Chapter 6 Gallo's Research Anthology -The AIDS Buck and Virus Stops Here EARLY the next morning, I made my way to Countway's Cumulated Index Medicus to look up all of Gallo's early work. I started my search in 1965, figuring it would have taken him at least five years to establish himself as an expert in the field of retrovirology by 1970. The 1965 and 1966 year-books cited nothing of Gallo's efforts, but 1967 held two such references in what became a long list of Gallo publications.
By days end, I held a stack of nearly
forty research reports published by Gallo and coworkers before 1975.
It took me about two weeks of reading, with frequent referencing of
medical texts for explanations to technical information that I found
difficult to understand. My earlier lessons in biochemistry, cell
physiology, genetics, and virology all needed refreshing. With my
head buried in scientific literature, I saw very little of my family
those weeks.
I began my review of Gallo's papers by
organizing them chronologically. I read each paper, highlighted
important details in yellow, then noted the purpose, conclusions,
and potential relevance to the development of AIDS-like viruses. In
the end, I held six pages of tables summarizing the data (see fig.
6.8).
Introduction to Retrovirology A fundamental understanding of what HIV is and how it works is required before discussing the development of AIDS-like viruses by Gallo and his coworkers. The AIDS virus is an extremely unique germ. Most astonishing is that it incorporates elements that cause normal white blood cells (WBCs) to produce more viruses through a somewhat unnatural and uniquely backward process. One of HIV's main components is a single chain of genetic material.
This single strand is called RNA, short
for ribonucleic acid. It comprises sugars combined with chemical
(molecular) rings called purines and pyrimidines (see fig. 6.2).
After the virus gets into a T4lymphocyte or CD4 helper cell (a type
of WBC), its RNA genetic code directs the blood cell to produce a
similar nucleic acid chain called DNA, short for deoxyribonucleic
acid. DNA is the genetic blueprint all cells use to reproduce
normally. DNA directs the manufacture of all new proteins and other
cell parts, including RNA.
In the case of an RNA retrovirus
infection, however, this natural direction is commandeered to run in
reverse. In this case, the viral RNA directs the manufacture of
deadly foreign DNA, which then commands the cell's reproductive
machinery to produce more viruses rather than healthy new cells.
This switch in reproductive control is accomplished partly because
RNA and DNA are very much alike. The only difference between them is
the substitution of one sugar-linked molecule, called uracil in RNA,
for another one, called thymine, in the DNA (see figs. 6.1 and 6.2).
As shown in fig. 6.3, AIDS viruses have
a special attraction for T4 lymphocytes. These blood cells possess
special magnet-like CD4 receptors. These attachments normally serve
to detect and help destroy foreign invaders, called antigens, via a
complex immunological defense system. These CD4 receptors bind to a
portion of HIV's outer envelope known as the gp 120 antigen.
The CD4-gp 120 interaction allows the
AIDS virus to be transported across the lymphocyte's protective
outer membrane, and once inside the cell, the viral envelope opens
releasing the unique RNA and special enzymes into the human cell.
[1] Then, by means of the special reverse transcriptase enzyme-so
named because it prompts the "reverse" process of copying DNA to RNA
- the RNA code is copied to produce a new "proviral DNA" strand.
This enzyme is technically called RNA-dependent DNA polymerase.
It directs the cell to produce a DNA
gene sequence from the viral RNA template, the exact opposite of
what normally occurs in the non-infected cell. This DNA provirus
then enters the cell's nucleus where genetic materials are stored.
Here the provirus is inserted into the host's normal gene sequence
through the work of another unique enzyme known as viral
endonuclease. The endonuclease enzyme functions like a pair of
scissors. It cuts open the cell's normal DNA strand allowing the
newly formed provirus to be inserted.
Later, during normal cell operation, the provirus directs new viral proteins to be produced, which eventually bud off the cell forming new viruses. [1] This is the theory Gallo advanced first in 1972 during the "war on cancer" in order to explain retrovirus related cancers such as lymphoma, leukaemia, and sarcoma.
Twelve years later, he advanced the same
theory to explain AIDS.
Gallo's Cancerous Creations
In 1971, the year following the $10 million DOD appropriation for the development of AIDS-like viruses the NCI acquired the lion's share of the Fort Detrick facilities, and the Cell Tumor Biology Laboratory's output increased as measured by the publication of eight scientific articles by Gallo and his coworkers compared to at most four in previous years.
Among Gallo's earliest reports was the
discovery that by adding a synthetic RNA and cat leukaemia virus
"template" to "human type C" viruses - those associated with cancers
of the lymph nodes - the rate of DNA production (and subsequent
provirus and virus reproduction) increased as much as thirty times.
Gallo and company reported that such a virus may cause many cancers
besides leukaemias and lymphomas, including sarcomas. [10]
Regarding Gallo's widely accepted 1983
speculation that the AIDS virus arose from an African monkey virus
that naturally jumped species and then was carried by Portuguese
seamen to Japan (see fig. 6.4), in 1971 he and his team published a
seemingly conflicting statement.
At the time, simian foamy viruses were
known to be common, humanly benign, vaccine contaminants. Had the
simian virus simply jumped species then, I considered, it is
doubtful it would have gained the cancer-causing capabilities seen
in AIDS. Additional mutations would have been needed to make it so
carcinogenic.
Gallo and company, including frequent
coauthor Robert Ting from Litton Bionetics, reported modifying
simian monkey* viruses by
infusing them with cat leukaemia RNA to make them cause cancers as
seen in people with AIDS (see fig. 6.5). [9,10]
[* The
word "simian" before monkey, introduced by the mass media, is
actually redundant. Since most people now associate the two,
however, particularly in connection with the origin of the AIDS
virus, the phrase "simian monkey" will be used in this book to mean
just "monkey."]
Furthermore, Gallo and his coworker
Seitoku Fujioka concluded from studies conducted in late 1969 or
early 1970 that they would need to further "evaluate the functional
significance of tRNA changes in tumor cells." To do this, they
designed an experiment in which "specific tumor cell tRNAs" were
"added directly to normal cells."
They explained that one way of doing
this was to use viruses to deliver the foreign cancer producing tRNA
to the nonnal cells. The viruses that they used for this purpose,
were the simian monkey virus (SV 40) and the mouse parotid tumor (polyoma)
virus. [11] These experiments, I realized, could have easily
established the technology for the development of HIV-allegedly of
simian virus descent - which similarly delivers reverse
transcriptase and a foreign cat leukemia/sarcoma-like RNA to nonnal
human white blood cells.
Obvious Link to NATO
That same year, Gallo and his coworkers presented research describing the experimental entry of bacterial RNA into human WBCs before a special symposium sponsored by the North Atlantic Treaty Organization (NATO)? The paper published in the Proceedings of the National Academy of Sciences discussed several possible mechanisms prompting the "entry of foreign nucleic acids" into lymphocytes.
I flashed back to my knowledge of the
controversial symposium on the entry and control of foreign nucleic
acids, held on April 4 and 5, 1969, at Fort Detrick, and noted
Gallo's link to this work. Here was documented evidence that senior
investigator Robert Gallo presented the methods and materials used
to produce AIDS-like viruses before NATO military scientists at "the
NATO International Symposium on Uptake of Infonnative Molecules by
Living Cells" in Mol, Belgium, in 1970. [2]
I sat stunned while reading that Gallo
and his coworkers had also published studies identifying
A subsequent study published in 1970 by
Gallo and his colleagues identified RNA-dependent DNA polymerase.
Gallo's team noted that this enzyme was responsible for gene
amplification and biochemical cyto-differentiation (the development
of unique WBC characteristics including cancer cell production) and
leukaemogenesis (the production of leukemia). [6]
Another of their studies identified L-Asparaginase
synthetase - an important enzyme that, if blocked, will cause
treatment- resistant leukemias and other cancers. [7] Just what the
DOD ordered, I recalled,
Creating More AIDSLike Viruses
By 1972, Gallo and coworkers studied portions of simian monkey and mouse salivary gland tumor viruses to determine differences in RNA activity between infected versus uninfected cancer cells. [9]
They wrote:
The group was trying to determine the
importance of various viral genes on the development of human
cancers and immune system collapse. They reported their desire to
use this information to find a cure for cancer, but at this time
their activity was more focused on creating various cancers and
carcinogenic viruses that could infect humans. [9-11]
From this work, I also realized, Gallo
was actually cloning simian monkey viruses as early as 1970. So
allegations that he had cloned Montagnier's virus were buffeted by
the fact that he had over a decade of practice in the procedure.
Another example of Gallo's work in creating new viruses to cause
cancer in humans was published for the benefit of the NAS. Here
Gallo and company examined the activity of the special AIDS-linked
DNA polymerase enzyme in normal versus acute immature leukaemic
lymph cells, that is, lymphoblasts.
To do so, they evaluated the single
stranded "70S RNA retrovirus" found in chickens, which caused
prominent features of AIDS, including WBC dysfunction, sarcomas,
progressive wasting, and death (see fig. 6.5). [12] Gallo and his
team injected this chicken virus RNA into human WBCs to determine if
the cells were prompted to produce proteins and new viruses called
for by the viral RNA.13
Another Gallo team evaluated the human
cancer-causing effects of the single-stranded 70S RNA reverse
transcriptase enzyme-a genetic catalyst essentially identical to the
one found in HIV. They used cat leukemia viruses (FELV) and
Mason-Pfizer monkey viruses to deliver these carcinogens to normal
human lymphocytes. [14] I instantly realized that this work
foreshadowed the observation made ten years later by the CDC's chief
AIDS researcher, Don Francis, who noted the "laundry list" of feline
leukemia-like diseases associated with AIDS. [15]
Had Francis known about this early work?
I considered it most conceivable that he would have. Other Gallo
publications detailed the steps involved in creating
immune-system-destroying-cancer-causing viruses by adapting monkey,
rat, and bird leukemia and tumor viruses for experimental use in a
human (NC-37) cell line. 16
One Gallo team discussed the synthesis
of new RNA tumor viruses induced by 5-iodo-2'-deoxyuridine (IdU), a
constituent of RNA in rodent cell cultures, and noted that chemical
treatment might be used to halt the reverse transcriptase-linked
viral reproduction cycle. [17] They were apparently looking for a
cure for AIDS-like symptoms as early as 1972. Then I read a Gallo
team discussion in 1973, which concerned the origin of the RD 114
cat-human virus. "It can always be argued," they wrote, that a virus
that jumped species would be expected to have foreign protein
markers, that is, antigens, that differ "from the antigen found on
the viruses of known" origin. [18]
So if Gallo and his coworkers had
synthesized HIV for military or medical purposes from various animal
virus components, I realized, it would be difficult if not
impossible to prove. Finally, in another report published in the
'Proceedings of the National Academy of Sciences,' Gallo and
associates proclaimed they had isolated a virus-like particle from
human acute, that is, quick-acting, leukemic WBCs.
This particle, they noted, has a
specific density of 1.16-1.17 g/ml, which allowed it to be
repeatedly recovered without being destroyed by physical handling.
Moreover, it was capable of producing the principal rapidly growing
cancers seen in AIDS, including leukemias, sarcomas, and carcinomas.
[19] In conclusion, I learned that Gallo and his group of
researchers created numerous AIDS-like viruses for more than a
decade before Luc Montagnier announced the discovery of LA V.
Links to the DOD Throughout my review of Gallo's research, besides citing the NCI as his chief source of support, the names Bionetics, Bionetics Research Laboratories, and Litton Bionetics, Inc., repeatedly appeared (see fig. 6.6). For days, I wondered who or what Bionetics was?
This mystery ended when I retraced Ted Strecker's steps through the Ninety-first Congress's House hearings
on DOD appropriations for 1970. The Congressional Record contained
several sections dealing with chemical and biological weapons
funding. One contained the list of major Army contractors shown in
fig. 6.7. Bionetics Research Laboratories, a subsidiary of Litton
Industries, Inc. was sixth on the list of acknowledged biological
weapons contractors. [20]
Later congressional records showed that
Bionetics's affiliate - Litton Systems, Inc., a subsidiary of Litton
Industries, Inc. - was among the most frequently contracted
companies involved in BW research and development between 1960 and
1970.20
Additional BW contractors with whom Dr.
Gallo or his coworkers associated during the late 1960s and early
1970s included the Universities of Chicago, Texas, Virginia,
California, Yale, and New York. [21]
Breaking the News I emerged from my two weeks of laborious isolation noticeably pale. My mind raced with questions about the risk of continuing the investigation. I also wondered how I would break the whole truth about my findings to Jackie. The pragmatist in our family, she would immediately consider the sensitivity of the information and its potential affect on our lives.
Following a brief summation of my
findings aided by the six pages of tables I had developed (see fig.
6.8), Jackie shattered a long and anxious silence.
Choice and Preparation of Cells
RNA dependent DNA Polymerase Activity
[One of dozens of publications authored by
Robert C. Gallo and
colleagues affiliated with Bionetics Research Laboratories,
Bionetics, or Litton Bionetics. These subsidiaries of
Litton
Industries, Inc. were listed among most frequently contracted
companies involved in biological weapons research and development
during the 1960s and 1970s. [20,21]
Source: Gallo RC, Yang SS and
Ting RC. RNA Dependent DNA Polymerase of Human Acute Leukaemic
Cells. Nature 1970; 228:927.]
NOTES
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Monday, October 20, 2014
Ch 6 Emerging Viruses-Aids and Ebola-Nature Accident or Intentional: Gallo's Research Anthology -The AIDS Buck and Virus Stops Here by Dr. Leonard Horowitz from bibliotecapleyades.net
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