BioQuakes

AP Biology class blog for discussing current research in Biology

Tag: genetic alteration

How CRISPR Technology Can Potentially Reverse Extinction

Though Christmas Island rats went extinct over one hundred years ago, Anna Gibbs in sciencenews describes how genetically modifying the Norway brown rat would essentially reincarnate the Christmas Island rat. CRISPR is a relatively new technology that can be used to edit the genes of animals and has changed the science world of extinction. It works by editing “an existing animal’s genome so that it resembles that of the desired extinct animal… making that proxy as similar to the extinct species”.

Gibbs explains how using this technology, scientists compared fragments of the extinct rat’s genetic makeup, the Christmas Island rat, to that of their living relative, the Norway brown rat. By taking DNA from two preserved skin samples of the Christmas IslanRattus norvegicus - Brown rat 04d rat, the scientists were able to recover 95% of their genome. They compared the samples of the extinct species with the Norway brown rat and found that their genomes were very similar, 95% to be exact. Because of evolutionary divergence between the two species, the last 5% of the genetic information was lost forever. The missing genes were mostly located in the regions that controlled the rat’s immune responses and sense of smell. If they were to edit the Norway brown rat’s genome to resemble that of the Christmas Island rat, the differences in smell would be detrimental to their survival. This tiny difference in their genomes would prevent scientists from being able to recover the extinction of the Christmas Island rat. 

Though the scientists didn’t intend on actually reincarnating the rats, Gilbert says that what they discovered “could prove useful for people working on even more ambitious projects, like bringing back the wooly mammoth”. The hurdles of CRISPR technology lie in the tiny details of genetic engineering, even the smallest difference can prevent de-extinction. Ben Novak, a leading scientist at a nonprofit that uses genetic engineering for conservation projects, says that though there are MaclearsRatSkullways to capture some of the missing data, “the fact that some data will always be missing is a limitation that de-extinction scientists have already come to terms with”. The goal of de-extinction isn’t to completely recreate the extinct species but rather to formulate a new species out of the old that will fool its environment and live on. As we learned in AP biology this year, our bodies contain DNA polymerases that are constantly proofreading our DNA strands to make sure all of our nucleotides are correctly paired. If they are not, they are programmed to cut out the incorrect segment and replace it with the correct nucleotides. We even have a DNA ligase that acts as the glue in our DNA and keeps everything together. If the DNA polymerase were unable to detect the incorrect nucleotide matchup then it would stay and end up as a permanent mutation in the next cell division. Errors with the DNA polymerase, such a tiny part of our whole working body, are alike to the small error in CRISPR technology. The inability to recover all of the genomes due to the tiniest difference will cause scientists to miss out on the reincarnation of animals lost forever. 

Overall, though CRISPR findings are really “awesome”, it may not be the best use of money when we are struggling to keep our rhinos alive. In my opinion, CRISPR is not worth the funding until we are able to figure out how to recover 100% of the extinct genome. Comment your opinion on whether CRISPR should continue to receive additional funding, essentially is it worth it knowing we will never recover 100% of the extinct genome? 

CRISPR Scandal

Outrage is widespread in the scientific community, as one man’s choices may have ruined genome editing for everyone. With others calling his actions “premature,” “ethically problematic,” and “monstrous” Doctor He Jiankui remains confident in his File:He Jiankui at Second International Summit on Human Genome Editing.jpgactions. His action being creating the first genetically modified babies, twin girls born in November. “He had altered a gene in the embryos, before having them implanted in the mother’s womb, with the goal of making the babies resistant to infection with H.I.V..”

The chaos created by Dr. He’s actions are due to the fact that he failed to receive permission from an ethical board. He claims to have gotten the permission of the hospital, Shenzhen Harmonicare, but the hospital denies being involved. The hospital is even going as far as requesting a police investigation into the “fraudulent ethical review materials.” So without ethical approval, Dr. He seriously violated not only the Chinese government’s laws and regulations created by the Chinese Society for Cell Biology but also academic ethics and norms. He has risked opening the door to designer babies editing everything from eye color to I.Q and physical ability, while the CRISPR creators are attempting to limit the editing to cases of desperate unmet need where the cause cannot be prevented in any other way, unlike H.I.V. which is very easily avoidable in infants.

These twins, however, are the only known set of children to be produced from a trial of seven couples with an H.I.V. positive father and negative mother. Dr. He after deactivating the perfectly normal gene CCR₅ withFile:NHGRI-97218.jpg CRISPR-Cas9  implanted the embryos into their mothers. In deactivating the CCR₅, Dr. He made the girl’s resistant to H.I.V., but also made them more susceptible to West Nile virus and Japanese encephalitis. So while the babies were “born normally and healthy” according to Dr. He, Dr.Kiran Musunuru from the University of Pennsylvania said there was evidence of mosaicism in both twins embryos and Lulu’s placenta was also mosaic. Despite the mosaic placenta, both babies appear to be progressing well for now, but what will happen to them in the future is the unknown. While their health is positive for now, the effects will be felt in their progeny for generations to come in unknown ways as cells with CCR₅ and without are mixed.

With the unknown effects on future children, a lack of shared experimental notes/reports and ethical precautions, and a plea via youtube Dr. He only 34 years old is being shunned in the science community just days before his presentation at the Second International Summit on Human Genome Editing in Hong Kong.

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What does the future hold for CRISPR-Cas9?

Genome editing, or the technologies in which scientists can change the DNA of an organism, is on the rise, especially with its latest development, CRISPR-Cas9, the most efficient method of all of the methods to edit DNA.

Like many other discoveries in science, CRISPR-Cas9 was discovered through nature. Scientists learned that certain bacteria capture snippets of DNA from invading viruses, making DNA segments called CRISPR arrays, helping them remember the virus to prepare for future invasions of that virus. When they are confronted with that virus again, RNA segments from the CRISPR arrays are created which target the DNA of the virus, causing the enzyme Cas9 to cut the virus’ DNA apart, which would destroy the virus.

 

We use the same method in genome editing with CRISPR-Cas9 by creating RNA that binds to a specific sequence in a DNA strand and the Cas9, causing the Cas9 to cut the DNA at that specific sequence. Once this is done, the scientists create a sequence to replace the one that was cut to get the desired genome.

This technology is most prominently used to attempt to treat diseases, where the somatic cells’ genomes are altered which affect tissues, as well as prevent genetic diseases where the sperm or egg’s genome is changed. However, the latter causes some serious ethical concerns of whether we should use this technology to enhance human traits. But this begs the question that if we start using it more and more to prevent genetic diseases, will this open the door for it to be used in new ways?

Intentionally making the flu deadlier?

In a recent New York Times article, research has been put into actually genetically enhancing viruses, specifically avian flu, to become more lethal by increaing its transmission. This might sound crazy but the scientists argue that being able to produce a more lethal virus will enable the scientists to come up with a better way of preventing a future epidemic. Other people are afraid that the enhanced viruses could accidentaly get out of the laboratory or be stolen by terrorists to cause an epidemic. Whatever the argument is, it is important for scientists to be able to better understand viruses and their ability to become a pandemic or not. From what scientists know already, the main factors for a virus to be lethal are how the virus is transmitted, what cells the virus affects, and where it enters the body.

Two seperate groups have been working on the avian flu virus, a group at Erasmus Medical Center in Rotterdam and the other at the University of Wisconsin. Dr. Ron Flouchier led the team at the lab in Rotterdam and they were able to modify the virus to transmit through the air for short distances to infect other animals, in this case ferrets because the flu behaves similarly to ferrets as it does to humans. Although they have begun to find ways to make the virus more transmissable, the number of modifications to the temperature the flu can withstand, the location where the virus attacks, and other factors to make the virus actually be threatening to humans is large. The avian flu has only infected 600 people since its discovery in 1997 and even though more than half of them died the chances of people actaully getting the flu is very low and there are vaccines for the flu.

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