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To the Editor: I read “Necrosis used to kill cancer,” by John Dudley Miller and its source paper with great interest. I agree that this nice piece of research has much for cancer biologists to ponder. However, I also agree with comments from other investigators that in the field, this particular occurrence will likely be rare due to preemption by apoptotic mechanisms. As for the conclusion that necrosis induction would be preferable to apoptosis induction because apoptosis suppresses immunity, I'm with Dr. Evan that this suppression is not complete in any case when massive death occurs. In fact, it is a breakdown in such immune suppression that is thought to cause the temporary presence of anti-dsDNA antibodies in mononucleosis patients. The thought of inducing immune responses to tumor cells is of course not new. For example, about 100 years ago, the New York surgeon William B. Coley noted that cancer patients experiencing a bacterial infection would sometimes show spontaneous regression of a tumor. He then used bacterial extracts that he injected into tumors such as sarcomas. Occasional regressions were observed, and subsequent investigations co-injecting irradiated tumor cells together with bacterial adjuvans showed further limited responses. The immune system appears to be activated by such “vaccines” more or less nonspecifically, and the tumor cells were thought to be killed more as bystanders than as targets. I think it is most likely that a similar largely non–tumor specific immune responses would ensue from killing tumor cells piecemeal. My worry is that if any response does ensue in this situation, the tumor-specific response is not only going to be drowned out by other responses, but that we would actually induce very undesirable autoimmune responses. It is, I think (partially) for this reason that most investigations attempting immune induction focus on identification of tumor-specific antigens. Many investigators may say or feel that autoimmunity is not a problem, as their patients would otherwise be doomed anyway. I would argue that lupus-like diseases show that quality of life can be severely reduced by autoimmune diseases, and therefore we should be especially careful not to try therapies that potentially induce gross autoimmune reactions in anyone with a possibly appreciable amount of life ahead of them. I would use (drug-induced as well a ordinary autoimmune) lupus as a perfect example of why we actually require apoptosis to suppress the immune system and why we should not meddle with this too much before we understand immune regulation more fully. Nick Henriquez (N.V.Henriquez@lumc.nl) Department of Endocrinology, Leiden University Medical Centre, The Netherlands To the Editor: I wanted to correct some errors in your story, “Estonia genome project lives on.” First, professor Andres Metspalu is not head of the project. He was one of the initiators of the project. Today, he is a member of the Scientific Advisory Board of the Estonian Genome Project Foundation. Second, with the funds allocated by Egeen, the data of up to 5000 gene donors can be collected this year. Finally, the Estonian Genome Foundation and the Estonian Genome Project Foundation are different organizations. Aire Koik (aire.koik@geenivaramu.ee) Estonian Genome Project Foundation To the Editor: Re: “Estonia genome project lives on.” EGeen, being the exclusive commercial licensee to the Estonian Genome Project in return for its commitment to finance the project, has consistently been insisting on making certain that high quality is maintained while building the clinical database of the Estonian Genome Project. The focus on more specific in-depth questions to be added to the health data questionnaire to obtain research-quality clinical data has been an ongoing effort supported by EGeen since early 2003 to avoid a “garbage-in, garbage-out” problem. EGeen has made a recommendation to the Estonian Genome Project Foundation to accelerate implementation of clinical data quality checks to ensure viability of such a database in the global scientific landscape, but it has not made the financing conditional on what is referred to as “research priorities.” Kalev Kask (kalev.kask@egeeninc.com) Chief Executive Officer, EGeen To the Editor: I was very disappointed to read the title of your article “Vatican buys drug lab.” In the very next line, the subtitle continues with “Catholic charity with close links to the Holy See buys oncology lab From Pfizer.” I do not know the particulars of the situation, but what a gross misrepresentation the title—in fact, so gross for me to call it a lie. No matter how close the links are, the charity is not the Vatican and vice versa. As a Catholic and a subscriber to The Scientist, I am appalled and very disappointed. Burke Squires (burke@mac.com) MacroGenics, Inc.

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