Chapter 88

Li Lan blinked. So that was it.

The tutor had mainly wanted the details, and learning the revisions had only just gone back and publication was some way off, she said, "Right, I've got the picture. You've a lecture this afternoon, haven't you — go on. I'll speak to the registry and see what I can get you."

She worked fast, and rang between lectures that afternoon to say five thousand yuan had been approved. What Li Lan didn't know was that several of the School's leaders had considered running a piece about it, and reflecting that it was "only" an SCI paper, and that as employees of Peking University a certain reserve was called for, in the end the published paper got a short notice on the School's website — a notice consisting of the title, with an observation that the first author was a second-year. Not so much as a photograph.

So it made no waves, still less any difference to her life. A dry block of text without a picture is not something many people read closely, and those who do don't dwell on it, so beyond people who already knew her, not many learned she'd published in an SCI journal.

Second year, beyond being exceptionally busy, was no different: lecture room, dormitory, laboratory, and round again. The one difference was that by the end of it, without anybody much noticing, the papers had accumulated to four — all first-authored, all SCI.

At the end of the first semester, the research assistantship's year being up, Wang Xin talked to her and said she could stay in his group; and in the summer at the end of her second year she formally joined it, working under him on new projects alongside his doctoral students.

Wang Xin being one of the School's authorities, and one of the country's in Chinese medicine, what one learns behind him is a great deal deeper than a lecture course. She followed him ravenously, and with his supervision set against the shop's methods, her progress went vertical.

And as that summer ended she gave the group an enormous surprise: on more than a year of work on Trollius chinensis, in the week before her third year began, she established the structure of a candidate drug.

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Establishing a candidate is the critical stage of drug development and decides the fate of the clinical work. The process is complicated and a candidate is not arrived at simply.

The first step is identifying the target molecule associated with the disease — a biological molecule connected with it, which may be a protein or a nucleic acid — so that intervening in it cures or relieves the disease.

The second is finding a compound that acts on the target, which is called finding a hit compound. This isn't achieved in one stroke either: a hit may lack activity, behave erratically or be toxic, so it has to be expanded.

If a hit is confirmed to be active, a series of structurally similar compounds is chosen and optimised and screened — the optimisation of lead compounds — and it is during that process that the ideal candidate emerges.

Then comes development, and preclinical toxicology, which requires synthesis, toxicology and pharmacology to work together. And all of the above is only preclinical: the first stage of development, and a long way from a finished drug.

Finally, if the candidate passes preclinical work, you can apply for clinical studies, and then comes the long road of burning money. Sorry — the long road of clinical trials.

The whole thing takes about ten years, and development costs over a hundred million dollars are common. That being the process for a genuinely new drug; Li Lan's work was nowhere near that level, which is Wang Xin's tier of project.

In hers, Trollius chinensis clears heat and toxicity well, tonsillitis and otitis media in particular, so the condition she'd identified was inflammation. The target molecules in the plant, orientin and vitexin, relieve inflammation well; the target settled, a hit had to be found, and a carbon glycosyltransferase reacts well with both — which was the content of her first paper.

Then came experiments with a series of structurally similar carbon glycosyltransferases against orientin and vitexin, observing the different results, and a year of it produced the ideal candidate — and the rest of her papers.

So while her drug was new, the newness was structural rather than a new drug in the real sense. Even so, for somebody still a student, arriving at a candidate at all is a considerable achievement, whether or not the preclinical work succeeds.

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Hearing about it, Wang Xin called her to his office alone, went through the material and couldn't help an exclamation. "Li Lan, this really is a very large surprise." He hadn't expected a year to produce a candidate. He'd taught a great many students and a good many had filed patents while enrolled; she was the first to reach candidate stage.

He set the file down and looked at her with a rare mildness. "If I remember rightly, the project you're on is Discovery and Optimisation of Carbohydrate Drug Lead Compounds?"

"Yes." She'd been on it since joining his group, and time being what it was, hadn't taken on anything else since.

"And what do you intend to do next?"

Because there was a problem: the preclinical stage needs a great deal of raw material for toxicology, and at least a million yuan, never mind the clinical work after it, where the money is enormous. His project funding could never stretch that far — it isn't a new-drug project and the money is limited — so counted within the carbohydrate lead compound project, it would very likely stop here with nothing following.

She hadn't thought of that. She'd got this far because the shop's L2 route for Trollius chinensis runs straight through to a finished drug, and a year had brought her only to a candidate, a long way short. Her first drug, and she wasn't willing to have it stop dead.

But if the work continued, where would the money come from?

She wasn't ready to give up. "Professor, does it have to stop here?" Could we apply for more development funding? She didn't quite feel able to say it.

It bothered him too. Project budgets are fixed and the management committee would certainly not increase one, least of all by that much. She wasn't formally his student and she'd studied under him long enough that he'd come to think of her as one, and being a man who values ability he couldn't bear to see the work die. If she actually produced a new anti-inflammatory, her ability would exceed most people working in pharmaceutical research.

He thought. "Let's not rush it. Carry on with what you're doing and I'll consider whether there's another way. Your group meeting is the day after tomorrow — I'll tell you if I find one."

After she'd gone he looked at the material she'd left on the desk, and the longer he looked the less willing he was to let it die. A bold thought crossed his mind: if counting it within the project would kill it, why count it within the project?

A vague notion at first, and the more he turned it the more possible it looked. Discovery and Optimisation of Carbohydrate Drug Lead Compounds is primarily theoretical feasibility work, and the applied stage strictly falls outside it; the carbohydrate lead compound work was complete at the hit-finding step, and that step, with the papers and patents produced along the way, constitutes the project's results.

Establishing a candidate is a further translation into application, closer to new-drug research built on carbohydrate lead compounds, and strictly outside the project's scope — and the acceptance criteria contain no hard requirement for a specific applied result, carbohydrate lead compounds being applicable in all directions rather than merely to an anti-inflammatory.

So saying the candidate didn't belong to the project wasn't quite right either; her funding and her theory had both come out of it. To continue, though, the best course was to keep the candidate out of the project's results and set up a separate new-drug project.

As for money, he thought a partnership with a pharmaceutical company the best option. A national fund application isn't done in a day or two, and neither the university nor the committee would produce a million and the clinical costs afterwards. A pharmaceutical company has no such difficulty.

One worry resolved, he felt lighter, and started going through his contacts for a company to work with. As a professor of the School he'd worked with a good many — and this time, for a favourite student, he was going to make an effort.