20091007-12

The idea sounds like science fiction. But it might someday come true. A group of Boston scientists is pushing the bounds of regenerative medicine.
BostonGlobe.com, October 6, 2009, by Cynthia Graber  —  According to Greek mythology, the god Prometheus granted human beings the gift of fire. As punishment, an angry Zeus condemned Prometheus to a life of torture. An eagle swooped down and tore out his liver every day. But each night, his liver grew back. While this created a nightmare for Prometheus, one element of his story represents the dream of a number of scientists in the Boston area: regrowing cells, tissues, perhaps someday even entire organs or limbs.

Starfish and salamanders are familiar, nonmythological examples of regeneration. Cut an arm off a starfish, and an exact duplicate emerges. The salamander, upon losing a tail, sprouts another. The conventional thinking has been that we, along with all other mammals, lost the ability to regrow entire organs and limbs. Yet there are exceptions. Deer show off new antlers every year. Even children retain vestiges of regenerative capacity: Up to an age of between 7 and 11, if a child loses the top third of a finger, that tip will reemerge.

How can we, like Prometheus and like starfish and salamanders, harness the power of regeneration? If every cell in our body contains an exact copy of the DNA we were born with, the DNA that bears the code for the creation of our body in the first place, is there a way to reactivate that genetic ability? Scientists at the region’s top universities and hospitals — who collectively have created what many in the field regard as this country’s center of regenerative medicine — are determined to answer those questions.

>> Understanding the promise of regenerative medicine begins with the process of conception. Sperm and egg meet, combine genetic material, and form a single cell that divides again and again. The external layer of cells gets ready to latch onto the uterus wall. Only a small handful of cells, perhaps even a single cell, at the center of the mass, or embryo, prepares to grow into a human being. That cell has the potential to branch off and differentiate into every cell, every tissue and organ in our body. Scientists call that ability pluripotency.

“The cells start making different lineage decisions to become this cell but not that cell,” says M. William Lensch, a stem cell scientist at Children’s Hospital Boston. “The complexity is mind-boggling.” Some eventually become adult stem cells, which maintain the potential to turn into an assortment of specialized cells: Various stem cells in the bone marrow, for instance, can produce blood, bone, and cartilage.

In 1981, scientists placed mouse embryos onto a petri dish and managed to generate mouse embryonic stem cells. Seventeen years later, human embryonic stem cells were isolated and grown in a laboratory — and their use has provoked controversy ever since. These cells are generally taken from embryos created during in vitro fertilization but never implanted in a patient; IVF clinics around the country have hundreds of thousands of these leftover frozen embryos. Critics argue that life begins at conception and these human embryos should not be used for research. Proponents disagree that life begins at conception and explain that these frozen masses of cells are otherwise destined for destruction. In 2001, President Bush banned scientists from using federal funds to study stem cells from sources other than those that had already been grown. In what researchers see as a boon for the field, President Obama relaxed that ban in March.

Research into cellular differentiation is the basis for regenerative medicine. In a uterus, cells are responding to complex influences including nutrients and chemicals called growth factors, and scientists in Boston have been teasing out the recipes for coaxing cells down a particular pathway.

Three years ago, Japanese researcher Dr. Shinya Yamanaka electrified the field with a startling announcement: He had taken normal skin cells from mice, used viruses to insert four genes, and forced those cells to behave like embryonic stem cells. Such transformed cells are now known as induced pluripotent stem (iPS) cells, referring to the fact that scientists caused skin cells to revert to an earlier, pluripotent state. “There was a lot of skepticism,” says Dr. Rudolf Jaenisch, a founding member of the Whitehead Institute for Biomedical Research. “The first cells he made in 2006 were not really embryonic stem cells. They were pretty abnormal. But that showed the principle and shattered the view that differentiation was a one-way path.”

Yamanaka’s discovery prompted a flurry of activity among Boston stem cell researchers. Jaenisch’s lab at the Whitehead Institute, along with Konrad Hochedlinger at the Harvard Stem Cell Institute and Yamanaka himself in Japan, replicated and refined the results a year later. Dr. George Daley, director of the stem cell transplantation program at Children’s Hospital Boston, was one of the first to apply the technique to human skin cells in the lab. “I think the great power of that discovery is going to be the next frontier in regenerative medicine,” says Jonathan Garlick, director of the division of cancer biology and tissue engineering at Tufts University School of Dental Medicine.

With this discovery, scientists realized they could reverse a seemingly one-way developmental process. In theory, someday an ordinary cell could be taken from a patient, then turned back into an all-powerful pluripotent cell. That cell could be used to create tissue that would match the patient’s genetic profile. In a hint of what the future may hold, in 2008, Harvard Stem Cell Institute researcher Kevin Eggan created the first patient-specific neurons, derived from iPS cells from two women with the neurodegenerative disease ALS.

There are, however, limitations to iPS cells. Because remnants of the viruses used to insert the genes could lead to mutations or cancer, researchers are investigating improved methods for delivering the genes. They’re continuing to study how iPS cells differ from embryonic stem cells. But the creation of iPS cells raised an additional question: Could scientists alter a specialized cell and make it perform a different but related function?

Just last year, this question was answered, when Harvard Stem Cell Institute co-director Douglas Melton published another landmark finding. Melton started with pancreatic cells that do not produce insulin. He introduced new genes and transformed a cell into an insulin-producing pancreatic cell, the kind destroyed in diabetes.

>> These days, Robert Langer is attempting to help mend spinal cords. A video shows two mice with spinal-cord injuries. One drags his legs behind him, paws splayed. The second has been treated with a piece of engineered spinal cord that has been seeded with nervous-system stem cells. The treated mouse can walk, if a bit clumsily, and his paws appear normal. “It isn’t perfect, but it’s a huge improvement,” Langer says. The MIT researcher is now working with spinal surgeons to test this therapy on primates.

Langer, approachable and talkative, oversees one of Boston’s largest and busiest labs. He has his name on more than 750 patents and has won more than 170 awards. Langer is considered the father of the field of tissue engineering, and in the past few decades, he and the hundreds of scientists who have worked with him have revolutionized the creation of artificial structures on which cells live and thrive, much as they do on natural tissue. This allows the work of regenerative medicine to leap from a petri dish to a more realistic three-dimensional world.

Building on Langer’s principles of tissue engineering, Garlick, the Tufts researcher, in July presented the first skinlike tissue crafted from human embryonic stem cells. To create the skinlike tissue, Garlick and his lab nurtured two different types of cells derived from embryonic stem cells and brought them together on a substance that approximates skin building blocks. Tiny dimes of a pale opaque pink, the color of a wound beginning to heal, float atop their nutrient bath. “Sometimes I swear I can see little fingerprints on top,” says Garlick, visibly thrilled.

But providing a three-dimensional structure itself isn’t always enough. Cells are subject to external forces such as tension and pressure. In a fetus, it is the very force of the beating of an early heart that causes blood cells to form, as both George Daley’s and Dr. Leonard Zon’s labs at Children’s Hospital demonstrated.

In his laboratory off Harvard’s main yard, Kevin Kit Parker of the Harvard Stem Cell Institute borrows from computer microchip technology to create patterns on a film that force cells to grow in a specific shape and in a certain direction. This not only affects how the cells look but also how they behave.

Parker has teamed with Dr. Kenneth Chien, director of Massachusetts General Hospital’s Cardiovascular Research Center, to use Parker’s technology to force heart stem cells, grown from embryonic stem cells, to take on the shape of cardiac muscle cells. “They actually start thinking they’re cardiac muscle cells,” says Parker. Within confines, the cells link up to one another, as do normal cardiac muscle cells. The results of their collaboration could lead to the first example of a fully functional strip of heart muscle tissue created from embryonic stem cells.

Regenerative medicine can be viewed as the meeting of cellular biology and tissue engineering; combining those two fields allows researchers to grow rudimentary examples of living tissue. Still, challenges remain, such as how to encourage the growth of blood vessels that will then connect an engineered tissue to the patient. And scientists need to be able to regulate the dividing capability of introduced stem cells so they do not turn cancerous. But even were these problems solved, the complexity of an entire organ would still need to be mimicked. The heart, for instance, contains a variety of cells in a delicate dance within a structure that includes chambers, vessels, and pumps. How do our cells know to design such complex growth?

This question is one that has kept Michael Levin awake at night. “How does a single cell reliably self-assemble into a snake or ostrich or fish? It’s a remarkable process,” says Levin, a Tufts University professor and director of the Tufts Center for Regenerative and Developmental Biology. He believes one answer might lie in electricity.

Each and every cell has an electric flow across its membrane, says Levin, “and, in fact, cells spend a lot of energy maintaining various electrical signals that they’re sending out to themselves and other cells around them.” Levin says researchers have known for some time that the site of a wound produces an electrical field. But only recently have research instruments allowed this flow to be investigated at the molecular level.

Levin says electrical signals tell cells what to repair and how to re-create what was lost. Levin deciphered one of those cues, a protein in a tadpole that creates a flow of protons, which produces an electric field at the site of a lost tail, starting a voltage flow. “If you block that flow, the tail won’t grow back.” Levin took a tadpole that matured past the ability to regenerate a lost tail. He removed the tail, then manipulated proteins to turn on the switch. This “triggers tail regeneration and stops the tail growth when it’s complete. The tadpoles end up with perfectly sized tails like their siblings.”

Levin is now working with tissue engineer David Kaplan to develop what he calls a bioreactor, which could encourage the same regeneration in mammals, starting with rats. “Down the line, we hope to translate this into biomedical applications that can help people,” says Levin.

>> Scientists say the more they learn, the more they realize what lies beyond their grasp. “These are exciting times in stem cell biology, and there have been exponential advances,” notes Chien, the MGH researcher. “And at the same time, the gap between stem cell biology and true regenerative medicine has never been wider.”

Some diseases, however, might be cured with changes to a single cell. Jaenisch’s lab at the Whitehead Institute created iPS cells from a mouse with sickle cell anemia, a blood disorder. They corrected the gene that causes the disease, then coaxed those cells into adult blood stem cells. Upon injection, stem cells found their way to the animal’s bone marrow and cured the disease. Demonstrating the promise of adult stem cells, a Colombian woman received an entirely new windpipe last year. The donor pipe came from a cadaver, was stripped clean of its original cells, and then was repopulated with the patient’s adult stem cells, which grew into the appropriate tissues.

But when it comes to cultivating entire organs from scratch, research is still in its infancy. What energizes scientists today, however, is the promise that iPS cells hold for a deeper understanding of diseases. George Murphy, a researcher at the Boston University Center for Regenerative Medicine, likens iPS cells to a flight recorder that contains information on a crash. “You can see all the events that led up to this disastrous event,” he says. “You can take a cell from a patient with a genetic disease and replay the onset of that disease again and again.”

Another source of enthusiasm is the potential for drug discovery. Lab animals do not always show how a chemical will affect humans, but lab-created human tissue may soon offer a rapid and efficient model for drug testing.

Scientists caution that the ultimate promise of readily available, personally matched tissue may remain decades away. Still, the pace of discovery has raced ahead, surprising even those involved in the search. “This is the ultimate in terms of creative science, to think about cells capable of becoming anything,” says Dr. David Scadden, co-director of the Harvard Stem Cell Institute. “The field is wide open for innovation.”

20091007-11

“If somebody told me they overdosed on Tylenol, I’d laugh if it hadn’t happened to me,” says Allison Sullivan, of Dover, N.H., who became seriously ill this past spring after taking too many Extra Strength Tylenols while feeling sick

Acetaminophen, the active ingredient in Tylenol and other drugs, can have serious side effects if overused

BostonGlobe.com, October 6, 2009, by Carolyn Y. Johnson  —  When Allison Sullivan started feeling sick this spring, she thought nothing of taking Extra Strength Tylenol to get through the misery of what seemed like a stomach flu. She was used to taking the drug for migraines, and never thought of it as a serious medication.

Days later, she was so disoriented she could not remember how many pills she had taken, and her liver was failing because she had overdosed on acetaminophen, the active ingredient in Tylenol. In pain and near death, Sullivan was taken to Massachusetts General Hospital and put on the liver transplant list. Her mother and sister flew in from the West Coast, fearing she would not live.

“So many people take Tylenol for nothing, just because they have a headache or whatever – nobody thinks it could hurt them,” said Sullivan, a 33-year-old resident of Dover, N.H., who has recovered but still has tests of her liver function once a month. “If somebody told me they overdosed on Tylenol, I’d laugh if it hadn’t happened to me. It’s almost like Americana.”

Sullivan’s scare sheds a light on an issue that has recently caught the attention of federal regulators: the potential for acetaminophen, the active ingredient in Tylenol and an often-overlooked component of drugs that range from Vicodin to some formulations of NyQuil, to have toxic effects on the liver if too much is taken.

Acetaminophen is safe and effective when taken as directed. What concerns medical professionals is that the commonly used drug can – unbeknownst to many of the people who take it and may think of it casually – have severe effects if misused.

According to numbers collected by the American Association of Poison Control Centers, 348, or nearly a third of the poison-related deaths in 2007 involved acetaminophen – 208 from acetaminophen in combination with another drug, and 140 from acetaminophen alone. Poison Control centers also reported 34,953 calls involving acetaminophen in combination with another drug, and 57,325 calls regarding acetaminophen in 2007.

About half of acetaminophen overdoses are intentional, because they are an accessible way to commit suicide; but that means about half arise because people inadvertently take too much of the drug. Acetaminophen is most familiar as Tylenol, but is also part of prescription painkillers like Percocet and Vicodin and present in over-the-counter drugs like some forms of Benadryl and Triaminic.

“Somewhere along the way, acetaminophen entered the therapeutic lexicon as safe, proven, as a completely acceptable over-the-counter drug that was free of baggage,” said Dr. Raymond T. Chung, chief of hepatology at Massachusetts General Hospital. “The remarkable fact is that its toxicity has always been known about . . . Somewhere along the way, a culture of permissiveness took root, and with that sort of faded away the sense of threat.”

Given the enormous number of people who take acetaminophen each year, the liver side effect is rare, and doctors are not suggesting that people stop taking the drug. Still, some doctors – and the US Food and Drug Administration – have been scrutinizing acetaminophen because it is a leading cause of acute liver failure. Dr. William M. Lee, founding principal investigator of the Acute Liver Failure Study Group, says that there are an estimated 2,000 cases of acute liver failure each year, about 40 percent of which are due to acetaminophen overdoses. Furthermore, he said, many other people are hospitalized with serious liver injury and would not be counted in that number.

Lee said that one striking thing was that new drugs now sometimes fail in development or are rejected by regulators because of effects on the liver. He cited Exanta, an anticoagulant developed by AstraZeneca, that never made it onto the market because of a potential risk of severe liver injury. Meanwhile, acetaminophen’s potential toxic effects – which are entirely preventable – are not clear to all consumers.

The scenarios, he said, often include someone who is taking medication for chronic pain and may also be using alcohol or have an underlying liver problem, or not be eating well. But it also can be as simple as a patient being told to take two painkillers every four hours following surgery, regularly taking three because of intense pain.

“That’s kind of getting up to the area where if other things weren’t in place – like you weren’t eating well – that you could certainly develop toxicity,” Lee said. “It’s just tragic to see someone die after bunion surgery.”

This spring, the FDA issued a rule that labels for over-the-counter pain relievers and fever reducers include warnings about safety risks, such as liver damage. Then this summer, the FDA sought the advice of a joint advisory committee on what changes, if any, need to be made. In a two-day meeting, advisory committee members narrowly voted to recommend eliminating combination prescription products that contain acetaminophen. They also advised lowering the recommended maximum total daily dose of acetaminophen from its current four grams per day, and voted to recommend reducing the maximum single adult nonprescription dose. The FDA has not yet acted on the recommendations.

“It’s not been made clear enough to consumers that you can get acetaminophen from many different places,” said Dr. Peter Lurie, deputy director of the Health Research Group at Public Citizen, a consumer advocacy organization, who said the recommendations were a step in the right direction.

However, some doctors expressed concern that patients would stop taking the drug altogether, even though the side effect is a result of misusing the drug – and switching to another drug could have negative side effects. Non-steroidal anti-inflammatory drugs such as ibuprofen carry a risk of gastrointestinal bleeding. The Consumer Healthcare Products Association, a trade group for companies that manufacture over-the-counter medicines, critiqued some of the recommendations, and emphasized the safety of acetaminophen when used as directed.

Dr. Dennis Dimitri, president of the Massachusetts Academy of Family Physicians, said that most physicians do not encounter patients who suffer from misusing acetaminophen, and said he had mixed feelings about the recommendations. What the debate about acetaminophen correctly highlights, he said, is a point that has been missing from the discussion of using any medication: Precautions should be taken.

“I think there’s a false impression on the part of many people that because something is available without a prescription, that must mean it’s perfectly safe,” Dimitri said. “The fact of the matter is any medication you take, whether it be a prescription drug, an over-the-counter drug, an herbal supplement or vitamin, or other medication has some potential for causing problems.”

That point hits home with Sullivan, who said she has gone over all the drugs that she takes now to be alert for potential interactions.

“It’s so not a drug when you think about it, and that’s how most people look at it,” she said. “I was completely thrown.”

By Gabe Mirkin MD, Autumn 2009  —  You can tell if you are at high risk for diabetes if you store fat primarily in your belly. Pinch your belly; if you can pinch an inch, you are at increased risk and should get a blood test called HBA1C. Having high blood levels of triglycerides and low levels of the good HDL cholesterol that helps prevent heart attacks also increases your risk for diabetes.

When you eat sugar or flour, your blood sugar rises too high. This causes your pancreas to release insulin that converts sugar to triglycerides, which are poured into your bloodstream. Then the good HDL cholesterol tries to remove triglycerides by carrying them back into the liver, so having high blood levels of triglycerides and low blood levels of the good HDL cholesterol are both individual risk factors for diabetes.

High blood levels of insulin constrict arteries to raise blood pressure, so many people who have high blood pressure are also prediabetic. High insulin levels also constrict the arteries leading to your heart to cause heart attacks directly. People with insulin resistance have an increase in small, dense, low-density lipoprotein (LDL) cholesterol, which is more likely to cause heart attacks than the large, buoyant regular LDL cholesterol. High levels of insulin also cause clotting to increase your risk for heart attacks.

A study from Sweden showed that many people discover that they are diabetic only after they have had a heart attack. Researchers recorded blood sugar levels in men who had had heart attacks and then did sugar tolerance tests at discharge and three months later. They found that 40 percent had impaired sugar tolerance tests three months later. This suggests that 40 percent of people who have heart attacks are diabetic, even though they may not know it. The authors recommend that all people with heart attacks be tested for diabetes (1).

You can help to prevent diabetes and heart attacks by avoiding sugar and flour, exercising and eating lots of vegetables.

  • 1) Lancet 2002; 359: 2140-44.

    2) Current concepts in insulin resistance, type 2 diabetes mellitus, and the metabolic syndrome. American Journal of Cardiology, 2002, Vol 90, Iss 5A, Suppl. S, pp 19G-26G. JEB Reusch. Denver Vet Adm Med Ctr, 1055 Clairmont St, M-C 111 H, Denver,CO 80220 USA.

    3) A rational approach to pathogenesis and treatment of type 2 diabetes mellitus, insulin resistance, inflammation, and atherosclerosis. American Journal of Cardiology, 2002, Vol 90, Iss 5A, Suppl. S, pp 27G-33G. P Dandona, A Aljada. Dandona P, WNY, Diabet Endocrinol Ctr, 3 Gates Circle, Buffalo,NY 14209 USA.

    4) Rationale for and role of thiazolidinediones in type 2 diabetes mellitus. American Journal of Cardiology, 2002, Vol 90, Iss 5A, Suppl. S, pp 34G-41G. HE Lebovitz. SUNY Hlth Sci Ctr, Dept Med, Div Endocrinol, 450 Clarkson Ave, Brooklyn,NY 11203 USA.

    5) Pathogenesis of skeletal muscle insulin resistance in type 2 diabetes mellitus. American Journal of Cardiology, 2002, Vol 90, Iss 5A, Suppl. S, pp 11G-18G. KF Petersen, GI Shulman. Shulman GI, Yale Univ, Sch Med, Howard Hughes Med Inst, Gen Clin Res Ctr, Dept Internal Med, Dept Cellular & Mol Physiol, 295 Congress Ave, BCMM 254C, New Haven,CT 06510 USA

www.DrMirkin.com

20091007-10


Town Prospers as Witch Hazel Sees Double-digit Growth
BostonGlobe.com, October 6, 2009, by David Filipov – Nothing signals the presence of a venerable remedy in this quiet suburb 30 minutes southeast of Hartford. No garish signs, no proud slogans, no roadside stands proclaim the world-famous properties of the humble shrub that flourishes beyond the shores of Lake Pocotopaug.

The only clue is the lone plant growing a dozen feet high in front of a brown stucco building on Connecticut Route 66. This is witch hazel, hamamelis virginiana. It stands outside the business that has made the astringent distilled from the shrub’s ridged bark a household staple for generations.

Native Americans used witch hazel as a cure-all. So did the early European settlers. Your grandmother used it; a bottle of the clear, nut-scented liquid is probably still tucked away in the back of her medicine cabinet. And so, perhaps without your knowing it, have you: Witch hazel from East Hampton is an important ingredient in shampoos, mouthwashes, high-end facial toners, acne treatments, and eyewash, to name just a few items.

Because of that, Dickinson Brands Inc., the world’s largest producer of witch hazel, has quietly prospered here, in what is arguably the witch hazel capital of the world.

Owners and employees say they have avoided the layoffs, furloughs, and pay cuts that have benighted so many companies. And in this season of shrinking sales and mounting losses, the privately owned company says it has experienced double-digit growth.

The challenge for Dickinson, which bottles and sells the astringent under the brand name Witch Hazel, is how to make the remedy relevant for today’s generations. “It’s become a part of Americana,” said Bryan Jackowitz, the company’s marketing director. “People say: ‘Oh yeah, yeah, I know Witch Hazel. My grandmother used it. What do I use it for?’ ”

No one at the factory knows for sure the origins of the name of the plant, a shrub that grows in northern forests and is distinguishable by its yellow flowers, which bloom in late autumn, after most trees have shed their leaves. A popular version has it that “witch” is derived from an old English word, “wyche,” which means pliant or bendable. The word “hazel,” it is suggested, may have come from the use of twigs from the shrub as divining rods, the way twigs from the hazel plant once were used in England. Dickinson is hoping to tap into the increased demand for all-natural skin-care products. In recent years, it has phased out the word “astringent” from one of its two versions of Witch Hazel, the yellow-label one, which it now markets as “pore perfecting toner.” The more powerful blue-label Witch Hazel, for treatment of bites, scrapes, and irritation, is still sold as “100 percent natural astringent.”

The approach jibes with the public’s renewed interest in historical remedies with a short list of recognizably natural, home-grown ingredients, said Laurie Demeritt, president of the Hartman Group, a market research firm based in Bellevue, Wash.

“That fact that grandma used it is probably more of a plus than a minus to some of these folks,” she said.

Jackowitz declined to provide specific financial figures for the company. But Jeffrey J. O’Keefe, town manager of East Hampton, said Dickinson has helped buoy the town’s fortunes.

“We’re probably one of the few towns that were able to weather the recession last year,” O’Keefe said. “They are a very important part of the fabric of this community.”

Since 1866, the Dickinson astringent has been composed of the same two natural ingredients, alcohol and witch hazel. More recently, a sister company of Dickinson Brands, American Distilling Inc., has been producing and selling witch hazel – the ingredient – in bulk to hundreds of companies worldwide.

The Dickinson company was founded by the Rev. Thomas Newton Dickinson, who made his fortune selling uniforms to Union forces during the Civil War before switching to witch hazel.

The families of some employees have roots that go back almost as far. Alfred Bowser, a Dickinson employee for about 30 years, is the fifth generation of his family to work here.

“That should tell you how much witch hazel is in my blood,” Bowser said on a factory walkway overlooking a pile of witch hazel wood chips, waiting to be loaded into a giant silo, the first step in the process of pressing and distilling them into the astringent liquid. “About 98 percent witch hazel.”

Curtis Strong, who oversees the harvesting of the shrub, is also a fifth-generation employee. His great-grandfather used to cut the plant and load the branches into horse- and ox-drawn carts for delivery to the factory.

His grandfather taught him how to identify witch hazel, which is tricky because the harvesting is done in winter, when the branches are bare.

Strong still prefers an ax to a chainsaw. But he also personifies the company’s modernization – an electrical engineer, he designed the control panel that runs the automated, zero-waste distilling process.

The Jackowitz family are relative newcomers, but they also think of themselves as part of the lore. “The father of modern Witch Hazel” is how Bryan Jackowitz refers to his father, Edward C. Jackowitz, the chief executive who acquired the company in 1973.

Sometimes the product’s rich history as an all-round remedy intrudes upon the company’s attempt to place the Witch Hazel brand as a gentle skin-care product for the modern woman.

“Back in the day, they used to use it a lot on the animals” who had cuts and scrapes,” Bowser recalled. “As a matter of fact, most of the race horses of today use it. After they work out, they wipe the horses with it. Yep, cools the horses down.”

Ann Silvio of the Globe staff contributed to this report.

20091007-1

Axolotl- a unique type of Tiger Salamander that fails to undergo metamorphisis and so stays in larval form its whole life. You may have heard about them through the soothing voice of David Attenborough. Axolotl can breath through lungs, gills or even its skin, and it has amazing healing powers. Axolotl’s are fully capable of complete limb re-growth.

Prior to the growth of Mexico city, the Axolotl was native to both Lake Xochimilco, and Lake Chalco. Because of human construction only the remnants of Lake Xochimilco  canals can be seen today. So now the Axolotl is very high on the endangered species list.

“Fortunately”, the use of the Axolotl as a laboratory animal ensures its survival (in captivity). “It has the added scientific attraction of having especially large embryos, making it easier to deal with under laboratory conditions. Its embryo is also very robust, and can be spliced and combined with different parts of other axolotl embryos with a high degree of success.”

GoogleNews.com, October 6, 2009, by Peter Ker  —  HOPES that a quirky aquatic species could lead Australian scientists to major medical breakthroughs are resting with the federal Environment Department.

Melbourne medical researchers have lobbied the department to allow the importation of axolotls – sometimes dubbed ”Mexican walking fish” – in the belief they could help research into regenerative medicine in humans.

Native to Mexico but almost extinct in their natural environment, the axolotl has excited medical scientists for its ability to regenerate body parts.

Dr James Godwin from the Australian Regenerative Medicine Institute said axolotls were capable of regenerating bones, limbs and even parts of their heart and head when lost to predators.

Dr Godwin, who submitted the application to have axolotls added to Australia’s live import list, said the institute wanted to learn more about the species and their incredible regenerative powers.

Axolotls can be bought in pet stores around Australia, but cannot legally be brought into the country.

Dr Godwin said the genetic background of axolotls in pet stores was never known, and his research would require a special type of axolotl to be imported from the US.

Australia has a bad record of allowing exotic species such as rabbits and cane toads into the country. But in 2005 the Australian government investigated the risk of axolotls establishing themselves in the wild, and the risk was found to be very low.

The Environment Department has invited submissions before it makes a final decision.

More Info On the Endangered Axolotl

Ambystoma mexicanum

Axolotl

20091007-2

Synonyms Mexican Salamander
Mexican Walking Fish

Range        Mexico – originally Lakes Xochimilco and Chalco

IUCN Red Book          Critically Endangered

CITES        Appendix II

First described           Shaw, 1789

A leucistic axolotl.

Description
The Axolotl is the largest member of the family Ambystomatidae, with specimens over 43 cm (17 inches) total length known, though typical adult length is somewhere between 20 and 28 cm (8 – 11 inches). Unlike most of the group, this species exists totally in the perrenibranchiate state, retaining some larval features into adulthood (gills, larval skin morphology, caudal fins, etc). It becomes sexually mature in this state, and it develops small rudimentary lungs with which it can augment gaseous exchange if necessary, hence the term “cryptic metamorphosis”. Suspected to be an offshoot from the Tiger Salamander complex (Ambystoma tigrinum, A. mavortium, etc), metamorphosed specimens bear close resemblance in pattern and colouration to the sympatric race of Tiger Salamander, A. valasci, though exact scientific nomenclature has yet to be resolved. Most scientific authorities recognise that it is a true obligatory neotene (Gould 1977), that can only be induced to metamorphose by hormone treatment. Accounts of spontaneous metamorphosis are generally attributed to the influence of hybridisation with the tiger salamander, or in some cases, to water chemistry: unusually high levels of iodine can affect the levels of growth hormones.

20091007-3

Axolotls are often prized for their variety of color mutants. Here, an albino, a golden albino, and a black melanoid.

Several other members of the Ambystomatidae occur in wholly perrenibranchiate populations in Central America, including A. andersoni, A. taylori and the CITES-listed A. dumerilii, the last species being noted for its hyperfilamentous gills. Although these are all sometimes referred to as axolotls, the name “axolotl” is best confined to the species Ambystoma mexicanum.

Captive axolotls come in many colour varieties, including the traditional wild type (brown, grey or almost black, with dark spots), albino (golden with pink eyes), leucistic (white with black eyes), melanoid (absence of iridescent pigment and very little yellow), axanthic (lacking iridescent and yellow pigment), and any combination of these, such as white albino (white with pink eyes), or melanoid albino (white with almost invisible yellow spots and no shiny pigment).

Natural Range and Habitat          
The Axolotl was originally native to Xochimilco and Chalco, two freshwater lakes south of Mexico City. Sadly, Chalco is now gone, and Xochimilco survives only as a network of canals and lagoons. These bodies of water are muddy bottomed and rich in plant and animal life.

20091007-4

An appopriate setup for a group of axolotls. Fine sand is used to prevent problems associated with gravel ingestion. A large volume of water buffers the system against water quality problems. A large number of hiding places and visual barriers help to prevent problems with aggression.

Housing
Never leaving the water, these salamanders require completely aquatic conditions. A 60 x 30 x 37 cm (24 x 12 x 15 inches) aquarium is adequate for two adults. Water depth is not important, but 15 cm (6 inches) or more is recommended. Not being used to small gravel in their natural habitat, substrate should consist of either sand or pebbles/gravel that is too large to swallow. Axolotls feed by evacuating their mouths of water, then suddenly opening them very wide, thus causing anything in the immediate vicinity to enter, be it food or substrate, so it’s important to bear this in mind. An aquarium bare of substrate, while perhaps less attractive, is safest and generally easier to clean. In the wild, the water temperature in Xochimilco rarely rises above 20°C (68°F), though it may fall to 6 or 7°C (43°F) in the winter, and perhaps lower. In captivity, any temperature between 14 and 22°C (57 to 72°F) is reasonable for adults. Any temperature over 25°C (77°F) is unsuitable for anything more than a few days. High temperatures stress axolotls, and anorexia, fungal and bacterial infections often result. Filtration, if required, can be accomplished in any of the usual ways, but it is known that axolotls are stressed by flowing water, so make sure that the water flow from a power filter, for example, is reduced or diffused in such a way as to prevent large volumes of water flowing about the tank at speed. Plants are not essential, unless breeding is planned. In any case, either choose robust plant species or those easily replaced, because axolotls tend to dredge up and damage delicate plants in their tank. Hiding places, though not essential, are a good idea – axolotls seem to like to have the option to hide at times. Lighting is not required either, unless ease of viewing is required. Remember to ensure water quality is maintained by making regular water changes – 20% or so every two weeks is usually adequate unless large numbers are being kept in a small tank or over feeding is taking place. Remember to treat tap water with a water conditioner prior to use as it may contain harmful substances (chlorine, chloramine, metals).

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Feeding
Axolotls are voracious feeders. They will eat earthworms, tubifex worms (live, frozen, or freeze-dried – sometimes incorrectly labelled as “bloodworms”), bloodworms (the larvae of chironomid midges), blackworms (an aquatic relative of earthworms), crustaceans like shrimp, pieces of fish (avoid salted fish and marine fish), strips of beef heart or other lean red meat, small invertebrates like insects, tadpoles and feeder fish. The last two should probably be avoided because they often harbour parasites, and these can be passed on to the axolotls. Most axolotls will also eat the sinking pellets sold commercially to feed trout and salmon. These are an excellent food. Products such as Tetra’s Reptomin will also be eaten, but because they float, they’re generally not ideal. Large adult axolotls will consume several whole “night crawler” earthworms with no difficulty. The warmer the axolotls are kept, the more regularly they should be fed. As much food as they will eat in 15 minutes is a good guide. If kept at 22°C (72°F) they should only require feeding every two to three days. Don’t leave food to spoil the water after feeding.

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Breeding
Axolotls can reach sexual maturity anywhere between 6 months and in excess of a year, usually at about 20 cm (8 inches). Sexually mature males have a much more swollen cloaca than sexually mature females. It’s generally a not a good idea to breed female axolotls until they reach at least 18 months of age. This gives them time to reach their full size and condition. Most sources state that the breeding season for axolotls is from December to June, although most success is reported in December and January, though breeding can take place at any time of the year. If the water temperature and light levels are allowed to vary throughout the year, spawning will usually take place in late winter. If kept at roughly the same temperature throughout the year, spawning can take place at any time. Some people recommend a sudden decrease in water temperature to stimulate breeding, but this generally only stimulates the male, but if the water temperature is allowed to vary with the seasons, though not allowed to get too warm in summer, mating usually takes place once or twice a year in winter. Female axolotls shouldn’t be allowed to breed more than once every two months for health reasons.

The breeding tank should be furnished with plants (plastic plants are good because they don’t rot) for the female axolotl to affix her eggs. Flat, rough pieces of stone should be placed on the bottom of the tank onto which the male can deposit his spermatophores.

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After the courtship dance and uptake of the sperm capsule by the female, it’s a good idea to remove the male. Spawning takes place between a few hours and two days later. Eggs are laid individually, usually on plants. There may be between one hundred and over a thousand eggs laid in one spawning, depending on the size of the female. After the female has finished laying, it’s best to remove her too. Eggs hatch after 14 days at 24°C (75°F), and after a few hours, the larvae will begin to eat anything small enough to fit in their mouths. Young daphnia, micro worm, and newly-hatched brine shrimp (minus the cyst shells) are ideal first foods. Once the larvae are 3 cm (just over 1 inch) in length, they can take larger foods, such as frozen bloodworm, chopped earthworms, chopped tubifex and white worms. Most bloodlines of axolotl are quite cannibalistic, so don’t keep many in one tank. At 24°C (75°F), they should be fed twice a day as much as they will eat in 20-30 minutes, until they measure 10 cm (4 inches). Less frequent feedings will result in lots of lost limbs, gills and deaths. At lower temperatures they can be fed less frequently. Once past 15 cm (6 inches), they become more docile. Well fed and kept at 24°C (75°F) it is possible for them to reach 25 cm (10 inches) and sexual maturity in less than 6 months.

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