- Open Access
The power of stories in Pediatrics and Genetics
© Opitz et al. 2016
- Received: 28 February 2016
- Accepted: 2 March 2016
- Published: 5 April 2016
On the occasion of the opening ceremony of the 43rd Sicilian Congress of Pediatrics, linked with Italian Society of Pediatrics SIP, SIN, SIMEUP, SIAIP and SINP, held in Catania in November 2015, the Organizing Committee dedicated a tribute to Professor John Opitz and invited him to give a Masters Lecture for the attendees at the Congress. The theme expounded was “Storytelling in Pediatrics and Genetics: Lessons from Aesop and from Mendel”. The contribution of John Opitz to the understanding of pediatric clinical disorders and genetic anomalies has been extremely relevant. The interests of Professor John Opitz are linked not only to genetic disorders but also extend to historical medicine, history of the literature and to human evolution. Due to his exceptional talent, combined with his specific interest and basal knowledge in the genetic and pediatric fields, he is widely credited to be one of the best pediatricians in the world.
John Opitz was born in Hamburg in 1935, but at a young age he moved with his mother from Germany to the US. Soon after his arrival in the US he attended the University of Iowa, where he was introduced to the famous embryologist, geneticist, and zoologist professor Emil Witschil, with whom he started to work scientifically. In Iowa, one of the most ancient and accredited Universities in the US, he completed the medical course where he was appreciated for his scientific capacity by all the teachers of this University including the pediatrician Professor Hans Zellweger, who was also in Iowa having been formerly at the famous school of Fanconi in Zurich. Soon after, he moved from Iowa City to Madison where Klaus Patau was teaching and subsequently studied in Wisconsin with David W Smith. During his long stay in Wisconsin he continued to develop his great interest in fetal/pediatric genetic pathology and explored the concept of atavism and the hypothesis of human developmental fields in congenital disorders. Accepting the invitation of Dr. Philip Pallister he moved from Wisconsin to the appointment as Director of the Shodair Montana Regional Genetic Service Program in Helena, Montana, where he remained for 8 years. Subsequently, he joined the University of Utah School of Medicine as Professor of Pediatrics in the Division of Medical Genetics.
The contribution of John Opitz to the understanding of pediatric clinical disorders and genetic anomalies has been extremely relevant. The interests of Professor John Opitz are linked not only to genetic disorders but also extend to historical medicine, history of the literature and to human evolution. Due to his exceptional talent, combined with his specific interest and basal knowledge in the genetic and pediatric fields, he is widely credited to be one of the best pediatricians in the world. He has received numerous awards and distinctions, and honorary degrees from the University of Montana, Kiel, Copenhagen and Ohio, to mention just a few. He was designated winner of the William Allan Award of the American Society of Human Genetics and in 1999, at the instigation of Professor Liborio Giuffrè from Palermo, he was awarded with the ‘Laurea Honoris Causae’ at Bologna University.
Sicilian Universities have kept in contact with this great scientist in the course of the years. With the collaboration of the Professor Giovanni Neri from the Catholic University of Rome, the three Sicilian universities and the Oasi of Troina regularly invited him in turn each year, with his prompt approval. Some of us had the opportunity to assist with the physical examinations performed by Professor Opitz during his stay in Sicily. He showed his great talent with scientific and clinical competence, professionalism, empathy and delicacy in talking with the parents of the affected children.
We were fortunate indeed to have the opportunity to take part in his clinical performance and each time it was a lesson in human behavioral and clinical professionalism.
“We believe in the power of Science, Exploration, and Storytelling to Change the World.”
Mission Statement, National Geographic Society of the USA 288(4), Oct 2015 .
“… to change the world,” we all hope, (contrary to ISIS), for the better.
First, allow me to express to my most distinguished colleagues and friends of decades Giovanni Corsello of Palermo and Lorenzo Pavone of Catania, and the members of the Organizing Committee, my gratitude for their most gracious invitation to participate at this congress of the Italian (Sicilian) Society of Pediatrics. Inability to participate personally for various reasons has been a strong impetus for me to prepare this review. To pay homage also to the Italians of immortal fame who were storytellers, e.g. Boccaccio, Petrarch, Dante, Tasso and those working more recently as scientists e.g. Italo Barrai, Angelo Serra, Paul Polani, Luigi Cavalli-Sforza, Mario Capecchi, Guido Pontecorvo, Salvador Luria, Renato Dulbecco, a.o., who had made lasting contributions to genetics, basic, human and medical.
A process for combinatorial capacity emerges, “prolonged and extensive in humans leading eventually to spoken language.” What I find remarkable from an evolutionary perspective is that the “brainstem – midbrain systems for call production are common in vertebrates.” Margoliash and Tschernichowski  postulate that species- specific differences in vocal production “might have evolved through gradual increase in the interaction between these primitive brain structures and the…. forebrain” with resulting species – specific differences in combinatorial and symbolic processes. Thus, the results of Takahashi et al. seem to identify an ancient capacity for vocal learning refined by an enlarging human brain continuing an evolutionary process that led to communication in other animals.
Since, in the mouse, adult cortical plasticity depends on stimulation during an early postnatal critical period , it seems prudent to assume the same for humans and to promote it within reasonable physiological limits.
“I cannot think it will hold. The tendency of hybrids to revert to either parent is part of a wider law… that crossing races as well as species tends to bring back characters which existed in progenitors hundreds and thousands of generations ago. Why this should be so, God knows” .
Thus, in “The Variation of Plants and Animals under Domestication” (including The Provisional Hypothesis of Pangenesis) of 1868 Darwin ended up postulating (again, after Hippokrates ~ 400 BCE) the existence of “gemmules” produced by every part of the body affecting germ cells and offspring modified by the parental internal and external conditions of life. As Hippokrates put it: “… the seed comes from all parts of the body, healthy seed from healthy parts, diseased seed from diseased parts” quoted in . In other words, pure and plain Lamarckism i.e. Darwinism imposed on a theory of blending inheritance.
For me, this is the final time this year to recollect 2015 as the sesquicentenary of Mendel’s two presentations, on 2/8 and 3/8/1865 of his Versuche über Pflanzenhybriden published in 1866 as the methodologically soundest cornerstone of the science of genetics.
Öttinger L. 1837. Die Lehre von den Combinationen nach einem neuen Systeme bearbeitet und erweitert. Freiburg, Gebrüd. Groos. Öttinger was then Professor of Mathematics at the University of Freiburg.
Ettinghausen A von. 1826. Die combinatorische Analysis als Vorbereitungslehre zum Studium der theoretischen höhern Mathematik. Wien, JB Wallingshauser, with a note by Cotterman that this copy of the work had been inscribed by the author to a “dear friend Stephan, April 7, 1863.”
Both of these were highly advanced treatises. Von Ettinghausen was one of Mendel’s teachers at the University of Vienna, successor of Doppler as Professor of Physics.
In any event, it seems that as early as 1851 or 1852, Mendel had a research plan in mind. He returned to the Augustinian monastery of St. Thomas of Alt-Brünn on 21 Juli 1852; soon thereafter (Mawer, 2006) Mendel ordered his seed peas a.o from the Benary company in Erfurt, Germany, the same firm from which both of my grandfathers ordered their seed a lifetime later.
Aa1: seed shape, round vs wrinkly
Bb: Seed color, yellow vs green
Cc: Pod color, gray brown vs white with blossom color violet red vs white
Dd: Pod form, smooth vs serially constricted
Ee: Color of immature pod, green vs yellow
Ff: Position of flowers, axial vs terminal
Gg: Length of plant axis, tall vs short
Clearly, Mendel knew what he was doing. Also, he was fortunate in that all traits were unlinked except for 2 (Gg, Dd) on the same chromosome (4), but far enough apart so as to appear unlinked in his work .
He finished in 1864, analyzed the data, and prepared his manuscript in his characteristically beautiful handwriting. One can imagine that writing the paper for presentation in two sessions on 2/8 and 3/8/1865 and for publication the following year in the proceedings of the Natural History Society of Brünn must have given Mendel considerable headaches. Because for both purposes he had to condense, hence select, hence leave off all of those data, we now wish to know and now lost as Mendel’s successor as Abbot destroyed (burned) what was left at Mendel’s death. It must be remembered that his two presentations were a didactic exercise, structured to convince, and not a peer-reviewed research paper in the modern sense. Also, that the chi-squared test was not introduced into biology until after Mendel’s death.
Anticipated the genes, or as he called them: Die formbildenden Elemente.
Enuntiated clearly the concept later called allelism.
Showed that the dominant and recessive (Mendel’s terms) members of a pair of alleles in a hybrid did not blend but remained discrete and intact and could segregate in future crosses.
Counted the offspring of crosses between hybrids and found consistently a ratio of 3 dominants to 1 recessive with 1/3 of the former purebreeding dominants and 2/3 hybrids, called heterozygotes nowadays, i.e. a ratio of 1:2:1 of AA to Aa to aa.
Intuited that this 1:2:1 ratio in fact represented the expansion of the binomial (a + b)2 = a2 + 2ab + b2 one pair of alleles at a time.
And that if this assumption were correct and each plant could be expected to yield a constant 4 seeds/generation, then continued selfing of heterozygotes (Aa, or 2ab combinatorially) should result in a gradual (asymptotic) diminution of the fraction of hybrids, i.e.
In a ratio of
Aristotle (Harvey, Wolff): Epigenesis (the formed arises from the unformed);
K.E. von Baer Pander, Wolff: Germ layers
Humboldt: Plant geography
Wallace, Darwin: Natural selection
Mary L: Lyonization
Immediately after the rediscovery of Mendel in 1900 these data and their combinatorial consequences were confirmed and became the axiomatic cornerstone of genetics as genetics will become the cornerstone of medicine in the future going as we are already going from exome to genome sequencing. Mendel’s “shoes” were our baby shoes in genetics reminding us that if we don’t know where we came from we won’t know where we are going to.
Linkage. In 1905 Bateson and Punnett crossed 2 white types of sweet peas (“Emily Henderson”) which differed only in shape of pollen grain (normal long, and less common “roundish”). The initial focus was solely on the inheritance of pollen shape. But to their surprise, when they crossed the white hybrids between the 2 pollen types the offspring were purple-flowered “like the wild Sicilian plant from which our cultivated seed peas are descended” . Even more remarkable was the fact that these 2 allelomorphs (white-purple blossoms; long-round pollen grains) did not reassort independently but appeared to show linkage, “coupling” as they called it, a phenomenon soon confirmed in Drosophila. This deviation from the 9:3:3:1 offspring ratio expected for a dihybrid cross of unlinked genes became the basis for later mapping studies, placing genes, in linear order, on the chromosomes, later aided by the discovery of the polytene (salivary gland) chromosomes in diptera.
“The beauty of the earth is like a dumb voice arising from it. You observe it and look on its beauty, fertility and sources. You observe how the seed begins to germinate and gives a completely new thing which was sown. You take note of all of it, and it is as though you were asking in your mind why it is so. Filled with wonder, you search on, going to the root of things and finally you discover a great beauty and a magnificent strength.”
Ennaration in ps. 133, 13, 1876
Substitute Mendel for “you” in the above; Mendel, the Aesop of genetics.
Prof. John M. Opitz
To Renata Laxova, native of Brno, my successor at the University of Wisconsin, friend and collaborator, for the gentle reminder of 2015 as the 150th anniversary of Mendel 1865; to Max Muenke of the NIH (and CHOP) for calling Rheinberger to my attention ; to Angel Peatross for data research and expert illustration and document preparation; and to Giovanni Corsello, President of Italian Society of Pediatrics, for occasioning this opportunity in the first place.
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