In this action, plaintiffs allege that the decedent John Rogers' ("Rogers") multiple myeloma was exacerbated by stress resulting from defendants' conduct during the last several years of their approximately 15-year landlord-tenant relationship.^[FN1]

Defendants moved for summary judgment to dismiss, inter alia, plaintiffs' cause of action for the intentional infliction of emotional distress on the grounds that plaintiffs cannot establish by competent medical evidence that defendants' conduct resulted in severe emotional distress. Defendants also argued that Rogers cannot establish his allegations that defendants' conduct exacerbated his multiple myeloma since there is no general acceptance in the scientific community that a cause and effect relationship exists between stress and the exacerbation of multiple myeloma.

In connection with the motion, the parties submitted conflicting affidavits of their respective medical experts. In the affidavit submitted by defendants, Jeffrey Schneider, M.D., a board certified physician specializing in oncology/hematology,^[FN2] opined that there is no medical support for plaintiffs' theory that stress exacerbates multiple myeloma, and that there are no [*2]reported studies in the medical literature to support this theory.

In opposition, plaintiffs relied on the affidavit of Dr. Brian Durie, a physician who is board certified in oncology, hematology and internal medicine and who specializes in multiple myeloma and related diseases and is the Chairman and Medical Director of the International Myeloma Foundation.^[FN3] Dr. Durie opined that there is a strong correlation between stress and multiple myeloma, and that there is a "link between stress which John Rogers describes and the progression of his case from MGUS ^[FN4] to myeloma which occurred during the same period [as the stress] is clear and medically predictable."^[FN5] Based on the conflicting opinions stated in the affidavits, a hearing was ordered to determine the admissibility of evidence regarding plaintiffs' theory of causation.

New York courts apply the standard established by Frye v United States, 293 F 1013 (1923) for screening of novel scientific evidence. Under the rule in Frye, scientific evidence, including expert testimony, must be based on "a principle or procedure [which] has gained general acceptance' in its specified field." People v Wesley, 83 NY2d 417, 422 (1994)(quoting Frye, supra, at 1014).

"The particular procedure need not be unanimously endorsed' by the scientific community but must be generally accepted as reliable.'" Id at 423 (quoting People v Middleton, 54 NY2d 42, 49 [1981]). " [G]eneral acceptance does not necessarily mean that a majority of the scientists involved subscribe to the conclusion. Rather, it means that those espousing the theory or opinion have followed generally accepted scientific principles and methodology in evaluating clinical data to reach their conclusions." Zito v. Zabarsky, 28 AD3d 42, 44 (2d Dept 2006)(quoting Beck v. Warner-Lambert Co., 2002 WL 31107923, NY Slip Op. 40431(U) [Sup Ct. NY Co. 8-16-02]).

The question is "whether the proffered expert opinion properly relates existing data, studies or literature to the plaintiff's situation, or whether instead it is connected to existing data only by the ipse dixit of the expert.'" Marsh v. Smythe, 12 AD3d 307, 312 (1st Dept 2004) (concurring opinion, Saxe, J.)(quoting General Elec. Co. v. Joiner, 522 US 136, 146 [1997]). When, as here, the issue concerns a causal connection, a plaintiff's expert must set forth scientific evidence based on generally accepted principles showing such a causal link. Selig v. Pfizer, Inc., 290 AD2d 319, 320 (1st Dept), lv denied, 98 NY2d 603 (2002). Such a showing can be made "through judicial opinions, texts, laboratory standards or scholarly articles." Marsh v. Smythe, 12 AD3d at 311 (quoting People v Wesley, 83 NY2d at 437, concurring opinion, Kaye, J.). However, it is not necessary that "the underlying support for the theory of causation consist of cases or studies considering circumstances exactly parallel to those under consideration in the litigation. It is sufficient if a synthesis of various studies or cases reasonably permits the [*3]conclusion reached by the plaintiff's expert." Marsh v. Smythe, at 312-313.

Here, plaintiffs do not rely on studies or literature which specifically and directly find that stress exacerbates multiple myeloma. Rather, plaintiffs rely on a synthesis of the opinion and research of Dr. Durie, a clinical oncologist/hemotologist, Dr. Janice Kiecolt-Glaser, a psychologist, and Dr. Ronald Glaser, a psychologist/virologist and various scientific studies and articles which they reference in their testimony.^[FN6] Plaintiffs contend that their theory is generally accepted in the field of psychoneuroimmunology "PNI" which Dr. Durie identified as an emergent interdisciplinary field of psychiatrists, neurologists and immunologists. Dr. Ronald Glaser described the field as beginning to coalesce in the late 1970's early 1980's and involving the study of the interaction of the central nervous system, and the immune and endocrine systems. Plaintiffs acknowledge that PNI is not recognized by the American College of Physicians nor by the American Medical Association. However, they contend the lack of recognition is not relevant, as the American College of Physicians identifies categories of clinical specialties and PNI is not such a specialty, and the American Medical Association identifies areas of treatment and PNI is not an area of treatment.

Plaintiffs contend, as Dr. Ronald Glaser testified, that recognition of a field of study such as PNI occurs gradually when the field through research, publications, grants and other means gains credibility in the medical and scientific community. Plaintiffs further contend that PNI is a recognized field based on the publication in the field of numerous articles and studies subject to peer review, on a review of PNI by the Institute of Medicine, the medical arm of the National Academy of Science to identify areas of research being conducted within PNI, on the decision of the National Cancer Institute to encouraged research in PNI as to the relationship between stress and cancer, and on the existence of the Society of PNI which publishes a journal, "Brain, Behavior and Immunology." Furthermore, Dr. Kiecolt-Glaser and Dr. Ronald Glaser testified their research is conducted in PNI, they and others have published numerous studies in the field, and have received substantial grants, including finding from the National Institute of Health. Furthermore, Ronald Glaser testified that he is the Director of the Institute for Behavioral Medicine Research ("IBMR") at the Ohio State University Medical Center which has faculty engaged in research involving various disciplines, which comprise PNI, including psychology, endocrinology, immunology and neuroscience.

Defendants contend that PNI, while an area of interdisciplinary research, is not the relevant scientific community relevant to the issues raised in the Frye hearing. Rather defendants contend that the relevant community is the medical community, and specifically the specialty of hematology/oncology, i.e. the treatment and study of cancer of the blood. Defendants' expert, Dr. Schneider, who, as previously mentioned, is board certified in hematology/oncology, testified that there is no support in the medical literature nor is it generally accepted in the hematology/oncology community that stress exacerbates multiple myeloma. According to Dr. Schneider, the official position of the National Cancer Institute is that it has not [*4]been established that there is any connection between stress and worsening multiple myeloma

It is well settled law, that plaintiffs as the proponents of the theory have the burden of proof at the Frye hearing. See Lara v. New York City Health & Hospitals Corp., 305 AD2d 106 (1st Dept 2003). For the reasons delineated below, this court concludes that plaintiffs have failed to meet their burden. This court rejects plaintiffs' contention that PNI is the relevant scientific community, and their contention regarding the general acceptance and implications of the studies and research cited as a basis for a synthesis supporting their theory. In essence, plaintiffs argue that general acceptance in the relevant scientific/medical community of a causal relationship between stress and the progression of multiple myeloma can be extrapolated from certain discrete research showing that stress increases levels of hormones and cytokines, and that research as to one type of cancer is applicable to other cancers.

Plaintiffs' theory was explained by Dr. Durie, who testified that his opinion was based on a three-step analysis: first, that scientific studies show stress can impact on the course of cancer generally; second, that stress produces changes in the lymphocytes in the immune system and an increase in levels of certain hormones and cytokines ^[FN7] that affect the immune system in a deleterious way; and third, that the hormones or cytokines that are influenced by stress are central to the growth of myeloma.

As support of the first prong of this analysis that stress impacts generally on the progression of cancer, at the hearing Dr. Durie pointed to data and publications referenced in his verified opinion. As to the second and third prongs, that stress results in changes in the levels of certain hormones and cytokines and in the immune system and that these changes are critical and central to the growth of myeloma, Dr. Durie relied on his clinical experience, including the clinical histories of stress in his myeloma patient population, his own research, and studies of others that scientific and biologic data support these principles. Dr. Durie specifically referenced the research of Dr. Janice Kiecolt-Glaser and Dr. Ronald Glaser, as providing support as to the effects of stress on certain cytokines in issue, as well as the research of, among others, Dr. Anil Sood and Dr. Reiche.

Dr. Durie, who as indicated above, is a hematologist/oncologist ^[FN8] specializing in multiple myeloma and related diseases, testified that multiple myeloma is a cancer of the plasma cell, a cell which arises in bone marrow and is an important part of the immune system as it provides antibodies which help fight infection and other diseases. If a plasma cell becomes malignant, it is called a myeloma cell. An individual with myeloma has an abnormal build-up of myeloma cells in the bone marrow with displacement of normal marrow and which results in tumors that involve and destroy surrounding bone. As described by Dr. Durie, in response to myeloma, certain types of cells are produced in the immune system, including T-helper lymphocytes which help control myeloma. His published research ^[FN9] indicates that when the level of the T-helper cells [*5]drops, the ability of the immune system to regulate myeloma is reduced and the myeloma worsens. Dr. Durie further explained that other research shows that stress results in the increased production of hormones and cytokines.

Dr. Durie testified that the deleterious impact of stress is mediated by cell-to-cell messages carried, inter alia, by certain hormonal and cytokine mediators or pathways.^[FN10]

The mediators identified by Dr. Durie are the hormones adrenaline (epinephrine) and non-adrenaline (norepinephrine) and cytokines, interleukin-6 (IL-6), interleukin-1 (IL-1) and tumor neocreses factor-aplpha (TNF-alpha). According to Dr. Durie, hormones are produced by certain glands in higher levels as a result of stress, and cytokines are produced when a macrophage, a cell in the immune system which regulates other cells, is activated by stress.

Dr. Durie testified that within the emerging field of interdisciplinary research, PNI, IL-6 and other cytokines, and the hormones epinephrine and norepinephrine are recognized as mediators of both normal and aberrant physiologic responses to triggers such as stress. Dr. Durie further testified that "it is generally accepted in the field of PIN that IL-6 is a growth factor for multiple myeloma" and since it is a growth factor, "if the IL-6 level increases, the tumor grows."^[FN11] In support of this statement regarding IL-6 and the stress hormones, Dr. Durie referenced the work and expected testimony of Dr. Kiecolt-Glaser and of Dr. Ronald Glaser.

Dr. Durie also referenced, among others, the research of Dr. Sood regarding ovarian cancer and the hormone norepinephrine, and of Dr. Reiche regarding an article on the effect of stress on hormones and cytokines in the development and progression of cancer. It must be noted that Dr. [*6]Reiche's article ^[FN12] is an overview of research regarding stress and depression-induced immune dysfunction in various cancers. Significantly, as to the effects of stress on myeloma, Dr. Reiche specifically references the work of Dr. Keicolt-Glaser and Dr. Glaser that chronic stress enhances the production if IL-6 and that high plasma IL-6 levels are associated with "a spectrum of age related conditions including ... multiple myeloma." Thus, Dr. Reiche's article is not independent support for the effects of stress on the progression of myeloma.

In further support of the theory that the IL-6 is a growth factor for myeloma, Dr. Durie pointed to the effect of certain drugs which when given, the "myeloma gets better," that is, the tumor shrinks. As described by Dr. Durie, two drugs, Thalomid and Revlimid, inhibit cytokine TNF-alpha, and a new agent Belcade "a proteasine inhibitor, blocks cytokine pathways including IL-6, IL-1 and TNF alpha."^[FN13]

As to Dr. Kiecolt-Glaser, she testified about her research involving caretakers whose spouses were afflicted with Alzheimer's disease and the effects of chronic stress on such caretakers' immune systems. Specifically, Dr. Kiecolt-Glaser testified the research showed that chronic stress increases the levels of IL-6 and impaired the caretaker's ability to respond to certain vaccines and to heal wounds. She further testified that a consequence of chronic stress and depression is that the production of IL-6 sensitizes inflammatory response, so that exaggerated levels of IL-6 arise in response to subsequent stressful events. Furthermore, Dr. Kiecolt-Glaser testified research demonstrated that chronic stress in older adults permanently altered their immune system and accelerated age related changes in levels of IL-6.

Dr. Ronald Glaser testified concerning his opinion about the relationship between myeloma and IL-6, that myeloma cells have receptors for IL-6 and the ability to synthesize IL-6 into the surrounding cell milieu. Dr. Glaser explained that IL-6 could be a trigger to band a receptor and another myeloma cell, thus stimulating the growth of the tumor. When asked if this opinion was generally accepted, Dr. Glaser responded that "[w]ell, it's really good papers ... Maybe I should say, in reality if I was at a multiple myeloma meeting, I'm sure there might be people who would disagree with that, there's always people who disagree with something, but I think the majority of the people in that room would feel pretty comfortable with that association." Although Dr, Glaser further indicated that data to support this opinion is published in peer review journals, the articles he cited do not specifically discuss IL-6 and multiple myeloma.^[FN14]

Dr. Ronald Glaser also testified about his own research regarding stress induced immune dysfunction in the progression of cancer and specifically about his research with the Epstein Barr Virus ("EBV"). According to Dr. Glaser the research shows that certain hormones produced by stress activates latent EBV which lead to increased levels of IL-6. Dr. Glaser testified that this is [*7]of significance as EBV "has been associated with myeloma to some degree in ways that are not understood."

Additionally, Dr. Glaser testified that his research involving the effect of stress hormones on nasopharyngeal carcinoma cancer, and that of Dr. Sood involving ovarian cancer, showed that certain tumor cells "express beta adrenergic receptors" to which two of the stress hormones, epinephrine and norepinephrine, can bond, thus affecting the growth of cancer cells. Dr. Glaser explained that his and Dr. Sood's research showed that such receptors when treated with norepinephrine can induce tumor cells to produce vascular endothelial growth factor ("VEGF") and two different matrix matalloproteinases ("MMP's"). The MMPs allow tumor cells to break down the extra cellular matrix and migrate, and thus, to metastasize. The VEGF attracts nearby blood vessels, i.e. capillaries, to migrate into the tumor and provide a blood supply to it. While neither of these studies relates to myeloma, Dr. Glaser testified that his recent research shows that cells derived from myeloma tumor cells also express beta adrengeric receptors. Dr. Glaser opined that the stress hormone, norepinephrine, would stimulate myeloma tumor cells to produce MMPS and VEGF, enhancing a myeloma tumor's progress. According to Dr. Glaser, the significance of this research regarding myeloma is that this pathology directly links the stress inducing hormone norepiphrine to tumor progression independent of the immune system. However, it must be noted that this research is yet to be conducted with myeloma cells and norepinephrine.

Defendants challenge the sufficiency of plaintiffs' proof, arguing that absent studies or clinical data specifically linking stress to the exacerbation of multiple myeloma, plaintiffs failed to sustain their burden of proof. Defendants argue, as indicated above, that the relevant scientific community is that of hematology/oncology, the study of cancer of the blood, and not PNI. Defendants' expert, Dr. Schneider, who as previously mentioned, is board certified in hematology/oncology, testified that there is no support in the medical literature nor is it generally accepted in the hematology/oncology community that stress exacerbates multiple myeloma. According to Dr. Schneider, the official position of the National Cancer Institute is that it has not been established that there is any connection between stress and worsening multiple myeloma.^[FN15]

In order to conduct a scientifically reliable study to show that stress exacerbates multiple myeloma, Dr. Schneider testified that the methodology used must analyze the course of the multiple myeloma, examine where a factor is varied, and examine where there is a decrease or increase in the occurrence of the disease. Dr. Schneider stated it would be necessary to follow stress levels of people with multiple myeloma to see if stress affects the outcome, and if there is a high incidence of multiple myeloma in people subjected to certain levels of stress.

As to Dr. Durie's testimony, defendants argue that he did not author any peer review articles regarding this theory, that neither the medical text "Multiple Myeloma and Related Disorders" which Dr. Durie edited in 2004, nor the Patient Handbook he authored in 2006, [*8]discusses that stress exacerbates myeloma,^[FN16] and point out that Dr. Durie is a frequent lecturer on myeloma and he testified to a single lecture he gave recommending stress reduction as an approach to improving quality of life, and a single slide presentation referencing stress and IL-6.

As to the relevance of the testimony of Dr. Kiecolt-Glaser and Dr. Ronald Glaser, defendants point out that both are clinical psychologists, and although Dr. Ronald Glaser is also a virologist, they testified as to acceptance of certain aspects of plaintiffs' theory in the field of PNI, which defendants argue is not the relevant medical community. As to Dr. Kiecolt-Glaser's testimony relating her research to a number of publications regarding effects of chronic stress on several health conditions and diseases,^[FN17] defendants argue that none of the articles specifically relates stress to increased IL-6 and the progression of multiple myeloma. Defendants also point to Dr. Kiecolt-Glaser's testimony that the National Cancer Institute thinks the relationship between stress and multiple myeloma is an important area "to explore."

As to Dr. Ronald Glaser's testimony that myeloma cells have the ability to synthesize the IL-6 into surrounding tissue so that it binds to receptor cells, defendants argue that Dr. Glaser did not cite one article specifically supporting this opinion, and that the articles Dr. Glaser cites ^[FN18] are unrelated to multiple myeloma research.

Finally, defendants argue that Dr. Sood's studies regarding ovarian cancer cells and stress are animal studies, and that neither these studies nor Dr. Glaser's studies involving nasopharyngeal carcinoma cancer are related to multiple myeloma.^[FN19] Defendants also argue that Dr. Reiche's article does not specifically address stress and myeloma and merely hypothesizes a link between stress and cancer.

Based on the evaluation of the evidence presented at the hearing as delineated above, this court concludes that plaintiffs have failed to establish that their theory, that stress exacerbates the progression of multiple myeloma, is generally accepted in the relevant scientific community, which this court concludes is the medical community. This court finds that hematology/oncology is the proper area of medical expertise as that area involves the treatment and study of cancers of the blood, including multiple myeloma. In reaching the conclusion that plaintiffs' theory is not generally accepted in hematology/oncology, the court considered the following factors: the nature of plaintiffs' proof as discussed below, Dr. Schneider's testimony that this theory is not generally accepted, the absence of literature or controlled studies which are accepted in oncology/ hematology, and the absence of this theory in the medical text Dr. Durie edited in 2004 and the Patient Handbook he authored in 2006.

As to the relevant medical community, while not dispositive, the court notes that as [*9]acknowledged by Dr. Durie, PNI is an emergent interdisciplinary field of psychiatrists, neurologists and immunologists. Although evidence indicates significant work conducted by researchers in this field, and some recognition of the field by the Institute of Medicine and the National Cancer Institute, plaintiffs have failed to show that the field of PNI is recognized or has gained general acceptance in the medical/scientific community so as to establish that it is the relevant medical/scientific community for the purposes of determining whether it is generally accepted that stress exacerbates multiple myeloma.

Furthermore, as an evolving field comprised of psychiatry, neurology and immunology, which involves the study and interaction between the nervous, endocrine and hormone systems, it is unclear how general acceptance in PNI is ascertained. This difficulty is compounded by the nature of plaintiffs' proof, which consists of a synthesis of opinions and discrete studies in different disciplines to support the conclusion that stress exacerbates myeloma.

While the law specifically allows for a synthesis of various studies and/or cases to support an expert's theory or opinion (Marsh v. Smythe, 12 AD3d at 312-313), plaintiffs have failed to show any integrating scientific principles underlying the synthesis which plaintiffs seek to demonstrate from the individual studies. Plaintiffs propose a synthesis based on the testimony of Dr. Durie regarding his research including a study showing an association between lower T-helper cells and relapse of myeloma, clinical histories of his patients and the effect of certain drugs in shutting down cytokine pathways. Plaintiffs' proposed synthesis is also based on studies of various researchers, including Dr. Keicolt-Glaser as to the effect of chronic stress and levels of the cytokine IL-6 in caregivers; Dr. Ronald Glaser and Dr. Sood as to the effect of the hormone norepinephrine on respectively, nasopharyngeal and ovarian cancer; Dr. Ronald Glaser as to the effect of IL-6 on myeloma cells; and Dr. Reiche as to an overview of stress and the development and progression of cancer.

Plaintiffs' argument when stripped to its essentials is that a causal relationship between stress and the progression of multiple myeloma can be extrapolated from certain discrete research showing that stress increases levels of specific hormones and cytokines which are associated with the growth of myeloma and that research regarding other types of cancer applies to multiple myeloma. This court finds that plaintiffs have failed to establish that a synthesis of the research is legally sufficient to support the conclusion that stress exacerbates myeloma.

Accordingly, it is

ORDERED that defendants' motion to exclude plaintiffs' evidence that stress exacerbates multiple myeloma is granted.

Dated: January , 2008_______________________

J.S.C.