Telomeres: Ways to Prolong Life

Catalyst Volume 10

Two hundred years ago, the average life expectancy oscillated between 30 and 40 years, as it had for centuries before. Medical knowledge was fairly limited to superstition and folk cures, and the science behind what actually caused disease and death was lacking. Since then, the average lifespan of human beings has skyrocketed due to scientific advancements in health care, such as an understanding of bacteria and infections. Today, new discoveries are being made in cellular biology which, in theory, could lead us to the next revolutionary leap in life span. Most promising among these recent discoveries is the manipulation of telomeres in order to slow the aging process, and the use of telomerase to identify cancerous cells.

Before understanding how telomeres can be utilized to increase the average lifespan of humans, it is essential to understand what a telomere is. When cells divide, their DNA must be copied so that all of the cells share an identical DNA sequence. However, the DNA cannot be copied all the way to the end of the strand, resulting in the loss of some DNA at the end of the sequence with every single replication.¹ To prevent valuable genetic code from being cut off during cell division, our DNA contains telomeres, a meaningless combination of nucleotides at the end of our chromosomal sequences that can be cut off without consequences to the meaningful part of the DNA. Repeated cell replication causes these protective telomeres to become shorter and shorter, until valuable genetic code is eventually cut off, causing the cell to malfunction and ultimately die.¹ The enzyme telomerase functions in cells to rebuild these constantly degrading telomeres, but its activity is relatively low in normal cells as compared to cancer cells.²

The applications of telomerase manipulation have only come up fairly recently, with the discovery of the functionality of both telomeres and telomerase in the mid 80’s by Nobel Prize winners Elizabeth Blackburn, Carol Grieder, and Jack Sjozak.³ Blackburn discovered a sequence at the end of chromosomes that was repeated several times, but could not determine what the purpose of this sequence was. At the same time, Sjozak was observing the degradation of minichromosomes, chromatin-like structures which replicated during cell division when introduced to a yeast cell. Together, they combined their work by isolating Blackburn’s repeating DNA sequences, attaching them to Sjozak’s minichromosomes, and then placing the minichromosomes back inside yeast cells. With the new addition to their DNA sequence, the minichromosomes did not degrade as they had before, thus proving that the purpose of the repeating DNA sequence, dubbed the telomere, was to protect the chromosome and delay cellular aging.

Because of the relationship between telomeres and cellular aging, many scientists theorize that cell longevity could be enhanced by finding a way to control telomere degradation and keep protective caps on the end of cell DNA indefinitely.¹ Were this to be accomplished, the cells would be able to divide an infinite number of times before they started to lose valuable genetic code, which would theoretically extend the life of the organism as a whole.

In addition, studies into telomeres have revealed new ways of combatting cancer. Although there are many subtypes of cancer, all variations of cancer involve the uncontrollable, rapid division of cells. Despite this rapid division, the telomeres of cancer cells do not shorten like those of a normal cell upon division, otherwise this rapid division would be impossible. Cancer cells are likely able to maintain their telomeres due to their higher levels of telomerase.³ This knowledge allows scientists to use telomerase levels as an indicator of cancerous cells, and then proceed to target these cells. Vaccines that target telomerase production have the potential to be the newest weapon in combatting cancer.² Cancerous cells continue to proliferate at an uncontrollable rate even when telomerase production is interrupted. However, without the telomerase to protect their telomeres from degradation, these cells eventually die.

As the scientific community advances its ability to control telomeres, it comes closer to controlling the process of cellular reproduction, one of the many factors associated with human aging and cancerous cells. With knowledge in these areas continuing to develop, the possibility of completely eradicating cancer and slowing the aging process is becoming more and more realistic.

References

1. Genetic Science Learning Center. Learn.Genetics. http://learn.genetics.utah.edu (accessed Oct. 5, 2016).
2. Shay, J. W.; Woodring W. E.  NRD. [Online] 2016, 5. http://www.nature.com/nrd/journal/v5/n7/full/nrd2081.html (accessed Oct. 16, 2016).
3. The 2009 Nobel Prize in Physiology or Medicine - Press Release. The Nobel Prize. https://www.nobelprize.org/nobel_prizes/medicine/laureates/2009/press.html (accessed Oct. 4, 2016).

Wearable Tech is the New Black

Catalyst Volume 10

What if our clothes could detect cancer? That may seem like a far fetched, “only applicable in a sci-fi universe” type of concept, but such clothes do exist and similar devices that merge technology and medicine are actually quite prominent today. The wearable technology industry, a field poised to grow to $11.61 billion by 20201, is exploding in the healthcare market as numerous companies produce various devices that help us in our day to day lives such as wearable EKG monitors and epilepsy detecting smart watches. Advancements in sensor miniaturization and integration with medical devices have greatly opened this interdisciplinary trade by lowering costs. Wearable technology ranging from the Apple Watch to consumable body-monitoring pills can be used for everything from health and wellness monitoring to early detection of disorders. But as these technologies become ubiquitous, there are important privacy and interoperability concerns that must be addressed.

Wearable tech like the Garmin Vivosmart HR+ watch uses sensors to obtain insightful data about its wearer’s health. This bracelet-like device tracks steps walked, distance traveled, calories burned, pulse, and overall fitness trends over time.² It transmits the information to an app on the user’s smartphone which uses various algorithms to create insights about the person’s daily activity. This data about a person’s daily athletic habits is useful to remind them that fitness is not limited to working out at the gym or playing a sport--it’s a way of life. Holding tangible evidence of one’s physical activity for the day or history of vital signs empowers patients to take control of their personal health. The direct feedback of these devices influences patients to make better choices such as taking the stairs instead of the elevator or setting up a doctor appointment early on if they see something abnormal in the data from their EKG sensor. Connecting hard evidence from the body to physical and emotional perceptions refines the reality of those experiences by reducing the subjectivity and oversimplification that feelings about personal well being may bring about.

Not only can wearable technology gather information from the body, but these devices can also detect and monitor diseases. Diabetes, the 7th leading cause of death in the United States,³ can be detected via AccuCheck, a technology that can send an analysis of blood sugar levels directly to your phone.⁴ Analysis software like BodyTel can also connect patients with doctors and other family members who would be interested in looking at the data gathered from the blood test.⁵ Ingestible devices such as the Ingestion Event Marker take monitoring a step further. Designed to monitor medication intake, the pills keep track of when and how frequently patients take their medication. The Freescale KL02 chip, another ingestible device, monitors specific organs in the body and relays the organ’s status back to a Wi-Fi enabled device which doctors can use to remotely measure the progression of an illness. They can assess the effectiveness of a treatment with quantitative evidence which makes decision-making about future treatment plans more effective.

Many skeptics hesitate to adopt wearable technology because of valid concerns about accuracy and privacy. To make sure medical devices are kept to the same standards and are safe for patient use, the US Food and Drug Administration (FDA) has begun to implement a device approval process. Approval is only granted to devices that provably improve the functionality of traditional medical devices and do not pose a great risk to patients if they malfunction.⁶In spite of the FDA approval process, much research is needed to determine whether the information, analysis and insights received from various wearable technologies can be trusted.

Privacy is another big issue especially for devices like fitness trackers that use GPS location to monitor user behavior. Many questions about data ownership (does the company or the patient own the data?) and data security (how safe is my data from hackers and/or the government and insurance companies?) are still in a fuzzy gray area with no clear answers.⁷ Wearable technology connected to online social media sites, where one’s location may be unknowingly tied to his or her posts, can increase the chance for people to become victims of stalking or theft. Lastly, another key issue that makes medical practitioners hesitant to use wearable technology is the lack of interoperability, or the ability to exchange data, between devices. Data structured one way on a certain wearable device may not be accessible on another machine. Incorrect information might be exchanged, or data could be delayed or unsynchronized, all to the detriment of the patient.

Wearable technology is changing the way we live our lives and understand the world around us. It is modifying the way health care professionals think about patient care by emphasizing quantitative evidence for decision making over the more subjective analysis of symptoms. The ability for numeric evidence about one’s body to be documented holds people accountable for the actions. Patients can check to see if they meet their daily step target or optimal sleep count, and doctors can track the intake of a pill and see its effect on the patient’s body. For better or for worse, we won’t get the false satisfaction of achieving our fitness goal or of believing in the success of a doctor’s recommended course of action without tangible results. While we have many obstacles to overcome, wearable technology has improved the quality of life for many people and will continue to do so in the future.

References

1. [Hunt, Amber. Experts: Wearable Tech Tests Our Privacy Limits. http://www.usatoday.com/story/tech/2015/02/05/tech-wearables-privacy/22955707/ (accessed Oct. 24, 2016).
2. Vivosmart HR+. https://buy.garmin.com/en-US/US/into-sports/health-fitness/vivosmart-hr-/prod548743.html (accessed Oct. 31, 2016).
3. Statistics about Diabetes. http://www.diabetes.org/diabetes-basics/statistics/ (accessed Nov. 1, 2016).
4. Accu-Chek Mobile. https://www.accu-chek.co.uk/gb/products/metersystems/mobile.html (accessed Oct. 31, 2016).
5. GlucoTel. http://bodytel.com/portfolios/glucotel/ (accessed Oct. 31, 2016)
6. Mobile medical applications guidance for industry and Food and Drug Administration staff. U. S. Food and Drug Administration, Feb. 9, 2015. http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM263366.pdf (accessed Oct. 17, 2016).
7. Meingast, M.; Roosta, T.; Sastry, S. Security and Privacy Issues with Health Care Information Technology. http://www.cs.jhu.edu/~sdoshi/jhuisi650/discussion/secprivhealthit.pdf (accessed Nov. 1, 2016).

East Joins West: The Rise of Integrative Medicine

Catalyst Volume 10

An ancient practice developed thousands of years ago and still used by millions of people all over the world, Traditional Chinese Medicine (TCM) has undoubtedly played a role in the field of medicine. But just what is TCM? Is it effective? And can it ever be integrated with Western medicine?

The techniques of TCM stem from the beliefs upon which it was founded. The theory of the yin and yang balance holds that all things in the universe are composed of a balance between the forces of yin and yang. While yin is generally associated with objects that are dark, still, and cold, yang is associated with items that are bright, warm, and in motion.¹ In TCM, illness is believed to be a result of an imbalance of yin or yang in the body. For instance, when yin does not cool yang, yang rises and headaches, flushing, sore eyes, and sore throats result. When yang does not warm yin, poor circulation of blood, lethargy, pallor, and cold limbs result. TCM aims to determine the nature of the disharmony and correct it through a variety of approaches. As the balance is restored in the body, so is the health.²

Another fundamental concept of TCM is the idea of qi, which is the energy or vital force responsible for controlling the functions of the human mind and body. Qi flows through the body through 12 meridians, or channels, that correspond to the 12 major organ systems, and 8 extra meridians that are all interconnected with the major channels. Just like an imbalance between yin and yang, disruption to the flow causes disease, and correction of the flow restores the body to balance.² In TCM, disease is not viewed as something that a patient has. Rather, it is something that the patient is. There is no isolated entity called “disease,” but only a whole person whose body functions may be balanced or imbalanced, harmonious or disharmonious.³ Thus, TCM practitioners aim to increase or decrease qi in the body to create a healthy yin-yang balance through various techniques such as acupuncture, herbal medicine, nutrition, and mind/body exercise (tai chi, yoga). Eastern treatments are dismissed by some as superfluous to the recovery process and even harmful if used in place of more conventional treatments. However, evidence exists indicating Eastern treatments can be very effective parts of recovery plans.

The most common TCM treatments are acupuncture, which involves inserting needles at precise meridian points, and herbal medicine, which refers to using plant products (seeds, berries, roots, leaves, bark, or flowers) for medicinal purposes. Acupuncture seeks to improve the body’s functions by stimulating specific anatomic sites—commonly referred to as acupuncture points, or acupoints. It releases the blocked qi in the body, which may be causing pain, lack of function, or illness. Although the effects of acupuncture are still being researched, results from several studies suggest that it can stimulate function in the body and induce its natural healing response through various physiological systems.⁴ According to the WHO (World Health Organization), acupuncture is effective for treating 28 conditions, while limited but probable evidence suggests it may have an effective value for many more. Acupuncture seems to have gained the most clinical acceptance as a pain reduction therapy. Research from an international team of experts pooled the results of 29 studies on chronic pain involving nearly 18,000 participants—some had acupuncture, some had “sham” acupuncture, and some did not have acupuncture at all. Overall, the study found acupuncture treatments to be superior to both a lack of acupuncture treatment and sham acupuncture treatments for the reduction of chronic pain, suggesting that such treatments are a reasonable option for afflicted patients.⁵ According to a study carried out at the Technical University of Munich, people with tension headaches and/or migraines may find acupuncture to be very effective in alleviating their symptoms.⁶ Another study at the University of Texas M.D. Anderson Cancer Center found that twice weekly acupuncture treatments relieved debilitating symptoms of xerostomia--severe dry mouth--among patients undergoing radiation for head and neck cancer.⁷ Additionally, acupuncture has been demonstrated to both enhance performance in the memory-related brain regions of mild cognitive impairment patients (who have an increased risk of progressing towards Alzheimer’s disease),⁸ and to provide therapeutic advantages in regulating inflammation in infection and inflammatory disease.⁹

Many studies have also demonstrated the efficacy of herbal medicine in treating various illnesses. Recently, the WHO estimated that 80% of people worldwide rely on herbal medicines for some part of their primary health care. Researchers from the University of Adelaide have shown that a mixture of extracts from the roots of two medicinal herbs, Kushe and Baituling, works to kill cancer cells.¹⁰ Furthermore, scientists concluded that herbal plants have the potential to delay the development of diabetic complications, although more investigations are necessary to characterize this antidiabetic effect.¹¹ Finally, a study found that Chinese herbal formulations appeared to alleviate symptoms for some patients with Irritable Bowel Syndrome, a common functional bowel disorder that is characterized by chronic or recurrent abdominal pain and does not currently have any reliable medical treatment.¹²

Both TCM and Western medicine seek to ease pain and improve function. Can the two be combined? TCM was largely ignored by Western medical professionals until recent years, but is slowly gaining traction among scientists and clinicians as studies show that an integrative approach has been effective. For instance, for patients dealing with chronic pain, Western medicine can stop the pain quickly with medication or interventional therapy, while TCM can provide a longer-lasting solution to the underlying problem with milder side effects and a greater focus on treating the underlying illness.¹³ A study by Cardiff University’s School of Medicine and Peking University in China showed that combining TCM and Western medicine could offer hope for developing new treatments for liver, lung, bone, and colorectal cancers.¹⁴ Also, studies on the use of traditional Chinese medicines for the treatment of multiple diseases like bronchial asthma, atopic dermatitis, and IBS showed that an interdisciplinary approach to TCM may lead to the discovery of new medicines.¹⁵

TCM is still a developing field in the Western world, and more research and clinical trials on the benefits and mechanisms of TCM are being conducted. While TCM methods such as acupuncture and herbal medicine must be further examined to be accepted as credible treatment techniques in modern medicine, they have been demonstrated to treat various illnesses and conditions. Therefore, while it is unlikely for TCM to be a suitable standalone option for disease management, it does have its place in a treatment plan with potential applications alongside Western medicine. Utilizing TCM as a complement to Western medicine presents hope in increasing the effectiveness of healthcare treatment.

References

1. Yin and Yang Theory. Acupuncture Today. http://www.acupuncturetoday.com/abc/yinyang.php (accessed Dec. 15, 2016).
2. Lao, L. et al. Integrative pediatric oncology. 2012, 125-135.
3. The Conceptual Differences between Chinese and Western Medicine. http://www.mosherhealth.com/mosher-health-system/chinese-medicine/chinese-versus-western (accessed Dec. 15, 2016).
4. How Acupuncture Can Relieve Pain and Improve Sleep, Digestion, and Emotional Well-being. http://cim.ucsd.edu/clinical-care/acupuncture.shtml (accessed Dec. 15, 2016).
5. Vickers, A J. et al. Arch of Internal Med. 2012, 172, 1444-1453.
6. Melchart, D. et al. Bmj. 2005, 331, 376-382.
7. Meng, Z. et al. Cancer. 2012, 118, 3337-3344.
8. Feng, Y. et al. Magnetic resonance imaging. 2012, 30, 672-682.
9. Torres-Rosas, R. et al. Nature medicine. 2014, 20, 291-295.
10. Qu, Z. et al. Oncotarget. 2016, 7, 66003-66019.
11. Bnouham, M. et al. Int. J. of Diabetes and Metabolism. 2006, 14, 1.
12. Bensoussan, A. et al. Jama. 1998, 280, 1585-1589.
13. Jiang, W. Trends in pharmacological sciences. 2005, 26, 558-563.
14. Combining Chinese, Western medicine could lead to new cancer treatments. https://www.sciencedaily.com/releases/2013/09/130928091021.htm (accessed Dec. 15, 2016).
15. Yuan, R.; Yuan L. Pharmacology & therapeutics. 2000, 86, 191-198.

Transplanting Time

Catalyst Volume 10

Nowadays, it is possible for patients with organ failure to live for decades after receiving an organ transplant. Since the first successful kidney transplant in the 1950s,^1,2 advances in the procedure, including the improvement of drugs that facilitate acceptance of the foreign body parts,³ have allowed surgeons to transplant a wider variety of organs, such as the heart, lungs, liver, and pancreas.^2,4 Over 750,000 lives have been saved and extended through the use of organ transplants, an unthinkable feat just over 50 years ago.² Limitations to organ transplantation, such as the lack of available organs, and the development of new advancements that can improve the process promote ongoing discussion regarding the ethics of transplants.

The idea behind an organ transplant is simple. When both the recipient and the new organ are ready, surgeons detach the blood vessels attached to the failing organ before putting the new one in its place by reattaching the patient’s blood vessels to the functioning organ. To prevent rejection of the new organ, the recipient will continue to take immunosuppressant drugs³. In exchange for this lifelong commitment, the patient often receives a longer, more enjoyable life.²

The organs used in transplants usually originate from a cadaver or a living donor.^1-3 Some individuals are deterred from becoming an organ donor because they are concerned that doctors will not do their best to save them if their organs are needed. This concern is further complicated by blurred definitions of “dead”; in one ethically ambiguous situation, dying patients who are brain dead may be taken off of life support so that their organs may be donated.^1-3 Stories of patients who reawaken from comas after being pronounced “dead” may give some encouragement, but a patient’s family and doctors must decide when to give up that hope. Aside from organs received from the deceased, living donors, who may be family, friends, or strangers to the recipient, may donate organs that they can live without, such as a lung or a kidney.^1-3 However, the potential injuring of a healthy person for the sake of another may contradict the oath that doctors take, which instructs physicians to help, not harm their patients.¹

One of the most pressing issues today stems from the following question: who receives the organs? The transplant waiting list is constantly growing because the number of organs needed greatly exceeds the number of organs that are available.^1-3 Unfortunately, 22 patients die every day while they are waiting for a new organ.⁴ Because the issue of receiving a transplant is time-sensitive, medical officials must decide who receives a transplant first. Should the person who needs a transplant the most have greater priority over another who has been on the waiting list longer? Should a child be eligible before a senior? Should a lifelong smoker be able to obtain a new lung? Currently, national policy takes different factors into account depending on the organ to be transplanted. For example, other than compatibility requirements, patients on the waiting list for liver transplants are ranked solely on their medical need and distance from the donor hospital.⁴ On the other hand, people waiting for kidneys are further considered based on whether they have donated a kidney previously, their age, and their time spent on the waiting list.⁴

Despite various efforts to increase the number of organ donors through education and legislation, the supply of organs does not meet the current and increasing need for them.^1-3 As a result, other methods of obtaining these precious resources are currently being developed, one of which is the use of animal organs, a process known as xenotransplantation. Different animal cells, tissues, and organs are being researched for use in humans, giving some hope to those on the waiting list or those who do not quite qualify for a transplant.^2,3 In the past, surgeons have attempted to use a primate’s heart and liver for transplantation, but the surgical outcomes were poor.2 Other applications of animal tissue are more promising, such as the use of pigs’ islet cells, which can produce insulin, in humans.² However, a considerable risk of using these animal parts is that new diseases may be passed from animal to human. Additionally, animal rights groups have protested the use of primates as a source of whole organs.²

Another possible solution to the deficit of organs is the use of stem cells, which have the potential to grow and specialize. Embryonic stem cells can repair and regenerate damaged organs, but harvesting them destroys the source embryo.^2,3 Although the embryos are created outside of humans, there are objections to their use. What differentiates a mass of cells from a living person? Fortunately, adult stem cells can be used for treatment as well.² Researchers have developed a new method that causes adult stem cells to return to a state similar to that of the embryonic stem cells, although the efficacy of the induced adult stem cells compared to the embryonic stem cells is still unclear.⁷

Regardless of the continuous controversy over the ethics of transplantation, the boundaries for organ transplants are being pushed further and further. Head transplants have been attempted for over a century in other animals, such as dogs,⁵ but several doctors want to move on to work with humans. To attach a head to a new body, the surgeon would need to connect the old and new nerves in the spinal cord so that the patient’s brain could interact with the host body. Progress is already being made in repairing severe spinal cord injuries. In China, Dr. Ren Xiaoping plans to attempt a complete body transplant, believed by some to be currently impossible.⁶ There is not much information about the amount of pain that the recipient of a body transplant must endure,⁵ so it may ultimately decrease, rather than increase, the patient’s quality of life. Overall, most agree that it would be unethical to continue, considering the limited success of such projects and the high chance of failure and death.

Organ transplants and new developments in the field have raised many interesting questions about the ethics of the organ transplantation process. As a society, we should determine how to address these problems and set boundaries to decide what is “right.”

References

1. Jonsen, A. R. Virtual Mentor. 2012, 14, 264-268.
2. Abouna, G. M. Med. Princ. Prac. 2002, 12, 54-69.
3. Paul, B. et al. Ethics of Organ Transplantation. University of Minnesota Center for Bioethics [Online], February 2004 http://www.ahc.umn.edu/img/assets/26104/Organ_Transplantation.pdf (accessed Nov. 4, 2016)
4. Organ Procurement and Transplantation Network. https://optn.transplant.hrsa.gov/ (accessed Nov. 4 2016)
5. Lamba, N. et al. Acta Neurochirurgica. 2016.
6. Tatlow, D. K. Doctor’s Plan for Full-Body Transplants Raises Doubts Even in Daring China. The New York Times. http://www.nytimes.com/2016/06/12/world/asia/china-body-transplant.html?_r=0 (accessed Nov. 4, 2016)
7. National Institutes of Health. stemcells.nih.gov/info/basics/6.htm (accessed Jan. 23, 2017)

Graphene Nanoribbons and Spinal Cord Repair

Catalyst Volume 10

The same technology that has been used to strengthen polymers¹, de-ice helicopter wings², and create more efficient batteries³ may one day help those with damaged or even severed spinal cords walk again. The Tour Lab at Rice University, headed by Dr. James Tour, is harnessing the power of graphene nanoribbons to create a special new material called Texas-PEG that may revolutionize the way we treat spinal cord injuries; one day, it may even make whole body transplants a reality.

Dr. Tour, the T.T. and W.F. Chao Professor of Chemistry, Professor of Materials Science and NanoEngineering, and Professor of Computer Science at Rice University, is a synthetic organic chemist who mainly focuses on nanotechnology. He currently holds over 120 patents and has published over 600 papers, and was inducted into the National Academy of Inventors in 2015.⁴ His lab is currently working on several different projects, such as investigating various applications of graphene, creating and testing nanomachines, and the synthesizing and imaging of nanocars. The Tour Lab first discovered graphene nanoribbons while working with graphene back in 2009.⁵ Their team found a way to “unzip” graphene nanotubes into smaller strips called graphene nanoribbons by injecting sodium and potassium atoms between nanotube layers in a nanotube stack until the tube split open. “We fell upon the graphene nanoribbons,” says Dr. Tour. “I had seen it a few years ago in my lab but I didn’t believe it could be done because there wasn’t enough evidence. When I realized what we had, I knew it was enormous.”

This discovery was monumental: graphene nanoribbons have been used in a variety of different applications because of their novel characteristics. Less than 50 nm wide ( which is about the width of a virus), graphene nanoribbons are 200 times stronger than steel and are great conductors of heat and electricity. They can be used to make materials significantly stronger or electrically conductive without adding much additional weight. It wasn’t until many years after their initial discovery, however, that the lab discovered that graphene nanoribbons could be used to heal severed spinal cords.

The idea began after one of Dr. Tour’s students read about European research on head and whole body transplants on Reddit. This research was focused on taking a brain dead patient with a healthy body and pairing them with someone who has brain activity but has lost bodily function. The biggest challenge, however, was melding the spine together. The neurons in the two separated parts of the spinal cord could not communicate with one another, and as a result, the animals involved with whole body and head transplant experiments only regained about 10% of their original motor function. The post-graduate student contacted the European researchers, who then proposed using the Tour lab’s graphene nanoribbons in their research, as Dr. Tour’s team had already proven that neurons grew very well along graphene.

“When a spinal cord is severed, the neurons grow from the bottom up and the top down, but they pass like ships in the night; they never connect. But if they connect, they will be fused together and start working again. So the idea was to put very thin nanoribbons in the gap between the two parts of the spinal cord to get them to align,” explains Dr. Tour. Nanoribbons are extremely conductive, so when their edges are activated with polyethylene glycol, or PEG, they form an active network that allows the spinal cord to reconnect. This material is called Texas-PEG, and although it is only about 1% graphene nanoribbons, this is still enough to create an electric network through which the neurons in the spinal cord can connect and communicate with one another.

The Tour lab tested this material on rats by severing their spinal cords and then using Texas-PEG to see how much of their mobility was recovered. The rats scored about 19/21 on a mobility scale after only 3 weeks, a remarkable advancement from the 10% recovery in previous European trials. “It was just phenomenal. There were rats running away after 3 weeks with a totally severed spinal cord! We knew immediately that something was happening because one day they would touch their foot and their brain was detecting it,” says Dr. Tour. The first human trials will begin in 2017 overseas. Due to FDA regulations, it may be awhile before we see trials in the United States, but the FDA will accept data from successful trials in other countries. Graphene nanoribbons may one day become a viable treatment option for spinal injuries.

This isn’t the end of Dr. Tour’s research with graphene nanoribbons. “We’ve combined our research with neurons and graphene nanoribbons with antioxidants: we inject antioxidants into the bloodstream to minimize swelling. All of this is being tested in Korea on animals. We will decide on an optimal formulation this year, and it will be tried on a human this year,” Dr. Tour explained. Most of all, Dr. Tour and his lab would like to see their research with graphene nanoribbons used in the United States to help quadriplegics who suffer from limited mobility due to spinal cord damage. What began as a lucky discovery now has the potential to change the lives of thousands.

References

1. Wijeratne, Sithara S., et al. Sci. Rep. 2016, 6.
2. Raji, Abdul-Rahman O., et al. ACS Appl. Mater. Interfaces. 2016, 8 (5), 3551-3556.
3. Salvatierra, Rodrigo V., et al. Adv. Energy Mater. 2016, 6 (24).
4. National Academy of Inventors. http://www.academyofinventors.org/ (accessed Feb. 1, 2017).
5. Zehtab Yazdi, Alireza, et al. ACS Nano. 2015, 9 (6), 5833-5845.

Cognitive Neuroscience: A Glimpse of the Future

Catalyst Volume 10

Cognitive Neuroscience is a branch of science that addresses the processes in the brain that occur during cognitive activity. The discipline addresses how psychological and cognitive activities are caused by and correlated to the neural connections in our brain. It bridges psychology and neuroscience.

Dr. Simon Fischer-Baum, an assistant professor and researcher at Rice University,  co-directs the neuroplasticity lab at the BioScience Research Collaborative. He received his B.A. in Neuroscience and Behavior from Columbia University in 2003 and received his Ph.D. in Cognitive Sciences from Johns Hopkins University in 2010.

Dr. Fischer-Baum describes his research as the “intersection of psychology and neuroscience and computer science to some extent.” He is interested in instances of how we understand and pronounce a word once we see it. He also studies memory and how information is encoded in the brain. In his opinion, functional magnetic resonance imaging (fMRI) and other tools of cognitive neuroscience are extremely relevant to cognitive psychology despite public perception. For example, he believes that there is a “serious disconnect” as a result of the belief that the methods and findings of cognitive neuroscience do not apply to cognitive psychology. Cognitive psychologists have been attempting to discover the variation between the different levels of processing and how information travels between these levels. Cognitive neuroscience can help achieve these goals through the use of fMRIs.

fMRI shows which parts of the brain are active when the subject is performing a task. During any task, multiple regions of the brain are involved, with each region processing different types of information. For example, reading a word involves processing both visual information and meaning; when you are reading a word, multiple regions of the brain are active. However, one problem with fMRIs is that while they demonstrate what regions of the brain are active, they do not convey what function each region is carrying out.  One of the main objectives of Dr. Fischer-Baum’s work is to pioneer new methods similar to computer algorithms to decode what data from an fMRI tells us about what tasks the brain is performing. “I want to be able to take patterns of activity and decode and relate it back to the levels of representation that cognitive psychologists think are going on in research,” Dr. Fischer-Baum explains.

Recently, Dr. Fischer-Baum published a study of a patient who suffered severe written language impairments after experiencing a hemorrhagic stroke. Although this patient’s reading of familiar words improved throughout the years, he still presented difficulties in processing abstract letter identity information for individual letters. Someone who is able to utilize abstract letter representations can  recognize letters independent of case or font; in other words, this person  is able to identify letters regardless of the whether they are upper case, lower case, or a different font. In the studied patient, Dr. Fischer-Baum’s team observed contralesional reorganization. Compromised regions of the left hemisphere that contained orthography-processing regions (regions that process the set of conventions for writing a language) were organized into homologous regions in the right hemisphere. Through the use of fMRI, the research team determined that the patient’s residual reading ability was supported by functional take-over, which is when injury-damaged functions are taken over by healthy brain regions. These results were found by scanning the brain of the patient as he read and comparing the data with that of a control group of young healthy adults with normal brain functions.

While Dr. Fischer-Baum has made substantial progress in this project, the research has not been without challenges. The project began in 2013 and took three years to complete, which is a long time for Dr. Fischer-Baum’s field of study. Due to this, none of the co-authors from Rice University know each other despite all working on the project at some point in time with another. Because of the amount of time spent on the project, many of the students rotated in and out while working on various parts; the students never worked on the project at the same time as their peers. In addition, the project’s  interdisciplinary approach required the input of  many collaborators with different abilities. All of the Rice undergraduate students that worked on the project were from different majors although most were from the Cognitive Sciences Department and the Statistics Department. At times, this led to miscommunication between the different students and researchers on the project. Since the students came from different backgrounds, they had different approaches to solving problems. This led to the students at times not being harmonious during many aspects of the project.  

Another major setback occurred in bringing ideas to fruition. “You realize quickly when you begin a project that there are a million different ways to solve the problem that you are researching, and trying to decide which is the right or best way can sometimes be difficult,” Dr. Fischer-Baum said. As a result of this, there have been a lot of false starts, and it has taken a long time in order to get work off the ground. How did Dr. Fischer-Baum get past this problem? “Time, thinking, discussion, and brute force,” he chuckled. “You realize relatively quickly that you need to grind it out and put in effort in order to get the job done.”

Despite these obstacles, Dr. Fischer-Baum has also undertaken other projects in order to keep his mind busy. In one, he works with stroke patients with either reading or writing deficits to understand how written language is broken down in the mind. He studies specific patterns in the patients’ brain activity to investigate how reading and writing ability differ from each other. In another of Dr. Fischer-Baum’s projects he works with Dr. Paul Englebretson of the Linguistics Department in order to research the brain activity of blind people as they read Braille. “There is a lot of work on how the reading system works, but a lot of it is based on the perspective of reading by sight,” Dr. Fischer-Baum acknowledged. “I am very interested to see how the way we read is affected by properties of our visual system. Comparing sight and touch can show how much senses are a factor in reading.”

Ultimately, Dr. Fischer-Baum conducts his research with several goals in mind. The first is to build an approach to cognitive neuroscience that is relevant to the kinds of theories that we have in the other cognitive sciences, especially cognitive psychology. “While it feels like studying the mind and studying the brain are two sides of the same coin and that all of this data should be relevant for understanding how the human mind works, there is still a disconnect between the two disciplines,” Dr. Fischer-Baum remarked. He works on building methods in order to bridge this disconnect.

In addition to these goals for advancing the field of cognitive neuroscience, there are clinical implications as well to Dr. Fischer-Baum’s research. Gaining more insight into brain plasticity following strokes can be used to build better treatment and recovery programs. Although the research requires further development, the similarity between different regions and their adaptations following injury can lead to a better understanding of the behavioral and neural differences in patterns of recovery. Additionally, Dr. Fischer-Baum aims to understand the relationship between spontaneous and treatment-induced recovery and how the patterns of recovery of language differ as a result of the initial brain injury type and location. Through the combined use of cognitive psychology and fMRI data, the brains of different stroke patients can be mapped and the data can be used to create more successful treatment-induced methods of language recovery. By virtue of Dr. Fischer-Baum’s research, not only can cognitive neuroscience be applied to many other disciplines, but it can also significantly improve the lives of millions of people around the world.  

Haptics: Touching Lives

Catalyst Volume 10

Everyday you use a device that has haptic feedback: your phone. Every little buzz for notifications, key presses, and failed unlocks are all examples of haptic feedback. Haptics is essentially tactile feedback, a form of physical feedback that uses vibrations. It is a field undergoing massive development and applications of haptic technology are expanding rapidly. Some of the up-and-coming uses for haptics include navigational cues while driving, video games, virtual reality, robotics, and, as in Dr. O’Malley’s case, in the medical field with prostheses and medical training tools.

Dr. Marcia O’Malley has been involved in the biomedical field ever since working in an artificial knee implant research lab as an undergraduate at Purdue University. While in graduate school at Vanderbilt University, she worked in a lab focused on human-robot interfaces where she spent her time designing haptic feedback devices. Dr. O’Malley currently runs the Mechatronics and Haptic Interfaces (MAHI) Lab at Rice University, and she was recently awarded a million dollar National Robotics Initiative grant for one of her projects. The MAHI Lab “focuses on the design, manufacture, and evaluation of mechatronic or robotic systems to model, rehabilitate, enhance or augment the human sensorimotor control system.”¹ Her current research is focused on prosthetics and rehabilitation with an effort to include haptic feedback. She is currently working on the MAHI EXO- II. “It’s a force feedback exoskeleton, so it can provide forces, it can move your limb, or it can work with you,” she said. The primary project involving this exoskeleton is focused on “using electrical activity from the brain captured with EEG… and looking for certain patterns of activation of different areas of the brain as a trigger to move the robot.” In other words, Dr. O’Malley is attempting to enable exoskeleton users to control the device through brain activity.

Dr. O’Malley is also conducting another project, utilizing the National Robotics Initiative grant, to develop a haptic cueing system to aid medical students training for endovascular surgeries. The idea for this haptic cueing system came from two different sources. The first part was her prior research which consisted of working with joysticks. She worked on a project that involved using a joystick, incorporated with force feedback, to swing a ball to hit targets.² As a result of this research, Dr. O’Malley found that “we could measure people’s performance, we could measure how they used the joystick, how they manipulated the ball, and just from different measures about the characteristics of the ball movement, we could determine whether you were an expert or a novice at the task… If we use quantitative measures that tell us about the quality of how they’re controlling the tools, those same measures correlate with the experience they have.” After talking to some surgeons, Dr. O’Malley found that these techniques of measuring movement could work well for training surgeons.

The second impetus for this research came from an annual conference about haptics and force feedback. At the conference she noticed that more and more people were moving towards wearable haptics, such as the Fitbit, which vibrates on your wrist. She also saw that everyone was using these vibrational cues to give directional information. However, “nobody was really using it as a feedback channel about performance,” she said. These realizations led to the idea of the vibrotactile feedback system.

Although the project is still in its infancy, the current anticipated product is a virtual reality simulator which will track the movements of the tool. According to Dr. O’Malley, the technology would provide feedback through a single vibrotactile disk worn on the upper limb. The disk would use a voice coil actuator that moves perpendicular to the wearer’s skin. Dr. O’Malley is currently working with Rice psychologist Dr. Michael Byrne to determine which frequency and amplitude to use for the actuator, as well as the timing of the feedback to avoid interrupting or distracting the user.

Ultimately, this project would measure the medical students’ smoothness and precision while using tools, as well as give feedback to the students regarding their performance. In the future, it could also be used in surgeries during which a doctor operates a robot and receives force feedback through similar haptics. During current endovascular surgery, a surgeon uses screens that project a 2D image of the tools in the patient. Incorporating 3D views would need further FDA approval and could distract and confuse surgeons given the number of screens they would have to monitor. This project would offer surgeons a simpler way to operate. From exoskeletons to medical training, there is a huge potential for haptic technologies. Dr. O’Malley is making this potential a reality.

References

1. Mechatronics and Haptic Interfaces Lab Home Page. http://mahilab.rice.edu (accessed   Nov. 7, 2016).
2. O’Malley, M. K. et al. J. Dyn. Sys., Meas., Control. 2005, 128 (1), 75-85.