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Organization and Significant Accounting Policies, Fair Value Measurements (Details) - USD ($) $ in Thousands | Dec. 31, 2021 | Apr. 30, 2021 | Dec. 31, 2020 | Dec. 31, 2019
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0.125% Notes [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Interest rate on convertible senior notes |  | 0.125% |  |  | 0.125% |  | 0.125%
0% Notes [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Interest rate on convertible senior notes |  | 0.00% |  | 0.00% |  |  | 0.00%
Recurring Basis [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Cash equivalents | [1] | $ 541,199 |  |  | $ 221,125 |  |
Total |  | 1,807,528 |  |  | 1,745,363 |  |
Recurring Basis [Member] | Bicycle Therapeutics plc [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Investment | [2] | 14,330 |  |  |  |  |
Recurring Basis [Member] | ProQR Therapeutics N.V. [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Investment | [2] | 3,875 |  |  | 2,031 |  |
Recurring Basis [Member] | Corporate Debt Securities [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | 764,059 | [3] |  | 846,315 | [4] |
Recurring Basis [Member] | Corporate Debt Securities [Member] | Cash and Cash Equivalents [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | 2,300 |  |  | 10,000 |  |
Recurring Basis [Member] | Debt Securities Issued by U.S. Government Agencies [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities | [3] | 120,868 |  |  | 174,861 |  |
Recurring Basis [Member] | Debt Securities Issued by U.S. Government Agencies [Member] | Cash and Cash Equivalents [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  |  |  |  | 17,500 |  |
Recurring Basis [Member] | Debt Securities Issued by the U.S. Treasury [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | 182,634 | [3] |  | 358,497 | [5] |
Recurring Basis [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | 174,464 | [6] |  | 136,309 | [3] |
Recurring Basis [Member] | Other Municipal Debt Securities [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities | [3] | 6,099 |  |  | 6,225 |  |
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Cash equivalents |  | 541,199 |  |  | 221,125 |  |
Total |  | 727,708 |  |  | 581,653 |  |
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Bicycle Therapeutics plc [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Investment |  | 0 |  |  |  |  |
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | ProQR Therapeutics N.V. [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Investment |  | 3,875 |  |  | 2,031 |  |
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Corporate Debt Securities [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | 0 |  |  | 0 |  |
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by U.S. Government Agencies [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | 0 |  |  | 0 |  |
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by the U.S. Treasury [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | 182,634 |  |  | 358,497 |  |
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | 0 |  |  | 0 |  |
Recurring Basis [Member] | Quoted Prices in Active Markets (Level 1) [Member] | Other Municipal Debt Securities [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | 0 |  |  | 0 |  |
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Cash equivalents |  | 0 |  |  | 0 |  |
Total |  | 1,065,490 |  |  | 1,163,710 |  |
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 0.125% Notes [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Fair value of convertible notes |  | 495,400 |  |  |  |  |
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | 0% Notes [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Fair value of convertible notes |  | 559,200 |  |  |  |  |
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Bicycle Therapeutics plc [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Investment |  | 0 |  |  |  |  |
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | ProQR Therapeutics N.V. [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Investment |  | 0 |  |  | 0 |  |
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Corporate Debt Securities [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | 764,059 |  |  | 846,315 |  |
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by U.S. Government Agencies [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | 120,868 |  |  | 174,861 |  |
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by the U.S. Treasury [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | 0 |  |  | 0 |  |
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | 174,464 |  |  | 136,309 |  |
Recurring Basis [Member] | Significant Other Observable Inputs (Level 2) [Member] | Other Municipal Debt Securities [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | 6,099 |  |  | 6,225 |  |
Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Cash equivalents |  | 0 |  |  |  |  |
Total |  | 14,330 |  |  | $ 0 |  |
Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Bicycle Therapeutics plc [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Investment |  | 14,330 |  |  |  |  |
Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | ProQR Therapeutics N.V. [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Investment |  | 0 |  |  |  |  |
Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Corporate Debt Securities [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | 0 |  |  |  |  |
Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Debt Securities Issued by U.S. Government Agencies [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | 0 |  |  |  |  |
Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Debt Securities Issued by the U.S. Treasury [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | 0 |  |  |  |  |
Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Debt Securities Issued by States of the U.S. and Political Subdivisions of the States [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | 0 |  |  |  |  |
Recurring Basis [Member] | Significant Unobservable Inputs (Level 3) [Member] | Other Municipal Debt Securities [Member] |  |  |  |  |  |  |
Fair Value Measurements [Abstract] |  |  |  |  |  |  |
Available-for-sale securities |  | $ 0 |  |  |  |  |
[1] | Included in cash and cash equivalents on our consolidated balance sheet.
[2] | Included in other current assets on our consolidated balance sheet.
[3] | Included in short-term investments.
[4] | $10.0 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.
[5] | $17.5 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.
[6] | $2.3 million included in cash and cash equivalents on our consolidated balance sheet, with the difference included in short-term investments on our consolidated balance sheet.

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