Central  South  Dakota Medical News
The Clinical View
by P.E. Hoffsten, MD
1 May 2002

HOW TO FIX A HEREDITARY DEFECT

      Although it is hard to imagine, the information on how to create an adult human being  was at one time contained in a single cell.  That single cell that results from the union of a sperm and an egg contains all of the information on how to grow your legs, your brain, the color of your eyes, whether you will be tall or short, whether you will struggle with your weight or be thin through no effort and a host of other physical and mental characteristics a person will have. This information is coded in the DNA contained in the nucleus of a single cell.  That DNA can be thought of as the instruction manual on how to make you.

       Anyone that has ever used an instruction manual to try and put something together has experienced knowing that things do go wrong.  This is also true of the instruction manuals for all of the people in world. Various different sentences or paragraphs , or even whole pages of the instruction manual can have mistakes and then whatever you are trying to put together just doesn’t work.  This same problem can happen in the DNA in the nucleus of that first cell that becomes you.  By the way, unless you have an identical twin, no two of us look exactly alike and  therefore the instruction manual for each one of us is a little bit different.  Unless you have an  identical twin, each one of us has a different instruction manual.

       Suppose something happens and there is a mistake in your instruction manual.  How can we fix that?  The term used to describe the fixing process is called “ genetic engineering”. Recently, that term has gotten a lot of bad press especially in light of the resistant forms of corn and other crops that are genetically engineered to resist certain diseases to yield a better crop. There are some among us that think that this type of genetic meddling is inappropriate for human beings.  While there will be some mistakes as we go forward the intent of the effort in human beings is to relieve disease and suffering.  Below I will describe a glorious  success.

       There is a rare hereditary disease called combined immunodeficiency that occurs primarily in males and is secondary to a defect in their Y chromosome.  These babies lack normal   immunity and will die within the first year or two of life because of multiple recurrent devastating infections.  These babies are a tragedy for themselves and the families that they live in.

     Many years ago, it was found that these babies could be transplanted with bone marrow from a normal individual and they would then be able to live to become  adults  although they would require frequent injections of antibodies all of their lives.  This was  because  the transplanted  cells  were  not exactly the same as the person’s  own cells and the cooperative effort to make antibodies to protect the individual didn’t occur.

       Through genetic engineering, the complete solution to this problem has now been achieved.  Scientists were able to isolate the defective DNA these babies had and identify what was wrong.  They then were able to isolate a normal piece of DNA that would correct the defect.  The next step was to figure out how to get the good DNA into the baby with combined immunodeficiency to render these babies normal.

       Some bright smarty-pants in a research laboratory thought that a way to do this was to put the good DNA into a harmless virus.  You would then use the harmless virus as a delivery truck that would infect the cells of the baby with combined immunodeficiency and hope the good DNA would be incorporated into that babies genetic code.  The thought was that the baby with combined immunodeficiency now in possession of the good DNA message on how to make antibodies would become normal.  Believe it or not that is what happened.  This has now been done on five individuals who were afflicted with this rare disease as published in a recent issue of the New England Journal of Medicine.  These five babies are now more than two years old and are growing normally without infections.  They are able to make their own antibodies without the need for injections because their own cells cooperate with each other.  They appear now to be normal human beings.

      The message of the article is two.  First of all, not all viruses are bad.  There are viruses that are either harmless or in this particular case even highly beneficial.  A virus is something that attaches to a cell and injects some DNA or RNA into the cell.  What happens next depends on what is injected.  In the case of the young boys in this article, it was something very good. Not all viruses are bad.

       The next message is that genetic engineering is neither good nor bad anymore than a hammer or a spoon is good or bad.  It is a tool being used to change genetic defects that would leave a person with a mortal or a very unpleasant outcome.  The object of genetic engineering is to improve the quality and quantity of life.   Agriculturally it will improve the yield and the quality of our crops.  Scientists, researchers, and doctors are not out there to try to make Frankenstein’s.  They are out there to make things better and as the article above shows, for the very first time they have cured a genetic human disease.