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home : columnists : columnists July 25, 2017


2/22/2017
Messrs. Mendel, Watson & Crick

By Dr. John Roberts
thedoctor@thetimes24-7.com


I received two queries from readers asking me to address how "DNA and stem cells" might be used to treat inherited medical conditions. That's a tall order for the space allotted, so I'll tackle DNA this week and stem cells next week.

Modern genetics started with Gregor Mendel's work on the inheritance of various traits in pea plants in the mid-1800s. A century later, James Watson & Francis Crick (with a lot of help from Rosalind Franklin) determined the structure of DNA in 1953. There is no doubt that the expansive scientific knowledge borne from the discovery of the structure of DNA will continue to revolutionize medical science.

DNA is an extremely elegant molecule that carries all the information needed to construct a living organism. The structure of DNA is described as a "double helix" which can be represented by imagining a ladder that has been doubly-twisted along its length (see diagram).

The "rungs" of the DNA ladder are comprised of chemical units called base pairs. Each half of a rung is comprised of a base (also known as a nucleotide) that binds in the middle of the rung to the base on the other side. DNA contains four different nucleotides. The genetic code contained in the DNA molecule is determined by the sequence of these nucleotides.

The entire complement of DNA in an organism is known as its genome. The human genome contains 3 billion base pairs, while that of a simple bacterium contains about 600,000. The race to determine the entire base pair sequence of the human genome was completed for the most part in late 2003.

Genomes contain smaller segments of DNA known as genes. Each gene contains the DNA nucleotide sequence to code for one protein. Normal proteins are critical to not only build the framework of a person, but to also run all the chemical reactions that keep us alive. Humans have a little over 20,000 known genes.

There are thousands of medical conditions that are inherited in various ways that are too complex to describe here. The basic problem in any inherited disease is that the affected person has received a defective copy of a gene from one or both parents.

Genes become defective when their sequence of DNA base pairs gets out of order. This can happen in many different ways. Recall that in order for cells to build a protein correctly, the DNA sequence must be in the correct order. If a protein is not constructed properly, it can't function normally in the body and this is what causes the signs and symptoms of disease.

Knowledge of DNA and how it works provides a number of different avenues for diagnosis and treatment of diseases. The discovery of specific genes that cause certain diseases has allowed early identification of individuals who carry the genes. This can allow for treatment to be initiated early on, before the abnormal proteins cause severe problems.

Some diseases are amenable to "gene therapy." This involves introducing normal copies of a gene into a person to allow their cells to make normal proteins. This is sometimes done by putting the normal genes into viruses that are very efficient in delivering DNA to the recipient's cells. You may have been reading a lot about a new technique to manipulate DNA called CRISPR. This technique allows very specific editing of the DNA sequence which has the potential to allow scientists to "rewrite" errors in the genetic code. CRISPR has the potential to revolutionize medicine, but also presents many ethical issues as well.

The identification of genetic DNA sequences is also becoming very important in treating diseases like cancer. Identification of specific abnormal DNA sequences in cancerous cells can offer clues as to which chemotherapy, immunotherapy or other treatments will work best to limit tumor growth.

This methodology can be applied to many diseases and treatments. It is well known that some people will respond to a certain medication while others won't or will have unacceptable side effects. Genetic sequencing holds the promise of being able to predict who will respond best to a certain drug and who will have problems.

Mendel, Watson & Crick (and Franklin) - what a legacy they left!

Dr. John Roberts is a local physician. His column appears in Monday's edition of the Times, and he has a daily health tip on the front page. Dr. Roberts is one of the owners of Sagamore News Media, parent company of The Times.





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