Hypocrite's Isle

Twelve

Gavin couldn’t sleep. His mind was like a busy road junction, only it was information that was the problem, not traffic. A jumble of images and data about tumour cell growth and regulation — much of which he had absorbed at the library over the past few days — was vying for his attention. He had learned a lot in a short time, but the difficulty came in trying to put it into any structured form. He didn’t know the nature of the problem so he couldn’t decide which bits were relevant or which were not. There was no way round this.

He threw his head from side to side on the pillow, trying to escape the images and find peace of mind, but without success. Poohsticks floated into the troubled mix to drift with the cells that floated before his eyes in a race from one side of a microscope slide to the other. The biggest Poohstick always won, followed by the biggest cell, and then the race started all over again.

In his fitful state, Gavin construed this as survival of the fittest — the fastest and strongest winning — before having to concede that Poohsticks were inanimate: Darwinian rules didn’t apply. He didn’t know much about sailing, which was about as foreign to back-street Liverpool as three-day eventing, but did seem to recall hearing once that the longer the hull of a boat the faster it would go through the water. He pondered this, before wondering why on earth he was thinking about hydrodynamics in the small hours of this or any other morning. But as soon as he closed his eyes, the cells swam back into view, the big ones nudging the small out of the way — the fastest, the strongest, the fittest... That was it!

Gavin sat bolt upright in bed as the pieces of the puzzle fell into place. The eureka moment had arrived. Cell growth rate was the key to the whole puzzle. When he’d been forced to change the cell culture medium, he’d made up one that wasn’t as rich as the original: it hadn’t contained human serum. The cells would therefore have grown more slowly. There was a direct relationship between cell growth rate and size — the slower they grew, the smaller they’d be.

Cells growing in the poorer medium had shown the membrane blips associated with Valdevan. They’d been damaged, but they had survived because they were smaller and therefore... more stable. It was as simple as that. He had the key to the riddle. Cells growing in a rich medium would be bigger, so, when Valdevan damaged their membranes, they became unstable and burst. Tumour cells grew slowly in the body compared to cells growing in the lab, so they would be smaller and therefore remain stable too. It all made sense.

The bottom line was that Valdevan didn’t kill cells at all; it caused membrane changes which slow-growing cells could accommodate but fast-growing cells could not. This was why it killed cells in the lab but not the body. The S16 gene was not essential: it was a stability problem associated with size that caused cell death.

Gavin turned on the bedside light as everything became beautifully clear. As Trish in the tissue culture lab had pointed out, everyone wanted their cells to grow as fast as possible because they were anxious to get results. The same would have been true for the scientists at Grumman Schalk. They would have used the best culture medium available. If they had tested their drug on slow-growing cells they would have got a completely different result, and possibly saved themselves twenty million dollars.

Gavin wanted to call Caroline and tell her about his discovery, but realised as he picked up his mobile that waking her at three in the morning to tell her why Valdevan hadn’t worked might not be such a good idea, particularly as it would involve a short introductory lecture on cell growth and division kinetics before he could deliver the punch line. He got out of bed and shivered as he turned on the fire. He had to write all this down, just in case it still had elements of a dream about it which might not transfer to conscious memory.

On the first Monday morning of the new term, Frank Simmons drove to the medical school feeling relieved that the long break was over. It had been nice to spend time with his family and enjoy his kids’ delight at Christmas, but always at the back of his mind was the thought that the research effort had stopped. Now, things could get back to normal. He found people gathered in the corridors, standing in small groups, telling tales of what they’d been doing over the break and exchanging New Year greetings. Cheek-kissing and handshakes were the order of the day. He opened the door of the lab and was surprised to find Gavin there.

Gavin got up, shook hands with him and wished him a happy new year before asking, ‘Can we talk?’

Simmons was a little taken aback at the sudden end to small talk. ‘Sure,’ he agreed. ‘Just let me get my coat off...’ He shrugged off his overcoat and hung it on a hook behind his office door before settling in behind the desk. He crumpled up an old desk calendar and threw it in the bucket. ‘Out with the old, eh? What’s on your mind?’

‘I know exactly why Valdevan didn’t work.’

Simmons had to deal with a host of competing emotions ranging from surprise to disbelief. Apart from that, being wrong was never a good feeling. Was it really possible that this boy had succeeded where one of the biggest pharmaceutical companies in the world had failed? He would happily have bet his house against the possibility. He distilled his thoughts into, ‘I’m all ears.’

Gavin told Simmons about his experimental work over the vacation and what he had discovered, ending with, ‘So you see, it all makes perfect sense.’

Simmons smiled, conceding that the science had been good and the logic flawless. The pleasure he took from this did much to wipe out the other things he’d been feeling. Scientific truth had a beauty all of its own. ‘It does, and I’m sure you’re right,’ he said. ‘Congratulations, that was a first-class piece of work. In fact, it was better than that; it was bloody brilliant.’

‘Thanks, Frank,’ said Gavin. ‘It just sort of fell into place...’

‘My God, Grumman Schalk will have a fit when they hear about this. How many millions did they flush down the drain?

‘Twenty, I think.’

‘And that was twenty years ago...’

Simmons looked thoughtful for a moment, leaning back in his chair and fiddling with his pen before saying, ‘I think you should write this up immediately and chalk up your first publication. My inclination would be to submit to Antibiotic and Chemotherapy but we can have a think about that. In the meantime, as you’ve now shown that knocking out the S16 gene is not lethal, there’s nothing to stop you reverting to our original plan and working on Valdevan-treated cells. All you have to do is keep the growth rate slow.’

Gavin adopted a slight grimace. ‘Actually,’ he began hesitantly. ‘I was wondering if you might give me a bit more time to work on Valdevan treatment of tumours?’

‘But you’ve just shown why it didn’t work and never could,’ exclaimed Simmons. ‘Game set and match to you. What’s left to do?’

‘I think there may be some more mileage in it. I’m not sure but I’d really like to do a few more experiments.’

Simmons was doubtful. ‘What did you have in mind?’

Gavin, who had not yet formulated a definite plan of action, shrugged uncomfortably. ‘I’m not quite sure yet... We know that the faster cells grow, the more unstable they become in the presence of Valdevan, and we know that tumour cells grow faster in the body than normal cells, so...’

‘There’s no way on earth you’re going to make tumour cells grow as fast in the body as they do in the lab,’ interrupted Simmons.

‘No, of course not, I accept that — but there just might be some other way to exploit the difference.’

‘Like what?’

‘I don’t know yet... I need to get a feel for it.’

Simmons felt sceptical but then said, ‘I was about to lecture you again about heading up blind alleys, but that’s what I thought last time and I was wrong.’ He paused for a moment to assess Gavin’s likely disappointed reaction if he turned him down, before saying, ‘Look, I’ll make a deal with you. If you’ll agree to give a seminar to the department about your work, I’ll give you three weeks to chase rainbows. Deal?

‘Deal.’

Gavin was talking to Mary Hollis when Simmons returned from lunch. He glanced in Gavin’s direction and said, ‘I told Jack, Thursday at 1 p.m. if that’s all right?’

Gavin nodded.

‘What was all that about?’ asked Mary.

‘I’m giving a seminar, on Thursday apparently.’

‘You? A seminar? Now I’ve heard it all. Is this something to do with a new you or does Frank have some dodgy negatives?’

‘Neither. One forty-minute seminar gets me three more precious weeks to work on Valdevan.’

‘But you’ve just told me why it can never work. What are you going to do?’

‘Make it work.’

Mary’s jaw fell open as she saw Gavin was serious. ‘Ye gods, Gavin. You’re nothing if not ambitious. Can I ask how, or is that a secret?’

‘I haven’t worked that out yet,’ said Gavin, holding up and examining the plastic bottle he’d just removed from the fridge door. ‘In fact, the only thing I’m sure of right now is that I’m going to need more Valdevan. I wonder if Frank would ask his contact. It would be quicker than writing.’

Gavin turned away and left Mary looking after him with an amused smile while he went to make his request to Simmons, who said that he’d actually been intending to call Grumman Schalk anyway. There were things he needed to ask about their new research grants scheme. He’d do it before lunch.

Gavin went on down to the tissue culture suite to wish the staff a happy new year and put in an order for more cell cultures.

‘Did you use all the ones I made for you just before the break?’ asked Trish.

‘Every last one,’ said Gavin, ‘And like I said, I’ll love you forever.’

‘And a day,’ Trish reminded him.

‘And a fortnight if you like. I got some really good results and you’ll be top of the acknowledgement list when the paper gets written.’

‘Always nice to be appreciated,’ said Trish, her cheeks colouring slightly. ‘I’ll give you a call when your cultures are ready. I take it you need both tumour and primary cells?’

‘That would be great.’

Frank Simmons’ intended phone call to Grumman Schalk had been precipitated by an internal mail message from Graham Sutcliffe to all academic staff, announcing a meeting on Tuesday to discuss their application for a block grant. Sutcliffe had formulated a draft over the break, but said he wanted to discuss it with his colleagues and add the finishing touches to it before sending it off. Time was of the essence, he stressed. Simmons took this to mean that any discussion would not be lengthy: Sutcliffe was looking for a rubber stamp. He thought that he might have more success in finding out about the conditions attached to such grants by asking Max Ehrman directly about company policy.

Simmons paused as he lifted the phone and wondered for a moment how much he should tell Ehrman about Gavin’s discovery. There was a need for tact and diplomacy over it. He didn’t know if Ehrman had had any personal involvement in the Valdevan project — probably not, but he wouldn’t be human if he didn’t feel some embarrassment, and maybe even a little resentment towards a first-year postgrad student who had succeeded where his company and all its resources had failed. He decided he’d have to play it by ear.

Max Ehrman was his usual helpful self, and proved only too happy to fill Simmons in on the conditions attached to his company’s new research grants scheme. As Simmons had suspected, the company would insist on the final say in whether or not results could be published. Simmons’ silence when Ehrman told him this prompted Ehrman to add, ‘This hasn’t proved to be too much of a problem in the past, Frank.’

‘I suppose it’s more potential problems I’m worried about.’

‘Well, there has to be some degree of symbiosis in all this,’ said Ehrman. ‘We’re not philanthropists and don’t pretend to be: we’re in the business to make money. On the other hand, we’re not monsters either. New discoveries can bring glory to researchers, relief to sufferers and profits to drug companies. Everybody wins.’

‘In a perfect world,’ said Simmons.

‘You worry too much, Frank,’ said Ehrman. ‘The chances are that such a conflict will never arise, and if it should, it would be resolved without bad blood.’

‘Mmm.’

‘How is your student getting along, the one who asked us for Valdevan?’

Simmons’ pulse rate rose a little and he felt his mouth go dry. ‘Fine, very well in fact. As we thought, it seems clear that the drug does target the S16 gene. Actually, I was just about to ask you for some more of the drug if that’s possible? Gavin mentioned this morning that he’s running low.’

‘Of course it is,’ laughed Ehrman. ‘We’re renowned for our generosity here at Grumman Schalk. By the way, I’m going to be coming to Edinburgh shortly. I’m attending the conference at Heriot Watt University at the beginning of February, and I’m also taking part in some TV programme that your BBC are doing. They’ve asked me to say something about the company’s range of anti-cancer drugs. No doubt we will be cast in the role of big bad profit-maker, but we’re used to that. I’ll do my best to convince them otherwise. Maybe we could meet up at some point and I could talk to your student?’

‘Of course. I’ll look forward to that. Our department is going to be involved in the programme too,’ said Simmons. ‘It would be really nice if we could all sit round the table and talk... maybe over some dinner?’

‘Great. I’ll keep you informed about dates.’

Simmons felt relieved. It would be much better to discuss Gavin’s work with him present and with everyone face to face in the same room.

A knock came at the door. It was Jack Martin. ‘I take it you’ve had Sutcliffe’s letter?’

Simmons nodded.

‘Ever felt you were being steam-rollered into something?’

‘I phoned Grumman Schalk this morning. If we got the block grant, all research carried out using their funding would have to be submitted to them for approval before we could publish.’

‘Just like you thought, so what do we do?’

‘Difficult. Sutcliffe wants to empire build and he’s really got the hots for Grumman Schalk money. He’s dangling the prospect of a couple of personal chairs in front of the senior staff to keep them onside, and the young ones will be keen to grab research money wherever it comes from, so he’s virtually got all the backing he needs. Any objections from us will go down like the Titanic.’

‘So what do we do?’

‘Be pragmatic,’ sighed Simmons. ‘Don’t get into a fight we can’t win?’

‘I suppose,’ agreed Martin. ‘Maybe brave gestures are best left to the young anyway. Has he said anything about a personal chair to you?’

Simmons shook his head. ‘You?’

Martin said not.

‘It’s my guess he’ll want to keep everyone guessing. If he picks two out at this stage he’ll figure the rest of us might gang up on him — for the most noble of reasons, of course.’

‘You know, for such a nice guy you really have quite an impressive grasp of human nature,’ said Martin.

‘And it doesn’t make for pretty reading.’

‘You’ll probably find a few more pointers at the meeting tomorrow. Did you tell your Gavin that he’s giving the internal seminar this week?’

‘I did.’

‘You don’t think he’s going to call off at the last minute with a headache?’

Simmons shook his head. ‘If he does, the trade-off gets cancelled. I said he could have another three weeks to work on his pet theories if he gave a seminar to the department.’

‘Like I said, an impressive grasp... How’s his work coming along?’

‘Brilliantly; you’ll hear all about it at the seminar.’

Gavin met Caroline at seven and they went to eat at a Mexican restaurant in Victoria Street, starting with margaritas while they waited.

‘I nearly called you at three this morning.’

‘I’m awfully glad you didn’t,’ said Caroline. ‘What did you want?’

‘I worked out why Valdevan didn’t work on cancer patients.’

‘You’re kidding,’ said Caroline, pausing in mid-sip and licking the salt off her upper lip. ‘You have to be.’

‘I’m not.’

‘Bloody hell, I’m impressed. Tell me more.’

Gavin explained his discovery over a nachos starter, pausing at intervals to wrestle with strands of melted cheese that were reluctant to part from the bowl.

‘It seems so simple now,’ said Caroline when he’d finished. ‘But then so did DNA once Crick and Watson had worked it out. That was a brilliant piece of work, Gavin, but...’

‘But what?’

Caroline appeared uncomfortable. ‘I really mean it when I say it’s a brilliant piece of work, but the bottom line is that you have found out why Valdevan didn’t work... I mean... it still doesn’t, right?’

‘No,’ agreed Gavin. ‘But Frank’s agreed to give me three more weeks to work on that.’

‘Three weeks?’

‘To make it over the next hurdle, then maybe he’ll give me some more time. That’s how I see it.’

Caroline looked at him. ‘My God, you’re determined. I’ll give you that. You’ve come this far against all the odds and in spite of all the doubters, including me. Sometimes I wonder what I’ve got myself into.’

‘A love affair,’ smiled Gavin.

‘Is that what it is?’ teased Caroline.

‘Yep, and it’s going to be the longest, most beautiful love affair in the history of love affairs. It will go on to the end of time and our children and our children’s children will speak of it long after we are dead and walking hand in hand along the road to eternity knowing we’ll be together for ever.’

‘Oh well... if you say so.’

‘I do.’

‘Two burritos,’ said the waitress.

Gavin spent Tuesday going through the Grumman Schalk report again. Although no longer interested in anything they had done, or their reasons for doing it, he was looking for something that might help him decide on the concentration of the drug to use, to induce membrane damage in tumour cells but not in healthy ones. He found what he was looking for in a case report on biopsy material taken from a patient with lung cancer. Under his magnifying lens the photographs clearly showed that the tumour cells were displaying membrane blips, while the adjacent healthy tissue looked unaffected. Gavin noted the patient number and traced his finger down the column of relevant drug levels. Patient 2453F had shown a steady level of 25 micrograms per millilitre of blood. The suffix, F, told him she had been female. ‘Thank you, patient 2453F, aged 43,’ murmured Gavin. ‘RIP.’