Today's Globe: proteins tied to HIV virus, wrong body taken

I was surprised to learn the Harvard study led by Professor Stephen Elledge was conducted in highly aneuploid “HeLa-derived TZM-bl cells”. I've worked the past 11 years studying the consequences of aneuploidy and feel I should pass along some of my concerns about the study’s experiments and the authors’ conclusions.

As I say, HeLa cells are massively aneuploid cervical cancer cells from the 1950s, containing typically 76–80 chromosomes and 22–25 abnormal chromosomes per cell instead of the normal complement of 46 (Macville M, Schrock E, Padilla-Nash H, Keck C, Ghadimi BM, Zimonjic D, Popescu N, Ried T: Comprehensive and definitive molecular cytogenetic characterization of HeLa cells by spectral karyotyping. Cancer Res 1999, 59:141-150).

No two HeLa cells are genetically alike, in fact no two use the same network of genes, gene products, transcription factors, receptors, etc. Furthermore, the HeLa cells are highly genomically unstable; they change with each cell division.

Thus, the claimed “273 proteins that the AIDS virus needs to survive in human cells” are probably an artifact of performing the experiments in the HeLa cells and actually have little or nothing to do with what goes on in people.

Ultimately, the multi-million dollar question is even if one can prevent HIV from replicating in HeLa cells by removing the susceptible human proteins, will the same thing happen in normal human cells in patients? The odds are strongly against it.

There is also the conceptual problem of administering drugs against human proteins since these drugs will be inherently toxic. I was in the drug design and development business for 20 years. The first principle in coming up with drugs against infectious agents was to target proteins specific to the pathogen and not human in order to minimize potential and actual toxic consequences.

Researchers should ponder these questions before going down the very expensive road suggested by the Harvard group.

Sincerely,

David Rasnick, PhD

I must disagree with Mr. Rasnick. If he read the paper carefully he would realize that in each case for which it was tested, the proteins needed in the Hela cells were also needed in T cells, the natural host cell for HIV. Many of the proteins identified are used both in Hela and normal cells for the same purpose. Simply because Hela cells are aneuploid, does not mean the results are artifacts.

With respect to the second assertion that any drugs made to these proteins would be highly toxic, I would simply point out that Mr. Rasnick has no idea whether they would be or not. Every protein in a cell is potentially needed, yet the vast majority of non-antibiotic drugs people take are against human proteins. People seem to be able to tolerate these drugs so the the thesis proposed by Mr. Rasnick is untenable in a general sense.