| ... |
After more than 3 years,
UH Cancer Center director
still has no employment
agreement
Posted: May 28, 2013 7:14
PM PST Updated: May 30,
2013 9:06 PM PST
By Keoki Kerr
Hawaii News Now
Dr. Michele Carbone;
University of Hawaii Cancer
Center Director Dr.
Michele Carbone;
University of Hawaii Cancer
Center Director
HONOLULU
(HawaiiNewsNow) -
University of Hawaii Cancer
Center Director Dr.
Michele Carbone asked for
an employment agreement
a year ago, after nearly
two and a half years on the
job, but still has not
received such an
agreement from his boss,
UH Manoa Chancellor Tom
Apple.
Carbone has recruited top
researchers from Yale,
Brown, the University of
North Carolina and other
well-known research
universities. He said the
center has tripled its
research grant funding
under his leadership to
$32 million and raised
another $22.5 million in
donations during his
tenure.
But he has also been
criticized by some UH
faculty and staff for his
management style and a
my-way-or-the-highway
approach to leadership.
Carbone is paid $391,416
a year and has been
administrator of the
Cancer Center since
September of 2009. He is
the fourth highest-paid
administrator in the UH
system, behind UH Medical
School Dean Jerris
Hedges, UH President
MRC Greenwood and
Apple.
"So far I'm still on a
handshake," Carbone told
Hawaii News Now in one of
his two offices at the
Cancer Center last Friday.
He said he made a
handshake agreement –
and no written contract --
with former UH Chancellor
Virginia Hinshaw when he
took the job in the fall of
2009.
Carbone said few people
expected UH to be able to
renew its designation from
the National Cancer
Institute last year, but that
happened.
"The agreement was if I
didn't renew the Cancer
Center designation, that
was it. Out! I was going to
go, end of it," Carbone
said.
Then, in early June of last
year, right after the cancer
center won re-designation
from the National Cancer
Institute, just before
Hinshaw stepped down,
Carbone met with Hinshaw.
"I said to her, "You know
chancellor, I am in this job
with a shake hand with
you. But you are leaving.
Maybe I need a contract
now," Carbone said.
But he said since Hinshaw
was leaving her post, she
didn't feel it was right for
her to approve a new
contract for him in her final
days so she wrote up an
offer and left it for Apple,
the incoming UH
chancellor. That was one
year ago.
In an email, Apple told
Hawaii News Now, "The
fact that Dr. Carbone has
not been offered a
reappointment contract is
not an oversight. His
reappointment is being
actively discussed."
Apple said it would be
inappropriate to discuss
details of the
conversations he's having
with Carbone, Cancer
Center faculty and others
involved with the Cancer
Center as he decides what
to do about Carbone's
contract.
"This is not a rubber stamp
situation," Apple said.
"There are important
conversations that need to
be wrapped up before this
facet of the Cancer
Center's future can be
determined."
Carbone had this
exchange in an interview
with Hawaii News Now's
Keoki Kerr:
Carbone: I think that it
would be nice for the
university to give me a
contract, considering the
fact that in fact, things
have worked fantastically
well around here. But
that's where we are.
Kerr: But they haven't said
no, they just haven't gotten
back to you, is that right?
Carbone: I have not heard
from them, yes, exactly.
Sources said while some
top UH administrators feel
Carbone has the
personality of a start-up
CEO who's a brilliant
researcher, they don't feel
he's been a good manager
and administrator.
Four researchers have
successfully filed
complaints against him.
After disagreements with
the UH Manoa Vice
Chancellor for Research
and Graduate Education's
office over spending and
hiring issues, Carbone
began reporting directly to
then-Chancellor Hinshaw.
Carbone described the
situation this way:
"The previous vice
chancellor office, was
difficult to get things done
quickly and so often I had
to go to Chancellor
Hinshaw and say 'Look,
this thing needs to be
done now. I can't wait
another six months. We
agreed to do this. We had
to do it.' So many, many
times, she had to step in
and in the end, in fact, I
was working only with her,
because that was the only
way to get things done
quickly," Carbone said.
"It worked very well. You
see how we did," he said,
gesturing to the new
Cancer Center, that was
completed three months
before schedule and about
13 percent under budget
at $104 million. The UH is
still paying $1 million a
year to rent space at the
former Gold Bond building
a few blocks away, even
though between 35 and 30
percent of the space in the
new center and the rented
site is empty.
Even if he's not retained
as director, Carbone can
remain at the Cancer
Center, where he has a
tenured professorship.
Before being elevated to
the director's post,
Carbone was interim
director of the UH Cancer
Center, at the salary of
$356,112. When the UH
Board of Regents
approved his hiring as
director in August 2009,
Carbone's UH hiring memo
said his $412,008 salary
was appropriate, since the
median salary for cancer
center directors across the
country was slightly higher
at $415,000. Carbone,
like all UH administrative
staff, took a pay cut to
match the pay reductions
faced by other UH
employees, so his
temporary salary reduction
in 2009 brought his pay
down to $379,056, and it
was increased in June
2011 to $391,416, which
continues today, UH
officials said.
The following article says, "Complete coverage of the Kops article appeared in
the January 2001 issue of COLUMNS-Asbestos...Referred to by ABC News
anchor Peter Jennings as a fierce debate among the scientific community, the
issue of SV40's role in mesothelioma and certain bone and brain tumors was
among the topics discussed during a meeting held yesterday in Bethesda, Md.,
according to ABC News."
Peter Jennings died in 2005, so I'm guessing this article was published between
2001 and around 2005.
ABC News
Cancer Experts Puzzled By Monkey Virus
March 12
By Kevin Newman
It is a mystery with enormous implications that has stumped some of the
smartest minds in cancer research: How did a cancer-causing monkey virus
end up in human tumors?
If it is indeed in humans, its role in causing human cancers is unknown.
Scientists say it may play a key part — or possibly no part at all.
The puzzle began in 1994, when Dr. Michele Carbone, a Loyola University
researcher, found the virus SV40, which had never before been
detected in humans, in half of the human lung tumors he was studying.
SV40 is known to create tumors in animals, but how it might have gotten into
humans was unclear.
"I thought there must be something wrong. I must have made a mistake," he
said, remembering the discovery.
Eventually, 60 different lab studies confirmed the results.
"This finding has been replicated in New Zealand, in China, in Britain, in
France, in Switzerland, in Belgium," Carbone said.
Several labs did not find any evidence of SV40, and some researchers
continue to question Carbone's findings. Efforts in general to explain the SV40
mystery have been hampered by unusual acrimony among those studying the
problem.
Could It Have Been Transmitted By Polio Vaccine?
If the monkey virus SV40 is indeed in humans, there are several possible
explanations for how it got there, says Janet Butel, a virologist at Baylor College
of Medicine and one of America's leading virus researchers.
"One is that it has always been there in humans, and no one has detected it in
the past," Butel said.
There is another, much more controversial theory as well, however.
Some researchers contend SV40 was transmitted to humans through the polio
vaccine, which has saved many lives. The vaccine is made in monkey kidney
cells, and from 1955 to 1963 an estimated 20 million Americans were given
doses contaminated with SV40.
Still, the virus was not detected in humans until Carbone's 1994 research,
possibly because no one had thought to look for it.
In 1961, the Food and Drug Administration ordered the vaccine's
manufacturers to screen out the SV40, which they say they did.
But a lawyer involved in a recent polio case has just published a report claiming
contamination continued.
"In certain instances, no [SV40] tests were ever performed," the lawyer, Stan
Kops, wrote about one of the vaccine's manufacturers, Lederle.
‘Every Batch Was Screened,’ Insists Vaccine Maker
Lederle strongly disputes Kops' claim, telling ABCNEWS in a statement "every
batch of the polio virus used to manufacture vaccine underwent tissue culture
testing for SV40."
If that is true, it suggests another possible reason SV40 has been found in the
brain tumors of people born after 1963: transmission from mother to child.
"I think studies need to be done to figure out precisely what the role of the virus
might be in human cancer," said Butel.
Scientists specializing in SV40 met today in Bethesda, Md., to sort through
some of the controversies.
Some still question whether SV40 truly exists in humans, but the vast majority of
scientists attending the conference believe the role of SV40 in humans needs
urgent attention.
"We need to find out what it's doing there," said Butel. "It will be a great
significance if it's proven to have a role in human cancer because then … it
may be possible to block infection and the formation of a tumor."
There may be several viruses linked to cancer in humans.
ABCNEWS' Nicholas Regush, whose column Second Opinion appears weekly
on ABCNEWS.com, produced this report.
the January 2001 issue of COLUMNS-Asbestos...Referred to by ABC News
anchor Peter Jennings as a fierce debate among the scientific community, the
issue of SV40's role in mesothelioma and certain bone and brain tumors was
among the topics discussed during a meeting held yesterday in Bethesda, Md.,
according to ABC News."
Peter Jennings died in 2005, so I'm guessing this article was published between
2001 and around 2005.
ABC News
Cancer Experts Puzzled By Monkey Virus
March 12
By Kevin Newman
It is a mystery with enormous implications that has stumped some of the
smartest minds in cancer research: How did a cancer-causing monkey virus
end up in human tumors?
If it is indeed in humans, its role in causing human cancers is unknown.
Scientists say it may play a key part — or possibly no part at all.
The puzzle began in 1994, when Dr. Michele Carbone, a Loyola University
researcher, found the virus SV40, which had never before been
detected in humans, in half of the human lung tumors he was studying.
SV40 is known to create tumors in animals, but how it might have gotten into
humans was unclear.
"I thought there must be something wrong. I must have made a mistake," he
said, remembering the discovery.
Eventually, 60 different lab studies confirmed the results.
"This finding has been replicated in New Zealand, in China, in Britain, in
France, in Switzerland, in Belgium," Carbone said.
Several labs did not find any evidence of SV40, and some researchers
continue to question Carbone's findings. Efforts in general to explain the SV40
mystery have been hampered by unusual acrimony among those studying the
problem.
Could It Have Been Transmitted By Polio Vaccine?
If the monkey virus SV40 is indeed in humans, there are several possible
explanations for how it got there, says Janet Butel, a virologist at Baylor College
of Medicine and one of America's leading virus researchers.
"One is that it has always been there in humans, and no one has detected it in
the past," Butel said.
There is another, much more controversial theory as well, however.
Some researchers contend SV40 was transmitted to humans through the polio
vaccine, which has saved many lives. The vaccine is made in monkey kidney
cells, and from 1955 to 1963 an estimated 20 million Americans were given
doses contaminated with SV40.
Still, the virus was not detected in humans until Carbone's 1994 research,
possibly because no one had thought to look for it.
In 1961, the Food and Drug Administration ordered the vaccine's
manufacturers to screen out the SV40, which they say they did.
But a lawyer involved in a recent polio case has just published a report claiming
contamination continued.
"In certain instances, no [SV40] tests were ever performed," the lawyer, Stan
Kops, wrote about one of the vaccine's manufacturers, Lederle.
‘Every Batch Was Screened,’ Insists Vaccine Maker
Lederle strongly disputes Kops' claim, telling ABCNEWS in a statement "every
batch of the polio virus used to manufacture vaccine underwent tissue culture
testing for SV40."
If that is true, it suggests another possible reason SV40 has been found in the
brain tumors of people born after 1963: transmission from mother to child.
"I think studies need to be done to figure out precisely what the role of the virus
might be in human cancer," said Butel.
Scientists specializing in SV40 met today in Bethesda, Md., to sort through
some of the controversies.
Some still question whether SV40 truly exists in humans, but the vast majority of
scientists attending the conference believe the role of SV40 in humans needs
urgent attention.
"We need to find out what it's doing there," said Butel. "It will be a great
significance if it's proven to have a role in human cancer because then … it
may be possible to block infection and the formation of a tumor."
There may be several viruses linked to cancer in humans.
ABCNEWS' Nicholas Regush, whose column Second Opinion appears weekly
on ABCNEWS.com, produced this report.
| San Diego Education Report |
| SDER |
San Diego
Education Report
Education Report
| SDER |
| SDER |
| SDER |
"Dr. Michele Carbone openly acknowledged HIV/AIDS was spread by the hepatitis B
vaccine produced by Merck & Co. during the early 1970s. It was the first time since
the initial transmissions took place in 1972-74, that a leading expert in the field of
vaccine manufacturing and testing has openly admitted the Merck & Co. liability for
AIDS."
CDC Admits 98 Million Americans Received Polio Vaccine In An
8-Year Span When It Was Contaminated With Cancer Virus
by DAVE MIHALOVIC
Prevent Disease
July 17, 2013
The CDC has quickly removed a page from their website, which WAS cached here
(since removed by google so you can view an image of the cache here), admitting that
more than 98 million Americans received one or more doses of polio vaccine within an
8-year span from 1955-1963 when a proportion of the vaccine was contaminated with
a cancer causing polyomavirus called SV40. It has been estimated that 10-30 million
Americans could have received an SV40 contaminated dose of the vaccine.
SV40 is an abbreviation for Simian vacuolating virus 40 or Simian virus 40, a
polyomavirus that is found in both monkeys and humans. Like other polyomaviruses,
SV40 is a DNA virus that has been found to cause tumors and cancer.
SV40 is believed to suppress the transcriptional properties of the tumor-suppressing
genes in humans through the SV40 Large T-antigen and SV40 Small T-antigen.
Mutated genes may contribute to uncontrolled cellular proliferation, leading to cancer.
Michele Carbone, Assistant Professor of Pathology at Loyola University in Chicago,
has recently isolated fragments of the SV-40 virus in human bone cancers and in a
lethal form of lung cancer called mesothelioma. He found SV-40 in 33% of the
osteosarcoma bone cancers studied, in 40% of other bone cancers, and in 60% of the
mesotheliomas lung cancers, writes Geraldo Fuentes.
Dr. Michele Carbone openly acknowledged HIV/AIDS was spread by the hepatitis B
vaccine produced by Merck & Co. during the early 1970s. It was the first time since the
initial transmissions took place in 1972-74, that a leading expert in the field of vaccine
manufacturing and testing has openly admitted the Merck & Co. liability for AIDS.
The matter-of-fact disclosure came during discussions of polio vaccines contaminated
with SV40 virus which caused cancer in nearly every species infected by injection.
Many authorities now admit much, possibly most, of the world's cancers came from the
Salk and Sabin polio vaccines, and hepatitis B vaccines, produced in monkeys and
chimps.
It is said mesothelioma is a result of asbestos exposure, but research reveals that 50%
of the current mesotheliomas being treated no longer occurs due to asbestos but
rather the SV-40 virus contained in the polio vaccination. In addition, according to
researchers from the Institute of Histology and General Embryology of the University of
Ferrara, SV-40 has turned up in a variety other tumors. By the end of 1996, dozens of
scientists reported finding SV40 in a variety of bone cancers and a wide range of brain
cancers, which had risen 30 percent over the previous 20 years.
The SV-40 virus is now being detected in tumors removed from people never
inoculated with the contaminated vaccine, leading some to conclude that those
infected by the vaccine might be spreading SV40.
Soon after its discovery, SV40 was identified in the oral form of the polio vaccine
produced between 1955 and 1961 produced by American Home Products (dba
Lederle).
Both the oral, live virus and injectable inactive virus were affected. It was found later
that the technique used to inactivate the polio virus in the injectable vaccine, by means
of formaldehyde, did not reliably kill SV40.
Just two years ago, the U.S. government finally added formaldehyde to a list of known
carcinogens and and admitted that the chemical styrene might cause cancer. Yet, the
substance is still found in almost every vaccine.
According to the Australian National Research Council, fewer than 20% but perhaps
more than 10% of the general population may be susceptible to formaldehyde and
may react acutely at any exposure level. More hazardous than most chemicals in 5 out
of 12 ranking systems, on at least 8 federal regulatory lists, it is ranked as one of the
most hazardous compounds (worst 10%) to ecosystems and human health
(Environmental Defense Fund).
In the body, formaldehyde can cause proteins to irreversibly bind to DNA. Laboratory
animals exposed to doses of inhaled formaldehyde over their lifetimes have developed
more cancers of the nose and throat than are usual.
Facts Listed on The CDC Website about SV40
SV40 is a virus found in some species of monkey.
SV40 was discovered in 1960. Soon afterward, the virus was found in polio vaccine.
SV40 virus has been found in certain types of cancer in humans.
Additional Facts
In the 1950s, rhesus monkey kidney cells, which contain SV40 if the animal is infected,
were used in preparing polio vaccines.
Not all doses of IPV were contaminated. It has been estimated that 10-30 million
people actually received a vaccine that contained SV40.
Some evidence suggests that receipt of SV40-contaminated polio vaccine may
increase risk of cancer.
A Greater Perspective on Aerial Spraying and SV40
The Defense Sciences Office of the Pathogen Countermeasures Program, in
September 23, 1998 funded the University of Michigan's principal investigator, Dr.
James Baker, Jr. Dr. Baker, Director of Michigan Nanotechnology Institute for Medicine
and Biological Sciences under several DARPA grants. Dr. Baker developed and
focused on preventing pathogens from entering the human body, which is a major goal
in the development of counter measures to Biological Warfare. This research project
sought to develop a composite material that will serve as a pathogen avoidance barrier
and post-exposure therapeutic agent to be applied in a topical manner to the skin and
mucous membranes. The composite is modeled after the immune system in that it
involves redundant, non-specific and specific forms of pathogen defense and
inactivation. This composite material is now utilized in many nasal vaccines and vector
control through the use of hydro-gel, nanosilicon gels and actuator materials in
vaccines.
Through Dr. Baker's research at the University of Michigan; he developed dendritic
polymers and their application to medical and biological science. He co-developed a
new vector system for gene transfer using synthetic polymers. These studies have
produced striking results and have the potential to change the basis of gene transfer
therapy. Dendrimers are nanometer-sized water soluble polymers that can conjugate
to peptides or arbohydrates to act as decoy molecules to inhibit the binding of toxins
and viruses to cells. They can act also as complex and stabilize genetic material for
prolonged periods of time, as in a "time released or delayed gene transfer". Through
Dr. Baker's ground breaking research many pharmaceutical and biological pesticide
manufacturers can use these principles in DNA vaccines specific applications that
incorporate the Simian Monkey Virus SV40.
WEST NILE VIRUS SPRAYING
In 2006 Michael Greenwood wrote an article for the Yale School of Public Health
entitled, "Aerial Spraying Effectively Reduces Incidence of West Nile Virus (WNV) in
Humans." The article stated that the incidence of human West Nile virus cases can be
significantly reduced through large scale aerial spraying that targets adult mosquitoes,
according to research by the Yale School of Public Health and the California
Department of Public Health.
Under the mandate for aerial spraying for specific vectors that pose a threat to human
health, aerial vaccines known as DNA Vaccine Enhancements and Recombinant
Vaccine against WNV may be tested or used to "protect" the people from vector
infection exposures. DNA vaccine enhancements specifically use Epstein-Barr viral
capside's with multi human complement class II activators to neutralize antibodies. The
recombinant vaccines against WNV use Rabbit Beta-globulin or the poly (A) signal of
the SV40 virus. In early studies of DNA vaccines it was found that the negative result
studies would go into the category of future developmental research projects in gene
therapy. During the studies of poly (A) signaling of the SV40 for WNV vaccines, it was
observed that WNV will lie dormant in individuals who were exposed to chicken pox,
thus upon exposure to WNV aerial vaccines the potential for the release of chicken pox
virus would cause a greater risk to having adult onset Shingles.
CALIFORNIA AERIAL SPRAYING for WNV and SV40
In February 2009 to present date, aerial spraying for the WNV occurred in major cities
within the State of California. During spraying of Anaheim, CA a Caucasian female
(age 50) was exposed to heavy spraying, while doing her daily exercise of walking
several miles. Heavy helicopter activity occurred for several days in this area. After
spraying, she experienced light headedness, nausea, muscle aches and increased low
back pain. She was evaluated for toxicological mechanisms that were associated with
pesticide exposure due to aerial spraying utilizing advanced biological monitoring
testing. The test results which included protein band testing utilizing Protein Coupled
Response (PCR) methods were positive for KD-45. KD-45 is the protein band for
SV-40 Simian Green Monkey virus. Additional tests were performed for Epstein-Barr
virus capside and Cytomeglia virus which are used in bioengineering for gene delivery
systems through viral protein envelope and adenoviral protein envelope technology.
The individual was positive for both; indicating a highly probable exposure to a DNA
vaccination delivery system through nasal inhalation.
The question of the century is how many other viruses and toxins are within current
day vaccines that we'll only find out about in a few decades?
vaccine produced by Merck & Co. during the early 1970s. It was the first time since
the initial transmissions took place in 1972-74, that a leading expert in the field of
vaccine manufacturing and testing has openly admitted the Merck & Co. liability for
AIDS."
CDC Admits 98 Million Americans Received Polio Vaccine In An
8-Year Span When It Was Contaminated With Cancer Virus
by DAVE MIHALOVIC
Prevent Disease
July 17, 2013
The CDC has quickly removed a page from their website, which WAS cached here
(since removed by google so you can view an image of the cache here), admitting that
more than 98 million Americans received one or more doses of polio vaccine within an
8-year span from 1955-1963 when a proportion of the vaccine was contaminated with
a cancer causing polyomavirus called SV40. It has been estimated that 10-30 million
Americans could have received an SV40 contaminated dose of the vaccine.
SV40 is an abbreviation for Simian vacuolating virus 40 or Simian virus 40, a
polyomavirus that is found in both monkeys and humans. Like other polyomaviruses,
SV40 is a DNA virus that has been found to cause tumors and cancer.
SV40 is believed to suppress the transcriptional properties of the tumor-suppressing
genes in humans through the SV40 Large T-antigen and SV40 Small T-antigen.
Mutated genes may contribute to uncontrolled cellular proliferation, leading to cancer.
Michele Carbone, Assistant Professor of Pathology at Loyola University in Chicago,
has recently isolated fragments of the SV-40 virus in human bone cancers and in a
lethal form of lung cancer called mesothelioma. He found SV-40 in 33% of the
osteosarcoma bone cancers studied, in 40% of other bone cancers, and in 60% of the
mesotheliomas lung cancers, writes Geraldo Fuentes.
Dr. Michele Carbone openly acknowledged HIV/AIDS was spread by the hepatitis B
vaccine produced by Merck & Co. during the early 1970s. It was the first time since the
initial transmissions took place in 1972-74, that a leading expert in the field of vaccine
manufacturing and testing has openly admitted the Merck & Co. liability for AIDS.
The matter-of-fact disclosure came during discussions of polio vaccines contaminated
with SV40 virus which caused cancer in nearly every species infected by injection.
Many authorities now admit much, possibly most, of the world's cancers came from the
Salk and Sabin polio vaccines, and hepatitis B vaccines, produced in monkeys and
chimps.
It is said mesothelioma is a result of asbestos exposure, but research reveals that 50%
of the current mesotheliomas being treated no longer occurs due to asbestos but
rather the SV-40 virus contained in the polio vaccination. In addition, according to
researchers from the Institute of Histology and General Embryology of the University of
Ferrara, SV-40 has turned up in a variety other tumors. By the end of 1996, dozens of
scientists reported finding SV40 in a variety of bone cancers and a wide range of brain
cancers, which had risen 30 percent over the previous 20 years.
The SV-40 virus is now being detected in tumors removed from people never
inoculated with the contaminated vaccine, leading some to conclude that those
infected by the vaccine might be spreading SV40.
Soon after its discovery, SV40 was identified in the oral form of the polio vaccine
produced between 1955 and 1961 produced by American Home Products (dba
Lederle).
Both the oral, live virus and injectable inactive virus were affected. It was found later
that the technique used to inactivate the polio virus in the injectable vaccine, by means
of formaldehyde, did not reliably kill SV40.
Just two years ago, the U.S. government finally added formaldehyde to a list of known
carcinogens and and admitted that the chemical styrene might cause cancer. Yet, the
substance is still found in almost every vaccine.
According to the Australian National Research Council, fewer than 20% but perhaps
more than 10% of the general population may be susceptible to formaldehyde and
may react acutely at any exposure level. More hazardous than most chemicals in 5 out
of 12 ranking systems, on at least 8 federal regulatory lists, it is ranked as one of the
most hazardous compounds (worst 10%) to ecosystems and human health
(Environmental Defense Fund).
In the body, formaldehyde can cause proteins to irreversibly bind to DNA. Laboratory
animals exposed to doses of inhaled formaldehyde over their lifetimes have developed
more cancers of the nose and throat than are usual.
Facts Listed on The CDC Website about SV40
SV40 is a virus found in some species of monkey.
SV40 was discovered in 1960. Soon afterward, the virus was found in polio vaccine.
SV40 virus has been found in certain types of cancer in humans.
Additional Facts
In the 1950s, rhesus monkey kidney cells, which contain SV40 if the animal is infected,
were used in preparing polio vaccines.
Not all doses of IPV were contaminated. It has been estimated that 10-30 million
people actually received a vaccine that contained SV40.
Some evidence suggests that receipt of SV40-contaminated polio vaccine may
increase risk of cancer.
A Greater Perspective on Aerial Spraying and SV40
The Defense Sciences Office of the Pathogen Countermeasures Program, in
September 23, 1998 funded the University of Michigan's principal investigator, Dr.
James Baker, Jr. Dr. Baker, Director of Michigan Nanotechnology Institute for Medicine
and Biological Sciences under several DARPA grants. Dr. Baker developed and
focused on preventing pathogens from entering the human body, which is a major goal
in the development of counter measures to Biological Warfare. This research project
sought to develop a composite material that will serve as a pathogen avoidance barrier
and post-exposure therapeutic agent to be applied in a topical manner to the skin and
mucous membranes. The composite is modeled after the immune system in that it
involves redundant, non-specific and specific forms of pathogen defense and
inactivation. This composite material is now utilized in many nasal vaccines and vector
control through the use of hydro-gel, nanosilicon gels and actuator materials in
vaccines.
Through Dr. Baker's research at the University of Michigan; he developed dendritic
polymers and their application to medical and biological science. He co-developed a
new vector system for gene transfer using synthetic polymers. These studies have
produced striking results and have the potential to change the basis of gene transfer
therapy. Dendrimers are nanometer-sized water soluble polymers that can conjugate
to peptides or arbohydrates to act as decoy molecules to inhibit the binding of toxins
and viruses to cells. They can act also as complex and stabilize genetic material for
prolonged periods of time, as in a "time released or delayed gene transfer". Through
Dr. Baker's ground breaking research many pharmaceutical and biological pesticide
manufacturers can use these principles in DNA vaccines specific applications that
incorporate the Simian Monkey Virus SV40.
WEST NILE VIRUS SPRAYING
In 2006 Michael Greenwood wrote an article for the Yale School of Public Health
entitled, "Aerial Spraying Effectively Reduces Incidence of West Nile Virus (WNV) in
Humans." The article stated that the incidence of human West Nile virus cases can be
significantly reduced through large scale aerial spraying that targets adult mosquitoes,
according to research by the Yale School of Public Health and the California
Department of Public Health.
Under the mandate for aerial spraying for specific vectors that pose a threat to human
health, aerial vaccines known as DNA Vaccine Enhancements and Recombinant
Vaccine against WNV may be tested or used to "protect" the people from vector
infection exposures. DNA vaccine enhancements specifically use Epstein-Barr viral
capside's with multi human complement class II activators to neutralize antibodies. The
recombinant vaccines against WNV use Rabbit Beta-globulin or the poly (A) signal of
the SV40 virus. In early studies of DNA vaccines it was found that the negative result
studies would go into the category of future developmental research projects in gene
therapy. During the studies of poly (A) signaling of the SV40 for WNV vaccines, it was
observed that WNV will lie dormant in individuals who were exposed to chicken pox,
thus upon exposure to WNV aerial vaccines the potential for the release of chicken pox
virus would cause a greater risk to having adult onset Shingles.
CALIFORNIA AERIAL SPRAYING for WNV and SV40
In February 2009 to present date, aerial spraying for the WNV occurred in major cities
within the State of California. During spraying of Anaheim, CA a Caucasian female
(age 50) was exposed to heavy spraying, while doing her daily exercise of walking
several miles. Heavy helicopter activity occurred for several days in this area. After
spraying, she experienced light headedness, nausea, muscle aches and increased low
back pain. She was evaluated for toxicological mechanisms that were associated with
pesticide exposure due to aerial spraying utilizing advanced biological monitoring
testing. The test results which included protein band testing utilizing Protein Coupled
Response (PCR) methods were positive for KD-45. KD-45 is the protein band for
SV-40 Simian Green Monkey virus. Additional tests were performed for Epstein-Barr
virus capside and Cytomeglia virus which are used in bioengineering for gene delivery
systems through viral protein envelope and adenoviral protein envelope technology.
The individual was positive for both; indicating a highly probable exposure to a DNA
vaccination delivery system through nasal inhalation.
The question of the century is how many other viruses and toxins are within current
day vaccines that we'll only find out about in a few decades?
SV40 (Simian virus 40)
SV40 is an abbreviation for Simian vacuolating virus 40 or Simian virus 40, a
polyomavirus that is found in both monkeys and humans. Like other polyomaviruses,
SV40 is a DNA virus that has the potential to cause tumors, but most often persists as a
latent infection.
SV40 became a highly controversial subject after it was revealed that millions were
exposed to the virus after receiving a contaminated polio vaccine produced between
1955 and 1961.[1]
History
The virus was first identified by Bernice E. Eddy (based on a work of her and Sarah
Stewart about Polyoma viruses) in 1960 in cultures of rhesus monkey kidney cells that
were being used to produce polio vaccine.[2][3] It was named for the effect it produced
on infected green monkey cells, which developed an unusual number of vacuoles. This
observation was repeated and confirmed by Hilleman and Sweet who were employed by
Merck in their vaccine division. The complete viral genome was sequenced by Walter
Fiers and his team at the University of Ghent (Belgium) in 1978.[4] The virus is dormant
and is asymptomatic in Rhesus monkeys. The virus has been found in many macaque
populations in the wild, where it rarely causes disease. However, in monkeys that are
immunodeficient—due to, for example, infection with Simian immunodeficiency virus—
SV40 acts much like the human JC and BK polyomaviruses, producing kidney disease
and sometimes a demyelinating disease similar to PML. In other species, particularly
hamsters, SV40 causes a variety of tumors, generally sarcomas. In rats, the oncogenic
SV40 Large T-antigen was used to establish a brain tumor model for PNETs and
medulloblastomas.[5]
Multiplicity Reactivation
SV40 is capable of multiplicity reactivation (MR).[6][7] MR is the process by which two,
or more, virus genomes containing otherwise lethal damage interact within an infected
cell to form a viable virus genome. Yamamato and Shimojo observed MR when SV40
virions were irradiated with UV light and allowed to undergo multiple infection of host
cells.[6] Hall studied MR when SV 40 virions were exposed to the DNA crosslinking
agent 4, 5’, 8-trimethylpsoralen.[7] Under conditions where only a single virus particle
entered each host cell, approximately one DNA cross-link was lethal to the virus, and
could not be repaired. In contrast, when multiple viral genomes infected a host cell,
psoralen induced DNA cross-links were repaired; that is, MR occurred. Hall suggested
that the virions with cross-linked DNA were repaired by recombinational repair.[7]
Michod et al. reviewed numerous examples of MR in different viruses, and suggested
that MR is a common form of sexual interaction that provides the advantage of
recombinational repair of genome damages.[8]
Transcription
The early promoter for SV40 contains three elements. The TATA box is located
approximately 20 base-pairs upstream from the transcriptional start site. The 21 base-
pair repeats contain six GC boxes and are the site that determines the direction of
transcription. Also, the 72 base-pair repeats are transcriptional enhancers. When the
SP1 protein interacts with the 21 bp repeats it binds either the first or the last three GC
boxes. Binding of the first three initiates early expression and binding of the last three
initiates late expression. The function of the 72 bp repeats is to enhance the amount of
stable RNA and increase the rate of synthesis. This is done by binding (dimerization)
with the AP1 (activator protein 1) to give a primary transcript that is 3' polyadenylated
and 5' capped.
Theorized role in human disease
The hypothesis that SV40 might cause cancer in humans has been a particularly
controversial area of research.[9] Several different methods have been used to detect
SV40 in a variety of human cancers, although how reliable these detection methods
are, and whether SV40 has any role in causing these tumors, remains unclear.[10] As a
result of these uncertainties, academic opinion remains divided, with some arguing that
this hypothesis is not supported by the data,[11] and others arguing that some cancers
may involve SV40.[12][13] However, the United States National Cancer Institute
announced in 2004 that although SV40 does cause cancer in some animal models,
"substantial epidemiological evidence has accumulated to indicate that SV40 likely
does not cause cancer in humans".[14] This announcement is based on two recent
studies.[15][16] This 2004 announcement is in contrast to a 2002 study performed by
The National Academy of Sciences Immunization Safety Review committee that stated,
"The committee concludes that the biological evidence is moderate that SV40 exposure
could lead to cancer in humans under natural conditions.”[17]
p53 Damage and carcinogenicity
SV40 is believed to suppress the transcriptional properties of the tumor-suppressing
p53 in humans through the SV40 Large T-antigen and SV40 Small T-antigen. p53 is
responsible for initiating regulated cell death ("apoptosis"), or cell cycle arrest when a
cell is damaged. A mutated p53 gene may contribute to uncontrolled cellular
proliferation, leading to a tumor.
SV40 may act as a co-carcinogen with crocidolite asbestos to cause both Peritoneal
and Pleural Mesothelioma [18] (review [19]).
When SV40 infects nonpermissive cells, such as 3T3 mouse cells, the dsDNA of SV40
becomes covalently integrated. In nonpermissive cells only the early gene expression
occurs and this leads to transformation, or oncogenesis. The nonpermissive host
needs the Large T-antigen and the Small t-antigen in order to function. The Small T-
antigen interacts with and integrates with the cellular phosphatase pp2A. This causes
the cell to lose the ability to initiate transcription.
Polio vaccine contamination
Soon after its discovery, SV40 was identified in the oral form of the polio vaccine
produced between 1955 and 1961 produced by American Home Products (dba
Lederle). This is believed to be due to two sources: 1) SV40 contamination of the
original seed strain (coded SOM); 2) contamination of the substrate—primary kidney
cells from infected monkeys used to grow the vaccine virus during production. Both the
Sabin vaccine (oral, live virus) and the Salk vaccine (injectable, killed virus) were
affected; the technique used to inactivate the polio virus in the Salk vaccine, by means
of formaldehyde, did not reliably kill SV40.
It was difficult to detect small quantities of virus until the advent of PCR; since then,
stored samples of vaccine made after 1962 have tested negative for SV40, but no
samples prior to 1962 could initially be found. Then, in 1997, Herbert Ratner of Oak
Park, Illinois, gave some vials of 1954 Salk vaccine to researcher Michele Carbone.[20]
Ratner, the Health Commissioner of Oak Park at the time the Salk vaccine was
introduced, had kept these vials of vaccine in a refrigerator for over forty years.[21][22]
Upon testing this vaccine, Carbone discovered that it contained not only the SV40
strain already known to have been in the Salk vaccine (containing two 72-bp
enhancers) but also the same slow-growing SV40 strain currently being found in some
malignant tumors and lymphomas (containing one 72-bp enhancers).[23] It is unknown
how widespread the virus was among humans before the 1950s, though one study
found that 12% of a sample of German medical students in 1952 had SV40 antibodies.
Although horizontal transmission between people has been proposed,[24] it is not clear
if this actually happens and if it does, how frequently it occurs.
An analysis presented at the Vaccine Cell Substrate Conference in 2004[25] suggested
that vaccines used in the former Soviet bloc countries, China, Japan, and Africa, could
have been contaminated up to 1980, meaning that hundreds of millions more could
have been exposed to the virus unknowingly.
SV40 is an abbreviation for Simian vacuolating virus 40 or Simian virus 40, a
polyomavirus that is found in both monkeys and humans. Like other polyomaviruses,
SV40 is a DNA virus that has the potential to cause tumors, but most often persists as a
latent infection.
SV40 became a highly controversial subject after it was revealed that millions were
exposed to the virus after receiving a contaminated polio vaccine produced between
1955 and 1961.[1]
History
The virus was first identified by Bernice E. Eddy (based on a work of her and Sarah
Stewart about Polyoma viruses) in 1960 in cultures of rhesus monkey kidney cells that
were being used to produce polio vaccine.[2][3] It was named for the effect it produced
on infected green monkey cells, which developed an unusual number of vacuoles. This
observation was repeated and confirmed by Hilleman and Sweet who were employed by
Merck in their vaccine division. The complete viral genome was sequenced by Walter
Fiers and his team at the University of Ghent (Belgium) in 1978.[4] The virus is dormant
and is asymptomatic in Rhesus monkeys. The virus has been found in many macaque
populations in the wild, where it rarely causes disease. However, in monkeys that are
immunodeficient—due to, for example, infection with Simian immunodeficiency virus—
SV40 acts much like the human JC and BK polyomaviruses, producing kidney disease
and sometimes a demyelinating disease similar to PML. In other species, particularly
hamsters, SV40 causes a variety of tumors, generally sarcomas. In rats, the oncogenic
SV40 Large T-antigen was used to establish a brain tumor model for PNETs and
medulloblastomas.[5]
Multiplicity Reactivation
SV40 is capable of multiplicity reactivation (MR).[6][7] MR is the process by which two,
or more, virus genomes containing otherwise lethal damage interact within an infected
cell to form a viable virus genome. Yamamato and Shimojo observed MR when SV40
virions were irradiated with UV light and allowed to undergo multiple infection of host
cells.[6] Hall studied MR when SV 40 virions were exposed to the DNA crosslinking
agent 4, 5’, 8-trimethylpsoralen.[7] Under conditions where only a single virus particle
entered each host cell, approximately one DNA cross-link was lethal to the virus, and
could not be repaired. In contrast, when multiple viral genomes infected a host cell,
psoralen induced DNA cross-links were repaired; that is, MR occurred. Hall suggested
that the virions with cross-linked DNA were repaired by recombinational repair.[7]
Michod et al. reviewed numerous examples of MR in different viruses, and suggested
that MR is a common form of sexual interaction that provides the advantage of
recombinational repair of genome damages.[8]
Transcription
The early promoter for SV40 contains three elements. The TATA box is located
approximately 20 base-pairs upstream from the transcriptional start site. The 21 base-
pair repeats contain six GC boxes and are the site that determines the direction of
transcription. Also, the 72 base-pair repeats are transcriptional enhancers. When the
SP1 protein interacts with the 21 bp repeats it binds either the first or the last three GC
boxes. Binding of the first three initiates early expression and binding of the last three
initiates late expression. The function of the 72 bp repeats is to enhance the amount of
stable RNA and increase the rate of synthesis. This is done by binding (dimerization)
with the AP1 (activator protein 1) to give a primary transcript that is 3' polyadenylated
and 5' capped.
Theorized role in human disease
The hypothesis that SV40 might cause cancer in humans has been a particularly
controversial area of research.[9] Several different methods have been used to detect
SV40 in a variety of human cancers, although how reliable these detection methods
are, and whether SV40 has any role in causing these tumors, remains unclear.[10] As a
result of these uncertainties, academic opinion remains divided, with some arguing that
this hypothesis is not supported by the data,[11] and others arguing that some cancers
may involve SV40.[12][13] However, the United States National Cancer Institute
announced in 2004 that although SV40 does cause cancer in some animal models,
"substantial epidemiological evidence has accumulated to indicate that SV40 likely
does not cause cancer in humans".[14] This announcement is based on two recent
studies.[15][16] This 2004 announcement is in contrast to a 2002 study performed by
The National Academy of Sciences Immunization Safety Review committee that stated,
"The committee concludes that the biological evidence is moderate that SV40 exposure
could lead to cancer in humans under natural conditions.”[17]
p53 Damage and carcinogenicity
SV40 is believed to suppress the transcriptional properties of the tumor-suppressing
p53 in humans through the SV40 Large T-antigen and SV40 Small T-antigen. p53 is
responsible for initiating regulated cell death ("apoptosis"), or cell cycle arrest when a
cell is damaged. A mutated p53 gene may contribute to uncontrolled cellular
proliferation, leading to a tumor.
SV40 may act as a co-carcinogen with crocidolite asbestos to cause both Peritoneal
and Pleural Mesothelioma [18] (review [19]).
When SV40 infects nonpermissive cells, such as 3T3 mouse cells, the dsDNA of SV40
becomes covalently integrated. In nonpermissive cells only the early gene expression
occurs and this leads to transformation, or oncogenesis. The nonpermissive host
needs the Large T-antigen and the Small t-antigen in order to function. The Small T-
antigen interacts with and integrates with the cellular phosphatase pp2A. This causes
the cell to lose the ability to initiate transcription.
Polio vaccine contamination
Soon after its discovery, SV40 was identified in the oral form of the polio vaccine
produced between 1955 and 1961 produced by American Home Products (dba
Lederle). This is believed to be due to two sources: 1) SV40 contamination of the
original seed strain (coded SOM); 2) contamination of the substrate—primary kidney
cells from infected monkeys used to grow the vaccine virus during production. Both the
Sabin vaccine (oral, live virus) and the Salk vaccine (injectable, killed virus) were
affected; the technique used to inactivate the polio virus in the Salk vaccine, by means
of formaldehyde, did not reliably kill SV40.
It was difficult to detect small quantities of virus until the advent of PCR; since then,
stored samples of vaccine made after 1962 have tested negative for SV40, but no
samples prior to 1962 could initially be found. Then, in 1997, Herbert Ratner of Oak
Park, Illinois, gave some vials of 1954 Salk vaccine to researcher Michele Carbone.[20]
Ratner, the Health Commissioner of Oak Park at the time the Salk vaccine was
introduced, had kept these vials of vaccine in a refrigerator for over forty years.[21][22]
Upon testing this vaccine, Carbone discovered that it contained not only the SV40
strain already known to have been in the Salk vaccine (containing two 72-bp
enhancers) but also the same slow-growing SV40 strain currently being found in some
malignant tumors and lymphomas (containing one 72-bp enhancers).[23] It is unknown
how widespread the virus was among humans before the 1950s, though one study
found that 12% of a sample of German medical students in 1952 had SV40 antibodies.
Although horizontal transmission between people has been proposed,[24] it is not clear
if this actually happens and if it does, how frequently it occurs.
An analysis presented at the Vaccine Cell Substrate Conference in 2004[25] suggested
that vaccines used in the former Soviet bloc countries, China, Japan, and Africa, could
have been contaminated up to 1980, meaning that hundreds of millions more could
have been exposed to the virus unknowingly.
Cancer Incidence in
Denmark Following
Exposure to Poliovirus
Vaccine Contaminated
With Simian Virus 40
Oxford University Press
Accepted February 4, 2003.
Early poliovirus vaccines
were accidentally
contaminated with simian
virus 40 (SV40). In
Denmark, poliovirus vaccine
was administered to most
children from 1955 through
1961. SV40 DNA
sequences have been
detected in several human
malignancies, including
mesothelioma,
ependymoma, choroid
plexus tumors, and non-
Hodgkin’s lymphoma. To
clarify whether SV40
infection increases risk of
these cancers or of cancers
arising in children, we
examined cancer incidence
in three Danish birth
cohorts. Methods:
Population-based cancer
incidence data from 1943
through 1997 were obtained
from the Danish Cancer
Registry. The relationship
between exposure to SV40-
contaminated vaccine and
cancer incidence was
evaluated by examining
incidence in birth cohorts
that differed in exposure to
SV40-contaminated
vaccine. In addition, cancer
incidence was examined in
children who were 0–4
years of age before, during,
and after the period of
vaccine contamination.
Incidence was compared
using Poisson regression,
adjusting for age
differences. All statistical
tests were two-sided.
Results: After 69.5 million
person-years of follow-up,
individuals exposed to SV40-
contaminated poliovirus
vaccine as infants (i.e., born
1955–1961) or children (i.
e., born 1946–1952) had
lower overall cancer risk
(age-adjusted relative risk
[RR] = 0.86, 95%
confidence interval [CI] =
0.81 to 0.91 and RR = 0.79,
95% CI = 0.75 to 0.84,
respectively; P<.001 for
both) than unexposed
individuals (i.e., born 1964–
1970, after the vaccine was
cleared of SV40
contamination). Specifically,
SV40 exposure was not
associated with increased
incidence of mesothelioma,
ependymoma, choroid
plexus tumor, or non-
Hodgkin’s lymphoma. After
19.5 million person-years of
follow-up, incidence of all
cancers combined, of
intracranial tumors, and of
leukemia among children
aged 0–4 years was also
not associated with SV40
exposure. Ependymoma
incidence was higher during
the exposed period than
during the unexposed
period (RR = 2.59, 95%CI =
1.36 to 4.92; P = .004
versus the period before
contamination); however,
incidence peaked in 1969,
after the vaccine was
cleared of SV40.
Conclusion: Exposure to
SV40-contaminated
poliovirus vaccine in
Denmark was not
associated with increased
cancer incidence.
Eric A. Engels Hormuzd A. Katki,
Nete M. Nielsen, Jeanette F. Winther,
Henrik Hjalgrim, Flemming Gjerris,
Philip S. Rosenberg and Morten
Frisch
Affiliations of authors: E. A. Engels, H.
A. Katki, P. S. Rosenberg, Division of
Cancer Epidemiology and Genetics,
National Cancer Institute, Department
of Health and Human Services,
Rockville, MD; N. M. Nielsen, H.
Hjalgrim, M. Frisch, Department of
Epidemiology Research, Danish
Epidemiology Science Center,
Statens Serum Institut, Copenhagen,
Denmark; J. F. Winther, Institute of
Cancer Epidemiology, Danish Cancer
Society, Copenhagen; F. Gjerris,
University Clinic of Neurosurgery,
Neuroscience Center, H.S.,
Rigshospitalet, Copenhagen.
Correspondence to: Eric A. Engels, M.
D., M.P.H., Viral Epidemiology
Branch, Division of Cancer
Epidemiology and Genetics, National
Cancer Institute, 6120 Executive
Blvd., EPS 8010, Rockville, MD
20892 (e-mail: engelse@exchange.
nih.gov).
Received July 11, 2002.
Revision received January 27, 2003.
Denmark Following
Exposure to Poliovirus
Vaccine Contaminated
With Simian Virus 40
Oxford University Press
Accepted February 4, 2003.
Early poliovirus vaccines
were accidentally
contaminated with simian
virus 40 (SV40). In
Denmark, poliovirus vaccine
was administered to most
children from 1955 through
1961. SV40 DNA
sequences have been
detected in several human
malignancies, including
mesothelioma,
ependymoma, choroid
plexus tumors, and non-
Hodgkin’s lymphoma. To
clarify whether SV40
infection increases risk of
these cancers or of cancers
arising in children, we
examined cancer incidence
in three Danish birth
cohorts. Methods:
Population-based cancer
incidence data from 1943
through 1997 were obtained
from the Danish Cancer
Registry. The relationship
between exposure to SV40-
contaminated vaccine and
cancer incidence was
evaluated by examining
incidence in birth cohorts
that differed in exposure to
SV40-contaminated
vaccine. In addition, cancer
incidence was examined in
children who were 0–4
years of age before, during,
and after the period of
vaccine contamination.
Incidence was compared
using Poisson regression,
adjusting for age
differences. All statistical
tests were two-sided.
Results: After 69.5 million
person-years of follow-up,
individuals exposed to SV40-
contaminated poliovirus
vaccine as infants (i.e., born
1955–1961) or children (i.
e., born 1946–1952) had
lower overall cancer risk
(age-adjusted relative risk
[RR] = 0.86, 95%
confidence interval [CI] =
0.81 to 0.91 and RR = 0.79,
95% CI = 0.75 to 0.84,
respectively; P<.001 for
both) than unexposed
individuals (i.e., born 1964–
1970, after the vaccine was
cleared of SV40
contamination). Specifically,
SV40 exposure was not
associated with increased
incidence of mesothelioma,
ependymoma, choroid
plexus tumor, or non-
Hodgkin’s lymphoma. After
19.5 million person-years of
follow-up, incidence of all
cancers combined, of
intracranial tumors, and of
leukemia among children
aged 0–4 years was also
not associated with SV40
exposure. Ependymoma
incidence was higher during
the exposed period than
during the unexposed
period (RR = 2.59, 95%CI =
1.36 to 4.92; P = .004
versus the period before
contamination); however,
incidence peaked in 1969,
after the vaccine was
cleared of SV40.
Conclusion: Exposure to
SV40-contaminated
poliovirus vaccine in
Denmark was not
associated with increased
cancer incidence.
Eric A. Engels Hormuzd A. Katki,
Nete M. Nielsen, Jeanette F. Winther,
Henrik Hjalgrim, Flemming Gjerris,
Philip S. Rosenberg and Morten
Frisch
Affiliations of authors: E. A. Engels, H.
A. Katki, P. S. Rosenberg, Division of
Cancer Epidemiology and Genetics,
National Cancer Institute, Department
of Health and Human Services,
Rockville, MD; N. M. Nielsen, H.
Hjalgrim, M. Frisch, Department of
Epidemiology Research, Danish
Epidemiology Science Center,
Statens Serum Institut, Copenhagen,
Denmark; J. F. Winther, Institute of
Cancer Epidemiology, Danish Cancer
Society, Copenhagen; F. Gjerris,
University Clinic of Neurosurgery,
Neuroscience Center, H.S.,
Rigshospitalet, Copenhagen.
Correspondence to: Eric A. Engels, M.
D., M.P.H., Viral Epidemiology
Branch, Division of Cancer
Epidemiology and Genetics, National
Cancer Institute, 6120 Executive
Blvd., EPS 8010, Rockville, MD
20892 (e-mail: engelse@exchange.
nih.gov).
Received July 11, 2002.
Revision received January 27, 2003.
SV 40