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The history of immunology
Immunology Today, Vol. 11, No 9 199(J
do not reflect those of the mother at the end of pregnancy, but reflect the average levels of insulin-anti-insulin complexes throughout gestation. They may theoretically interfere with placental circulation and explain some of the neonatal complications of diabetic pregnancy.
Gestational diabetes mellitus GDM is defined as carbohydrate intolerance of variable severity that begins, ol is first recognized, during the present pregnancy. GDM is a risk factor for both type II and type I diabet.~s. R. Acton (Univ. Birmingham, Alabama) stressed the fact that various HLA phenotypes and autoantibodies have been found to be associated with GDM it, black~ from Jefferson County, Alabama. The increased fre-
The historyof immunology Sir, After reading Jonathan Trager's review of Arthur Silverstein's book on historical precedents in immunology (Immuno/. Today, 1990, 11, 182183), I was struck by the large number of concepts contained in the book that are now considered 'new' ideas because they have recently been evoked. Indeed, it is disconcerting that students nowadays are presented with ideas that, in many cases, were published earlier, quickly forgotten, and as Silverstein points out, are resurrected by somebody else who receives most, if not all, of the credit. It seems that we could advance immunology conceptually by searching obscure and moldering papers in the libraries rather than rediscovering them as 'new' in the laboratory ~.2. Silverstein's book gives some examples of this, to which I would like to add my own. Picking up immunology journals today, one is confronted with a virtual blizzard of papers that use what is popularly known as 'transfection' a process that generally involves insertion of alien DNA or RNA into recipient cell populations with, presumably, subsequent expression of specific molecules. Transfection of cells with nucleic acids is not a new idea, and indeed many papers from different laboratories worldwide were published in
quencies of HLA phenotypes reportedly associated with NIDDM as well as IDDM in his GDM subjects suggest that the population is highly heterogeneous with regard to the type of diabetes for which these women are at risk. Long-term follow-up studies could possibly clarify this situation. The data available seem to suggest that smooth muscle and nuclear antibodies are risk factors for blacks for the development of GDM. However, it will be necessary to identify and follow up women who have these autoantibodies present before development of GDM to de~ermine their value as a predictor of the disease.
J. Roth (NIH, Bethesda) who, using the chicken as a model, showed that insulin and insulin-like growth factor I (IGFI) are present in the unfertilized egg. He also detected insulin in early embryos even before organogenesis, that is before islet 13 cells appear. Since anti-insulin antibodies and antibodies against the receptors for insulin retard the growth and development of the embryo, biochemically and morphologically, Roth concluded that the hormone and its receptors play an important role in the early stages of normal development. The teratogenic effects of insulin at high dcses appear to be mediated by an IGF receptor.
The chickenand the egg Finally, another fascinating problem was discussed at this congress by
Carla Giordano is at the Laboratoryof Immunology, Clinica Medic-a,Universityof Palermo, Italy.
the late 1950s and earlier, describing the specific expression of 'transfected' molecules from recipient cell populations after incubation of lymphoid cells with ribonucleic acid 1-3. Spending a good part of my career doing 'conversion/transfection' experiments during the late 1960s through to the 1970s, I heard all of the arguments from scores of 'right-
nology has been considerable. On the other hand, young people entering the field of immunology today believe that construction of immunological tools to address certain questions using transfection techniques is routine, perfectly acceptable, non-controversial and relatively recent. Some techniques are recent, but the idea itself is over 30 years old -J---:~'u~pwt~ the fact .ola[ . . . . . .a, OT-• our contemporary transfectionists fail to cite any of the earlier studies4. The example is another piece of evidence that science moves in fits and starts and, in many cases, resurrection of earlier ideas. It may be worthwhile to consider when we look at immunology curricula, that perhaps our younger colleagues should be exposed to some historical immunology before anything else. The ideas represented by earlier thought will most certainly bear fruit later in the laboratories, as the history of cell 'transfection' has so vividly demonstrated.
+k;,,L.,nn' ..... ~^~.-+~ of ~.L._ u,~ day L,,,,,,~,,,~ "-. l,H~wuw~wv~w:Jw.~ for w h y such a p h e n o m e n o n could not work, and could not be believed
as 'real '4. How such information could be expressed was questioned; and the idea that lymphokines, antibodies, or any other products of lymphoid cells could be expressed after 'transfection' with nucleic acid was considered a!most impossible, even absurd. The criticism, intellectual resistance and, in some cases, hostility to the idea eventually had a negative influence on study sections, killing any chance for further progress on the subject. Today, in a historical perspective, I see this as one more example of what Silverstein suggests in his book. Nowadays, nobody questions whether gigantic molecules of DNA obtained by enzyme snipping, and insertion into even larger plasmid vectors get into cells. Complex molecules are readily expressed in the form of everything from antibodies, histocompatibility antigens, cytokines, enzymes, hormones and receptors; the list is almost endless. The impact on molecular biology and immu-
~) 1990, ElsevierScience Publishers Ltd, UK. 0167--4919/90/502.00
Ronald E. Paque UT Health ScienceCenter, 7703 Floyd Curl Dr, San Antonio, TX 78284-7758, USA.
References 1 Fishman,M. (1959) Nature 183, 1200-1201 2 Cohen, EP. and Parks,J.J. (1964) Science 144, 1012- 1013 3 Askonas, B.A. and Rhodes,J.M. (1965) Nature 205, 470-474 4 Paque,R.E.(1983)J. Biol. Response ModiE 2, 563-576 3O3
do not reflect those of the mother at the end of pregnancy, but reflect the average levels of insulin-anti-insulin complexes throughout gestation. They may theoretically interfere with placental circulation and explain some of the neonatal complications of diabetic pregnancy.
Gestational diabetes mellitus GDM is defined as carbohydrate intolerance of variable severity that begins, ol is first recognized, during the present pregnancy. GDM is a risk factor for both type II and type I diabet.~s. R. Acton (Univ. Birmingham, Alabama) stressed the fact that various HLA phenotypes and autoantibodies have been found to be associated with GDM it, black~ from Jefferson County, Alabama. The increased fre-
The historyof immunology Sir, After reading Jonathan Trager's review of Arthur Silverstein's book on historical precedents in immunology (Immuno/. Today, 1990, 11, 182183), I was struck by the large number of concepts contained in the book that are now considered 'new' ideas because they have recently been evoked. Indeed, it is disconcerting that students nowadays are presented with ideas that, in many cases, were published earlier, quickly forgotten, and as Silverstein points out, are resurrected by somebody else who receives most, if not all, of the credit. It seems that we could advance immunology conceptually by searching obscure and moldering papers in the libraries rather than rediscovering them as 'new' in the laboratory ~.2. Silverstein's book gives some examples of this, to which I would like to add my own. Picking up immunology journals today, one is confronted with a virtual blizzard of papers that use what is popularly known as 'transfection' a process that generally involves insertion of alien DNA or RNA into recipient cell populations with, presumably, subsequent expression of specific molecules. Transfection of cells with nucleic acids is not a new idea, and indeed many papers from different laboratories worldwide were published in
quencies of HLA phenotypes reportedly associated with NIDDM as well as IDDM in his GDM subjects suggest that the population is highly heterogeneous with regard to the type of diabetes for which these women are at risk. Long-term follow-up studies could possibly clarify this situation. The data available seem to suggest that smooth muscle and nuclear antibodies are risk factors for blacks for the development of GDM. However, it will be necessary to identify and follow up women who have these autoantibodies present before development of GDM to de~ermine their value as a predictor of the disease.
J. Roth (NIH, Bethesda) who, using the chicken as a model, showed that insulin and insulin-like growth factor I (IGFI) are present in the unfertilized egg. He also detected insulin in early embryos even before organogenesis, that is before islet 13 cells appear. Since anti-insulin antibodies and antibodies against the receptors for insulin retard the growth and development of the embryo, biochemically and morphologically, Roth concluded that the hormone and its receptors play an important role in the early stages of normal development. The teratogenic effects of insulin at high dcses appear to be mediated by an IGF receptor.
The chickenand the egg Finally, another fascinating problem was discussed at this congress by
Carla Giordano is at the Laboratoryof Immunology, Clinica Medic-a,Universityof Palermo, Italy.
the late 1950s and earlier, describing the specific expression of 'transfected' molecules from recipient cell populations after incubation of lymphoid cells with ribonucleic acid 1-3. Spending a good part of my career doing 'conversion/transfection' experiments during the late 1960s through to the 1970s, I heard all of the arguments from scores of 'right-
nology has been considerable. On the other hand, young people entering the field of immunology today believe that construction of immunological tools to address certain questions using transfection techniques is routine, perfectly acceptable, non-controversial and relatively recent. Some techniques are recent, but the idea itself is over 30 years old -J---:~'u~pwt~ the fact .ola[ . . . . . .a, OT-• our contemporary transfectionists fail to cite any of the earlier studies4. The example is another piece of evidence that science moves in fits and starts and, in many cases, resurrection of earlier ideas. It may be worthwhile to consider when we look at immunology curricula, that perhaps our younger colleagues should be exposed to some historical immunology before anything else. The ideas represented by earlier thought will most certainly bear fruit later in the laboratories, as the history of cell 'transfection' has so vividly demonstrated.
+k;,,L.,nn' ..... ~^~.-+~ of ~.L._ u,~ day L,,,,,,~,,,~ "-. l,H~wuw~wv~w:Jw.~ for w h y such a p h e n o m e n o n could not work, and could not be believed
as 'real '4. How such information could be expressed was questioned; and the idea that lymphokines, antibodies, or any other products of lymphoid cells could be expressed after 'transfection' with nucleic acid was considered a!most impossible, even absurd. The criticism, intellectual resistance and, in some cases, hostility to the idea eventually had a negative influence on study sections, killing any chance for further progress on the subject. Today, in a historical perspective, I see this as one more example of what Silverstein suggests in his book. Nowadays, nobody questions whether gigantic molecules of DNA obtained by enzyme snipping, and insertion into even larger plasmid vectors get into cells. Complex molecules are readily expressed in the form of everything from antibodies, histocompatibility antigens, cytokines, enzymes, hormones and receptors; the list is almost endless. The impact on molecular biology and immu-
~) 1990, ElsevierScience Publishers Ltd, UK. 0167--4919/90/502.00
Ronald E. Paque UT Health ScienceCenter, 7703 Floyd Curl Dr, San Antonio, TX 78284-7758, USA.
References 1 Fishman,M. (1959) Nature 183, 1200-1201 2 Cohen, EP. and Parks,J.J. (1964) Science 144, 1012- 1013 3 Askonas, B.A. and Rhodes,J.M. (1965) Nature 205, 470-474 4 Paque,R.E.(1983)J. Biol. Response ModiE 2, 563-576 3O3