Gregory Dolin

Neuronal localization of the adenomatous polyposis coli tumor suppressor protein

Recent biochemical studies have demonstrated that the adenomatous polyposis coli gene, initially identified via its link to colon cancer, is expressed at high levels in the brain. Furthermore, the ability of this tumor suppressor protein to bind to Discs-Large and beta-catenin, proteins implicated in organizing synaptic structure, point to a role for APC in neuronal signalling. However, anatomical studies have provided conflicting results regarding its localization in brain. In situ hybridization studies predict neuronal expression of APC, while immunostaining studies performed with a panel of N-terminal antibodies detected staining of glial cells, especially oligodendrocytes. In this study, we have examined the basis for this discrepancy and provide evidence that the glial staining pattern detected in previous studies reflects cross-reactivity with an unrelated antigen rather than the localization of APC. Furthermore, we have performed immunohistochemical studies with a C-terminal APC antibody which reveal a neuronal pattern of staining closely matching that predicted by the in situ studies. For example, in the hippocampus APC immunostaining is detected in the pyramidal neurons and dentate granule cells, which fits well with the localization of APC mRNA. Examination of APC immunostaining in other regions revealed that particularly intense staining was displayed by large neurons, including layer V cortical pyramidal neurons, cerebellar Purkinje cells, and olfactory bulb mitral cells. Within labeled neurons, APC staining was apparent in the cytoplasm, as well as in dendritic and axonal processes. To help clarify the localization of APC in brain, we have conducted additional in situ hybridization and immunohistochemical studies. These results provide compelling evidence that APC is expressed predominantly in neurons rather than in glial cells as reported previously.

One Model of Collaborative Learning for Medical and Law Students at the University of Baltimore and Johns Hopkins University

Courses on medical malpractice litigation help medical students learn what is expected of them as expert witness and defendant through a mock deposition.

Exclusivity Without Patents: The New Frontier of FDA Regulation for Genetic Materials

Over the last twenty years, the legal and scientific academic communities have been embroiled in a debate about the patent eligibility of genetic materials. The stakes for both sides could not be higher. On one hand are the potential multi-billion dollar profits on the fruits of research (from newly discovered genes), and on the other is scientists’ ability to continue and expand research into the human genome to improve patients’ access to affordable diagnostic and therapeutic modalities. This debate is currently pending before the Supreme Court, which is considering a petition for certiorari in Ass’n for Molecular Pathology v. U.S. Patent & Trademark Office. Both sides have legitimate concerns. Given the unique nature of DNA, patents that broadly cover genetic materials and prevent their use (except by the license of the patentee) create insurmountable roadblocks for future research. However, denying exclusive rights to the fruits of laborious and costly research will remove the necessary incentives for investment in these endeavors, thus delaying scientific and medical discoveries.To remedy these problems, this Article proposes a non-patent exclusivity system administered by the Food and Drug Administration. Under such a system, the innovators who bring new therapeutic or diagnostic products to market would receive exclusive rights to market their products for a limited time. This regime would provide sufficient market-based incentives to continue with the research and investment in this area. At the same time, because genetic sequences would no longer be broadly protected by patents, the public would be able to access these basic research tools without fear of infringement litigation. This approach addresses the concerns of both sides to the debate and leads to a cheaper, more predictable, and easier to administer system of exclusive rights.

Nonprice Competition in 'Substitute' Drugs: The FTC's Blind Spot

As the recent case of United States v. Lundbeck illustrates, the Federal Trade Commissions lack of knowledge in medical and pharmacological sciences affects its evaluation of transactions between medical and pharmaceutical companies that involve transfers of rights to manufacture or sell drugs, causing the agency to object to such transactions without solid basis for doing so. This article argues that in order to properly define a pharmaceutical market, one must not just consider the condition that competing drugs are meant to treat, but also take into account whether there are “off-label” drugs that are used to treat a relevant condition, whether drugs actually compete with each other on price or whether they are selected based on their side-effects (or lack thereof), mechanism of action, physician knowledge, and other noneconomic considerations, and finally whether the drugs in question enjoy any patent or nonpatent-based exclusivity that prevents generic manufacturers from entering the market.

Improving Legislation with the Help of Objective Scientific Advice

The United States Congress enacts legislation that can significantly advance or stall scientific and medical research and progress. Yet, many of these laws are enacted without a full understanding of the underlying science or the impact of the law once enacted. In the current legislative process, it is rare that a bill is fully debated, either in committee or on the house floor. For legislation that involves complex scientific issues, Congressmen with no training in science are unable to predict the effect of their actions in the real world, which can have a devastating effect on scientific progress. This chapter starts with a discussion of the legislative process and the ways in which it can stymie research efforts, followed by a description of the Dickey-Wicker Amendment as a perfect example of how Congress, acting without full knowledge of the science, can impact progress in the sciences. The chapter concludes by proposing a solution: the development of a nonpartisan Congressional Science Office, much like the Congressional Budget Office, that would solicit input from its trained staff as well as the broader scientific community and the general public to evaluate the impact of specific legislation on scientific progress.

Additional Opportunities in the Legal Field and Applying to Law School

Opportunities in the legal arena include organized medicine, teaching, patents, healthcare law, business, among others. Career path includes taking the LSAT, getting admitted into a law school, passing the bar exam, and doing a judicial clerkship. While one can hold both a medical and a law degree, both professions require a great deal of time commitment and continuing education.