John Beatty

A new miniature x-ray device for interstitial radiosurgery: dosimetry.

A miniature, battery operated 40 kV x-ray device has been developed for the interstitial treatment of small tumors ( < 3 cm diam) in humans. X rays are emitted from the tip of a 10 cm long, 3 mm diameter probe that is stereotactically inserted into the tumor. The beam, characterized by half-value layer (HVL), spectrum analysis, and isodose contours, behaves essentially as a point isotropic source with an effective energy of 20 keV at a depth of 10 mm in water. The absolute output from the device was measured using a parallel plate ionization chamber, modified with a platinum aperture. The dose rate in water determined from these chamber measurements was found to be nominally 150 cGy/min at a distance of 10 mm for a beam current of 40 microA and voltage of 40 kV. The dose in water falls off approximately as the third power of the distance. To date, 14 patients have been treated with this device in a phase I clinical trial.

On the Tyranny of Hypothesis Testing in the Social Sciences

Gerd Gigerenzer, professor of psychology at the University of Salzburg (Austria), is coeditor, with L. Kruger, L.J. Daston, and M. Heidelberger, of The Probabilistic Revolution, Vol. 1: Ideas in History. •Zeno Swijtink is assistant professor f history and philosophy of science at Indiana University Bloomington. •Theodore Porter is associate professor of history at the University of Virginia (Charlottesville) and author of The Rise of Statistical Thinking. •Lorraine Daston is professor of the history of science at the University of Gottingen (Germany) and author of Classical Probability in the Enlightenment. •John Beatty is associate professor of the history of science and technology at the University of Minnesota (Minneapolis). •Lorenz Kruger is professor of philosophy at the University of Gottingen (Germany). •Geoffrey R. Loftus, professor of psychology at the University of Washington (Seattle), is coauthor, with E.F. Loftus of Essence of Statistics (2nd ed.).

The proximate/ultimate distinction in the multiple careers of Ernst Mayr

Ernst Mayrs distinction between “ultimate” and “proximate” causes is justly considered a major contribution to philosophy of biology. But how did Mayr come to this “philosophical” distinction, and what role did it play in his earlier “scientific” work? I address these issues by dividing Mayrs work into three careers or phases: 1) Mayr the naturalist/researcher, 2) Mayr the representative of and spokesman for evolutionary biology and systematics, and more recently 3) Mayr the historian and philosopher of biology. If we want to understand the role of the proximate/ultimate distinction in Mayrs more recent career as a philosopher and historian, then it helps to consider hisearlier use of the distinction, in the course of his research, and in his promotion of the professions of evolutionary biology and systematics. I believe that this approach would also shed light on some other important “philosophical” positions that Mayr has defended, including the distinction between “essentialism: and “population thinking.”

Dosimetric results from a feasibility study of a novel radiosurgical source for irradiation of intracranial metastases

PURPOSE A feasibility study addressing the role of a new miniature x-ray device, the Photon Radiosurgery System (PRS), for interstitial radiosurgical treatment of intracranial metastatic neoplasms, was conducted at our institution. To gain insight into the role of PRS vis-à-vis other currently available radiosurgical treatment modalities, dosimetric comparisons of Linac Radiosurgery and proton beam therapy were performed in the treatment of a small approximately spherical metastasis. METHODS AND MATERIALS The photon radiosurgery system is a miniature, battery operated, high-voltage x-ray generator that produces low-energy x-rays with an effective energy of 10-20 keV emanating from the tip of a probe stereotactically inserted into small tumors (< 3 cm in diameter) in humans. Patients, 18 years or older, with supratentorial mass lesions less than 3 cm in diameter were eligible if they were likely to survive their systemic cancer and be capable of self-care for more than 4 months. Patients were ineligible if presenting with infratentorial lesions, contraindications for biopsy, or receipt of chemotherapy or radiotherapy within 4 weeks were ineligible. RESULTS Fourteen patients with metastatic supratentorial lesions were treated from December 1992 to December 1993 for metastatic tumors to the brain. Single doses of 10-20 Gy were delivered to spherical targets of 10 to 35 mm in diameter. Treatment, including biopsy, pathologic review and radiation treatment, generally took less than 3 h. One patient, later found to have an ischemic stroke, developed a small hemorrhage from the biopsy that preceded interstitial irradiation. There were no other complications. Median survival was 10 months. Three locally recurrent lesions failed at 3.5, 4, and 10 months after treatment. All patients had stable or improved Karnofsky status for 2 weeks to 21 months after treatment. The PRS dosimetry appears at least as good as that obtained using 6 MV Linac or 160 MeV protons. Analyses of dose-volume histograms comparing the volumes of normal CNS tissue irradiated employing each of the respective modalities suggest a small sparing of normal tissue with PRS, as opposed to linac or protons, in this patient population with small, approximately spherical tumors. CONCLUSIONS The PRS device provides a unique cost and time efficient procedure for providing interstitial radiation therapy immediately following histologic confirmation of malignancy in patients undergoing biopsy of intracranial lesions. The PRS treatment appears safe, and preliminary data suggest no evidence of treatment-related morbidity within the life span of the selected patient population. When treating small, spherical lesions, PRS appears to offer a modest dosimetric advantage over Linac or proton beam therapy in sparing normal tissue. These encouraging results have prompted a Phase II trial that is currently underway. Further efforts are necessary in the design of a clinically relevant trial addressing the role of fractionated external beam radiation therapy with boost vs. PRS treatment with WBRT in the treatment of single metastases.

Weighing the risks: Stalemate in the classical/balance controversy

ConclusionThe classical/balance controversy continued along these lines throughout the first half of the sixties. Then, at about the same time that the classical position lost its leading advocate, the balance position received striking new support from Harry Harris, and independently from Dobzhanskys former student Lewontin, and Lewontins research partner, Jack Hubby.80 These developments served more to reorient the controversy than to end it — and the resulting “neoclassical”/balance controversy is different enough to be grist for another mill.Social policy considerations no longer play a role in keeping the dispute alive. This particular respect in which the issues have changed is, as Diane Paul suggests in her contribution to this volume, as striking as any other.82 There is, however, little danger of our forgetting that this was once much more than just a narrowly technical controversy — the additional social policy issues were far too blatant.However, although blatant, they were by no means the only, or even the most important, issues. In choosing to concentrate on the social policy considerations, I do not mean to suggest that the empirical issues were irrelevant, or simple and straightforward, or otherwise uninteresting. That is by no means the case. What I have tried to show is that there was much more to the classical/balance stalemate than just the empirical underdetermination of the theoretical issues, and that the empirical issues cannot be treated adequately without taking into account the social policy considerations that were involved. Dobzhansky and Muller both appealed to the dangers of misguided social policy that might have resulted from prematurely resolving their controversy in the others favor. They called for high empirical standards on those grounds, more than once seeking to forestall the resolution of their dispute in this way.

Chance Variation: Darwin on Orchids

How, according to Darwin, does chance variation affect evolutionary outcomes? In his 1866 book, On the Various Contrivances by which British and Foreign Orchids are Fertilised by Insects, Darwin developed an argument that played an important role in his overall case for evolution by natural selection, as articulated in later editions of the Origin. This argument also figured significantly in Darwins reflections on the theological dimensions of evolution by natural selection.

The Synthesis and the Synthetic Theory

Commentators on the evolutionary synthesis frequently identify that event with the formulation of the “synthetic theory.” According to the simplest such characterization of the synthesis, Mendelian genetic theory and Darwinian evolutionary theory — once considered irreconcilable — were eventually reconciled in the theory of population genetics, which is the core of the synthetic theory. That reconciliation itself constituted the much-heralded synthesis.1

Two-dimensional dose distribution of a miniature x-ray device for stereotactic radiosurgery.

The Photon Radiosurgery System is a miniature x-ray device developed for the treatment of small intracranial neoplasms. The x-rays are generated at the tip of a 10-cm-long, 3-mm-diam probe with a nearly isotropic distribution. Results from measurements of the two-dimensional dose distribution around the x-ray source are presented using two methods: (1) dose measurement with an ionization chamber and a water phantom system and (2) dose measurement with radiochromic film and a solid water phantom. The shape of the two angular dose distributions in the axial plane agree with each other to with approximately 10% and the dose at 10 mm from the source, orthogonal to the probe axis, was about 20% lower than at the same distance along the axis. The relative dose difference of 20% corresponds to a change in distance from the source of +/- 0.3 mm at 10 mm. It is shown that the anisotropy of radiation distribution in the axial plane can be improved to approximately 10% by adjusting the electron beam with a 12% reduction in the overall radiation output.

The Insights and Oversights of Molecular Genetics: The Place of the Evolutionary Perspective

A general case about the insights and oversights of molecular genetics is argued for by considering two specific cases: the first concerns the bearing of molecular genetics on Mendelian genetics, and the second concerns the bearing of molecular genetics on the replicability of the genetic material. As in the first case, it is argued that Mendels law of segregation cannot be explained wholly in terms of molecular genetics--the law demands evolutionary scrutiny as well. In the second case, it is argued that an account of the replicability of the genetic material in terms of molecular genetics is not entirely independent of evolutionary considerations, in the sense that it raises further evolutionary questions. The limitations of the molecular-genetic approach in these cases point to the limitations of that approach in general.

What are narratives good for

Narratives may be easy to come by, but not everything is worth narrating. What merits a narrative? Here, I follow the lead of narratologists and literary theorists, and focus on one particular proposal concerning the elements of a story that make it narrative-worthy. These elements correspond to features of the natural world addressed by the historical sciences, where narratives figure so prominently. What matters is contingency. Narratives are especially good for representing contingency and accounting for contingent outcomes. This will be squared with a common view that narratives leave no room for chance. On the contrary, I will argue, tracing one path through a maze of alternative possibilities, and alluding to those possibilities along the way, is what a narrative does particularly well.