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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 magnetlike
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.
- - - - -
Fig 6.1 - The Molecule Structures Compriising Nucleic Acids
RNA and DNA - Life's Building Blocks:
PENDING
Source: Asimov I. The Intelligent Man's Guide To Science.
Volume II, The Biological Sciences. Basic Books, 1960. pp.526-
527.
- - - - -
Fig 6.2 - A Model of the Nucleic-Acid Molecule:
PENDING
The drawing at the left shows the double helix; in the center a
portion of it is shown in detail (omitting the hydrogen atoms); at
the right is a detail of the nucleotide combinations. Source:
Asimov I. The Intelligent Man's Guide To Science. Volume II,
The Biological Sciences. Basic Books, 1960. p.532. Reprinted
with permission.
- - - - -
Fig 6.3 - Replication of the AIDS Virus - HIV/CD4 Cell
Interaction:
PENDING
Source: Germain RN. Antigen processing and CD4+ T cell
depletion in AIDS. 'Cell' 1998;54:441-414
- - - - -
Gallo¹s Cancerous Creations
In 1971, the year following the $10 million DOD appropriation
for the development of AIDS-like viruses,s the NCI acquired the
lion's share of the Fort Detrick facilities, and the Cell Thmor
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 Portugese seamen to
Japan (see fig. 6.4), in 1971 he and his team published a
seemingly conflicting statement. "Only one virus [of 27 then
known RNA retroviruses] which contains reverse transcriptase,"
they wrote, "does not seem to be oncogenic [cancer causing]" -
the simian foamy virus. [10]
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.
Then, suddenly, there it was. "Mama Mia!" I exclaimed. "I can't
believe he published this." 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]
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
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Dobre pomysły nie mają przeszłości, mają tylko przyszłość. Robert Mallet
De minimis - o najmniejszych rzeczach.
Dobroć jest ważniejsza niż mądrość, a uznanie tej prawdy to pierwszy krok do mądrości. Theodore Isaac Rubin
Dobro to tylko to, co szlachetne, zło to tylko to, co haniebne.
Dla człowieka nie tylko świat otaczający jest zagadką; jest on nią sam dla siebie. I z obu tajemnic bardziej dręczącą wydaje się ta druga. Antoni Kępiński (1918-1972)
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