Collateral Damage

“I name you Baqir Iftikhar; my son. Baqir because you are my beloved and Iftikar because you fill me with pride,” exulted the new father Intaj Iqtidar Raza, better known as Barq Bhai in the Indian underworld.

His name, Barq, had evolved because he struck like lightning. Like lightning, no one knew where he would strike and he struck with equally devastating effect and swiftness. Yet, Intaj was also a devoted family man and Noor Banu, his wife, closed her eyes for the last time secure in the knowledge that he would give their new-born every luxury the world had to offer. 

***

Diwakar Dighe, Intaj’s right-hand man for over three decades wiped his eyes. “I told you; Baba listen to me. Do not buy Baqir a Lamborghini Aventador for his seventeenth birthday. Our roads are not ready for it. I begged you, Baba, listen to me.”

The writing was on the wall.

Baqir Iftekhar and his Lamborghini Aventador were both “totalled.” 

The doctors said as much about their seventeen-year-old patient.

“But he is breathing,” cried Manya Munir, Baqir’s best friend, who had been flung out of the car and sustained only minor injuries. He had rushed to be at Intaj Uncle’s side. “His eyes are open. He is alive…do something.”

The doctor patiently explained again. He knew better than to show his irritation. “His cerebrum, the part of the brain that controls thought and behaviour, has shut down. But his hypothalamus and brain stem, the parts of the brain that control vital functions, such as sleep-wakefulness cycles, body temperature, breathing, and blood pressure are still functioning.”

***

Manya beset with survivor’s guilt came every day to visit his friend. For three weeks Baqir hovered between life and death and then, miraculously his condition stabilized. He opened his eyes when his name was called and appeared to smile when he saw familiar faces. He could now breathe on his own with only occasional support.

Intaj’s question now changed to, “When can I take him home?”

“Baba, I think we should bring Baqir home. You know we can build a medical care suite at Rehmat Manzil and have him shifted there…if Michael Schumacher’s family can do it; so can we.”

So, Baqir was shifted home. Prominent neurologist and other specialists visited him regularly. Round the clock nursing, excellent physiotherapy and continuous monitoring meant that Baqir lacked for nothing even while he was in a semi-coma. Meanwhile his father, Manya and Dighe, continued to search for alternative therapies.

Dighe visited every temple of note and called on every Ayurvedacharya worth his name.

Intaj and his minions fanned out in search of any expert in Unani medicine, any maulavi or learned person who could cure Baqir.

Manya who was a college dropout suddenly discovered science. Since he did not know any scientist or even a science Professor, he began to devour science articles that were published in newspapers. One day he burst in with a big grin on his face.

“See, this article on stem cells.”

“Stem cells? What are these?” Dighe was curious.

Manya hesitated just a bit and then said, “As far as I have understood stem cells are special cells. These can develop into many different cell types. Like maybe muscle cells or brain cells. Stem cells have the ability to repair damaged tissues. It is cutting edge therapy for damaged brains.”

“Then we have a chance…let us tell Baba.”

“Wait, wait …the girl who has written the article on stem cells says these are also being used to treat brain cells…but after that I have not really understood what she wrote.”

“Never mind, Baba will speak with Baqir’s neurosurgeon. He will understand.”

***

Intaj rang up Dr. Tridib Kar, the neurosurgeon who had operated on Baqir. Dr. Kar arrived at Rehmat Manzil wondering what new idea or process he would have to explain. He was a little surprised to hear that Intaj was considering stem cell therapy.

He said, “Like I have said earlier, stem cells are collected from the brain and implanted directly around the site of the injury. However, in Baqir’s case his physical condition…though it is improving…is still not stable enough for brain surgery. Besides, his brain trauma is across a largish area. It is impossible to consider him to be a likely candidate for brain surgery or even stem cell therapy.”

Intaj was not convinced. “What if I get the surgeons from China and in Korea. You said they have made pioneering studies.”

“Stem cell treatment for brain injury is at a very early stage anywhere in the world. But China? Korea? Are you seriously considering…” Dr. Kar wiped his brow.  Despite the air-conditioning he was sweating. “The ethical standards of these countries … Besides how will you take Baqir there? The journey itself will kill him.”

Intaj cut him short. “I am desperate. I understand your misgivings but I am willing to try anything…anything at all…even experimental protocol….do we have nothing in India? I am willing to sign any document…invest any amount of money…even if there is a five per cent chance I will take it.”

Dr. Kar whispered, “A five per cent chance? That is not good odds.”

“I will still take it doctor…Baqir is a vegetable now…worse than a vegetable…this way he is either restored to me or goes to the arms of his mother. Either way, one of us has him entirely. I just cannot see him like this. Here…but not here! No, every day is a burden…for him…for us who love him.”

Dr. Kar said, “I am a Consultant at a military hospital where advanced trauma research is carried out. We work on cutting-edge treatment to treat all sorts of brain trauma in soldiers. I will pull some strings and see if they will bend the rules for a civilian. But remember, the odds are NOT in your favour…be prepared for the worst. Don’t blame me later.”

“I am living the worst, doctor. Now it has to is either iss paar ya uss paar…either this side of the chasm or that side…no more dangling between life and death.”

***

Military Brain Trauma Research Hospital

Dr. Sriram Nanda, the In-charge addressed Intaj, “I agree with Dr. Kar that Baqir has extensive brain trauma. This is not an easy case. It is a very difficult one but something that we are very interested in. Brain trauma in combat soldiers is a tragic reality.”

“That is why we have come to you. You have not said it is an impossible case; but a difficult one. The others…” Intaj’s voice broke.

Dr. Nanda smiled reassuringly. “I have a new…may I say, a unique take on brain regenerative surgeries. Our government has been kind enough to allow me to carry out the protocol in the hope that we may offer hope to injured soldiers. As you know, no government condones the use of humans as experimental models. However, my protocol runs at very low level of risk. I aim to repair the brain bit by bit by bit. I do not carry out major brain surgery so there is little extra trauma to the damaged brain. I merely inject a special cocktail of special cells and nutritive fluids. I do this multiple times so that the brain repairs itself bit by bit by bit.”

“Bit by bit by bit?”

“Yes…in three steps; because our brain has three parts.

Dighe said, Yes… we now know. Cerebrum, cerebellum and brainstem. Baqir has managed to damage all the three parts to a lesser or greater extent.”

Dr. Nanda beamed. “Yes, but it goes beyond that. First is the brainstem which is continuous with the spinal cord. Then there is the part called basal ganglia which is buried deep in the cerebrum. Together, these two are the most ancient or earliest evolved part of the brain. We call it the reptilian brain.”

“Reptilian brain…why would human beings, the best creation of the Almighty, have reptilian brains?”

 “No, no…this is just a name… Evolutionarily, the oldest part of the brain is the reptilian area.  It is responsible for instinctive reactions and all primitive drives related to survival. So, it handles temperature-control, hunger, thirst, and habits or things we often do without thinking. You can think of the reptilian brain as a mammalian brain without most of its newer parts. This is the part of the brain that is keeping your son alive.”

Intaj swallowed. Then in a humble voice he asked. “My son could play the guitar and sing very well…I do not think the reptilian brain takes care of that.”

Dr. Nanda went on as if he had not heard the pleading tone in Intaj’s voice or indeed his words. He continued. “The old mammalian part of the brain includes the hypothalamus, hippocampus, amygdala, and cingulate cortex. This takes care of our emotions and memory. The youngest part …evolutionarily speaking is the neo-cortex. It enables language, reasoning, and planning.”

He laughed.

 “Carl Sagan…once said … “  on the outside, living in uneasy truce with the more primitive brains beneath, is the cerebral cortex; civilization is a product of the cerebral cortex.” Then Dr. Nanda stopped. The looks on Intaj’s and Dighe’s faces telegraphed clearly that they had no clue who Carl Sagan was.

 Dr. Nanda sighed.

 Intaj and Dighe were confused but their singularity of purpose did not allow them to mentally disintegrate under incomprehensibility.

Dighe mumbled. “Brains got more and more complex as animals evolved. As humans we have the most evolved brains of all. So, we have three brains in one.”

“Yes, and it is my practice to start by repairing the oldest part of the brain first and then make our way to the newest.”

“And once even the newest part of the brain is repaired; Baqir will be like before!” Intaj’s eyes filled with tears. Anyone seeing him now would have trouble reconciling him with the bloodthirsty mafia don; the scarred survivor of many underworld battles. He was simply the father who was willing to accept even a five per cent chance of recovery.

 “One step at a time…first we will need stem cells.”

Dighe burst out. “Are there banks…like blood banks, we can buy…money is no object.”

Dr. Nanda stared at Dighe for a minute and then replied, “No…there are no stem cell banks. Usually all experimental protocols call for stem cells to be harvested from the patient but I see, from his reports, that in Baqir’s case that is not possible.”

“So, Dr. Nanda…if we cannot collect Baqir’s stem cells…does that mean we brought him here only to return empty-handed. On the phone you reassured us that…”

Dr. Nanda raised his hands to stop Dighe who was in full flow.

“I did not say that we cannot do anything for Baqir. I have something radical in mind. I can do SOMETHING for Baqir but it has only been done twice before. The first patient died during the operation and the second one is still in recovery. You may think of it as an experimental protocol…but apart from this I see no other option. Any—where—in –the –world.”

Intaj and Dighe nodded. Manya blinked. The three of them knew what Dr. Nanda was saying was true. There was no established treatment protocol ANYWHERE in the world. Dr. Kar had explained to them that Dr. Nanda’s protocol had only been tried out twice before. It was a gamble. What other choice did they have? Dr. Kar had said Baqir could last for years in this state or he could die suddenly of a stroke. Life itself was a gamble. Intaj’s clenched jaw betrayed his inner turmoil. However, his voice was soft as he said, “Dr. Nanda, I am listening.”

“I understand none of you have a back ground of science so I will simplify my explanation. Please feel free to interrupt or ask for more clarification. Mr. Munir please come and join us.”

Manya took the last of the free chairs across the table from Dr. Nanda. “Please, go on Sir,” he said. He was feeling a little scared because it was he, who had raised the possibility of using stem cells to treat Baqir and now, it was happening. No one…not even the doctors were confident. What if Baqir died? Would he be blamed?

Dr. Nanda began with a simple statement. “Hmm… all of us have backbones, right?”

The three men nodded.

“Well, in the very early days of evolution there was just a stiff rod of cartilage called noto-chord. You know what cartilage is, don’t you? Our external ears are made of cartilage. So, go on feel your ears…”

The three did as instructed.

“Cartilage is a tremendously strong and flexible fibrous tissue. However, it is not bone. A noto-chord is a sort of precursor backbone. Any animal that has a noto-chord is called a chordate.”

Manya asked, “Did the noto-chord evolve to become the back bone in more advanced species?”

“Yes, the vertebral column replaced the noto-chord in the more advanced species. These creatures are called vertebrates.”

Manya blurted out. “I know the word vertebrate…human beings are vertebrates. They taught us in school.”

Dr. Nanda smiled encouragingly at him. “Indeed. You see the back bone we have is also called the vertebral column. It serves as protection for the spinal cord which is an extension of the brain.”

Brain! The word made Intaj and Dighe sit up…all this talk about noto-chord and vertebrates had passed over their heads. However, with brain they were back on terra firma.

Dr. Nanda continued with his practiced spiel. “Remember I told you about the most ancient part of our brains…well to repair it we have to go back in evolution to find one of the first chordates…the one with the first-ever noto-chord and take stem cells from it. A primitive organism has to be found to harvest primitive stem cells to repair the most primitive part of the brain.”

Dr. Kar interjected. “This was first postulated by American scientists at Stanford University.  They showed that cells from a very distant human evolutionary ancestor – can be used correct tissue abnormalities. We think a similar regenerative process might be possible in people.”

Dr. Nanda agreed, “Yes, damaged organs can be coaxed to regenerate. Tissues can self-heal. Cut skin, scarred hearts, broken bones, damaged nerves and torn muscles always try to repair themselves, but total success is never achieved naturally. We have to augment the ability to heal.”

“You will repair Baqir’s brain; beginning with the most primitive part first…the foundation on which the newly-evolved brain rests…” Intaj mused.

Dighe asked, “Do you have a donor organism in mind?”

“Life first bloomed in the sea. The first chordate is also a marine creature. Stem cells have been harvested from it.”

“Really?”

“Yes, really!  It is the sea-squirt. Sea-squirts are chordates; actually the Grand-mummy of all chordates with a lineage lost in the antiquity of time. Baby sea-squirts have primitive spinal cords.”

Dighe objected. “Yes but why should scientists across the world be interested in stem cells from this primitive chor…chor…date?”

“Scientists believe that sea-squirts are very like what the very first human chordate ancestor was…about 550 million years ago.”

The collective gasp from Intaj, Manya and Dighe made Dr. Kar smile. Nanda has caught their attention alright, he thought.

Meanwhile, Dr. Nanda ploughed on. “See, manipulating stem cells to differentiate into chosen types of tissues and organs is a major goal of biomedical science. Now, the genome…that is the genes of sea-squirts predates the dramatic increase in genetic-complexity that we see in modern vertebrates. Therefore, the sea squirt is the basic template for decoding vertebrate genomes. The sea-squirt genes are the letters with which the book of vertebrates is written.”

Intaj and Dighe did not understand much but Manya shook his head. He had understood a large part of the argument. “I have two questions,” he said and Dr. Nanda looked encouragingly at him.

“First. Did the evolution of back bones happen from sea-squirts onwards?”

Dr. Nanda nodded Yes. “Evolution moves forward you know; things improve. From cartilaginous noto-chord we evolved to have a bony backbone. From swimming in the oceans, we evolved to crawling on land. From crawling on fours, evolution taught us to stand on two legs. Evolution is going forward.”

Dighe and Intaj nodded in agreement. What the learned doctor was saying was true. Humans evolved from monkeys. Evolution was a forward-moving force!

Manya went on. “Second, if the sea-squirt is going to be the donor animal of choice for repairing the primitive part of the brain…the reptilian part…. which animal are you going to use to repair the most recent part of the brain…the part where our intelligence…our human-ness lies?”

Intaj and Dighe sat up straight…they had not thought about this. Thank God they had Manya with them. Youngsters were so smart; young brains after all! Baqir’s brain was going to be repaired bit by bit by bit. So, after the sea-squirt stem cells succeeded in repairing the reptilian brain, they needed to have the next round of stem cells ready. Deep in his heart Dighe hoped Dr. Nanda would not say monkeys. Baqir was naughty enough without monkey genes in his brain.

Dr. Nanda said, “Dolphins.”

 “Why dolphins?” stammered Intaj. “Because these live in the seas with sea-squirts?”

“No.” Dr. Nanda smiled steepling his fingers. “Dolphins, because these are intelligent creatures with brain development equal to or even better than ours. Bottlenose dolphins have bigger brains than humans although the brain to body weight ratio is less than ours. As far as brain development is concerned these are the second-most “brainy” animals on Earth. In biological terms we say encephalized!”

Manya’s mouth opened and closed twice before he actually got some sounds out. “Dolphins live deep in the sea…how are you going to catch one; let alone collect stem cells?”

Dr. Nanda giggled. It was a little creepy to hear a respected medical researcher giggle but what he said brought smiles to the wan faces of the three listeners. “There are dolphin stem cells available for research. You see Bottlenose dolphins suffer from diabetes, kidney and liver ailments just like us. Stem cells from dolphins have been collected from their umbilical cord and successfully used to cure ailments of the liver, kidney and pancreas in humans.”

“But…but…doctor,” Manya appeared to be struggling with his thoughts. “Surely dolphin stem cells will give rise to dolphin muscle cells or dolphin nerve cells…not human cells.”

Dr. Nanda sat up straight. He had not expected this question but was happy to explain. “Stem cells can be nudged to grow into any type of cell that we want.  As we are using non-human stem cells, we will use human growth factors in the liquid in which the stem cells will be suspended. These growth factors will gently nudge the stem cells to produce cells that are compatible with the human system. Do not fear rejection. That will not happen.”

Dr. Nanda looked at the three upturned faces. Then he added,
“The additional good news is that dolphins can completely repair tissue —— without any scar mark on their bodies to indicate where the tissue has healed.  They get this regenerative ability from special stem cells in their skins. Missing flesh, along with the associated fat or blubber, plus blood vessels and nerve connections are regenerated without leaving a mark! Think how powerful dolphin stem cells are! Because we deal with trauma, my hospital actually maintains a line of stem cells from dolphins. So, sourcing that is not going to be a problem.”

He smiled. “Any other questions?”

Manya asked, “Has repair of the higher brain using stem cells from dolphins ever been attempted before?”

The smile vanished. “There have been reports from North Korea that indicated mixed results; apparently if it works it works.”

Dighe said, “Sea-squirts and dolphins…these are animals after all…will the human body accept?” He broke off mid-sentence.

Dr. Nanda reassured them confidently, “The basic neuronal stem cell biology is similar in all mammals…and the sea-squirt is at the base of every chordate family tree…it belongs to all of us…like the very first Grand-mother.”

Intaj let out a long and weary sigh. “It is in now the hands of the Almighty…we have exhausted all other options. Noor, you cannot say I did not try.”

Dr. Kar said. “Ok then…let us move forward. We have full facilities for your stay. You have to sign documents waiving your rights to prosecute us or the research centre or the government should anything go wrong. This is a military research hospital. You will also have to agree not to speak with the Press or post anything in social media.”

Internal report 1

The condition of the first patient who was brain-damaged following a violent brawl in the barracks is said to be improving.  He is slated to undergo a second round of stem cell treatment in a weeks’ time under Dr. Nanda’s care. The stem cells will be sourced from dolphins.

Newspaper reports

Mahabir Rana, the first recipient of Dr. Nanda’s pioneering experimental protocol for brain regeneration has been shifted to the Orthopedic Ward following an unforeseen complication. Dr. Nanda said the orthopaedic complication could not and should not be linked to brain regeneration attempts because the neural and the skeletal systems are two totally different systems.

The second patient; a civilian remains in Critical care.

Whatsapp news forwarded by the Rana family 

Our beloved Mahabir Rana was hastily cremated by the hospital. Why was his body not handed over to us? Did the authorities wish to eliminate evidence? According to the Wardboy who handled the corpse, and who now appears to have vanished, Mahabir’s body flopped about like a guy with no bones. We will be writing to the PM. We will hold a candle light vigil outside the hospital.

Dr. Nanda’s Research Centre

Intaj, Dighe and Manya had been allowed up into the observation gallery as Dr. Nanda injected the special cocktail of stem cells and nutritive fluids all along the backbone and at the base of the skull. There was no incision and no sutures were needed. Indeed, there was little if any trauma, to the already damaged brain thought Intaj. Later, he asked, “Dr. Nanda, why did you inject seas squirt-stem cells all along the spine?”

“Good question. You see every human foetus has a noto-chord. It is a salute to its chordate past. As it grows, the bony backbone replaces the noto-chord, which becomes part of the discs that separate the bony vertebrae that protect the spinal cord. I have injected stem cells into and around these cartilaginous discs near the spinal cord to help jump-start the regenerative process up and down the spine. I have also used copious amounts of human cell growth factors. These will help to make the sea-squirt’s stem cells develop into human nerve cells.”

“So, you are targeting the spine as well as the brain from where it originates.”

“Yes.”

Dr. Nanda’s private notes

Baqir’s condition continues to be stable but there are early signs that Mahabir Rana’s condition is being replicated in Baqir too. His father appears to have sensed that something is amiss. I have to ally his fears for a while.

It is obvious that sea-squirt biology is to be blamed. Evolution does not always move forward. Evolution always facilitates survival; even if that is by going backwards. Washing the slate clean and making a fresh start with a slightly more evolved chordate may be the way to go. Baqir’s body poses no problem; the hospital’s incinerator is good enough. I just have to concoct a story that Baqir had an infection that killed him… and that we cannot risk releasing his body because of a risk that the infection will spread.

***

 Intaj was frantic with worry. While Baqir had definitely improved following the first round of inoculations. He had even tried to speak. Yet, something was definitely wrong. Intaj had noted that when the nurses attempted to shift him because they needed to change the sheets, Baqir’s body flopped a lot. However, Dr. Nanda brushed aside his concern saying it was loss of muscle tone because Baqir had been lying in bed for so long. He prescribed additional physiotherapy and more vitamins.

But by the next week it became clear that Baqir was not progressing at all. If anything, he was reverting to a state that was worse than what he had been when they had brought him to the military hospital.

Dr. Kar was brutally honest. “We made a mistake by choosing sea-squirt stem cells. We would have been better off choosing its cousins, the fish-like lancelets.”

Manya cried out, “Why? Why do you say so…has the experiment failed?”

 “The experiment has worked…it has worked much better than I thought but I am afraid it is too late for Baqir. You see while the sea-squirt is indeed the earliest of all chordates…it has a peculiar life cycle. Once the free-swimming, notochord-containing, sea-squirt larva settles down somewhere, the notochord is absorbed. It disappears. The sea-squirt cannot move now. It becomes attached to the surface”

“So? How does it affect Baqir? I mean if an adult sea-squirt loses its notochord and becomes sessile…why should that worry us? All we took were a few stem cells…after that the sea- squirt can go do what it likes…how does it impact Baqir?”

“Listen closely. The sea-squirt is a chordate alright. It has a notochord. However, the notochord does not persist lifelong. In time the sea-squirt loses its notochord; much like a tadpole loses its tail. When we injected chordate stem cells, we wanted these to enervate the primitive nervous system…to start by jacking up the nervous system by its roots so to say…and it did. Initially, that is. The stem cells from the sea-squirt’s notochord meshed with the remnants of human notochord in the inter-vertebral discs. The cells recognized each other. The injections worked on the inter-vertebral discs and secretions from it energised the spine and signals went right up to the brain. You saw it. Baqir spoke a few words too. Right?”

Intaj, Dighe and Manya stared mutely at the doctor, sensing the approach of impending doom but not knowing what was happening or from which direction the bad news would strike.

Dr. Kar continued; his face impassive. “These stem cells gave rise to nerve cells just like we wanted them to. Some even went on to form notochord cells and propped  up the discs.

“If everything went the way you wanted it to…what is the problem?” Manya sounded quite aggressive.

 “The problem is that sea-squirt notochord cells are genetically programmed to self-destruct.”

“Why would the notochord cells be genetically pre-programmed to self-destruct?”

“No one knows why an adult sea-squirt no longer needs a notochord but their notochord cells die.”

“Is this what happened to the sea-squirt notochord cells inside Baqir?”

“As the notochord cells began to self-destruct- the intervertebral discs began to weaken, dissolve and collapse. The notochord cells play an important role in signalling to surrounding tissues and in influencing the skeletal elements of the developing embryo. In Baqir’s case, the disappearing notochord triggered a meltdown of skeletal elements as well. That is why Baqir appeared to be wobbly that day when the nurses shifted him. His backbone has dissolved into nothingness. Effectively, he is almost—an invertebrate.”

Dr. Nanda’s private notes

The Director of the hospital has been most kind. He has agreed to let me wipe the slate clean and begin again; this time using the notochord cells from the lancelet fishes which are a step higher up than sea-squirts in chordate hierarchy. I think he is also impressed with my ability to rebound from a setback. Brain regeneration is a huge step that the army is interested in.

 Now to turn the page and move on.