UAS-Ricin A constructs are quite useful for studies of Drosophila development, because intracellular expression of the A protein subunit of the Ricin toxin ablates cells rapidly and efficiently. The Ricin A subunit must be combined with the Ricin B subunit for entry into cells. In the absence of the B subunit, Ricin A poses no increased health risks to researchers.
Select Agents are biological agents that have the potential to pose severe threats to public, animal or plant health. Facilities possessing Select Agents must register with the National Select Agents Program. The Ricin holotoxin (A and B subunits together) has been designated a Select Agent by the U.S. Department of Health and Human Services (HHS) under Federal Regulation 42 CFR 73.
Because flies carrying UAS-Ricin A constructs in the absence of Ricin B coding sequences cannot produce functional holotoxin, they are excluded from the requirements of Select Agent regulations. Consequently, scientists do not need special permission to grow them in lab or use them in experiments. The specific section of the regulations excluding nonfunctional toxins is 42 CFR 73.3(d):
- § 73.3 HHS select agents and toxins.
- (a) Except for exclusions under paragraphs (d) and (e) of this section, the HHS Secretary has determined that the biological agents and toxins listed in this section have the potential to pose a severe threat to public health and safety.
- (b) HHS select agents and toxins:
- (d) HHS select agents or toxins that meet any of the following criteria are excluded from the requirements of this part:
- (2) Non-viable HHS select agents or nonfunctional HHS toxins.
The National Select Agents Program has issued Select Toxin Guidance, which specifically lists Ricin A as an unregulated item in the absence of Ricin B.
Warning: If you are one of the rare scientists working with the Ricin B subunit in your lab and you order UAS-Ricin A stocks, you should take the necessary precautions to prevent the accidental production of Ricin holotoxin. Currently, to our knowledge, there are no transgenic fly strains carrying Ricin B sequences.