‘And this didn’t happen to Lena?’ interrupted Jack.
‘It did. The very same thing happened to her as well—’
‘But wasn’t Lena cured? The Auschwitz operation?’ interrupted Jack again. ‘She lived for another seventy odd years.’
‘Yes. Both twins had brain cancer, and both were operated on, but only one survived and was cured. The Auschwitz notes are quite clear about this. They were among Professor K’s papers – remember?’
‘How, and why?’ asked Jack.
‘That’s the ultimate question here, and that was precisely what Professor K was working on when he died. He believed that Lena was cured with the help of a compound extracted from that Mexican jungle plant Dr Steinberger had obtained from José Gonzales in Paris.’ Alexandra reached for a glass phial on her desk and held it up. ‘This here.’
‘Is that what Lola brought back from Kenya for you? The stuff from the experiments in that dreadful Somali death camp we discovered?’
‘Not quite. I have substantially modified the compound to make it more effective, and so had Professor K. However, the composition of the drug from Somalia gave me an important clue, which was a big help. Essentially, it’s very similar, reaching right back to Auschwitz and what Professor K’s father used on Lena, only it’s stronger and more refined, I suppose. Miriam didn’t receive any drug treatment and she succumbed to the tumour.’
‘How does this compound work?’
‘Ah. That’s what those dreadful experiments in Somalia were all about. It appears to work in some cases – spectacularly – and fails miserably in others. This was also what Professor K was wrestling with just before he died. He wanted to know why that was so, and what could be done about it. Macbeth’s scientists were doing the very same thing.
‘Are you suggesting that Blackburn Pharmaceuticals and Professor K were working on the same problem?’
‘Yes. Only their methods were vastly different. Blackburn Pharmaceuticals were using real people, Professor K was using mice and his intuition. And it would appear that he was winning.’
‘How?’
‘Just like his father before him, he had a hunch that turned into an inspired idea.’
‘Oh?’
‘He developed more active forms of the compound extracted from the Mexican medicinal plant and experimented on mice. He even gave the compound a name – Demexilyn, would you believe. A new drug based on a Mexican jungle plant extract with demethylation properties. A play on words; clever. I have painstakingly reconstructed the experiments described in his notes and examined the tissue specimens he concealed here in the lab. The results are clear. They have shown that this compound is not only able to prevent growth of gliomas – brain tumours – in mice, but it can also inhibit the growth of a number of different types of cancer. The compound was stimulating immune T-cells to recognise and destroy cancer cells. In short, it was mobilising the body’s own defence mechanism.’
‘But that’s fantastic, isn’t it?’ said Jack.
‘In mice, Jack. In mice,’ Alexandra reminded Jack.
‘So?’
‘Let me explain where Professor K was up to just before he died.’
‘Please.’
‘For years, he had carefully studied “non-coding” RNAs.’
‘What’s that?’
‘RNA copies from parts of the genome that do not code for proteins.’
‘What, the junk DNA? The 98.5%?’
‘Spot on. And by carrying out new in-depth “next-generation” sequencing of RNA from different types of cells, Professor K had been able to identify an RNA with an unusual structure found only in immune T-cells that are important for fighting cancer.’
‘And that was important?’
‘Oh, yes. This RNA was encoded by a gene – let’s call it gene X for the moment – located hundreds of thousands of bases away from the nearest gene known to code for a protein. Needless to say, Professor K was intrigued by this and began to experiment. He made “knockout” mice.’
‘What on earth are knockout mice?’ asked Jack, shaking his head.
‘Mice in which one copy of the gene had been deleted. These mice seemed healthy and normal, except that they were very susceptible to cancers, which grew rapidly and they were unable to suppress.’
‘And this was significant?’
‘Yes. Absolutely. When Professor K examined the T-cells of these mice, he found that expression of a number of genes was altered, especially a protein-coding gene, DD1alpha, which played an important role in suppressing recognition of cancer cells. The new gene X was located on the same chromosome – Chromosome 10 – as DD1alpha, but more than two hundred thousand bases away. And this brings me to Professor K’s last experiment that had so excited him. In fact, he had the results of that experiment in front of him when he called me just before he died.’
‘Incredible! And you were able to reconstruct all of this?’
‘Yes. From his notes. It wasn’t easy, I can tell you.’
‘So, what was that last experiment all about?’
‘He tested the effect of that new compound – Demexilyn – on mouse and human immune T-cells in culture right here in his laboratory. And I’ve just done the same.’
‘And?’
‘The results were surprising, to say the least. Demexilyn activated expression of the newly discovered gene X and blocked expression of DD1alpha, making the T-cells much more potent in fighting cancer.’
Jack held up his hands in defeat. ‘Stop right there! You’ve lost me. This is far too complicated for a bloke like me.’
‘Bloke? All right.’ Alexandra reached for a small notebook on the table in front of her. ‘This is the last entry in Professor K’s notebook. I believe he wrote it in a great hurry just before he died. His writing is barely legible. This is what it says:
“Abramowitz puzzle: Why did the tumour kill one twin and not the other? Their genomes were the same and both carried the same mutation in the P53 gene that fuelled their tumours. Possible solution? What if they had epigenetic differences?”’
Alexandra paused, and looked at Jack. ‘If Professor K was right, then the next sentence is the inspired idea I mentioned earlier; his genius.’
‘What does it say?’
‘This: “If so, then the difference had to be something that responded to Demexilyn, the extract from the Mexican medicinal plant”.’
‘Do we know what that difference is?’ asked Jack.
‘Professor K believed it had to be the new RNA gene X. That’s what could have cured Lena. She was able to defeat her cancer with the help of a revitalised immune system, and this was made possible by gene X, which had been switched on by Demexilyn. This process activated the body’s own defence system against cancer and destroyed it.’
‘Wow! Will we ever know if he was right?’
‘Yes, we will.’
‘How?’
‘Because of a critical test that unfortunately eluded Professor K.’
‘And you can perform?’
‘Yes.’
‘My God! When?’
‘Tomorrow.’
113
Isis sat in a comfortable wicker chair on the terrace overlooking the Kuragin Chateau garden. François had brought her home from the hospital that afternoon, and just smelling the fresh evening air rising from the pond and listening to the hum of the insects felt like hope after those horrible few days in intensive care. However, Isis realised hope was but an illusion as she remembered that dreadful hologram the director of cancer imaging had shown her on his computer screen earlier that day. In hindsight, Isis almost regretted having insisted on being present at the briefing arranged by Sir Humphrey. It had been a most terrifying experience.
Isis had seen her cancer, which had rapidly spread to various parts of her body, including her lungs and bones, in stunning, three-dimensional detail. There were now several tumours putting pressure on her brain. The Emperor of Darkness was advancing with relentless det
ermination, preparing for his final triumph.
Sir Humphrey walked over to his patient, and sat down next to Isis. He had desperately wanted to spare her from the horror of viewing her own approaching death, but his headstrong patient had insisted.
‘How much time have I got?’ asked Isis.
‘Difficult to tell …’
‘Don’t beat around the bush.’
‘You saw …’
‘Not long then. But I’m a fighter; you watch!’
‘I know you are. And we have a white knight talking to our queen Down Under – right now.’
‘Dr Delacroix. Have you heard from Jack?’
‘Yes.’
‘And?’
‘The research is at a critical stage.’
‘When will we know?’
‘Tomorrow.’
‘And then?’
Sir Humphrey shrugged. ‘Uncharted waters, I’m afraid,’ he said.
Isis reached for the wooden box on the small table next to her and opened it. With the last rays of the setting sun caressing the gleaming crystal, the spectacular skull seemed to come to life. ‘The Emperor of Darkness better get ready for a fight, then,’ said Isis, smiling for the first time since her return.
‘I couldn’t have put it better myself,’ said Sir Humphrey. ‘Let’s go inside and join the others. It’s getting a little chilly out here.’
Unable to sleep, Alexandra kept tossing restlessly in her bed. Feeling hot and clammy, she sat up and looked again at the clock on the bedside table. It was four in the morning. She realised that the test scheduled for later that day was not only critical, but a watershed moment in her life. It was the culmination of a long sequence of extraordinary events bringing together the work and vision of several gifted people, who had each made it their life’s work to improve the journey of man.
Jack was peacefully asleep next to her. He’s like a child, she thought, watching Jack and envying his ability to switch off. Telling Jack all about her ordeal had been both liberating and cathartic, and jumping into bed together after the dinner he had prepared for her as a surprise, had seemed the most natural thing to do. Jack – a good listener and experienced lover – had sensed Alexandra’s needs, and knew exactly how to banish loneliness and make her feel wanted. The paralysing blemish had been removed.
Jana and Marcus had moved out weeks ago and were looking for a house to buy. Thanks to the spectacular success of ‘Operation Blowhole’, Jana had re-joined the Federal Police and been given her old job back. Marcus had landed the hottest brief in town, and was preparing the case for the prosecution. This had left Alexandra by herself in Jack’s apartment, which had quickly become her home. She didn’t mind living by herself, even after the traumatic events leading up to Van Cleef’s spectacular bridge-jump suicide, but having Jack around felt good.
Alexandra reached for her dressing gown and tiptoed out of the room to make some tea. She knew going back to sleep wasn’t an option. Instead, she would go over the notes she had prepared for the critical test to make sure nothing had been overlooked. She also had an idea for a name for that new gene, should it turn out to be as groundbreaking as Professor K had believed it would be.
Jack stood in the doorway and watched Alexandra. Hunched over the kitchen table, she was reading her notes, her concentration making her oblivious to anything going on around her. It was just after sunrise, and the still waters of the harbour below reflected the first light of the new day, making the striking sails of the Opera House glow in hues of pink and mauve. Jack walked over to Alexandra, kissed her gently on the neck and looked over her shoulder. She turned around, surprised, and smiled.
‘KALM 30? What’s that?’ he asked, reading the scribbled letters in the margin.
‘Every new discovery needs a name. This is a name for a new gene. If Professor K was right, then this hidden gene has the power to change medicine and the journey of man.’
‘Wow! What does KALM stand for?’
‘K for Kozakievicz; A for Abramowitz; L for Lena and M for Miriam. KALM.’
‘Clever. And 30?’
‘The twins were born in 1930, and so was the gene.’
‘Brilliant!’
‘You like it?’
Jack nodded. ‘So, that’s how it works,’ he said. ‘Full-on hanky-panky at night, followed by a little sleep, and then up at first light to tackle the challenges of another day in the lab. I don’t know if I can keep up with this. More tea?’
Alexandra raised an eyebrow. ‘Hanky-panky, you call it? Unable to keep up?’ she said. ‘I expected a little more from such a dangerous bloke.’
‘French sheilas …’
‘Is that a complaint?’
Jack held up his hands. ‘No! Definitely not.’
‘Good. You had me a little worried there,’ said Alexandra, laughing.
‘Tell me about this test.’
‘This is it; crunch time. Today we’ll find out if Professor K was right. We are lifting the curtain to find out what’s hidden behind it and the DNA of the Abramowitz twins should provide the answer. Extraordinary, isn’t it? After all these years and everything that’s happened, it all comes down to this.’
‘Destiny?’
‘Yes, I think you’re right.’
‘The test?’
‘I believe we have just enough DNA left from the hair samples to perform it. We have to read the methylation code on the DNA.’
‘How do you do that?’
‘First, we treat the DNA with sodium bisulphite, a chemical, then we amplify the DNA that regulates the new RNA gene – KALM 30, and read its methylation sequence. If this works, we should have all the answers.’
‘And this could help Isis?’
‘I believe so.’
‘How?’
‘By treating patients like Isis with Demexilyn, we could switch on this amazing new gene – KALM 30, and thereby activate the body’s own defence against cancer.’
‘And this could fight the cancer even at an advanced stage?’
‘No reason why not. I’ve seen spectacular new immunotherapy drugs like Keytruda and Yervoy do just that in a few months. It’s almost miraculous, but it works. They attack and destroy cancer cells, and Demexilyn could do the same, perhaps even a lot better. However, I believe we’ll have to “tailor” the drug – its dose and application – to each patient’s needs. That’s the key. This has become clear to me from the Somali trials. The drug has to be slightly modified from patient to patient to make it work. Professor K realised this from the beginning. Blackburn Pharmaceuticals did not. That’s why they failed. And Professor K also knew how the drug could be customised to make it more effective.’
‘How?’
‘Through personalised medicine. The way I see it, we would have to sequence each patient’s genome to ascertain the precise dose, composition, strength, etc. of Demexilyn application to make it work effectively. Otherwise, it could be effective in some cases, but not in others. Hit and miss, just as it did in Somalia. But fortunately for us, it appears to have worked for Lena, just as it did for the young Aztec chief in the De Medicina codex. That was luck. We need more. All going well, we should know for sure later today exactly how, and why it all works.’
‘So, the Somali drug we brought back did help?’
‘Hugely. It was another important piece in the puzzle, which pointed us in the right direction and provided a massive shortcut. In some way, it worked like a crude clinical trial, telling us where we had to go.’
‘Incredible. But before we could help Isis with this drug and activate this new wonder-gene, we would have to sequence her genome to make it work?’
‘Yes. That’s right.’
‘How long would that take?’
‘About a week. Why?’
‘Give me a second,’ said Jack and hurried out of the kitchen. He returned moments later with a small ivory box in his hand. ‘Here, this is for you,’ he said and handed the box to Alexandra. ‘From Isis.’
‘What is it?’
‘Open it.’
Alexandra opened the box and looked inside. ‘Hers?’ she asked.
‘Yes. Hair, complete with follicles. I’m a fast learner – see?’
‘You’re an amazing guy, Jack Rogan,’ said Alexandra.
‘Not really, just an attentive sorcerer’s apprentice.’
‘I’m getting a little confused here. I thought you were a dangerous bloke?’
‘Most sorcerer’s apprentices are.’
‘I give up,’ said Alexandra, holding up her hands. ‘Give me genomics any time; much simpler, I tell you.’
Sir Humphrey, an early riser, was enjoying breakfast with Countess Kuragin on the terrace when his phone rang. It was Jack.
‘I hope I’m not too early, but we wanted you to be the first to hear this,’ said Jack.
‘Oh? What have you got for me?’
‘Hope … Here’s someone who can explain this much better than I – Dr Delacroix.’ Jack handed his phone to Alexandra.
‘I just received the results of the test we spoke of, Sir Humphrey,’ said Alexandra, the excitement in her voice obvious.
‘And?’
‘The amplification of the DNA from Professor K’s new gene – we gave it a name: KALM 30 – has been successful, and we were able to read its methylation sequence.’
‘That’s great news!’ exclaimed Sir Humphrey.
‘It is. When we had a close look at the sequence, all the pieces of the puzzle began to fall into place. In the DNA from Miriam’s hair, one copy of the KALM 30 gene was methylated, but in the DNA of the survivor – Lena, who had successfully fought her brain cancer, both copies of the gene were completely free of methylation and would therefore have been active and able to fight the disease. That’s why she was cured and lived well into her eighties.’
‘Extraordinary!’ said Sir Humphrey. ‘And do we know how that happened?’
‘Yes, we do. It’s all thanks to Demexilyn, the new drug. The reason Lena was able to successfully fight her cancer was with the help of this drug. What it did was to switch on Professor K’s hidden gene – KALM 30 – and this activated the body’s own defence against cancer.’
‘Fantastic! This new drug works then?’
The Hidden Genes of Professor K Page 55
