PRESENTACIÓN DE CARNE DE VACUNO GENERADA EN UN LABORATORIO

The Cow-Free Beef… Well, Almost.

Using Biotechnology to produce real meat protein grown from stem cells from donor animals.

“A vegetarian with a Hummer is actually better for the environment than a meat-eater with a bicycle,” remarked a facetious, yet serious Mark Post at a 2013 TEDx conference in Netherlands, when explaining the impact of conventional animal farming on the environment and the enormous resources it takes to grow a little bit of meat: a lousy “bioconversion rate,” he informs an astute audience. Post is a pioneer in a dynamic application of biotechnology called tissue engineering, which involves building biologically-functional matter like blood vessels, or bone, using adult cells and specific biochemical factors, to potentially replace or improve damaged tissues, largely circumventing the need for the controversial fetal stem cell research to engineer life-saving therapeutics. However, instead of using tissue engineering to grow human organs, Post has chosen to grow a beef burger, an out-of-the-box approach to preparing for the inevitable surge in population and the ensuing rise in demand for meat, expected to double over the next few decades.

The process requires muscle stem cells, precursor cells that are destined to mature only into muscle cells, obtained from a donor cow (or potentially a pig, fish, chicken, turkey, or any other meat one wants to eat) through a simple and innocuous procedure.  Like growing a plant, the cells are given everything they need to survive and multiply into real muscle cells, including nutrients, correct temperature, and anchor points to direct their assembly. What you get after eight weeks of multiple rounds of cell division are strands of muscle fiber that can be assembled into a beef patty, the prototype of which was showcased last year in a widely-covered event in London.

Post admits that several key details need to be worked out. The authentic red color of the meat, which comes from blood and specific protein called myoglobin, has to be induced; the fat in the meat has to be added to give it taste. Moreover, thickness, characteristic of a stake, has to be somehow achieved, without a vasculature to nourish and irrigate the cells in the middle, as is the case in an animal. Yet, Post boldly envisions a future where household pantries will come with packs of a variety of muscle stem cells (perhaps somewhat like a dry yeast pack) that will be cultured and grown into edible authentic meat in a simple kitchen incubator.

And Post isn’t the only one with this vision. The father and son team of Modern Meadow, Gabor Forgacs and Andras Forgacs, are also developing ways to use tissue engineering and 3D bioprinting– systematically layering of cells on a particular matrix to achieve a three-dimensional biological structure– to not only produce animal-free meat but also animal-free leather.

So, in this almost sci-fiish future, we can expect to be able to buy cultured meat as well as cultured leather.  What about cultured milk? An offshoot of biotechnology devoted to reinventing the way we look at food is the production of animal-free milk, spearheaded by a start-up company called Muufri.

Regardless of how long it will take, it seems likely that, as techniques in tissue engineering and 3-D bioprinting improve, achieving authentic cultured animal products at an affordable price is a reasonable prediction of the future. The question is, Would you eat it?

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How Flowers Make Love

Biologist David Haskell holds the magnifying lens to the fascinating lives of forest dwellers in his Pulitzer Prize finalist book The Forest Unseen: A Year’s Watch in Nature

“Biochemical matchmaking” the term used by Haskell says it all. The union is a unique arrangement among two, not one, sperm cells encased within a pollen grain and the “fleshy ovule” burrowed deep in the base of the style. The sperm cells drift passively all the way down to the base and prove their merit by outlasting others.

Once united, one sperm cell embraces the egg to make an embryo, while the other sperm cell finds his mates in two small plant cells that join to give rise to a larger cell with a triplet DNA, one from each participant. Like the yolk of an egg, this plant cell grows and fattens to provide nutrients to the rapidly dividing embryo eager to become a seed.

The plants that are unable to find a mate do not give up so easily either. Many choose “desperate self love” using their own pollen sperm cells to self fertilize their egg if no suitable match lands on their sticky landing pad-the stigma-  sacrificing genetic enrichment for mere survival and an opportunity to try their luck again in the next season of love making.

Unable to travel to their lovers’ nest themselves, these flowers rely on bees, birds and other pollinators to carry their pollen to other flowers. In return they reward these mailmen with nectar. As always there are thieves like ants that want the reward without doing the work.  These bypass the pollen and go right for the sugar.

Like the interwoven lives of the creatures that inhabit the forest, Haskell seamlessly stitches together the tales of interdependence among species with the elegance of a wordsmith and the prowess of a seasoned scientist. The premise of the book is a year’s worth of ecological observations focused on a “singe square meter” of a forest in Tennessee- Haskell’s mandala, Sanskrit for microcosm. What he does beautifully and successfully as a popular science writer is tie everything he sees back to the scientific explanations behind the phenomenon, inspiring a deep appreciation for other species and nature in general.

The reading offers an animated experience with Haskell spotting a member of the forest- xylem, moth, Chickadee birds, or simply a snow flake- and zooming into its colossal inner world, revealing how beautifully complex and complete its life is. You read the book and realize a moth is not just a moth, a flower not just a flower, a snail not just a snail, but each a functioning organ supporting the intricate anatomy of the forest, keeping it alive in inclement weather, drought, and other hardships.

All the questions you asked as a kid: how does a snowflake get its shape; Why are there rings on a tree trunk, some diffuse, some distinct; what’s moss- get answered in an experiential and fascinating narrative. A must read for nature lovers!

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Relishing Southern Biodiversity

My trip to South Carolina was full of the expected- great food, beaches, vintage houses, horse carriage rides, as well as some of the unexpected- an opportunity to explore the biodiversity unique to this region.

The most prominent and distinct element is of course the Spanish moss, a fascinating flowering plant that extracts moisture not from soil, but from the air using its aerial roots- an adaptation that frees it up to explore unconventional habitats, such as branches of tall trees, maximizing sun exposure, without spending the energy it takes to grow as tall as the tree.  This quality of Spanish moss, scientifically known as Tillandsia usneoides, to use aerial roots classifies it as an epiphyte- plants that can be thought of as renters, relying on other trees to grow on, without causing any major harm to their host. Other commonly known epiphytes include orchids and moss.  I witnessed Spanish Moss for the first time and found them breath-taking. Bundles of curls decorated large oak trees, hanging like chandeliers from a massive ceiling. At night, these ornaments look rather eerie; boosting the economy of the state’s many ghost tours.

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Another opportunity to relish southern biodiversity came from touring the Audubon Swamp Garden of the magnolia plantation. Originally a rice plantation, first established in 1679, the Magnolia plantation was set on hundreds of acres of land on the banks of the Ashley River. The abandoned paddies now serve as habitat for myriad species of animals, birds, and trees. Some highlights included:

Duckweed, of the family Lemonideae, is a small flowering plant that floats on the surface of swampy water, forming a discontinuous green sheet on the surface. Aerenchymas, tiny, air-filled cavities in the plant, serve as the plants’ floatation device. Lacking the usual plant anatomy, i.e., stem or leaves, Duckweed are essentially little spheres that reproduce rapidly by budding, the process by which a new cell is formed as an outgrowth or bud from an existing cell. These plants provide essential nutritional support to other species living in the swamps, including birds and fish. By blocking sunlight and consuming excess nutrients, they also prevent the formation of destructive algal blooms that can be harmful to other inhabitants of the water. Interestingly, the algae also form a green film on the surface of water, so distinguishing duckweed from algae isn’t easy.

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Also growing in the swampy waters were towering bald Cypress trees, scientifically known as Taxodium distichum, especially adapted to thrive in swampy environments. Accompanying their trunks were several curious little woody stumps called Cypress knees – above-surface projections from the roots of the trees that do not grow into large trees. Although many theories abound, including stability and enhanced oxygen exchange, the exact function and utility of these knees remains unknown. Another notable water- resistant tree at the Swamp was the Tupelo gum tree, also known for its height, growing as much as 90 feet, and living up to 1000 years.

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Our good fortune allowed for many sunny and warm days during our December trip, which meant that several hibernating animals made appearances to soak up the sun, a behavior that proved deadly for one snake that went by the weather, and not by the calendar, succumbing to imminent colder temperatures of the night. Other than the dead snake, we saw a couple of alligators and turtles in the swamp.

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Flowering plants at the swamp included Camellia japonicum, also known as rose of winter, native to China, Japan, and Korea. They were brought to the US in the 1800s with the intended use as greenhouse plants. In the 19th century, however, the Magnolia plantation became the first site that used these flowers as outdoor plants. As a result, even today, the swamp is peppered with these beautiful flowers that blossom between January to March. Interestingly, azaleas were first introduced to America also at the Magnolia plantation. We didn’t see any flowers since unlike Japonicum, azaleas bloom in late March- early April.

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Other natural treasures outside the plantation, included long stretches of savannah, grasslands with trees spaced sufficiently apart to permit sunlight to reach the ground, allowing shorter, grassy species to thrive, and the Angel Oak tree, a colossal 20 meters tall Oak aged 400- 1400 years, definitely a must see wonder!

Study Reveals Low EMR Adoption Rates despite the HITECH Act

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In an effort to streamline patient data acquisition and management and decrease healthcare costs, the US congress passed the 2009 Health Information Technology for Economic and Clinical Health (HITECH) Act- a subsidy program that provides up to $27 billion to motivate hospitals to adopt the Electronic Medical Records (EMR) system. However, results from a recent study indicate that the incentive program may be only marginally successful in its goal of integrating EMR in hospitals. The study was conducted by David Dravone and colleagues at the Kellogg School of Management and published by the National Bureau of Economic Research.

What is EMR?

EMR is an electronic (as opposed to paper-based) repository of patient or population data that promises to transform the healthcare industry by decreasing costs, reducing errors, increasing data quality, and facilitating data storage and management. EMRs can be categorized as either basic or advanced (also see Box 1). Basic EMR includes applications such as Clinical Decision Support and Clinical Data Repository that are easy to implement and have been widely adopted even before the advent of the HITECH act. Advanced EMRs such as Physician Documentation and Computerized Physician Order Entry are more expensive and complicated. Adopting advanced EMRs can cost hospitals $10 million or more, depending on the hospital size and complexity of the applications. Thus, it is of no surprise that hospitals have been reluctant in integrating advanced EMRs with their system.

The HITECH Act

The 2009 subsidiary act has allocated Medicare and Medicaid payments of up to $27 billion for clinicians and hospitals that use EMRs in their daily practices. To qualify, providers should own an EMR system and demonstrate an integral use in patient data collection and storage.

The Study

In their study, the researchers sought to determine the extent to which the HITECH incentive program increased EMR adoption. To do so, a baseline was determined with EMR adoption rates from 2006- 2008. Compared to baseline, the team found that adoption rate increased from 48% in 2008 to 77% in 2011. Using statistical analyses, the team also determined that without the HITECH incentives, the adoption rate for 2011 would have been 67% and 77% by 2013. Thus, the authors concluded that only 10% of hospitals adopted the EMR system as a result of the HITECH act.[i]

The Good News

The study findings prognosticate a general upward trend in hospital adoption of EMR, given that only 10% of the total adoption rate in 2011 was attributed to the HITECH incentive program. Interestingly, according to a 2013 CDC report, 69% of office-based physicians surveyed intended to apply to the HITECH program to incorporate EMR in their practices, indicating a generally positive buzz about the program among providers.[ii] Nevertheless, the news is good for patients, given the fact that quality of care is indeed better in hospitals using EMR.[iii]

BOX 1: Types of EMR[iv]

  1. Physician- Hosted System: An EMR system where the data is stored in the provider’s own server. The provider holds the responsibility of purchasing all relevant hardware and software and storing, securing, and maintaining the data.

2: Remotely-Hosted system: An EMR system where the data is stored with an independent vendor’s servers. The independent vendor holds the responsibility of maintaining and storing the data. The vendor also controls the data.

[i] Dravone et al. Investment Subsidies and the Adoption of Electronic Medical Records in Hospitals. NBER Working Paper Series. 20553: Oct 2014

[ii] Hsiao CJ and Hing E. Use and characteristics of electronic health records systems among office-based physician practices: United States 2001-2013. NCHS Data Brief. 2013

[iii] Cebul, Randall D.; Love, Thomas E.; Jain, Anil K.; Hebert, Christopher J. (2011). “Electronic Health Records and Quality of Diabetes Care”. New England Journal of Medicine 365 (9): 825–33

[iv] Neal D. Choosing an Electronic Health Records System. Innovations in clinical neuroscience 8:6 2011 Jun pg 43-45

Exploring muscular disease in humans and cattle

Originally published in ASBMB Today

Insights into treatment of Brody disease through inhibition of the ubiquitin-proteasome system

A recent study in the Journal of Biological Chemistry about a muscular disease in cattle may offer clues about how to treat a similar disease found in humans.

Both the Chianina cattle muscular disease pseudomyotonia and the human Brody disease are characterized by an inability of skeletal muscles to relax after strenuous physical exercise, leading to temporary muscle stiffness. The cause is a mutation in the ATP2A1 gene encoding a protein called SERCA1, which is crucial for pumping calcium from the cytosol back to the lumen of sarcoplasmic reticulum, thus enabling muscle relaxation. Because of such phenotypic and genetic overlap, Chianina pseudomyotonia is studied as a model for Brody disease.

Interestingly, the mutated SERCA1 protein retains its basic calcium-dependent ATPase activity like the normal protein, suggesting that the mutation does not affect its function. What is affected, however, is the amount of the mutant protein in skeletal muscles, which is much lower in comparison to normal protein levels. This is despite normal mRNA levels of the ATP2A1 gene. These key observations prompted Roberta Sacchetto and Dorianna Sandona at the University of Padova in Italy to join forces and investigate the potential roles of the ubiquitin-proteasome system in degrading the mutant proteins.

The team blocked the ubiquitin-proteasome system with different chemical inhibitors and measured the effect on the levels of mutant SERCA1 in a cellular model. Disrupting the pathway dramatically rescued the expression levels and membrane localization of SERCA1 as determined by Western blot analysis and immunofluorescence analyses.

To corroborate further the role of the ubiquitin-proteasome system in degradation of the mutant SERCA1, the team measured polyubiquitination of the mutant against that of the normal protein. Their rationale was that since the chemical inhibitor used to disrupt the ubiquitin-proteasome system pathway works downstream of the ubiquitination step, it would not affect the accumulation of polyubiquitaned forms of mutant SERCA1 protein. Results from immunoprecipitation assays confirmed the scientists’ hypothesis, and, indeed, there was an increase in the polyubiquitinated mutant SERCA1.

The researchers demonstrated that the pharmacologically rescued SERCA1 was able to restore cytoplasmic calcium homeostasis in a cellular model and was also fully active in muscle fibers isolated from a PMT-affected cow.

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A Chianina cow and calf in a field in Tuscany. Images courtesty of Steven Walling, a wikimedia commons user

The significance of the study is that it demonstrates for the first time the role of the ubiquitin-proteasome system in degrading the mutant SERCA1 protein, explaining the symptoms associated with Chianina cattle pseudomyotonia and some forms of Brody disease. The findings also suggest specific inhibition of the ubiquitin-proteasome system could be a sound therapeutic strategy against the two diseases.

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Gamification of Science: Making Science Fun

The Video Gamers United recently convened in Washington DC. As I glanced at its imposing, back-lit poster decking the otherwise drab walls of the metro station on my way to work, I started thinking about science-based video games and their impact on science education. It turns out, science-based video gaming is a flourishing field, with numerous games being developed for the purposes of edutainment and advancement of science: EteRNA, FoldIt, Genomics Digital Lab, History of Biology game, Phylo, and Nanomission to name a few. These video games are designed to solve complex scientific problems, develop interest in the area, and serve as a tool for learning. The question is: Do they work?

Several science games take advantage of citizen science by crowdsourcing complex scientific challenges sometimes too hairy for even advanced computer programs. The idea is that many minds together can solve a complex problem better than one mind or one machine alone. Stemming from this principle of game with a purpose is EteRNA, a puzzle-based game that enables development of new designs of RNA molecules by the gaming community. Created by researchers at the Carnegie Mellon University and Stanford University in 2010, the game allows players to contribute to a large scale library of RNA designs, helping reveal “new principles for designing RNA-based switches and nanomachines– — new systems for seeking and eventually controlling living cells and disease-causing viruses.” Interestingly, playing the game does not require any training in biology.  EteRNA is considered a successful project, with over 150,000 players engaged in designing novel RNA molecules to be used in real-life research.

Another crowdsourced game Phylo, designed to augment genetic disease research, looks a lot like the classic Tetris at first glance. Players are asked to align blocks of similar colors. Unbeknownst to many players, the blocks represent gene sequences from different species. The better a player does at matching the sequences the more points she accrues.  The computer programs designed for doing this type of multiple sequence alignment do not necessarily produce superior results, often requiring scientists to manually align some sequences to attain the most appropriate alignment. This is where the Phylo players come in. More than 300,000 people have played Phylo since its launch in 2010.

Another big motivation for developing science-based video games is helping players develop an interest in science. The History of Biology is a good example. Designed by Spongelab Interactive, the game follows a scavenger hunt format, where players solve a mystery based on clues illustrating seminal discoveries in the world of scientific research. Spongelab Interactive is a major developer of several other educational games, covering a wide-range of subjects such as chemistry, physics, mathematics, and history.

Many video games are also built as tools for learning. The idea is to use a cultural tool, something that students of a particular culture respond to, aka video games, to enable learning in a familiar and friendly format (see article by Morris et al, 2013). Students learn the process of scientific thinking as well as key concepts in a self-paced environment, where learning is assessed by ability to overcome increasingly difficult levels, and rewarded through a feeling of achievement. NanoMission is an educational game, with the goal to teach players about the up and coming field of nanotechnology. Through multiple modules of the game, players engage in a variety of stimulating activities, such as guiding a nanorobot in killing cancer cells in a patient; or creating improved nanomedicine or nanomachines; or destroying harmful algae.

While video games can help in accomplishing all of the above, an important criterion for judging their potency is assessing the accuracy of the science they represent. Caution must be taken when facts are misrepresented in an attempt to make the game interesting or technically feasible. Reinforcing inaccurate concepts about science can not only be ineffective in generating interest and increasing knowledge, but also detrimental to the overall learning experience of the player (see review of Spore by John Bohannon).

Though gradually gaining popularity, gamified science, so to speak, has yet to become integrated into the vast world of conventional video games. Hinting towards a positive future, however, is the fact that the Washington DC Video Gamers United Convention featured several keynote speakers specializing in serious games, including Christopher Spivey, Sande Chen, and Trey Reyher- an excellent move for science gamification.

One Thousand Self-Organizing Robots Emulate Elements in Nature

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A few months ago, in a desperate attempt to save time in cleaning up after an active toddler, we bought the Roomba iRobot, an automated vacuum cleaner. The awe we felt from watching the Roomba pick up hair and Cheerios under the bed must have been the same awe that man felt after inventing fire. A hands-free, self-guided, self-charging machine doing our dirty work: now that’s technology! As the Roomba did its thing, my husband and I imagined a time when the big Roomba would come with little baby Roombas that would spawn from its base, and reach inaccessible turfs like the corners of the walls, curtains, or window sills, clean-up, and go back to base to charge with mama Roomba.

That time seems quite upon us, with the invention of the thousand self-organizing robots by Harvard researchers, Michael Rubenstein, Alejandro Cornejo, Radhika Nagpal, published today in Science. The behavior of these robots emulates similar elements in nature, such as self-organizing ants and termites that practice meticulous coordination to achieve complex tasks. This adds to the myriad technological advances stemming from a basic understanding of biological life. Self-organization is a behavior seen throughout nature: in bees, ants, birds, and even bacteria. In fact, the bacterium I studied for my doctoral work, Myxococcus xanthus, is a remarkable species, capable of self-organizing via chemical communication with members of its colony to accomplish motility and predation on bacteria of other species. The Kilobots, as the researchers call their army of thousand robots, perceive each other through the transmission and reception of infrared signals from their bases, to independently self-organize into complex shapes from stars to the letter K.

And what could these Kilobots be useful for? A variety of applications come to mind, from cleaning up chemical spills to environmental surveillance for pathogens, to digging for mines, and, most importantly, cleaning up the corners of your house!

The only thing now left to do is to give these Kilobots a cute body. I wonder if Wall-E is available!

New protein may be the Achilles’s Heel of Treatment-Resistant Head and Neck Cancer

The human Head by Leonardo Da Vinci

The human Head by Leonardo Da Vinci

Researchers at the University of Michigan, Ann Arbor believe they have solved the mystery behind why some head and neck cancer cells are refractory to the effects of radiation and chemotherapy and extremely adept at repairing and thriving under such aggressive insults. According to the findings of a new study from the group of Dr. Nisha J D’Silva that appeared in Nature Communications this week, a protein named TRIP-13 is responsible for enabling cancer cells to repair their damaged DNA using a process called error-prone non-homologous end joining. Using recombinant DNA technology, the group also showed that normal cells could be transformed into malignant cancer cells by overexpression of TRIP-13.

Head and neck cancer is one of the most common cancers in the world, and often afflicts users of tobacco and alcohol, as well as people infected with the Human Papillomavirus (HPV). The malignancy often starts in the squamous cells lining the moist surfaces of the head and neck, and can quickly spread through most of the oral cavity. Adding to its severity is the fact that the cancer is notoriously resistant to treatment and comes with a high recurrence rate.

Dr. D’Silva’s research findings offer a plausible explanation for such a high recurrence rate and overall intractability of head and neck cancer. Adding to the hope is the group’s  identification of an existing molecule potent in killing these TRIP-13-expressing cells, offering a direct and potentially speedy treatment option for the near future.

Five Inspirational Non-Fiction Books by Physician-Writers You Won’t Want To Put Down

  1. Becoming Dr. Q: My Journey from Migrant Farm Worker to Brain Surgeon

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In this spellbinding memoir, Dr. Q, short for Alfredo Quinones-Hinojosa, reveals his tumultuous, yet exciting journey, from his impoverished childhood in Mexico, to literally jumping the fence to enter the United States, to farming tomatoes for pennies under the unforgiving California sun, while also taking evening English classes, to graduating from Harvard Medical School, and finally becoming an internationally celebrated neurosurgeon and cancer researcher at the Johns Hopkins University. Dr. Q’s descriptions of his brushes with death are both gripping and uplifting, and his life is the American Dream personified.

  1. The Emperor of All Maladies: A Biography of Cancer

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Dr. Siddhartha Mukherjee elegantly and effortlessly breaks it down for his readers, connecting the present with the past of cancer origins and the evolution of its treatment. Thorough, yet succinct, Dr. Mukherjee’s writing recounts the key events and figures that fundamentally changed the way we look at cancer today. After reading this biography of cancer, you will come out feeling educated and optimistic. A must read for anyone curious about the past, present, and future of this age-old disease.

  1. Mountains Beyond Mountains

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Although not exactly written by a Physician-Writer, the book covers the life of an amazing and inspiring infectious disease specialist, Dr. Paul Famer, who is also a professor of medical anthropology at Harvard and the recipient of the MacArthur Genius Grant. In this biography of Dr. Farmer, author Tracy Kidder takes the reader to Haiti, where Dr. Farmer is literally working day and night to treat patients in a remotely-situated Haitian village. The book highlights Farmer’s unyielding efforts to improve the health of marginalized people, culminating in the founding of Partners in Health, in collaboration with his long time friend, Jim Yong Kim, who recently served as the president of the World Bank. By following Farmer around, Kidder captures how on more than one occasion, Farmer puts his patients’ needs before his own health, money, family, safety and even life. Kidder’s Mountains Beyond Mountains highlights the best humanity has to offer. A great read for anyone looking to feel motivated and inspired.

  1. Gifted Hands

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Is the autobiography of the renowned Dr. Benjamin Carson, the first neurosurgeon in the world to successfully separate conjoined twins. A gripping narration of personal and professional challenges, the autobiography illustrates the victory of hard-work and determination over the many hurdles of poverty and discrimination that Dr. Carson faced as an African American child, growing up in a disadvantaged neighborhood of Detriot, Michigan, or even as a doctor, having his credibility repeatedly questioned by colleagues and patients alike. As a bonus, Dr. Carson skillfully describes several groundbreaking surgeries he pioneered in his fertile career as a neurosurgeon.

  1. When the Air Hits the Brain

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This riveting memoir by Dr. Frank Vertosick Jr. presents some of the most challenging cases of his medical career as a neurosurgeon. Dr. Vertosick consciously chooses to narrate the cases with rather unhappy endings and contends that one learns more from failures than from successes, especially in surgery. The book is often recommended for medical students, but is also relevant to anyone interested in learning how doctors make some very difficult, life or death choices.