BioQuakes

AP Biology class blog for discussing current research in Biology

Author: osmosisjohn

A Vision For a Better Future

CRISPR is a world changing technology that is essentially used to edit genes. The discovery of CRISPR took place in the University of Alicante, Spain. Reported in 1993, Francisco Mojica was the first to characterize CRISPR locus. Throughout the 90s and early 2000s, Mojica realized that what was once reported as unique sets of repeat sequences actually shared common features, which are known to be hallmarks of CRISPR sequences. Through this finding, Mojica was able to correctly hypothesize that CRISPR is an adaptive immune system. In the year 2013, Feng Zhang, was the first scientist to successfully adapt CRISPR-Cas9 for genome editing in Eukaryotic Cells. Zhang was able to engineer two different Cas9 orthologs and he then demonstrated targeted genome cleavage in both human and mouse cells. They discovered that this system could then be used to target multiple genomic loci and could also drive homology directed repair.

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How Does it Work?

“Clustered regularly interspaced short palindromic repeats,” also known as CRISPR, are repeats found in bacteria’s DNA. CRISPR-Cas9 was adapted by scientists from a naturally occurring genome editing system in bacteria. This bacteria captures parts of DNA from invading viruses and it uses them to create DNA segments known as CRISPR arrays. This DNA allows the bacteria to recognize and remember the virus’s. If the same virus, or a similar one, attacks again, the bacteria will consequently RNA segments in order to target the viruses DNA. After, the bacteria uses the enzyme Cas9 in order to cut the DNA apart, thus disabling the virus. Scientists in a lab will create small pieces of RNA that attach to a specific target sequence of DNA and also the Cas9 enzyme. In this process, the RNA is used to recognize DNA and the Cas9 will cut the targeted DNA. Once cut, researchers will utilize the cell’s ability to repair DNA in order to add or remove pieces of genetic material. It can also replace existing DNA with custom DNA in order to make changes.

How is it used?

CRISPR is a tool that can be used to fight cancer among other known diseases. The therapy involves making four modifications to T-cells. T-cells are cells that help fight cancer. CRISPR adds a synthetic gene that gives the T-cells a claw-like receptor. This receptor can locate NY-ESO-1 molecules on cancer cells. CRISPR is then used to remove three genes. Two of the removed genes can interfere with the NY-ESO-1 receptor and the third limits a cell’s cancer killing abilities.

Another way CRISPR is used is against Leber’s Congenital Amaurosis(LCA). LCA is a family of congenital retinal dystrophies that results in vision loss. Patients tend to show nystagmus, sluggish pupillary responses, decreased visual acuity and photophobia. The CRISPR trial focuses on one gene mutation that causes a severe form of degeneration. It is said that this mutation creates somewhat of a “stop sign,” and RNAs will target sequences on either part of the stop sign. The Cas9 enzyme will then cut them out, allowing the DNA to then repair itself.

A New Hope For Remission

Cancer is defined as a disease that is caused by cells dividing uncontrollably and spreading to nearby tissue. Cancer can start almost anywhere in the human body and it is made up by a build up of cells called a tumor. Cancer lives throughout recorded history just as it does today, an unsolved mystery. The earliest findings of tumors and cancer can be found in ancient Egyptian Mummies, and the first recordings were found in 3000 BC in Egypt. Although they didn’t refer to it as cancer, they described it as 8 cases of tumors that were surgically removed. The words, “there is no treatment,” were written in those early recordings. They couldn’t be more wrong! I’ll let it slide though because their technology was 5000 years behind ours. There are in fact many treatments in the world for cancer and there are new ones being discovered every day. While there may not be a cure for cancer, there are many treatments that show more and more signs of remission.

What Treatments Are Available?

The most common and well known treatment for cancer is Chemotherapy. Chemotherapy is a drug treatment that relies on the injection of chemicals to kill all of the fast growing cells in the human body. Chemotherapy is somewhat of a flexible treatment because it doesn’t have to be the primary treatment. Chemotherapy can be used without using other treatments, after using other treatments, and to prepare you for other treatments. While this may sound very appealing and hopeful, the success rate of Chemotherapy isn’t as high as we’d like it to be. The success rate varies, but it’s evident that as the severity of the cancer increases, the effectiveness of treatment decreases. Furthermore, the side effects of chemotherapy are not only excruciating, but scarring. As stated, the treatment attacks all of the fast growing cells, including hair, skin blood intestinal cells. This will cause hair loss, nausea, vomiting, diarrhea, loss of appetite, fatigue, easy bruising and fever.

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There are other treatments for cancer that are not related to Chemotherapy, such as surgery, targeted therapies, and supportive care. Surgery is one of the biggest options for early stage cancers that are not blood cancers. Surgically removing the tumor from the body is the motive of this form of treatment. One must take into account the size, location and stage of the tumor in question. Targeted therapies (precision medicine) are tailored to specific patients. Through this therapy, scientists are able to find five or six gene processes that essentially turn a cancer “on or off.” While supportive care isn’t exactly considered medicine, forms of meditation and fitness are said to ease the effects of cancer and cancer treatment.

A New Hope

Through extensive research and testing, a new hope for remission has been discovered. Immunotherapy is a known, newer method of treating cancer that, instead of directly killing the cancer cells, boosts one’s immune system and natural defenses. This is a type of biological therapy because it uses substances made from living organisms as treatment. A recently discovered form of Immunotherapy called  CAR T-cell therapy has proven to show a lot of promise. T-cells are a type of white blood cell that kills cells infected with a pathogen. In this new therapy, doctors take blood from the patient and separate the T-cells from it. They then genetically change these cells so that they specifically attach to a protein on cancer cells. After expanding the number of T-cells, the doctors inject them back into the body. This treatment, however, is not without its side effects. As these T-cells cells multiply, they release cytokines into the blood, causing nausea, vomiting, fever, headaches, and diarrhea. How has CAR T-cell therapy been effective? An experiment was done in 2010 on two individuals with Chronic lymphocytic leukemia using CAR T-cell therapy. Just after this experiment, both patients saw complete remission in their cancer. And now ten years later, these two individuals show complete remission. Although more research needs to be done, CAR T-cell therapy proves to be an effective, long term treatment for cancer.

 

 

 

 

Are You Happy With Your Current Cell Provider?

Stem cells are defined as a specific type of cell that is capable of evolving into many different types of cells throughout the human body. Although they may be one of the most promising medical and biological discoveries, not many people know enough about them. The term “stem cell” has actually been dated back to the 19th century, but it wasn’t until 1981 that the first embryonic cells were isolated. In the year 1981, scientists Martin Evans and Gail Martin conducted separate studies and they were able to derive pluripotent stem cells from the embryos of mice.

Why Are They Useful?

In 1959 Physician E. Donnall Thomas conducted the first human hematopoietic stem cell transplant. The transplant was actually conducted on twin sisters. One sister with end stage leukemia received total body irradiation in order to kill the cancer. Soon after, her twin sister donated bone marrow, resulting in the regression of her twin sister’s leukemia. Because of stem cells’ ability to repair, regenerate and develop into specific specialized cell types, they prove to be therapy for many diseases and disorders. People that benefit from stem cell therapy are people who suffer from:

  • Spinal cord injuries
  • Type 1 diabetes
  • Parkinson’s disease
  • Amyotrophic lateral sclerosis
  • Alzheimer’s disease
  • Heart disease
  • Stroke
  • Burns
  • Cancer
  • Osteoarthritis

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Types of Stem Cells and Their Therapies

There are three types of stem cells, each with their own respective therapies and uses. The first types are Adult Stem Cells (ASCs). ASCs are found in small numbers in tissues such as bone marrow or fat. Researchers used to think that ASCs could create only similar types of cells. New evidence shows that ASCs may be able to create various types of cells. This means that bone marrow stem cells, for example, could be able to create bone and heart muscle cells. The other kind of stem cells are Embryonic Stem Cells (ESCs). ESCs come from embryos that are three to five days old. These stem cells are pluripotent, which means they can divide into more stem cells or become any cell in the body. This means that ESCs can be used to regenerate and repair diseased tissue and organs. The third kind of stem cells are induced pluripotent stem cells (iPSCs). These kinds of stem cells are ones created in a laboratory and they are a mixture of adult stem cells and embryonic stem cells. Scientists altering genes in adult cells allows them to reprogram the cells into behaving like embryonic stem cells.

 

 

 

 

 

 

 

Needle in a Haystack

Immunization is defined as the action of making a person immune to infection by the process of inoculation. While the COVID-19 vaccine may be new, vaccines have actually been around for a lot longer than you may think. We’re used to getting vaccines through needles when we go to the doctors office, but what if I told you that that’s not the only way to receive one. Hundreds of years ago, Buddhist monks actually used to drink snake venom in order to build immunity to it. Though more formally, Edward Jenner is considered the founder of vaccinology after successfully inoculating a 13 year old boy in 1796 with a smallpox vaccine. The 13 year old actually demonstrated immunity and the first small pox vaccine was officially developed in 1798. While that may be just a brief recount of the history of vaccines, the significance of their revolutionary effects will follow humanity to the end of time. Through vaccines we’ve immunized viruses such as Chicken Pox, Polio, Influenza, Hepatitis A, Hepatitis B, HPV, Measles and many more. These viruses plagued the world in the past, but many of them are now obsolete.

While these vaccines may be different in nature, they all have one similarity… They are administered through needles. The “proper” term inoculation, however it is not specified how the virus needs to be administered. Monks used to drink snake venom and that was considered inoculation. So that begs the question… Does a needle really need to inject a vaccine? The answer is no.

The sterility of each batch of vaccine is tested before it leaves the laboratory. USPHS (United States Public Health Service) Rocky Mountain Laboratory, Hamilton, Montana 

Title and other information from caption card.Transfer; United States. Office of War Information. Overseas Picture Division. Washington Division; 1944.More information about the FSA/OWI Collection is available at http://hdl.loc.gov/loc.pnp/pp.fsaowiTemp. note: owibatch1Film copy on SIS roll 1, frame 1090. 01/01/1942

How does the COVID-19 vaccine work?

The COVID-19 vaccine is considered an mRNA vaccine. Normal vaccines would put an inactivated germ into our bodies in order to build immunity. An mRNA vaccine uses mRNA that is created in a laboratory in order to instruct our cells on how to make a protein. The COVID-19 is administered through the upper arm muscle and it enters muscle cells. Inside these cells, the mRNA is assembled in the Endoplasmic Reticulum to form spike proteins. The mRNA that is injected is coded to constantly recreate the spike protein and it is displayed on the surface of the cell and our immune system will respond with antibody production.

What are other Methods of Vaccination?

According to Victoria University, there is more than one way to administer a vaccine. While they’re usually administered with a needle, you could also administer one using Jet Injectors. These Jet Injectors date back to the mid 1860s. They penetrated the skin and administered the vaccine without a needle. The method included a spring-loaded injector where a spring is released to deliver the vaccine. Another method of administering the vaccine is a liquid jet injector that uses very small volumes of liquid that is forced through very tiny microscopic holes in your skin, also not requiring a needle. This method was used during clinical trials against HIV and it is also utilized in some influenza vaccinations. A third method of vaccination is a band-aid-like patch that contains 400 tiny needles. It is said that if the vaccine were administered through antigen-presenting cells in the skin than into muscle cells the chances of the DNA (A DNA based vaccine) entering the nucleus would increase. The researchers created a delivery system by attaching DNA sequences encoding SARS-CoV-2 spike protein on the surface of nano-particles. The tiny needles were then coated with the nano-particles. After this, the patch would then be applied onto the skin, painlessly penetrating it.

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Quit Hogging All the Kidneys

Xenotransplantation is defined as the process of transplanting organs between members of different species. Saying it out loud it sounds like mad science but the it’s not as crazy you might think. Xenotransplantation has actually been a process that has been used for many years, even dating back to the 1960s. This journey began with apes and monkeys. Scientists believe that it would make the most amount of sense to use because they were essentially the most promising source of organs and tissue due to their being primates. However, this unraveled into a series of problems that were due to them being contaminated with viruses that are pathogenic to human beings. Baby monkeys were also researched but the idea was dismissed due to ethical reasons. This consequently led to the study of pig tissue.

We have actually been utilizing things from pigs that most people may not even be aware of. One example of this is pig insulin. It would replace the insulin that your body would usually make in order to get blood sugar into your cells. We obviously can’t take just any part of a pig and use it. We can, however, utilize a pig’s kidneys and transplant it into a human body. On September 25th, scientists and researchers  successfully transplanted a kidney from a genetically altered pig into a human patient and discovered that it functioned normally.

Little piggies

How Did It Work?

According to the an article by the New York Times, the pig needed to be genetically altered in order to be transplanted into the patient. What was altered? Essentially the kidney in the procedure was obtained by removing a pig gene that encodes a sugar molecule that elicits an aggressive human rejection response. Interestingly enough, the genetic difference between pig DNA and human DNA is 98 percent.

What Were The Risks?

While pigs and humans may share a lot of DNA, they are not a match right away. A non altered pig would cause many risks if any part of it were transplanted into the human body. A way it could pose an issue is through the viruses they may contain. Pig viruses may not cause disease in pigs, but they can in fact be pathogenic to humans. The human proteins that are expressed onto the transgenic pig cells can be receptors for viruses. An article on pig DNA from PMC explains that CD55 is a receptor for human Coxsackie B and ECHO viruses (these are relatives of poliovirus), and these cause a disease called myocarditis. The protein CD46 can act as as a receptor for the measles virus, so it is possible that morbilliviruses of animals could be preadapted in the same pigs used for xenotransplantation.

Another way that these transgenic pigs may heighten risk of virus is through viruses with lipid envelopes that are from host cell membranes would be less likely to inactivated by human compliment. What could have been a protective mechanism against infections from viruses derived from farm animals could be broken down in attempts to make xenografts for humans (The tissue or organ being transplanted from the other species).

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Diagram of a pig kidney

The future of xenotransplantation looks promising. While it may have worked, scientists are still doing studies and still trying to find out more about the viruses pigs may carry. While we can weed out the viruses we are aware of, we still can’t account for the ones we don’t know exist. There is a reason this topic is somewhat new and that is because of ethics. Apes and Monkeys could’ve actually been genetically altered the same way these pigs were, however it was deemed unethical. I personally agree that apes and monkeys shouldn’t be harvested, but that begs the question of whether harvesting organs from pigs is ethical. And with that I ask you what you ate for breakfast, lunch or dinner. Pigs and other animals are already being harvested for food and I believe that if there is a problem with xenotransplants, there would be a problem with the food industry. With that being said, if you’re ever in the market for a kidney, you have options.

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