Using Polio to Kill Brain Cancer

Rarely, am I super impressed with medical discoveries.

I can't say that for this piece I just saw on the news magazine 60 Minutes.

Cancer treatment has gone through various stages. First surgery. Then came the advent of radiation therapy followed by chemotherapy.

But now, the newest frontier in the fight against cancer is your body's own immune system which makes the most sense, right? If we could train the immune system to seek and destroy cancer cells like it does bacteria and viruses then whole hosts of people wouldn't have to face death related to this, often times, devastating diagnosis.

I've blogged here about the use of the measles virus in treatment of cancer.

Now, researchers at Duke University are using a genetically modified polio virus to kill brain cancer . . . and it's working.

Glioblastoma is a particularly aggressive, nasty brain tumor. As stated in the piece, it's usual for this cancer to double its size in 2-4 weeks.

What I learned about cancer cells in this piece that I didn't know before is that they are smart. I remember learning in my pathophysiology class in college that cancer cells were merely your own cells running amok-- dividing uncontrollably and invading normal functioning tissue. Perhaps this is why our own immune systems don't attack it as the potential killer that it is-- because it is our own cells.

The doctors at Duke University are attempting to change this. They took a small group of patients who had glioblastoma for the second time. These patients had already been through standard therapy at it failed.

They surgically implanted a catheter into the center of the tumor and then gave the patient an infusion of modified polio virus directly into the tumor.

What happens is two things. One, the body recognizes the polio and begins to attack it. Second, the virus seems to also strip the protective coating of the cancer cells so the body recognizes it and begins to attack it as well. The body amounts an impressive immune response and MRI's initially show massive inflammation around the tumor, but then, over a period of 4-8 months, the body's immune system begins breaking down the tumor.

Two patients who received this treatment first are now cancer free for nearly three years. That is unheard of with this kind of brain tumor. I mean-- it is miraculous.

After the researchers had success with the first several patients, they attempted to double the dose to see if they could get a better immune response. In fact, they did get a massive immune response but it proved to be too much for the patients and several of them died.

Now, they are using smaller doses and it remains to be seen if this is a cure but it's so promising that in a year, the FDA may cut their red tape to make it available to lots more patients.

Truly, truly impressive. I mean for us medical nerds-- it is jaw dropping.

Now, of course, there is always worry that modifying viruses could lead to potential breakouts of untreatable illness. That's definitely fodder for any medical thriller.

But today, let's bask in the glory of this amazing discovery and what it could mean for patients who receive this deadly diagnosis.

For more information on this study you can view the piece here.

Sarah Sundin: Historical Polio-- Part 3/3

It's been such a pleasure having Sarah Sundin back. There was a lot I didn't know about the history of polio and its occurrence that I learned from these posts. Great job, Sarah!

Polio Part 3—Vaccines

Papa had never truly forgiven Helen for catching polio, as if the doctor’s daughter should have been immune, should have been healthy and strong like Betty, should never have stooped to wearing braces. Some parents coddled their invalids, but not Papa. He’d been harder on her, required more of her. And it was never enough.

In my novel, Blue Skies Tomorrow, which takes place during World War II, Helen Carlisle deals with many repercussions of a childhood bout with polio. Thanks to vaccination, polio is quickly being forgotten, but it was a dread threat in the first half of the twentieth century. If you write fiction set in this time period, it helps to be familiar with this much-feared disease.

On August 22^nd, I discussed the disease, on August 24^th, I discussed treatment, and today the vaccines.

Immunization is the process of artificially creating immunity by deliberate infection with viral proteins, weakened viruses, or killed viruses. Vaccination results in the production of antibodies which protect the patient against infection.

 On January 3, 1938, polio survivor President Franklin D. Roosevelt established the National Foundation for Infantile Paralysis to fund polio research. Nationwide campaigns urged citizens to mail in dimes. The nickname March of Dimes stuck, a play on the popular newsreel, The March of Time. In 1946, the picture of Mercury on American dimes was replaced with the image of Roosevelt to commemorate his work.

The Salk Vaccine

The most famous recipient of those dimes was Dr. Jonas Salk, a medical researcher at the University of Pittsburgh. In 1952 he conducted small trials of a vaccine, and in 1954, a massive nationwide trial. On April 12, 1955, the tenth anniversary of Roosevelt’s death, an announcement was made that the vaccine was effective and available. Church bells rang throughout the nation.

The Salk Vaccine, now more commonly known as IPV (inactivated polio vaccine) uses a killed virus and is administered by injection. The vaccine is safe, since it does not cause the disease. On the negative side, immunized people do not shed the virus in the feces, so the desired “herd immunity” does not occur.

The Salk Vaccine was used in the United States from 1955-1962, when the Sabin Vaccine gained favor. As polio was eradicated, the dangers of the Sabin Vaccine became greater than the risk of the disease itself. In 1998, the United States returned to the use of IPV. Salk’s vaccine is currently in use in the Americas and Europe, where polio has officially been eradicated.

The Sabin Vaccine

What is science without controversy? Dr. Albert Sabin publicly disapproved of Salk’s work and did not receive funding from the National Foundation for Infantile Paralysis. Sabin conducted his clinical studies in the USSR and other countries from 1957-1960.

The Sabin Vaccine, also known as OPV (oral polio vaccine), is a weakened live virus administered orally, either by squirting into the mouth or ingested on sugar cubes. The Sabin Vaccine closely mimics wild-type virus transmission and produces long-term immunity. Virus is shed in the feces of vaccinated people, leading to immunity among contacts as well. These advantages led the United States to switch to the oral vaccine in 1962.

The vaccine is inexpensive and easily administered by volunteers with minimal training, making it ideal for administration in third-world countries, where it is still used.

However, in some cases the oral vaccine leads to actual poliomyelitis, paralysis, and death. Since the last polio case was seen in the US in 1979, the decision was made to return to the safer IPV in 1998.

Eradication

The effectiveness of the polio vaccine can’t be argued. Tens of thousands of cases were seen in the United States each year before 1955. By 1957, the rate fell 90 percent. The last case in the US was seen in 1979 among the Amish, who rejected vaccination. Polio was officially eradicated in the western hemisphere in 1994, in Australia and eastern Asia in 2000, and in Europe in 2002. Currently it remains endemic only in Nigeria, India, Pakistan, and Afghanistan, but hope remains for eventual worldwide eradication.

Resources

http://www.americanhistory.si.edu/polio (Smithsonian Institute’s display on polio)

http://www.marchofdimes.com/

Wilson, Daniel J. Living with Polio: the Epidemic and Its Survivors. Chicago: University of Chicago Press, 2005. (An excellent book describing the disease and its treatment from the patient’s point of view.)

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Sarah Sundin is the author of the Wings of Glory series from Revell: A Distant Melody (March 2010), A Memory Between Us (September 2010), and Blue Skies Tomorrow (August 2011). She has a doctorate in pharmacy from UC San Francisco and works on-call as a hospital pharmacist.

Sarah Sundin: Historical Polio-- Part 2/3

Polio Part 2—Treatment

Helen pedaled down Sixth Street, harder with the left leg than the right, punishing the left leg for its weakness, as she’d learned on the polio ward.

In my novel, Blue Skies Tomorrow, which takes place during World War II, Helen Carlisle deals with many repercussions of a childhood bout with polio. Thanks to vaccination, polio is quickly being forgotten, but it was a dread threat in the first half of the twentieth century. If you write fiction set in this time period, it helps to be familiar with this much-feared disease.

On August 22^nd, I discussed the disease, today I’ll discuss treatment, and on August 26^th, the vaccines.

There is no cure for poliomyelitis. All treatment revolved around keeping the patient alive and preventing further disability.

Isolation

Since polio is contagious, patients were quarantined, sometimes at home, but more often in hospital polio wards. Early diagnosis was vital, since muscle rest in the acute phase of the illness reduced paralysis.

During the acute febrile phase of the illness, patients were placed in isolation wards, separated from all family and friends. For a young child, this was a frightening experience. They were kept on the isolation ward 2-4 weeks, then transferred to a polio convalescence ward. Visitors were allowed once or twice a week. Since live virus was shed in the feces for 17 weeks after infection, and recovery could take 6-8 months, patients were kept in the hospital for many months.

According to psychological theory of the day, coddling produced hypochondria, so children were often treated in a brusque and unsympathetic manner. A societal stigma against disability caused many families to be ashamed of their polio-afflicted children or to pretend nothing was wrong. Children were encouraged to work hard to overcome their disability, and these patients often became overachievers.

Immobilization

Up until the 1940s, the accepted treatment for polio was to immobilize the affected body parts. Rigid splints, braces, and casts were used, and children’s feet were strapped to boards in the flexed position to prevent foot drop. Immobilization reduced skeletal deformities, but recovery of muscle strength and function remained low.

Iron Lung

The majority of deaths due to polio occurred from paralysis of the diaphragm. About half of patients with respiratory involvement died from the illness. In 1928 the first iron lung was introduced. The iron lung is a negative-pressure ventilator consisting of a cylindrical tank in which the patient lay. Pumps alternately increase and decrease the pressure inside the tank, causing the lungs to inflate and deflate. Improvement in the iron lung occurred throughout the 1930s, and in 1939 the National Foundation for Infantile Paralysis made one available for mass production. The use of iron lungs reduced the death rate from respiratory involvement to about 15 percent.

Tracheotomies also saved many lives during polio epidemics.

Sister Kenny’s Massage Therapy

Australian nurse Sister Elizabeth Kenny (“Sister” being the title for British and Australian chief nurses) arrived in the United States in 1940 and immediately caused controversy. In Australia in the 1930s she had developed a system of polio treatment which rejected immobilization and relied on hot packs, stretching, and massage. Originally derided by the medical community, Sister Kenny’s treatment slowly gained favor. Her patients were more comfortable and had higher and faster rates of recovery.

In the late 1940s and the 1950s, polio patients received a form of Sister Kenny’s treatment. Strips of hot wet wool were wrapped around affected limbs hourly, an often uncomfortable procedure, especially in summer. Stretching and massage was usually painful but was seen as vital to “re-educate” paralyzed muscles.

Rehabilitation

When muscle weakness persisted, braces of metal and leather helped patients to stand and walk. Corsets straightened weakened torsos. Crutches, canes, and wheelchairs aided mobility. Water therapy—performing exercises in warm water—was used on the convalescence wards and at home to relax and strengthen muscles.

Due to the absence of a cure, vaccination was the only hope to avoid polio’s high rate of death and disability.

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Sarah Sundin is the author of the Wings of Glory series from Revell: A Distant Melody (March 2010), A Memory Between Us (September 2010), and Blue Skies Tomorrow (August 2011). She has a doctorate in pharmacy from UC San Francisco and works on-call as a hospital pharmacist.

Sarah Sundin: Historical Polio-- Part 1/3

I'm so pleased to have Sarah Sundin back. I've missed having her here over the last several months as I'm sure you have as well. This week, she'll be guest blogging about historical polio, the disease, and the polio immunization.

Welcome back, Sarah!

Polio Part 1—The Disease

For months, Helen had lain in the county polio ward. No matter how hard she’d concentrated, her legs wouldn’t do what she asked from them, demanded from them, pleaded from them.

In my novel, Blue Skies Tomorrow, which takes place during World War II, Helen Carlisle deals with many repercussions of a childhood bout with polio. Thanks to vaccination, polio is quickly being forgotten, but it was a dread threat in the first half of the twentieth century. If you write fiction set in this time period, it helps to be familiar with this much-feared disease.

Today I’ll discuss the disease, on August 24^th, I’ll discuss treatment, and on August 26^th, the vaccines.

Cause

Poliomyelitis, also known as infantile paralysis or polio, is caused by an RNA virus and only occurs in humans. It’s transmitted by the fecal-oral or oral-oral route. From the gastrointestinal tract, the virus can travel to the spinal cord, where it leads to inflammation of the gray matter. Spinal or cranial motor neurons die, which causes paralysis of the affected muscles and eventually atrophy of those muscles from lack of use. During recovery, other neurons in the vicinity can sometimes grow extra “buds” to re-inervate those muscles.

Epidemics

Although polio has been known since ancient times, it rarely caused paralysis or death. Due to poor sanitation, most children were infected at a very young age when they were still protected by maternal antibodies, and therefore, had asymptomatic or mild infections. However, as sanitation improved, children didn’t become infected until they were older, and the disease increases in virulence with the age of the patient. The first major epidemic in the United States occurred in Vermont in 1894. Epidemics occurred most years, with severe epidemics in 1916 and 1952. The 1952 epidemic was the worst, with 58,000 cases and 3000 deaths.

Epidemics were most common in July, August, and September. Due to the fecal-oral and oral-oral transmission route, people avoided swimming pools, ponds, drinking fountains, and crowds during the summer. Children who had previous tonsillectomies were at significantly increased risk, not only of contracting polio but of contracting more dangerous forms.

Symptoms

About 95 percent of those infected had no symptoms at all, and another 5 percent had only mild flu-like symptoms—fever, headache, nausea, fatigue, and muscle weakness. Less than 1 percent of those infected developed paralytic polio. Within a week of the development of symptoms, patients experienced neck and back stiffness, asymmetrical muscle weakness and pain, sensitivity to touch, a “pins and needles” sensation, and a sudden onset of paralysis. Paralysis became complete within two to three days of onset.

Spinal Polio

Spinal polio was the most common form of paralytic polio and occurred when the motor neurons in the spinal cord were afflicted. Patients experienced weak and floppy muscles, then paralysis often accompanied by painful spasms. Because sensory neurons were not affected, patients still felt pain, temperature changes, and itching. This form of polio was rarely fatal. About half of patients recovered fully, one quarter experienced minor long-term disability, and a quarter experienced severe disability.

Bulbar Polio

About 2 percent of cases of paralytic polio affected the cranial nerves, leading to difficulties in swallowing, speaking, and breathing. This was fatal in about half of cases if mechanical ventilation was not available.

Bulbospinal Polio

The most dangerous form of polio represented about 1 percent of cases. These patients had paralysis of the diaphragm as well as arms or legs. Respiratory involvement led to death in about half the patients if mechanical ventilation was not used.

Diagnosis

Patients presenting with high fever, fatigue, and nausea were asked to touch their chins to their chest, since a stiff spine was an early sign. Usually diagnosis was made due to sudden falls and paralysis, and was confirmed with a lumbar puncture (spinal tap).

Recovery and Complications

Muscle strength often began to return within one month of illness, and improvement usually in 6-8 months. Any paralysis remaining after 18 months would rarely resolve.

Complications often resulted from imbalanced muscles. When the muscle on one side of the joint was paralyzed and the other wasn’t, the joint became distorted, leading to syndromes such as “foot drop,” and “back knee.” If a child was paralyzed on one side early in development, often one leg would grow longer than the other, leading to a lurching limp. Due to residual muscle weakness, polio survivors are at greater risk for bone fractures, and at higher risk from complications due to those fractures. Later in life they’re at higher risk of osteoporosis.

Post-Polio Syndrome

In the 1970s a new syndrome began to be recognized in former polio patients. New muscle weakness and fatigue in formerly affected muscles appeared after decades of strength. This Post-Polio Syndrome is now known to affect 25-50 percent of people who had childhood polio. The severity of weakness is directly related to the severity of the original acute illness.

Poliomyelitis was a major cause of death and disability through the 1950s and caused great fear for children and parents. Be very thankful for vaccination.

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Sarah Sundin is the author of the Wings of Glory series from Revell: A Distant Melody (March 2010), A Memory Between Us (September 2010), and Blue Skies Tomorrow (August 2011). She has a doctorate in pharmacy from UC San Francisco and works on-call as a hospital pharmacist.