Broccoli/Cheddar Stuffed Potato Skins with Avocado Cream Topping


Truly delicious! Pick up and eat out of your hand. Dinner, lunch, brunch, snack, barbecue, any time of day or night ©Joyce Hays, Target Health Inc.




8 small Idaho potatoes, scrubbed and dried

4 teaspoons olive oil

Pinch salt, pinch black pepper (optional), pinch chili flakes

2 garlic cloves, minced

5 cups broccoli florets (2 bunches), coarsely chopped

Olive oil cooking spray

Pieces of artificial bacon (garnish option)

1 cup extra sharp cheddar cheese, grated


Avocado Cream Topping (recipe below)


1 ripe avocado

2 Tablespoons sour cream

1 handful fresh cilantro, chopped well

1 clove fresh garlic, squeezed

Pinch black pepper (optional)




At my market, avocados are very good now. Get them firm, but with a little give, when you squeeze them. ©Joyce Hays, Target Health Inc.


Directions – Bake the Potatoes


1. Preheat oven to 450 degrees to bake the potatoes until done.

2. Pierce potatoes with fork a couple of times and wrap in paper towel.

3. Turn to high and microwave these potatoes for about 15 minutes.

4. Take out and allow to cool down or bake in oven until done.

5. Slice your baked potatoes after they’ve cooled, in half the long way.

6. Then using a spoon, remove the flesh, but leave enough on the skins to support them with the filling. Leave about 1/8“ of skin with flesh.

7. Don’t damage the skin when scraping. You can use the insides of the potatoes for another recipe, like potato pancakes, or just whipped garlic potatoes.




Brushed with olive oil and about to go into the oven ©Joyce Hays, Target Health Inc.


Brush all the potato skins with olive oil, place on baking sheet, skin side down, and bake for about 20-30 minutes, until the skins are crisp with toasty brown edges. Then remove from oven and set aside.




Make the avocado cream sauce. Food processers make cooking so much easier. ©Joyce Hays




While the skins are in the oven, prepare the avocado cream topping and the filling.


To make the avocado cream, get out your food processor and add the avocado, sour cream, cilantro, pinch salt, the juice of one squeezed fresh garlic clove and set it on high, and process until the topping is smooth. This should take no more than one minute or less. With a small spatula, get all of this good topping out of the food processor and into a medium to small serving bowl. Put this on your dining table for people to add themselves.




While the potato skins are in the oven getting crispy, sautee the garlic and add the steamed broccoli with a pinch of salt. Stir for 2-3 minutes. ©Joyce Hays, Target Health Inc.


Next, steam the broccoli florets for about 3 to 4 minutes. Drain and set aside.


Spray a pan with olive oil spray and sautee the minced garlic for 1 or 2 minutes. Then add the broccoli florets and stir the two veggies for about 3 or 4 minutes, over medium high flame. Add a pinch of salt and pepper, if you wish, or omit the salt.


With a spatula get all of the broccoli florets and little pieces of garlic out of the pan and into a large bowl.


Stir in the cup of freshly grated cheese and a few of the artificial bacon bits (they come in a small jar and I bought mine on Amazon). You could also stir in a little of the chopped cilantro.




Here, the skins are baked, then filled with the broccoli/cheese mixture and ready to go back into the oven for about 5 more minutes or until the broccoli gets a bit softer and the cheese melts. ©Joyce Hays, Target Health Inc.


Next, lower oven to 400 degrees or lower, like 350 degrees.


With a tablespoon, fill the potato skins with the broccoli/cheese mixture (divide it evenly). Wait until you’re ready to serve the meal. Then bake the filled skins for 5 minutes, or until you see that the cheese has melted and looks yummy and gooey.


Now, carefully with a tablespoon, add the stuffed potatoes to a serving platter and serve while warm. Sprinkle with some of the bacon bits.





Here’s the avocado cream sauce, ready to serve over the baked broccoli/cheese potatoes. ©Joyce Hays, Target Health Inc.



©Joyce Hays, Target Health Inc.


Topped with the Avocado sauce, this is actually a balanced meal in itself, especially if you double the recipe. Add some chilled white wine (or red) and you’re all set. This recipe is very versatile . . . good with fish, steak, poultry. These stuffed potatoes are great out of doors, because they’re easy to pick up and eat right out of your hand.


Jules returned home after a week out of the country seeing clients and attending a conference. Exhausted after a 12 hour flight, he tried to stay awake, to resume the NY time zone. These stuffed potato skins were perfect and he loved them.


We started with Le Volte a high rated Tuscany blend of merlot and cabernet sauvignon, and one of our favorite salads (lush ripe tomatoes, avocado, green olives, cucumbers, sliced endive, in a simple refreshing dressing of fresh lemon juice, olive oil and 1 minced fresh garlic clove.) Then the warm stuffed broccoli/cheese potatoes with delicious topping, and finally turkey meatballs with pasta. Dessert was cut up fresh mandarin orange segments.


We purposely made no weekend plans. We will sleep and eat and drink and nap all weekend until the jet lag is no more.




We’re drinking a delicious Tuscany blend of merlot and cabernet sauvignon. You can almost smell the Mediterranean and feel the breezes. Leave it to the languishing Italians to create this liquid silk. Tenuta dell’Ornellaia, le Volte IGT, 2011


From Our Table to Yours!


Bon Appetit!


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May 11, 2015

Salk Institute for Biological Studies

A single molecule has been identified that controls the fate of mature sensory neurons, scientists report. By studying sensory neurons in mice, the team found that the malfunction of a single molecule can prompt the neuron to make an “early-career” switch, changing a neuron originally destined to process sound or touch, for example, to instead process vision.



An embryonic mouse forebrain shows the genetically modified neurons in the neocortex (orange/yellow). Cortical stem cells and neurons in other brain regions remain unaltered.
Credit: Courtesy of Andreas Zembrzycki/Salk Institute



Scientists at the Salk Institute have discovered that the role of neurons — which are responsible for specific tasks in the brain — is much more flexible than previously believed.

By studying sensory neurons in mice, the Salk team found that the malfunction of a single molecule can prompt the neuron to make an “early-career” switch, changing a neuron originally destined to process sound or touch, for example, to instead process vision.

The finding, reported May 11, 2015 in PNAS, will help neuroscientists better understand how brain architecture is molecularly encoded and how it can become miswired. It may also point to ways to prevent or treat human disorders (such as autism) that feature substantial brain structure abnormalities.

“We found an unexpected mechanism that provides surprising brain plasticity in maturing sensory neurons,” says the study’s first author, Andreas Zembrzycki, a senior research associate at the Salk Institute.

The mechanism, a transcription factor called Lhx2 that was inactivated in neurons, can be used to switch genes on or off to change the function of a sensory neuron in mice. It has been known that Lhx2 is present in many cell types other than in the brain and is needed by a developing fetus to build body parts. Without Lhx2, animals typically die in utero. However, it was not well known that Lhx2 also affects cells after birth.

“This process happens while the neuron matures and no longer divides. We did not understand before this study that relatively mature neurons could be reprogrammed in this way,” says senior author Dennis O’Leary, Salk professor and holder of the Vincent J. Coates Chair in Molecular Neurobiology. “This finding opens up a new understanding about how brain architecture is established and a potential therapeutic approach to altering that blueprint.”

Scientists had believed that programming neurons was a one-step process. They thought that the stem cells that generate the neurons also programmed their functions once they matured. While this is true, the Salk team found that another step is needed: the Lhx2 transcription factor in mature neurons then ultimately controls the fate of the neuron.

In the mouse study, the scientists manipulated Lhx2 to make the switch in neuronal fate shortly after birth (when the mouse neurons are fully formed and considered mature). The team observed that controlling Lhx2 let them instruct neurons situated in one sensory area to process a different sense, thus enlarging one region at the expense of the other. The scientists don’t know yet if targeting Lhx2 would allow neurons to change their function throughout an organism’s life.

“This study provides proof that the brain is very plastic and that it responds to both genetic and epigenetic influences well after birth,” says O’Leary. “Clinical applications for brain disorders are a long way away, but we now have a new way to think about them.”

“Since this study was conducted in mice, we don’t know the time frame in which Lhx2 would be operating in humans, but we know that post-birth, neurons in a baby’s brain still have not settled into their final position — they are still being wired up. That could take years,” Zembrzycki says.

However, the findings may be an ingredient that contributes to the success of early intervention in some very young children diagnosed with autism, adds Zembrzycki. “The brain’s wiring is determined genetically as well as influenced epigenetically by environmental influences and early intervention preventing brain miswiring may be an example of converging genetic and epigenetic mechanisms that are controlled by Lhx2.”

Story Source:

The above story is based on materials provided by Salk Institute for Biological Studies. Note: Materials may be edited for content and length.

Journal Reference:

  1. Andreas Zembrzycki, Carlos G. Perez-Garcia, Chia-Fang Wang, Shen-Ju Chou, and Dennis D. M. O’leary. Postmitotic regulation of sensory area patterning in the mammalian neocortex by Lhx2. PNAS, 2015 DOI: 10.1073/pnas.1424440112


Source: Salk Institute for Biological Studies. “Brain cells capable of ‘early-career’ switch.” ScienceDaily. ScienceDaily, 11 May 2015. <>.

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May 13, 2015

Woods Hole Oceanographic Institution

River transport of carbon to the ocean is not on a scale that will solve our carbon dioxide problem, but we haven’t known how much carbon the world’s rivers routinely flush into the ocean, until now. Scientists calculated the first direct estimate of how much and in what form organic carbon is exported by rivers. The estimate will help modelers predict how this export may shift as Earth’s climate changes.



Plants convert carbon dioxide from the atmosphere into organic carbon via photosynthesis. Most of this carbon eventually returns to the atmosphere when plant material (or animals that eat plants) decompose. A small fraction of this material, however, ends up in rivers. They carry it out to sea, where some settles to the seafloor and is buried and disconnected from the atmosphere for millions of years and eventually makes its way back to the surface in the form of rocks. At the same time, rivers also erode carbon-containing rocks into particles carried downstream. The process exposes carbon to air, oxidizing the previously locked-up carbon into carbon dioxide that can leak back out to the atmosphere.
Credit: Illustration by Eric Taylor, Woods Hole Oceanographic Institution



Humans concerned about climate change are working to find ways of capturing excess carbon dioxide (CO2) from the atmosphere and sequestering it in the Earth. But Nature has its own methods for the removal and long-term storage of carbon, including the world’s river systems, which transport decaying organic material and eroded rock from land to the ocean.

While river transport of carbon to the ocean is not on a scale that will bail humans out of our CO2 problem, we don’t actually know how much carbon the world’s rivers routinely flush into the ocean — an important piece of the global carbon cycle.

But in a study published May 14 in the journal Nature, scientists from Woods Hole Oceanographic Institution (WHOI) calculated the first direct estimate of how much and in what form organic carbon is exported to the ocean by rivers. The estimate will help modelers predict how the carbon export from global rivers may shift as Earth’s climate changes.

“The world’s rivers act as Earth’s circulatory system, flushing carbon from land to the ocean and helping reduce the amount that returns to the atmosphere in the form of heat-trapping carbon dioxide,” said lead author and geochemist Valier Galy. “Some of that carbon–‘new’ carbon–is from decomposed plant and soil material that is washed into the river and then out to sea. But some of it comes from carbon that has long been stored in the environment in the form of rocks– ‘old’ carbon–that have been eroded by weather and the force of the river.”

The scientists, who included Bernhard Peucker-Ehrenbrink, and Timothy Eglinton (now at ETH Zürich), amassed data on sediments flowing out of 43 river systems all over the world, which cumulatively account for 20 percent of the total sediments discharged by rivers. The representative rivers also encompassed a broad range of climates, vegetation, geological conditions, and levels of disturbance by people.

From these river sediment flow measurements, the research team calculated amounts of particles of carbon-containing plant and rock debris that each river exported. They estimated that the world’s rivers annually transport 200 megatons (200 million tons) of carbon to the ocean. The total equals about .02 percent of the total mass of carbon in the atmosphere. That may not seem like a lot, but over 1000 to 10,000 years, it continues to add up to significant amounts of carbon (20 and 200 percent) extracted from the atmosphere.

Generally, plants convert CO2 from the atmosphere into organic carbon via photosynthesis. But most of this carbon eventually returns to the atmosphere when plant material (or animals that eat plants) decompose. A small fraction of this material, however, ends up in rivers. They carry it out to sea, where some settles to the seafloor and is buried and disconnected from the atmosphere for millions of years and eventually makes its way back to the surface in the form of rocks.

At the same time, rivers also erode carbon-containing rocks into particles carried downstream. The process exposes carbon to air, oxidizing the previously locked-up carbon into carbon dioxide that can leak back out to the atmosphere. Until now, scientists had no way to distinguish how much of the carbon whisked away by rivers comes from either the biospheric or petrogenic (rock) sources. Without this information, scientists’ ability to model or quantitatively predict carbon sequestration under different scenarios was limited.

To solve this dilemma, the scientists found a novel way to distinguish for the first time the sources of that carbon–either from eroded rocks or from decomposed plant and soil material. They analyzed the amounts of carbon-14, a radioactive isotope, in the river particles. Carbon-14 decays away within about 60,000 years, so it is present only in material that came from living things, and not rocks. Subtracting the portion of particles that did not contain carbon-14, the scientists calculated the percentage that was derived from the terrestrial biosphere: about 80 percent.

But even though biospheric carbon is the major source of carbon exported by rivers, the scientists also discovered that rivers surrounded by greater amounts of vegetation didn’t necessarily transport more carbon to the ocean. Instead, the export was “primarily controlled by the capacity of rivers to mobilize and transport” particles. Erosion is the key factor–the more erosion occurs along the river, the more carbon it transfers to sea and sequesters from the air.

“The atmosphere is a small reservoir of carbon compared to rocks, soils, the biosphere, and the ocean,” the scientists wrote in Nature. “As such, its size is sensitive to small imbalances in the exchange with and between these larger reservoirs.”

The new study gives scientists a firmer handle on measuring the important, and heretofore elusive, role of global rivers in the planetary carbon cycle and enhances their ability to predict how riverine carbon export may shift as Earth’s climate changes.

“This study will provide geochemical modelers with new insights on an important link between the global carbon and water cycles,” says Don Rice, program director in the National Science Foundation’s Division of Ocean Sciences, a major funder of the research.

Story Source:

The above story is based on materials provided by Woods Hole Oceanographic Institution. Note: Materials may be edited for content and length.

Journal Reference:

  1. Valier Galy, Bernhard Peucker-Ehrenbrink, Timothy Eglinton. Global carbon export from the terrestrial biosphere controlled by erosion.Nature, 2015; 521 (7551): 204 DOI: 10.1038/nature14400


Source: Woods Hole Oceanographic Institution. “How rivers regulate global carbon cycle.” ScienceDaily. ScienceDaily, 13 May 2015. <>.

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May 12, 2015

Gladstone Institutes

Scientists have discovered a way to regrow bone tissue using the protein signals produced by stem cells. This technology could help treat victims who have experienced major trauma to a limb, like soldiers wounded in combat or casualties of a natural disaster. The new method improves on older therapies by providing a sustainable source for fresh tissue and reducing the risk of tumor formation that can arise with stem cell transplants.



Stem Cell research graphic. Scientists have discovered a way to regrow bone tissue using the protein signals produced by stem cells.
Credit: © kentoh / Fotolia



Scientists have discovered a way to regrow bone tissue using the protein signals produced by stem cells. This technology could help treat victims who have experienced major trauma to a limb, like soldiers wounded in combat or casualties of a natural disaster. The new method improves on older therapies by providing a sustainable source for fresh tissue and reducing the risk of tumor formation that can arise with stem cell transplants.

The new study, published in Scientific Reports, is is the first to extract the necessary bone-producing growth factors from stem cells and to show that these proteins are sufficient to create new bone. The stem cell-based approach was as effective as the current standard treatment in terms of the amount of bone created.

“This proof-of-principle work establishes a novel bone formation therapy that exploits the regenerative potential of stem cells,” says senior author Todd McDevitt, PhD, a senior investigator at the Gladstone Institutes. “With this technique, we can produce new tissue that is completely stem cell-derived and that performs similarly with the gold standard in the field.”

Instead of using stem cells themselves, the scientists extracted the proteins that the cells secrete–such as bone morphogenetic protein (BMP)–in order to harness their regenerative power. To do so, the researchers first treated stem cells with a chemical that helped coax them into early bone cells. Next, they mined the essential factors produced by the cells that send the signal to regenerate new tissue. Finally, the researchers delivered these proteins into mouse muscle tissue to facilitate new bone growth.

The current standard method involves grinding up old bones in order to extract the proteins and growth factors needed to stimulate new bone growth–a substance dubbed demineralized bone matrix (DBM). However, this approach has significant restrictions as it relies on bones taken from cadavers, which can be highly variable in terms of tissue quality and how much of the necessary signals they still produce. Moreover, as is the problem in organ donation, cadaver tissue is not always available.

“These limitations motivate the need for more consistent and reproducible source material for tissue regeneration,” says Dr. McDevitt, who conducted the research while he was a professor at the Georgia Institute of Technology. “As a renewable resource that is both scalable and consistent in manufacturing, pluripotent stem cells are an ideal solution.”

Story Source:

The above story is based on materials provided by Gladstone Institutes.Note: Materials may be edited for content and length.

Journal Reference:

  1. Ken Sutha, Zvi Schwartz, Yun Wang, Sharon Hyzy, Barbara D. Boyan, Todd C. McDevitt. Osteogenic Embryoid Body-Derived Material Induces Bone Formation In Vivo. Scientific Reports, 2015; 5: 9960 DOI: 10.1038/srep09960


Source: Gladstone Institutes. “Scientists regenerate bone tissue using only proteins secreted by stem cells.” ScienceDaily. ScienceDaily, 12 May 2015. <>.

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May 11, 2015

University Corporation for Atmospheric Research

Just as waves ripple across a pond when a tossed stone disturbs the water’s surface, gravity waves ripple toward space from disturbances in the lower atmosphere.



A model simulation illustrates how gravity waves kicked off by a cyclone east of Australia build as they travel toward space. The simulation was created using a high-resolution version of the Whole Atmosphere Community Climate Model (WACCM). Clockwise from upper left corner: Vertical winds at 11, 30, 87, and 100 km above Earth’s surface.
Credit: Image courtesy Hanli Liu, NCAR



Just as waves ripple across a pond when a tossed stone disturbs the water’s surface, gravity waves ripple toward space from disturbances in the lower atmosphere.

Gravity waves are born when air masses are pushed up or down — by a thunderstorm, perhaps, or when wind is forced up and over a mountain range — but in the lower atmosphere, their impacts usually remain regional. By the time they reach the upper atmosphere, however, the waves have built in amplitude and extent. There, they can dominate atmospheric processes on a much larger scale, sometimes threatening the reliability of Earth-based communication systems.

For the first time, scientists have found a way to “watch” the propagation of gravity waves toward space — and the view is captivating. The trick, according to a team of researchers led by NCAR Senior Scientist Hanli Liu, was to push the NCAR-based Whole Atmosphere Community Climate Model to a resolution that is fine enough to pick up gravity waves at their source, when they’re still relatively small.

“We’ve never seen a global picture of gravity waves in the upper atmosphere before, either from observations or simulations, even though we have suspected their importance up there,” said Liu, who studies the upper atmosphere at NCAR’s High Altitude Observatory. “This is the first time we have been able to capture these waves with a computer model of the whole atmosphere.”

The standard version of the model gets only a blurry look at phenomena that take place on scales less than 2,000 km (about 1,243 miles) across — and it’s blind to anything smaller than 200 km. The higher-resolution model has much sharper vision all the way down to 200 km. The intense computing power of the NCAR-Wyoming Supercomputing Center’s Yellowstone system made the higher-resolution runs possible.

In a study published in the journal Geophysical Research Letters, Liu and his colleagues demonstrated the finer-scaled model’s abilities by showing how gravity waves such as those created by a tropical cyclone east of Australia grew as they traveled upwards. The model shows that what starts out as a localized phenomenon extends across the entire Pacific Region at 100 km above Earth’s surface.

“For the middle and lower atmosphere, if you miss the gravity wave, you’re not missing too much,” Liu said. “But it’s a different story in the upper atmosphere.”

Disturbances in the upper atmosphere — which can endanger satellites, skew GPS readings, and shut down radio transmissions — are often thought about as originating from the Sun, where solar storms can kick off geomagnetic storms around Earth. But the ionosphere, the upper reaches of the atmosphere affected by this kind of space weather, is also influenced by disturbances originating on Earth.

These Earth-born disturbances can be difficult for scientists to disentangle when solar storm activity is strong, but the relative tranquility of the Sun during the last solar cycle has given scientists an opportunity to home in on the disturbances reaching the ionosphere from below, creating a fuller picture of processes in the ionosphere.

“When gravity waves propagate to the bottom side of the ionosphere, they can kick off instabilities,” Liu said. “If you want to have a better understanding of space weather — the ionosphere — you need this kind of modeling capability.”


Story Source:

The above story is based on materials provided by University Corporation for Atmospheric Research. The original article was written by Laura Snider.Note: Materials may be edited for content and length.

Journal Reference:

  1. H.-L. Liu, J. M. McInerney, S. Santos, P. H. Lauritzen, M. A. Taylor, N. M. Pedatella. Gravity waves simulated by high-resolution Whole Atmosphere Community Climate Model. Geophysical Research Letters, 2014; 41 (24): 9106 DOI: 10.1002/2014GL062468


Source: University Corporation for Atmospheric Research. “Watch invisible gravity waves rumble through the atmosphere.” ScienceDaily. ScienceDaily, 11 May 2015. <>.

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FDA Pre-Approval Inspection (PAI) of Target Health for eSource Program – May 2015


Several weeks ago, FDA conducted a pre-approval inspection (PAI) at Target Health and at 3 leading oncology medical centers for a de novo 510(K). For this program, Target Health performed the following services: Regulatory Affairs, Clinical Research Management and Monitoring, Data Management, Biostatistics and Medical Writing. We are pleased to announce that for this 2nd inspection of Target Health, the previous inspection occurring in 2008, again NO FORM FDA 483 was issued. There were also NO FORM FDA 483 issues at 2 of the 3 medical centers. The finding at the 3rd center was related to just one procedure at the medical center and outside of the control of Target Health.


What was unique about this study, besides the product itself, was that Target e*CRF® fully integrated with Target e*CTR® (eClinical Trial Record) ® was used for data collection. Upon FDA review, there were no issues related to the eSource documents. For a drug program, an NDA is planned in Q3 2015. For this program there will also be global submissions.


To our friends and colleagues in clinical research and quality assurance, note that FDA focused on confirming that the:


1. Informed consent was provided and managed properly;

2. Protocol was followed;

3. Protocol was properly monitored;

4. The primary endpoint was properly recorded

5. All safety events were properly reported; and

6. Device performed as intended


View from the top of Stone Mountain (Stone Mountain State Park, NC)


Another masterpiece from our friend and colleague, James Farley, Director, Data Management and Programming, TransTech Pharma. Here is what he had to say about the experience. “This was my first time at the park. My wife and I, with our daughter, hiked the full loop! We headed down the direction of the falls first – at the advisement of one of the NC State Park rangers – and then up to the top of the mountain. The composition is on purpose, with the tree above the horizon at the third, with the leading-line of the rock out to the rocky surface of the facing peak, which is also set at the third.


View from the top of Stone Mountain (Stone Mountain State Park, NC) – ©JFarly Photography 2015


ON TARGET is the newsletter of Target Health Inc., a NYC-based, full-service, contract research organization (eCRO), providing strategic planning, regulatory affairs, clinical research, data management, biostatistics, medical writing and software services to the pharmaceutical and device industries, including the paperless clinical trial.


For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.


Joyce Hays, Founder and Editor in Chief of On Target

Jules Mitchel, Editor


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Evolutionary Medicine


The bacteria Mycobacterium tuberculosis can evolve to subvert the protection offered by immune defenses


Evolutionary medicine or Darwinian medicine is the application of modern evolutionary theory to understanding health and disease. The goal of evolutionary medicine is to understand why people get sick, not simply how they get 1) ___. Modern medical research and practice has focused on the molecular and physiological mechanisms underlying health and disease, while evolutionary medicine focuses on the question of why 2) ___ has shaped these mechanisms in ways that may leave us susceptible to disease. The evolutionary approach has driven important advances in our understanding of cancer, autoimmune disease, and anatomy. Medical 3) ___ have been slower to integrate evolutionary approaches because of limitations on what can be added to existing medical curricula. Adaptation works within constraints, makes compromises and tradeoffs, and occurs in the context of different forms of competition.


Adaptations can only occur if they are evolvable. Some adaptations which would prevent ill health are therefore not possible. For example:


1. DNA cannot be totally prevented from undergoing somatic replication corruption; this has meant that 4) ___, which is caused by somatic mutations, has not (so far) been completely eliminated by natural selection.

2. Humans cannot biosynthesize Vitamin C, and so they/we risk scurvy, a Vitamin C deficiency disease, if dietary intake of the vitamin is insufficient.

3. Retinal neurons and their axon output have evolved to be inside the layer of retinal pigment cells. This creates a constraint on the evolution of the visual system such that the optic 5) ____ is forced to exit the retina through a point called the optic disc. This in turn creates a blind spot. More importantly, it makes vision vulnerable to increased pressure within the eye (glaucoma) since this cups and damages the optic nerve at this point, resulting in impaired vision.


Other constraints occur as the byproduct of adaptive innovations. One constraint upon selection is that different adaptations can conflict, which requires a compromise between them to ensure an optimal cost-benefit tradeoff. Here are some trade-offs and conflicts:


1. Running efficiency in women, and birth 6) ____ size

2. Encephalization, and gut size

3. Skin pigmentation protection from UV, and the skin synthesis of Vitamin D

4. Speech and its use of a descended larynx, and increased risk of choking


Different forms of competition exist and these can shape the processes of genetic change. Here are a few examples:


1. mate choice and disease susceptibility

2. genomic conflict between mother and 7) ___ that results in pre-eclampsia

3. Major histocompatibility complex and its effect on mate choice

4. Maternal-paternal genetic competition that by altering genetic imprinting might underlie autism and schizophrenia


Humans evolved to live as simple hunter-8) ___ in small tribal bands, a very different way of life and environment compared to that faced by contemporary humans. This change makes present humans vulnerable to a number of health problems, termed “diseases of civilization“ and “diseases of affluence“. Humans were designed to live off of the land, and take advantage of the resources that were readily available to them. They were designed for the stone-age, and the environments of today bring about many disease causing ailments, that may or may not be deadly. “Modern environments may cause many diseases-for example, deficiency syndromes such as scurvy and rickets“ In contrast to the diet of early hunter-gatherers, the modern Western diet often contains high quantities of fat, salt, and simple carbohydrates, which include refined sugars and flours. These create health problems like: trans-fat health risks, dental caries, high glucose foods.


Some examples of aging-associated diseases are atherosclerosis and cardiovascular disease, cancer, arthritis, cataracts, osteoporosis, type 2 diabetes, hypertension and Alzheimer’s disease. The incidence of all of these diseases increases rapidly with aging (increases exponentially with age, in the case of cancer). Of the roughly 150,000 people who die each day across the globe, about two thirds – 100,000 per day – die of age-related causes. In industrialized nations, the proportion is much higher, reaching 90%. Many contemporary humans engage in little physical exercise compared to the physically active lifestyles of our ancestral hunter-gatherers. It has been proposed that since prolonged periods of inactivity would have only occurred in early humans following illness or injury that it provides a cue for the body to engage in life-preserving metabolic and stress related responses such as inflammation that are now the cause of many chronic 9) ___.


Contemporary humans – due to medical treatment, frequent washing of clothing and the body, and improved sanitation – are mostly free of parasites, particularly intestinal ones. This causes problems in the proper development of the immune system although hygiene can be very important when it comes to maintaining good health. The hygiene hypothesis says that many modern humans are not exposed to microorganisms that have evolved in establishing the immune 10) ___ as they should be. “Microorganisms and macroorganisms such as helminths from mud, animals, and feces play a critical role in driving immuno-regulation“ (Rook, 2012). They play a crucial role in building and training immune functions to fight off and repel some diseases, and protect against excessive inflammation which has been implicated in several diseases (such as recent evidence for Alzheimer’s Disease).


ANSWERS: 1) sick; 2) evolution; 3) schools; 4) cancer; 5) nerve; 6) canal; 7) fetus; 8) gatherers; 9) diseases; 10) system


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Evolutionary Medicine


Charles Darwin (1809-1882). In 1881 Darwin was an eminent figure, still working on his contributions to evolutionary thought that had an enormous effect on many fields of science. Portrait by John Collier. Hangs today in The National Portrait Gallery, London.


Charles Robert Darwin was an English naturalist and geologist, best known for his contributions to evolutionary theory. He established that all species of life have descended over time from common ancestors, and in a joint publication with Alfred Russel Wallace introduced his scientific theory that this branching pattern of evolution resulted from a process that he called natural selection, in which the struggle for existence has a similar effect to the artificial selection involved in selective breeding. Darwin published his theory of evolution with compelling evidence in his 1859 book On the Origin of Species, overcoming scientific rejection of earlier concepts of transmutation of species. By the 1870s the scientific community and much of the general public had accepted evolution as a fact. However, many favored competing explanations and it was not until the emergence of the modern evolutionary synthesis from the 1930s to the 1950s that a broad consensus developed in which natural selection was the basic mechanism of evolution. Darwin’s scientific discovery is now the unifying theory of the life sciences, explaining the diversity of life.


Charles Darwin did not discuss the implications of his work for medicine, though biologists quickly appreciated the germ theory of disease and its implications for understanding the evolution of pathogens, as well as an organism’s need to defend against them. Medicine, in turn, ignored evolution, and instead focused (as done in the hard sciences) upon proximate mechanical causes. Medicine modeled itself after a mechanical physics, deriving from Galileo, Newton, and Descartes. As a result, until recently, medicine was mechanistic, materialistic, reductionistic, linear-causal, and deterministic (capable of precise predictions) in its concepts. It sought explanations for diseases, or their symptoms, signs, and cause in a single, materialistic – i.e., anatomical or structural (e.g., in genes and their products) – changes within the body, wrought directly (linearly), for example, by infectious, toxic, or traumatic agents.


George C. Williams was the first to apply evolutionary theory to health in the context of senescence. Also in the 1950s, John Bowlby approached the problem of disturbed child development from an evolutionary perspective upon attachment. An important theoretical development was Nikolaas Tinbergen’s distinction made originally in ethology between evolutionary and proximate mechanisms. Randolph Nesse summarized its relevance to medicine by stating that all biological traits need two kinds of explanation, both proximate and evolutionary. The proximate explanation for a disease describes what is wrong in the bodily mechanism of individuals affected by it. An evolutionary explanation is completely different. Instead of explaining why people are different, it explains why we are all the same in ways that leave us vulnerable to disease. Why do we all have wisdom teeth, an appendix, and cells that can divide out of control? The paper of Paul Ewald in 1980, “Evolutionary Biology and the Treatment of Signs and Symptoms of Infectious Disease“, and that of Williams and Nesse in 1991, “The Dawn of Darwinian Medicine“ were key developments. The latter paper “drew a favorable reception“, and led to a book, Why We Get Sick (published as Evolution and healing in the UK).


Evolutionary medicine as a field began in the early 1990s, but has grown dramatically in recent years. These developments include the creation of the online publication, The Evolution & Medicine Review (which has served as a clearinghouse for important information in the field), two peer-reviewed journals (Evolution, Medicine and Public Health and Journal of Evolutionary Medicine), the founding of several evolution and cancer centers (The Center for Evolution and Cancer at UCSF and The Darwinian Evolution of Cancer Consortium in Montpellier) and The Center for Infectious Disease Dynamics at Penn State. There is now a national working group on evolutionary medicine education at the NSF sponsored National Evolutionary Synthesis Center, Infusing Medical Education with Evolutionary Thinking. Evolutionary Medicine programs have been established at a growing number of Universities, including UCLA, Arizona State University and Durham University in the UK.


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NIH Study Solves Ovarian Cell Mystery, Shedding New Light on Reproductive Disorders


According to an article published online in the journal Nature Communications (28 April 2015), scientists at the National Institutes of Health have solved a long-standing mystery about the origin of one of the cell types that make up the ovary. The team also discovered how ovarian cells share information during development of an ovarian follicle, which holds the maturing egg. The authors believe this new information on basic ovarian biology will help them better understand the cause of ovarian disorders, such as premature ovarian failure and polycystic ovarian syndrome, conditions that both result in hormone imbalances and infertility in women. According to the authors, the ovarian follicle is the basic functional unit of the ovary, which contains the egg surrounded by two distinct cell types, known as granulosa cells and theca cells. Until now, the cellular origins of the egg and granulosa cells were known, but it was not known where theca cells came from or what directed their development. Without theca cells, women are unable to produce the hormones that sustain follicle growth. One of the major hormones theca cells produce is androgen, which is widely thought of as a male hormone. But, in a superb example of teamwork, the granulosa cells convert the androgen to estrogen.


The answer to this question remained unanswered for decades, but using a technique called lineage tracing, it was determined that theca cells in mice come from both inside and outside the ovary, from embryonic tissue called mesenchyme. According to the authors, “We don’t know why theca cells have two sources, but it tells us something important — a single cell type may actually be made up of different groups of cells.” As a result of this work, the authors uncovered the molecular signaling system that enables theca cells to make androgen. This communication pathway is derived from granulosa cells and another structure in the ovary called the oocyte, or immature egg cell. The crosstalk between the egg, granulosa cells, and theca cells was an unexpected finding, but one that may provide insight into how ovarian disorders arise. Now that it is known what makes these cells grow, the next steps are to search for possible genetic mutations or environmental factors that affect the process leading to ovarian cell disorders. For future work, the team wants to explore the two types of cells that make up theca cells. Since the research has been carried out in mice, it will need to be determined if the same holds true for humans. Either way, the research may potentially uncover several roles theca cells play in female fertility.


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Near-Atomic Resolution of Protein Structure by Electron Microscopy Holds Promise for Drug Discovery


Drug development efforts often involve mapping contacts between small molecules and their binding sites on proteins. These mappings require the highest possible resolutions so that the shape of the protein chain can be traced and the hydrogen bonds between the protein and the small molecules it interacts with can be discerned. According to a study published online in Science Express 7 May 2015) a new study shows that it is possible to use an imaging technique called cryo-electron microscopy (cryo-EM) to view, in near-atomic detail, the architecture of a metabolic enzyme bound to a drug that blocks its activity. This advance provides a new path for solving molecular structures that may revolutionize drug development.


The protein imaged in this study was a small bacterial enzyme called beta-galactosidase; the drug to which it was bound is an inhibitor called phenylethyl-beta-D-thiogalactopyranoside (PETG), which fits into a pocket in the enzyme. Enzymes are typically proteins that act to catalyze biochemical reactions in the cell. Understanding what an enzyme looks like, both with and without a drug bound to it, allows researchers to design new drugs that can either block that enzyme’s function (if the function is responsible for a disease), or enhance its activity (if lack of activity is causing a problem).


In this study, the researchers were able to visualize beta-galactosidase at a resolution of 2.2 angstroms (or A — about a billionth of a meter in size), which is comparable to the level of detail that has thus far been obtained only by using X-ray crystallography. At these high resolutions, there is enough information in the structure to reliably assist drug design and development efforts. To determine structures by cryo-EM, protein suspensions are flash-frozen at liquid nitrogen temperatures (-1960C to -2100C , or -3200F to -3460F) so the water around the protein molecules stays liquid-like. The suspensions are then imaged with electrons to obtain molecular images that are averaged together to discern a three-dimensional (3D) protein structure. In the study, using about 40,000 molecular images, the authors were able to compute a 2.2 A resolution map of the structure of beta-galactosidase bound to PETG. This map not only allowed the authors to determine the positioning of PETG in the binding pocket but also enabled them to pick out individual ions and water molecules within the structure and to visualize in great detail the arrangement of the amino acids that make up the protein.


The authors have recently used cryo-EM to understand the functioning of a variety of medically important molecular machines, such as the envelope glycoproteins on HIV and glutamate receptors found in brain cells. Their new finding, however, represents the highest resolution that they or others have achieved to date for a structure determined by cryo-EM.


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