CHAPTER 4

Agarwal Rakesh 

Agarwal and his wife hardy ever talk shop at home. He might make a brief announcement if there is good news. Perhaps if one of his papers is accepted by a top journal, or he receives an invitation to speak at a notable, overseas location. Other than that, he leaves work matters at the lab before driving home. In any case, Agarwal has always considered that Myra’s experience as a business analyst does not equip her with an appropriate skill-set to offer career advice to a protein biochemist. And vice versa. He does not encourage his wife to share her own office dramas. Consequently, it is a surprise when Myra enters their bedroom to question him while he accumulates piles of clothes on his side of the split, king-sized bed. He is preparing to pack for his flight to New Orleans early tomorrow. 

It also puzzles him that her words seem to drip with suspicion. “You seem upbeat this evening. “You’re typically a little jaded about the thought of traveling.”

He steps on his toes to retrieve a suitcase from their closet’s highest shelf, as he wonders why it is problematic that he might be happy in his preparations to visit New Orleans for a meeting of the American Academy of Gerontologists. “It's different being one of the organizers,” Agarwal explains. “I'll be in the limelight.” 

He has his back to her when a sharp pain shoots through his groin. He prays he hides the discomfort from Myra. She has been nagging him about his hip for some months. Are you keeping up with the physical therapy exercises? Are you working on losing weight?

“Also, I’m hyped about my presentation.” He turns to face her, careful not to reveal his  discomfort, and places the carry-on upon a surplus towel that he has previously laid over the white storage ottoman at the foot of their bed. The towel keeps him out of trouble. According to Myra, white upholstery is a magnet for the dirt that inevitably accumulates on travel bags. “I’m going to show some of Steve’s unpublished data. He’s been working with a new kinase inhibitor.  It’s a candidate anti-aging drug that we’ve been testing in cultured cells. It repairs the damage caused by high metabolism and inflammation.”

Even that abbreviated account of his recent work contains more information than he would typically provide, but there again, she did ask why he was in a good mood. 

“Really?” She does not give up. “I thought you never show unpublished data at a conference. You’ve told me it’s too risky, because a competing lab might reproduce your work, publish it first, and steal all of the credit. So, what’s changed? Have you decided you could weaponize Deepak? It would be gratifying if he could finally make one positive contribution to our lives.”

In deference to he and his brother being tight, Myra usually avoids criticizing Deepak directly. But she is not averse to occasional innuendo. She dislikes that he is pompous, arrogant and ostentatious, whereas Agarwal views these characteristics as worthy credentials. Because they have helped Deepak become a highly-successful DC attorney. 

“Unlike your corporate world,” Agarwal counters, “any disputes that we might have with our competitors are not resolved through lawsuits.”

He refrains from pointing out that scientific disagreements are, in fact, rarely resolved; there is no judge and jury, no formal arbitration process to turn to. Occasionally there may be a long meeting, or a conference phone call, at which the participants each express their views, but the outcome is one that makes nobody happy. More often, the victor of a dispute is the one who works behind the scenes with the more effective badmouth. 

“Anyway, we don’t fear being scooped.”

“Why not?” Myra asks.

There is a long answer to that question. 

His lab’s unpublished data are included in a manuscript he submitted to a journal several weeks ago. He had requested the paper be handled by the same editor he had recently met at a conference. It had been a fortuitous opportunity. Editors act as gatekeepers – they decide whether or not to send a manuscript out for peer review. If they reject the paper, it is also their job to invent the excuse. The specifics of the study are rarely impugned, because that would encourage the authors to email back with counter-arguments. And digital dialog is not the objective. Instead, a paper will be rejected through generalities that are too vague to be refuted. It may be the study is deemed too broad in scope for the journal’s specialized readership. Or too specialized for a journal’s multidisciplinary audience. 

Agarwal had subverted this triage system by convincing the editor that it would be in the journal’s interest to publish his work. Because, he had claimed, his study directly connects with the most popular hashtags for life extension: #Longevity and #HealthyAging. This in turn will ensure a high citation rate, so the journal will attract larger numbers of famous scientists (along with their publication fees), and their academic libraries (and their journal subscription fees).  

He had also won the duel with the journal over their choice of referees for his study. He had successfully excluded key rivals (by inferring they were biased competitors), and indirectly recruited his friendly kinase colleagues (by heavily citing them in the manuscript, so as to advertise their expertise to judge his work). They had loved his paper. Only one small additional experiment had been requested, plus minor changes to the text. One week to do that, Steve had calculated. 

He provides a much shorter answer to Myra. “The paper has essentially already been accepted. It should be posted on-line within two to three weeks. We have also identified who are our main rivals among the conference delegates. None of them have the capacity to take advantage of our new results within such a short time line.” 

Myra presets him with a smirk of superiority to accompany the hands on her hips. “You’ve always been scornful of the corporate world’s methods and constraints. And yet, here you are, borrowing techniques from the business sector. Scenario analysis, competitive profiling and risk assessment.”

Agarwal has the urge to dispute this idea that their working lives are somehow similar. Debate is an instinctive reaction for a scientist. It is natural for them to stress-test hypotheses, challenge methodologies, and question presented data. He could assert that academic research is pursuit of knowledge for its own sake. As such, it sits above the fray of private sector science, that is driven solely by profit margins. 

He will not throw that argument at Myra. Even he thinks it is bullshit; only minutes earlier, acting as a salesman, he had claimed that his studies may lead to improved therapy for ageing. That is precisely how he justifies his applications for research funding. Because science in an academic setting is all about whatever it takes to generate income for the lab.

In any case, Agarwal knows there are occasions in his domestic life when being argumentative, or even just expressing an opinion, is simply a bad idea. He recognizes this is one of those situations. Similar to the time when he did not fight Myra’s desire to decorate their bedroom walls with abstract art. One blurry painting might be an attempt to depict ghostly trees shrouded in mist. In another, an unnatural cloud formation meets a surreal horizon of unrealistically static water. She calls it spontaneous brushwork, and claims it brings tranquility to the room. He has never voiced his distress at either the lack of structural clarity in these images, or their four-figure price-tag. He wishes it were possible to receive relationship credit for those occasions when he did not speak out. 

Myra, however, is determined to pursue a point of view. “Maybe our two careers are more aligned than you thought?”

He suspects an undertone. An emotional plea perhaps, but encrypted as passive communication. A message that could only be accurately decoded if he were able to read her mind. It would be good for us to talk more about work. Is that the hidden meaning? Or perhaps the request is more ominous. It would be good for us to talk more. 

It is not in his design to confront a relationship problem. He treats it like a check engine light. His inclination is to wait for a problem to simply fade away. So, he says nothing.

Unimpressed by his silence, she retaliates by criticizing the attitude he takes towards his unreliable hip. He is informed he could work on that problem by losing ten pounds. She follows up that initial volley with a new accusation that he is going from stocky to flabby, and the extra weight is not attractive.  

Agarwal is not too perturbed by the thinly veiled threat of less frequent sex. He feels it is his fate anyway. An inevitable consequence of having the same partner for almost 35 years. By which time, he thinks, it is normal that enthusiasm cools - the Coolidge effect. An unintentionally apropos moniker that Agarwal has gleaned from the scientific literature. It designates a phenomenon that has not only been observed in humans, but also in other mammals. It is named after the 30th US President, who allegedly disappointed the First Lady with his lack of enthusiasm for the physical side of their long marriage. 

As for the accusation that he carries too much fat? No, he tells himself that Myra’s elfin physique is the outlier. She is forever adjusting clothing purchases with her sewing machine so as to fit a double zero anatomy. That, he had decided, is a biased marker for determining what qualifies as being overweight. Everyone she knows is bulkier than her.

Nevertheless, he grudgingly gives his agreement to perform more exercise when he returns home, but not because he actually intends to. He just wants to quieten his wife, finish packing, and get some sleep. Hopefully uninterrupted by one of those extended and frustrating dreams in which he is unable to reach the airport before his flight takes off.

It is eight o'clock, the evening before the conference begins, as Agarwal passes through the bollards that pedestrianize Bourbon Street, at its southwest boundary with Canal Street. He knows he cannot return home from New Orleans without visiting this famous area. Even though Deepak had told him it has gone downhill. 

The high earlier that day had surpassed eighty, which is unusual for mid-March. The warmth lingers, so Agarwal is troubled by the extent to which young women underdress.

Throngs of inebriated visitors funnel through the narrow roadway in both directions. He has read somewhere that if you stand still for just one minute, over a hundred people will walk past. It would be a larger number, he concluded, if a normal walking pace were possible. 

It is much louder than he had expected. Partly because voices elevated by excitement and alcohol reverberate off the brick and stucco buildings that flank this narrow street. There are also tap dancers, who amplify their dance routines with shoes to which bottle caps or the bottoms of steel cans are attached. Plastic builder’s buckets are repurposed as drum kits.

Each intersection is guarded by either local police on horseback, or State Troopers with their distinctive brimmed hats and shiny cars. One of their policing accomplishments had been in the news the previous month. An arrest of a street hawker for disobeying a court order prohibiting public displays of an albino python. Agarwal knows these reptiles are not venomous, so the tourists were not in danger. The real question is whether the rule of law is applied evenly. He sees evidence that dealers are comfortable taking care of business on the side streets. Drugs might be fine, but zero tolerance for harmless snakes. 

He is both surprised and disappointed that the street does not offer a cultural harvest of vibrant blues and jazz joints. There are just invasive weeds: strip clubs, tacky T-shirt stores, and hole-in-the-wall bars where Agarwal learns of a new social aspiration. Being photographed double fisting a pair of fluorescent high-alcohol cocktails: hand-grenades.

Young male revelers leer over balconies, broadcasting bead necklaces and catcalls: “let’s see your tits!” Their tone is aggressive, almost menacing. As if they are releasing all of their pent-up outrage that wolf whistles have become culturally outlawed. And yet, despite their belligerence, a couple of obliging blouses are raised. Agarwal looks away in embarrassment.

A steamy bar draws his attention. At first, it is the dangerously relaxed attitude towards building capacity that catches his eye. Then he sees that among those who struggle for service are a group Agarwal recognizes from the conference, members of the information theory caucus. These researchers share the belief that the molecular instructions to defy aging remain with us all, immutably, and it is the ability to read this information that becomes corrupted over time. Reverse those miscues, and our innate anti-aging protocols will all be refreshed.

This concept grew out of a description of epigenetic reprogramming in the early embryo, the process of erasing markers of aging that are inherited from the egg and sperm. This was a startling demonstration that human cells can naturally rejuvenate into a younger version of themselves. Suddenly, rejuvenation became a buzzword among a certain section of the aging research community: could youth be regained experimentally? Absolutely. So says a Harvard geneticist, David Sinclair. He has claimed that his lab partially rejuvenated cultured cells after they were either genetically manipulated, or treated with a bespoke chemical cocktail. This announcement was accompanied by a barrage of his dramatic media bites. We can reverse human aging! In a decade there will be a pill to rejuvenate youth! There is no biological limit to human lifespan! 

Agarwal had naively proposed Sinclair be invited to speak at the AAG meeting, but the other co-organizers had vetoed the idea. Have you heard about Sirtris Pharmaceuticals? They explained that Sinclair had created this company on the foundation that sirtuin is an anti-aging protein that is stimulated by resveratrol, the red wine compound. In 2008, Sirtris and its promise of an elixir of youth were sold to GlaxoSmithKline for the tidy sum of $720 million. However, clinical trials faltered, and the magic of resveratrol was exposed as the ultimate of scientific smackdowns: an assay artifact in Sinclair’s lab. Undaunted, he banked his share of the GSK buy-out, swapped out labels on the bottle, and cofounded Tally Health, a company that markets an alternative longevity supplement. It still retains resveratrol as one of its alleged active ingredients.

The co-organizers had hurled other accusations. The same diatribes are in abundance on the internet, on Facebook and X; in YouTube videos. Sinclair is conning people. He’s a snake oil salesman. And there are dire warnings too. Is cellular rejuvenation therapy doomed to induce cancer?

Agarwal had countered by raising the possibility of some professional jealousy. In a system in which competition for limited research funding has become so intense, what are our options? Hyperbole – even if it sometimes ascends into flights of fancy – is now an essential monetary strategy. One that Sinclair happens to master more successfully on a much grander scale. He is a leading social media influencer, a virtuoso of self-promotion. Small wonder that the level of his lab resources spreads envy among his scientific competitors. Some may be business rivals too, as anti-aging startups look to take advantage of a flood of venture capital. Can we trust Sinclair’s detractors to be completely unbiased? In this field, a conflict of interest is less a red line, and more a fuzzy contour. But Agarwal’s point of view had been soundly rejected. 

Controversy inevitably bubbles to the surface of a sea of chaos. Which, as far as Agarwal can deduce, is the current status of aging research. That became clear to him during his first conclave with the organizing committee; he had been shown the results of a survey circulated to those who had attended the previous AAG symposium. The questionnaire had included the most fundamental of questions: what causes aging? Surely a consensus could be expected to emerge from an international panel of the leaders in this area of research.  

The sole source of agreement? A dislike of surveys. Less than half of those polled took the time to respond.

The answers that were received underscored the state of discord between the advocates of multiple, competing theories concerning how and why we age. No single proposal garnered goodwill. As if the prize is more important than the process; the prestige that comes from being the one who solves the problem is more important than the solution itself.  

Couldn’t these researchers have managed just one point of agreement? Agarwal had assumed loss of function – too little of something – would be a unifying point. For example, too little telomerase enzyme, and hence the erosion of telomeres, those DNA sequences that act as shoelace sheaths; once worn out, either the shoelace or the chromosome unravels. But no, he had been surprised to learn there is an antithetical theorem: hyperfunctionality. The too much hypothesis. Too much fat, or blood pressure, or blood clotting. Tumors arise from too many cells. Male pattern baldness is the result of too much dihydrotestosterone.

Some in the survey – the wear-and-tear clique – had banded together to denounce both the information theorists and their aversion to the hypothesis that aging arises from the accumulation of molecular and cellular injuries. Not that the latter concept is built on unanimity. There is intense disagreement over the origin and functional significance of the damage. Is it causation or correlation? Is it sustained at the genetic, protein, or cellular level? Is it increased damage or decreased ability to repair? 

All of this disharmony discourages Agarwal from approaching the group in the bar. This is so unlike conferences with his kinase colleagues. He views them as far more collegiate. Like Roger Spinnit, who is always willing to share his reagents to everyone in the field. Such as SP-210, which was key to the success of Agarwal’s recent paper. And Traci Weber, who has invited him to visit her institute next month, to give a seminar. Nick Robbins – yes, he is rather full of himself – but last month in Texas he had expressed the importance of protecting Chuck Standish’s legacy. That is true camaraderie. 

Chuck Standish. He feels sad for those who were directly impacted by this killing. Standish’s close friend Barry Pike for example, who went into retirement shortly afterwards. And Roger Spinnit. On the morning the remains had been discovered, all of the attendees were obliged to provide statements to the police, but poor Spinnit was taken away for further questioning. Voluntarily, they said. His career never fully recovered from the stigma. Even though no charges were filed. How could they be? There was no motive. Scientists have no need to resort to murder. They can be content with simply wreaking vengeance upon a competitor’s reputation. Usually behind their back, in the conference bar. Or by writing about it, typically in an article that reviews the current status of the field.

Agarwal doomscrolls deeper into his dark memories of the tragedy. The shock of the event, and the termination of the last day of the conference (and his own presentation, damnit!). The stress of his own police interview. The terrible passing of a colleague he is proud to have collaborated with. He is suddenly very drained and lost. Like he has unplugged from his physical body, and is now as formless as Myra's abstract wall art. 

It is being bumped by a staggering drunk that reconnects him. That, and the street’s unwelcome smelling salts. An earthy aroma of manure, the pungency of urine, and the sulfurous odor of cannabis. 

There is a disturbance ahead. Between two groups of inebriated young men, naturally. “Come down here and say that”, shout those in the street, arms wide and beckoning. “How ‘bout you come up here,” is the response from the balcony.  

The confrontation reinforces his distress. Being unhappy in a crowd of strangers is a sure way to become lonely. He turns back towards the hotel, dodging discarded beads, and pools of fluorescent green vomit. All-in-all, Agarwal concludes, this is one sordid theme park. A Westworld scenario, but without assistance from androids. Even the daily sanitation routine is a nod to the 1973 movie: before dawn every morning a cleanup crew is on site. This true-life version is armed with disinfectant spray, mechanical sweepers, and high-pressure hoses. 

And everyone turns a blind eye as the debris is flushed into the bayous.

By nine-thirty Agarwal is in bed, texting Deepak. You are dead right. Bourbon Street is terrible.