Betting against biotechnology stocks and exchange traded funds has been, broadly speaking, a fool’s bet and borderline heresy over the past several years.

That much has been on display in 2015 as the top six non-leveraged ETFs are all biotech funds. However, that is not stopping some market participants from making bearish prognostications regarding high-flying biotech ETFs. On Monday, Goldman Sachs advised clients purchase the December $230 puts on the SPDR S&P Biotech ETF (NYSEArca: XBI).

“These puts are about 10% out-of-the-money and cost about 6.2% of spot. If shares saw a 27% drawdown like they did in early 2014, these puts could have a 4-to-1 payout. If shares fell back to the levels of a year ago, these puts could have a 5-to-1 payout,” John Marshall, a Goldman Sachs derivatives strategist advised clients in a pre-market trading advisory, reports Ben Levisohn for Barron’s.

XBI is the third-largest biotech ETF by assets and the third-best sector ETF this year with a gain of almost 35%. XBI was 2014’s second-best sector ETF behind, you guessed it, another biotech ETF. [More Upside for Healthcare ETFs]

That is to say betting against XBI and its brethren is hard, but it also means when those bets payoff, as Goldman notes, they payoff handsomely. For the adventurous, risk-embracing trader that wants to eschew the options but still make a bearish wager on XBI, there is the newly minted Direxion Daily S&P Biotech Bear 3X Shares (NYSEArca: LABD).

LABD, which debuted in late May, attempts to deliver three times the daily inverse performance of the S&P Biotechnology Select Industry Index, XBI’s underlying index. “The companies included in the Index have a median market capitalization of $1.54 billion and are concentrated in the energy and biotechnology sectors as of April 30, 2015. Component securities have capitalizations ranging from $320.9 million to $149.0 billion as of April 30, 2015,” according to Direxion.