Francis (Frank) Ruddle (from Yale Univ. web site, picture by Michael Marsland)
“Yale scientist Francis Hugh (Frank) Ruddle, a pioneer in genetic engineering and the study of developmental genetics, died March 10 in New Haven. He was 83 years old“. This is how a text in memoriam of Frank Ruddle, who passed away last Sunday, begins, at the Yale University web site. Frank Ruddle was Professor Emeritus at the Department of Molecular and Developmental, Yale University. In collaboration with Jon W. Gordon, from the Mount Sinai School of Medicine in New York, at the time one of his post-docs, Frank Ruddle devised and succeeded in creating the first transgenic mice, the first animals genetically modified after microinjecting a plasmid DNA into the pronuclei of fertilized mouse eggs. These seminal papers were published in 1980 and 1981. In order to remember Frank Ruddle’s pioneer contributions to the field of transgenic technologies, to highlight the relevance of their findings among our youngest colleagues, and to adequately assess, in perspective, their fantastic achievements, made more than 30 years ago (or only 30 years ago, depending how you would like to see the case) I am citing here the full abstracts, as they appear published in their respective journals, PNAS (in 1980) and Science (in 1981).
Genetic transformation of mouse embryos by microinjection of purified DNA.
Gordon JW, Scangos GA, Plotkin DJ, Barbosa JA, Ruddle FH.
Proc Natl Acad Sci U S A. 1980 Dec;77(12):7380-4.
ABSTRACT: “A recombinant plasmid composed of segments of herpes simplex virus and simian virus 40 viral DNA inserted into the bacterial plasmid pBR322 was microinjected into pronuclei of fertilized mouse oocytes. The embryos were implanted in the oviducts of pseudopregnant females and allowed to develop to term. DNA from newborn mice was evaluated by the Southern blotting technique for the presence of DNA homologous to the injected plasmid. Two of 78 mice in one series of injections showed clear homology, though the injected sequences had been rearranged. Band intensities from the two positive mice were consistent with the presence of donor DNA in most or all of the cells of the newborns. These results demonstrate that genes can be introduced into the mouse genome by direct insertion into the nuclei of early embryos. This technique affords the opportunity to study problems of gene regulation and cell differentiation in a mammalian system by application of recombinant DNA technology.”
Integration and stable germ line transmission of genes injected into mouse pronuclei.
Gordon JW, Ruddle FH.
Science. 1981 Dec 11;214(4526):1244-6.
ABSTRACT: “Genetic material has been successfully transferred into the genomes of newborn mice by injection of that material into pronuclei of fertilized eggs. Initial results indicated two patterns of processing the injected DNA: one in which the material was not integrated into the host genome, and another in which the injected genes became associated with high molecular weight DNA. These patterns are maintained through further development to adulthood. The evidence presented indicates the covalent association of injected DNA with host sequences, and transmission of such linked sequences in a Mendelian distribution to two succeeding generations of progeny.”
In summary, they injected some heterologous DNA into the pronuclei of fertilized mouse eggs. This DNA was eventually covalently associated with the host DNA (integrated) and was also successfully transmitted to the progeny of the resulting genetically-modified mice (transgenic), therefore it was inherited as a new DNA piece, a new genetic trait, thereby creating a new mouse strain, a new animal model, a trangenic mouse. Isn’t that splendid and beautifully simple? Indeed, but someone had to envisage first the experiment, someone had to carry out the injections successfully. Someone was first in demonstating this was actually possible. This was Frank Ruddle.
On behalf of the International Society for Transgenic Technologies (ISTT) I want to express my most sincere condolences to his family, colleagues and friends. This is a great loss for the transgenic community.
