MadSci Network: Science History

Re: How did they discover prions and micro-viruses?

Date: Mon Feb 18 19:40:26 2002
Posted By: Ana Bozas, Staff, Microbiology & Immunology, Toxikon
Area of science: Science History
ID: 1013452549.Sh

1) First, I'll try to get our definitions straight. I presume that by 
micro-viruses you are referring to subviral organisms. I have enclosed a 
very nice description of these organisms.
"There are basically two types of subviral agents: self replicating and 
self non-replicating. Self replicating agents are plant viroids. The non-
self replicating agents are usually parasites of viruses. They depend on a 
host virus for repl ication and sometimes encapsidation. This type of 
subviral agents include satellite RNA, satellite virus, virusoid, 
defective interfering (DI) RNA, and hepatits delta virus.

Viroids: Viroids are autonomously replicating pathogens that consist 
solely of unencapsidated, single-stranded, circular RNAs of 246-375 
nucleotides. Viroids do not code for any protein products including a 
capsid protein. The native structure of viroids is an extremely stable and 
highly basepaired rod. Some viroid RNAs have ribozyme activity (self-

Satellite RNA: Satellite RNA are small RNA molecules that require a host 
virus for replication. They may or may not reduce the titer of the host 
virus. Satellite RNAs ranges from 200 to 1700 nt. Larger satellite RNAs 
may encode a protein.

Virusoid: viroid-like satellite RNA. They are small satellite RNA with a 
circular, highly basepaired structured like a viroid. Virusoids depend on 
a host virus for replication and encapsidation. Like a viroid, it does not 
encode any protein. All virusoid RNAs studied so far have ribozyme 

Satellite Virus: When a satellite RNA encodes its own capsid protein and 
encapsidate it own RNA, it is called satellite virus. Satellite viruses 
still depend on host virus for replication. 

Defective Interfering (DI) RNA. Small RNA molecules that derived from 
viral RNA by extensive deletion. They are mosaic of viral genomic RNA. DI 
depends on the original virus for replication and usually reduce the 
replication of the host v irus.

Hepatitis delta virus: a covalently closed, circular ssRNA of 
approximately 1700 nt. It can fold into a unbranched rod-like structure 
and replicate through a rolling circle mechanism. Both genomic RNA and 
complementary RNA are capable of self cleavage. Hepatitis delta virus 
depends on hepatitis B virus for replication. Hepatitis delta virus is the 
only viroid-like infectious agent infecting animals.

Another class of pathogens, yet to be reported infecting plants, are worth 
mentioning. They are Prions (Proteinaceous infectious particles). Prions 
have been defined traditionally as " small proteinaceous infectious 
particles which resist inactivation by procedures that modify nucleic 
acids." Prion are a form of a normal cellular protein (PrP, prion protein) 
existing in a special tertiary structure (conformation). Upon transmission 
to healthy individuals, prion can lead a change in conformation of the 
normal cellular prion protein into the diseased prion protein. " (web site 
quoted from

2) Your question is about the discovery of prions and "micro-viruses". 
Here again there could be a confusion of intent: do you mean what were the 
actions of people who discovered prions and micro-viruses, or do you mean 
what made them suspect inheritance through other forms than DNA 
replication or with naked RNA?
I will presume that you are interested in how scientists thought, and 
since in biology one method of investigation tends to be repeated many 
times over (and a similar mechanism of action pops up in differing 
organisms, environments etc.), I will remind you of how DNA was 
established to have a hereditary function. Basically, in science (and for 
that matter in any thorough and logical investigation), you must list all 
possible options and methodically eliminate the impossible ones. Any 
theory left standing after the eliminatory process must be the correct 
one. (Sherlock Holmes speech in one of Arthur Conan Doyle's books, but 
very pertinent to science). Of course, any theory must be proven, so after 
guessing the correct mechanism, another round of experiments must be 
devised to go through the postulated process and obtained the predicted 
So, in finding the role of DNA, scientists took proteins and DNA (both 
suspected of being the replicating material) and tagged them with 
irradiated labels and looked at which material showed up in the newly 
replicated cells. DNA showed up, won and was declared the blueprint of all 
living things. 
(DNA function:;;

However, later on there were some diseases investigated that were 
transmitted by, it seems, other ways than simple DNA replication of 
bacteria or viruses. So scientists got back to square 1, confirmed that it 
was not DNA that was ruining cows' brains (in the case of prions) and 
reinvestigated the possibility of proteins. And while logically this is 
just how investigating mysteries in science works, both the discovery of 
the function of DNA and prions were important discoveries because they 
went against the traditional thought regarding inheritance at the time (at 
the beginning of the century protein was supposed to be the replicating 
material, and after DNA was declared the blueprint af life, protein 
infection by protein, rogue DNA becoming infectious and other 
possibilities were thought at best bizarre).

3) In the case you just wanted a histoy of prion discovery, Stanley B. 
Prusiner, a professor at the University of California at San Francisco, 
discovered prions . Here is a little more detail as to the investigative 
"Scrapie, Creutzfelt-Jakob disease, and kuru are all shown to be 
transmissible by injecting material from diseased brains into the brains 
of healthy mammals. But it was unknown for many years just how this 
phenomenon occurred. Ultraviolet or ionizing radiation can degrade nucleic 
acids in the form of DNA or RNA, which are present in all other known 
pathogens. But when the nucleic acids in scrapie-infected brains were 
destroyed by these methods, the brain material was still able to transmit 
scrapie.   This observation suggested that nucleic acids such as those 
present in DNA and RNA are not required for the transmission of spongiform 
Determined to solve this mystery, although other researchers had failed at 
their attempts, Prusiner began to purify the infectious material in his 
U.C.S.F. laboratory in 1974. By 1982, Prusiner's research confirmed 
previous evidence that DNA and RNA were absent in the infectious material 
of the diseases. He eventually came across a further discovery that the 
responsible agent was in fact a protein. This was supported by the fact 
that in experiments where proteins were denatured, or unfolded, the 
infectivity of the diseased material decreased. Prusiner later found a 
single protein that was responsible for scrapie, and named it PrP, short 
for "prion protein." " 
(web site quoted from: Were Prions 
For the latest news in prion science try this web site:, 
or search using copernic search engine (at 

Regarding subviral organisms, you can also do a search (as above) and read 
about Barbara McClintock research on "jumping genes" (mobile genetic 
elements) in any biology book .

Hope I have been of some help (as opposed to confusing you further).


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