CRISPR-Cas gene editing causes crisper debates

It is sufficiently easy to make designer babies using the technique

February 07, 2016 09:00 am | Updated February 09, 2016 05:31 pm IST

Kathy Niakan, a developmental biologist at the Francis Crick Institute in London has received permission to use a powerful new genome editing technique on human embryos.

Kathy Niakan, a developmental biologist at the Francis Crick Institute in London has received permission to use a powerful new genome editing technique on human embryos.

Many people are born with inherited disorders of one form or another. Such conditions are only managed and not cured — at least for now. Even the ‘gene therapy’ of today, which is to administer the correct DNA sequence of the gene into the body, is only a temporary form of treatment and only for the individual and not his (or her) children. What one would like is to heal the future generations of the family as well. In other words, can the error in the DNA of the gene be corrected once and for all?

That such a holy grail may be on hand say some researchers who have found that some bacteria have a gene editing machinery in them, and that this could be modified and applied to human conditions as well.

Just as we are invaded by bacteria and find immunological ways to fight such infection and protect ourselves, the bacteria themselves have similar mechanisms. They too are infected by viruses and plasmids and have evolved, over time, to protect themselves. Such a protection system is found when we study the DNA sequences in their genome. Microbiologists have found a set of interesting repeats in the bacterial DNA sequences. These involve a cluster of repeat segments, and as palindromes at that, of DNA. (A palindrome is a sequence of letters in a word or sentence, arranged in such a fashion that you may read front to back or back to front and it reads the same and makes the same sense; the most famous palindrome is Napoleon Bonaparte’s quote: Able was I ere I saw Elba ).

And each such repetition is followed by a short segment of ‘spacer’ DNA sequence. Such spacer sequences actually come from the DNA of viruses that had invaded the bacterium. Such an elaborate arrangement of the bacterial DNA is referred to as the Clustered Regularly Inter-spaced Short Palindromic Repeats — or not so elegantly abbreviated CRISPRs (pronounced crispers ). Attached to the Crispr sequence is also a set of genes that code for enzymes that can cut the spacer DNA sequence. These are referred to as cas or crispr-associated sequences. Together, the CRISPR-Cas sequence of the bacterial DNA is the bacterial immune-machinery that can remember and cut the invading viral genome precisely at specific places and prevent their propagation. Researchers have now devised tools to engineer this bacterial machinery to cut and insert any desired DNA sequence in higher organisms including humans. In a sense, this is genome editing in much the same way that the proof-reader in a printing press edits manuscripts.

It was in 2012 that two groups simultaneously (and competitively) adapted the CRISPR-Cas gene editing method to correct gene mutations in human cells. One was the group of Jennifer Doudna and Emmanuelle Charpentier at Berkeley, San Francisco, while the other was that of George Church and Feng Zhang from Harvard and the Broad Institute, both in the Boston area. (For a summary of the work, the claims and the patent fight, read A. Pollock in the New York Times , issue of May 11, 2015).

That it can be done at the cellular level is acceptable. For example, the group led by Dr. Benjamin Freedman has taken human skin cells, induced them to become pluripotent stem cells, corrected the error in a gene there through the CRISPR-Cas method, differentiated them into generate what are called kidney ‘organoids’ in an effort to treat a kidney disease ( Nature Communication. October 23, 2015).

What about inborn errors that run in families? Should we start correcting inborn genetic errors by doing it at the embryonic stage of the pregnant mother, so that the child that is born has the genetic error corrected and therefore normal? The debate has already started when in 2014 such a gene editing was done on a cynomolgus monkey twin by Dr. Yuyu Niu and others (leave it to the Chinese to compete), and most recently on human embryos at the experimental stage as well, again by a Chinese group. What then about humans? “Should we be playing God?” ask ethicists. “Would changing an embryo’s DNA have unknown harmful consequences throughout a person’s body and be passed on down the generations?” as others.

The debate has intensified last week when the Human Fertilization and Embryology Authority (HEFA) of Britain allowed Dr. Kathy Niakan of the Francis Crick Institute, London to use (discarded) human embryos and edit the DNA therein using CRISPR-Cas9 to switch genes on and off at the early stage. She wants to look for the effects such modifications on the formation of the placenta. These experiments might throw some light on how different cell types are specified at the pre-implantation stages in the human embryo.

But sooner or later, someone will try and make ‘designer babies’. CRISPR-Cas methodology is sufficiently easy for any good lab to do so. Scientific academies are already addressing this issue and have so far unanimously resolved that such attempts should not be allowed, either by science bodies or governments.


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