20
2. Galton F. Inquiries into Human Faculty and Its Development.
London: Macmillan,1883.
3. Cowan RS. Sir Francis Galton and the Study of Heredity in the
Nineteenth Century. New York, NY: Garland Press, 1985.
4. Gillham NW. A Life of Sir Francis Galton: From African
Exploration to the Birth of Eugenics. Oxford, UK: Oxford
University Press, 2001.
5. Galton F. Hereditary Genius. London: Macmillan, 1869.
6. Zirkle C. The Inheritance of Acquired Characters and the
Provisional Hypothesis of Pangenesis. The American Naturalist
1935;69:417–45.
7. Green JC. The Death of Adam: Evolution and its Impact on
Western Thought. New York, NY: Mentor, 1961.
8. Burkhardt RW. The Spirit of System: Lamarck and Evolutionary
Biology. Cambridge, MA: Harvard University Press, 1977.
9. Jordanova LJ. Lamarck. Oxford, UK: Oxford University Press,
1984.
10. Darwin C. The Variations of Animals and Plants under
Domestication. 2 vols. London: John Murray, 1868.
11. Located in Galton Papers, Archives, University College London,
London UK.
12. Galton F. Experiments in pangenesis by breeding from rabbits of
a pure variety, into whose circulation blood taken from other
varieties had previously been transfused. Proc R Soc 1870-71;
19:404.
International Journal of Epidemiology, 2016, Vol. 45, No. 1
13. Pearson K. Life, Letters and Labours of Sir Francis Galton. Vol.
2. Cambridge, UK: Cambridge University Press, 1914-30.
14. Darwin C. Pangenesis. Nature 27 April 1871:502–03.
15. Galton F. Pangenesis. Nature 4 May 1871:5–6.
16. Galton F. On blood relationship. Proc R. Soc 1872;21:394–401.
17. Galton F. A theory of heredity. J R Anthropol Inst 1876;5:
329–48.
18. Cowan RS. Francis Galton’s statistical ideas: the influence of eugenics. Isis 1972;63:509–28.
19. Weismann A. Essays upon Heredity and Kindred Biological
Problems. Oxford, UK: Clarendon, 1889.
20. Weismann to Galton, 23 February 1889. In: Pearson K. Life,
Letters and Labours of Sir Francis Galton. III. Cambridge, UK:
Cambridge University Press, 1914-1930.
21. Churchill FB. August Weismann, Development, Heredity and
Evolution. Cambridge, MA: Harvard University Press, 2015.
22. Schwartz Cowan R. Sir Francis Galton and the continuity of
germplasm: a biological idea with political roots. In: Proceedings
of the 12th International Congress of the History of Science, vol.
8. Paris: Albert Blanchard, 1970.
23. Galton F. English Men of Science: Their Nature and Nurture.
London: Macmillan, 1874.
24. Galton F. The history of twins as a criterion of the relative
powers of nature and nurture. Fraser’s Magazine 1875;12:
566–76. Reprinted in Int J Epidemiol 2012;41:905–11.
International Journal of Epidemiology, 2016, 20–23
Commentary: Inheritance of
doi: 10.1093/ije/dyw031
acquired characteristics: eliminating
alternatives in the search for mechanisms.
Commentary on Galton F: Feasible experiments
on the possibility of transmitting acquired
habits by means of inheritance
BG Dias
Emory University School of Medicine, Department of Psychiatry and Behavioral Sciences, Yerkes
National Primate Research Center, Atlanta GA 30329, USA. E-mail: [email protected]
Accepted 11 January 2016
Increasing scientific evidence suggests a role for the inheritance of physiological and behavioural traits across
generations.1–17 By way of clarification, the inheritance
being talked about refers to traits that have first been
acquired by an ancestral generation as a consequence of an
environmental trigger and then subsequently inherited by
the descendant generations. This is in contrast to congenital traits that are inherited from the ancestral lineage.
Several broad conceptual questions dominate critiques
about the inheritance of characters acquired by ancestral
populations and ought to be addressed if such inheritance
is to be proven unequivocally.18–20 Among these: (i) is the
acquisition of the trait in question a case of true biological
inheritance or a consequence of information transmitted
across generations via social means? and (ii) over how
many generations should this acquisition be observed to
C The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association
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International Journal of Epidemiology, 2016, Vol. 45, No. 1
qualify as inheritance?19–21 Francis Galton’s work reproduced in this issue (F Galton. Feasible experiments on the
possibility of transmitting acquired habits by means of
inheritance. Int J Epidemiol 2016;45:) serves as a blueprint
for stringent criteria that would strengthen the case for an
inheritance of acquired characteristics. Strikingly, his suggestions still ring true for researchers in this field.
Galton proposes that experimentation on organisms artificially reared from eggs would distinguish between the possibilities of biological inheritance and social transmission,
and lists experiments using them. He begins by mentioning
certain insects being avoided by fowl because they resemble
or mimic noxious insects (called mimetics), despite these
mimetics being palatable. In his proposed design, Galton
suggests feeding young chicks these mimetic insects, thereby
teaching them to not avoid them, and then querying
whether descendants of these mimetic-fed chicks would
have a lower avoidance toward these mimetic insects. He
suggests a similar experiment with the larvae of moths, capitalizing on their short life cycle and lack of parental care,
thereby eliminating any social transmission of information
from parent to offspring. Finally, Galton uses examples of
pike being trained that they cannot have access to minnows
while in the same tank (using a transparent barrier), and
then asks whether future generations of pike will learn
quicker to make ‘no further attempt on the lives of the minnows’. Of note in this regard are studies using an egg-laying
species, C. elegans, that have reported the transgenerational
inheritance of an anti-viral response, starvation-induced
alterations in nutrition and longevity.6,22,23
At the core of Galton’s suggestions is being able to eliminate the possibility of parental care and information transfer from that care. Whereas it is feasible to do so in the
organisms that he talks about and in the worm, C. elegans,
it is more difficult when working with species that give
birth to live young that require extensive care and consequently exhibit high levels of parental provisioning. In
such scenarios, in vitro fertilization (IVF) and cross-fostering are crucial to demonstrating acquired traits as being
biologically inherited vs socially transmitted.24 This is in
essence the equivalent of Galton’s recommendation on
‘eliminating the influence of parental education and of
social tradition from the children’ and also ensuring homogeneity in the rearing environment.
Take for example the naturally occurring variation in
maternal care in rodents, with rat mothers exhibiting high
or low maternal care.25–27 Seminal work with this system
established that high maternal care exhibited by rat dams
resulted in their offspring also demonstrating high care
toward their own offspring. This could be termed ‘inheritance’, but the fact that cross-fostering reverses this effect
implies that maternal care was crucial to this transmission
21
of quality of maternal care. That is, pups born to a high
maternal care dam but fostered by a low maternal care
dam, then themselves exhibited low maternal care toward
their offspring. These data emphasized the importance of
experiencing a certain quality of maternal care on subsequent adult behaviour and make a compelling case for
transmission of information across generations sculpting
physiology and behaviour.
More recently, at least two studies have used IVF to
demonstrate transgenerational inheritance with mixed
results. First, Dietz and colleagues28 used sperm from
socially defeated mice to generate descendant generations
via IVF. These authors suggest that the effects on anxietyand depressive-like behaviour seen in the F1 and F2 generations of these socially defeated mice generated via traditional matings do not survive after IVF and therefore by
definition are presumably related to some form of social
transmission. In contrast is the study demonstrating that
subjecting adult male mice to olfactory fear conditioning
(odour þ shock) results in the F1 and F2 generations demonstrating a behavioural sensitivity to the conditioned
odour.4 In addition, an increased representation for the
conditioned odour in the olfactory nervous systems of the
F1 and F2 generations was observed despite these animals
having no prior history with the conditioned odour. Effects
persisting into the F2 generation suggest an inheritance of
these effects, and further demonstration of this inheritance
was confirmed by conducting IVF with sperm from the F0
conditioned males and the aforementioned effects still persisting. Cross-fostering and IVF will become the norm in
the establishing an inheritance of acquired traits as more
such studies accumulate.
Focusing on the matter of over how many generations
should acquired traits be observed so as to qualify as inheritance, Galton leaves us with the recommendation of
‘many’ but also interestingly exhorts us to ‘economise
time, labor and money’. Whereas obviously we should
strive for ‘many’, a discussion of inter- vs trans-generational inheritance of traits provides a more realistic framework at a time when animal housing per diem and research
personnel costs are important practical considerations. A
thorough discussion of this dichotomy is beyond the scope
of this commentary, and readers can peruse other reviews
on this subject including treating animals from a litter
(therefore born to a single male or female) as independent
samples or treating the whole litter as a sample size of
1.20,29 Briefly, the time at which a parental generation
experiences a perturbation to their environment (e.g. preconceptional, in utero, postnatal) and whether the gametes
of subsequent generations are also affected will determine
inter- vs trans-generational inheritance.1,24,30 Addressing
this distinction and incorporating cross-fostering and IVF
22
International Journal of Epidemiology, 2016, Vol. 45, No. 1
studies represent a robust manner to demonstrate the
inheritance of acquired characteristics across generations.
Whereas reports of transgenerational inheritance continue to accumulate, the biggest elephant in this room pertains to mechanism.18 How does an environmental stimulus
mark the sperm and egg of the parental generation, to then
result in inheritance of the effect of this stimulus? If such
marking does indeed take place, how do they escape erasure
that normally occurs via a process called epigenetic reprogramming?30 Eloquent prose, penned by Charles Darwin31
and Francis Galton,32 outlined theories, experiments and
experimental design that would be considered prescient to
the contemporary conversation about this inheritance. Most
recently, experiments that inject small non-coding RNA species into zygotes have made strong cases for non-coding
RNA being carriers of information about stress and nutrition across generations.3,9,33–35 Being able to recapitulate
effects of parental stressors in future generations by injecting
non-coding RNA into zygotes and then employing embryo
transfer techniques is exactly the approach that Galton
exhorts in the reproduced article.
It is a privilege for us to pursue the scientific enterprise
with technology as audacious as it currently is. Marrying
technical advancements in neuroscience, nanotechnology
and reproductive biology with creative experimental
design will allow us to comprehensively demonstrate the
existence and mechanisms of the inheritance of acquired
characters. Or not. Either way, solving this puzzle that
vexes the mind and prevailing scientific dogma, moves science forward.
Conflict of interest: The author has no conflicts to
disclose.
Funding
BGD would like to acknowledge funding support from the
Department of Psychiatry and Behavioral Sciences, the
Brain Health Institute, and Yerkes National Primate
Research Center (YNPRC) at Emory University.
Additional support was provided by Office Research
Infrastructure Programs/OD P51OD11132 to YNPRC.
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David J Galton
Wolfson Institute of Preventive Medicine, Charterhouse Square, London EC1M 6BQ, UK. E-mail: [email protected]
Accepted 11 January 2016
Francis Galton is mainly remembered for his work on eugenics (a word he coined) which he unfortunately referred
to on occasion as Race Improvement—naturally raising
much opprobrium today. His other major contribution is
in statistics to analyse results of studies of inheritance of
quantitative traits such as height of parents related to
height of offspring. He originated correlation analysis to
determine if one variable has any relation to another and,
after modification by people like Pearson, Spearman,
Kendall and others, the method has found its way into
school textbooks.
In some ways Galton’s mental energy was his own
worst enemy. Some would say he worked on too many
topics, including meteorology with the invention of isobars
and weather maps, fingerprints to identify an individual
(which is still in use), African exploration (opening up
parts of Namibia in South West Africa) and problems of
heredity. The latter was a major field of interest and he
gained the reputation of a Victorian polymath.1
The date of this present paper—1889—is long after his
work on eugenics started with his book on Human
Faculty,2 which he pursued with almost religious zeal until
his death in 1911. So it is interesting that he is still pondering ideas of heredity in 1889. His work on heredity started
in about 1865, culminating in his two major books:
Heredity Genius3 and Natural Inheritance.4 He had
studied with Charles Darwin the possible change of fur colour in rabbits after blood transfusions, to determine if
there were any blood-borne particles that may be involved
in inheritance. The results were negative and, going against
Darwin’s wishes, Galton published them in the
Proceedings of the Royal Society of 1871. Darwin was not
a co-author. Galton also studied the inheritance of coat
colour of Basset hounds and the occurrence of diseases in
identical and non-identical twins; and came very close to
Mendel’s experiments, studying the inheritance in the
sweet pea (not the edible pea that Mendel studied). He
measured how the seed size and weight related between
parents and progeny. If only he had measured the shape of
pollen grains of the sweet pea (either oblong or round—a
Mendelian trait) he might have replicated the results of
Mendel only 5 years after Mendel’s great publication of
C The Author 2016; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association
V