Triggle D J
The Graduate School, State University of New York, Buffalo 14260, USA.
Ann Pharmacother. 1999 Feb;33(2):241-6. doi: 10.1345/aph.18337.
Even a cursory survey of this article suggests that the pharmaceutical sciences are being rapidly transformed under the influence of both the new technologies and sciences and the economic imperatives. Of particular importance are scientific and technological advances that may greatly accelerate the critical process of discovery. The possibility of a drug discovery process built around the principles of directed diversity, self-reproduction, evolution, and self-targeting suggests a new paradigm of lead discovery, one based quite directly on the paradigms of molecular biology. Coupled with the principles of nanotechnology, we may contemplate miniature molecular machines containing directed drug factories, circulating the body and capable of self-targeting against defective cells and pathways -- the ultimate "drug delivery machine." However, science and technology are not the only factors that will transform the pharmaceutical sciences in the next century. The necessary reductions in the costs of drug discovery brought about by the rapidly increasing costs of the current drug discovery paradigms means that efforts to decrease the discovery phase and to make drug development part of drug discovery will become increasingly important. This is likely to involve increasing numbers of "alliances," as well as the creation of pharmaceutical research cells -- highly mobile and entrepreneurial groups within or outside of a pharmaceutical company that are formed to carry out specific discovery processes. Some of these will be in the biotechnology industry, but an increasing number will be in universities. The linear process from basic science to applied technology that has been the Western model since Vannevar Bush's Science: The Endless Frontier has probably never been particularly linear and, in any event, is likely to be rapidly supplanted by models where science, scientific development, and technology are more intimately linked. The pharmaceutical sciences have always been an example of use-directed basic research, but the relationships between the pharmaceutical industry, small and large, and the universities seems likely to become increasingly developed in the next century. This may serve as a significant catalyst for the continued transformation of universities into the "knowledge factories" of the 21st century. Regardless, we may expect to see major changes in the research organizational structure in the pharmaceutical sciences even as pharmaceutical companies enjoy record prosperity. And this is in anticipation of tough times to come.
即使对本文进行粗略的审视也会发现，在新技术、新科学以及经济需求的影响下，制药科学正在迅速变革。特别重要的是那些可能极大加速关键发现过程的科技进步。围绕定向多样性、自我复制、进化和自我靶向原则构建药物发现过程的可能性，暗示了一种新的先导化合物发现范式，一种直接基于分子生物学范式的范式。结合纳米技术原理，我们可以设想包含定向药物工厂的微型分子机器，它们在体内循环，能够自我靶向缺陷细胞和信号通路——终极的“药物递送机器”。然而，科学技术并非下个世纪将改变制药科学的唯一因素。当前药物发现范式成本的迅速增加，使得降低药物发现成本成为必要，这意味着减少发现阶段并将药物开发纳入药物发现过程的努力将变得愈发重要。这可能涉及越来越多的“联盟”，以及制药研究小组的创建——制药公司内部或外部高度灵活且具有创业精神的团队，它们为开展特定的发现过程而组建。其中一些将出现在生物技术行业，但越来越多的将出现在大学。自万尼瓦尔·布什的《科学：无尽的前沿》以来一直作为西方模式的从基础科学到应用技术的线性过程，可能从来都不是特别线性，而且无论如何可能会迅速被科学、科学发展和技术联系更为紧密的模式所取代。制药科学一直是应用导向型基础研究的典范，但制药行业，无论大小，与大学之间的关系在下个世纪似乎可能会愈发紧密。这可能成为大学持续转变为21世纪“知识工厂”的重要催化剂。无论如何，即便制药公司正享受创纪录的繁荣，我们仍可能预计制药科学的研究组织结构会发生重大变化。而这是预期未来艰难时期的到来。
