It was almost eight years ago, when I was completing my doctoral studies at the University of Illinois, that I seriously began reviewing literature regarding mammalian cloning. After exhaustive reading and critical analysis of all the published literature, I came to the conclusion that mammalian cloning was a possibility. I came to this conclusion after reading couple of papers from Dr. DiBerardino’s laboratory (Science, 219,1983; Science, 224, 1984) where she and her colleagues had succeeded in making an adult frog cell “totipotent”; a specific stage of DNA where it is capable of directing the development of a complete organism, by culturing these adult frog cells in the laboratory for some time followed by nuclear transfer. Although her group reported the development to the tadpole stage only, but it was obvious to me that the failure to get adult frogs from these nuclear transfer experiments was not that “differentiated DNA” taken from an adult cell had undergone some mysterious irrevocable transformation, but that DNA taken from adult frog cell had not been de-differentiated enough. Tissue culturing of cells under starving conditions causes DNA to de-differentiate. Subsequently I called Dr. DiBerardino, who was at that time at Medical College in Philadelphia and discussed my thoughts about her observations. She agreed that it might be possible to get fully formed adult frogs by manipulating tissue culture conditions but she did not have funds to continue research along these
At this point, I wrote a three-page proposal describing the possibility of making an adult differentiated mammalian cell nucleus “totipotent” by tissue culturing under limiting conditions. I mailed this proposal along with my resume to many scientists in this country, who are working in mammalian development. I was hoping to do my post-doctoral work on my proposal. They all said that it was a very interesting proposal, but would not want to undertake this line of research. They never explained the reasons to me. I have both the original proposal and the response letters from many of these top ranked scientists with me. One of the scientists that I mailed my proposal to was Dr. Devor Solter, who was at that time at Wistar Institute in Philadelphia. I was especially curious to hear from him because he and Dr. McGrath had published a paper in Science (226, 1984) on cloning of adult mice and had failed. They concluded that “mammalian cloning” was impossible, because of “irreversible changes happening to mammalian DNA as it differentiates”. But, they had not tried to de-differentiate the differentiated DNA by tissue culturing the adult cells as Dr. DiBerardino’s group had done with amphibian cells. I called him after I did not hear from him. We discussed my proposal but he seemed to be convinced that “mammalian cloning was impossible”. At this point, I dropped my proposal and instead began studies on hypertension at the Baylor College of Medicine. This work I am continuing here at the Vanderbilt University Medical Center.
One other person that I had sent my proposal to was Dr. Neal First at the University of Wisconsin. I called him and again we discussed my proposal. He said that perhaps mammalian cloning was unlikely because of the work done by Solter and McGrath. Some month’s back this year, I sent e-mail to Dr. First and reminded him of my proposal and our telephonic conversation. I did this in context of success of “Dolly” the sheep cloning done by Dr. Ian Wilmut and colleagues (Nature, 1997). Dr. First said that I was right in my proposal about the need to de-differentiate the adult differentiated nucleus prior to nuclear transfer. This is the single most important step which Scottish scientists did in their successful cloning of “Dolly”. I have the e-mail response from Dr. Neal First. Indeed the reason why there is such a low frequency (only 1 in 277 nuclear transfers) with sheep cloning is that the other 276 nuclei have not been de-differentiated enough. I am in correspondence with Dr. Wilmut about this point. Also, recently Dr. Yanagimachi and colleagues have successfully cloned mice (Nature, 23 July, 1998).
In my opinion, human cloning will not just bring hope to infertile couples but will provide a higher level (next step) in human evolution. Human cloning will not just mean that Mankind has achieved the technology to defeat death and achieve immortality but such a feat will immeasurably enhance human spirit, confidence and spirituality. Human cloning, I am totally convinced about its likelihood of happening, will bring human race into a different dimension. In spiritual repercussions, human cloning will mean same as the resurrection of Jesus Christ or the birth of Gautam Buddha. It was these very significant consequences of human cloning that initially fired my imagination and led me to question the dogma that “mammalian cloning was impossible”.
E-mail: K. Razdan, Ph.D. at Kuldeep.Razdan@mcmail.vanderbilt.edu
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