We're all familiar with the central dogma of biology - or at least we should be. I remember first learning it back in Dr. Campisi's Molecular and Cell Biology class. DNA is transcribed into RNA, which is then translated into proteins. This central dogma has formed the basis of our understanding of genetics and all forms of life on earth. DNA has 2 base pairs: adenosine (A) to thymine (T), and cytosine (C) to guanine (G). This is true of all life on earth. Or it was, at least, until recently.
Back in 2014, researchers successfully created the first synthetic nucleotide base pair. The artificial base pair does not engage in hydrogen bonding like the A-T and C-G base pairs do; rather, X and Y bond through hydrophobic interactions, which may limit the number of synthetic bases that can be integrated without disrupting the helical structure of DNA. This opened up new possibilities for the world of synthetic biology, and has sparked research into
Last week, a paper was published in Nature magazine. The researchers were able to demonstrate that the XY base pair can replicate in living bacterial cells, create atypical proteins, and partake in information storage (Zhang et al., 2017). First the researchers placed the X-Y pair into the green fluorescent protein (GFP) gene, which changed a codon from TAC to AXC. RNA created the anti-codon, GYT, and that was translated into the GFP protein containing a novel artificial amino acid. The gene was expressed in semi-synthetic bacteria which produced GFP proteins with the synthetic amino acid.
This is a monumental development. The central dogma of biology has been retained even with a synthetic base pair. The potential for synthetic biology is now suddenly much more feasible, with the promise of new medications and synthetic organisms. However, there is much work to do, and there is certainly much criticism over the stability and efficiency of the new alphabet: after all, there are now two more letters to think about, but millions more combinations of DNA that could potentially alter life on the planet.
Zhang, Y., Ptacin, J. L., Fischer, E. C., Aerni, H. R., Caffaro, C. E., San Jose, K., . . . & Romesberg, F. E. (2017). A semi-synthetic organism that stores and retrieves increased genetic information. Nature, 551, 644-647. doi:10.1038/nature24659
Link to full article without paywall: https://sci-hub.bz/https://www.nature.com/articles/nature24659
Monday, December 4, 2017
But who will save the savior sibling?
In my Immunology class a few weeks ago, we were discussing Severe Combined Immunodeficiency Disorder (SCID) - a rare primary immunodeficiency that results in disturbed B-cell and T-cell development, leading to persistent infections and an increased risk of fatal outcomes. The term "bubble boy" originates from one form of SCID known as ADA-SCID, which should indicate how serious this disease can be. We learned in class that hematopoetic stem cell transplants (HSCT, aka bone marrow transplants) are the current preferred method of treatment as gene therapy is still being researched, and CRISPR is still too early in its clinical infancy to be used.
HSCTs require close matches to a number of proteins collectively referred to as human leukocyte antigens (HLAs) which are important for the recognition of self-cells to prevent the immune system from attacking the host. HLAs are found on all organs and self-cells, if I remember correctly, which is why donor matches are critical to minimize the risk of rejection. Although near matches can be found in complete strangers and such transplants have been successful, the lowest-risk donor tissues can be found in family members due to genetic similarity.
While I was researching alternative SCID treatment options, I stumbled across several news articles referring to what are called "savior siblings." Wondering why this might be newsworthy, I read a few of the articles. It seems that savior siblings are children born for the express intent of harvesting an organ or bone marrow to obtain a close HLA match to maximize the chances of another child's survival. I had a rather visceral reaction to reading this: on the one hand, a life was being saved, but on the other hand a life was being brought into the world chiefly to be viewed as a bag of organs.
This isn't to say these children do not go on to live normal lives, but imagine learning that you were only born so your elder sibling would not die. Heroic bragging rights aside, this seems cruel, as though the savior sibling's existence is only qualified by the need for his or her organs. Now, I speak from a point of view in which I have never had children, nor needed a savior sibling, so perhaps my view is narrow and ignores several critical deciding factors. For parents who already have a child and consider this course of action, surely two living children are better than no children at all. But I wonder whether the validity of a life is challenged when it is conceived as a means to an end. Is life worth living when your life wasn't intended for you?
HSCTs require close matches to a number of proteins collectively referred to as human leukocyte antigens (HLAs) which are important for the recognition of self-cells to prevent the immune system from attacking the host. HLAs are found on all organs and self-cells, if I remember correctly, which is why donor matches are critical to minimize the risk of rejection. Although near matches can be found in complete strangers and such transplants have been successful, the lowest-risk donor tissues can be found in family members due to genetic similarity.
While I was researching alternative SCID treatment options, I stumbled across several news articles referring to what are called "savior siblings." Wondering why this might be newsworthy, I read a few of the articles. It seems that savior siblings are children born for the express intent of harvesting an organ or bone marrow to obtain a close HLA match to maximize the chances of another child's survival. I had a rather visceral reaction to reading this: on the one hand, a life was being saved, but on the other hand a life was being brought into the world chiefly to be viewed as a bag of organs.
This isn't to say these children do not go on to live normal lives, but imagine learning that you were only born so your elder sibling would not die. Heroic bragging rights aside, this seems cruel, as though the savior sibling's existence is only qualified by the need for his or her organs. Now, I speak from a point of view in which I have never had children, nor needed a savior sibling, so perhaps my view is narrow and ignores several critical deciding factors. For parents who already have a child and consider this course of action, surely two living children are better than no children at all. But I wonder whether the validity of a life is challenged when it is conceived as a means to an end. Is life worth living when your life wasn't intended for you?
Running Farther With a Partial Lobectomy
Diane Van Deren has won several of the world most grueling ultra-marathons.
At 57 she is still considered one of the world top endurance runners. In 2009,
she became the first women to complete and win the 430 mile Yukon Arctic Ultra. Diane
had previously been a professional tennis player, that is until she began
having epileptic seizures. Her success as an ultra-marathoner, for better or
worse, has been attributed to a procedure she had in 1997.
After enduring 17 years of epileptic seizures, having up to
four per week, Diane and her doctors decided to remove a portion of her brain. In
1997 Diane underwent a partial right temporal lobectomy, removing the portion
of her brain that was causing the seizures. The procedure ended her epilepsy. She
has not had a seizure since, but the operation has left some residual
complications.
Diane now has a blind spot in the upper left part of her
vision and cannot track time very well. Her husband says she is always running
late and has no sense of direction. Her memory has also been impaired. She can’t
remember the ages of her three children or remember where she went on her
honeymoon. Diane’s doctors say that her surgery may have helped her distance
running. The portion of her brain that was removed is involved in processing
emotion, specifically the emotional reaction to pain. They also hypothesize
that her spatial unawareness leads to loss of time, increasing her ability to
run long distances without being cognizant of it.
The question becomes: is it safe? Our bodies have control
mechanisms to sense pain in order to prevent serious injury. Furthermore, did
her procedure give an unfair advantage over her fully intact brained peers? If
lance Armstrong had a partial right temporal lobectomy instead of using the
complicated blood doping scheme, would he have been stripped of his medals?
References
Havey, M. L. (2014,
December 12). Running From the Seizures. Retrieved December 04, 2017, from
https://www.theatlantic.com/health/archive/2014/12/running-from-the-seizures/383123/
Is the Practice of Neuromarketing Immoral?
Neuromarketing
is the science behind what why buy and why we buy. It is based on several different
principles from areas of study such as marketing, economics, biology and
psychology.
This idea argues
that we consume because we are genetically and biologically programmed to maximize
our probability of increasing fitness. Fitness is defined as the number of
individuals that we produce. In order to maximize fitness, organisms behave in
ways that preserve their energy and resources, frequently at the expense of
another organism. A doctor of neuroscience by the name of Dr. Schwartz
explained that our model of how society should be run is based on these ideas
of sociobiology. Companies then correspondingly advertise products that will
supposedly help people to meet these predetermined goals. Schwartz argues that “We are living in a time
in which the pursuit of self-interest in the free-market economy provides the
primary metaphor for understanding social relations. As a result, our social
and cultural categories overlap with our economic ones,” (Schwartz). The
problem with this way of thinking is that we must always be the best and
brightest in order to maximize our fitness, and the easiest way to accomplish
all of that is to consume. What began as a simple biological theory as do why organisms
behave the way they do has now developed into an excuse for why we continue to
act this way currently in the developed world.
Additionally, Neuromarketing uses technology
such as fMRI scans to record changes in blood flow as a result of a stimulus,
as well as EEG, or Electroencephalography. This system measures the electrical
activity in the brain using tiny sensors attached to the top of the head (NeuroSky).
Although none of this seems particularly invasive, the conclusions drawn from
this data have astounding effects. In one study, a group of individuals were hooked
up to an eye-tracking device and asked to choose a type of cereal from a long
aisle of choices. The technology measured how long each individual’s attention
was given to a particular object, and which ones it skipped over. From here,
the marketers were able to interpret this data and formulate their marketing strategy
to make their product receive more attention from people (TedX).
Neuromarketing goes beyond simply understanding why we consume what we do. It also allows for companies with access to different technologies to be able to manipulate their advertising in a way that would increase products. It brings up the question of moral ethics and asks whether researchers are acting beneficently. The idea behind beneficence is when a customer, consumer, participant or patient is treated in a way that respects his or her welfare. This includes their health, and happiness. By manipulating a shopping experience in a way that points a consumer in a certain direction without being transparent about this action, marketers are not acting beneficently, nor autonomously, as they are simply not allowing the customer to make their own choice. Additionally, they learning how to make a product that may not be beneficial much more appealing.
Neuromarketing goes beyond simply understanding why we consume what we do. It also allows for companies with access to different technologies to be able to manipulate their advertising in a way that would increase products. It brings up the question of moral ethics and asks whether researchers are acting beneficently. The idea behind beneficence is when a customer, consumer, participant or patient is treated in a way that respects his or her welfare. This includes their health, and happiness. By manipulating a shopping experience in a way that points a consumer in a certain direction without being transparent about this action, marketers are not acting beneficently, nor autonomously, as they are simply not allowing the customer to make their own choice. Additionally, they learning how to make a product that may not be beneficial much more appealing.
Schwartz,
B. (1987). The battle for human nature:
science, morality, and modern life. New York: Norton
TedX: https://www.youtube.com/watch?v=jeQ7C4JLpug
Need a new kidney? Be prepared to use sunscreen
I am starting this blog with a lot more research needs to be
done before any real conclusions are come. However, saying that, there was
previously stated to be an increased risk of skin cancer in those that undergo organ
transplants with kidney transplants in particular showing an increase in
cancer. Researchers in Sweden have challenged this fact recently with a 45 year
study in which they tracked organ transplant patients. Their results showed
that there was no increased risk of cancer. To go along with this, a Dutch
study has also come forth and said that patients with an organ transplant was
seen to have a decline in the incidence of squamous cell carcinoma.
Within the Norway study, from the years 1968 to 2012, after
a patient had an organ transplant, they followed them for a mean time length of
6.7 years and recorded all incidences of skin cancer found. From 1983-1987
there was a massive decline in the incidences of skin cancer, along with
decreases from 1998-2002, 2003-2007, and 2008-2012. The most common thoughts to
go along with this is that medicine and treatment methods have gotten more
specialized and individualized and with the increase of immunosuppressants, a
decrease in skin cancer incidences.
Overall from this study, they concluded that of patients
that had undergone organ transplants, there was a decrease in squamous cell
carcinoma since the mid-1980s. As stated above this reduction is most likely
due to the advance of immune suppression treatment. Dermatologists and
transplant physicians still fear a higher incidence of skin cancer in
transplant patients over the general population however.
https://www.medicalnewsbulletin.com/organ-transplants-risk-skin-cancer/
Is genetics the cause of obesity?
Obesity has
become a huge problem in the world’s population with about 13% (about 650
million) of the adult population being obese in 2016. Most people attribute
obesity to eating too much food and unhealthy food and not exercising enough.
New research has come to light that indicates that obesity may be caused from
genetics. Variants in a gene called Ankyrin-B has become a new focus for
obesity studies. In a study using mice, it was found that variations in this
gene causes fat cells to intake glucose at a faster rate than normal and in
people with an aging metabolism or high-fat diet, it is near impossible not to
become obese.
Researchers
have been able to link variations in Ankyrin-B genes to diseases including
autism, muscular dystrophy, aging, diabetes, and irregular heartbeats. Studies
were done by knocking out and creating different mutants of Ankyrin-B gene in
mice. It was found that mice with these mutant genes became obese while having
the same diet and exercise as the other mice with normal Ankyrin-B genes. The
results showed the excess amount of lipids in the fat cells leaked into the
liver and muscles which led to inflammation and disruption of response in
insulin. It was found that mutating the Ankyrin-B genes led to the change of
Glut4 which allows glucose to enter the fat cells at a faster rate.
Observational
research needs to be done with the general population looking at whether or not
obese people have these mutated Ankyrin-B genes as well as looking at familial
histories, height, weight and glucose metabolism in order to determine the
effect of these variants on the human population.
“New Research Shows How a Gene Can Fuel Obesity in Mice.” News-Medical.net, 16 Nov. 2017, www.news-medical.net/news/20171116/New-research-shows-how-a-gene-can-fuel-obesity-in-mice.aspx.
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