Once Upon a… BioJournal

Biology | University | Culminating

The Gene Hackers

Link to Article:

Michael, Spectre. “The Gene Hackers.” Web. 18 Jan. 2016. <http://go.galegroup.com.ezproxy.torontopubliclibrary.ca/ps/retrieve.do?sort=DA-SORT&docType=Article&tabID=T003&prodId=AONE&searchId=R1&resultListType=RESULT_LIST&searchType=BasicSearchForm&contentSegment=¤tPosition=1&searchResultsType=SingleTab&inPS&gt;.

Article relates to: Genetic Processes

Article Obtained: January 6, 2016

Article Written: November 16, 2015

It has been a long-standing goal for biomedical researchers to develop efficient and reliable ways to make precise, targeted changes to the genome of living cells (Reis, 2014). Targeted genome editing using engineered nucleases has rapidly gone from being a niche technology to a mainstream method used by many biological researchers (Sander, 2014).

(CRISPR) Clustered Regularly Interspaced Short Palindromic Repeats technology, is a relatively new approach for generating RNA-guided nucleases, such as Cas9, with customizable specificities (Sander, 2014). It has also been used to rapidly, easily and efficiently modify the genetic sequences of genes in a wide variety of biomedically important cell types and in organisms which have been traditionally challenging to manipulate genetically (Sander, 2014)

The CRISPR technology

CRISPR has two components. The first is essentially a cellular scalpel that cuts DNA which is based on how bacteria mutate (Spector, 2016). The other consists of RNA, the molecule most often used to transmit biological information throughout the genome (Spector, 2016). It serves as a guide, leading the scalpel on a search past thousands of genes until it finds and fixes itself to the precise string of nucleotides it needs to cut (Spector, 2016).

It has been clear at least since Louis Pasteur did some of his earliest experiments into the germ theory of disease, in the nineteenth century, that the immune systems of humans and other vertebrates are capable of adapting to new threats (Spector, 2016). But few scientists had considered the possibility that single bacterial cells could defend themselves in the same way. The day after Zhang heard about CRISPR, he flew to Florida for a genetics conference (Spector, 2016). Rather than attend the meetings, however, he stayed in his hotel room and kept Googling. “I just sat there reading every paper on CRISPR I could find,” he said. “The more I read, the harder it was to contain my excitement,” (Spector, 2016).

Researchers soon learned how to create synthetic versions of the RNA guides and program them to deliver their cargo to virtually any cell (Spector, 2016). Once the enzyme locks onto the matching DNA sequence, it can cut and paste nucleotides with the precision we have come to expect from the search-and-replace function of a word processor (Spector, 2016).

The power of these systems to perform targeted, highly efficient alterations of genome sequence and gene expression will undoubtedly transform biological research and spur the development of novel molecular therapeutics for human disease (Sander, 2014)

The functions of CRISPR and CRISPR-associated (Cas) genes are essential in adaptive immunity in select bacteria and archaea. (Reis, 2014)  Thus enabling the organisms to respond to and eliminate invading genetic material. (Reis, 2014) These repeats were initially discovered in the 1980s in E. coli (9) (Reis, 2014)

Therefore, because prokaryotes can often proliferate rapidly, mutations can quickly increase a population’s genetic variation, making adaptive evolution possible (Reeve, 2004). For example, a prokaryote reproducing by binary fission through multiple divisions, most of the offspring cells are genetically identical to the original parent cell (Reeve, 2004). Therefore the phenotype and genotypes of the individual are passed down through heredity (Reeve, 2004). However, if errors occur during DNA replication—such as insertions, deletions, or substitutions—some of the offspring cells may differ genetically with a variation to their DNA (Reeve, 2004).

Genetic diversity in prokaryotes also can arise by recombination of the DNA from two different cells -via transformation, transduction, or conjugation. By transferring advantageous alleles, such as ones for antibiotic resistance, genetic recombination can promote adaptive evolution in prokaryotic

populations (Reeve, 2004). This diversity quickly in species with short generation times and large populations (Reeve, 2004). This diversity, in turn, can lead to rapid evolution with individuals that are genetically better equipped for their environment tend to survive and reproduce more prolifically than an individual that doesn’t have traits proved advantageous to the environment.

Feng Zhang

The article follows, Feng Zhang is the youngest member of the core faculty at the Broad Institute of Harvard and M.I.T, decided to become a biological engineer (Spector, 2016). This meant he did research on forging tools to repair the broken genes that are responsible for many of humanity’s most intractable afflictions and diseases such as cystic fibrosis caused by a small mutation in the human DNA sequencing (Spector, 2016). With CRISPR, scientists can change, delete, and replace genes in any animal and human to help correct faults on DNA sequences and pathological traits (Spector, 2016). With lab mice, researchers have already deployed the tool to correct the genetic errors responsible for sickle-cell anemia, muscular dystrophy, and the fundamental defect associated with cystic fibrosis, replace a mutation that causes cataracts and destroy receptors that H.I.V. uses to infiltrate our immune system (Spector, 2016). Japanese scientists used the technique to prolong the life of tomatoes by turning off genes that control how quickly they ripen (Spector, 2016).

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However, advances in this technology brings up controversy on the ethics of being able to edit people’s DNA sequences which we have studied in our genetics essay. With genetic enhancement, abilities become a product of science and not on talent.

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One potential problem with genetic enhancement is that, possibility of suppressing  genetic traits that could prove advantageous down the road,  therefore shrinking human gene pool.  It questions the purpose of diversity, as well as its importance in survival through natural selection and global epidemics. It also questions our ability to play with god and play with nature and raises questions of the promotion of altering traits for non-medical purposes and the psychological, behavioural effect it will have on both the parents and children such as, “designer babies.” In addition, the outcome of CRISPR use is unpredictable and could potentially create more mutations that could create a new disease based on how genes are modified.  In addition, this technology may lead to social hierarchy and gaps in society socially.

In China, scientists have reported editing the genomes of human embryos (Reardon, 2015). In the case there were a surprising number of  reported ‘off-target’ mutations assumed to be introduced by the CRISPR/Cas9 complex acting on other parts of the genome. The team injected 86 embryos and then waited 48 hours, enough time for the CRISPR/Cas9 system and the molecules that replace the missing DNA to act (Reardon, 2015). Of the 71 embryos that survived, just 28 were successfully spliced, and that only a fraction of those contained the replacement genetic material (Reardon, 2015).