<CONTROL-X><CONTROL
-V> CRISPR WAY TO A BETTER LIFE
I am sure
all of us are proficient in Cut – Paste / Copy-Paste
operations. Most of us have used this route to improve of our output one way or
other. My generation was regrettably not able to use these operations for getting
better grades but surely we too have used these to embellish our presentations
and project reports. At least I have.
Now just
suppose that you could use the same operation for improving your life by
getting rid of some bad genes you may have inherited – no fault of yours or your
parents though – because they had no control on what they received from their own
parents and so on. This may appear as a sci-fi fantasy but the scientists are
now confident that they can do so and do so fairly easily.
In April
this year, a team of Chinese researchers created a global uproar when they
published a paper describing attempts to edit the genomes of human embryos. Led
by Junjiu Huang of Sun Yat-sen University, Guangzhou, they used a new
technology called CRISPR / Cas9 to try and edit non-viable, single-cell embryos
obtained from fertility clinics.
CRISPR is an
acronym for ‘clustered, regularly interspaced, short palindromic repeats’ and
Cas9 is an enzyme or a protein which can be guided to specific sites on any
gene and can be used to cut one or both the strands of the DNA double helix. It
essentially does what we do with our reports, cut out the strings of letters
and words and either paste them where we require them or just consign these cut
pieces into oblivion. Only in this case, the words and letters CRISPR/Cas9 operates
upon are the letters which make up the genetic code, DNA.
A technique
using CRISPR/Cas9 has now been developed which can ensure that specific sites
on genes can be targeted and the genetic sequence can be modified suitably
either by cutting out a few words or patching new ones or adding new ones.
As you can imagine
the implications are tremendous. We now know which genes are responsible for
causing as many as three thousand genetic disorders. In theory, if we knew the
mutations that give individuals a severe disorder, correcting that genetic
defect might now be possible.
A quick
backdrop for meaningful understanding of what is involved : Probably all of us
are familiar by now with the building blocks of our DNA - A(Adenine), T(Thiamine), C(Cytosine) and
G(Guanine). Any three of these four building
blocks combine to form groups of three called “codons”. There are 64 different
codons which can get formed, each of three letters. These codons are “words”
which make up a “sentence” which actually represent a “gene”. A gene can be a
short sentence or a very long sentence. Any misspelling of one or more words or
a repetition or omission of a word can cause malfunction of the gene in
question. All of us inherit two copies of any particular gene, one from each
parent. Normally even if there is some disorder in one copy of a gene, the
other copy takes over and if that one is without any defect, the gene functions
normally.
But there are some diseases where a defective
gene controls the functioning irrespective of a “normal” other half being
present. One such disease is Huntington’s disease. The gene responsible for
this is located on Chromosome 4 of human genome. The gene sequence contains a
“word” CAG which is repeated a number of times in a stretch. It could be just 6
times in some individuals, some 30 odd times in others and more than 100 times
in a few individuals. If you have up to 35 repeats of CAG in your gene, you
will be fine (most of us have 10 to 15 repeats) but if the number exceeds 39
then you are definitely going to get the dreaded disease.
The onset of disease
begins with slight deterioration of mental faculties and progresses to jerking
of limbs and deep depression, hallucinations and delusions leading to premature
death.
The relation
between the number of repeats and the age at which the disease sets in is correlated
to a remarkable degree. If you have 39 repeats, on an average you will get
symptoms by the age of 66; with 40 repeats at 59; with 41 repeats at 54; with
42 repeats at 37; if you have 50 repeats then by the age of 27.
Apparently
no other factor can influence this progressive deterioration. There is no cure
or any drug which can even slow the march of this dreaded disease. This is a
sort of disease where CRISPR/Cas9 is the only solution. The families in which
Huntington’s is common may soon get relief through this technology. It is not
clear if patients already affected by onset of this disease can benefit from
this treatment but surely the younger patients should be able to get full
relief.
Similar to
this, another 5 diseases have been identified which are caused by mistakes in sequence of CAG in other genes.
All are neurological diseases. Hopefully, patients suffering from these can
also look forward to relief through this technology.
This
technology can be used for altering genetic structure of any organism,
bacteria, plants or animals. This is bound to open up a large number of
potential areas of application.
Designing of
bacteria which can combat infections and even bacteria for specialized
industrial applications should now be possible.
Botanists
will be able to script another green revolution by creating modified plant species
which will drastically improve the agricultural output. Disease resistant genes
can easily be “cut-pasted” into plants which will yield more output under more
stringent climatic conditions which global warming is bound to bestow upon us
soon enough.
A modified
strain of (male) mosquitoes has already been developed which will yield
predominantly male off-springs; drastically reducing the female mosquito
population. In keeping with the conventional wisdom ‘female of the species
being deadlier than the male’ it is the female mosquito which feeds on animal
blood and is responsible for spreading dengue, malaria and filariasis. One can
expect more such initiatives under “gene drive” which will be used to control
population of pests. Hopefully the ecology will receive due consideration as
this will surely lead to big changes in food-chain which may backfire on us
humans.
Surely no one
will have any objections to this technology as long as treating diseases and
containment of pests are concerned, but it is doubtful if any one (read governments)
can restrict this technology solely for
prevention and cure of diseases. George Orwell stated once ‘Any technology
which can be used, will be used’.
With such a
powerful tool in hand, research is already afoot to modify genes for a better
progeny. Junjiu Huang is just one of the numerous scientists frantically
working on such projects. Francis Galton, who happened to be a first cousin of
Charles Darwin, had coined a term ‘Eugenics’ to denote the science of improving
the stock of human species – like we have done with other species. This had set
in motion a strong debate in Britain, Germany and US in the early part of the
19th century. (It will be worth our while to revisit that debate at
some other juncture). Luckily the matter did not progress then even after a
strong push from Hitler’s Nazi Germany. But with these new easy-to-employ gene-altering
tools available to any friendly-neighborhood bio-engineering /
genetic–engineering laboratory, the
probability of this technology being kept out of reach of common man is, as mathematicians
love to put it, vanishingly small.
There is
every likelihood that both you and me will end up with great grand-kids all looking
like either Dev Anand or Madhubala and all with IQ of 160+ to boot. Aldous
Huxley must be chuckling in his grave. His ‘brave new world’ would perhaps arrive
a few hundred years earlier than he had anticipated.
LazyBee
25th September 2015
References : Wikipedia, ‘Genome’ By Matt
Ridley etc
PS Just when I was sitting down to do this
article, I came across one in Times of India which essentially offered most of
the details that I was planning to give. So I had to do some mid-course
correction and add some specific examples about how CRISPR is likely to make
our lives easier. I am enclosing that article from Subodh Verma of Times of
India which will give you more information on the subject matter. (You can also figure out for yourself where
and what I have cut-pasted from his article).
Editing Our Genes
In April
this year, a team of Chinese researchers created a global uproar when they
published a paper describing attempts to edit the genomes of human embryos. Led
by Junjiu Huang of Sun Yat-sen University, Guangzhou, they used a new
technology called CRISPR to try and edit 86 non-viable, single-cell embryos
obtained from fertility clinics.
They wanted
to edit the gene responsible for B-thalassemia, a fatal blood disorder. CRISPR
(pronounced like ‘crisper’) has swept through the scientific world in the last
few years and is now poised for commercial use. It is thought to be
revolutionary because it gives humankind a powerful tool to edit, delete, add,
replace, activate or suppress specific genes. Humans can, theoretically, change
the genetic basis of various traits — from correcting disease causing mutated
genes to genes that determine whether you will have brown eyes or black.
The
discovery has led to a dramatic rise in funding for research based on CRISPR
and a patent war between various scientific institutions. It has also left
scientists sharply divided over whether such a technology can be allowed to
pick and choose characteristics of future human generations.
CRISPR is an
acronym for ‘clustered, regularly interspaced, short palindromic repeats’. This
mouthful of a name was given two decades ago when scientists found a strange
thing in bacteria genomes. There were these repeating sequences with no known
use. Genetics was still developing and the scientists thought no more of this.
Sometime
later it was found that these CRISPR sequences were used by bacteria to ward
off predatory viruses. The mechanism was unravelled but again nothing more was
thought of it. Then, around 2011, several genetic scientists in the US and
Europe hit pay dirt. They found that the CRISPR mechanism could be turned
around and manipulated for performing cut-and – paste functions on genomes. And
the control was fantastic. You could precisely snip off a bit of DNA from a
gene and replace it with another pre-fabricated bit of DNA.
Jennifer
Doudna, professor at the University of California, Berkeley, led one of the
research groups. She told TOI the technology is a “site-specific DNA
‘scissors’, allowing researchers to cut and then either remove or replace
genetic material in a cell or organism.” What this means is: first, a piece of
RNA is created for unzipping a DNA strand at the target site; then it is lodged
in a protein called Cas9 which is the scissors part of the machinery; this
complex unzips and cuts away the specific DNA bit. You can replace it with a
totally new DNA bit or a corrected version, as needed.
Another
pioneer is Prashant Mali, professor at University of California, San Diego.
Born in Rajasthan and educated at IIT-B, John Hopkins and Harvard, Mali
explains the intricate working of CRISPR: “The remarkable aspect is that the
ability to target a new genomic site simply requires one to alter the sequence
on the guide-RNA — this makes the technique really democratic in its ease of use. This has spurred its widespread
adoption by thousands of labs around the world in only a few years.”
After four
different groups announced their success with CRISPR in 2013, within eight
months various groups used it to cut and change targeted genes in human cells,
mice, rats, zebrafish, bacteria, fruit flies, yeast, worms and even crops.
The
mechanism is breathtakingly simple and cheap. Doudna says it “can be undertaken
in a basic lab environment at remarkably low cost”. Mali confirms that it is
“very easy to use and also cost-effective enough that it will be soon be a
routine procedure in most biology labs.”
Another
pioneer, Feng Zhang of Broad Institute, has founded a company called Editas
Medicine for using CRISPR in therapeutics. Its CEO Katrine Bosley said they are
working to translate the promise of CRISPR/Cas9 genome editing technology into
a new class of medicines to treat serious, genetically driven diseases. “This
technology enables precise corrections to errors in DNA, and we are working to
apply it to treat a broad range of diseases at the genetic level where patients
don’t have good therapeutic options.”
The ethical
debate that has erupted around CRISPR is because it can also be used to edit
germline cells or pluripotent stem cells. Germline cells are eggs and sperm
cells. Any changes in these will naturally be inherited by subsequent
generations. Pluripotent stem cells can develop into any kind of tissue, and
changes in these would affect large number of cells. Mali says one should
venture into this area only after thoroughly understanding “the underlying
scientific and ethical implications”. “Using CRISPR-Cas9 to engineer specific
traits is still a long way off, but the bioethical implications of the
technology are currently being reviewed in many regulatory agencies in the US
and elsewhere,” Doudna said.
In other
words, the technology is at hand. The question is whether we should use it or
not .
Times Of India,
Times & Trends
Sept 13 2015, Mumbai Edition
No comments:
Post a Comment