What it’s used for: Tyrosinemia Type 1 (a rare genetic disorder that can cause liver failure in infants and young children)
Where it’s from: Red bottlebrush shrub
Sold by: Swedish Orphan International/Rare Disease Therapeutics
Can traditional Chinese medicine become a potent source of new drugs for the West? Asia’s richest man is betting on it.
by Kerry A. Dolan
Hold your nose if you take a tour of Shanghai Hutchison Pharmaceuticals’ factory on the industrial outskirts of China’s largest city. It’s where they make She Xiang Bao Xin, a pill made from synthetic deer musk, synthetic ox gallstones, an enemy-repelling toad secretion and four herbs. The odor hits you on the first floor, where masked workers shake the pills on enormous metal trays to separate the oversize ones. One floor up another large batch is brewing in a dozen 3-foot-tall metal vats. Adherents of traditional Chinese medicine cherish these pills for their heart-protecting powers. Shanghai Hutchison sold 200 million doses last year for $8.7 million, with sales up 17% from 2005.
Forty-five minutes away from the musk are the gleaming labs of Shanghai Hutchison Pharma’s sibling company, Hutchison MediPharma. This place is easier on the senses. A cadre of Chinese nationals with medical degrees and doctorates in biology and chemistry from North American universities and résumés that include Pfizer, Johnson & Johnson and Amgen, screen thousands of chemicals found inside Chinese herbs and plants on the latest high-speed machines. They’re looking for promising drug candidates to patent, like all the many labs in Shanghai’s pharma gulch. Roche is right across the street, Novartis and Eli Lilly down the block.
The two companies, Shanghai Hutchison and Hutchison MediPharma, straddle the old and new worlds of Chinese medicine, yet, amazingly, they share the same parent, Hutchison China MediTech, or Chi-Med. The Hong Kong company is going forward and backward at once. It aims to expand the market for traditional Chinese medicine while harvesting modern drugs from Asian flora. “It’s a massive objective we’ve set. We’re trying to modernize and globalize Chinese medicine,” says Chi-Med Chief Executive Christian Hogg, 42.
The name Hutchison can only mean one thing: the presence of Li Ka-shing, Asia’s richest man and chairman of the globe-girdling conglomerate Hutchison Whampoa, which has invested $72 million in Chi-Med since its inception in 2000. Chi-Med listed 28% of its outstanding shares on London’s AIM exchange last May; Hutchison owns the other 72%.
Chi-Med is a minnow compared with Hutchison Whampoa’s other concerns. The company lost $10 million last year on revenue of $58 million, up 52% over 2005, mostly from sales of the musk pill, a treatment for respiratory infection and an angina drug. But Li, 78, is so keen on the growth opportunity that he devotes some of his valuable time to signing off on Chi-Med joint ventures.
MediPharma has two drugs in mid-stage clinical trials in the U.S., one to augment radiation therapy on head and neck cancer and the other to treat Crohn’s disease, a chronic inflammation of the digestive tract. The active ingredient in the Crohn’s drug is a chemical found in an herb common in China called Indian echinacea or rice bitters. If approved, the drug would compete with J&J’s Remicade, which brought in $3 billion last year from treating Crohn’s and other diseases.
In November Procter & Gamble signed a two-year agreement with Chi-Med to screen traditional medicines for new ingredients for P&G beauty products. That same month Merck KGaA of Germany agreed to develop anticancer drugs with Chi-Med. The terms of these deals were not disclosed.
China’s approach to medicine is in transition. Many doctors trained in Western medicine scoff at traditional Chinese medicine’s lack of scientific grounding (even as they plumb its medicine cabinet for secrets). “We are not a folklore-based company,” says Samantha Du, the U.S.-trained biochemist in charge of Chi-Med’s drug development. The nation’s booming middle class readily embraces Western medicine but thinks nothing of adding a dash of ancient herbs to a meal. Chi-Med’s business development manager, Michael Leung, lives in Hong Kong with his wife, a private banker. “She takes bird-saliva nest and puts it in soup to help her skin look young,” he says.
Sales of Western pharmaceuticals in China grew 91% in five years to $13 billion in 2005, according to the Boston Consulting Group. That’s one-twentieth the size of the U.S. market but roughly equal, by some estimates, to the traditional Chinese medicine market. Some of this growth has been tainted by corruption. In 2005 Zheng Xiaoyu, the former head of China’s State Food & Drug Administration, was booted from office for taking bribes to obtain drug approvals, the Chinese media alleged. A fake version of one drug and improper production of another killed 21 people last year. Since last fall the agency has revoked 350 manufacturing licenses and vowed to tighten inspections, according to Chinese media.
A wave of herbal prospecting in China in the 1990s turned up little for several big firms such as Bayer, Eli Lilly and Pfizer. Novartis, however, scored a hit in 1998 with Coartem, an antimalarial drug that combines artemisinin, an extract from sweet wormwood, with a compound called lumefantrine. Sweet wormwood is used by Chinese herbalists to treat fever.
Last year MediGene of Germany got approval from the FDA for U.S. marketing of an ointment extracted from green tea leaves to treat genital warts. Sales in the U.S. are being handled by Bradley Pharmaceuticals. Cephalon sells a leukemia drug called Trisenox (arsenic trioxide). A similar active ingredient, arsenic stone, has long been used in China and elsewhere to treat fevers, depression and arthritis.
Chi-Med’s plant-finding took root in 1995, when Christian Hogg, an Englishman then at Procter & Gamble, was sent to introduce the Chinese to the company’s laundry detergents. While there, he got to know managers at Hutchison Whampoa, which owns 30% of P&G’s Chinese unit. In 1999 P&G transferred Hogg to Brussels, but he kept his passion for China.
Within six months he had hatched a business plan to bring Chinese medicine to the West, to be sold in fancy shops that would also offer acupuncture, massage and herbal treatments. Hutchison Managing Director Canning Fok liked that idea but also saw an opportunity to get in on sales of traditional Chinese medicine in China, a segment of the pharma business that had not yet opened to foreign investment. In 2000 Hutchison China MediTech was born. Hogg got enough money to go off and build the first few of what are now six Chinese herbal medicine shops in London, operating under the name Sen.
In 2000, when China finally opened the traditional medicine sector to foreign investment, Chi-Med was one of the first in. In 2001 it invested $35 million in joint ventures with two Chinese medicine companies, including the newly renamed Shanghai Hutchison Pharmaceuticals, and in 2005 put $17 million into a third firm.
Hogg wanted to set up an R&D arm but hadn’t the faintest idea how to run one. A recruiter found Samantha Du, a Chinese-born biochemist with a Ph.D. from the University of Cincinnati and eight years’ experience at Pfizer. Du, now 42, was being groomed for management at Pfizer but decided it might be better to run her own operation. She moved from Groton, Conn. to Hong Kong in 2001.
The next year Du set up a new research lab in Shanghai, which has a good supply of disciplined scientists and is cosmopolitan enough to lure back Chinese scientists from U.S. drug firms. Chi-Med promised her a $27 million startup budget. Du recruited from companies such as Amgen, Pfizer and J&J.
Plant-derived drugs, called botanicals, are devilishly hard to develop because herbs and flowers contain so many chemical entities that it’s hard to pinpoint their biological targets at a molecular level. Still, pharmacy shelves are chockablock with drugs that are either derived from plants (morphine, from poppies) or inspired by herbal remedies (aspirin, from an ancient willow-bark extract). The best-understood Chinese herbs have already been well covered, but in the past few years Du and her staff have screened 10,000 traditional Chinese medicines looking for ones that influence cancers and the immune system and have come up with a handful of new prospects.
In 2004 the FDA streamlined the development of botanical drugs by allowing drugmakers to skip early-stage safety trials if a drug candidate comes from an herbal remedy that is safe and legally marketed already. Chi-Med took its Crohn’s disease drug into midstage trials two years earlier than it would have otherwise. Results are expected later this year. Chi-Med’s second compound, which sensitizes head and neck cancer cells to radiation, is approved for use in China. U.S. trials are under way.
Funds to fuel Chi-Med’s research will come from the brisk sales of deer-musk pills and Hutchison Whampoa’s deep purse. In a few years China’s economy will develop enough to support lucrative Western-style drug reimbursements. Says Hogg: “We’ll see 10% to 20% growth for the next 10 to 20 years.”
Mouse Baldness Treatment – Hope For Humans
Scientists at the U. of Penn School of Medicine have found that hair 1) ___ in adult mice regenerate by re-awakening genes once active only in developing embryos. These findings provide unequivocal evidence that, like other animals such as newts and salamanders, mammals have the power to 2) ___. A better understanding of this process could lead to novel treatments for hair loss, other skin and hair disorders, and wounds. It was shown, that 3) ___ healing triggered an embryonic state in the skin which made it receptive to receiving instructions from wnt proteins, which are a network of proteins implicated in hair-follicle development. It was previously believed that adult mammal 4) ___ could not regenerate hair follicles, and that, mammals had no true regenerative qualities. However, researchers found that wound healing in a mouse model created an “embryonic window” of opportunity. Dormant 5) ___ molecular pathways were awakened, sending stem cells to the area of injury. Unexpectedly, the regenerated hair follicles originated from non-hair-follicle 6) ___ cells. Scientists, now, can influence wound healing with wnts or other 7) ___ that allow the skin to heal in a way that has less scarring and includes all the normal structures of the skin, rather than just a scar. By introducing more wnt proteins to the wound, the researchers found that they could take advantage of the embryonic 8) ___ to promote hair-follicle growth, thus making skin regenerate instead of just repair. Conversely by 9) ___ wnt proteins, they also found that they could stop the production of hair follicles in healed skin. In fact, increased wnt signaling 10) ___ the number of new hair follicles. This suggests that the embryonic window created by the wound-healing process can be used to manipulate hair-follicle regeneration, leading to novel ways to treat hair loss and hair overgrowth. (Source: Nature 17 May 2007).
ANSWERS: 1) follicles; 2) regenerate; 3) wound; 4) skin; 5) embryonic; 6) stem; 7) proteins; 8) genes; 9) blocking; 10) doubled
“an interesting point is that, this spiral pattern [found in plants] has also been observed in the arms of galaxies.”
“could these number sequences and the golden angle growth patterns be used to measure human interference with the environment against various control subjects?”
“a curious relationship also exists between such [pattern] series and fractal space. This exists at all magnitudes, from repeating amino acid groups in DNA all the way to galaxy formations.”
The Mathematical Lives of Plants
By Julie J. Rehmeyer
The seeds of a sunflower, the spines of a cactus, and the bracts of a pine cone all grow in whirling spiral patterns. Remarkable for their complexity and beauty, they also show consistent mathematical patterns that scientists have been striving to understand.
Each yellow nub in the center of this daisy is actually its own miniature flower, complete with a full set of reproductive organs. The buds form interlocking clockwise and counterclockwise spirals.
A surprising number of plants have spiral patterns in which each leaf, seed, or other structure follows the next at a particular angle called the golden angle. The golden angle is about 137.5º. Two radii of a circle C form the golden angle if they divide the circle into two areas A and B so that A/B = B/C.
The golden angle is closely related to the celebrated golden ratio, which the ancient Greeks and others believed to have divine and mystical properties. Leonardo da Vinci believed that the human form displays the golden ratio.
The golden angle is the angle subtended by the smaller (red) arc when two arcs that make up a circle are in the golden ratio.
Plants with spiral patterns related to the golden angle also display another curious mathematical property. The seeds of a flower head form interlocking spirals in both clockwise and counterclockwise directions. The number of clockwise spirals differs from the number of counterclockwise spirals, and these two numbers are called the plant’s parastichy numbers (pronounced pi-RAS-tik-ee or PEHR-us-tik-ee).
These numbers have a remarkable consistency. They are almost always two consecutive Fibonacci numbers, which are another one of nature’s mathematical favorites. The Fibonacci numbers form the sequence 1, 1, 2, 3, 5, 8, 13, 21 . . . , in which each number is the sum of the previous two.
This sunflower has 21 clockwise and 34 counterclockwise spirals.
The Fibonacci numbers tend to crop up wherever the golden ratio appears, because the ratio between two consecutive Fibonacci numbers happens to be close to the golden ratio. The larger the two Fibonacci numbers, the closer their ratio to the golden ratio. But this relationship doesn’t fully explain why parastichy numbers end up being consecutive Fibonacci numbers.
Scientists have puzzled over this pattern of plant growth for hundreds of years. Why would plants prefer the golden angle to any other? And how can plants possibly “know” anything about Fibonacci numbers?
Initially, researchers thought these patterns might provide an evolutionary advantage by somehow promoting plants’ survival. But more recently, they have come to believe that the answer lies in the biochemistry of plants as they develop new leaves, flowers, or other structures. Scientists have not entirely solved the mystery, but a basic understanding of the process seems to be emerging. And the answers are sending botanists back to their electron microscopes to re-examine plants they thought they had already understood.
Mathematicians made the first contribution to the puzzle. In 1830, two brothers, Auguste and Louis Bravais, worked out a mathematical proof that spiral lattices generated by the golden angle have parastichy numbers that are consecutive Fibonacci numbers. But their proof still left the question of why the plants prefer the golden angle and Fibonacci numbers in the first place.
Plants form new seeds or buds from the center. In this picture, the circle labeled 0 would be the most recent bud. The circle labeled 1 would have been formed just previously, and it forms the golden angle with bud 0. Similarly, bud 2 forms the golden angle with bud 1. Buds 0, 13, and 26 form a clockwise spiral and buds 0, 8, 16, 24, and 32 form a counterclockwise spiral.
The first suggestion that the biochemistry of plant development might provide the key came in 1868. German botanist Wilhelm Hofmeister was studying the growing tips of plants, which contain cells that haven’t yet acquired a particular function in the plant. These unformed cells are called stem cells in plants and, derivatively, in animals as well. The stem cells form tiny bumps called primordia, which then turn into flowers, stems, or other plant structures.
The primordia form in a small region at the tip of a stem. Hofmeister proposed that the precise spot in which they form within that region is the spot that is furthest from older primordia. The primordia then move outward and downward along the stem as the tip continues to grow.
An image of the tip of a Norway spruce branch, viewed through an electron microscope, shows small buds that are called primordia. In this case, they will eventually turn into needles. The primordia form at the tip and then move outward and downward.
Images from electron microscopes have confirmed Hofmeister’s theory. Furthermore, in 2000, Didier Reinhardt of the University of Fribourg worked out the biochemistry within a plant that creates this behavior. As a primordium forms, it absorbs a plant hormone called auxin that promotes growth. The most auxin is left in the area furthest from other primordia, so the primordium moves in that direction.
But how does this explain the spiral patterns, golden angle, and Fibonacci numbers? Two physicists, Stéphane Douady and Yves Couder from the Laboratory for Statistical Physics in Paris, performed a compelling experiment in 1992 that tied these ideas together. They dropped a magnetized liquid into a dish that was magnetized at its edge and filled with silicone oil. The droplets were simultaneously attracted to the edge of the dish and repelled from one another.
When the team dropped the oil in slowly, the droplets moved directly away from each other. But when they increased the speed, two older droplets would repel the new droplet simultaneously. So instead of simply marching to one side or the other, the droplet would move in a third direction—at the golden angle from the line connecting the drop’s landing point with the previous droplet. The resulting pattern formed spirals.
In this movie (click here or on the image, above, to watch), a magnetized fluid drops into a pool of silicone oil. The droplets are attracted to the edge of the pool and repel one another. When they fall slowly, the droplets move in precisely opposite directions to one another. But when the speed increases, they move away from one another at the golden angle, ultimately forming spirals.
Douady and Couder
Douady and Couder’s result gave a beautiful analogy for plant growth, but Scott Hotton of Harvard University still wondered why the golden angle would emerge from this. He reduced Douady and Couder’s experiment to a simple mathematical model, which showed that the forces Hofmeister described—outward, downward, and away from other primordia—produced golden angle spirals.
But Douady and Couder’s work, along with Hotton’s, had a surprising implication. Golden angle spirals weren’t the only patterns that could emerge from Hofmeister’s forces. The flowers could also produce their primordia at angles of approximately 99.5º. In that case, the numbers of spirals in each direction would not be Fibonacci numbers, but the closely related Lucas numbers, which begin with 1, 3, 4, 7 . . . , and continue with the sum of each two consecutive numbers forming the next number. Researchers have identified a few plants that grow in this pattern.
The researchers also found some even more peculiar possibilities. Instead of producing primordia at the same angle each time, plants could produce them at angles that vary but repeat. For instance, Hotton found that the angle could be 131, then 88, then 88 again, then 131, then 89, then 87, then 131, then 315, and then go back to 131 and start over.
This cactus, a Mammilaria moellerana, has golden-angle spirals.
“What’s interesting about this is that the pattern that actually forms would be hardly distinguishable from the one where the angle was the same,” Hotton says. “You could actually see opposing pairs of spirals. You could count them and see that there were five in one direction and eight in the other. But the angles wouldn’t be the same every time; it would be following this periodic sequence.”
Do any plants show this peculiar growth pattern? Botanists are still working to find out. Some preliminary results suggest that such patterns exist, but no one has yet found any conclusive evidence.
Plants tend to arrange their stems and florets so that each successive one is at an angle of about 137.5° relative to the previous one. This Demonstration lets you see what would happen if plants used other angles.
Most of us feel a rush of righteous certainty in the face of a moral challenge, an intuitive sense of right or wrong hard to ignore yet difficult to articulate.
A provocative medical experiment conducted recently by neuroscientists at Harvard, Caltech and the University of Southern California strongly suggests these impulsive convictions come not from conscious principles but from the brain trying to make its emotional judgment felt.
Using neurology patients to probe moral reasoning, the researchers for the first time drew a direct link between the neuroanatomy of emotion and moral judgment.
Knock out certain brain cells with an aneurysm or a tumor, they discovered, and while everything else may appear normal, the ability to think straight about some issues of right and wrong has been permanently skewed. “It tells us there is some neurobiological basis for morality,” said Harvard philosophy student Liane Young, who helped to conceive the experiment.
In particular, these people had injured an area that links emotion to cognition, located in the ventromedial prefrontal cortex several inches behind the brow. The experiment underscores the pivotal part played by unconscious empathy and emotion in guiding decisions. “When that influence is missing,” said USC neuroscientist Antonio Damasio, “pure reason is set free.”
Bringing medical tools to bear on moral questions, cognitive scientists are invading the territory of philosophers, theologians and clerics.
Usually, the human brain is of two minds when it comes to morality — selfish but self-sacrificing, survivalist yet altruistic, calculating but also compassionate. Many dilemmas force a choice between the lesser of two evils, invoking a clash of competing neural networks, said Harvard neuroscientist Joshua Greene. Intuition tempers rational deliberation, especially when our actions to help some people will harm others.
At this level of inquiry, the mind is a special effect generated by neurons. Trust is a measure of neuropeptide levels, while fairness is an electromagnetic pattern in the right prefrontal cortex. Disrupt it with a strong magnet, as did University of Zurich researchers in 2006, and any sense of fair-dealing fades away like a radio station subsumed by static.
Not everyone reasons through moral conundrums in the same way, of course. Decisions hinge on family values, cultural heritage, legal traditions and religious beliefs — or on the kind of brain you can bring to bear on the problem.
At the University of Iowa Hospital, the researchers singled out six middle-age men and women who had injured the same neural network in the prefrontal cortex. On neuropsychological tests, they seemed normal. They were healthy, intelligent, talkative, yet also unkempt, not so easily embarrassed or so likely to feel guilty, explained lead study scientist Michael Koenigs at the National Institutes of Health. They had lived with the brain damage for years but seemed unaware that anything about them had changed.
To analyze their moral abilities, Dr. Koenigs and his colleagues used a diagnostic probe as old as Socrates — leading questions: To save yourself and others, would you throw someone out of a lifeboat? Would you push someone off a bridge, smother a crying baby, or kill a hostage?
All told, they considered 50 hypothetical moral dilemmas. Their responses were essentially identical to those of neurology patients who had different brain injuries and to healthy volunteers, except when a situation demanded they take one life to save others. For most, the thought of killing an innocent prompts a visceral revulsion, no matter how many other lives weigh in the balance. But if your prefrontal cortex has been impaired in the same small way by stroke or surgery, you would feel no such compunction in sacrificing one life for the good of all. The six patients certainly felt none. Any moral inhibition, whether learned or hereditary, had lost its influence.
The effort to understand the biology of morality is far from academic, said Georgetown University law professor John Mikhail. The search for an ethical balance of harm is central to medical debates on vaccine safety, organ transplants and clinical drug trials. It colors political disputes over embryonic stem-cell research, capital punishment and abortion. It is the essence of much military strategy and the underlying logic of terrorism.
For Harvard neuroscientist Marc Hauser, the moral-dilemma experiment is evidence the brain may be hard-wired for morality. Most moral intuitions, he said, are unconscious, involuntary and universal. To test the idea, he gathered data from thousands of people in hundreds of countries, all of whom display a remarkable unanimity in their basic moral choices. A shared innate capacity for morality may be responsible, he concluded.
Many scientists think his theory needs more proof. Since no two brains are exactly alike, each brain’s ability to perceive right and wrong might be unique. The world is a thicket of moral maxims we readily ignore. Even so, it would be curious if, in the neural substrates of morality, we find common ground.
Scary news that ice is melting in Antarctica!
Supposedly, if that continent remainded intact, the planet would not suffer from global warming as much. However, if the ice in the Arctic Circle and Antarctica is melting, then the sea levels will surely rise.
From Yahoo News
Rising temperatures caused a layer of snow blanketing a California-sized region of Antarctica to melt, US space agency NASA said in a statement on Tuesday.
Dire times: This image shows what a team of Nasa and university scientists say is clear evidence that extensive areas of snow melted in west Antarctica (in January 2005) in response to warm temperatures.
A team of scientists from NASA’s Jet Propulsion Laboratory in Pasadena, California, and the University of Colorado said new satellite imagery had revealed a vast expanse of snow melt in 2005 where it had previously been considered unlikely.
The NASA statement described the findings as “the most significant melt observed using satellites during the past three decades.”
Konrad Steffen, director of the Cooperative Institute for Research in Environmental Sciences at the University of Colorado, said it was the first time melting on such a scale had been detected.
“Antarctica has shown little to no warming in the recent past with the exception of the Antarctic Peninsula, but now large regions are showing the first signs of the impacts of warming,” said Steffen.
“Increases in snowmelt, such as this in 2005, definitely could have an impact on larger-scale melting of Antarctica’s ice sheets if they were severe or sustained over time.”
The melting occurred in multiple areas, including far inland, at high latitudes and high elevations, where melt had once been considered unlikely.
The melting was discovered using satellite scatterometry, a sophisticated imaging system which is able to distinguish between recently frozen ice or snow from snow that has been frozen for years.
The 2005 melt was intense enough to create an extensive ice layer when water refroze after the melt, the statement said. However, the melt was not prolonged enough for the melt water to flow into the sea.
Steffen said water from melted snow could penetrate ice sheets through cracks and glacial shafts known as moulins, which can cause the ice mass to slip and move toward the ocean faster.
Son Nghiem, of NASA’s Jet Propulsion Laboratory, said while no further melting had been detected through March this year, more monitoring is needed.
“Satellite scatterometry is like an X-ray that sees through snow and finds ice layers beneath as early as possible,” he said.
“It is vital we continue monitoring this region to determine if a long-term trend may be developing.”
The full results from the study “Snow Accumulation and Snowmelt Monitoring in Greenland and Antarctica,” appears in a recently published book “Dynamic Planet,” the statement added.
Twenty minutes may not really be enough time to fully understand the implications of the so-called Fab Lab, invented by, Neil Gershenfeld, the director of MIT’s Center for Bits and Atoms. But it’s a mind-blowing place to start!
Whippets are bred for speed. These dogs have the appearance of a small greyhound and have been clocked sprinting to speeds approaching 40 miles per hour over a 200-yard racing course. Recently, scientists at the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH), discovered a genetic mutation that helps to explain why some whippets run even faster than others.
In a study published online May 1, 2007 in PLoS Genetics, a research team led by Elaine A. Ostrander, Ph. D., chief of the Cancer Genetics Branch in NHGRI’s Division of Intramural Research, reports that a mutation in a gene that codes for a muscle protein known as myostatin can increase muscle mass and enhance racing performance in whippets.
Like humans, dogs have two copies of every gene — one inherited from their mother and the other from their father. Dr. Ostrander and her colleagues found that whippets with one mutated copy of the myostatin (MTSN) gene and one normal copy to be more muscled than normal and to account for a large share of the breed’s fastest racers. However, their research also showed that whippets with two mutated copies of the MTSN gene have a gross excess of muscle and are rarely found among competitive racers.
“Our work is the first to link athletic performance to a mutation in the myostatin gene and could have implications for competitive sports in dogs, horses and possibly even humans. However, extreme caution should be exercised when acting upon these results because we do not know the consequences for overall health associated with myostatin mutations,” said Dr. Ostrander, noting that dogs provide an excellent system in which to investigate genes associated with disease, behavior and other traits.
Whippets are medium-size dogs that have been bred for centuries for hunting, racing, show and companionship. Sometimes, litters of whippet puppies include heavily muscled offspring referred to as “bully” whippets that are prone to shoulder and thigh cramping. The bully whippet’s muscle structure looks similar to “double muscling” previously observed in mice, cattle, sheep and in one case, a human. Previous research has linked mutations in the MTSN gene to the double muscled trait in these cases. To gain a better understanding of the MTSN gene in whippets and its role in racing performance, the NHGRI-led team undertook an analysis of whippet DNA samples collected through the efforts of breeders and owners.
First, the researchers sequenced the MTSN gene in 22 whippets: four bully whippets, five whippets that had given birth to or sired bully whippets, and 13 normal whippets that had no known relation to a bully.
In the bully whippets, the researchers found that both copies of the MTSN gene had a tiny mutation — a deletion of just two of the gene’s 5,083 DNA bases. The deletion leads to the production of an abnormally shortened version of the myostatin protein.
Of the whippets that had bully whippet offspring, all had one normal and one mutated copy of the MTSN gene, or were “carriers” of the MTSN mutation. No mutations were found in the MTSN genes of the other whippets tested. The findings were confirmed by genetic testing of another 146 whippets.
Dr. Ostrander’s group went on to investigate whether a dog’s MTSN status correlated with its racing performance. Analysis of the racing records of 85 whippets entered in the study revealed a significant association between a dog’s genetic profile and its speed, as assessed by racing grade. There were significantly more carriers of the MTSN mutation among the fastest dogs.
The prevalence of the MTSN mutation among whippets appears to be a relatively recent phenomenon in the evolution of dogs, caused by selective breeding. “We found many more carriers of this mutation among the fastest whippets, since breeders inadvertently selected for this trait,” said NHGRI’s Dana Mosher, who is the study’s first author.
To see if this MTSN mutation plays a role in muscle mass and speed in other types of dogs, the researchers sequenced DNA from multiple dogs from 14 additional breeds, including the greyhound. While the findings did not exclude the possibility that the mutation occurs in other breeds, researchers said it appears that the double muscle structure may be unique to the whippet breed.
In addition to Dr. Ostrander and Mosher, other members of the team from NHGRI are Pascale Quignon, Ph. D., Heidi G. Parker, Ph. D. and Nathan B. Sutter, Ph.D. Collaborators included Carlos D. Bustamante, Ph. D., Cornell University, Ithaca, N.Y., who provided instrumental statistical analysis; and Cathryn S. Mellersh, Animal Health Trust, Center for Preventive Medicine, Newmarket, England, who contributed canine DNA samples for the study.
The article is available online in PLoS Genetics and may be accessed at here.
A novel catheter technique for patching holes in the heart may make it possible for many patients to avoid 1) ___ altogether and others to regain enough strength to safely undergo surgical repair at a later date. The patch has successfully closed VSDs 2) (___ ___ ___) –or ruptures in the wall between the right and left ventricles–in nearly all patients, allowing blood to circulate normally again and relieving fluid back-up in the lungs. After recovery, patients were able to return to active lives. Patients with acute VSDs may be critically ill with heart failure and perhaps be in 3) ___ shock. This procedure offers an alternative for patients who are too sick to undergo emergency heart surgery or simply don’t want surgery. A variety of patches were used in the study, but all were some form of 4) ___ Occluder. The VSD patch is composed of two discs connected by a thick shaft. The discs are made of flexible 5) ___metal and covered in polyester fabric that encourages heart tissue to grow over the discs, completely covering them during healing. Before 6) ___, the flexible double-disc patch is pulled into a catheter, collapsing and compressing it lengthwise. It is then threaded through a 7) ___ into the right ventricle and across the rupture into the left ventricle. The patch is pushed partially out of its catheter sheath until the first disc pops open. The catheter is then withdrawn back into the right ventricle, with the first disc positioned against the left ventricular wall and the connecting shaft filling the hole created by the rupture. From inside the right ventricle, the patch is pushed forward again, releasing the second disc, which covers the 8) ___ on the right side of the heart. The procedure was successful in all patients, without complications. The VSD patch allows patients to regain enough strength to withstand surgery. When surgery is the long-term answer for patients, the VSD occluder successfully bridges the patients to surgery.
Source: 30th Annual Scientific Sessions of the Society for Cardiovascular Angiography and Interventions, May 9-12, 2007, Orlando, FL. Note: The AMPLATZER Muscular VSD Occluders are for investigational use only in the U.S. The Membranous VSD Occluder is not available in the U.S.
ANSWERS: 1) surgery; 2) ventricular septal defects; 3) cardiogenic; 4) AMPLATZER; 5) nitinol; 6) implantation; 7) vein; 8) rupture
Target Health is pleased to announce the appointment of Adrian Pencak, as VP of Business Development. Adrian brings over 18 years of experience in the Pharma and software industry and has held positions at Oracle, PPD and other software and services based companies supporting clinical research. A graduate of Rutgers University, Pencak has degrees in software engineering and business. Adrian will leverage his industry and technical expertise to ensure our clients continue to get the best value from our CRO services and our eClinical Trial Toolbox which includes Target e*CRF®, Target Document™, Target Encoder™ and Target Newsletter™
Executive director of SELF, Robert Freling, is lighting up the developing world and empowering self-sufficiency by delivering solar power to more than 2 billion people on the planet living without electricity.