Daily Archives: February 14, 2016

Telomeres: Fountain of Youth or Grim Reaper?

Kailyn Valido

The majority of people dread the inevitability of aging, a genetically programmed process. It is evident that many wish that they could somehow rewind time to relive their 20’s and 30’s—a range of years where most people do not have wrinkles, graying hair, and frequent thoughts about the enigmatic nature of “The Great Unknown.”

What if one can extend this period of youthfulness and vivacity? What if one can delay this seemingly undesirable process of aging?

This is where the notion of telomeres comes into play.

Telomeres are essentially repeated sequences of DNA at the end of eukaryotic chromosomes. These sequences are in the form of repeated TTAGGG bases on one strand of DNA and AATCCC bases on the complementary DNA strand. Analogous to the plastic tips on shoelaces, telomeres ultimately provide the chromosome with protection—up to a certain point.

Synthesized by the enzyme telomerase, telomeres get shorter every time a cell undergoes division. Because there is not enough telomerase for somatic—or body—cells, the gene for telomerase is inactive and telomeres consequently shorten. The shorter the telomere length, the lesser amount of times a cell can divide. Once the telomeres become too short, the cell can no longer divide, and so it ages and inevitably dies.

For this reason, telomere shortening has been linked to the aging process. Through his research, geneticist Richard Cawthon at the University of Utah discovered that shorter telomeres correlate with shorter lives. Working with a group of people older than 60 years old, he and his colleagues found that those who had significantly shorter telomeres were three times more likely to die from heart disease and eight times more likely to die from infectious disease.

The main issue with this finding, however, relates to the correlation versus causation argument, in which it is commonly believed that correlation does not equal causation. Scientists are currently unsure of whether telomere shortening is merely a sign of aging, such as wrinkles, or an actual contributing factor.

If telomere shortening is proven to be a definite cause of aging, this information would be an immense breakthrough in the medical field. Scientists may be able to extend human lifespan greatly by somehow devising a mechanism to restore or preserve telomere length, allowing cells to divide more and not become senescent.

In a small-scale scientific study at the University of California at San Francisco, scientists wanted to research if telomere length can be affected by certain lifestyle changes. In this study, which began in 2008, 35 men who had early-stage prostate cancer were closely monitored. Ten men altered their lifestyle habits by having a plant-based diet, moderate exercise six days a week, and stress reduction exercises. Additionally, they attended a weekly support group. The 25 other men who had early prostate cancer were not asked to make any major lifestyle alterations.

After five years of surveillance, the 10 men with the lifestyle changes had an increase in telomere length by about 10 percent. In contrast, those 25 men who did not change any lifestyle habits had significantly shorter telomeres, about 3 percent shorter when the study was concluded.

This pilot study has major implications. Because of the small size of the study, however, the legitimacy of this research finding needs to be confirmed by more large-scale studies to assess the sample size and find repeatability in results. The scientists at UCSF hope to inspire larger research studies for confirmation.

The lead scientist in this study, Dean Ornish, MD, powerfully states, “Our genes, and our telomeres, are not necessarily our fate…[The] findings indicate that telomeres may lengthen to the degree that people change how they live.”

If scientists can preserve telomere length, one might be wondering then, will humans be able to attain that much desired Fountain of Youth and ultimately become immortal like many science fiction movies portray? Very unlikely.

Although the concept of telomere lengthening and preservation can potentially postpone aging, unnaturally active telomerase and incessant division of cells may be problematic. Cancer cells, for instance, escape their death by having a consistently active telomerase, preventing telomeres from shortening. This, in turn, allows these cells to grow an abnormal amount of times and form tumors. Scientists are aware that replicative aging of cells occurs to combat against these malignancies.

This complex part of telomerase and its product, telomeres, is what is still confounding experts today. If telomerase can be systematically lengthened to extend one’s lifespan, would that increase that person’s risk of cancer? Questions similar to these and their respective multifaceted issues are currently being explored. Perhaps one cannot delay the aging process without certain repercussions, such as a higher chance of having cancer.

Scientists, however, are still hopeful. Many are attempting to utilize the notion of telomeres as a target for cancer treatment. If they can find a way to shorten cancer cell telomeres and allow these cells to age and die, it can be revolutionary.

Some researchers have already started testing this in the lab with prostate cancer cells, but results had unfortunate consequences, such as significant impairment of both fertility and production of immune cells. Knowledge is still being gathered about how differentiation in normal cells and cancer cells can be related to telomeres and the enzyme telomerase.

Despite scientists’ extraordinary efforts in fighting against the aging process by manipulating and observing telomeres, the only seemingly possible result is to delay aging rather than terminating the process altogether. In addition to the preservation of life, research on telomeres could be a key to unlocking the cure to cancer— a colossal discovery that would prevent a lot of emotional, physical, and mental suffering in the world.

Why is U.S. healthcare so expensive as compared to Europe?

 Helathcare cost photo

 

 

 

 

 

 

 

Photo credit: Stockphoto. April 6, 2015

 

Keenan Cromshaw

 Americans have the highest healthcare costs as a percentage of GDP and therefore pay the most per capita for healthcare as compared to any European nations. Despite this, we have lower marks in overall health indicators, such as life expectancy. Essentially, our healthcare system is sick. But why is this? The answer, like many, is very complex.

One of the biggest factors as to why the U.S. spends more on healthcare is the fact that the U.S. has a much higher rate of obesity as compared to every other European nation. In short, we’re fat! The United States in 2009 (and the rates are higher now) had an obesity rate of nearly 35%–nearly 5% higher than the next OECD nation (Mexico), about 10% higher than the next European nation (the UK), and almost 20% higher than the OECD (Organization for Economic Cooperation and Development) average. A 2012 study by the Obesity Prevention Source revealed that costs related to obesity in 2005 totaled nearly $190 billion, a number that is likely significantly higher now.

Data also shows that the United States has a significantly higher rate of diabetes as compared to the majority of European nations. Obesity and diabetes usually lead to higher medical costs due to conditions and treatments related to these diseases, such as hypertension and even cancer. As many can imagine, costs from these conditions and treatments will certainly inflate the costs of healthcare. The simple fact is that if you have a greater amount of unhealthier people, the higher the total healthcare costs.

One of the best (and probably the one most people can agree on) solutions is to simply get more Americans healthier! Americans need to both exercise and eat better to achieve this. When more people are healthy (and less people are obese), they go to the doctor less, need less treatments, and ultimately spend less on healthcare.

Another huge factor as to why U.S. healthcare is so expensive is due to the fact that many taxpayers and insurance payers pay for a phenomenon called “defensive medicine.” Defensive medicine is essentially medical practitioners ordering unnecessary diagnostic tests, procedures, and treatment plans that may include surgery. The tests to determine a patient’s condition can be extremely expensive along with procedures and treatment plans. These added costs are paid for mainly by insurance companies including Medicare and Medicaid, driving up the costs of healthcare.

The reasons why medical practitioners do this can be varied. Sheer uncertainty of a patient’s condition may prompt practitioners to order diagnostic tests and treatment plans, but a cause that many people believe is very prevalent is the notion that medical practitioners are afraid of having malpractice lawsuits against them. The total costs of defensive medicine practices in the United States may range up to $650 billion annually according to a recent study, although numbers may range lower. Nevertheless, this is still a significant reason as to why our healthcare is expensive and can and should be cured.

Reforming laws regarding malpractice may significantly help to decrease the amount of defensive medicine practiced by showing healthcare providers that they can provide ethical and effective healthcare without fearing an unjust lawsuit.

The next factor as to why the U.S. spends more on healthcare is the fact that the U.S. spends more than all of Europe combined on buying and researching prescription drugs ($365 billion compared to $216 billion). U.S. pharmaceutical research costs alone account for nearly 17.9% of total pharmaceutical revenue-which totals about $67 billion and accounts for nearly 40% of pharmaceutical market growth, the most of any country in the world.

Interestingly, the U.S. has a much higher usage of generic drugs (that are much cheaper as compared to band name drugs), yet spend a higher per capita amount for prescription drugs in general. The reason for this discrepancy is likely because Americans typically buy the MOST POPULAR drugs from brand name prescription companies (which are more expensive). These pharmaceutical companies also hold on to the patents of these drugs until they become non cost effective, decreasing competition. Additionally, the majority of prescription drugs in development are anti-cancer drugs, which are typically more expensive than other medications. The U.S. also prescribes more medicines per capita on average on prescription medicines compared to Europeans, thus driving up medical costs.

Decreasing the amount of time a brand name company has to hold on to the patent of a drug would help to increase competition and lower prices by allowing generic companies to sell the drug at a cheaper price. Moreover, insurance companies increasingly cover non cost-effective drugs/treatments (drugs/treatments that have a high cost of development but are used little and/or have marginal positive health effects) that premium holders are told are necessary, and thus raise insurance premiums. Regulating which drugs can be covered by analyzing cost vs effect would help to decrease total insurance costs and encourage research of cost effective pharmaceuticals.

The U.S. has a higher per capita usage and ownership of advanced diagnostic technologies such as MRI’s and CT scans. This means not only do we own more of the technology per capita, but these machines are used at a rate much higher than those of European nations. The price of using these machines is also typically higher in the United States. All three of these factors compound to drive up insurance costs and put a burden on premium payers and taxpayers at large.

But of course that’s not it. People in the United States also receive a greater amount of surgeries than their European counterparts per capita, which helps to further drive up medical costs. The higher use and ownership of diagnostic medical technology along with the higher rate of surgical procedures may also tie into defensive medicine practices, as the high use of many of these technologies and procedures helps lead to the conclusion that many of these things are NOT entirely necessary to diagnose and treat a patient. Keeping medical practitioners accountable by both decreasing the fear of malpractice lawsuits and also increasing patient-practitioner communication will help to ensure wasteful practices and procedures are reduced.

The last large factor as to why U.S. healthcare is so expensive is because of the immense complexity and inefficiency of healthcare administration. Healthcare administration is essentially everything but the actual diagnosis and treatment of disease, which could include insurance to patient communication, forms medical providers use to document aspects of their patients’ diseases, communication between insurance companies and healthcare providers, and much, more. Administration costs in 2012 reached an estimated $361 billion– and the numbers are rising every year. Some believe that the costs of this administration could be cut nearly in half through a variety of methods (which I won’t go into detail about) that essentially include standardization of records and increased and/or more efficient communication between healthcare providers, insurance companies, and patients.

In conclusion, healthcare in the United has many unique problems that must be individually addressed with precise care. Increasing the overall health of Americans, decreasing fear of malpractice claims, increasing patient-practitioner communication, abating administrative inefficiencies, and restructuring/amending pharmaceutical regulations will ensure healthcare costs go down.

From Cutting Bacteria to Helping Humans Fight Infectious Diseases: The New Age of Gene Editing

Muznah Khan 

The World Health Organization has proclaimed the current outbreak of the Zika virus a public health emergency with potential repercussions around the world. This troubling virus is known to be transmitted from person to person through the bite of a mosquito, and at the moment there is no solid prevention method.

However, what if there was a way to stop this outbreak from spreading by genetically removing a mosquito’s ability to carry the virus, thereby ending its ability to transfer it to humans? This option would have been improbable a few years ago, but a gene-editing tool called CRISPR has made it a viable solution.

Overview of Genome Editing

Genome editing, the process of editing or changing an organism’s DNA (genetic makeup), has been around for many decades now. Various gene-editing methods have been successfully utilized to modify genes in animals and agricultural crops, even in humans. However, no past method compares to the efficiency of the CRISPR/Cas9 immune system process. CRISPR stands for “Clustered Regularly Interspaced Short Palindromic Repeats” and it is the newest and most promising gene editing method yet.

Zinc finger nucleases and TALENs were the main gene editing methods in use before CRISPR. Both of these work in similar ways to CRISPR but have significant drawbacks.

Zinc fingers are engineered proteins that can be programmed to target specific genes in an organism. These proteins have two ends: one end is tailored to recognize a specific DNA sequence while the other end cuts the DNA at a certain point. Each DNA edit done using this process required scientists to create a new zinc finger protein designed specifically for the targeted DNA sequence. This was a long, costly process that didn’t always produce positive results.

Soon after zinc fingers, the TALEN (Transcription Activator-Like Effector Nucleases) method was created. TALENs are proteins that work similarly to zinc fingers. While an improvement over zinc fingers, TALENs are too large to work with and take more time to construct making the method ineffective in time-sensitive scenarios as ones presented by disease outbreaks such as the Zika virus outbreak.

What Makes CRISPR Different?

In 2012, researchers studying bacteria observed their unique ability to fight viral infections using an immune system they called CRISPR. The researchers realized they could use the CRISPR system as a tool for highly targeted genetic engineering in other organisms.

Unlike previous methods, CRISPR does not require a series of steps that, if performed incorrectly, could be quite harmful. To target a new DNA sequence, scientists only need to create a new RNA strand (genetic cousin to DNA that attaches to DNA at its bases), not a whole new protein as needed for other gene-editing processes. In a study conducted by Spencer Knight and his team, it was shown that even though the Cas9 protein complex within CRISPR can attach to the wrong site at times, it is very uncommon for cleaving, the cutting of DNA, to occur. The protein quickly moves onto the next DNA segment not giving it enough time to cleave.

Simplified Cas9/CRISPR complex

How Does CRISPR Work in an Organism?

To understand how CRISPR works, let’s use the example of its interaction with viruses. With the CRISPR immune system, virally infected bacteria are able to use a protein called Cas9 which can detect, cut, and then degrade viral DNA. After viral DNA enters the bacterial cell, the cell creates complementary RNA, the genetic cousin of DNA, which matches the viral DNA at each of its bases. The RNA and Cas9 protein create a complex that searches through the cell’s entire DNA to find and cut matching viral DNA, inactivating the virus.

The CRISPR complex is customizable so researchers can program it, by creating new RNA strands, to recognize ANY DNA sequence in an organism’s cells, making it an important genome engineering method for all organisms, not just an immune system in bacteria.

Real World Applications

The flexibility and efficiency of CRISPR presents itself to many useful applications, especially in the fight against infectious diseases. In one of a number of successful projects, researchers have been able to use CRISPR to create mosquitoes resistant to the malaria parasite. They were able to remove a segment of mosquito DNA that allowed it to carry the parasite and replace it with a DNA sample synthetically engineered in the lab. 100% of these mutated mosquitoes’ offspring are resistant to the malaria-causing parasite that they otherwise would transfer to humans.

Similar to malaria, the Zika virus is spread by mosquitoes. Currently there is no conclusive way of stopping the spread of the virus.

But maybe there is.

Researchers have actually started considering CRISPR as a solution. Scientists could potentially remove the gene segment that gives mosquitos’ their ability to carry the Zika virus. Similar to the malaria experiment, these mosquitoes could become genetically unable to carry and transmit Zika virus.

Proving CRISPR’s versatility, further studies show CRISPR being successfully used in the editing of both plants and animals. Scientists in China have created goats with deletions in the gene that inhibits muscle and hair growth. These goats are better able to support the country’s meat and wool industries.

Also in China, Gao Caixia’s group has used CRISPR to disable four rice genes with positive results and removed a gene in wheat that could lead to plants resistant to powdery mildew. These plants are the first of many shown to be responsive to the Cas9/CRISPR technology.

CRISPR also promises significant advancements in disease control and gene therapy—the prevention of disease through alterations in an organism’s genome. From studies on animals, CRISPR could be used to treat blindness, HIV and many other diseases in humans. In addition to treating diseases, CRISPR could be used to enhance the human body.

Ethical Concerns

There have been ethical concerns raised about gene editing right from the earliest days of the technology, and CRISPR is no different. With the technology moving so quickly, many scientists feel it’s necessary to discuss the ethical implications of CRISPR.

One major concern is in editing the human genome. Is it right to edit human embryos and alter genes for generations to come? Is it even safe to do such a thing?

Another concern is the environmental impact genetically engineered organisms can have. Genetically modified organisms can be harmful to humans and other organisms if they are not watched carefully. Furthermore, mutated insects (i.e mosquitoes) can cause an imbalance in the environment and be detrimental to species around them.

Ethical concerns will always be a concern for every new technology as societies grapple with the pros and cons of scientific advancements. However, carefully considered regulations and guidelines can eliminate many safety and ethical concerns.


Like any new technology, more studies need to be conducted before widespread use of CRISPR is seen. Researchers are still trying to better understand the CRISPR system, but from what they have gathered, CRISPR is the best gene editing technology yet. And with millions of lives at stake, we can at least consider CRISPR’s promising role in combatting debilitating diseases such as malaria and Zika virus.

References:

  1. Doudna, Jennifer. “We Can Now Edit Our DNA. But Let’s Do It Wisely.” TED. TED Conferences, Sept. 2015. Web. 26 Jan. 2016.
  2. Pennisi, E. “The CRISPR Craze.” Science 341.6148 (2013): 833-36. Web. 25 Jan. 2016.
  3. Caplan, A. L., B. Parent, M. Shen, and C. Plunkett. “No Time to Waste–the Ethical Challenges Created by CRISPR.” EMBO Reports 16.11 (2015): 1421-426. Web.

 

Women Stronger than Men? – Studies show Women may have better flu defenses than Men

 

Elondra Harr

Virtually everyone knows about the influenza (flu) virus. But not many people know, or even think about, which sex it seems to hit the hardest. For quite some time, many people have believed that men were actually “stronger” than women. But recently, studies have shown that women may actually be stronger than men in at least one category: Fighting the flu. International research teams have been studying what exactly might be helping women fight off this virus and what makes men more susceptible to getting the flu virus.

In the U.S, the flu season is usually at its worst during the months of January and February. But, it can actually start as early as October. After the flu virus has already infiltrated the body, the virus reacts the same way in both men and women.

During the first 24 to 48 hours, the flu virus gets into your system through the respiratory tract. That could be from breathing in someone’s cough or sneeze, or touching a surface contaminated with the flu virus and then touching your mouth, nose, or eyes. You typically don’t have any symptoms during this time. After the virus makes its way in, it begins to replicate.

The next five days, your body’s immune cells are sent to the places in your body where the virus is replicating. These cells send out signaling molecules to tell the body to turn on its immune response. This is where women and men’s bodies seem to differ. Your body then rounds up an immune system response to attack the virus so it can’t infect other cells.

Eventually, in the last few days the flu virus begins to leave your system. The inflammation finally decreases.

Estrogen’s Effect on the Flu Virus

Studies are now showing that the female sex hormone, Estrogen, seems to be the reason women are more likely to be able to fight off the flu virus than men. At first, recent studies showed the estrogen hampers the replication of viruses including HIV, Ebola, and hepatitis. The estrogen lessens the infection’s severity and makes the infection less likely to spread to other people. But then, Sabra L. Klein, an associate professor in the Departments of Molecular Microbiology and Immunology, and Biochemistry and Molecular Biology at the John Hopkins Bloomberg School of Public Health, decided to investigate whether or not estrogen might have the same effect on the flu virus.

She and the rest of her research team decided to collect nasal cells. Why nasal cells? Because typically the first cells in the body to get infected with the flu virus are in your nose. She collected nasal cells from both men and women volunteers. The researchers exposed bunches of these nasal cells to different types of estrogens including normal levels of naturally occurring estrogen, different types of selective estrogen receptor parts called SERMs, which are synthetic estrogen-like chemicals used for hormone replacement therapy and infertility treatments, or bisphenol A, an estrogen-like chemical that is found in many plastics. Then, they exposed the nasal cells to the influenza A virus, which is a variant strain of the flu virus.

The tests showed that the female cells the received all three of different types of estrogen, showed sign of a significantly less amount of flu virus replication – Nearly 1,000 times less than other cells that hadn’t been exposed to the estrogens. More research showed that the hormones that caused this effect actually act on the estrogen receptor Beta. With the male nasal cells they tested, it seemed that the nasal cells didn’t have any receptors for the estrogen hormones therefore they didn’t have the same protective effects as the female nasal cells.

When Klein and her research team looked for the reasoning behind estrogen’s protective effect again this virus, they discovered that flu viruses binding to Beta decreases the activity of more than 30 genes used in cell metabolism, slowing the metabolic rate of these cells and preventing them from creating new viral particles.

Men and Testosterone Levels

Well now we talked about the female hormone involved in flu defenses but what about male hormones? Studies are now showing that high levels of the male sex hormone, testosterone, can actually weaken men’s immune systems.

For reasons that have not yet been found out, men are more susceptible to bacterial, viral, fungal, and parasitic infections than women are, and men’s immune systems don’t respond as strongly to vaccinations against the flu and many other diseases. A new study may explain why this seems to be the case.

A multinational team consisting of researchers from Stanford University, France, and the University of North Carolina conducted an experiment taking blood from 54 women and 37 men, all from different age groups and studied a variety of immune system proteins and cells to detect gene expression. They then gave flu vaccinations to all of these volunteers and then checked them for any signs of changes. Men, as a group, responded less to the vaccine.

Thirty-three women and 10 men actually responded to the vaccine out of the 54 women and 37 men. Most of the male non-responders had high levels of testosterone. Men with lower testosterone levels showed to have roughly an equal amount of response to the flu vaccine as the women.

When the team finished the analysis of the genes, they discovered that men with high levels of testosterone had high activation levels of a multi-gene cluster that is involved with immune system regulation called Module 52. This high activation level of Module 52 correlates with reduced antibody levels post-vaccination. But, this only has an effect on men with higher levels of testosterone. Module 52 has no effect on the amount of antibodies produced in men with lower levels and women post-vaccination.

Additional analysis showed that testosterone actually reduces level of certain regulatory proteins that usually prevent Module 52 genes from activating. In other words, higher testosterone levels result in more Module 52 gene expression. Module 52 prevents antibodies from forming in men with high testosterone levels, causing their immune systems to be weak and in turn makes them more susceptible to getting the flu even after they get vaccinated.

So scientifically speaking, women are actually stronger! Their immune systems are stronger due to estrogen and the lack of Module 52 gene expression. Men are more susceptible to getting the flu virus, but especially men with higher levels of testosterone. Even though the odds may be stacked against you, there are some things you can do to help prevent yourself from getting the flu.

Preventing The Flu

The Center for Disease Control and Prevention (CDC) has formulated three steps that they believe will be beneficial to the prevention of the flu.

Step 1: Get the Flu vaccination.

The CDC recommends an annual flu vaccination as the first and most important step in protection again the flu virus. Even for males, some protection is better than no protection!

Step 2: Take everyday preventative actions to stop the spread of germs.

This includes: washing your hands often with soap and water, covering your nose and mouth when you sneeze, keeping your area clean, and while sick, limit contact with others as much as possible to keep from infecting them.

Step 3: Take flu antiviral drugs if your doctor prescribes them.

Even if you believe they won’t work, it’s better to not risk getting worse and possibly spreading it to others by taking the medicine your doctor prescribes for the flu. The world will thank you!