Income Taxes - Reconciliation of income taxes (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Reconciliation of income taxes at the U.S. federal statutory rate to the provision for income taxes
Provision (benefit) at U.S. federal statutory rate	$ 119,793	$ (48,766)	$ 102,226
State and local income taxes	34,461	(21,637)	15,109
Foreign tax rate differential	55,171	30,839	57,351
Income tax credits	(55,139)	(38,221)	(60,072)
Change in valuation allowance	(523,279)	158,815	(70,264)
Foreign-derived intangible income	(28,259)	(22,830)	(9,153)
Stock based compensation	15,497	2,802	(414)
Other	3,618	2,477	5,102
(Benefit) provision for income taxes	$ (378,137)	$ 63,479	$ 39,885
Federal corporate tax rate (as a percent)	21.00%	21.00%	21.00%
Deferred tax assets:
Net operating loss carry forwards	$ 137,935	$ 128,088
Federal and state research credits	206,184	305,099
Capitalized research and development	59,247	43,806
Deferred revenue and accruals	42,326	27,467
Non-cash compensation	83,002	75,867
Acquisition-related contingent consideration	31,450	32,658
Intangibles, net	305,228	289,848
Long term investments	34,733	25,968
Other	15,991	26,422
Total gross deferred tax assets	916,096	955,223
Less valuation allowance for deferred tax assets	(408,180)	(930,209)
Net deferred tax assets	507,916	25,014
Deferred tax liabilities:
Property and equipment	(33,259)	(19,880)
Other	(7,119)	(3,080)
Total gross deferred tax liabilities	(40,378)	(22,960)
Net deferred tax assets	467,538	2,054
Deferred tax assets valuation allowance
Increase (decrease) in valuation allowance	$ (522,000)	$ 159,700	$ (66,500)