Michael Poyfair

Bio Blog

2/28/17

This mental health article, found in Scientific American, helps to explain how recent discoveries in brain imaging techniques have allowed for the measurement and study of specific biological markers, which could possibly result in a more specific treatment to the many differing types of clinical depression.

The article starts by describing a specific case of a New Jersey woman who has suffered from depression symptoms her entire life with no noticeable relief. She is not alone. The author states that currently in the United States, over 16 million adults who have had a depressive episode in the last year haven’t really found any relief from their mental or physical pain. This is included with those who were taking anti-depressants at the time as well.

The author goes on to explain that the problem with these millions of depressive cases originates in the way they are diagnosed. He explains how difficult it is to actually pinpoint a specific mental disorder due to the non-objective nature of mental illness. One may receive a blood test, CT scan, or biopsy for any kind of investigation of a physical disorder, but mental illness can only be identified through varying reported symptoms of previous cases. Even though there are broad and common symptoms for depression, it may manifest itself differently from person to person.

However, new research has allowed doctors and scientists to create a more effective way to identify and quantify the symptoms of depression through the use of biological markers in the brain. Using a procedure called an fMRI, medical professionals can measure the strength of the connections between neurons in the brain. After testing over 1000 people (40% had been diagnosed with depression), they were able to classify four unique categories of depression. Most differences were noticed in the limbic and frontostriatal regions. These new categories will lead to more specific diagnoses and more personalized treatments of future depression patients.

The discovering scientist was prompted to take on this study after seeing the neural connection strength variation in rats who were placed in stressful situations. After seeing data similarities between the rats and depressed humans, the researchers suspected that depression may be triggered by more than one origin and, therefore, might require more than one diagnosis. This conclusion has resulted in the study and relation of various biological markers that may affect noticeable levels of depression.  These markers include: cortisol levels, epigenetics, and toxic free radicals. Though the study is not complete, this is great news for the medical field as we come closer to identifying the specific causes and treatments for mental diseases that plague millions of people around the world.

I find this article to be extremely helpful in explaining the complexity of depression and the damage it causes. I have often considered myself a nonbeliever in the sense that I didn’t ever feel like depression was a real disease. I always thought that one could simply “get over it.” However, this article has shown that doctors not only believe that depression is a serious physical disorder, but that its complex nature may be treated through specific medical treatment. 

https://www.scientificamerican.com/article/brain-imaging-identifies-different-types-of-depression/

A New Model for Defeating Cancer: CAR T Cells

Joshua Kofford

BIO 1610-009

Dr. Michaela Gazdik-Stofer

February 28, 2017

Since I was little, I can remember people asking what I wanted to be when I grew up and I always responded with, “a doctor!” This still holds to be what I want to do, but I have started to narrow it down a little more. I have shown a lot of interest in the field of radiology, and have decided I want to do interventional radiology. This may change, but for now it is what I have my eyes set on. Interventional radiologist performs minimally invasive image guided diagnosis and treatments of diseases in every organ. A lot of these procedures deal with cancer in different organs. This is why I chose this article. After a close friend died from leukemia in high school, I’ve become interested in the causes, cures and preventions of this disease.

This article discusses a new form of treatment for leukemia, a cancer that forms in our blood cells. The treatment involves genetically mutating the T cell found in our immune system to target and destroy cancerous cells.

For decades, tumor immunologists have known the important role the immune system can play in fighting cancer. Early attempts to prove its potential were disappointing. Investigators had not done enough to stimulate the T, or CAR T, cells, a key component in the immune system identifying and attacking cancer cells. The immune system was not provided with enough ‘fire power’ to destroy the cancer cells.

The strategy now used and developed by this team of immunologists was discovered while searching for new HIV treatments. The T cells are “turbocharged,” after being drawn from the patients. This is done by using magnetic microbeads, infused with dendritic mimicking proteins (dendritic cells are the cells that activate the T cells). This makes the “cells more abundant, powerful and longer-acting than previous methods.” About 10 years ago, another method was discovered that is used along with this method. This method allows the T cells to efficiently home in on and attack certain kinds of cancers that stem from the white blood cells.

Even with the “turbocharged” T cells, our body still faces two major challenges when mounting an immune response to cancer. The first is that malignant cancers cells come from our own cells. Second, cancer cells “exploit various tricks to thwart an immune response.” This posed a problem, because the cancer cells could basically trick the T cells into thinking they are not a harmful cell to our body.

To get around these two major challenges, the CAR T cells were discovered, and how powerful they could be in destroying cancerous cells. The CAR T cells were altered, so that instead of picking a target based upon antigens released by all cells, they would pick an antigen released by all tumor cells, that could not be hidden. 

In 2010, after these cells were tested on mice, clinical trials were performed on 3 adult patients who had chronic lymphocytic leukemia, and were not responding to other treatments. William Ludwig was one of the first. Having been diagnosed for over 10 years, he was now carrying over 5 pounds of leukemic cells. After being injected with 1 billion of his own genetically modified CAR T cells, he soon developed a fever, low blood pressure and difficulty breathing. This was because his immune system had gone into triple overdrive in response to the CAR T cells. Ludwig did come through though, and 1 month later his doctor could find no evidence of leukemia in his body.

Tests have now been performed in children, and the researches latest results show an overall survival rate after 12 months of 62 percent, with less than 10 percent of these patients using standard treatment for leukemia after a year. There is no proven reason why some people respond to the CAR T cell treatment, and others do not. Some relapses of the leukemia have been reported, due to the fact that the CAR T cells did not multiple in the patients, or new types of leukemic cells evolved that the CAR T cells could not target. Even though the challenges have arisen, as a research community, there are still developments and tests surrounding this breakthrough.

It's what's on the outside that matters!

Ashley Hullinger

Bio 1610-009

Dr. Michaela Gazdik-Stofer

February 27, 2017

Cancer. It’s an ugly word that brings about ugly memories and emotions. Everyone has either lost someone to cancer, or loved someone who has lost someone to cancer. It is an ever-growing problem in our world. There is ongoing research on the topic; however, there are so many variations of the disease and they effect people of every age so differently, that it is difficult to pinpoint an exact cause, and a cure. 

Researchers from the University of Pennsylvania and The Wistar Institute have discovered it is what is outside a cell that matters. Cancer cells are an irregularity in DNA. When that mutation occurs, you get a mass of mutated cells, or in other words a tumor. When cancerous cells inside a tumor divide at a ridiculously fast rate, additional mutations in the DNA occur. Eventually so many mutations have occurred that the growth of the cells in the tumor becomes unregulated. This is what turns a benign tumor, into a malignant one. The researchers have discovered an important factor; however, that might be responsible for the spread of these cancerous cells. 

For the cancerous cells to spread, they must break away from the tumor and make their way through the extracellular matrix (ECM). They are pulled into the ECM due to physical forces between the cells and the ECM. To fit through the spaces of the ECM, a cell must change its shape from a round cell, into one that is more torpedo like.  They realized this change in shape and wondered more about the cell itself and why, or how, it changes shape to be able to spread. They learned that it is dependent on the stiffness of the ECM. They stated, “The cells in a tumor are sticky, without the collagen fibers of the ECM pulling on those cells, you can’t break that cell-cell adhesion. But, if the ECM is too stiff, the pores in the matrix become too narrow and the cells can’t escape.” So, it is in controlling the stiffness of the ECM, that can potentially control the spread of cancer. 

To prove this, they ran multiple experiments. Initially they ran them through computer simulations. Once those proved accurate, they used melanoma spheroids in a collagen mixture, as a model to see what happens when a cancerous cell leaves a tumor when it is still inside the body. Those observations again, matched their findings and the results from the computer simulations. Of course, this raises other questions. How will increasing the stiffness of the ECM affect other processes that happen there? What happens if the cancerous cells have already begun to spread? How do you change the stiffness of the ECM? 

The main point in this study, is the fact that the outside environment of a cancerous cell, plays a crucial role on its spread. It decides if the tumor will spread at all. This is a huge step forward. If we can control the spread of cancerous cells, we can then plan treatment and the removal of malignant tumors before they spread. Of course, this will require regular cancer screenings to find tumors before they spread. Nevertheless, it is a great discovery that might move us forward in the right direction. 

I found this fascinating and wanted to write about this because cancer is something that affects everyone. I have know many wonderful people who have been taken by this horrible disease. It is a devastating thing to watch, and I'm sure an even more devastating thing to endure. I know some people come out of it stronger for what they have survived, and I know there are lessons to be learned there. However, I think the devastation this disease leaves behind, is too great. 

 

Sources:
https://news.upenn.edu/news/pennwistar-study-finds-sweet-spot-where-tissue-stiffness-drives-cancers-spread

https://www.oncolink.org/healthcare-professionals/oncolink-university/general-oncology-courses/science-of-cancer-101/how-does-cancer-begin

Gene Editing and the Question of Ethics

Imagine a world where expecting mothers and fathers could guarantee that their child would not inherit any genetic diseases such as muscular dystrophy, sickle cell anemia, cystic fibrosis, and Down syndrome. A world like that may seem too good to be true, but recent medical advances have made this medically idealized world a real possibility. A new, complex tool called CRISPR-CAS9 has the ability splice, delete, and insert portions of genetic code. This, "gene editing" is a process that can remove inherited diseases from human embryos, eggs, and sperm. The technology is not widely used nor tested because, while it is promising, the science is not perfected. The procedure is rare and has worked in some cases, but in others it has not and has instead increase the chances of genetic disease. Because of the great risk involved, ethics have forced scientists to ask: should research be spurred to perfect the science of genetic editing considering the risks involved? 

It is certain that more research is needed to eliminate the risks involved with genetic editing, but some would argue that research should be stopped altogether. Halting any practice of genetic editing would consequently halt any advances, but would guarantee that no child suffer the adverse effects of a high profile science experiment.

              Reversely, some scientists would say that research should be hastened and even practiced in clinics. The increase in procedures performed would result in the testing of thousands of human embryos and would surely risk negative results in some cases; however, some cases would yield positive results. Eventually, the procedure could be perfected and inherited diseases would be irradiated from our DNA and future generations would never be afflicted with such impairments.

              Moreover, it’s important to consider the option of simply continuing research at the current rate, which is slowly, but surely. In the United States, genetic editing research is only permitted in cases where it is predetermined that the child would, without the procedure, be born with major defects or die. This solution would take more time, but advancement after advancement would eventually yield enough research to guarantee the procedures success without risking a child’s health.

              If no more research is conducted, genetic disorders and diseases will continue to plague future generations. If research is spurred, many children could suffer at the expense of an experiment. And if research continues, albeit at a near standstill, it will take years to perfect the procedure and many who could have been helped, will live with a disease. One thing is certain. The subject in question, genetic editing and the CRISPR-CAS9 tool, exist in an ethical gray area.

Matt Mietchen
BIOL 1610-008
Dr. Dr. Gazdik Stofer

Source: https://www.nytimes.com/2017/02/14/health/human-gene-editing-panel.html?_r=0

View From the Deep

Karli Bouck

Bio 1610-008

Dr. Michaela Gazdik-Stofer

February 24,2017

After reading through many articles, the one that stood out to me was an article about an intriguing Squid. It is named the Histioteuthis Heteropsis, but it is also known as the Strawberry Squid because it is pink in color and also has black spots or photophores speckled on its body. The strawberry design is not the only thing that makes this squid unique. It’s amazing adapted eyes have also deemed it the cock eyed squid, and those eyes have given the squid a couple of incredible capabilities.

Kate Thomas (A Duke University Biologist) has spent a lot of time studying ocean life. She became intrigued when she first saw this particular squid and she wanted to know the reason behind its two very different eyes. She noticed the squid had one eye that pointed upward and was quite large and bulging, while its other eye pointed downward and was more flat. She decided the best way to learn about them was to watch them. Thomas watched clips from 30 years’ worth of videos that recorded the cock eyed squid. She studied their behavior and movements and in time she discovered the reason for their eyes. She learned from her studies that the large "bubble" eye was able to see the small amount of light that came from the ocean surface and that fragment of light helped the squid to see shadows coming towards it to help it catch food (or move away from predators) coming from above, While the downward pointing eye had adapted itself to be able to detect bioluminescent light coming from the dark ocean below. The eyes being able to see in opposite directions, for opposite purposes, really gives this squid an advantage in the lower depths of the ocean.

I chose this article because I have always been interested in the animals that live in the deeper parts of the ocean.  They have adapted to their surroundings in many ways that we do not see in land creatures. They are almost alien like. It is so interesting to know these creatures have such incredible abilities. The amazing thing about learning how different animals adapt is it helps us to discover new technologies that are beneficial for ever day life. Thomas’ research has not only been able to help the world discover new facts about the way we see with our own eyes, but it is also being used to help develop camera lenses. I imagine that these discoveries will lead to ocean cameras that will help us better explore what other amazing creatures lurk deep below the water’s surface.

Source: https://today.duke.edu/2017/02/mismatched-eyes-help-squid-survive-ocean’s-twilight-zone