Science

Artificial DNA: cure or catastrophe?

Review of Rewriting the Code of Life. by Michael Specter.  An article that appeared in the New Yorker of January 2, 2017.

In the past few year molecular biology has been progression by leaps and bounds.  Two new  discoveries CRISPR and Gene Drive, when used in conjunction, have the capability to  alter both genes and natural evolution and in doing so, can potentially revolutionize medicine.   Scientists are now contemplating using these new techniques in the real world in the very near future.  Doing this holds both huge promise to rid the earth of many horrific diseases like Malaria, which kills 1000 children daily, but also has nightmarish implications.

This article, “Rewriting the Code of Life” appears in The New Yorker of January 2nd, 2017.

It is by Michael Specter.   Specter is a New Yorker Staff writer who specializes in Science.  He has also written a book called Denialism.  His book is a great read by the way.

I thought the article was both very interesting and very important.  However, I’m not a biologist, so if you find problems with my descriptions of the science, let me know.

Kevin Esvelt is a professor of biological engineering at MIT.  This field is also called synthetic biology.  He wants to rid Nantucket and Martha’s Vineyard of Lyme disease  by using molecular tools.  About 1/4 of the people of Nantucket have been infected with Lyme disease and almost everyone on Nantucket is very much in favor of eliminating Lyme Disease on the island as the disease is serious, painful and life threatening.

Esvelt wants to rewrite the DNA of white-footed mice on Nantucket to make them immune to the bacteria that cause Lyme Disease.  White footed mice are the main reservoir of Lyme which they pass thru ticks to humans.  There is a vaccine for Lyme which works on dogs and mice but not humans.  Esvelt would first vaccinate the mice and then sequence the DNA of the most protective antibodies that result.  Then his team would implant the genes required to make those antibodies into the cells of mouse eggs.  The mice born from these eggs would be immune to Lyme.

If enough of these mice are released to mate with wild mice, the entire population would become resistant.  Also, very importantly, the antibodies in the mice would kill the lyme bacteria in any ticks that bites them.  The ticks suck blood from the mice.  This blood has the antigens that attack the lyme bacteria and these antigens kill the bacteria in the ticks.  And then the ticks reproduce and all progeny are Lyme resistant, i.e. immune to lyme.  Without infected ticks, there are no infected people.  Killing the bacteria in the ticks is the crucial element  and releasing mice with Lyme antibodies is the key that disrupts the entire transmission cycle.

CRISPR is a molecular scalpel that can be used to alter or delete or add a single sequence in a genome containing billions of nucleotides.  By placing this sequence in an organism’s DNA, scientists can insure that the new gene will copy itself in every successive generation.  For example, a mutation that blocked the parasite that causes malaria could be engineered into a mosquito.  If Gene Drive were pushing this particular gene, then each future generation would have more and more offspring having this trait until finally the entire species would have it.  This is a very powerful tool with huge potential to both improve and endanger the world.

Esvelt and his colleagues were the first to describe how the revolutionary gene-editing tool CRISPR could combine with  a natural phenomenon call a gene drive to alter the evolution of a species.  Gene drives work by overriding normal Mendelian inheritance.  Normally, the progeny of any sexually reproductive organism gets half of its genome from each parent, one gamete from each.   Male gametes unite with female gametes to form a zygote.  But since the 1940s, biologists have known that some genetic elements are selfish: evolution has given them better than a 50/50 chance of being inherited.  This makes it possible for certain characteristics to spread very rapidly.  This is gene-drive in the natural world.   CRISPR is the tool that is used to create gene drives artificially, genes that will transform species more rapidly than would normally happen.

At any rate, Esvelt would like to use CRISPR to create mice and then ticks that are immune to Lyme Disease and to also use gene drive to help these immune ticks to very rapidly replace the diseased ticks on Nantucket, much faster than normal evolution would work to replace the diseased ticks.  And thus the rapid end of Lyme Disease.

This sounds like a pretty simple plan.  However, the idea of humans  actually engineering genes and evolution has lots of implications, both good and bad.  On the good side, this technique could be used to produce sterile mosquitoes, those mosquitos which carry nasty tropical bugs.  If these sterile mosquitos could be pushed by gene drive to quickly become the dominant species of mosquito in the world, it would be the quick end of a lot of bad diseases.

However, there is also a bad side to this.  Would we really want to deliberately drive a natural species to extinction?  Even if it was just an insect or a microbe or a virus?   One of the basic premises of ecological science is that nature is a interdependent web of of all kinds of species inhabiting all kinds of niches.  It you destroy one species it effects the whole  ecological web and no one really knows what the consequences might be.  Isn’t this why the current extinction of many, many species every year, even every day, is something that biologist warn us about daily?  EO Wilson, one of the most prominent biologists in the world,  has practically made a career of such warnings.

And then there is the whole problem that this genie, once out of the bottle, certainly cannot ever be put back in the bottle.  And there is the fact that powerful science like this can be used not only for the good, but for really evil uses.  For instance dangerous bugs could be weaponized using these techniques and pushed to rapid prominence by using gene drive.  Nasty diseases could be released on select parts of the world while  the releasers vaccinate themselves and their citizens against the disease.  If a country wanted to wipe out all those evil Islamic people in the mid east, it would be very easy to release a disease there and then push it to prominence using gene drive.  And of course this would be a disease that most of the releaser’s world was already vaccinated against, or could be vaccinated for very quickly..  More than scary.

Gene Drive is a new idea that is not simple to understand.  To get the gist of this article it isn’t really necessary to understand gene drive, and Specter doesn’t attempt to do this.  However it is an interesting idea.  There is a good Wikipedia article on Gene Drives.  Below is the introduction to the Wiki article.  There is much, much more good information in the entire  Wiki article.

In genetics, gene drive is a technique that promotes the inheritance of a particular gene to increase its prevalence in a population.  The term is also used for specific genetic elements (i.e. a piece of DNA) that can implement the technique.

Applications of gene drive include preventing the spread of insects that carry diseases (in particular, mosquitoes that transmit malaria, dengue, and zika), to control invasive species, or to eliminate herbicide or pesticide resistance.   The technique can be used for adding, disrupting, or modifying genes, such as to cause a crash in the populations of a disease vector by reducing their reproductive capacity.

Several molecular mechanisms can mediate gene drive.  Naturally occurring gene drive mechanisms arise when alleles evolve molecular mechanisms that give them a transmission chance greater than the normal 50%. Synthetic genetic modules with similar properties have been developed as a technique for genome editing of laboratory populations. This entry focuses on endonuclease-based gene drive, the most versatile and actively developing molecular backend for synthetic gene drives. Since gene drives function only in sexually reproducing species, they cannot be used to engineer populations of viruses or bacteria.

Because it is a way to artificially bias inheritance of desired genes, gene drive constitutes a major change in biotechnology. The potential impact of releasing gene drives in the wild raises major bioethical concerns regarding their development and management

Esvelt feels that the only way to actually experiment with this new science is with absolute transparency and openness.  And he feels the rest of science should be this way also.  These tools could also be used to cure other diseases like dengue fever and malaria and zika.  Malaria kills 1000 children every day.  The Gates foundation invested tens of millions of dollars in a research team called Target Malaria.  Scientists have already used CRISPR to edit the genes of the mosquito that carries malaria to make that mosquito sterile in Africa.  A similar project is being funded in India.  Gene drives could also be used to wipe out schistosomiasis which is a horrifying disease that effects hundreds of millions of people every year.

Specter’s article in the Jan 2, 2017 New Yorker is a long one that explores all these ideas and a lot more.  For instance, he says new ideas like the human modification of genes and evolution, are always very scary, just because all sudden change is scary.  However, he says, maybe many new ideas aren’t really as horrific as they seem if they are explored logically and scientifically.  One of the real problems, says Specter, is that it is very easy for our fear of new ideas to overcome rational, objective thinking.  This, he says, has happened regularly in the recent past. ( This idea which he calls Denialism is the subject of his 2009 book called Denialism.)  All this is not to say that Specter is unaware of the possible horrific results of the unrestricted use of CRISPER and Gene Drives.

Specter is a very smart guy and a very good writer.  This is not a boring scientific article.  Like almost all New Yorker articles, this one is very down to earth and written in very concrete, easily understandable terms.  Much of the article consists of stories about the lives of the people doing the science.  It’s really a great and very worthwhile article to read.

Article Information

“Rewriting the Code of Life.”
Michael Specter
An article in the New Yorker, 1-2-2017
Lind to original article

 

11175-montana-ranch-and-sunset-16x24-pss-sp-6500-_w5p4630
Sunset and Ranch on the Rocky Mountain Front, Montana.   Picture by Hanselmann Photography. 

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