Syn 3.0 – A Model T Chassis For Synthetic Biology.

Posted on | March 29, 2016 | 1 Comment

J.Craig Venter Institute team

Mike Magee

A decade or so ago, I had the opportunity to moderate an educational forum that featured Craig Venter. Venter was relatively fresh off of the competitive race to define the human genome, a scientific battle that ended in a truce with current NIH director, Francis Collins. After shaking hands, the two headed in opposite directions. Collins remained in governmental service, and Venters formed the Institute for Genomic Research which later became the J. Craig Venter Institute in La Jolla, California.

Off that base, he consulted with a wide range of corporate entities focused on synthetic biology, that is, taking genetically modified microbes and pushing out a range of products from petroleum to pharmaceuticals. His efforts were financially underwritten by the likes of British Petroleum and Exxon in the hundreds of millions. Designer organisms have met multiple obstacles, not the least of which has been the plunging price of oil.

But at his core, Venter is as much an explorer as he is an entrepreneur. When I asked him, on behalf of the audience, “What percentage of the knowledge do we currently possess to take optimum care of human health?”, his response without delay was “Less than 1%.” He is committed to exploring the 99%.

What is his secret? Nobel Prize winner Sir Richard Roberts claims he’s a “managerial genius” with a history of holding together large, highly specialized and integrated teams for decades in pursuit of elusive endpoints. Twenty years ago, he and his co-workers began to wonder how many genes are actually necessary to create a living organism – one, as Venters says, that can “live, eat, and self-replicate.” Humans have 20,000 or so genes made of 3 billion individual building blocks. But it’s been known for some time that many of these wait on the sideline and are not an active part of the game of life. To get down to the simple essentials, you can either successively “edit out” genes of a existing organism and  see what happens, or create a brand new form of life, building it block by block.

Venters, with his commitment to synthetic biology, chose a middle road. As a model, he began with the 900 gene M. mycoides, a microbe that lives in sheep. Through a series of experiments over a number of years, they were able to identify 428 of these as non-essential for life of the microbe. They then created a brand new organism with just 473 genes and roughly a half million building blocks, and booted it up. the lifeform, dubbed JCVI-syn3.0 or Syn3.0 for short, not only came to life but, ate, grew and replicated in the specialized environment Venters lab had created.

Still, the team, in its publication, was quick to dampen expectations. First, the new creature needs the specialized environment to survive. Second, of the necessary 428 genes, the scientists have no idea what 149 of those genes (roughly 1/3) do, and why they are essential for life. Obviously, part of the goal is to explore those unknown functions, and in the process better understand the workings and evolutionary history of living cells.

But in addition, as it turns out, size matters when it comes to synthetic biology. And bigger is not better. As with the Model T, it pays to have a simple chassis with few moving parts, high reliability, and efficient productivity. Most scientists this week agreed that “minimal-DNA microbes” have a bright future that will likely include, with the help of selectively added genes, production of a wide range of products. For Venter and his colleagues, their “designer organism”, like other micro-tools embraced in Cambridge, Mass, or Silicon Valley, will eventually be a ubiquitous presence on biologic product lines everywhere. 

A Blood Test for Sports Concussions – Can Americans Stand The Truth?

Posted on | March 28, 2016 | 1 Comment

Source: CDC

Mike Magee

Two years ago, the Swedish Hockey League made medical history – but not in a good way. 288 members of the 12 teams fighting for the title in their 2012-2013 season agreed to participate in a head trauma medical study. An unfortunate 35 did sustain concussions, and of these 28 completed required blood testing at 1, 12, 36, and 144 hours after injury. In each case, their blood was tested for specialized protein biomarkers. Two of those markers, total tau and S-100 calcium-binding protein B, consistently rose and were confirmed to be associated with acute axonal and astroglial injury. In addition, the level of rise positively correlated with the extent of the injury, and the subsequent recovery of function.

The study was a breakthrough. It proved that traumatic injury of brain cells could be detected by a simply blood test because these injured cells released stress proteins, and these proteins crossed the blood brain barrier and entered the general blood circulation.

Medical science, especially diagnostic medical science, never exists in a vacuum. In the public light of recent documentaries, investigative reports and feature films, the tragic outcomes of NFL players with a history of traumatic injuries has been on full display. And parents of young children and high schoolers in competitive sports of all types have wasted no time raising the question, “Are our children safe, or at least safe enough to take on the risk of participating on a sport team?”

Emergency medicine and sports medicine specialists weighed in with data. About 250,000 children suffer traumatic brain injuries a year, the majority associated with sports. The level of injury is highly variable, and competitive sports associations, in association with sports medicine specialists, have agreed on protocols for on the field evaluation and acute response to injuries. But most have agreed that the evaluative measures (some basic neurologic evaluation and questions to assess balance, level of consciousness and orientation) are a very blunt tool.

But what if there was a blood test that could be administered on the field that could detect significant blunt trauma damage to the brain? Four months ago, an emergency medicine physician, NIH-funded, researcher from Florida reported on the results of just such a test. Dr. Linda Papa and her team described the results of 152 children who had suffered sports related head trauma, and who had received both CT scans and a blood test for glial fibrillary acidic protein (GFAP). Glial cells surround brain neurons, and the protein in released with injury and finds its  way into the general circulation.

The blood test was found to corollate with CT findings 94% of the time. In addition, levels of GFAP rose with severity of injury. The researchers left no doubt where they are heading with this. Papa said, “The idea is to get a point-of-care test that could be used on the field, to help the coaches, the trainers and the athletic directors, make a decision then and there about whether the child should go back to play.”

But she may be under-estimating the full impact of this test. Because it is quite likely that the question most of America’s increasingly risk-averse parents will ask is not “whether their child should go back to play”, but rather whether the child should have played in the first place. And it’s also likely that elevations will be a common finding not only in football, but also in a wide range of other sports including soccer, basketball, track and field, gymnastics and many more.

Could Optimizing The Carbon Sink Offer Immediate Short-Term Relief?

Posted on | March 23, 2016 | 1 Comment

Source: NOAA Video Carbon in Action

Mike Magee

OK. Let’s just all admit it. Al Gore was right – even if the truth was inconvenient at the time. For most of the civilized world, the present day truth is not only inconvenient, but also incontrovertible, inconceivable (in its potential destructive effects), and increasingly (almost) inevitable.

Most of the emphasis has been on the human creation and release of carbon into the atmosphere. Policy makers have focused on rules and incentives to encourage humans to act, well, more human. That hasn’t worked. Nor has public education, threats, or even perceptible changes in the weather related disasters. Some have sought refuge in possible technologic advances – say in new alternative, less polluting,  energy sources. But the economic and political clout of fossil fuel producers, and the real time energy needs of emerging economies around the globe have, for the time being, counter-balanced these progressive efforts.

But wait. Don’t give up on human ingenuity just yet. Maybe we’ve been looking for sanity in all the wrong places. Rather than focus on “carbon in” (which we need to continue to pursue with energy and determination), perhaps we should spend equal time on “carbon out”.

We’ve spent so much energy in associating the word carbon with a mountain of dirty coal that we have almost lost sight of the fact that this atom is the fundamental building block of all life, and of the planet we inhabit. It is anything but solid and static. It’s a highly mobile cycle – moving in and moving out constantly. It anchors the geosphere (soil), the hydrosphere (water), the atmosphere (air), and the biosphere (living organisms).

For the first time, NASA has recently launched a satellite whose purpose is to visualize the carbon cycle in action worldwide. What is already clear is that carbon release is highest, as you would expect in the northern hemisphere. But it moves fast and far with the trade winds. It accumulates in highest concentration during the winter months, when new plants lie dormant, not engaging in photosynthesis, which transmits atmospheric carbon into the soil.

Carbon sinks come in many shapes and sizes – oceans, forests, wetlands, undisturbed soils, grasslands and more. But the most important of these are the oceans. Their capacity to bind carbon is 50 times greater than the atmosphere. They alone absorb 48% of all atmospheric carbon – but that number is rapidly declining.

The movement and absorption of carbon is ocean water is effected by water temperature, the currents and the activity of biologic species through photosynthesis and respiration. In general the lower the ocean temperature, the more carbon it can hold. Northern oceans are colder and possess downward moving currents where the deeper water is colder than surface water. The net effect for carbon then is the “solubility pump” or mixer which delivers carbon to deep storage areas in the ocean where it lies relatively dormant. In contrast, warmer water favors upward currents and the release of stored carbon into the atmosphere.

But there is another piece to the puzzle, and its called the “biological pump”. It seems that when carbon is absorbed into the ocean, very little of it remains in the form of carbon dioxide. Instead it takes on a variety of different dissoved inorganic forms captured in living plankton or calcites, which move slowly but steadily downward. The carbon remains trapped in these living creatures until they decay or die, releasing carbon dioxide in the process.

The average acidity of today’s oceans is a pH of 8.2. That represents a drop of 30% over thew past 100 years. A balanced higher pH is essential for maintaining optimum marine life. But there is more to it than that. Acid pH destroys the shells and outer protective layers of plankton, coral, crabs, clams, and many others. Lose them, and you disable the “biological pump”.

All of the above is why some scientists are advocating incentives that focus on new technologies to enhance carbon capture. Some may focus on improving the viability and functioning of ocean solubility and biologic pumps. Others might reward farming approaches that conserve undisturbed soil and wetlands, or expand forest cover. And others might encourage new technologies that attract and capture carbon, and bury it deep in our earth or oceans, or beyond Earth’s atmospheric borders.

Obviously we need to focus on both over-release of atmospheric carbon and under-removal of the substance. But when it comes to short term and urgently needed actions, we should use our resources wisely, and invest where scientists believe there is the greatest potential for immediate success.

# of U.S. Water Systems With Dangerous Lead Levels?

Posted on | March 17, 2016 | 1 Comment

SOURCE

Death by Environment: The Boomerang Effect of Poor Environmental Policy

Posted on | March 16, 2016 | 1 Comment

Source:IndexMundi

 Mike Magee

The WHO released a report this week that suggested that nearly 1/4 of all human mortality (22.4%) in 2012 was secondary to unhealthy environments.

We have known for some time that planetary health has an important impact on human health. It effects not only the quantity of years an average planetary citizen lives, but also the quality of those years. This, in turn, can be a major determinant of human productivity and ingenuity, and an important factor in our efforts to maintain safe, stable and secure human societies.

When examining global human resources, social scientists often begin with the number of births and the number of deaths per 1000 in various geographic localities around the world. “Refreshing” the human population is essential to revitalizing the human workforce, and in maintaining the most productive demographic age balance. The reality is that we rely on new healthy workers to support the growing needs of aging populations who consume more health and social resources as they grow older.

The WHO has added a new wrinkle to their most recent studies by attempting to quantify the human mortality costs of an unhealthy environment. Environmental degradation increases the chronic burden of cardiovascular and pulmonary disease, as well as all types of cancer. Weak environmental laws and infrastructure also are  responsible for deadly poisoning by toxins and outbreaks of infectious diseases. Finally, extreme environmental degradation can be associate with collapse of adequate food and water support, mass migration and warfare and anarchy.

What do we know about the 56 million who died worldwide in 2012?  Let’s break it down. On average that year, just under 8 (7.99) people died per 1000 citizens during the course of 2012. That figure remained roughly the same in the 2014 readings. The highest death rates occured in South Africa (17.49/1000) and in the Ukraine (15.72), and the lowest occurred in Qatar (1.53/1000) and  United Arab Emirates (1.99/1000). The U.S. came in at 8.15/1000, just below Switzerland (8.1/1000), but higher than Canada(8.31/1000) and the U.K.(9.34/1000), Japan (9.38/1000) and Sweden (9.45/1000). But before we engage in too much self-congratulation, realize that higher mortality rates often reflect aging demographics rather than generalized poor health.

Going back to the UN report, here are a few interesting findings:

1. 12.6 million of the 56.4 million deaths worldwide were related to “living in an unhealthy environment”.

2. “Environmental risk factors, such as air, water and soil pollution, chemical exposures, climate change, and ultraviolet radiation, reportedly contribute to more than 100 diseases and injuries”, according to the report.

3. 2/3 of the “environmental deaths” (8.2 million) were the result of non-communicable disease such as stroke, cardiovascular disease, pulmonary disease, and cancer. In this arena, indoor and outdoor pollution, including the use of fossil fuels for domestic cooking, heating, and lighting, and secondary cigarette smoke, were the major offenders.

4. “Regionally, the report finds, low- and middle-income countries in the WHO South-East Asia and Western Pacific Regions had the largest environment-related disease burden in 2012, with a total of 7.3 million deaths.”

Children under five and adults age 50 to 75 were the most likely to suffer an “environmental death”. Approximately 1.7 million deaths in children and 4.9 million in adults were deemed preventable were appropriate health policies to be implemented.

What policies? The WHO report lays out a range of actions. Here are a few of their suggestions:

“Using clean technologies and fuels for domestic cooking, heating and lighting would reduce acute respiratory infections, chronic respiratory diseases, cardiovascular diseases and burns.”

“Increasing access to safe water and adequate sanitation and promoting hand washing would further reduce diarrhoeal diseases.”

“Tobacco smoke-free legislation reduces exposure to second-hand tobacco smoke, and thereby also reduces cardiovascular diseases and respiratory infections.”

“Improving urban transit and urban planning, and building energy-efficient housing would reduce air pollution-related diseases and promote safe physical activity.”

End-of-Life Care Options

Posted on | March 9, 2016 | 1 Comment

Sophia Bernazzani

When your loved one is given months or even weeks to live, it can result in a tidal wave of emotions for you and the rest of the family. Questions such as “Where will he stay?” or “How will we keep her comfortable?” immediately spring to mind. End-of-life care refers to the various types of services available to someone who is approaching death. Nursing@Simmons has created a guide that explains the five primary options for receiving end-of-life care. Below we explore the basics of each

1.Home

People who choose to live out their final days at home typically have family support and good financial resources combined with a desire for independence. The amount of external support required depends on the person’s condition and whether or not a nearby family member is available and willing to help out. Types of services needed by a homebound patient may range from help with daily activities and medical needs to transportation. In addition to a close family member, he or she may enlist the help of:

• Home health agencies
• Professional caregivers
• Community-based hospice or palliative care programs

 Payment sources: Medicare/Medicaid, private and/or long-term care insurance, Veterans Administration (VA), and patient/family resources

2. Hospice

Hospice is generally an option for those with a life expectancy of six months or less. Hospice care focuses on keeping a person comfortable rather than on finding a cure. It can be administered at home, in a hospital, in a long-term care facility, or at a freestanding hospice house. Hospice facilities cannot refuse care based on a patient’s inability to pay.

Payment sources: Medicare/Medicaid hospice benefit, private insurance, and patient/family resources

3. Hospital Inpatient Care/General Inpatient Hospice (GIP)

These options are usually for very ill individuals who require constant medical monitoring. They may be cared for on a general nursing floor of a hospital or in an intensive care unit (ICU). In these settings, a patient often has access to a palliative care team, which involves providers working together to tend to his or her physical, emotional, and spiritual needs.

Payment sources: Hospital inpatient costs to Medicare/Medicaid have increased significantly over the past five years, but out-of-pocket costs to patients/families remain minimal and unchanged.

4. Long-Term Care Facility

Long-term care settings include assisted living facilities, which cater to semi-independent people who need assistance with some daily living and nursing tasks, as well as skilled nursing facilities, which provide comprehensive care for more complex needs.

Payment sources: Long-term care insurance and Medicaid (covers room and board if eligible)

 5. Palliative Care

This type of end-of-life care is for seriously ill people who require ongoing pain and symptom management. Palliative care can be provided in any setting and can maximize quality of life for patients and families during the final days. Palliative care experts are qualified to assist with a variety of end-of-life issues, including goals for care and advance directives. Models of care include:

• Hospital-based consult teams
• Inpatient palliative care units
• Community-based palliative care programs

Palliative care has been shown to reduce costs for both patients and health care organizations. People who receive this type of care earlier in their hospitalization are less likely to be in the ICU. Plus, studies actually show lower inpatient costs with palliative care.

Easing a Difficult Decision

Choosing the location for end-of-life care is a tough decision that must be made with input from the patient, family, and primary care provider. Carefully evaluating the full range of options available — as well as their associated costs — can help you ensure affordable care, greater comfort for your loved one, and peace of mind all around.

Remembering My Parents and the Reagan’s

Posted on | March 7, 2016 | 3 Comments

Mike Magee

The words on the May 7, 1992, University of Pennsylvania report, signed by psychiatrist Gary Gottlieb, could hardly have been more definitive. They read, “Dr. Magee’s pattern of results suggests moderate to severe diffuse global impairment with functions mediated by the temporal and frontal lobes being affected to a greater degree. His performance on measures of higher cortical functioning appear to be consistent with a primary degenerative disorder such as Senile Dementia of Alzheimer’s Type (SDAT).”

The verdict was not a surprise, and still it was shocking to see it there on the page in black and white. My mother had quietly hidden my father’s growing disorientation and memory difficulties for quite some time. I had first noticed some mild changes at a celebration of my father’s 75th birthday in Florida three years earlier. In the past year, he had become more and more forgetful, and had gotten lost several times while driving. Lately he was intermittently confused, and repeating events and questions over and over. He was more easily frustrated, even dazed at times. My mother knew something was very wrong, and knew she finally needed help.

On the West Coast, another woman of similar age and disposition was noticing similar changes in her own husband. He too had been a remarkably capable individual, with a large following of devotees; a man quick to smile and converse with strangers; a man capable of inspiring hope and confidence with his social skills and aptitude; a man who also enjoyed being front and center, “on the stage”. His name was Ronald Reagan.

The two couples had never met each other, yet their similarities were striking. For both, their marriage, and commitment to each other was paramount. Both marriages would last 52 years, interrupted only by the death of a spouse – in one case the wife, in the other the husband.  Both wives would be the primary caregivers and protectors of their husbands, only grudgingly accepting support and help, remaining the primary and final arbiter, “until death do us part”.

In describing their marriage, one of the men wrote, “I more than love you, I’m not whole without you. You are life itself to me. When you are gone I’m waiting for you to return so I can start living again.” And his wife later explained, “If either of us ever left the room, we both felt lonely. People don’t always believe this, but it’s true. Filling the loneliness, completing each other – that’s what it still meant to us to be husband and wife.”

Both couples raised strong-willed children. But in both cases, there was a clear demarcation between parent and child, and no question about the supremacy of love. Their love for each other came first. Any good that they had to offer, in their eyes, whether for their children or others, flowed from that.

My parents connection to the Reagan’s was well established by the time the young psychiatrist, Gary Gottlieb, evaluated my father that Thursday morning. During his campaign for a second term as President in 1984, to my distress, my parents taped a color picture of Ron and Nancy to the front window of our home to proclaim their support for the “First Couple”.

Years later, the experience that Nancy Reagan and my mother shared, as a spouse who was the primary caregiver of an Alzheimer’s patient, was one that is at once indescribable, and at the same time ubiquitous today throughout human societies. As my parent’s child, quite independent of politics, it is easy for me to identify with the heavy burden as described in the final days by the Reagan’s daughter Patty.

She wrote: “My father is dying. Only a few days left now. Maybe a week. Maybe his soul is already gone. It looks like that—blue chalk eyes, more like a child’s drawing than real eyes. No life in them, just existence.

It’s been 10 years since the diagnosis. Alzheimer’s. A disease that arrives with death as its soulmate. I thought I was prepared. So many waves of grief have crashed over me during these years. But now I think there is another diving-down place that’s still waiting for me. Two days ago my father’s eyes stopped opening at all, his hand is as pale as the blanket covering him and sometimes his breath just stops as seconds pass by and I wonder and hold my own breath. My father is dying and it feels like I’ve never thought about it before. Even though I’ve been living with the thought for a decade.

My father’s voice fell silent weeks ago. Until then the sound of his voice hummed through the room sometimes—not with words, but maybe they were words to him. I said to my mother, maybe he’s getting us used to the silence. She lives with all that silence, with the ticking by of minutes and the knowledge that death has to be better than ragged breathing and chalk blue eyes.

Her husband is dying. The man she loved for 52 years. Here is a snapshot of the waiting: A daughter holding her mother while she weeps, tears staining skin, a body shaking with so much pain you think if you were at the center of the earth you could probably feel it. My mother is tiny, her weight against me light, the back of her head is cupped in my hand. But her grief is huge and so heavy it pulls on the joints of my body. It will be okay, I tell her. But I have no idea if it will be.”

Had my father publicly disclosed his disease, at the time of diagnosis, I am sure he would have included a paragraph that mirrored Ronald Reagan’s open letter to America.(76) It read, “Unfortunately, as Alzheimer’s Disease progresses, the family often bears a heavy burden. I only wish there was some way I could spare Nancy from this painful experience. When the time comes, I am confident that, with your help, she will face it with faith and courage.”

As with my father, Reagan’s love for his wife was paramount. He stated it succinctly at the dedication of his Presidential Library, “Put simply, my life really began when I met her and has been rich and full ever since.” As with my father, after his diagnosis, life, ever so slowly, slipped away. Reagan’s last visit to his California ranch for a ride in his open Jeep with the vanity license plate, GIPPER, came in August, 1995.  At around this time, the former First Lady commented that “It’s very lonely. Not being able to share memories is an awful thing. There really isn’t much you can do… and that’s the frustrating part of it. You know it isn’t going to get better, there’s only one way it can go. So you have to recognize that, and it’s very hard to watch.”  Certainly my mother would agree.

Ronald Reagan died a peaceful death on June 15, 2004.  Some time later, Nancy commented, “If a death can be peaceful and lovely, that one was. And when it came down to what we knew was the end, and I was on one side of the bed with Ron, and Patty was on the other side, and Ronnie all of a sudden turned his head and looked at me and opened his eyes and just looked … Well, what a gift he gave me at that point… I learned a lot from Ronnie, while he was sick – a lot. I learned patience. I learned how to accept something that was given to you, and how to die.”

My mother’s experience was different. She was not at my father’s side. She was not there to accept one last loving gaze, one final silent message of thanks and gratitude. My father died on September 15, 1998, under the loving care of my older brother, Bill, his wife, Kathy, and their family. My father no doubt felt my mother’s absence, as he continuously wondered aloud, “Where’s Grace?” But she was gone. On the morning she died, on December 9, 1995, she dressed and prepared my father for his ride to the Alzheimer Day Center. Once safely on his way, with the company of my sister, Kathy, a nurse, who by chance was visiting them at the time, she lay down on their couch and quietly and unceremoniously died, the victim of ovarian cancer whose diagnosis had been tragically delayed by inattention to herself while she labored in the service of her husband.

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