‘That’s where you are wrong!’ Saxena hissed, his annoyance apparent now. ‘These organisms give life! What you see on the computer screen here are not the original organisms that infected him. The retrovirus is a bacteriophage. A virus that infects bacteria.’
He changed the image on the screen. ‘Viruses cannot replicate by themselves. They need to hijack host cells in order to replicate. This is the virus replication process.’ He indicated the diagram on the screen. ‘A virus attaches itself to the target cell and then penetrates the cell wall of the host cell through either fusion with the cell membrane or translocation of the viral genetic material across the host cell membrane. Once the host cell has been penetrated, the virus uses the cellular machinery of the host cell to replicate and make functional and structural viral proteins. The newly formed viral nucleic acid and structural proteins are then brought together to form the nucleocapsid of the virus. The newly formed viruses or virions are then released through a process called cell lysis which leads to the bursting of the host cell to release the virions. This also leads to the death of the host cell.’
Another image appeared on the screen. ‘The virus we are dealing with,’ Saxena continued, ‘is a retrovirus. Its genetic information is encoded by RNA rather than DNA. A retrovirus also contains an RNA dependent DNA polymerase, which is a reverse transcriptase, which enables the synthesis of a DNA form of the viral genome after infection of a host cell.’
He stopped as he saw the blank expression on Radha’s face. It was clear that she hadn’t understood a word of what he had just said. ‘Okay,’ he tried again. ‘You understand that in all organisms, genetic information is encoded in DNA which is double stranded, right? Well, in retroviruses, genetic information is encoded by RNA which is single stranded. Normally, in any organism, when genetic information has to be duplicated during cell replication, DNA gets transcribed to RNA which then conveys the genetic information required to create proteins to replicate the DNA.’
Saxena paused to see if Radha was still with him. She nodded and he continued. ‘In retrovirus replication, however, the RNA has to be converted to DNA which is why it is called reverse transcription. Which is why the reverse transcriptase protein is required – to enable this process. Once the retrovirus is internalised by the host cell, its RNA is released and reverse transcribed into single stranded DNA. This single stranded DNA is then further reverse transcribed into double stranded proviral DNA. This provirus is inserted into the genome of the host cell using another enzyme from the virus – called integrase – and then transcribed into RNA. The RNA gets translated, as is done in normal replication, to produce proteins necessary to build a new virus and virions assemble and are extruded from the host cell.’
Radha began to see why Saxena was going into so much detail. ‘So a retrovirus actually becomes part of the host cell genome?’
‘Exactly. That’s when lifelong infection begins. Retroviruses have the ability to acquire and alter the structure of host cell sequences. They can even insert themselves into the germ line genome of the host cell and behave as a transposable or moveable element. Which means that they are pieces of DNA that can jump around in the host genome at random, altering the host genome in the process and causing mutations in the host DNA. They can activate or inactivate genes near the site of penetration into the genome. They can even rapidly alter their own genome by recombination and mutation under selective environmental stimuli. Which is why the HIV virus is so deadly. It is a retrovirus. And it can turn on DNA that is usually dormant in healthy people.’
Radha’s head was spinning. She tried to make sense of all the information she had just received. ‘I get it. But if a retrovirus is so deadly, how can it help build a shield against disease?’
52
Immortality
‘That’s the problem,’ Saxena sighed. ‘Viruses have a bad reputation, and rightly so. Most of them cause severe, untreatable infections. It is very, very difficult to kill a virus because they are tough little critters. Even if their host dies, they lie dormant, waiting for an opportunity to infect another host and carry on the viral cycle. They have been known to lie dormant for thousands of years without losing potency. But there’s another side to viruses which is less known. You know what the microbiome is?’
Radha recalled reading about it somewhere. ‘The community of microscopic organisms that coexist within people.’
‘Right. It is a symbiotic existence. Friendly collaboration. The best known are the bacteria that live in our guts. In exchange for food and shelter, bacteria aid digestion and help to regulate our metabolism. But there’s a little known story about symbiotic viruses that target nasty bacteria. And that’s where our little retrovirus comes in. As I explained before, it is a bacteriophage. So, for example, the mucus membranes of human beings – the soft tissue in our throats and noses – are rich in bacteriophage. Which is good for us because bacteria also tend to proliferate in mucus. So, by preying on the bacteria that could cause mucus related infections, these viruses actually form a shield or a backup immune system for the hosts.’
‘So the retrovirus you found inside Alexander’s body keeps bacteria at bay?’
‘Even better. And this is where the clinical trials have proved immensely useful. Without them we would never have made the discoveries that will lead us to success. You see, we found the virus and the bacterium in Alexander’s mummy. But we didn’t realise their association until we started infecting subjects separately with each one and then monitoring the results. One of the results was that the retrovirus by itself, in the absence of the bacteria, adapts rather well to the human body as a host organism. And, once it adapts to the human host environment, it proceeds to switch on genes that produce proteins that help slow down the ageing process. For example, IGF1, which is a key protein to continue building muscles. Absence of this protein leads to weakening of muscles and a poorer ability of muscles to repair and regenerate. Then, there is the key protein, telomerase, which is the topic of much debate over slowing the ageing process. There is strong evidence that the absence of telomerase is one of the major reasons why we age and die. The problem with telomerase is that its presence also leads to cells continuing to replicate without stopping – in other words, a cancer. But the presence of the retrovirus also leads to the production of BRAF, a protein that helps regulate the cycle of growth and division of healthy cells – a kind of a brake on cancer. The retrovirus also seems to somehow activate a protein called p53, which is present in a dormant form in all cells. P53 induces the expression of genes that cause cell cycle arrest and apoptosis, preventing the proliferation of malignant cells. This is easily explained, of course. The presence of a new retrovirus in the body induces greater production of Interferon, a protein that stimulates the transcription of the gene encoding p53, resulting in cellular p53 protein abundance.’ He stopped and looked at Radha. ‘I could go on forever. There are new genes it switches on that produce more, unknown proteins that have been proven through our research to have beneficial effects on the human body in terms of strength, regeneration and repair.’
‘That is amazing,’ Radha conceded. This did sound like a major medical breakthrough. ‘You also mentioned that the virus infects the bacteria. Does that kill them off? Is that the virus shield you meant?’
Saxena shook his head. ‘It is so much bigger than that. When we infected people with the bacteria alone, we found two things. First, the bacteria are deadly for humans. But not immediately. Once ingested, they form a biofilm in which the cells are surrounded by large expanses of matrix material. This happens to protect the bacteria from the natural immune responses of the body. At this point, the bacteria also go dormant as a result of a cell mediated immune response which contains the infection but does not eradicate it. So, for a while, there are no apparent clinical or symptomatic effects. We suspect that when the retrovirus infects the bacteria it causes changes in the bacterial genome that halt the production of these proteins that can kill a
human being. Maybe even enabling the bacteria to produce proteins beneficial to humans. We don’t know. For that, we need the original virus.’
‘But you said that you found the virus separate from the bacteria in Alexander’s mummy,’ Radha pointed out. ‘Isn’t that the original virus?’
‘No. I had said we made two discoveries as a result of the clinical trials. I’ve only told you about the first discovery. The second thing we found was that the bacterial genome already contained the virus in the form of a prophage. At some point in time, the retrovirus infected the bacterium but did not survive to replicate in the manner that I described earlier. Perhaps it died out for some reason, surviving only as genetic material incorporated into the genome of the bacteria – a prophage. And this is where things get interesting. Something – we still don’t know what – stimulates prophage induction after the bacterial infection occurs. The retrovirus then replicates within human cells via the lysogenic cycle.’
Saxena realised that he was getting too medical with his terms and held up his hands. ‘Basically what this means is that the latent form of the retrovirus – the prophage – is excised from the bacterial chromosome. This is called prophage induction. Once that happens, the virus replicates in the usual manner, commandeering human cells to create copies of itself. This is when the retroviral infection occurs. But, as I’ve explained earlier, this is good for the host because the retrovirus is beneficial.’
Saxena folded his arms and looked triumphantly at Radha. ‘So you see how powerful this virus is? And the benefits that it can deliver to mankind? And just think – the Order will control this. The power to stop ageing. The power to combat any disease. Forget about antibiotics! We will have the power to confer immortality! The world will be at our feet, begging for this. No wonder they called it the secret of the gods!’
Radha frowned. Something didn’t add up. ‘If the virus is all that great, then how come Alexander died after ingesting it? Why didn’t it change the genome of the bacteria as you suspect?’
‘Because something went wrong when he ingested them. We didn’t find the original virus. Only the prophage. I have no idea what exactly went wrong. But without the original virus, the bacteria didn’t change. They stayed dormant until something triggered their pathogenicity. When that happened, he didn’t stand a chance. We’ve seen this in our subjects. Time and again. Once the bacteria are activated, the subjects die within a few days. Sometimes they linger for a month or two. And this is why we need the original virus and the original bacteria. We need to find the place where Alexander sourced them. Once we have them we can find out how the retrovirus really works.’
‘So the reason you needed to excavate the tomb of Olympias was to find the cube, which would lead you to the source of the original organisms.’ Radha understood the connection now.
‘Exactly. Once we have that, we have the secret in our hands.’
‘So what makes you so sure that Alexander made a mistake? Maybe he didn’t. Maybe these are pathogens after all. Delivering death and suffering.’
Saxena frowned. ‘Two reasons. One, our clinical trials. They bear out what I have just told you. And the second is a much older, more credible reason.’ He paused. ‘Because the evidence is in the Mahabharata.’
Radha was taken aback. She hadn’t expected this reply. Saxena smiled, evidently pleased at her reaction. ‘Oh, yes,’ he said. ‘You’ve heard the myth. You just didn’t know what it actually meant.’
He paused and then launched into another explanation. When he had finished, Radha sat in stunned silence. What she had just heard would turn the world on its head. For anyone else, it was unbelievable. But, having seen for herself, last year, the science that was prevalent at the time of the Mahabharata, she could believe what Saxena was telling her.
And if he was right, the world would be a slave to the Order.
53
On the trail of Alexander
Alice, Colin and Shukla looked at each other despondently. The better part of the day had passed without any further breakthrough. They had sifted through all the papers, studied the maps and photographs and discussed the four remaining verses on the cube, and the additional verse from the journal of Eumenes. All to no avail. They still had only one deciphered verse, the one from yesterday.
Earlier in the day, Vijay had briefly called them on the landline in the fort. He had told them that he had been given a satellite phone by Cooper which would enable him to keep in touch with them even in the mountains of the Kunar valley where cellphone signals would not work. The call had been brief and he hadn’t been able to tell them much but he had sounded excited. And he had told them that the “secret of the gods” was the amrita – the secret of immortality — described in a myth from the Mahabharata. But he hadn’t been able to explain in detail since the time he was allowed on the call was limited. The only thing he had communicated to them as a parting shot was an ominous plea. He was running out of time. They had to find some more answers soon.
They had hoped to have some news for Vijay by now. The thought of him surrounded by potential terrorists and confirmed murderers was too terrible to contemplate. And their lives, including Radha’s, depended on the promise Vijay had made, which haunted them.
‘Let’s go through this again,’ Alice pressed Shukla. The linguist was also weighed down by his worry about his daughter. There was still no news regarding her whereabouts.
She sifted through the papers again and frowned. There was something about one of the maps that had bothered her from the start. But she just hadn’t been able to put her finger on it. What was it?
Pulling the map towards her, she studied it once more. It was a map showing Alexander’s route through Afghanistan. They had gone over this several times. The verses had to correspond to locations on this route. But they hadn’t been able to work out the correlations between the verses and the places Alexander had visited on his way to India.
Colin noticed her musing over the map. ‘See something there?’ he asked.
Alice pursed her lips. ‘There’s something nagging me, but I don’t know what it is. Something looks really familiar.’ She shook her head.
Colin adjusted the map so he could get a better look at it. ‘Alexander’s route,’ he remarked. ‘Interesting. He entered Afghanistan, headed south before turning north via Khandahar, Ghazni and Kabul. Then, he went north across the Hindu Kush mountains, circled around the Sogdian rock and returned to Balkh before turning towards Jalalabad and the Kunar valley. That looks pretty much like a very planned march across the region. I find it difficult to believe that this could have happened by accident.’
Alice stared at the map as if she couldn’t believe her eyes. Something Colin had just said had set off a blinding light in her brain. She saw it now. It had been staring her in the face all this time. And she hadn’t been able to figure it out.
‘That’s it!’ She snapped her fingers as Colin gave her a curious glance.
‘What’s it?’ he asked.
‘Vijay was right all along,’ Alice replied. ‘I should have seen it earlier. The secret lies in the Kunar valley. That’s their destination.’
Shukla looked puzzled. ‘How did you reach that conclusion, Alice?’
‘See here.’ Alice put her finger on the map at the location of the Sogdian rock indicated on the map. ‘Look at the sequence. The Sogdian rock comes before Jalalabad. We may not need the metal plate after all. It is possible that the verses in the journal of Eumenes are in geographical order and Alexander planned his route in the same order. If we can work out the locations that the first two verses refer to, then we can verify if my logic is correct.’
They bent over the map again.
After a while, Shukla looked up. ‘I guess I was distracted,’ he said sheepishly. ‘I should have seen this before. Vijay, in his call this morning, had given us a clue. And I still didn’t figure it out. But when Alice spoke about the order of the verses in the journal corresponding to the ro
ute Alexander took, it struck me. ’ He looked at Alice. ‘I think you are right.’
He pointed to a river running across the map. ‘This is the river Oxus. And I think the second verse refers to this river. The Sanskrit word used in this verse is “chakshu”. Which means “eye”. And that is how I have been translating it all this time. But, in the Mahabharata, the Oxus is referred to as the Chakshu. And the verse referring to the Oxus comes before the verse referring to the Sogdian rock. If the secret of the gods is the amrita from the Mahabharata, then it is very likely that the clues also have some reference to the Mahabharata. That would also explain the reference to Sukra who is also mentioned in the epic.’
Alice studied the map once again. ‘I think you’re right, Dr. Shukla,’ she said. ‘This makes sense. The verse is an instruction to cross the Oxus. Only a river can be “swiftly flowing”.’
‘And there’s the first verse –the one that is not on the cube, but is mentioned in the journal,’ Shukla continued. ‘Now that we know that the secret is somehow linked to the Mahabharata, this verse makes sense. The line of a mighty king that was felled was the line of the Kauravas. Dhritrashtra is the mighty king referred to in this verse. The Kauravas were his sons. They were all killed. There is a hint in the last two lines about the nature of the “ruse” that led to the destruction of the Kauravas: “roll the dice”. It refers to the dice rolled by Shakuni. He was the uncle of the Kauravas and the brother of Gandhari who was the wife of Dhritarashtra, the father of the hundred Kaurava brothers. Gandhari was the princess of Gandhar. And Shakuni was the prince of Gandhar. According to one version of the Mahabharata – I think it is from Andhra Pradesh – Shakuni’s father, Subala, was imprisoned by Bhishma, along with the rest of his family. Shakuni watched them die as they gave up their food so he could live and avenge them. According to that legend, Subala asked Shakuni to use his bones to make the dice that were used in the Mahabharata. That was the “ruse, born of death, sworn vengeance.” The dice, created by the death of Subala, and the vengeance sworn by Shakuni. Gandhar is the ancient name for Khandahar.’
THE MAHABHARATA QUEST:THE ALEXANDER SECRET Page 21
