Personalized Healthcare: The New Era

Catalyst Volume 7

In medicine, the advent of personalized healthcare is showing that “one size” does not necessarily “fit all.” Specifically, personalized healthcare implies an ability to use an individual’s genetic characteristics to diagnose his or her condition with more precision and finesse. With this development, physicians can select treatments that have increased chances of success and minimal possibilities of adverse reactions. However, personalized medicine does not just imply better diagnostics and therapeutics: it also underlies an ability to better predict any given individual’s susceptibility to a particular disease. Thus, it can be used to devise a comprehensive plan to avoid the disease or reduce its extent.¹ The advent of personalization in healthcare has brought a preventative aspect to a field that has traditionally employed a reactive approach,² where patients are generally treated and diagnosed after symptoms appear.

Medicine has always been personalized: treatment is tailored to individuals following examination. However, the new movement to personalize medicine takes this individualization to the next level. The initial genome sequence was reported by the International Human Genome Sequencing Consortium in 2001; now, scientists can determine information about human physiology and evolution to a detail never before possible, creating a genetics-based foundation for biomedical research.³ Genes can help determine an individual’s health, and scientists can better identify and analyze the causes of disease based on genetic polymorphisms, or variations. This scientific advancement is an integral factor in the personalized healthcare revolution. Technological developments that allow the sequencing of the human genome on a real time scale at relatively low costs have also helped to move this new era of medicine forward.²

The science behind such personalized treatment plans and prediction capabilities follows simple logic: scientists can create a guide by identifying and characterizing genomic signatures associated with particular responses to chemotherapy drugs, such as sensitivity or resistance. They can then use the aforementioned patterns to understand the molecular mechanisms that create such responses and categorize genes based on these pathways and mutations.⁴ Therefore, physicians can compare the genetic makeup of patients’ tumors to these libraries of information. This genetic profiling matches patients with successfully-treated individuals who have similar polymorphisms to provide effective treatment that increases the accuracy of predictions, minimizes allergic reactions, and reduces unnecessary follow-up treatments. For example, efforts are underway to create individualized cancer therapy based on molecular analysis of patients. Traditionally, prediction of cancer recurrence is based on empirical lessons learned from past cases to treat current patients, looking specifically at metrics such as tumor size, lymph node status, response to systemic treatment, and remission intervals.⁴ While this type of prediction has merit, it only provides generalized estimates of recurrence and survival for patients; those with no risk of cancer relapse are often put through potentially toxic chemotherapy. With the new age of personalized medicine, powerful analytical methods, such as protein profiles and dysfunctional molecular pathways, will allow physicians to predict the behavior of a patient’s tumors on a whole new level. Personalized oncologic treatment can plot the clinical course for each patient with a particular disease based on his or her own conditions rather than generalizations from a heterogeneous sample of past cases. This type of healthcare thus improves upon current medicine by creating a subset of homogeneous groups within past cases, allowing physicians to make a more accurate prediction of an individual’s response to treatment.

Additionally, personalized medicine can prevent medical maladies such as adverse drug reactions, which lead to more than two million hospitalizations and 100,000 deaths per year in the U.S. alone.⁵ It can also lead to safer dosing and more focused drug testing. However, this approach is hindered by the nascent nature of genomics technology and the difficulty in identifying all possible genetic variations. Particularly challenging are cases where certain drug reactions result from multiple genes working in conjunction.⁶ Furthermore, opponents of gene sequencing argue that harnessing too much predictive information could be frightening for the patient. For example, patients shown to possess a genetic predisposition towards a degenerative disease such as Alzheimer’s could experience serious psychological effects and depression due to a sense of fatalism; this knowledge could adversely impact their motivation to reduce risks. This possibility has been demonstrated in clinical studies regarding genetic testing for familial hypercholesterolaemia, which measures predisposition to heart disease.⁷ This dilemma leads back to a fundamental question of gene sequencing—how much do we really want to know about our genetic nature?

As of today, personalized medicine is starting to make its mark through some commonly available tests such as the dihydropyrimidine dehydrogenase test, which can predict if a patient will have severe, sometimes fatal, reactions to 5-fluorouracil, a common chemotherapy medicine.⁸ Better known are the genetic tests for BRCA1 and BRCA2 mutations that reveal an increased risk of breast cancer,⁹ popularized by actress Angelina Jolie’s preventative double mastectomy. With these and other such genetics-based tests, the era of personalized medicine has begun, and only time can reveal what will come next.

References

1. Center for Personalized Genetic Medicine. http://pcpgm.partners.org/about-us/PM (accessed Oct 24, 2013).
2. Galas, D. J.; Hood L. IBC. 2009, 1, 1-4.
3. Venter, J. C. et al. Science 2001, 291, 1304-1351.
4. Mansour, J. C.; Schwarz, R. E. J. Am. Coll. Surgeons 2008, 207, 250-258.
5. Shastry, B. S. Nature 2006, 6, 16-21.
6. CNN Health. http://www-cgi.cnn.com/HEALTH/library/CA/00078.html (accessed Oct 24, 2013).
7. Senior, V. et al. Soc. Sci. Med. 1999, 48, 1857-1860.
8. Salonga, D. et al. Clin. Cancer Res. 2006, 6, 1322.
9. National Cancer Institute Fact Sheet. http://www.cancer.gov/cancertopics/factsheet/Risk/BRCA (accessed Oct 24, 2013).

The Hyperloop: A Push for the Alternative is Real

Catalyst Volume 7

The drive down CA I-5 from San Francisco to L.A. takes six hours. That’s six grueling hours of negotiating the horrors of urban traffic, trying to stay awake over vast stretches of monotonous Central California farmland, and watching your gas tank guzzle your hard-earned dollars. A plane ride? A nonstop flight would take only an hour and a half, but that’s without considering the time it takes to pass through security or the price of checking in any luggage. In an age where a thought can be sent half-way around the world in mere seconds, this commute is one emphatic no-no to the time-strapped millennial American. Imagine an alternative. What if there was a way to travel this same distance in just half an hour—and for only twenty dollars a ride?

Say hello to the hyperloop.

The summer of 2013, entrepreneur Elon Musk suggested an alternative method of travel: the “Hyperloop,” a proposed form of high-speed transportation with the potential to travel up to 760 mph.¹ To put things into perspective, Japanese maglev (magnetic levitation) trains have maxed out at 361 mph, and the commercial Boeing 747 plane travels at an average of 570 mph.² The speed of sound is 767 mph. On top of it all, while the California High-Speed Rail Project is currently asking for over $68 billion dollars, Elon Musk estimates that constructing the Hyperloop would only cost $6 billion.

Subsonic speeds at one-tenth of the California High-Speed Rail Project—this audacious claim is not a first for Elon Musk, the man behind the Hyperloop. Take a look at his distinctive accomplishments as CEO and founder of the companies PayPal, Space X, and Tesla: today, the online payment service PayPal is ubiquitous; Space X is in the works of delivering its third interstellar manned vehicle prototype; and Tesla’s electric car stocks trade at over $170 a share. Clearly, Elon Musk has been the impetus behind phenomenal and successful ideas. Still, his history of successful ideas does not guarantee that the Hyperloop would be a successful project. Furthermore, Elon Musk has publicly announced that he will not be tackling the Hyperloop. However, he has released a 57 page report detailing his ideas, which are freely available for anyone to view online. Based on this information, let’s take a look at how this project might be able to work.

A brief technical breakdown

If the Hyperloop sounds like something straight out of science fiction, you wouldn’t be far from the truth. Science fiction authors have written about something that sounds very much like the Hyperloop since the 1900s. In addition to its basic design, the proposed technology for the Hyperloop has also been around for many years.

The technology behind the Hyperloop is the implementation of pneumatic action, which relies on the compression of air to induce movement. Starting in the mid-to-late 19th century, numerous major cities in the U.S. and other countries relied heavily on massive underground networks of pneumatic tubes to send mail. Although this technology has been replaced by email, pneumatic action is still at work in post offices and hospitals today. Pneumatic action is also integral to air hockey tables, which utilizes air to reduce friction. In fact, Elon Musk described the Hyperloop as a cross between a railgun, a Concorde, and an air hockey table.¹

More precisely put, the Hyperloop is a closed-tube transportation system that provides uninterrupted traffic in both directions, perhaps akin to the energy-efficient, tiny maglev pods inside of elevated tubes. This project differs from existing infrastructure developments in three predominant ways by combining a partially evacuated tube with pressure-regulating pods on elevated concrete pylons.¹ Though these features are not new, the combination of these attributes is indeed novel.

To carry passengers inside the tubes, two different distinct pod systems have been proposed: The first is an all-passenger version carrying 28 seats. The second, larger system would carry three automobiles and their passengers. No matter which system is utilized, each pod would have pressurized cabins containing backup air supply and oxygen masks in case of emergency, much like an airplane.¹

The pods would travel very fast—up to sub-sonic speeds—due to a nearly frictionless journey.¹ The steel tubes play an important role by containing a partial vacuum, one ideally one-sixth of the air pressure on Mars. Rather than relying solely on electromagnetism for the entirety of the trip, friction would also be greatly reduced thanks to electric compressor fans attached to the traveling pods.

The electric compressor fans can help overcome the Kantrowitz Limit, a limitation on mass flow related to the size ratio between pod and tube. If the space between a pod and the interior of the tube is too small, then the Hyperloop system will behave like a syringe, where the pod will push the entire column of air in the tube. The compressor fans address this problem by pushing high pressure air from the front to the rear to create a cushion of air underneath the pod.¹

To lower energy costs on the environment, the bulk of the system would be powered by a solar generator. This solar energy would be split between charging the pod batteries and the rest of the system. Musk’s plan would rev up the pods from their stations using magnetic linear accelerators resembling railguns;¹ once in the main travel tubes, the pods would be given periodic boosts by external linear electric motors similar to those in the Tesla Model S.

Finally, in order to lower the cost of construction, the partially-evacuated tubes would be elevated on concrete pylons. This type of system mitigates damage caused by earthquakes and reduces maintenance costs.¹ Additionally, elevation would allow the Hyperloop to travel without interruption, bypassing ground traffic, farmland, and wildlife. By building on pylons, the system could also follow the California I-5 highway, reducing the need for expensive land acquisition suits.

Again, these suggested attributes for the Hyperloop already exist in one form or another, but they have not yet been combined in such a manner. For instance, much of the Federal Highway System uses concrete pylons to elevate interwoven freeways. The subways of New York City and Chicago are enclosed systems, but they do not run on cushions of airs. Maglevs run on a cushion of air, but they are not enclosed.

So what does this mean?

All in all, the scientific community generally seems to agree that the Hyperloop is technically feasible. However, Elon Musk’s proposal does come with many caveats. The most significant problems seem to stem from economic and political concerns. Critics have claimed that Elon Musk’s idea is overtly conceptual and utilizes unrealistic cost estimations. The estimations are particularly contentious because the Hyperloop proposal is reminiscent of the California High-Speed Rail, a project with initial estimates that were much lower than the current budget; in 2008, state voters had approved $9.91 billion dollars for the California High-Speed Rail Project. By April 2012, High-Speed Rail estimates had reached $91.4 billion, nearly ten times original estimates, before public outcry triggered a budget revision.

However, the Hyperloop manages to avert many of the same issues plaguing the California rail project. One benefit of building on concrete pylons is a reduction in land acquisition, currently the most expensive and politically contentious issue affecting transportation projects. Another benefit of the project is an independence from federal funding. Without a reliance on bond measures or public coffers, the Hyperloop would not need to build in potentially unprofitable areas to keep policymakers satisfied. Free from political strings, it could focus on creating a profitable, sustainable venture.

Regardless of the advantages, it seems unlikely that construction on the Hyperloop following the proposed route between San Francisco and Los Angeles would begin during the construction of the California High-Speed Rail. This is unfortunate, as a route between L.A. and San Francisco guarantees a customer base. Furthermore, city pairs that are 120 to 900 miles apart are ideal for rail or similar transportation, as this distance is too far to comfortably travel by car and yet too close to efficiently travel by plane.⁷ L.A. and San Francisco fit perfectly in that niche.

Elon Musk has not made any plans to develop the Hyperloop, causing many to believe that the entrepreneur may be using the Hyperloop as an elaborate red herring. One critic has pointed out that the construction of the California High-Speed Rail would directly compete with automobiles in Silicon Valley, one of Tesla’s target market demographics. Could Musk trying to derail the already tenuous rail initiative in order to reduce economic competition? Interestingly, after the official Hyperloop press release, local politicians in the Silicon Valley area lobbied to prevent the California High-Speed Rail from developing in their respective constituent zones. Was this mere coincidence?

Regardless, the most valuable attribute of the Hyperloop project is its status as an open-source engineering project open to privatization. Using the same basic principles, one man has even built a working miniature prototype with the capacity to hover on a cushion of air. Autodesk, a 3D design software, has produced realistic, promotional renderings of the Hyperloop. ET3 is a company that is working on similar evacuated vacuum tube designs.³ In this day and age, crowdfunding platforms like Kickstarter and microfunding organizations like Kiva could potentially be used to financially support the construction of the Hyperloop. In the Netherlands, the company Windcentrale raised over 1.3 million Euros in only thirteen hours from 1700 Dutch households eager for a local wind turbine.⁵ Money for the Hyperloop could be similarly raised.

Whatever the case, one thing is clear: even if the Hyperloop remains a conceptual project, the idea has opened up an important dialogue regarding the future of mass transportation in America. It has bought attention to the inefficiencies of the California High-Speed Rail Project, and it has renewed interest in technological advances for public transportation. The Hyperloop might also lead the U.S. towards privatized or crowdfunded infrastructure. Perhaps most importantly, the buzz around the Hyperloop has reaffirmed the need for alternative transportation.

References

1. Musk, Elon. Hyperloop Alpha. https://www.teslamotors.com/sites/default/files/blog_images/hyperloop-alpha.pdf (accessed Oct 20, 2013).
2. 747 Family. http://www.boeing.com/boeing/commercial/747family/background.page (accessed Nov 4, 2013).
3. “The Evacuated Tube Transport Technology Network.” ET3, 24 Oct. 2013. <http://et3.net/>.
4. United States Bureau. The California Energy Commission. California Gasoline Statistics & Data. Energy Almanac. Web. 30 Oct. 2013. <http://energyalmanac.ca.gov/gasoline/>
5. “Dutch Wind Turbine Purchase Sets World Crowdfunding Record.” Renewable Energy World. Ed. Tildy Bayar. 24 Sept. 2013. Web. <http://www.renewableenergyworld.com/rea/news/article/2013/09/dutch-wind-turbine-purchase-sets-world-crowdfunding-record>.
6. “2012 Annual Urban Mobility Report.” Urban Mobility Information. Texas A&M Transportation Institute. Web. 11 Oct. 2013. <http://mobility.tamu.edu/ums/>.
7. “Competitive Interaction Between Airports, Airlines, and High Speed Rail.” Joint Transport Research Centre. Paris. Discussion Papers.7 (2009): 20. 8 Dec. 2013.
8. Central Intelligence Agency. The World Factbook. n.d. Web. 18 Nov. 2013. <https://www.cia.gov/library/publications/the­world­factbook/>.
9. Levinson, David. “Density and Dispersion: the Co­development of Land use and Rail.” London Journal of Economic Geography, 8 (1), 55­77. 10.1093/jeg/lbm038. 2007.

Electronic Foil: Blurring the Interface Between Computers and Bodies

Catalyst Volume 7

What if computer technology was to integrate within our bodies? Think of all the possibilities. We could install built-in health monitoring systems as well as technological communication devices. These seemingly far-off advances are exactly what material scientists are currently trying to accomplish.

In a landmark development, researchers have successfully designed electronic interfaces that can be fully implemented into the human body. Dubbed "electronic foils," this invention allows circuits to conform to any surface, giving them the unique ability to adapt to a moving body part. These electronics—which can be stretched, bent, and crumpled—may someday become as common as plastic wrap.¹ Wearable technologies have potential applications ranging from medical diagnostics and wound healing to video game control. Electronic skin has been shown to monitor patients' health measurements as effectively as conventional, state-of-the-art electrodes that require bulky pads, straps, and irritating adhesive gels.²

Traditional electronics are hard and unyielding, typically making them unable to serve in biological applications.¹ However, developments in materials science are transforming the way we think about electronics. Dr. John Rogers, an engineer at the University of Illinois at Urbana-Champaign, studies the characteristics and applications of "soft materials,” or those without physical restraints. Scientists have engineered “transient electronics,” a new class of electronics that can degrade completely after carrying out a designated task. The potential applications of this technology are impressive. For example, Rogers and his team successfully embedded heat-sensitive, transient circuits into surgical wounds of mice to fight infection. These devices were then absorbed into surrounding tissue after a threshold exposure to biological fluids.³

The secret to transient electronics’ disappearing act lies in their material composition. The circuits implanted in the mice were crafted from sheets of porous silicon and magnesium electrodes packaged in enzymatically-degradable silk. Its solubility in water is programmable thorough the addition of magnesium oxide to create a crystalline structure. By tweaking the framework, researchers can control how quickly the engineered silk dissolves, be it over a matter of seconds or several years.³ Scientists foresee applications in which these devices are placed on a wound or inside the body immediately after surgery, so they can integrate and wirelessly transmit information,¹ such as heart rate, blood pressure, and blood oxygen saturation levels.³

Using Roger’s work, Martin Kaltenbrunner, an engineer at the University of Tokyo, discovered how to further expand the applications of flexible electronics and demonstrated a number of uses for their virtually unbreakable circuits. For example, the researchers built a thin transistor incorporated into a tactile sensor that conforms to uneven surfaces. By placing such a device on the roof of a person's mouth, paralyzed patients could give yes or no answers by touching different spots of the sensor. Touch sensitivity could also help those with artificial limbs to gain feeling. Kaltenbrunner’s team also built a mini temperature sensor that adheres to a person's finger. In the future, this simple sensor could be implemented in an imperceptible adhesive bandage for health monitoring.³

The lines between human and machine are becoming blurred. As frightening as seems, the impact of electronic foils on biomedical devices is a positive one. Health monitoring will become commonplace, and the skin can be used as a signal transductor. With the onset of these human-integrable electronics, the field of biomedicine will be completely revolutionized.

References

1. Kaltenbrunner, M. et al. Nature 2013, 499, 458-463.
2. Kim, D. et al. Science 2011, 333, 838-843.
3. Hwang, S. et al. Science 2012, 337, 1640-1644. 

How to Live Forever

Catalyst Volume 7

Despite common debate over its desirability, immortality has been an object of fascination for humans since the beginnings of recorded history. Why do we die in the first place? Religious and philosophical explanations abound. Evolution also provides important insights, and we are just beginning to understand the detailed molecular underpinnings of aging. With knowledge, of course, comes application. Whether or not you seek immortality, the technology for significant life extension may become available in our lifetimes.¹ Eventually, with these new advances, every year we live will add more than a year to our lifespans; this is the point when we become immortal.

Immortality is a more complex concept than many realize. In the dictionary, it is defined simply as “the ability to live forever.”² What if you lived forever as an extremely old man or woman, physically and mentally weak and handicapped? This is not often the image associated with eternal life. Immortality, then, would be desirable only if it came hand-in-hand with another important concept: eternal youth. Another notion of immortality is embodied by Superman or the mythic Greek hero Achilles: invulnerability. By definition, however, invulnerability is not an essential feature of immortality. The real obstacles to immortality are not freak accidents or acts of violence but aging. Aging causes the loss of both youth and immunity to disease. In fact, no one dies purely from the aging process; death is caused by one of many age-related complications.

Eliminating aging is thus synonymous with achieving immortality. The first step in this direction, of course, is to understand the aging process and how it leads to disease. The best answer to this question has been offered by Cambridge biogerontologist Aubrey de Grey. De Grey argues that aging is the accumulation of damage as a result of the normal, essential biological processes of metabolism.² This damage accumulates over the course of our lifetimes and, once it passes a critical threshold, leads to pathological symptoms. The field of biogerontology mainly focuses on understanding the processes of metabolism in the hopes of preventing accumulation of damage. Geriatrics is a related specialty that focuses on mitigating the symptoms of age-related disease. De Grey points to the enormous complexity of understanding either process and offers an alternative: identifying and directly dealing with the damage.³

What types of damage does this entail? To begin, it is essential to understand that the body is a collection of billions of cells. The health of these cells directly translates to the wellbeing of our bodies. Aging is caused by deterioration of our cells, which typically destroy and recycle substances to prevent accumulation of damage over time. De Grey believes there are seven categories of damage that lead to aging. Two are mutations of DNA, the molecule that stores our genetic information. Two are accumulations of molecules that our cells have lost the ability to destroy. One is an accumulation of crosslinks between our cells, causing our tissues to become constrained and brittle. Another is the loss of irreplaceable cells, such as those in our heart or brain. The final classification is an accumulation of death-resistant cells that cause damage to our bodies. De Grey has proposed Strategies for Engineered Negligible Senescence (SENS) for repairing each source of damage. Some of these strategies, such as stem cell therapy, are theoretical and unproven; others, like gene therapy, are modeled after pharmaceuticals that have already gone through clinical trials. De Grey’s SENS are innovative and radical by the standards of the medical and scientific community, causing many to question their viability.

The first SENS therapies will not be perfect. They will eliminate enough damage to keep us below the threshold of developing age-related diseases for a few extra decades, but they will leave even more stubborn forms of damage behind. A few decades, however, is a long time for modern science. By the time our bodies start to show signs of aging, more effective therapies will be available. This process would continue indefinitely.

The fundamental weakness of SENS is that it is based on keeping an imperfectly understood biological organism functioning long after it was ever designed to be. The alternative is to switch out of our flesh and blood homes and into new territory: electronics. For our bodies, this seems relatively straightforward; while fully functioning humanoid robots are far from perfect, it is not a great leap to assume that they will be as capable, if not far more powerful than human bodies in the future-certainly by the time SENS would begin to wear out. Transferring our minds to an electronic medium offers far more considerable challenges. Amazingly, progress in this direction is already under way. Many scientists believe that the first step is to create a map of the synaptic circuits that connect the neurons in our brain.⁴ Uploading this map into a computer, along with a model of how neurons function, would theoretically recreate our consciousness inside a computer. The process of mapping and simulating has already started with programs such as the Blue Brain Project and Obama’s BRAIN initiative. In particular, the former has already succeeded in modeling an important circuit that occurs repeatedly in the mouse brain.⁵

Transferring our minds to computers would mean that any damage that occurred could be reliably fixed, making us truly immortal. Interestingly, the switch would also fulfill many other ambitions. Our mental processes would be significantly faster. We would be able to upload our minds into an immense information cloud, powerful robots, or interstellar cruise vessels. We would be able to fundamentally alter the architecture of our minds, eliminating archaic evolutionary vestiges (such as our propensity toward violence) and endowing ourselves with perfect memories and vast intelligences. We would be able to store and reload previous versions of ourselves. We would be able to create unlimited copies of ourselves, bringing us as close as possible to invulnerability as we may ever get.⁶

While you may have never seriously considered the idea that you might be able to live forever, theoretically it possible; technologies for radical life extension are currently in development. Whether such advancements reach the market in our lifetimes is in large part dependent on the level of public support for key research. Although the hope of living forever comes with the risk of disappointment, keep in mind that efforts toward achieving immortality will increase, if not your lifespan, that of your children and future generations.

References

1. Kurzweil, R. The singularity is near: when humans transcend biology. Penguin Books: New York, 2006.
2. Oxford Dictionaries. http://www.oxforddictionaries.com/us/definition/american_english/immortality (accessed March 13, 2014).
3. De Grey, A. D. ; Rae, M. Ending aging: the rejuvenation breakthroughs that could reverse human aging in our lifetime. St. Martin’s Griffin: New York, 2008.
4. Morgan, J. L.; Lichtman, J. W.  Nature Methods 2013, 10, 494–500.
5. Requarth, T. http://www.nytimes.com/2013/03/19/science/bringing-a-virtual-brain-to-life.html (accessed March 13, 2014).
6. Hall, J. S. Nanofuture: What’s Next for Nanotechnology. Prometheus Books: New York, 2005.