Pandora's Helix

Four

“Maybe we should talk first and then I’ll show you around the unit, suggested Neef.

“Whatever you say,” replied Pereira.

Pereira was nearly a foot shorter than Neef, despite the fact he was wearing cowboy boots with Cuban heels. Neef had to modify his stride to allow him to keep up as they crossed the courtyard from the administrative block to the unit. Pereira was also weighed down by a large battered briefcase which had the remains of many airline stickers plastered over one face of it.

Neef introduced him to Ann Miles and asked if coffee was possible.

“Of course,” she said. “How do you like yours, Dr Pereira?”

“White, lots of sugar,” Pereira replied without turning to face her. He had taken off his leather jacket but had kept his beret on.

Ann Miles exchanged an amused look with Neef before closing the door behind her.

“Are you medically qualified, Dr Pereira?” asked Neef.

Pereira shook his head. “My first degree was in medical microbiology, then a PhD at UCLA followed by post-doctoral fellowships at Harvard and Johns Hopkins, and then I joined Menogen.”

“You’re a molecular biologist?”

“I am but people tend to come to molecular biology from a range of scientific backgrounds. I was primarily a virologist, David Farro-Jones has a medical degree, I think.”

“He has,” agreed Neef. “But he keeps telling me that molecular biology is the science of the future.”

“He’s not wrong,” replied Pereira.

“But without a medical degree there’s no question of you being let loose on the patients on your own.”

Pereira laughed out loud. “That’s understood,” he said. “I couldn’t stick a plaster on a cut finger. On the other hand, I’ve forgotten more about viruses than most medics will ever know.”

It was Neef’s turn to smile. “I’ll gladly concede that,” he said. “So we work as a team.”

“Absolutely.”

“Then I have to know exactly what you have in mind. I must insist on understanding the theory behind everything you propose to do before I agree to it.”

“How much do you know about Gene Therapy?”

“I know that it involves introducing new genes into patients’ cells and that getting them in can present problems, beyond that, not a lot.”

Pereira nodded. “Constructing the working gene in the lab is the easy part. As you say, it’s getting it into the patient’s own cells that gives us the problems. We obviously can’t inject copies of the new gene into cells one at a time; we’d have to do it a hundred million times to even make a start on a tumour so we have nature do it for us. We use viruses as transport vectors.”

“Live viruses?” asked Neef.

“Live but disabled,” said Pereira. “We disable the virus genetically so that it can’t replicate itself inside the patient, then we introduce the new gene to the virus in the lab and let the virus carry it into the patient’s cells for us.”

“A sort of localised infection?”

“You got it.”

“It sounds straightforward,” smiled Neef. “So what are the pitfalls?”

“Lots,” admitted Pereira. “Viruses are still viruses, disabled or not. If we use too many virus particles the patient may react badly against the introduction of foreign protein, particularly if we have to repeat the treatment.”

“Anaphylactic shock?”

“That’s a possibility. On the other hand, if we use too few the whole strategy might not work. There are also another couple of things you should be aware of if you’re not already.

“Tell me.”

“Although the viruses we use are disabled by removing their replicating machinery, some researchers have suggested that they might reactivate themselves inside the body by finding their missing bits.”

“I don’t think I follow. How?”

“Many of the viruses we use as gene carrying vectors are pretty common. Most of us have been infected with them before through having colds and flu. The worry says that many of us will still have the odd live virus particle lurking around inside us. If the disabled vector virus should come up against one of these old particles it’s just possible that it could reactivate itself through DNA recombination.”

“You mean it could get back its missing bits and set off a full scale infection?”

“Yeah. But being aware of the problem is half way to solving it, as Grandma used to say. We at Menogen use retrovirus technology which doesn’t have that problem but it could have others.”

“Anything I should know?”

“Yes,” said Pereira. The advantage of using retroviruses is that they integrate into the host cell’s chromosome, the disadvantage is that some people think they could trigger off cancer.”

“I had read about that possibility,” admitted Neef.

“But this wouldn’t be a problem with your patients,” said Pereira. “They’ve already got the big C.”

Neef looked at Pereira who had opened his briefcase and was rummaging inside.

Neef looked at Pereira long and hard. He couldn’t make up his mind about the man. He was certainly different.

“What exactly are the chances of Gene Therapy actually helping my patients?”

“As opposed to what?”

“As opposed to just providing you with more data about your virus vectors.”

“Hopefully it will do both,” said Pereira.

“I have to know the chances,” insisted Neef.

Pereira seemed to sense that this might be the big money question. He stopped sifting through his papers and said, “All right, I admit, it would be nice to include some Neomycin tag experiments just to see how the vectors are distributed in the body.”

“No,” said Neef firmly.

“Why not?”

“Adult cancer patients are able to make up their own mind about helping medical science when there’s nothing in it for them. Kids can’t.”

“But their parents...”

“Will snatch at anything without fully understanding the implications so it’s me who has the final say-so round here and I say, no data experiments.”

Pereira sighed and let his head drop for a moment. “So what’s the deal?” he asked.

“The deal is that if we inject any Gene Therapy vector into my patients, it has to carry a viable gene with a real chance of improving my patients’ condition. Do you have such vectors?”

“Yes, I believe we do,” said Pereira. “And I believe that they’ll work. Given the right patients and the right conditions, I think we can pull off the big one here. I think we might be able eventually to zap cancer.”

“You honestly believe that?”

“I honestly do.”

Neef nodded non-committally. “Good. Now tell me about the side effects of this kind of therapy.”

“There really shouldn’t be any, certainly nothing like the side effects of standard chemotherapy.”

“Good. Can we get down to specifics? What gene do you intend introducing and why?”

Pereira separated a couple of diagrams from his pile of papers and pushed them in front of Neef. “For suitable tumours we would use a disabled murine leukaemia virus with altered envelope proteins and carrying a thymidine kinase gene (TDK). This would be injected directly into the tumour. The virus only infects dividing cells so, in the case of a brain tumour only the tumour cells will take up the TDK gene. We then treat the patient with Gancyclovir. This drug will only kill cells containing a working TDK gene.”

“It sounds simple in theory. Are you sure that only the tumour cells will be killed?”

“That’s what the theory says.”

Neef wondered if Pereira’s answer had been evasive but didn’t press the point for the time being. “What about different types of tumour?” he asked.

“Menogen’s success has been in developing a range of pseudotype viruses based on the virus I mentioned. They all have altered envelope proteins which gives them different affinities. It’s just a question of selecting the right vector for the right tumour.”

“Okay,” said Neef, after a moment’s thought. “That’s enough science. Let’s go meet everyone.”

After noting the unit nurses’ somewhat puzzled and muted response to meeting Pereira, Neef wondered what the patients were going to make of him. In the event, they treated Pereira with much the same caution the nurses had displayed. They seemed to sense that his smile was less than sincere and didn’t respond to his clumsy attempts at making jokes.

“I hope he’ll grow on me,” confided Kate Morse as she stood beside Neef, watching Max through the window of her office.

“That’s my hope too,” agreed Neef with a slight smile. “God knows what the ethics committee are going to make of him.”

“Mr Beavis was here earlier to see Thomas Downy,” said Kate. “He’s going to speak to you personally but...”

“Not operable?”

“Fraid not.”

“Damn, I hoped Beavis might give it a try.”

“Thomas’ parents are coming in at four. Will you be around or do you want Lawrence to tell them.”

“I’ll do it,” said Neef with a sigh of resignation. “I should be back by then.”

Neef called Tim Heaton from his office while Max was still with the children. ‘So far I think I’m in favour of the trial. Pereira’s a bit hard to take but he seems to know what he’s talking about.”

“Good,” said Heaton. “I understand from Phillip and Andrew that they are quite happy with the financial arrangements. I’ll try to convene the ethics committee for two thirty. Can we all have an early lunch, say twelve thirty?”

“Fine.”

Pereira returned to Neef’s office after giving up on making meaningful contact with the patients. “Okay,” he announced spreading his hands out from his sides, “Michael Jackson, I ain’t. I’m a scientist.”

“Not everyone gets on with kids,” said Neef with a smile.

“I don’t dislike them,” replied Pereira. “But I don’t go all misty eyed over them. Is that a problem?”

“I suppose not but I like to understand people’s motivations when I’m going to be working with them.”

“That must be difficult when most people in this game don’t tell the truth in the first place,” said Pereira.

“A cynical view.”

“A realistic one. In my experience, doctors become doctors because they figure it’ll provide them with a good living, social standing, nice car, membership of the golf club and so on. Any thoughts about fixing sick folks come way down the list. But they’ve got a good PR thing going for them, I’ll give them that. Most people believe they care.”

Neef was taken aback by Pereira. He was also puzzled. The words sounded as if they had been born of bitterness but Pereira didn’t sound bitter. He said it all quite dispassionately.

“So what motivates a medical scientist?” he asked.

Pereira smiled and said, “People like to believe it’s an unswerving desire to cure man’s ills and alleviate pain and suffering but it ain’t. No sir. Scientists are people like everyone else. They’re fired by notions of career advancement and increased academic status, all mixed up with the prospects of fame and fortune.”

“That sounds pretty awful.”

“It only sounds awful,” said Pereira. “In practice the system works very well from the patients’ point of view.”

“How so?”

“Researchers work their butt off, not because they want to help sick folks but because they want to be first past the post; there are no prizes for coming second. They know there’s a whole bunch of guys out there doing exactly the same sort of experiments. That means that the work has to get done as fast as possible. It’s also done as thoroughly as possible because every researcher knows that his competitors are just waiting to go through his published work with a fine-tooth comb to pick fault with it. And if they find any mistakes or unjustified assertions, they’ll crucify you, so no short cuts. The patient gets a good deal.”

“You paint an honest if somewhat depressing picture,” said Neef with a wry smile.

“I just face facts,” said Pereira. “Human nature is what it is. I accept it. Lots of folks don’t. They have to endow their actions with all sorts of noble sounding bullshit.”

“Between you and me, Max,” said Neef, “I wouldn’t come out with that to the ethics committee this afternoon. They just might take it personally.”

“Thanks for the warning.”

Half way through lunch Neef’s bleeper went off. He excused himself and went to call the unit.

“We’ve just had a referral from East Side General,” said Lawrence Fielding. “I think you should come over.”

Neef hurried back to the unit and found Fielding in the light-wall room. This was a long narrow room next to the duty room. One entire wall was translucent plastic with a fluorescent light source behind it. Scans and X-rays could be pinned up on it for examination.

“What have you got?” asked Neef as he entered and found Fielding examining a series of three X-rays with the aid of a hand-held lens.

“Jane Lees aged fourteen,” replied Fielding. “I’ve not seen anything quite like this before, especially not in a child. She has multiple tumours on both lungs.”

Neef felt a sudden sense of foreboding come over him. Fielding had more or less said what Frank MacSween had said the other day about Melanie Simpson.

“I have,” he said, as he took the lens from Fielding and took a closer look at the X-rays. “I saw exactly the same thing in Pathology on Monday. Frank MacSween was doing a PM on a patient from University College, a thirteen year old girl. She’d been admitted as a bilateral pneumonia, but the lab couldn’t find any bugs. She died and they called it viral.”

“They didn’t realise she had cancer as well?”

“Nobody did until Frank opened her up. We’ve had to call in the Public Health team because of the extent of the malignancy. This looks like number two.”

“In more ways than one,” said Fielding.

“How so?”

“Jane was admitted to East Side General, as a bilateral pneumonia! They didn’t find any evidence of bacterial involvement so they too called it viral. Unlike your girl, Jane recovered from the acute pneumonia but her clearance X-rays showed up the tumours so she was transferred here. The early X-rays were clouded by excess mucus and inflammation caused by the pneumonia. I suppose that must have been the case with the first girl too.”

“I suppose it was,” said Neef thoughtfully. “I want you to call the Public Health people. Ask for Dr Lennon and explain what’s happened. The sooner he traces the cause of this thing the better.”

“Will do,” said Fielding.

“How is the girl?”

“We’ve made her comfortable for the moment but once these tumours get a real grip there’s not going to be much we can do for her.”

“We’ll do our best,” said Neef, putting his hand on Fielding’s shoulder. “Like we always do.”

Lunch was over by the time Neef got back to the administrative block. He had opted to see Jane Lees himself before leaving the unit and this had taken a good thirty minutes. Although the girl was very ill, she was conscious and Neef had hoped she might have been able to shed some light on the nature and source of the carcinogen that she and Melanie Simpson must have been exposed to. Unfortunately, she hadn’t. Jane Lees lived in another part of the city and she had not known Melanie Simpson. Neef was thinking about this as he ran up the steps of the administrative block in time for the ethics committee meeting.

“Problems?” asked Tim Heaton who was just about to leave along with Phillip D’Arcy. They would not be required to attend the ethics committee meeting.

“I’ve never known a day without them,” replied Neef. He didn’t want to get into conversation with Heaton about the two girls before he himself had had time to consider the implications.

“Life’s rich pattern.” smiled Heaton and swept out, checking his watch as he did so and almost leaving Phillip Danziger in his wake.

The ethics and safety committee on this occasion comprised two churchmen, the Roman Catholic chaplain for University College Hospital and the Church of England chaplain for St George’s, Alan Brooks, the Dean of University College medical school, Major Ronald Jackson, a local magistrate, Dr David Farro-Jones, Reader in molecular biology in medicine at University College medical school and Miss Emma Taylor, area organiser of the Women’s Royal Voluntary Service. Major Jackson was in the chair. Steven Thomas, Max Pereira and Neef were present throughout. Andrew D’Arcy was available to be called upon. All members of the committee had copies of the formal written application in front of them.

Major Jackson opened the proceedings by requesting evidence of Menogen’s successful application to licensing authorities at national level.

Steven Thomas handed over a series of documents, one at a time, announcing each in turn. “Our formal application, which I think you already have, Approval Certificate from the Medicines Control Agency, and certification from the National Gene Therapy Advisory Committee.”

“Thank you Mr Thomas. A necessary formality you understand.”

“Of course.”

“As I understand it, no transfer of human genetic material is involved in the proposed therapy. Is that right?”

Max Pereira replied, “Quite right, sir.”

“I think that makes our task considerably easier,” said Jackson. “So what gene do you intend transferring to our patients?”

“It’s the thymidine kinase gene, taken from Herpes simplex virus, sir. The TDK gene for short.”

“Isn’t that dangerous?” asked the WRVS woman.

Neef thought for an awful moment that Pereira was about to be rude to her but he controlled himself.

“No Ma’am, it’s only a single gene from the Herpes virus, not the virus itself. Its presence will render the tumour cells sensitive to a drug called Gancyclovir so that when we give the patient the drug, it will kill the tumour.”

“I see,” said the WRVS woman vaguely.

Major Jackson turned to the two churchmen. “Is there anything you gentlemen would like to ask?”

Both men shook their heads. “Nothing here to concern us,” said the Roman Catholic priest. I hope it works.

“Then perhaps I should hand over to Dr Farro-Jones as our expert in this case. I’m told you two chaps know each other?”

“Indeed we do, Major,” smiled Farro-Jones, then to Max Pereira, “How are you Max? It’s been a while.”

“Fine, David. Good to see you.

Neef could not help but be aware of the striking physical differences between the two men. Farro-Jones was tall, blonde and athletic looking. He had the easy charm and accent that often comes from a public school and Oxbridge education while Pereira looked like a small, swarthy sailor and spoke like a New York cab driver.

“Max, I’m a bit worried about the gene transfer vector you intend using to take the TDK gene in; it’s a leukaemia retrovirus, isn’t it?”

Ears pricked up around the table at the mention of the word, leukaemia.”

“It’s the standard Moloney vector,” said Max. “It’s been around for a while. It’s never given any problems in the lab and we’ve disabled it even further.”

“Yes, I see that,” said Farro-Jones hesitantly. He looked down at the papers in front of him. “But you’ve also altered its envelope proteins?”

“We’ve made it much more effective and, because we have a range of them, much more specific. That’s what we’ve all been working towards, efficient transfer vectors that can be targeted at specific tumours?”

“Yes indeed,” agreed Farro-Jones. “And it all sounds very effective on paper but I really do worry about safety...”

Neef hadn’t anticipated David Farro-Jones being lukewarm to the proposal. If anything he had expected his support, being a fellow molecular biologist who had already been involved in the introduction of Gene Therapy at University College Hospital. He thought he would point this out.

“Is the Menogen vector significantly different from the one you and your colleagues used in your cystic fibrosis trial, David?” he asked.

“It is, Michael,” replied Farro-Jones. “We used a liposome delivery system on our patients because we felt it was safer than using a live virus.”

“And it didn’t work, right?” said Pereira.

“No it didn’t,” conceded Farro-Jones with a smile, “And I take your point. We’re having to move towards virus vectors too but there are safer ones around.”

There was an uneasy pause before Steven Thomas took the initiative and said, “I think there has to come a point, ladies and gentlemen, when you’ve carried out all the trials and safety checks possible without actually moving to a human subject. I think we are at that point with the Menogen vectors.”

“I just worry about the safety aspects,” confessed Farro-Jones. He turned to his colleagues with a slight grimace. “The patients’ welfare must be our first consideration. After all, as Florence Nightingale once said, ‘The first duty of a hospital is that it cause its patients no harm’.”

There was polite laughter.

“There are no named patients on the application,” said Major Jackson. “You’re asking for open permission?”

“Dr Pereira and I will agree this between us,” said Neef.

“I take it the request for open permission is because the subjects will be terminally ill.”

“Yes sir but I have made a stipulation that no child will be used for the sole purpose of gathering scientific data. Every child given Gene Therapy will be given it with the sole intent of improving his or her condition.”

Jackson nodded and turned to his colleagues and said, “I think I am inclined to agree with Mr Thomas in this instance. I think the time has come.”

Permission to proceed was approved. The committee members rose and David Farro-Jones came over to speak to Pereira and Neef.

“I’m sorry, Max if I appeared a bit sticky there. I just worry about the dangers of these new vectors.”

“You’ve got to call it like you see it David,” replied Pereira.

“No hard feelings, I hope?”

“None. I appreciate your concern but we’re sure that they’re safe and we’ve got the go ahead anyway.”

“Then let me be the first to wish you the best of luck,” said Farro-Jones. “And if you need any help with equipment or lab space just give me a call. Michael will tell you how to get in touch.”

“Of course,” said Neef.

“Thanks a lot, David, I appreciate it,” said Pereira.

“We must have dinner soon, talk about old times, eh?”

“I’d like that.”

“Nice chap,” said Neef as Farro-Jones hurried off.

“Yeah,” replied Pereira. “So when do we start in earnest?”

“How about Monday?”

“That sounds OK. I’ll start moving in stuff at the week-end. I may look in on your unit then if that’s all right with you?”

“Of course. I’ll tell the others to expect you.”

“Maybe I could take a copy of some patient notes before I go, ideally the ones you think might benefit from the therapy.”

“We can do that now if you like. I’ve just got time before I meet with some parents.”

“Bad news?”

“I’m afraid so. Their boy has a brain tumour. It’s inoperable.”

“A bitch,” said Pereira. “Inaccessible?”

“It’s in the cerebellum. I thought it was borderline but our neuro-surgeon gave it the thumbs down.”

“Afraid of litigation, huh?”

“I don’t think that came into it,” said Neef, mildly annoyed at Pereira’s interpretation.

“Woops. Sorry,” said Pereira, sensing that he had offended Neef. “Maybe things are different in England.”

Neef didn’t reply but it was food for thought. Maybe surgeons weren’t as afraid as their American counterparts of an action being raised against them in the courts but things had been heading that way and not just for surgeons. His own insurance premium for that sort of eventuality had risen dramatically over the past few years.

“If you thought the kid’s tumour was borderline, it must have been reasonably accessible?” asked Pereira.

“Yes but my hand wasn’t going to be wielding the knife. Why do you ask?”

“Do you think it could be reached with a needle?”

“I hadn’t thought about that,” said Neef. “You think we could include the boy in the trial?”

“Sounds like he might be a possible candidate to me,” said Pereira.

Neef suddenly felt better. He was always uneasy before an interview with parents when it was bad news he had to impart and this despite the fact that he’d had to do it hundreds of times before. It was an unpleasant, hollow feeling in his stomach. This was compounded today by the fact that he’d had no lunch. Pereira had introduced an unexpectedly welcome ray of hope into the proceedings but he reminded himself, if he felt this much better, how would Thomas Downy’s parents react when he threw them such a lifeline? He would have to be very careful. Raising false hopes would be unforgivable.

Neef and Pereira were going through the patient notes when Lawrence Fielding put his head round the door.

“I managed to catch Lennon at the Public Health Department,” he said. “He was pretty shocked to hear the news about the second case.”

“I’ll bet,” replied Neef. “Did he say if he’d made any progress with the Melanie Simpson case?”

“None at all,” replied Fielding. “But he feels that having a second case might help if he can just find out what the two girls had in common. He was going to speak with Jane Lees’ parents this afternoon and maybe Jane herself later if that’s all right with you?”

“As long as she’s well enough to see him,” said Neef. “I talked to her myself at lunch time but I couldn’t find out anything. She’d never heard of Melanie Simpson.”

“Jesus,” exclaimed Pereira who had been reading through the notes and had come to Jane Lees’ X-rays. “Is this the kid you guys are talking about?”

“Yes, we’ve had two like that in the past week. The girls have obviously been exposed to some powerful carcinogen. Our Public Health people are trying to trace it. I don’t suppose Jane Lees is a possible for Gene Therapy?” Neef asked Pereira.

Pereira shook his head. “No siree,” he said. “Not too much lab work has been done on lung cancer and the fact that we’re looking at multiple tumours would tend to rule it out anyway. Apart from that it looks like time is not on this kid’s side. What a mess.”

Pereira left at five minutes to four and Neef went to his office to prepare himself for the meeting with Thomas Downy’s parents. He put on a clean white coat, straightened his tie and made sure a box of tissues was close to hand on his desk. At precisely four o’clock Ann Miles showed in the Downys. They were a pleasant looking couple and huddled together for comfort as they entered. It was something Neef had seen a lot of. As they sat down they drew their chairs closer together so that they could hold hands while they listened to what Neef had to say.

“I’m afraid I have some bad news for you,” said Neef. He could almost feel the hopes and prayers of the couple evaporate into nothingness. “Our neuro-surgeon, Mr Beavis, examined Thomas this morning and reluctantly concluded that Thomas’ tumour was inoperable.”

“Oh my God,” whispered Mrs Downy. Her husband put his arm round her and manfully kept eye contact with Neef. “I see,” he said. “So there’s nothing can be done for him then?”

“Other than keep him comfortable, I’m afraid not.”

Mrs Downy started to sob and tears started to roll down Mr Downy’s own face although outwardly he strove to remain impassive. Neef felt a lump come to his own throat.

“How long, Doctor?”

“Hard to say, weeks rather than months,” replied Neef. “I’m desperately sorry.”

“Thank you, Doctor,” said Mr Downy.

Neef pushed the box of tissues across the desk.

“That is the reality of the situation, I’m afraid,” said Neef, “And I’m sorry I’ve had to be so brutally frank but its important that you understand this before I say what I’m about to.”

“What’s that, Doctor?”

“This unit is about to participate in trials of a new and largely untested cancer treatment known as Gene Therapy. It’s experimental and may even be dangerous but, with your permission, I would like to include Thomas in these trials. I must stress that I cannot offer you any realistic hope of a cure for Thomas, we have no way of knowing what to expect but, if you agree, we can at least give it a try.”

The tears stopped and hope replaced pain in the Downys’ eyes. “Of course, Doctor.”

“I must just stress again,” said Neef. “It’s all right to hope for the best but I think it would be wise to prepare yourself for the worst.”

“Yes Doctor. Thank you Doctor.”