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24. Dias BG, Maddox SA, Klengel T, Ressler KJ. Epigenetic mechanisms underlying learning and the inheritance of learned behaviors. Trends Neurosci 2014:1–12.
25. Meaney MJ, Szyf M, Seckl JR. Epigenetic mechanisms of perinatal programming of hypothalamic-pituitary-adrenal function
and health. Trends Mol Med 2007;13:269–77.
26. Weaver ICG, Cervoni N, Champagne FA et al. Epigenetic
programming by maternal behavior. Nat Neurosci 2004;
7:847–54.
27. Weaver ICG, Meaney MJ, Szyf M. Maternal care effects on the
hippocampal transcriptome and anxiety-mediated behaviors in
the offspring that are reversible in adulthood. Proc Natl Acad Sci
U S A 2006;103:3480–85.
28. Dietz DM, Laplant Q, Watts EL et al. Paternal Transmission of
Stress-Induced Pathologies. BPS 2011;70:408–14.
29. Lazic SE, Essioux L. Improving basic and translational science
by accounting for litter-to-litter variation in animal models.
BMC Neurosci 2013;14:37.
30. Dias BG, Ressler KJ. Experimental evidence needed to demon-
Commentary: Lamarckian
inheritance and epigenetics:
is there a connection?
International Journal of Epidemiology, 2016, 23–25
doi: 10.1093/ije/dyw003
strate inter- and trans-generational effects of ancestral experiences in mammals. Bioessays 2014;36:919–23.
31. Darwin C. Pangenesis. Nature 1871:502–03.
32. Galton F. Pangenesis. Nature 1871:5–6.
33. Gapp K, Jawaid A, Sarkies P et al. Implication of sperm RNAs in
transgenerational inheritance of the effects of early trauma in
mice. Nat Neurosci 2014;17:667–69.
34. Rassoulzadegan M, Grandjean V, Gounon P, Vincent S, Gillot I,
Cuzin F. RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse. Nature 2006;441:469–74.
35. Sharma U, Conine CC, Shea JM, Boskovic A, Derr AG, Bing
XY, et al. Biogenesis and function of tRNA fragments during
sperm maturation and fertilization in mammals. Science 2015,
Dec 31. pii: aad6780. [Epub ahead of print.]
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
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1866.5 Galton preferred quantitative rather than qualitative measurements. He advanced the study of quantitative
inheritance but based it wrongly on the transmission of
Darwin’s theoretical particles (gemmules), not discrete elements as Mendel had discovered. Galton’s statistics have
been of lasting value, as mentioned above.
Mendel on the other hand concentrated on just
one problem in heredity, working steadily on it for 8 years
and revealing some fundamental Laws or Principles
of Heredity. He is rightly regarded as the founding father
of modern genetics. Galton, an exact contemporary of
Mendel (both born in 1822), lived to see Mendel’s triumph
after three botanists replicated Mendel’s data in the early
1900s. He must have been disappointed to see how close
he had got to Mendel’s ideas. He generously acknowledged
in his Memories of My Life of 1908 that: ‘I must stop for a
moment to pay tribute to Mendel . . . Mendel clearly
showed that there were such things as alternative atomic
characters in equal potency in descent . . . ’ He writes for a
further one and a half pages on his work with his Basset
hound supporting Mendel’s ideas of discrete rather than
blending inheritance.6
Galton’s short note of 1889 raises the question of inheritance of acquired characters. For Lamarck (1744–1829)
this was the driving force behind his theory of evolution,
or transformation as he called it, of animal species changing into new forms. It has been an idea that many biologists from Darwin’s time onwards have strongly decried
but it never seems to die, unlike the deaths of false ideas
like phlogiston or vitalism. There might be some truth in
this idea of the inheritance of acquired characters, especially as the topic of Lamarckian epigenetics is alive and
debated today.
Galton’s experimental suggestions of 1889 show
some of his ways of tackling a problem. He often chooses to get hold of an issue from the complex rather
than the simpler end. He chooses as experimental material the vague and variable features of animal behaviour, rather than the more stable features of animal
anatomy. He mentions the discovery of August
Weismann that inherited traits must pass through the
sex or germ cells, in Weismann’s nomenclature; so that
acquired features of animal behaviour, such as the trout
being conditioned not to attack the minnows, must
somehow affect the hereditary material in the germline
to affect the behaviour of the progeny. This is a clear
anticipation of an epigenetic type of inheritance.
Epigenetics can mean epi (above, or in addition to) genetics as though it is in some way beyond and more important than germline genetics. Methylation, histone
phosphorylation, non-coding RNAs etc. are just the ways
the genome organizes its components. Epigenetics is no
International Journal of Epidemiology, 2016, Vol. 45, No. 1
more nor less important than crossing-over of chromosomes, transcription factors, transposable elements or the
variety of non-coding RNA species and other regulatory
molecules that occur. Long non-coding RNAs can silence
genes. The whole of the X chromosome in the female zygote is silenced by an X-inactivating specific RNA transcript
(Xist) which coats the X-chromosome to inactivate it. The
transcription of the Xist gene is in turn regulated by a
DNA methyltransferase, showing the close inter relationships of genomic regulation.7
Some biologists have taken up Lamarckian epigeneticswith enthusiasm. A study of the foraging behaviour
in chickens as a function of stress (an echo of Galton’s
suggestion) concluded that the transmission of acquired
behavioural traits across generations did not involve
changes in DNA sequence, but could possibly be due to
DNA methylation.8 Another study in mice suggested
that fathers can transfer the liability to obesity to their
daughters as a result of the father’s food intake even before the delivery of the daughter and is not due to their
genetics.9 Of course, as is usual with vaguely defined
hypotheses, there are plenty of opponents to the idea of
Lamarckian epigenetics.
As a contribution to Francis Galton’s original paper, a
feasible experiment that may help to validate Lamarckian
epigenetics would be to take a simple inherited structural
trait (not behavioural) that codes for a simple protein (A),
such as a lipid transport peptide, that can be shown to be
silenced to produce phenotype (a). The study would then
be to genotype grand-parents, parents and children and select those pedigrees where the grand-parents are both A.A
(the default setting), find a parent who is A.a (acquired by
DNA methylation as revealed by methylome analysis of
the specific gene region) and then find children genotyping
as A.A or A.a, thus demonstrating transmission of the
acquired structural feature of (a) from parent to child. This
to me would be very convincing evidence that epigenetic
inheritance occurs; the Lamarckian part of it affecting evolution would perhaps come later. If this experiment has
been done, please send me the reference.
Conflict of interest: None declared.
References
1. Gillham NW. A Life of Sir Francis Galton. New York, NY:
Oxford University Press, 2001.
2. Galton F. Inquiries into Human Faculty & Its Development.
London: J. M. Dent, 1883.
3. Galton F. Hereditary Genius. 1st edn. London: Macmillan, 1869.
4. Galton F. Natural Inheritance. London: Macmillan, 1889.
International Journal of Epidemiology, 2016, Vol. 45, No. 1
5. Mendel GJ. Versucheuber Pflanzen-Hybriden. Verknaturf.Ver in
Brunn; band iv 1866. English translation in: J R Hort Soc 1901;xxvi.
6. Galton DJ. Man of Science, Man of God. Mendel: Discovering the
Gene. London: Timaeus Press, 2015 (in press).
7. Sharon F. Briggs, Renee A. Pera. Chromosome inactivation: recent
advances and a look forward. Curr Opin Genet Dev 2014;28:78–82.
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8. Natt D, Lindqvist N, Stranneheim H, Lundeberg J, Torjesen PA,
Jensen P. Inheritance of acquired behaviour adaptation and brain
gene expression in chickens. PloS One 2009;4:e6405.
9. Ng S-F, Lin RC, Laybutt D, et al. Chronic high fat diet in fathers
programs B-cell dysfunction in female rat off spring. Nature
2010;467:963–66.