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Introducción a La Biología Molecular E Historia Del Adn INTRODUCCIÓN A LA BIOLOGÍA MOLECULAR E HISTORIA DEL ADN Dr. Raúl N. Ondarza Profesor Titular de Bioquímica, Facultad de Medicina, UNAM e Investigador en Ciencias Médicas, Centro de Investigaciones Sobre Enfermedades Infecciosas, INSP ¿QUÉ ES LA BIOLOGIA MOLECULAR ? Según Crick es un término ambiguo que se emplea en dos formas: La primera en un sentido muy general que puede ser entender algún problema biológico a nivel molecular. La segunda forma es más clásica, se refiere a moléculas biológicas de elevado peso molecular; ej. Acidos nucleicos y proteínas. La simplicidad y la universalidad de los mecanismos básicos que operan en Biología, han permitido el avance espectacular de la Biología Molecular, sobre todo en el sentido clásico del término. LA BIOLOGÍA MOLECULAR TIENE SU ORIGEN EN TRES ESCUELAS a) La estructural y tridimensional de los británicos: Cristalografía por rayos X de la hemoglobina por Perutz, la mioglobina por Kendrew y la hélice alfa de las proteínas por Linus Pauling, Norteamericano . Max F. Perutz 1914 - 2002 John C. Kendrew 1917-1997 Linus C. Pauling 1901-1994 b) La genética unidimensional con el grupo de los fagos por: Max L. H. Delbruck, Alfred D. Hershey y Salvador Luria. 1906-1981 1908-1997 1912-1991 c) La Escuela Francesa de la Biología Molecular: Uso de la Genética Microbiana. ➢ Francoise Jacob, André Lwoff y Jacques L. Monod abordaron un problema diferente que fue un paso conceptual más allá de la expresión del gen, o sea la regulación y la interacción de los eventos que determinan el gen. EL DESCUBRIMIENTO CIENTÍFICO SE PUEDE CLASIFICAR EN TRES CATEGORÍAS Segun D. Koshland (1993) Por Serendipia, “el hallazgo al azar requiere de una mente preparada”, por ejemplo: el descubrimiento de la Penicilina y la Lisozima por Alexander Fleming. Sir Alexander Fleming Premio Nobel en Fisiologìa o Medicina, 1945 Primero en 1921, descubriò en «tejidos y secreciones nasales» una substancia importante bacteriolìtica a la cual llamò Lisozima. Mas tarde en 1928, cuando trabajaba con el virus de la influenza, observó que un moho que se desarrolló accidentalmente en una caja de cultivo de Staphylococcus había creado un área circular libre de bacterias. Al continuar con nuevos experimentos halló que el cultivo del moho (hongo) impedía el crecimiento de los estafilococos, aún si se diluía hasta 800 veces. A esta substancia la llamó penicilina. ➢ La leyenda cuenta que Sir Alexander Fleming, por aquel entonces profesor de bacteriología del St. Mary’s Hospital, de Londres, descubrió la penicilina al volver a su laboratorio tras un mes de vacaciones y encontrar sus cultivos de la bacteria Staphylococcus aureus atacados por un hongo, que luego sería catalogado como Penicillium notatum. ➢ Fleming notó con sorpresa que en los rincones de los recipientes donde crecían los hongos las bacterias brillaban por su ausencia ➢ “ A veces, la suerte y la coincidencia también forman parte de la ciencia”, dijo el portavoz de la Real Sociedad de Química, James McNish, quien agregó: ➢ “La penicilina es un raro ejemplo del progreso a través del desorden”. Desorden, puede ser ... pero coincidencia, no tanto. ➢ La historia de la penicilina, la primera sustancia que demostró ser capaz de mantener a raya a las bacterias dentro del organismo humano, es en todo caso un buen ejemplo de que “la suerte y la coincidencia” no bastan, pues de nada sirven si quien se topa con ellas no es capaz de interpretarlas en el sentido que les imprimen los objetivos de su investigación. ➢ No es cuestión de restarle mérito a Fleming, pero no fue él el primero en darse cuenta que donde abundan los hongos escasean las bacterias. ➢ Ya en 1871 el cirujano inglés Joseph Lister notó que el moho que crece sobre los quesos y las frutas debilita el desarrollo de los microbios. ➢ Y Lister no fue el único: otros científicos, como William Roberts, Louis Pasteur, Jules Francois Joubert, Andre Gratia y Sara Dath, también tomaron nota de esta relación mucho antes que Fleming. ➢ Claro que quien pasó a la historia como el padre de la penicilina fue Fleming; por eso también lo nombraron caballero y le dieron nada menos que un merecido Premio Nobel de Fisiología y Medicina (este último junto con otros dos personajes, Florey y Chain). ➢ ¿Pero por qué este hijo de un granjero, nacido en Ayrshire, Escocia, fue quien dió el puntapié inicial al desarrollo de uno de los descubrimientos más relevantes del siglo XX? Sencillamente, porque Fleming estaba buscando una cura para las infecciones, y no otra cosa. Por eso no habría de dejar pasar ese golpe de “suerte”. ➢ Para 1928, año en que habría de encontrarse con su material de trabajo cubierto de moho, Fleming llevaba un buen rato buscando una cura para las infecciones que por aquel entonces eran mortales en la mayoría de los casos. ➢ Claro que poco faltó para que el descubrimiento de la penicilina se pospusiera quién sabe por cuánto tiempo. ➢ Cuenta la leyenda que cuando Fleming retornó a su laboratorio después de un mes de vacaciones y vio sus cápsulas de Petri llenas de moho, ¡no tuvo mejor idea que ponerse a limpiarlas! ➢ Pero dicen que un miembro de su laboratorio, ese día de visita, fue quien tomó los hoy famosos cultivos de Staphylococcus aureus que aún no habían sido limpiados y se los mostró a Fleming, quien observó cómo el moho eliminaba a las bacterias. ➢ Acto seguido, se abocó a la tarea de aislar el compuesto, que habría de llamar penicilina. ➢ Sin embargo en 1931 Fleming abandonó temporalmente el estudio y fué entonces cuando uno de sus ex alumnos, Cecil Paine, continuó con su investigación y fué el primero en demostrar el valor de la penicilina en la lucha contra las enfermedades infecciosas. ➢ Lamentablemente, el ex-alumno de Fleming no publicó ni divulgó los resultados de su trabajo, pues lo desalentaba el haber utilizado un extracto crudo de penicilina, sin mayor preparación ➢ El único que continuó sus investigaciones fue un profesor de patología recién llegado a Sheffield en 1932. Era un australiano llamado Howard Florey, quien un par de décadas más tarde ganaría el Premio Nobel. ➢ En 1938, diez años después del descubrimiento de Fleming, Florey retomó el estudio de la penicilina en el Sir William Dunn School of Pathology, de Oxford. ➢ A diferencia de Fleming que llevó su trabajo en un modesto laboratorio, Florey contaba con uno bien equipado y un grupo de investigadores. ➢ Uno de éstos era Ernst B. Chain, un bioquímico de origen judío que había logrado escapar de la Alemania nazi. Algo más que un melón podrido ➢ En 1943, Florey y Chain habían llegado a la conclusión de que a la cepa de Penicillium notatum con la que trabajaban, no se le podía pedir un rendimiento mucho mayor del obtenido hasta ese entonces. ➢ Esta vez, el hallazgo fue protagonizado por una empleada del laboratorio, de nombre Mary Hunt quien llegó a su lugar de trabajo un día de 1943 con un melón que había comprado en el supermercado, un melón cubierto por un moho de un “lindo tono dorado”. ➢ De la fruta podrida, los científicos aislaron el Penicillium chrysogenum, un hongo doscientas veces más rendidor que el de Fleming, el mismo que aún hoy se emplea para obtener penicilina. Howard Walter Florey (1898–1968) and Ernst Boris Chain (1906–1979) were the scientists who followed up most successfully on Alexander Fleming’s 1928 discovery of penicillin and shared with him the 1945 Nobel Prize in physiology and medicine. Por una Campaña estratégica, algo que planeamos en forma deliberada para escalar una alta montaña, tal es el caso de la conquista del Everest por Edmund Hillary en 1953 y establecer la secuencia de la insulina por Frederick Sanger en 1959. Hillary en 2006 Sanger en 2008 Por una Anomalía enigmática. Los genes móviles en el maìz, interpretado como un rearreglo de información genética por transposición del ADN. Los Transposones por Barbara Mc Clintock (1950`s). ➢ 1902-1992 DESCUBRIMIENTO, INVENCIÓN Y CREACIÓN DNA's STROKE OF GENIUS. Gunter Stent, NEW SCIENTIST,VOL. 138, April 1993. a.- Si no hubieran existido Watson y Crick, mas tarde otros habrían hecho el descubrimiento de la doble hélice.? b.- Si no hubiesen existido Cervantes y Shakespeare, podrían otros haber escrito las obras del Quijote y Hamlet.? En el primer caso (a), seguramente que tarde o temprano, vendrían otros investigadores que harían el descubrimiento, pero en el segundo ejemplo (b), el escribir una obra igual a las mencionadas y aceptar que esto sucediera, resulta casi imposible, ya que se trata de una creación, no de un descubrimiento. El descubrimiento de la doble hélice por Watson y Crick en Abril 23 de 1953, trajo el matrimonio de las dos escuelas, la "estructuralista“ y la "informacional“ (genètica unidimensional) lo que finalmente se denominó Biología Molecular. La Genética fue la primera especialidad biológica que sufrió esta transformación ideológica, después siguieron todas las disciplinas puras o aplicadas, como la evolución, la microbiología, la fisiología, la embriología, la neurobiología y la psicología, hasta la medicina, la nutrición y la agricultura. ERWIN SCHRÖDINGER: LA CONTRIBUCIÓN DE LA FÍSICA A LA BIOLOGÍA The Nobel Prize in Physics 1933 "for the discovery of new productive forms of atomic theory" b. 1887 d. 1961 Vale la pena detenernos por un tiempo sobre un gran personaje que contribuyó de forma radical al nacimiento de la biología molecular, se trata del físico Erwin Schrödinger, quien en febrero de 1943 dió una serie de conferencias en el Trinity College, en Dublín, donde asistieron alrededor de 400 personas que nunca abandonaron el curso. Estas conferencias fueron publicadas por la Cambridge University Press en 1944 como un pequeño libro que lleva el título de ¿Qué es la vida? Este libro de menos de 100 páginas está escrito con mucha claridad, contiene apenas unas cinco referencias y solamente unas diez ecuaciones desde el principio hasta el final, constituye una fina pieza de prosa inglesa (Schrödinger, E., 1951; Dyson, F., 1987).
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