Monday, December 12, 2011

My Professor's Dilemma

K.K.Vinod and M. Maheswaran

Yesterday my Professor, Dr M Maheswaran wrote me after reading the book “Emperor of All Maladies- A Biography of Cancer” by Siddhartha Mukherjee.

He wrote,

Genes talk to genes and pathways to pathways in perfect pitch, producing a familiar yet foreign music that rolls faster and faster into a lethal rhythm.

If the data did not fit the dogma then the dogma, not the data, needed to be changed.

After reading the book and understanding the biological causes behind the cancer genetics I felt very bad about things what we are teaching and doing in understanding the genetics of many of the traits we deal with crops and exploit the results in practical plant breeding. Many of the concepts of predictions we make based on the classical genetics, whether it is Mendelian or Galtonian, remain irrelevant considering the biological implications on a particular phenotype. For example, p53 gene, an unassuming name, has major role in the development of human cancer than any other component of the genome. The gene get its name from the product it encodes, p53, which is a polypeptide having a molecular weight of 53 kilo Daltons. p53 was thought for number of years to be a dominantly acting oncogene, but in 1990, it was recognized as the tumour suppressor gene that, when absent, is responsible for a rare inherited disorder called Li-Farumeni syndrome, whose victims are affected with a very incidence of certain cancers, including breast cancer and leukaemia (though there are separate and specific genes for breast cancer and leukaemia). Like individuals with the inherited form of retinoblastoma, persons with Li-Farumeni syndrome inherit only one functional copy of the p53 tumour suppressor gene and are thus highly susceptible to cancer as the result of random mutations that knock out the function of the remaining copy of the gene. Further, if we see the development of cancer in humans (for any type of cancer development), the possible sequence of genetic changes in a cell lineage are given below.

The complexity of cancer can be better understood if you read the above book. But in plant genetics we decide the genes based on the prediction methods and most of the gene predictions are based on the “breeder friendly phenotyping methods (whatever be the trait we have the simple means and many models to predict the genes). The advent of molecular marker technology made this simpler. Once there is co-segregation of DNA marker, the gene discoverer assumes he/she got gene for the phenotype (some where I read that there are 83genes identified for resistance to rice blast disease and we have 26 genes for brown plant hopper resistance in rice- just go back and read the situation of gene for Li-Farumeni syndrome). Gene identification based on breeder friendly phenotyping and pyramiding of those genes without knowing the functionality of the genes is a wasteful exercise. In recent times people started asking questions whether it is good to pyramid dominant genes or recessive genes without understanding the situation of obscurity prevailing over dominance or recessiveness. This can be remedied if every gene discoverer realizes the importance understanding the biology behind each of the phenotypes instead of evolving prediction methods.

My Professor stops his letter by saying “Predictions are always based on perceptions”.

Concern of my professor was of a genuine teacher, who attach paramount importance to imparting current and competitive knowledge to his students. He laments that except a very few teachers of plant genetics, none are ready to change the way science unfolds life’s mysteries. So instead of changing the dogma, we are often bending the data fit the dogma. Are we ruthlessly incompetent because we are afraid of deviating from the conventions?

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