In 1969, Rosenberg’s lab published the promising results on the antitumor property of cisplatin in mice [3, 8]. Then clinical trials followed. At first, it caused a public shock as heavy metal compounds were believed to be extremely toxic [4, 5]. Despite so, cisplatin turned out to be effective for many types of cancer when used in combination with other medications [4], especially for testicular cancer which had no known effective drug at that time [9]. In 1978, cisplatin was approved by the Food and Drug Administration (FDA) in the US, followed by other countries [4]. It remains as one of the key medicines for cancer treatment today [10]. Modern research shed light on how cisplatin works. Cisplatin inhibits DNA replication mainly by “tying” (or, forming crosslinks between) two purine bases (adenine and guanine) on the same strand together [11, 12], which eventually leads to failure in cell division and apoptotic cell death [11]. From the non-specific mode of action of cisplatin, it can also harm actively dividing cells in normal tissues, such as the intestine, thus causing severe side effects [13]. This partly explains why researchers were looking for new generations of platinum-based drugs. Notably, carboplatin entered the market in 1989 with a much lower systemic toxicity [5, 13, 14], and oxaliplatin was approved in 1994 with a high efficacy against colon cancer [5, 14]. Thanks to the Rosenberg’s serendipitous rediscovery, an array of platinum-based drugs was made available and saved the lives of many cancer patients. The rediscovery of cisplatin was an extremely lucky combination of events. Yet, it was also the open mindset and curiosity of Rosenberg that brought this fundamental discovery to all of us. The story of cisplatin also serves as a reminder of how multiple scientific fields can powerfully intertwine, as there is no actual boundary between chemistry, physics and biology. Chance favors only the prepared mind. Was it luck or a good grip? You decide for yourselves. 如果不是運氣，有些科學發現就不會發生：蘋果落在牛 頓身旁使他想到萬有引力 [1]，Roentgen對他實驗室裡神 秘發光小屏幕的調查最終使他發現了X射線 [2]。科學史 上從不乏偶然遇上的驚喜。本文將介紹另一個無意中的發 現，它拯救了無數生命 — 這是Barnett Rosenberg對順鉑 （cisplatin）的二次發現。 Rosenberg 於1948 年從布魯克林學院取得物理學學 士學位，並分別於1950 和1955 年從紐約大學獲得物理學 碩士和博士學位 [3]。由於他一直接受物理學訓練，使他能提 出生物學家未必能想到的獨特見解：他注意到細胞分裂中的 有絲紡綞體看起來就像兩個相反電荷之間的電場線（或兩個 相反極性之間的磁場線）（圖一）。這只是巧合嗎？還是電磁 學與細胞分裂有關？ 儘管大腸桿菌（Escherichia coli）並不使用有絲紡綞 體來進行細胞分裂，Rosenberg 還是於1965 年在大腸桿 菌上試驗了他這個不尋常的想法 [4, 5]。他使用了在生物和 化學上也被認為是具惰性的鉑電極，向以氯化銨作為pH 緩衝劑的細菌溶液傳送電流 [6]。不管他原來的預測結果 是甚麼，他也不會猜到接下來的事情：微生物並沒有分裂 得更快；反而，它們全部呈現被拉長，彷彿想分裂但不能成 功的樣子。與正常大小相比，它們的長度增加了足足300 倍 [7]！因此，Rosenberg認為是電流影響了細胞分裂。 然而，這不是正確的結論。在接下來的兩年， Rosenberg 發現阻礙細胞分裂的不是電流，而是在反應中 產生的順鉑（圖二）[4, 5]。這種化合物早於1854年已被意 大利化學家Michele Peyrone發現，但在Rosenberg二 次發現前並沒有人對其作出過深入研究 [4]。與當時許多具 有抑制細胞分裂能力的新物質一樣，順鉑被視為化療的候選 藥物之一 [4]。 圖一 分裂中的細胞，當中有絲紡綞體與染色體連接（左）和兩個相 反電荷之間的電場線（右） Fun fact: Is there transplatin? Yes, it is a stereoisomer of cisplatin with no anti-tumor activity [4]. transplatin
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