For years I assumed the eye-watering price on the most advanced drugs was, at bottom, a chemistry bill. Molecules that hard to build, I figured, must cost a fortune to make, and the sticker just passed that cost down to me. A method that came out of a Rice University lab this month convinced me I had it backward twice over: the chemistry did just get cheaper, and it still tells you almost nothing about the price.

On July 15, chemists in Hans Renata’s lab at Rice published a paper in Nature that takes one of the priciest ingredients in modern drug synthesis and makes it reusable. The molecule is called ATPγS, and until now every batch was a one-and-done expense. “To add thiophosphate to a chemical structure like a drug, you need to use a compound called ATPγS, which is a very expensive molecule,” said co-first author Xiangyu Wu in the Rice announcement. “Every time we wanted to add a thiophosphate, we had to use a new ATPγS, and each ATPγS was extremely expensive.” The Rice team found a way to use the same molecule over and over.

So why bother with ATPγS at all? A lot of drugs, especially the ones built from biological molecules, carry phosphate groups, and your cells treat phosphate as a switch: enzymes clip it on and clip it off to turn processes up and down. That is elegant inside a living cell and a headache for a drug designer, because the same enzymes that strip phosphate off your own proteins will strip it off a drug too, and a dephosphorylated drug can quietly stop working. So chemists swap in a lookalike called thiophosphate, where a single sulfur atom sits where one oxygen used to be. The sulfur holds on, the cell’s clippers slide off it, and the drug survives long enough to do its job. To install that swap with enzymes you need ATPγS as the sulfur donor, and here is the catch: the enzyme spends one ATPγS for every single thiophosphate it installs. Burn one, get one. At clinical scale that adds up fast.

Then I hit the part of the paper that actually made me sit up, because the fix they reached for is a trick your own body runs every second of the day. “Since ATP and ATPγS are so similar, we decided to see if we could adapt the ATP recycling process for ATPγS,” said co-first author Yu Fu. “It turns out with the right enzymes and the right sacrificial donor molecule, you absolutely can recycle ATPγS.” That sacrificial donor is a specially designed creatine derivative. Wait, why would a molecule best known from a gym supplement tub have anything to do with cutting-edge drug synthesis? Because creatine is exactly how your muscles keep ATP charged. In a working muscle, phosphocreatine hands its phosphate group back to spent ATP to regenerate it on the spot. The Rice team built a creatine-like donor that does the same favor for ATPγS: after the enzyme spends it, the donor recharges it, and the recharged molecule goes right back into the reaction. One expensive input, reused instead of discarded. They ran it through multi-enzyme cascades to build thiophosphate molecules from small to large, including nucleoside monothiophosphates, cyclic monophosphorothioates, and thiophosphorylated oligopeptides. “We were able to use this process to cheaply add thiophosphates to several different classes of drugs, from small molecules to macromolecules,” Renata said.

The application everyone points to is antisense oligonucleotides, the short strands of engineered genetic code used to treat inherited diseases. Their backbone is built from that same sulfur-for-oxygen swap, repeated bond after bond down the chain, which is why phosphorothioate chemistry holds about 41 percent of the antisense market, the largest single slice, and why clinical-grade building blocks run in the range of $80,000 to $120,000 a kilogram. A cheaper, greener route to that chemistry is a genuine advance, and I do not want to undersell it.

But I also will not let it be sold to me as something it is not. Look at the flagship antisense drug, nusinersen, sold as Spinraza, the first treatment FDA approved for spinal muscular atrophy. Its backbone is exactly this phosphorothioate chemistry. Biogen launched it at $125,000 per injection, and the loading schedule stacks several of those in the first year. So how much of that $125,000 is the sulfur donor in the flask? Almost none of it. That price was not set by the cost of ATPγS. It was set for an orphan drug with no competition, at whatever number payers could be made to swallow. A better recycling trick shaves the manufacturing bill. It does not touch the pricing logic that put six figures on a single dose.

So look at what the “cheaper way to synthesize drugs” headline actually earns. This is a lab-scale enzymatic method making model compounds, elegant and useful, but no patient’s drug got cheaper this month, and making a drug cheaper to build does not make it cheaper to buy unless the number at the counter actually moves. And look at who helped pay for the work. Alongside the Welch Foundation and Texas’s cancer research institute, the funders include the American Chemical Society’s Pharmaceutical Roundtable, an industry consortium. Nothing shady about that. But it does explain why “greener and cheaper” is a framing that lands in the interest of the companies whose input costs it lowers, well before it lands as anything a patient feels.

So here is my conclusion. I am genuinely delighted by the chemistry, by the cleverness of borrowing the body’s own recharge system to stretch one costly molecule across many reactions. I am not going to let a cheaper synthesis get dressed up as a cheaper prescription. The next time a lab breakthrough promises to bring drug prices down, I am going to ask the only question that settles it: did the price at the counter actually move? Until it does, the savings live in the flask, not in my copay, and that is exactly where I would keep my expectations.

Sources

  1. Nature – Wu, Fu, Renata et al., “An ATPγS recycling strategy for practical biocatalytic thiophosphorylation” (2026)
  2. Rice University News – “New method opens cheaper pathways to increased drug stability”
  3. News-Medical – “Rice University chemists develop cheaper way to synthesize drugs”
  4. Mordor Intelligence – Antisense Oligonucleotides Market (phosphorothioate share and building-block cost)
  5. ACCP – “FDA Approves SPINRAZA (nusinersen),” first approved treatment for spinal muscular atrophy
  6. Everyone.org – Spinraza (nusinersen) price and dosing