows
detection of Y-chromosomal or microbial DNA.