by Tim Neilson
He accepted that originators needed to be confident of keeping the profits of their successes to themselves, otherwise why bother funding research at all. If there was no funding, it was unlikely any research would get done, in which case no one would benefit. More importantly, he knew that people who worked for originators tended to be passionate in their convictions around these issues. If he was going to persuade this crowd to fund his idea, there was no point in antagonising them.
“OK, so if they’re not actually planning to apply their technique to painkillers and make money out of that themselves, couldn’t we cut some sort of deal with them to let us do it?”
The suits shook their heads in unison.
“It’s highly unlikely,” said one of them. “They may well not care about painkillers, but strategically they won’t want to be seen doing deals with anyone who might be conceivably infringing on their rights. They’d see that as encouraging other people to start nibbling at the edges of their other product rights in the hope of getting that kind of deal.”
“But they can’t stop everyone from using heavy isotopes, surely,” Cam pleaded.
“They can’t actually patent any of the laws of nature,” admitted one of the executives. “If heavy isotopes have particular properties, D & G can’t patent those properties any more than they can patent the law of gravity. They can only patent a product or process. The first question is whether the processes you’re hoping to use are similar to their processes, meaning that yours are probably going to breach their patent applications, or whether what you’re doing is different enough that you’re free to keep going. So, is what you’re doing really different to what they’re doing?”
“Well, they’re based on the same fundamental theory about subatomic particles,” Cam admitted. “You know the basis of the immune system of course, and how antibodies work. Well, D & G’s work is just trying to dial up the efficiency of that.”
Cam continued, summarising the general principles of immunology: how in the presence of disease-causing ‘antigens’ the human body responds to the danger by producing antibodies. He described ‘somatic hypermutation’ – the means by which the body somehow produced a variety of different antibodies until it produced one that, at the basic biochemical level, would interact effectively with the particular antigen then present in the body, so as to neutralise it. He told them how the body would commence producing that particular antibody in quantities sufficient to deal with the threat. He also mentioned how the body would produce ‘memory’ cells that would give the body acquired immunity against antigens of the same type, by providing the body with the stored capacity to produce the relevant antibody quickly whenever it needed to do so.
He referred briefly to the obvious fact that manufactured pharmaceutical antibiotics and antiviral medicines were an artificial means of achieving what the body itself might not be able to do quickly enough. The body worked, so far as current knowledge extended, using something like trial and error; if doctors were able to diagnose the type of bacteria or virus causing the problem, and then if medical science had devised an effective antibody, they could immediately start pumping it into the patient.
Cam’s listeners all knew that if bacteria bred quickly and in vast enough numbers, genetic mutations were common within the strains of bacteria that cause illness. They also knew those bacteria surviving an initial onslaught of antibiotics are mainly the ones with a mutation genetically equipping them to resist the treatment’s effects. The survivors multiply, handing to their progeny the ability to survive existing antibiotic remedies.
Cam therefore didn’t have to explain why there was a constant need for new research and development of newer treatments. His audience got it. That sort of research and development was their company’s reason for existence.
He briefly mentioned the issues caused by over-enthusiastic and widespread use of the early ‘broad-spectrum’ antibiotics – where the inexorable rules of natural selection rendered those treatments less effective after their initial successes, and how, over time, new treatments needed to operate against bacteria that had a history of inherited genetic resistance to antibodies.
He paused to look around the room before going on.
“So, we’re constantly working on ever-more specific antibiotics to deal with very specific aspects of the structure of particular antigens,” he said. “And we’re still having successes. But it’s only going to get harder as time goes on, and it’s an inherently piecemeal approach. Imagine if we could achieve some breakthrough that helped us make artificial antibodies that self-reconfigured each time in response to the mutations of bacteria and viruses. Then we wouldn’t have to spend time developing a specific cure for each strain. We would reduce the risk of an infection killing patients or becoming an epidemic while we are still researching the next treatment.”
Again, his eyes scanned the assembled executives as he spoke, eager that they should understand his enthusiasm and the potential leap forward that Derwent & Graham was trying to make.
“So what’s needed,” he said, “is a means of making pharmaceutical products that can adapt themselves to interact biochemically with differently configured antigens, so that those products can counteract new strains of antigens as they emerge. And that’s what’s so wonderful about the heavy isotope work that D & G is doing. The body’s own immune response essentially starts with a sort of trial-and-error experiment to find a biochemical agent that can successfully lock onto and neutralise the antigen. And when it finds one, it starts to produce it in large quantities. That ‘somatic hypermutation’ process is what we need to replicate artificially. But how would we do that with non-living products we turn into pills or solutions for injection? We need to give our non-living product the right kind of internal chemical instability that enables it to change itself, to shape-shift, in the right way to keep morphing until it hits on the configuration that interacts with the antigen.”
He smiled in unselfconscious delight at Derwent & Graham’s ingenuity in tackling the problem.
“And that’s in part where unusual, most often heavier than normal, isotopes of conventional atoms come in. They’re inherently less stable than the normal atom of whatever element we’re talking about, carbon or hydrogen, for example. So the more of them that are around in a specific type of molecule, the more likely there is to be a variation in the way those molecules react chemically. But that alone isn’t likely to make a product work effectively as a treatment. The variations may make it more likely that at least some of the molecules in the product will interact effectively with the antigen, but they may well create as many misses as hits. We’d really be just as well off making large numbers of slightly different products and pumping them all into the patient. To make the heavy isotope product work we need to give it some way to self-correct when it’s in contact with the antigen until it shapes into a structure that locks on.”
“Self-correct?” interrupted one of his listeners.
“Well, ‘self-correct’ isn’t quite right – the molecule obviously won’t be pursuing some conscious purpose,” admitted Cam. “There’s a biochemical mechanism by which the body selects which antibody to start producing in large numbers, but I’m not hanging out until we work out how to replicate that in a lifeless chemical compound. We need something else. And that’s where we go deeper, right down to fundamental subatomic physics.”
He paused, not for rhetorical effect, but because in his excitement he had almost forgotten that he was speaking to anyone, and the interruption had wrenched him back to an awareness of his surroundings. Slightly bewildered at the sight of varnished panels, office furniture and business attire, he regathered his thoughts.
“There’s a debate among physicists about whether subatomic particles can travel backwards in time. The majority consensus is that they can’t. But a substantial number of qualified people believe they can. But even the time-travel believers mostly say that the particles that travel backwards can then travel
forwards again only into a reality that’s the same as the one which they reversed out of. But …” he continued softly, “how would we know? How could we ever verify that ‘now’ hadn’t existed differently in some other type of time? Isn’t it inherently possible that if a particle could travel back in time, and then travel forwards again, and if it had altered reality by that doubling back and forward, we’d have no way of empirically verifying that the alteration had happened?”
A slight cough from one of his audience prevented him from drifting back into his own speculations.
“Anyway,” he announced, not so much to the others in the room but to bring himself back to the point, “what’s important here is everyone agrees, even if a particle is capable of reversing its previous action, some actions are harder to reverse than others. If the previous action didn’t have any substantial effect on reality, it’s easy to reverse. But if that previous action made a substantial difference to the situation, then that situation is harder to reverse. So if an antibody contains a particle that moves one way, and that move doesn’t affect the antigen, then it may be easy for the particle to go back and then make another, different, move which may lock the antibody and antigen together. But, conversely, if its first move does create the interaction between antibody and antigen, then it’s much harder for time travel to cancel that interaction.”
He looked around. The executives seemed to be following, but clearly hadn’t yet guessed what he was driving at.
“And so, maybe an artificial antibody can mimic the natural experimentation that’s part of the body’s fight against bacteria and viruses through somatic hypermutation. A normal tablet or injection contains vast numbers of molecules of the intended antibody. If enough of those compounds contained sufficient unstable isotopes, then there could be a lot of molecules having two or three goes at neutralising the antigen before finally latching onto the configuration that works. Which is better than a compound only likely to go one way, and which fails permanently if that one way doesn’t work. Especially where the virus or bacterium may be slightly different than what the antibody was designed for. The time-travelling antibody can do the work, in the patient’s body, that might take years and cost a fortune in the labs. That’s what’s so brilliant about what D & G is doing,” he concluded, eyes shining with admiration.
“But surely,” protested one of his listeners, “one single atom, or a very small number of them, can’t have such a crucial effect?”
“Good question,” nodded Cam. A difficult one, actually. But he was encouraged that at least someone in the group seemed interested in the science. That could be a help.
“We tend to think,” Cam explained, “of the ‘right’ antibody being one that is pre-configured so that it will instantly fit perfectly with the antigen, like a key going into the matching lock. But I think that’s an oversimplification. I think it’s more accurate to think of the crucial part of the antibody as being like the bottom part of a zip fastener. Once you get the insertion pin of a zip into the slider properly, then the rest follows easily. So if we can make the antibody’s equivalent of the slider or insertion pin flexible enough, then it’s got a better chance of locking on and the rest will follow. We’ll have a treatment that can beat the viruses and bacteria at their own game.”
“Great”, observed one of the suits, dryly, “but if D & G’s patent applications are valid, it’s got a lawful monopoly on it. If we do fund you it’s almost certain they’ll take action to try to stop you. And unless you’ve got a very strong, easily provable, point of relevant difference between your work and theirs, we’ll be tied up in the courts for so long we may never get any return on the investment. So why is your work so different?”
“It’s the same principle,” Cam admitted, “but applied to analgesics.”
The assembled throng seemed to understand his explanation of how the brain contains ‘receptors’ that affect the body’s feeling of pain, and how ‘neurotransmitters’, natural ones but also artificial ones, can biochemically interact with the receptors to alleviate pain.
“What is well established, even if we don’t know all the details, is that the body produces an ever-diminishing response to each succeeding dose of any given neurotransmitter. That’s widely known in relation to illicit drugs – how long-term drug users need to take ever-increasing doses to get the effect they want – but it’s true of medicinal pain relief as well. It seems most probable that, in some way, the receptors get dulled and don’t interact so readily with the neurotransmitters, so the body gets less relief from pain or a less positive sense of wellbeing. So much so, that if the body doesn’t keep getting pumped full of the neurotransmitters it may well feel pain even when there’s no longer a clinical cause for it. Again, that’s well known as the basis for addiction and withdrawal symptoms in illicit drug users.”
“D & G,” he continued, “is trying to use heavy, less stable isotopes to make antibodies that shape-shift, using minuscule backward time travel to have multiple goes at neutralising bacteria or viruses. I want to make artificial painkilling neurotransmitters that do the same thing with the body’s own pain receptors. Hopefully, then, instead of prescribing ever-increasing and ever-less-effective doses, a painkiller can remain effective for longer – even as receptors get dulled by its initial impact. Perhaps, if the drug acts in a variety of different ways, we can even mitigate withdrawal symptoms as the dosages get reduced. And, if we can do that with the substitutes for illegal drugs, like methadone is for heroin, maybe we can make rehabilitating drug addicts far easier and more effective, too.”
“That’s an interesting clinical prospect,” responded one of his listeners, before turning to a colleague and asking, “But does that mean he’s caught or not caught by D & G’s patent applications?”
Copies of legal documents were passed around, and a discussion ensued, during which Cam was a largely uncomprehending observer.
“It’s hard to quantify something like this,” mused the leader of the meeting. “We haven’t done any detailed financial modelling yet, but the concept doesn’t look like a self-evident gold mine, even if we weren’t facing the threat of D & G derailing it. Can the legal team please have a look at the D & G applications and let me know what they think? If there is a clear path ahead we’ll do some more on the financials. I’m sorry Doctor Fletcher, but I can’t say it’s likely we’ll be saying yes.”
Cam’s heart sank. He had half been expecting to be turned down on the spot, so the knowledge that they hadn’t yet definitely rejected the proposal should have been welcome, but it didn’t feel like good news.
“It’s a pity that D & G was the first to think of it,” someone remarked sympathetically. They meant it was a pity Derwent & Graham had thought of it before Cam, but he misunderstood.
“They weren’t,” he said. The response was offhanded, but he suddenly noticed the intense attention that his answer had provoked.
“What do you mean?” asked one of the lawyers eagerly. “You understand, don’t you, that if someone else did it first, or even showed how it’s done, then D & G isn’t really the inventor. Then its patents would very likely be invalid, and you could do what you liked without them interfering.”
“Well I first came across the idea in an odd way,” Cam explained, watching keenly for the reaction to his words. “I had to write an obituary for a former Fellow of my College for the College’s newsletter. It’s the kind of job a fairly junior Fellow gets landed with from time to time. Anyway, I was looking through some old archives to check on some details, and I came across a letter he had received from a colleague, which said something like ‘Crick has been getting nowhere with his isotope-based medical-treatments line of thinking’.”
“Francis Crick, the Nobel Prize winner, presumably,” someone intervened.
“Yes. I was curious since it didn’t seem to relate to any published work by Crick that I knew of. I can’t remember the exact wording, but it showed that Crick had been speculating about
the instability of some isotopes and the efficacy of biochemical treatments – nothing about time travel though. I did some thinking about why unstable isotopes would be any better than ordinary ones, and time travel seemed to fit. Then later I found out the hard way that D & G had also had the same idea.”
“But what did Crick do with it?” demanded the lawyer.
“Gave up on it, it seems. That letter I’d seen said he asked the Australian immunologist McFarland Burnet about it, and Burnet had said something to the effect that only a science fiction writer would ever come up with anything that would make it work. And Crick had agreed.”
The mood in the room fell flat.
“So there’s no chance that Crick took it as far as having a product in mind? He didn’t get past theorising?”
Cam stared pensively for a few seconds.
“It doesn’t look like it to me,” he admitted. “I know he contacted Burnet about the general concept that unstable atoms might react better clinically than stable ones. I’ve never seen anything to suggest he had any more definite ideas than that.”
A short silence followed.
“We’ll be in touch, Doctor Fletcher.”
The train journey from London back to Cambridge was usually a pleasant experience. After the early miles traversing some of London’s less scenic areas, the line passed through long stretches of idyllic countryside. Cam had made the trip too often to be captivated by the sight, but the undulating greenery was still tranquil. More importantly, the carriages were rarely full, so it was almost always possible to get a seat and devote a solid hour to some reading or thinking time, free of electronic distractions, if he wanted. But this time Cam couldn’t settle himself down to work, nor could he switch his mind to relaxed mental wandering. He brooded sullenly over the realisation that the project that had so much potential seemed certain to suffer death by financial strangulation.
