Tag: Rats

Developing an Impossible Vaccine with Animal Research

The Scientist recently published a long look at the development of a vaccine for staph infection — a vaccine that as recently as the 1960s was considered impossible to develop by most reputable authorities.

Without going into too much detail about the chemistry of it all, for a variety of reasons researchers in the 1960s concluded that the outer layer of the staph bacteria lacked polysaccharides.

In fact, the staph bacteria do contain polysaccharides. Researcher Walter Karakawa demonstrated this and then went on to develop a vaccine for staph that takes advantage of this. The vaccine has proven relatively successful in initial human tests on people with compromised immune systems, and should prove to be a boon in the routine protection of surgical patients against staph infection (patients are currently given antibiotics, but the staph bacteria has increasingly developed resistances to many antibiotics).

From that discovery Ali Fattom of Nabi Biopharmaceuticals worked to develop a vaccine for staph, which again many researchers said was impossible even if staph did contain polysaccharides. The major factor in Fattom’s proving that a vaccine would work was his development of an animal model of staph in mice. When Fattom looked back at previous efforts to locate polysaccharides he found that researchers had never created an animal model for the disease. According to The Scientist,

This brush with termination [when his vaccine project was almost cancelled] marked a turning point, for it convinced Fattom that he needed to demonstrate with an animal model that antibodies against polysaccharides protected against infection. This had not been done earlier because the NIH and Univax [who had both done polysaccharide vaccine development] researchers did not develop an animal model. [NIH vaccinologist John] Robbins’ goal had been to get the vaccine into the clinic quickly and safety, not to research the molecular basis of virulence. So animal model development had been deferred.

. . .

In 1996 Fattom finally developed a mouse model in which a reasonable innoculum caused infection. With this model he was the first to demonstrate that conjugate vaccines protected against lethal injections of Staphylococcus aureus. Knowing he would need corroboration, he then invited Jean C. Lee of Harvard to test his vaccines in her endocarditis model with rats. A year later the results were just as predicted — the vaccines protected Lee’s rats. Now, at last, skeptics started to come around. Maybe the vaccine would work.

And work it apparently does. A clinical trial of the vaccine in dialysis patients found the vaccine cut the rate of staph infections by 57 percent. The vaccine should perform even better in routine pre-surgical administration since the patients in that clinical trial had characteristics such as diabetes and high uric acid levels that inhibit production of white blood cells.

The vaccine is still undergoing further clinical trials, but barring any unforseen events should reach market within a few years. Not bad for a few people armed just with a hypothesis and some mice.

Source:

Impossible vaccine tames Staphylococcus aureus. Tom Hollon, The Scientist, 16[14]:24, July 8, 2002.

Japanese Researchers Claim Advance in Heart Research with Rats

The Japan Times reports that Japanese scientists claim to have developed cardiac muscle tissue derived from the heart-muscle cells of newborn rats that they used to treat rats with poorly functioning hearts.

The researchers apparently cultivated cells from newborn rats and used them to, in the words of The Japan Times, “form a sheet of cardiac muscle.” The researchers then combined four of these sheets of muscles and transplanted it into a rat, causing a 40 percent improvement in heart functionality.

Unfortunately, at the moment the research does not appear to have been peer reviewed.

Source:

Rat experiment gives hope to the weak-hearted. The Japan Times, Thursday, April 11, 2002.

Researchers Partially Regenerate Spinal Cord in Rats

Researchers at King’s College London reported in Nature that they had managed to restore movement to rats that were paralyzed by injuries to the spinal cord.

Normally spinal cord cells do not regenerate for a number of reasons. One of those reasons is that following an injury, scar tissue forms in the spinal cord which forms a barrier that nerve cells are unable to cross.

Researchers at King’s College used a bacterial enzyme called chondroitinase ABC that destroys molecules in the scar tissue and allows nerve cells a pathway to grow back.

Dr. Elizabeth Bradbury, who led the research, told The BBC,

After damage to spinal cord tissue, a complex jungle of molecules is deposited in the scarred area. Chondroitinase ABC acts like a ‘molecular machete’, cutting a path through the jungle of molecules that usually prevent spinal cord nerves growing back into these damaged areas.

When they applied the enzyme to rats, the animals recovered most — though not all — of their pre-injury neurological functioning. The rats were able to walk again, but did not completely recover all functioning in their spinal cord.

What does this mean for the ultimate goal of treating spinal cord injuries in human beings? Restoring neurological function is a complex task that will involve solving a number of distinct, but related, problems. This researcher suggests one approach to soling one of those problems.

As Dr. Bradbury told The BBC,

This is a great advance but not some sort of miracle cure. There are still many other blocks that must be overcome before complete spinal cord repair can be achieved in humans. In terms of treating people, we could see clinical trials involving this treatment as part of a multi-targeted therapy starting within the next five years.

Source:

Severed spinal cord regenerated. The BBC, April 10, 2002.

Is Pain Research Worthless?

Patricia Wolff of New West Research recently posted an e-mail to AR-NEWS about animal research conducted at the John Hopkins School of Medicine which Wolff headlined, “Painful, Worthless Animal Experiment.” In fact, while the experiment was, of necessity, painful, it was far from worthless.

The study involved research into whether or not a soy-based diet can reduce pain and inflammation, and was the result of a chance observation by John Hopkins researchers while collaborating with an Israeli researcher on sabbatical in this country.

The Israeli researcher had bred a strain of rats for use in studying nerve injury pain. Some of those rats were sent to the United States. But when he began his experiments in the United States, the rats did not experience as much pain as did his mice back in Israel. After eliminating a number of factors, it turned out that the two sets of rats had been fed different diets. The rats in the United States had been fed a soy-based diet.

John Hopkins researcher Jill Tall and her colleagues set out to discover if the soy-based diet was indeed responsible for the diminished pain. So they took 20 rats, and fed 10 of them a dairy protein diet and the other 10 a soy based diet. Then the rats were randomly injected with either a placebo or an inflammatory solution. The rats who received the inflammatory solution and were on the soy-based diet experienced significantly less inflammation than the rats fed the dairy protein diet.

The rats on a soy-based diet also exhibited a much higher pain tolerance than did the rats on the dairy protein diet.

This is obviously a small, preliminary study but will lead to further studies. Currently Tall and her colleagues are looking in detail at the soy protein trying to get a better idea of what might component might be helping to relieve pain.

Many people seem to think that such pain research is an unjustifiable use of animals. But Tall is a research fellow in anesthesiology and critical care who specializes in pain experienced by cancer patients. The reality is that the advent of safe, reliable anesthetics relied heavily on animal research (anesthetic techniques which are also used to minimize the pain of animals during medical research). Continued progress on relieving pain will also rely on animal research which, by its very nature, unfortunately involves intentionally inflicting pain on animals.

Wolff had it half right — such research is painful, but hardly worthless.

Source:

Soy diet eases pain, animal study finds. Nicolle Charbonneau, HealthScoutNews, March 15, 2002.

Helms Amendment Would Exempt Rats, Mice and Birds from Animal Welfare Act

Yesterday the U.S. Senate approved an amendment to a major farm bill that would exempt rats, mice and birds from the Animal Welfare Act. The amendment was introduced by Sen. Jesse Helms (R-North Carolina) and would overturn a successful legal victory by the Humane Society of the United States to have those animals included under the Animal Welfare Act.

Although the Animal Welfare Act did not specifically exempt rats, mice and birds, the U.S. Department of Agriculture never applied the law to those animals which together constitute 95 percent of animals used for medical research.

HSUS and other animal rights groups sued the USDA in 1990 arguing that it had no legal basis for exempting rats, mice and birds. After the USDA lost a court ruling on that matter, it reached an agreement with HSUS in which the USDA promised to draft regulations covering the formerly exempted species. Under the proposed rule changes, researchers would have to more thoroughly justify research involving such animals and demonstrate that they are not repeating previous research.

This change has been opposed by the medical research community on the grounds that it will create an expensive nightmare of forms that will not enhance the welfare of research animals but will increase the costs and hence slow the pace of medical research with animals.

Helms’ amendment specifically exempts rodents and birds used in medical research from USDA oversight.

HSUS vice president Michael Stephens accused Helms of not caring enough about research animals. He told the Associated Press,

Just because Senator Helms doesn’t care about birds, mice and rats doesn’t mean they shouldn’t have legal protections. This is an issue that concerns millions of animals used in research. No one doubts that they can feel pain.

Helms’ amendment passed on a voice vote in the Senate without debate, and the farm bill itself passed the Senate. Now a House-Senate conference committee will meet to reconcile the different farm bills passed by each chamber of Congress. If the amendment remains in the final version of the bill that emerges from that conference committee, it will become law as long as George W. Bush decides not to veto the farm bill (which would be highly unlikely).

Source:

Helms denies protections for rodents in lab experiments. The Associated Press, February 14, 2002.

Medical Researchers Successfully Treat Blindness in Rats with Human Retina Cells

British and American researchers announced in December that they had succeeded in using genetic engineering to restore sight to rats who went blind due to a condition that is the leading cause of sight loss in people over 50 in the Western world.

About 230,000 people are legally blind in the United States due to age-related macular degeneration, and many others have seriously impaired vision due to the disease. The disease is caused by the hardening of the arteries that bring blood to the retina. Deprived of some of the oxygen and nutrients the retina requires, vision in the center of the retina begins to deteriorate. The disease rarely leads to total blindness, but it can leave people with nothing but peripheral vision.

Researchers took genetically engineered human retinal pigment epithelial cells and transplanted them into rats who were born with a genetic predisposition to retinal degeneration. Not only did the cells survive — the first time this sort of cell has been successfully transplanted — but they restored the sight of the rats.

Professor John Greenwood of London’s Institute of Ophthalmology told the BBC,

The transplanting of genetically engineered RPE cells is totally unique. At present, there is no truly effective treatment or cure for age-related macular degeneration. We believe this work represents a tremendous leap forward in our endeavor towards developing a feasible strategy for treating patients with this debilitating disease.

Source:

Cell transplant reverses blindness. The BBC, December 17, 2001.