OxyFile #537

James Caplan is trying to contact as many physicians as possible to review current clinical data on sickle cell disease and to review current clinical research.

Mr. Caplan can be reached at:
610-394-1172
610-394-1175 Fax

The Wizard of Ozone

Is this Philadelphia businessman peddling Quackery?  Or is the profit-
driven American Medical Establishment ignoring Jim Caplan's Miracle 
Treatment?

By Brenda Fullick


"I knew my foot would have to be amputated, but I didn't think it 
would be this soon," says Adaria Young, 31, of Philadelphia.  She has 
been a diabetic since she was 4.  Because diabetes reduces the feeling 
of pain, Young didn't realize she had been walking around for several 
days with a thumbtack stuck in her right foot.  The foot became 
infected, the infection spread to her bone, and her foot was amputated 
in September.

"At first it was frustrating, but it was something I have to live 
with," Young says.  "I have a 6-year old, and I knew I had to be 
strong for him."

So far, her left foot seems to be OK.  "I have to be really careful," 
she says.  "I have to keep something on my feet at all times, and when 
I take a shower I have to check between my toes (for infection or 
drainage).  So far, I've been really lucky."

According to the Centers for Disease Control in Atlanta, Young is 
among an estimated 13 million Americans with diabetes, though only 
half of all diabetics have been diagnosed.  Diabetic circulatory 
disorders like Young's contributed to more than 162,000 deaths in 
1990, making it the seventh-leading cause of death that year, 
according to CDC records.

In 1994, the National Institutes of Health (NIH) earmarked $301.3 
million for diabetes research.  It is among this country's most 
broadly studied diseases, with 17 different institutes at NIH funding 
research on everything from blood-sugar levels to peripheral-nerve 
destruction.  Despite all the researchers have learned, American 
doctors still are poorly equipped to handle diabetic gangrene and 
infections that lead to amputations.

Meanwhile, for decades, doctors in Germany have been healing diabetic 
wounds with ozone, a very strong form of oxygen applied directly to 
the wound.  But the German technique is not available in the United 
States, partly because bringing it to market could cost tens of 
millions of dollars--or more--and no company could recoup that kind of 
an investment with a simple, unpatentable chemical.

"It feels like somebody's stabbing you with a knife," says Dorothy 
Simmons Hardy of Philadelphia.  "It's constant, sharp, achy pain.  It 
never lets up.  The pain is real severe, and it's real constant."

Simmons Hardy is one of about 72,000 people in the United States who 
suffer from sickle cell anemia.  When the oxygen level in her blood 
drops too low, her blood cannot flow normally.  The pain usually hits 
her legs, but sometimes she has arm and stomach pain.  Frequent 
hospital stays make it hard for her to hold a job.  She almost died 
twice during pregnancy because of sickle-cell complications, including 
a blood clot on the lung.

NIH spends about $70 million a year to study sickle cell anemia.  
Statistically, relatively few people suffer from this disease, 
compared to other ailments.  But American scientists say a 
disproportionate amount of energy is focused on sickle cell because 
they consider it a great medical challenge: In 1954, Linus Pauling won 
a Nobel prize for identifying sickle cell anemia as a genetic defect, 
making it the first genetic defect found in humans.

For years, NIH has funded research into lowering the percentage of 
sickle hemoglobin in the blood.  Drugs such as hydroxyurea and 
butyrate are being tested at Children's Hospital in Philadelphia and 
throughout the country.  But now those drugs are on the back burner, 
and the hottest sickle-cell research is in gene therapy, the idea that 
technology could permanently alter people's cell structures to cure 
diseases.  Dr. Junius Adams, a health-scientist administrator at NIH 
in Bethesda, MD., says gene therapy is "really the only thing we've 
got going that has potential to cure sickle-cell disease."

Some scientists predict gene therapy could become reality within five 
years; others say it's closer to 40 years, maybe more.  Meanwhile, 
Philadelphia businessman and ozone proponent Jim Caplan has convinced 
doctors in Cuba to treat sickle cell anemia with ozone, much as the 
Germans are treating diabetics.

At the moment, the best American doctors can do is put their sickle-
cell patients on antibiotics to stave off infections while the blood 
circulation is limited, and give them painkillers to help them ride 
out the painful crises.  But Cuban doctors have documented that in 
their research, the use of ozone cut the length and the severity of 
painful episodes in half.  So far NIH grant reviewers have opted not 
to put research money toward this treatment.

As his immune system has steadily fallen apart, one Philadelphia man 
says he has lost 40 pounds in four months from AIDS diarrhea, what 
doctors call "AIDS wasting."

"It's a severe problem," says this resident of Betak, a Philadelphia 
nursing home for AIDS patients.  The man, who asked not to be named, 
is resigned to his unrelenting diarrhea.  "It doesn't really ever go 
away.  They try to control it with medicines.  It works a little, but 
it's an ongoing thing...It has a tendency to drain you, make you very 
tired."

At the end of 1993, there were 54,000 AIDS patients across the United 
States who had AIDS wasting.  NIH has set aside $1.3 billion for AIDS 
research in 1995.  At least $4.6 million a year is reserved 
specifically to study AIDS wasting, which hit 14 percent of 
Philadelphia AIDS patients in the last year.

Some vaccines are being tested on AIDS patients in the United States, 
but most of the NIH-funded research focuses on the basic science of 
how HIV works, what causes the virus and how it spreads.

Meanwhile, a San Francisco researcher conducted a study in which four 
out of five AIDS-wasting patients found relief with ozone therapy.  A 
virologist in New York found that ozone was able to attack HIV-
infected cells in the laboratory, but healthy cells were not affected.  
Neither of them has been able to get NIH funding to continue their 
ozone research.

Too little research, too little profit

What if scientists came up with a stunning medical breakthrough that 
might be able to help doctors treat a variety of diseases, but nobody 
had the chance to get rich from it?

Thought Young, Simmons Hardy and the AIDS patient all suffer from 
different maladies, there are American researchers who say there is 
reason to believe that each of them could be helped with the same 
incredibly cheap, incredibly simple drug: enriched oxygen, a.k.a. 
ozone.

Ozone is used to treat patients in other countries, but not in the 
States.  Here, in the country with the highest medical standards in 
the world, it has hardly been tested.  The same costly, lengthy, 
bureaucratic approval process that protects Americans from potentially 
hazardous drugs also is keeping Americans from lifesaving therapies.

This is a story about a potential cure that on one has been able to 
research thoroughly in the United States, in part because trying to 
sell ozone would be like trying to sell air--there wouldn't be enough 
private profit in it.

This is a story about the American medical establishment considering 
itself more scientific and ethical than the medical systems of other 
countries--and, as a result, looking skeptically at what doctors in 
the rest of the world are doing.

Finally, this is a story about an idealistic man who wanted to do good 
in the world by introducing German successes to the American medical 
establishment.  He found that it isn't so easy.

Some say the American medical system is working as it should--that if 
ozone turns out to be a legitimate therapy, someday it will get its 
due.  Others say ozone research is held back because it's an 
unconventional approach competing with more conventional experimental 
treatments, in a system that bases its agendas on long years of 
preliminary laboratory testing.  Because there has been little 
American research to determine whether Germany's medical results are 
valid, there's no jumping-off point for the theory in the United 
States.

"It was a fresh idea," Rosemount resident Jim Caplan says.  "I just 
thought, 'My gosh, you open the window for them and they're going to 
fly.' They didn't fly."

Ozone: Dangerous and wonderful

Ozone (O3) is a form of oxygen (O2) produced when an electric spark or 
ultraviolet light is passed through air or oxygen.  When you flip a 
light switch and see a spark, you've created a small amount of ozone.  
"Any electrical discharge cross in the air will create a certain 
amount of ozone," says Bob Steeves, a lawyer and pharmacist at the 
Food and Drug Administration's Office of Orphan Products Development 
in Rockville, Md.  Ozone easily reverts to regular oxygen again.

Ozone has both very bad and very good properties.  It's good in the 
sky, bad in the lungs.

The ozone layer in the earth's atmosphere protects us from harmful 
ultraviolet radiation, which causes skin cancer and other problems.  
That's why environmentalists and public-health organizations are so 
concerned about automobile exhaust fumes combining with the sun's rays 
to burn holes in the ozone layer.

Ozone also is a severe lung toxin.  People working with it must be 
careful not to release it into the air they breathe.

"Ozone can do many, many things.  It's amazing," says Toshio Asakura, 
and M.D. and Ph.D. at Children's Hospital in Philadelphia, as well as 
a professor at the University of Pennsylvania.  "Ozone is also a very 
dangerous chemical."

Ozone "pretty much kills every known microbial thing out there," says 
Lt. Col. and Dr. Donald Skillman, chief of infectious diseases at 
Fitzsimons Army Medical Center in Denver.  It causes free radicals, 
chemicals that can kill.  It can lead to cancer.  "Like anything else, 
it's toxic in high concentrations."

Ozone is very unstable: The third oxygen atom likes to break off and 
attach to other things, including bacteria and viruses that do not 
grow in an oxygen environment.  The human immunodeficiency virus 
(HIV), for example, dies when exposed to air.  Ozone is the most 
powerful oxidant known.

In Japan, ozone has been bubbled into fish tanks with amazing results, 
Asakura says.  He doesn't know how it works, but "the fish grow so big 
as compared to the sibling fishes.  This is a fact."

Germans began using ozone as early as World War 1 for cleaning and 
disinfecting wounds, but it was difficult to handle because oxygen 
with just 5 percent ozone would corrode rubber and various metals.  
The development of modern plastics made it possible for Germans to 
resume ozone therapy in the 1960s.

Since then, German doctors have been working with ozone to treat a 
variety of problems.  They've had especially good results treating 
infections and wounds, like diabetic ulcers.

Sometimes they draw blood from the patient, bubble ozone into that 
blood and then re-infuse the oxygen-rich blood into the patient.  
Sometimes they apply ozone to the skin in a closed container, like a 
plastic boot.  Sometimes they give ozone enemas.  In each scenario, 
oxygen atoms break off from the ozone and bond to oxygen-poor blood or 
stubborn infections.

Ozone kills bacteria and fungi as well as improving circulation, 
according to German doctors S. Rilling and R. Viebahn, authors of The 
Use of Ozone in Medicine.  They write that ozone stimulates the body's 
ability to carry crucial, life-giving oxygen to the body's tissues.

American doctors know that oxygen helps tissues heal, but they're not 
always sure how to get oxygen to where it's needed.  Simply breathing 
oxygen doesn't seem to do much good.  Neither does putting people in 
pressure chambers with oxygen.

"I think in theory, ozone has potential to be helpful in eradicating 
many types of infections," Skillman says.  "It could be used in many 
different fields."

Starting with strawberries

For one thing, ozone is useful for shipping strawberries.  When Jim 
Caplan was 17 years old, he and his father started installing ozone 
generators on rail cars carrying strawberries from California and 
Texas to the East Coast.  The ozone, O3, would quickly decompose into 
more stable oxygen molecules, O2.  The extra oxygen atoms would attach 
themselves to mold spores and protect the delicate fruit.

As a teenager, Caplan was intrigued by ozone, in the 33 years since, 
Caplan has spent much of his spare time reading about, thinking about 
and talking about ozone.

For six years now, Caplan has been pushing and cajoling American 
doctors and researchers to consider ozone as a treatment for sickle 
cell disease.  His crusade, reminiscent of the parents' chase for an 
ADL cure in Lorenzo's Oil, hasn't made him a lot of friends in the 
American medical establishment.  "Oh God, not that guy.  Ozone Enemas 
himself," came the response from Adams at NIH.

"Mr. Ozone Enemas" actually is a comfortable businessman, husband and 
father to four children living in a white house in the suburbs.  He 
has a bachelor's degree in economics from Penn State.  As a National 
Science Foundation fellow, he studied at the London School of 
Economics and Yale.

Even as a child growing up in suburban Philadelphia, Jim Caplan was 
something of an independent spirit who like intellectual challenges.

"Growing up as an only child, you learn to fight your own battles," he 
says.  Without brothers or sisters, "there's no one to confer with."

He liked playing sports.  He read a lot.  When he was about 12, he 
read a Clarence Darrow biography and decided to become an attorney.  
That thought was short-lived.

"I didn't like the idea that you could end up defending an argument 
you didn't believe in," he says.  "I didn't want to be a lawyer after 
that."

"I wanted to understand everything about people," he says.  "I was 
interested in the labor movement.  I was interested in how people 
lived, how you had poor people and rich people, and what made the 
system what it was."

So Caplan studies economics to become a businessman, and he continued 
thinking about ozone.  Then while he was living in Tegernsee, Germany, 
from 19696 to 1972, Caplan found himself at a Waldfest drinking beer 
with Dr. Josef Issels, a German cancer specialist who tried to bring 
about remissions in terminal patients.  Issels told Caplan of his 
efforts to build up the immune system and reduce the spread of cancer 
with ozone.

Meanwhile, Caplan read about the work of Dr. Ottokar Freiherr von 
Rokitansky, chief surgeon at a Vienna hospital.  Rokitansky reportedly 
used ozone to decrease the number of gangrene-related amputations by 
40 percent.  In 1983, Caplan met Rokitansky at an ozone conference in 
Washington, D.C., where the researcher was reporting on his work with 
ozone to treat circulatory problems.

In 1987, Caplan became CEO of his father's Philadelphia business, 
Capp, Inc.  The business primarily makes temperature controls for 
melting things like metals, plastics, pharmaceuticals and Hershey's 
chocolate.  Caplan says the work sharpens his determination to find 
answers to technical problems.  "You can't leave a company like DuPont 
up in the air." he says, "or they won't do business with you anymore."

In 1988, he saw one of his employees, Dorothy Simmons Hardy, trying to 
recover from a sickle-cell crisis.  "At 2 o'clock in the afternoon I 
would see her with her head on her desk, terribly fatigued," Caplan 
says.

He wanted to help.  He turned to a general medical text, Boyd's 
Pathology, and looked up sickle cell anemia.  The book described red 
blood cells that lose their shape and elasticity when the blood's 
oxygen partial-pressure falls below 45 millimeters of mercury.

Oxygen pressure.  Caplan remembered the strawberries.  He remembered 
the doctors in Germany.  Then he wondered: Why not use German ozone 
techniques to treat sickle-cell crisis?  If Germany can do it, why not 
the United States?

Closed doors at Children's

"I reviewed the material Mr. Caplan sent me," says Dr. Alan Schechter, 
a sickle-cell specialist and chief of the Laboratory of Chemical 
Biology in NIH's National Institute of Diabetes and Digestive and 
Kidney Diseases in Bethesda.  "I was very impressed.  The data looked 
very nice."

"He's right," Schechter says.  "If you could increase the partial 
pressure of oxygen, it would probably have a beneficial therapeutic 
effect (on sickle-cell patients).  I think it's an interesting idea."

Schechter suggested that Caplan take his idea to Children's Hospital 
in Philadelphia, because Asakura is the person in the United States 
with the technology best able to measure the sickling of cells.  
Ironically, Caplan says he already tried to interest Children's.

Caplan says he first took the concept to Children's, which receives 
$1.5 million a year from NIH as well as large private grants 
specifically to study sickle cell anemia.  It has 22 sickle-cell 
studies going at the moment.

"I wanted them to join me and do the scientific research (one ozone 
therapy) in the United States," Caplan says.

Caplan says he left an ozone generator and other equipment at 
Children's, and that he spoke every week with Asakura for two years.  
"I think Asakura was very interested in the possibilities here," 
Caplan says.  He says he hosted Asakura, his wife and other Children's 
staffers in his home to witness German doctors using ozone therapy.

Asakura says he is "very interested" in studying the effects of ozone 
on sickle cell anemia, and that he remembers the hospital being 
approached by someone to study ozone.  He says he can't remember who 
it was, but that it definitely wasn't Caplan.  "The hospital rejected 
the company because their interest is not the research, but the name 
on our hospital," Asakura says.  "This hospital decided that it is 
inappropriate that I conduct the research for the company.

"(Children's) Hospital is very interested in any good research," 
Asakura says.  But Children's doesn't want him to accept research 
money from a for-profit company because there could be pressure to 
come up with certain findings, Asakura says.  However, "I may 
(research ozone) in the future, when I have time and money."

If Asakura can't remember Caplan by name, his supervisor certainly 
does.

"We just could not be pushed or coerced into an area of research we 
have no preparation for," says Dr. Kwaku Ohene-Frempong, who heads up 
Children's Sickle Cell Center.

"Ozone kills bacteria," he says.  "It will also supply a lot of oxygen 
to tissues that need to be repaired."  However, he adds, "medicine, or 
science, doesn't just run in fits and starts.  You have to develop 
some scientific basis for something."

He points to acupuncture, the ancient Chinese therapy that ever-so-
slowly is gaining credibility in the United States.  It takes time for 
the momentum and scientific paperwork to build up, Frempong says.  "If 
I propose an ozone study to my institutional review board, they will 
think I'm crazy."

Cutting the pain in half

After months of trying to interest American doctors, Caplan attended a 
1989 ozone conference in New York.  A delegation of Cuban scientists 
was reporting on their use of ozone to treat retinitis pigmentosa, a 
progressive retina disease that leads to blindness.  Caplan mentioned 
sickle cell to them.

Cuban doctors Sylvia Menendez, Manuel Gomez, and E. Espinosa were 
intrigued.  Perhaps they could use a therapy they already were using 
safely, but for a new purpose.  Statistically, sickle cell anemia 
strikes about 1 percent of all blacks--which is a significant number 
of people in a country that is more than half black.  Caplan sent 
Gomez his notes.

At the National Center for Scientific Research and the Institute of 
Hematology and Immunology, both in Havana, the Cuban doctors started 
their research with animals to prove the ozone-enema treatment wasn't 
toxic.  By May 1990, they already had conducted clinical trials with 
more than 100 sickle-cell patients.

The complex system of capillaries in the colon was able to pick up the 
oxygen and help the sickled blood cells flow more smoothly.  The 
doctors reported that ozone helped patients resolve their sickle-cell 
crises in half the time, and that patients treated with ozone suffered 
fewer recurrences in the six months afterward.  (Their findings are 
published in the January 1995 issue of the Townsend Letter for 
Doctors, which calls itself "an informal letter magazine for doctors 
communicating with doctors.")  By November 1990, the Cuban Minister of 
Health approved ozone as a treatment for sickle cell anemia.

As Caplan figures it, the Cuban doctors who conducted the sickle-cell 
research are "wonderful, caring human beings" who work 12 hours a day, 
six days a week.  "The seem to be extremely dedicated to patient 
care."

American doctors also want to improve patients' lives, but it's harder 
for them, Caplan says.  American doctors have to fight for their 
positions at hospitals, they have to plan their studies around grant 
money available if they work at research institutions, and they have 
to watch every step for fear of a lawsuit.

Cuban doctors "don't go through what our doctors go through," Caplan 
says.  "They can really practice medicine."

Caplan presented a paper on Cuba's ozone successes at the 18th annual 
meeting of the National Association for Sickle Cell disease, held in 
May 1993 at Children's Hospital in Philadelphia.  More than 100 care-
givers were present, but not one doctor showed interest.

Several medical experts told the Welcomat they dismiss evidence from 
Cuba because they see it as a troubled Third World country without so 
much as a free press.

A tortoise among hares

It isn't easy to get the American medical establishment to pay 
attention to the work of doctors in other countries.

When American researchers hear of foreign data, "they tend to say 'Who 
are these people?  Are they running a monkey-gland clinic?'" says Art 
Caplan, director of the Center for Bioethics at Penn.

"The fact that (a therapy) is used in Europe doesn't really imply that 
it really is valuable," says Schechter at NIH.

Realistically, the research findings might be less accurate outside 
the U.S. because, in most countries, researchers are allowed to try 
experimental treatments on people without double-blind studies.  In a 
double-blind study, neither the patient nor doctor knows who's getting 
the drug and who's getting a placebo.  Theoretically, patients could 
improve from a treatment simply because they expect to.

Other countries also are more willing to allow human experimentation 
without preliminary tests in test tubes and on animals, American 
researchers say.  Plus, researchers in other countries don't face the 
same significant studies to demonstrate a treatment is effective.

When American pharmaceutical companies have an idea, they often start 
their research in Europe.  By going overseas, drug companies can 
evaluate a drug faster and put it on the market there long before it 
hits the States, if it ever does.

"Their (European) procedures are much easier, so it takes less time," 
says Mark Grayson, a spokesperson for the Pharmaceutical Research and 
Manufacturers of America.  "The drug agencies aren't quite as 
intrusive, and they move much quicker than our FDA."

Schechter and other researchers are quick to point out that Americans 
don't want a drug that could be harmful to, say, one patient in 50.

It seems odd to talk about researching a toxic cure.  But German 
doctors seem to be able to use ozone without killing people, points 
out Art Caplan.  To study the effects ozone on people, American 
researchers first would have to prove that it can be delivered without 
hurting people--which would be redundant when it's already being used 
safely in Europe, Art Caplan says.

Unfortunately, Americans "don't have a way for systematically 
incorporating safety finding" from other countries, he says.

Perhaps worse yet, ozone's reputation in the U.S. suffers from people 
outside the medical profession who make claims before they have the 
scientific data.  Certain people have offered ozone to desperate AIDS 
patients as a cure-all without the research to back their promises, 
Poiesz says.  "If a concept gets associated with that, sometimes it's 
hard to break out of that cache of illegitimacy."

Many American researchers, people who like to know the microscopic 
scientific steps within the overall process, are befuddled by ozone.  
It isn't completely understood.

"If you look at the studies that are done by the Cubans, it looks like 
they have major effects...on their patients," says Frans Kuypers, a 
Ph.D. research scientist who has studied ozone at the Sickle Cell 
Center at Children's Hospital in Oakland, Calif.  But "none of those 
(Cuban) studies clearly defines why it is effective."

Test anxiety

The people who think ozone has potential therapeutic benefits are 
among the first to say ozone should be scrutinized with big, 
scientific American tests.  They just want those tests to be done.

Because so many people have promoted the use of ozone, "it deserves 
some legitimate study to say does this stuff have a potential or not, 
just to put it to rest," says Dr. Bernard Poiesz, a virologist who has 
studied the effect of ozone on the HIV virus at the State University 
of New York at Syracuse.  "There's a lot of clinicians that are using 
it for all kinds of things."

Here in the United States, Dr. Michael Carpendale of San Francisco has 
been studying the potential uses of ozone for 15 years.  He says all 
of his research has confirmed what German doctors have been saying 
about ozone's benefits.

Carpendale studied five AIDS patients who had suffered from AIDS 
diarrhea for an average of 38 weeks.  He found that four of the five 
patients improved after ozone-enema treatments.  The results were 
published in 1993 in the Journal of Clinical Gastroenterology.

"Although it was only five patients, it was very meticulously studied, 
very rigid," Carpendale says.  "We thought once we published that, 
that it would be easy to get funding for a proper study with 50 
patients or 60 patients."

A large study would be relatively expensive--$500,000 or so--because 
repeated lab tests would have to be done to track the treatment's 
progress, Carpendale says.  But "ozone isn't expensive in itself.  
It's just the price of oxygen, and that's very cheap."

Carpendale got some Veteran's Administration research money 10 years 
ago, and later he got some private funding that he stretched over two 
years, but he hasn't been able to catch the eye of NIH review 
committees.  As he sees it, that's because ozone has no credibility in 
the "official party line" of conventional American medicine.

"It's very hard to take that," Carpendale says.  "The thing is, I 
wouldn't mind if there were one good scientific study done...to say 
'Look, it doesn't work.'"

Double-blind "is certainly the right way to go," Carpendale says.  
"But to put something down which they haven't done any tests on...

"AIDS diarrhea is such a bad disease to have.  To die of it is really 
very hard.  But you really need to ask someone who's more 
dispassionate than I am."

At State University of New York, Poiesz has been frustrated, too.

In his study, he found that ozone could be used for "almost seemingly 
complete destruction" of HIV without affecting blood protein.  It's 
too early to jump to conclusions, he says, but the HIV-infected cells 
were more vulnerable to ozone than healthy cells.  This raises the 
possibility that AIDS patients could be treated with ozone.

His study also showed that a system to sterilize human plasma with 
ozone could be safe for handlers, he says.  He thinks that 
theoretically, ozone could protect medical staff and patients from HIV 
and other viruses that have not yet been identified.  The results were 
published in 1991 in Blood, the leading medical journal on blood and 
blood diseases.

Poiesz collaborated with Medizone, a New York company that hopes to 
get approval to use ozone to decontaminate blood products as well as 
treat viral diseases, including hepatitis B, herpes and HIV.  Medizone 
International has worked with the Italian Scientific Society for Ozone 
Oxygen Therapy (ISSOT) on clinical trials at the University of Naples.  
If the process is approved, Medizone has patent rights to the process 
in the United States, Canada, Japan, Hong Kong and other countries.

Poiesz is interested in doing more ozone studies, but his research 
hospital can't afford it.  Medizone president Joe Latino has tried to 
find additional funding, but he hasn't gotten very far.  NIH generally 
funds just 15 percent of research proposals, and this idea wasn't 
among them.

"The government deemed it not worthy of funding," Poiesz says.  He 
says there was a bias among certain project reviewers that ozone 
wouldn't be very useful.  "They just didn't think it had a priority."

"What I really think we know about (ozone) is somewhere between 
nothing and not much." Penn's Art Caplan says.  "What bothers me is 
that people aren't trying to push hard to get it tested" in the U.S.

A matter of money

American scientists spend many years studying individual steps in the 
basic science long before actual human beings are introduced to the 
equation.  Then the clinical trials go on for years.  Schechter has 
spent the last 10 years at NIH studying three drugs to try to increase 
fetal hemoglobin in the blood of sickle-cell patients.  "It's very 
slow going," he says.  "We probably will not know the answers for 
three or four years."

"Historically, maybe on in 100 people who advocate an offbeat approach 
to medicine will turn out to have something important," Schechter 
says.  Unfortunately, nobody knows which Wonka bar has the golden 
ticket.

"I can tell you that there are 25 or 50 other types of compounds that 
people are advocating for sickle-cell therapy," he says, adding that 
of 20 to 30 sickle-cell proposals in the '70s, "virtually none" are 
considered viable today.

At least half a dozen companies have potential sickle-cell drugs in 
the pipeline right now, he says.  "They're having the same type of 
frustration.  What Mr. Caplan is experiencing with ozone is not 
unique.?

Realistically, researchers say, choices must be made.

"There are always many more important questions that can't get 
answered for lack of funds," says Dr. David Asch, a senior fellow at 
the Leonard Davis Institute of Health Economics, University of 
Pennsylvania.  Getting federal research money is a matter of 
convincing people that an idea has merit, he says.  "You can't test 
everything.  I don't know if sucking on truck tires will cure cancer, 
but my guess is it won't."

Scientists know that oxygen can make sickled cells normal again, but 
ozone studies would have to progress from test-tube studies to animal 
studies and then to human studies, says Frempong at Children's 
Hospital.  "You can't jump over all those steps and just say, 'I'm 
going to test this on humans.'  You can't just have a hunch and test 
it."

All this research takes money, and most of the money for research in 
this country comes from private industry.  The pharmaceutical industry 
spends more than $13 billion a year on research--far more than the 
$700 million NIH allocates for studies, Grayson says.

Some of the proposals never pan out.  On average, pharmaceutical 
companies spend $359 million per drug to get FDA approval, Grayson 
says.  As a result, drug companies spend their research dollar "where 
they feel they've got a real breakthrough.  You don't set up to do 
something somebody else is already doing."

Financially, it doesn't make sense for drug companies to pump research 
money into ozone because drug companies are for-profit businesses.  
Ozone is a naturally occurring compound that can't be patented.

The FDA realized that these financial realities and its strict 
regulations limit research into potentially useful drugs.  So the 
agency set up an orphan drug designation to encourage research on 
disease that affect 200,000 or fewer people in the United States.

The orphan drug program provides $9 million in grants each year, tax 
credits on research done, and a seven-year exclusive license if the 
process is approved by the FDA for that particular disease.

Jim Caplan has orphan-drug designation for ozone to treat sickle-cell 
anemia.  If the process is approved, he would own the patent on the 
delivery process in sickle-cell cases for seven years.

He says he hasn't even applied for orphan-drug research funding yet 
because he doesn't have the American scientists to conduct ozone 
research on sickle cell anemia.

An outsider looking in

Jim Caplan says he's frustrated.  He doesn't feel he's being taken 
seriously because he doesn't have "the right pedigree," a medical 
degree.

People from outside the medical world can been seen as the equivalent 
of snake-oil peddlers with "the latest bottle of feel-good stuff," Art 
Caplan says.

But it's also hard for people within the system, Schechter points out.

As Poiesz puts it, a businessman suggesting a medical idea is like a 
doctor trying to get a bill through Congress.  He says he's not 
surprised Caplan, and outsider to the medical establishment, has met 
with such resistance.

"Oftentimes, they get pretty chilly receptions," Art Caplan agrees.

"Always there are people who like to make money," says Asakura at 
Children's Hospital.  He says he would not be willing to join forces 
with a business that would sell ozone generators.  "For pure science I 
am interested."

"I wonder if they ever asked people like Frempong and Asakura how much 
Children's Hospital makes on sickle cell anemia," Jim Caplan says.

He says that if he were interested in profits, he wouldn't have 
devoted about 15 percent of his business week for years on end to an 
idea that might never see the light of day.

"I've gone all over the world and pursued this thing," he says.  "My 
whole motivation was to establish this mode of thinking and treatment.  
There are many other areas where I can make a profit."

Improving lives

If a large, wealthy pharmaceutical company were steering ozone through 
the testing process, perhaps it would have a better shot.  But the 
fact remains that pharmaceuticals would have no reason to take on a 
product as simple as ozone.  As soon as the seven-year protection 
period ends, says Whitmore at the FDA, "29 companies are pumping it 
out in New Jersey."

Jim Caplan doesn't care.

"So you've got competition," he says.  "So you make a better product."  
The real issue, he says, is the number of people whose lives might be 
improved with this cheap and simple process that needs to be tested.

"I grew up playing an awful lot of athletics.  I like to win.  If I 
think I'm right, I will persevere." Jim Caplan says.  He's trying to 
get as many people on his team as he can.  "There are people out there 
who will fight to fight.  You just have to find them."

Even if he gets a seven-year ozone delivery patent for sickle-cell 
treatment, Jim Caplan believes he could not make nearly as much money 
from ozone therapy as the American health system could save if it were 
approved.

Take the use of ozone to prevent diabetic amputations, for instance.  
He clicks some conservative numbers into his adding machine: "If you 
had 50,000 amputations a year and you reduced it by 35 percent, that 
would be...let's say the operation is $15,000, conservatively, with a 
stay in the hospital, and the rehabilitation afterwards is another 
$15,000..."

Let's see...17,500 people at $30,000 a head...

"That would be a savings of $525 million in this society."

That's every single year.  And that's beyond the humanitarian side of 
things.

In May 1990, Jim Caplan saw a young Cuban woman lying on a treatment 
bench.  "I came into the ward, and she was actually being treated for 
the ulcers on her leg," he says.  With repeated ozone treatments, he 
says her sores were going away.

"I was introduced as the man from the United States who introduced the 
ozone/oxygen treatment to Cuba," Jim Caplan says.  "The gal's eyes lit 
up...(Through an interpreter) she said, 'You know, all my life I've 
had these ulcers on my legs.  I've never been able to wear a dress.'

"She hugged me, and tears came to her eyes, and tears came to my 
eyes," Jim Caplan says.  "It was an extremely moving experience.  It 
just makes you want to fight it through."

Source: Welcomat Newspaper.  (The Philadelphia Weekly: News, Arts & 
                              Opinion)
        Volume XXIV, No. 26, January 11, 1995