Some thoughts on ecology, evolution and economics

Gene therapy

Siddartha Mukherjee is a compelling author and a respected authority on medical science. His latest book, The Gene, traces the history of genetics -the prediction of heredity. Gregor Mendel, the 19th century monk who launched the discipline, features prominently with his experiments on breeding peas . Connecting a particular trait to a piece of DNA is still difficult despite a century of research, including the Human Genome Project. Just as interesting from the author’s perspective is what we should use this knowledge for. Any technology worth its salt has implications in the real world. Few have implications as permanent and as profoundly linked to the human identity as gene therapy.

Where an individual produces a defective protein, gene therapy can introduce a patch that  will improve the effectiveness of the proteins produced for the rest of that person’s life. It cannot change the proteins that have already been produced. Unless it is applied to the cells that make sperm and eggs, it will not change the inheritance of that defective trait. Safely introducing enough of these patches to make a difference in a person’s health is a difficult obstacle. These problems are compounded when there is more than one defective protein.  Muhkerjee uses three criteria to justify gene therapy: 1) the severity of suffering, 2) the potential effectiveness of the treatment (or the penetrance of the gene) and 3) the risk to the patient and to others.

The risks of gene research were first underlined by the researchers themselves at the Asilomar conference in 1975, calling for strict containment of viruses and bacteria carrying human genes – especially those that cause cancer.  The ethics of creating genetically modified humans was not discussed at Asilomar.  Viewed from the world of genomics, swapping genes between species is not a big deal – since most of the human genome is shared by all animals.  In fact, the only reason that we know what many of our genes do is because they were identified first in worms, flies or mice. Introducing novel genes into humans  – making them stronger, smarter or more attractive -would be exceedingly difficult, despite the dreams of eugenicists for over a century.  These traits fail to meet two, if not three of Muhkerjee’s criteria for good gene therapy and lead us to examine who is doing the choosing when it comes to improving the genes of our species.

Muhjkerjee concludes by proposing the completion of three research projects on a similar scale to the Human Genome Project to enhance our abilities to use gene therapy:

  1. ENCODE – the ENCyclopedia Of DNA Elements – a listing of all functional elements of the human DNA sequence. This goes beyond the Human Genome project by identifying pieces of DNA that are not genes – do not lead to protein production – but still control our biology.
  2. The 1000 genome project -which will sequence a representative sample of humans around the world and complete a thorough survey of their health and fate.  Predicting gene expression depends on this long-term extensive study of who we become to be.
  3. Safety and efficiency in gene editing – this work is well advanced with the recent discovery of a bacterial immune system called CRISPR .  This enzyme complex cuts DNA at very specific places and replaces the sequence found there.  Last week, the technique was used to repair a genetic disease in human zygotes, confirming work first conducted in China.

Like other medical technology, there will be far-reaching consequences from understanding and manipulating heredity. More and more, we are playing a conscious role in what it is to be a human.  Though the potential for harm is great, I am hopeful that this knowledge will be directed primarily at alleviating suffering.  That is a goal that Mendel would have appreciated as he tended the peas in his garden.