,, November 17, 2009, by Mark Henderson  —  Over the past decade increasing understanding of both adult and embryonic stem cells has opened a new frontier for science through regenerative medicine.

As research has revealed how the body’s master cells can be coaxed to form new tissue, it has raised the prospect of producing new organs to replace those that have been damaged.

Growing new cells with specialised functions, however, is only the first hurdle that has to be cleared before regenerative medicine can help patients. A clump of cells is rarely, by itself, much use to anybody. They also need to be properly plumbed into blood vessels, to be protected from the body’s immune system and to be structured in a shape that allows them to perform.

This means that regenerative medicine is not reliant only on the cell biologists who can coax stem cells to make the right sort of tissue. It also needs engineers and immunologists. It is by its nature an interdisciplinary field.

Where scientists are starting to make strides in regenerative medicine, it is often because other challenges are being addressed. The development of biocompatible scaffolds, which guide the growth of new cells, has underpinned most advances such as the breast reconstruction technique.

Last year, a team led by Professor Anthony Hollander successfully replaced that part of a woman’s trachea called a bronchus with a version grown in the lab. This achievement was also made possible by the use of a bronchus from a dead donor that was stripped of its living tissue. The patient’s stem cells were seeded around this inert cartilage tube to create the new organ.

Artificial scaffolds can also be used, as when Anthony Atala’s team at Wake Forest University grew artificial bladders. The same group reported another advance this week, placing rabbit cells on to a matrix to generate functional erectile tissue. The technique could eventually be used to reconstruct the penises of men with genital injuries or cancer.

As fast as this technology is advancing, however, there is still a long way to go before scientists can re-create more complex organs. Professor Hollander said: “The early successes have involved organs without moving parts or complicated biology.”

The creation of new breasts, windpipes and bladders is an amazing step forward for medicine, but it remains a different challenge to grow new hearts or livers.


The Freaks of Nurture  Image: Edyta Zielinska, November 17, 2009, by Edyta Zielinska  —  On a recent Monday night at World Cafe Live in Philadelphia, four bands took to the stage to determine who ruled rock. But manning the mics, guitars, and drums weren’t your typical hipsters — the members of these bands were students and administrators from Philadelphia’s premier medical schools, and their scientific credentials are almost as hot as their licks. For example, the nine members of funk band the Freaks of Nurture are publishing in prestigious scientific journals such as Nature Medicine, Nature Neuroscience, Blood and PNAS.

The musicians hailed from four area medical schools (Thomas Jefferson University, the University of Pennsylvania, Drexel University, and Temple University) and were brought together by the local chapter of Physicians for Social Responsibility (PSA), an organization that promotes social consciousness and activism among physicians.

Putting the event together wasn’t easy, said Pat Harner, executive director of the Philly PSA chapter. “You can’t always count on med students because of their schedules,” said Harner, sounding a bit tense the Friday before the concert.

Acoustic guitar duets and soloists opened the concert, but the first real surprise performance came from The Novack Experience, led by internist Dennis Novack, an associate dean of medical education at Drexel University. His was actually the only rock band in the line-up, playing covers of popular classic and Indie-rock hits, such as Walk This Way by Aerosmith and I Got a Feeling by Black Eyed Peas. As his band set up, Novack walked around the stage with a cup of hot tea in hand, a subtle suggestion that the crowd was in for a subdued performance. Not so. This 63 year old professor rocked out like Steven Tyler as his more demure band members backed him up with vocals, drums, keyboards, and guitars. “He has more energy than the rest of us put together,” said guitar player and lab technician Kamal Laroiya from Drexel.

After The Novack Experience warmed up the crowd, the Freaks of Nurture came on, magnetizing a small group of dancers to the front of the room. Their well polished sound kept the dancers in their ecstatic funk-grooves, inspiring the next band to boogie down offstage.

When they aren’t practicing their original songs like “Sumo pigeon” and “Horny toad,” the Freaks of Nurture are working on their MD/PhDs, residencies and even orthodontics degrees. “We don’t discriminate” against the dentists, said trumpeter David Hill. The band mates’ roller-coaster work schedules make meeting for practice once a week challenging. But most band members are able to make it to at least one three-hour practice per week, said band leader Alec Schmaier. “This is just about the only thing I do outside of school,” said Hill.

Despite the intense pressure of PhD programs and demands of med school, the band members have found support for their music among their academic mentors. After hearing the band play, “the chair said I should spend more time on my music,” laughed Schmaier. Being known as the scientist or resident who plays in a band has its benefits, say band members. In the sea of medical school students, having a unique hobby allows you to stand out in the crowd, said singer Ehimare Akhabue. The dual identity can have other benefits, added bass player Rob Fenning. Rather than getting grilled on the difficult questions during med school interviews, questions invariably veer to what it’s like to play in a band, he said.

The Freaks often geek out during a rehearsals. “Half of our conversations are about working in the lab” or residency, said Hill. The band is currently working on a new album. “We have four new songs” already, Hill noted. “It’s statistically significant.”


A drug developed to treat Lou Gehrig’s disease undergoes clinical trials.


MIT Technology Review, November 17, 2009, by Jennifer Chu  —  Finding a cure for amyotrophic lateral sclerosis (ALS)–also known as Lou Gehrig’s disease–has been a frustrating and elusive quest. Even after decades of research, the biological roots of ALS are only partially understood. Now a new form of treatment offers fresh hope.

Trophos, a company based in Marseilles, France, has discovered a drug compound that appears to protect neurons from the effects of ALS, a rapidly debilitating degeneration of motor neurons in the brain and spinal cord. These effects lead to muscle atrophy and, ultimately, complete loss of motor control. The company’s researchers have found that a compound named olesoxime promotes survival and regeneration of neurons deprived of neurotrophic factors–proteins essential for maintaining healthy neurons. This deprivation is similar to what occurs in the neurons of ALS patients.

The company is currently conducting Phase II clinical trials to test the drug’s efficacy in ALS patients. Although the compound’s mechanism of action isn’t exactly clear, researchers believe it acts like a molecular “stopper,” preventing motor neurons from dying off by blocking a key structure that triggers the degeneration of nerve cell mitochondria.

For the past decade, researchers have increasingly focused on mitochondria as a potential target for treating ALS and other neurodegenerative diseases. Often referred to as the powerhouse of cells, mitochondria churn out ATP, a nucleotide that transfers the energy needed by cells. Researchers have found that in ALS patients, something causes the mitochondria to swell up and burst. Scientists believe that the accumulation of dead mitochondria deprives neurons of energy. This causes the neurons to die and thus lose their connection with associated muscles.

It’s unclear how mitochondria become dysfunctional in ALS patients in the first place, but over the past two years, scientists have identified a tiny pore within a membrane that may act as a fatal floodgate, letting in unwanted molecules that destabilize mitochondria. This gateway, called the mitochondrial permeability transition pore (mPTP), forms when two proteins within the inner and outer membrane come together. The resulting channel lets in a flood of calcium and other molecules, the source of the swelling in mitochondria.

Lee Martin, a professor of pathology and neuroscience at Johns Hopkins University in Baltimore, who was not involved with the research, says this mitochondrial opening may have evolved in order to get rid of damaged cells and make way for new, healthy cells. However, in diseases such as ALS, membrane proteins may come together more often, and the resulting pore may stay open longer than normal, causing otherwise healthy mitochondria and neurons to die off. “Normally this pore is in a state of flicker,” says Martin. “However, in disease states, this flicker may be transformed into a more permanent, more stable opening, and this is really bad.”

Martin and others believe that designing drugs to block mPTP from forming may prevent neuron death, and thus slow the progression of diseases such as ALS, Huntington’s, and Parkinson’s disease. Scientists at Trophos have found that olesoxime binds with a membrane protein in mitochondria that is responsible for forming mPTP. “Our compound binds to the outer membrane of mitochondria, and prevents the pore from opening in pathological conditions,” says Trophos CEO Damian Marron. “This is how we believe [the compound] prevents neuronal cell death.”

The company screened thousands of compounds before discovering the drug. The researchers’ method involved depriving motor neurons of their neurotrophic factors in order to produce neurons that resemble those found in ALS. They then studied the effects of thousands of compounds on these neurons, and found that olesoxime, a cholesterol-like molecule, was best at promoting neuron survival and growth.

In tests on mice with ALS, olesoxime significantly improved survival rates. Researchers went on to determine the drug’s safety performance in healthy volunteers and ALS patients. The company determined the drug to be safe in both groups, and is now going forward with an 18-month clinical trial in Europe, testing the drug’s efficacy in 480 ALS patients.

Marron says that in the European trial, the compound will be used in combination with riluzole, the only drug currently approved by the U.S. Food and Drug Administration to treat ALS. Riluzole, which is marketed as Rilutek in the United States, has been found to increase survival in patients by three to five months. “What we’re looking for is a 12 percent improvement over 18 months, which is a six-to-nine-month increase in survival in patients,” says Marron. “We’ve set a high hurdle, but we feel that if that could be provided, it would be clinically worthwhile.”

Other researchers caution that there is more work to be done to tease out the exact mechanism of the drug. “This molecule has great potential for delaying the disease progress in ALS patients, but still, there is a lot more to be done,” says Hemachandra Reddy, assistant professor of physiology and pharmacology at Oregon Health and Science University, who investigates the role of mitochondria in neurodegenerative diseases. “If we know the mechanism, then this molecule can be used not just for ALS patients, but also for a broad range of diseases like Parkinson’s and Huntington’s.”


Virtual reconstruction of the pelvis of a female Neanderthal from Tabun (Israel). The colours indicate the individual bone fragments that were fit together. The gray wedge shows the estimated configuration of the sacrum (lower part of the spinal column). (Credit: Tim Weaver, University of California),  Max Planck Society  –  Researchers from the University of California at Davis (USA) and the Max Planck Institute for Evolutionary Anthropology in Leipzig (Germany) present a virtual reconstruction of a female Neanderthal pelvis from Tabun (Israel).

Although the size of Tabun’s reconstructed birth canal shows that Neanderthal childbirth was about as difficult as in present-day humans, the shape indicates that Neanderthals retained a more primitive birth mechanism than modern humans. The virtual reconstruction of the pelvis from Tabun is going to be the first of its kind to be available for download on the internet for everyone interested in the evolution of humankind (PNAS, April 20th, 2009).

Childbirth in humans is more complicated than in other primates. Unlike the situation in great apes, human babies are about the same size as the birth canal, making passage difficult. The birth mechanism, a series of rotations the baby must undergo to successfully navigate its mother’s birth canal, distinguishes humans not only from great apes but also from lesser apes and monkeys.

It has been difficult to trace the evolution of human childbirth because the pelvic skeleton, which forms the margins of the birth canal, tends to survive poorly in the fossil record. Only three fossil female individuals preserve fairly complete birth canals, and they all date to earlier phases of human evolution.

Tim Weaver of the University of California (Davis, USA) and Jean-Jacques Hublin, director at the Max Planck Institute for Evolutionary Anthropology in Leipzig (Germany) now present a virtual reconstruction of a female Neanderthal pelvis from Tabun (Israel). The size of Tabun’s reconstructed birth canal shows that Neanderthal childbirth was about as difficult as in present-day humans. However, its shape indicates that Neanderthals retained a more primitive birth mechanism than modern humans, without rotation of the baby’s body.

A significant shift in childbirth apparently happened quite late in human evolution, during the last 400,000 – 300,000 years. Such a late shift underscores the uniqueness of human childbirth and the divergent evolutionary trajectories of Neanderthals and the lineage leading to present-day humans.

The virtual reconstruction of the pelvis from Tabun is going to be the first of its kind to be available for download on the internet for everyone interested in human evolution. The computer files will be available from the websites of University of California at Davis and the Max Planck Institute for Evolutionary Anthropology.

By Gabe Mirkin MD, November 15, 2009  —  At the University of Toronto School of Medicine’s “Diagnosis and Treatment of Vitamin D Deficiency” conference on November 3, 2009, thirty of the world’s leading researchers on vitamin D recommended 2,000 IU of vitamin D daily (the current recommendation is 600 IU). Vitamin D3 blood levels should be 100-150 nmol/L (40-60 ng/ml); the existing recommendation is 30-50 nmol/L.

Vitamin D pioneer Dr. Cedric Garland presented data showing that raising vitamin D levels to 200 nmol/L decreased breast cancer risk more than 77 percent. He said: “Breast cancer is a disease so directly related to vitamin D deficiency that a woman’s risk of contracting the disease can be virtually eradicated by elevating her vitamin D status to near that level.” Recent work has shown that all cells in the body have “vitamin D receptors” to control normal cell growth. Garland presented new evidence that low vitamin D status compromises the integrity of calcium-based cellular bonding within tissues, which allows rogue cancer cells to spread more readily.

Vitamin D deficiency is associated with at least 24 cancers, diabetes, multiple sclerosis, heart disease, falls and fractures, psoriasis and many other health problems.


Check Vitamin D Levels this Winter

By Gabe Mirkin MD, October/November 2009  —  I have reported that low vitamin D levels are associated with increased risk for heart attacks, strokes, at least 17 different cancers, diabetes, autoimmune diseases, depression and osteoporosis. Adequate blood levels of vitamin D are thought to be over 75nmol/L. Researchers at the University of Toronto have now shown that in the winter, more than 93 percent of the people in Toronto have concentrations below 75 nmol/L, and 75 percent have concentrations below 50 nmol/L (BMC Public Health, September 26, 2008).

Only those with light skins had average vitamin D intakes exceeding the current Recommended Adequate Intake (RAI = 200 IU/day). Those with dark skin and/or excess weight had very low levels of vitamin D. Dark skin blocks ultraviolet light. Obesity sequesters vitamin D so it is not available for use. Aging also lowers vitamin D levels as the skin of older people doesn’t make vitamin D as well as during younger years.

In the wintertime, I recommend getting a blood test called D3. If it is below 75 nmol/L, you need more sunlight or vitamin D pills. The blood test for the active form of vitamin D (1,25 dihydroxy-vitamin D) is of little value as it often is normal when a person has a severe deficiency. Lack of vitamin D causes the parathryroid gland to produce massive amounts of parathyroid hormone that causes these falsely high levels.


The term ‘The Big Apple’ was coined by touring jazz musicians of the 1930s who used the slang expression ‘apple’ for any town or city.  Therefore, to play New York City is to play the big time – The Big Apple.