A landmark study conducted by researchers at the Centre for Addiction and Mental Health (CAMH) found elevated levels of a brain protein associated with chronic stress and anxiety in the brains of young long-term cannabis users.

Published on September 18 in the JAMA Psychiatry medical journal, this study was one of the first to use the Positron Emission Tomography (PET), an imaging technique, to study the association between cannabis and the neuro-immune function in the brain.

The brain protein that was studied is called a translocator protein, or TSPO. It is involved in immune functions and is associated with levels of stress and anxiety.

In an interview with The Varsity, Dr. Romina Mizrahi, the lead author of the study and Senior Scientist at the CAMH Research Imaging Centre, talked about the motivation behind the research.

“Young people use cannabis a lot and they usually think or perceive cannabis as harmless,” she said.

“I, as a scientist, I know that the brain develops and is still developing until the age of 25, so I wanted to understand how cannabis affects the developing brain.”

The study’s design and results

Mizrahi and her co-authors conducted the study in Toronto. The participants included 24 long-term cannabis users, who met the criteria for Cannabis Use Disorder (CUD).

The study also consisted of 27 non-cannabis users, who acted as the control group to compare the protein levels in the brain.

Each participant underwent a scan with the PET imaging technique, which the researchers used to measure the subjects’ levels of TSPO.

The study found that long-term cannabis users had significantly higher levels of the biomarker associated with stress and anxiety compared to the non-users.

Limitations of the study

Mizrahi warns readers, however, that this experiment only studied the relationship between cannabis use and the biomarker associated with stress.

While she and her co-authors studied the biomarker’s levels, they did not examine the impact of its elevated levels on the subjects’ behaviour. The study therefore does not provide a direct link between long-term cannabis use and the symptoms of stress and anxiety.

“We cannot say that cannabis causes this increase in this protein or that it causes stress and anxiety,” said Mizrahi. “We know they are related, but we don’t know which comes first.”

However, Mizrahi spoke about the potential future research that aims to study causation. Such studies could also examine whether the biomarker’s levels would normalize after a period of abstinence for long-term cannabis users.

These findings could refine research and have major future implications regarding attitudes toward the consumption of cannabis for adolescents.

Effects of cannabis on the developing brain still unknown

Mizrahi still added that she would caution adolescents against using cannabis due to their developing brains.

“What I would tell them is that they should be careful when using cannabis because their brains are still developing until the age of 25,” she said. “Whether [the effects are] long-term or short-term, we need to study this moving forward.”

“But I would still caution them not to use cannabis. To use or to not use cannabis while the brain is developing… is an important decision [that adolescents] have to make.”

Dr. Jay Stephen Keystone, a travel and tropical medicine specialist at the Toronto General Hospital and a professor of medicine at U of T, passed away from cancer while surrounded by family on September 3. He was 76 years old.

He is remembered fondly for his empathy and frequent use of humour as he trained residents, treated patients, and worked with colleagues through difficult days in the hospital.

“When people found out he had passed away, there was an outpouring of love and support from people all over the country and even worldwide,” said Dr. Isaac Bogoch, a close friend and colleague of Keystone, to The Varsity.

Bogoch recalled that Keystone fostered a working environment “where you don’t really recognize that it’s work, because you’re enjoying yourself too much.”

“He’d always be smiling and enjoying life along the way,” even on days with heavy workloads, said Bogoch. “That’s one thing I certainly picked up from him.”

Keystone’s empathy in medical education

Dr. Sumontra Chakrabarti, who is now an infectious disease specialist at Trillium Health Partners, recalled his time working with Keystone as a resident for three years. He recounts those years as some of the “most enriching” of his career.

He wrote to The Varsity that Keystone was a “very outgoing, friendly and warm individual” with a “larger than life presence.” He attributed Keystone’s personality in large part to his “amazing sense of humour, that made everyone around him smile.”

“From a resident’s standpoint,” continued Chakrabarti, “any room Dr. Keystone was in, was one guaranteed to be relaxed, jovial, and a place where you would leave knowing much more than when you walked in.”

“It was because of him [that] I have pursued my special interest of tropical infections within my infectious diseases practice,” wrote Chakrabarti. “The type of clinician I am today is in large part my efforts to emulate the type of physician he was.”

Dr. Christopher David Naylor, the former president of U of T, also commented on the empathy of Keystone’s mentorship style, which sharply contrasted the approach that other medical educators used at the time.

“What stood out is that he was humble and kind to his students and residents at a time when, frankly, some of the older clinical teachers were into ritualized humiliation as a mode of instruction,” wrote Naylor.

Naylor also recalled one incident from Keystone’s education that he would never forget.

It involved Keystone teaching medical students that Ascaris lumbricoides infections could be almost asymptomatic. This means that, in Keystone’s words, on many occasions the only “presenting symptom of the patient [would] be horror.’’

“Why?” Keystone would ask rhetorically, “Well, how would you feel if you defecated and found a large worm wriggling in the toilet bowl?”

Keystone’s impact on clinical research

Reflecting on Keystone’s research, Naylor highlighted how he brought the Canadian medical community’s attention to the implications of globalization on the spread of infectious diseases at a time when its impact was not widely recognized.

Keystone graduated as a gold medallist in the U of T Medical School’s class of 1969, and conducted postgraduate work and fieldwork on multiple continents. He returned to Toronto in 1977 to found and lead the Tropical Medicine Unit at the Toronto General Hospital.

His legacy includes more than 200 scientific papers and textbook chapters that he co-authored, a premier travel medicine textbook he wrote as a senior author, and the organizations he was a part of, including the International Society of Travel Medicine where he served as president.

In 2015, he received the Order of Canada for his contributions to tropical and travel medicine.

But despite Keystone’s stature, wrote Naylor, “Jay himself often said that his greatest professional accomplishment was to teach himself out of a job.”

In an article published in May, co-authored with twin brother and rheumatologist Dr. Edward Keystone, Dr. Jay Keystone encouraged those reading “to think about the people who made an impact or provided you with mentorship, and how you can pay it forward to others.”

This fits with Dr. Jay Keystone’s approach to education. In Naylor’s words, Keystone was “involved in inspiring, recruiting, and educating literally hundreds of postgraduate medical trainees.”

“Those individuals, practising all across the country and all over the world, along with his beloved family, are Jay’s living legacy and most important gift to the world.”

How do male black widow spiders find potential mates? According to a recent UTSC-affiliated study, they follow the silk trails left by their competitors.

In a majority of mate-seeking insect species, the males follow pheromones — chemicals released by an individual of the same species — in order to find available mates. Traditional thinking would suggest that males follow pheromones from female spiders, while avoiding those released by males, to prevent any vicious competition during courtship.

However, according to the study’s results, the male black widow spider instead leverages the scent and the silk trails released by other males to efficiently find potential mates.

The motivation for the adaptation

The reproductive success of the black male widow spider hinges on its ability to locate a potential mate as quickly as possible, due to the low number of available female black widow spiders and lengthy courtship behaviour.

“On any given night, there are only a handful of sexually receptive females. Hence competition is inevitable,” explained Catherine Scott, the study’s author and a PhD candidate at UTSC, to The Varsity.

“Furthermore, courtship can last hours. So, even if a male is not the first to arrive and if he gets to the female quickly enough, he might just be able to win the competition and be the first one to mate.”

Given the intense competition male black widow spiders face in courtship, it is best for them to follow the trails of other males rather than completely lose the chance to mate.

However, these are not the only hurdles that male black widow spiders face. Even after successful mating, the male spider is sometimes cannibalized by its partner, as the females are much larger than the males of the species.

The study’s design and results

To conduct the study, the researchers set up a series of races to track the spiders’ behaviour on the sand dunes of Vancouver Island.

Before the races, each male was weighed on a scale. The length of his legs were then measured, and his body was painted with unique racing stripes for identification. The race’s finish line was set up with cages containing the pheromone-releasing females.

Due to the nocturnal behaviour of black widow spiders, the males were released at sunset in 10-metre intervals from the finish line. The shortest race was 10 metres away from the finish line, while the longest was a length of 60 metres.

The great “Black Widow Races of 2016 and 2017,” as Scott nicknamed them, enabled the researchers to determine the speed taken by each male to find the cages.

Unexpectedly, they found that the males were able to locate the females faster if they also had access to the pheromones of other males.

While further research needs to be done, Scott hypothesizes that the study’s results could be generalized to other species of spiders.

“In other spider species where there is a similarly high level of competition over access to receptive females, and where the last male to mate has an advantage, I would expect that males may use similar tactics,” wrote Scott.

Commonly-held post-concussion practices have been upended at U of T as researchers join a growing international consensus for concussion recovery by calling for less hiding away in a dark room and more activity.

On the frontline of this new research is U of T’s own Dr. Nick Reed, who is an associate professor at the Department of Occupational Science & Occupational Therapy. Reed, along with Dr. Roger Zemek from the University of Ottawa and the rest of their team, published an online resource in September called Brain Injury Guidelines, assembling the most up-to-date studies into a tool for patients and medical professionals alike.

Previous reccomendations suggested that concussion patients be prescribed what Reed calls a “bedroom jail,” effectively staying in a dark room until they are feeling better. Now, studies are finding that locking someone away from their life can lead to more harm than good.

Updated concussion guidelines recommend rest for the first 24–48 hours following the injury, as the cells in the brain are undergoing an energy crisis. “After those first couple of days, sort of 24–48 hours, we want to start gradually reintroducing activities which are tolerable,” Reed said in an interview with The Varsity.

Medical consensus says that concussions may cause volatile emotions, and so it’s important to take care of one’s mental health during recovery from a brain injury. With the everyday pressures faced by most U of T students, anxieties are only exacerbated as papers and midterms are pushed off to the near future while they are being told to take a break.

The greatest challenge faced by those resuming activities after a concussion is moderation. In the early stages, going to half of a lecture can sometimes make you feel more aware of what you may be missing. Students struggling with post-concussion symptoms should reach out to their faculty and use the supports and accommodations in place to find and keep their own pace.

Griffin Giles, who plays on the Varsity Blues men’s rugby team, experienced a concussion last October which “messed up [his] whole year.” Giles clarifies that while the university itself was very understanding, most of the pressure came from himself, as he didn’t want to take more than four years to graduate.

Giles spoke highly of U of T’s MacIntosh Sport Medicine Clinic and their staff. “U of T was really helpful”, said Giles. “They gave me extra time [on exams]; I could write them in a darkened room.”

“One of the goals of this guideline is to get everyone on the same page and to create a culture that supports the individual first and foremost,” Reed explains.

“At the end of the day, concussion is an injury that most people can recover quite well from,” said Reed. Having played lacrosse at U of T in the past, he is a strong advocate of “sports and the values sports instills,” but he wants to ensure people are “engaging in it safely.”

The Brain Injury Guideline is a living document, meaning it will remain up-to-date as new studies come out. “What we want to make sure is that this great product is used… We need to make sure people are aware of it, spread the word, and make sure that people are using this tool,” Reed said.

Taking risks and testing new ideas are the cornerstones of advancing science and technology. But when it comes to developing new surgical techniques, experimentation can be a matter of life or death for patients who volunteer.

To understand how and why surgeons innovate, The Varsity interviewed Dr. Sunit Das, an Assistant Professor at U of T’s Department of Surgery and neurosurgeon at St. Michael’s Hospital. 

Why innovate?

Although the practice of surgery has come a long way, there is considerable potential to improve surgeries in order to make them safer, quicker, more efficient, and less expensive.

“Engineers talk about the fact that it’s the existence of problems that drive their work,” explained Das. “And, in a way, surgical innovation could say much the same.”

Of course, innovation inevitably carries the risk of failure. Das explained that part of the ethical dilemma of surgical innovation stems from weighing the benefits of testing an unfamiliar technique against a proven and well-known procedure. 

The difficulty of this decision depends on the effectiveness of existing procedures. When surgeons test a new technique against one that is rarely effective, ethically it might not be a costly risk to take. For example, according to Das, physicians can often test new chemotherapeutic agents with patients who have recurrent cancers, since there are usually no effective alternative therapies for their conditions.

New surgeries for these conditions are often worth the risks. It is much harder to try to innovate when a technique that is relatively safe and effective already exists.

For any innovative procedure, ethical practice requires doctors to fulfill certain responsibilities when offering experimental treatments to patients. Currently, there is a four-step process in place for approving new surgical techniques in Canada. 

The stages of surgical innovation

Surgical innovation begins with preclinical work and the development of a technique. Stage 1 follows, at which surgeons use the experimental technique for the first time on a human patient. In this early stage, the goal is to determine the safety and efficacy of the procedure in a small, select group of patients.

In Stage 2, surgeons apply the surgical procedure to a broader selection of patients to determine the reproducibility of Stage 1’s results. They also determine how to best apply the intervention, as well as develop the technique’s efficiency.

Throughout the development of any new surgery, patients and their caregivers must give special consent to receive it. This suspends or modifies the duty of surgeons to minimize harm. By the conclusion of Stage 3, the new surgery becomes a standard procedure, removing the need for physicians to require special consent from patients.

How do experimental surgeries receive ethical oversight?

Monitoring the progress of surgical innovation is critical — a lack of oversight could lead to mistakes that present patients with unnecessary risks.

For many hospitals, Research Ethics Boards (REBs) ensure experimental techniques meet ethical requirements. When surgeons intend to make an experimental procedure available for patients, they must submit a clearly defined protocol to an REB for approval.

However, there are drawbacks to placing an REB in charge of surgery. To start, REBs often do not have surgeons on them. Service on an REB is a time-consuming responsibility and “time is one of the things that surgeons tend to lack,” said Das.

An REB’s oversight can also substantially slow the development of a surgical technique, said Das, in ways he believes are unnecessary.

To develop a surgical technique, explained Das, researchers undergo a process that is iterative. That is, surgeons often apply an experimental technique, learn how they could improve it during the process of the surgery, and change the protocol to reflect the improvement.

“The nature of an REB is antagonistic to [iteration],” said Das. Under an REB’s oversight, each time the surgeons decide to alter their protocol, they need to apply for an amendment, causing their application to require review by the REB.

While Das noted that the additional review does ensure that the REB is on the same page as the surgeons, he believes that an alternative approval process could increase the efficiency of surgical innovation.

The Surgeon-in-Chief as an alternative source of oversight

Das believes in placing the burden of responsibility on the Surgeon-in-Chief of a hospital to ensure that experimental surgeries meet ethical requirements.

The expertise of the Surgeon-in-Chief addresses the first perceived shortfall of REBs — that such boards lack physicians directly experienced in surgery. He noted that “there are nuances to the idea of surgical innovation [that he believes] are more available to a Surgeon-in-Chief than they necessarily might be to an REB.”  This could allow the Surgeon-in-Chief to have a better grasp of how an experimental procedure works.

Das also addressed the issue of REBs reducing efficiency. He said that a Surgeon-in-Chief with the onus of responsibility would allow “a type of communication and a type of nimbleness to change that simply is not inherent to the way that something works with an REB” and would therefore support iterative development.

“I think Toronto has been a leader in the world in terms of thinking about this problem [of obstacles to iteration],” said Das. In fact, he noted that the model of placing the Surgeon-in-Chief of a hospital in charge of oversight, instead of an REB, evolved at Toronto General Hospital.

Since then, institutions, such as St. Michael’s Hospital and Toronto Western Hospital, have adopted this model of ethical approval. As an advocate of this approach, Das has co-authored a paper about this in The American Journal of Bioethics. 

He acknowledged, however, that the model does have shortfalls. “One of the inherent dangers to placing the oversight element to innovation with a Surgeon-in-Chief is that there might be [conflicts of interest] that could get in the way of proper oversight,” he said.

A conflict of interest, said Das, could result from the promise of prestige of a successful innovation overshadowing the Surgeon-in-Chief’s responsibilities to the hospital, surgeons, and patients to ensure proper oversight when approving experimental procedures.

“For me, being involved in surgical innovation has had beneficial effects on my career and on my standing in the international community of neurosurgery. I gain prestige by work that I do as an innovator… and the hospital gains prestige from the work that I do,” said Das.

“There’s the danger that those risks, those responsibilities could be clouded by the possibility of benefit in terms of prestige to a surgeon and to a hospital by innovation.”

Always innovating

Surgeons think about research ethics to address the conflict between the goals of securing patient safety and improving patient outcomes by developing new procedures. They cannot advance what they offer patients without stepping outside a place that is comfortable and known. Taking risks is fundamental to making progress.

“Surgical innovation in a way is deciding to do something differently, despite knowing that we have a way of doing things safely and well,” said Das. “It’s simply that we think we can finally do something that, in a way, will be safer and be better.”

What does scientific discourse have to do with artistic expression? For a research team at the Princess Margaret Cancer Centre, the answer is “everything.”

We once thought of our right and left brains as separate forces responsible for logical and creative thought, respectively. But scientific progress has shown us otherwise, as mental processes require that the whole brain works together in harmony to approach a task.

Just as the corpus callosum brings our hemispheres together as a band of nerve fibres, so too should science and art harmonize — so believes Dr. Mathieu Lupien, a Senior Scientist at the Princess Margaret Cancer Centre. 

Lupien incorporates art into his professional sphere to generate creative discourse between his close-knit team of researchers. He offers a unique approach to team-building by inviting his team to take a stroll through the Art Gallery of Ontario.

Each team member takes the time to walk through and choose a piece of artwork that speaks to them. Lupien then has the team come together as a group to share their chosen piece and engage in dialogue about what inspired them.

“I get to see the world from their perspective and they get to see mine from theirs,” said Lupien in an interview with The Varsity. The process helps the researchers better understand how they see the world through different lenses.

Lupien expresses that this is an exercise in using something creative, like art, to share who we are as scientists. It gives the team a glimpse into each other’s worlds. For example, if a member really enjoys the intricate detail in a piece, we can understand that the fine details they reflect in their own work are something they value. This helps us interpret the work they do in a more meaningful way.

“Our imagination is the only way to explore the unknown,” said Lupien. “We are working in uncharted territory sometimes, so creating an environment that is conducive to open, creative thought is important for our work.”

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How can students integrate art and science into their own research methods?

Lupien describes that translating scientific works in an intelligible way is an art in itself. Science, technology, engineering, and mathematics can be highly complex areas, full of jargon which can be intimidating for many students interested in the field. Using creative expression is one way to translate complexities in an imaginative way.

He demonstrates this idea in his description of his research on epigenetics: the study of how the activity of our genes can change, without changing our DNA sequences. He describes the genome as six billion letters of DNA that form words that are different in nature. When they are organized into sentences, each of them tells a unique story.

In order to form specific parts of our body, such as muscle and brain tissue, we organize our genome, represented here as letters, in different ways to create distinct sentences. The folding process is guided by epigenetic events, or post-it notes, which highlight the regions of our genome that need to be read.

Perhaps we can say that art relates in the same way. Each stroke of the brush or strike of the pen creates a unique image, and the artist goes over certain areas of the painting with these tools to highlight parts of the piece. Sometimes this disrupts the image, which can create chaos. Other times, this enhances the image with clarity.

Like epigenetics, one must follow these fine lines or broad strokes to understand how the larger image, or genome, has come to be. Lupien emphasizes that fostering creative thought can open a world of possibilities for all walks of life. “Bringing these values into your everyday practice as a researcher can serve to nourish your approach to work,” he said.

Experiencing art can also serve as time for our ideas to incubate, perhaps creating a period of unconscious processing for approaching problems in research. Taking from the famous 1929 works of Graham Wallas, The Art of Thought, incubation allows us to process problems in a manner whereby no direct effort is exerted.

We can optimize the way we process pre-existing knowledge by exposing ourselves to creative mediums such as art. This may lead to new approaches in scientific work. Ultimately, generating a scientific discourse with the expression of art can bring forth creative magic that inspires research. 

“In research, there are two things of value — there is knowledge and creativity,” said Lupien.

“You need to have balance. Never shy away from engaging in creative thought. You never know where it will take you.”

On a cloudy afternoon on May 11, professors, students, parents, and children enjoyed the annual Science Rendezvous street festival at U of T’s St. George campus. The event let them celebrate and learn more about advancements and achievements in research.

The unifying theme of the festival this year was “S.T.E.A.M Big!”, which focused on the intersections between science, technology, engineering, art, and mathematics (STEAM). While art is often seen as separate from STEM disciplines, it is becoming increasingly common in the scientific community to encourage taking inspiration from the arts to drive innovative research.

Street stalls and displays exhibited the relationship between art and science

Displays that exemplified the relationship between art and science included outdoor music and dancing, as well as a visual art gallery inspired by math and science.

The focal points were the stalls and displays lining all of St. George Street. These exhibits presented some of the hottest topics and projects in science today, focusing on big interdisciplinary innovations found at the intersections of these rapidly advancing fields.

Over 80 faculties and community organizations set up exhibits. Highlights included displays of solar-powered cars, rockets, robots, and a wide array of other projects that would fascinate even those who have a passing interest in scientific inquiry.

This wide range and diversity of subjects represented by the participating volunteers brought the 2019 theme of STEAM to vibrant life.

Booths and demonstrations were highlights of the festival

The street festival included over 100 fascinating and interactive booths. Some leaned toward the classic science fair vibe, such as displaying glowing bacteria and allowing patrons to look through a solar telescope. Others opted to take a more creative approach, such as the station inviting attendees to paint with acids, bases, and plant juices.

Some displayed student innovations, such as the demonstration set up by U of T Blue Sky Solar Racing, an undergraduate team that designs, builds, and races solar powered vehicles. There was also a plethora of digital demonstrations interspersed between all the other projects, ranging from virtual reality tours of archeological sites to demos of the many student-made video games.

Street fairs like Science Rendezvous increase engagement with science

One of the goals of the festival was to raise interest in U of T’s science programs, as many high school students attended and participated in the event. An example was the molecular genetics-focused science fair that took place in Bahen Centre for Information Technology.

Besides attracting prospective students, the festival is intended to improve public involvement and investment in STEAM fields. From the number of students competing in the science fair, sporting U of T shirts with palpable excitement on their faces, to the sizeable crowds drawn in by the street festival, it is safe to say that both of these goals were achieved.

A rendezvous is a meeting or an appointment. In a way, St. George Street is a science rendezvous every day, with labs, classes, and seminars running regularly. What was special about this festival was that it took experiences that are often inaccessible and presented them in a way that could appeal to all.

The pretension and exclusivity that often seems to follow research was stripped away, and all that was left was mystery, excitement, and curiosity. This contributed to why the event drew in hundreds of people, and why volunteers and attendees come back year after year.

During sperm transfer and climax, the male redback spider does a somersault of sorts, placing his abdomen in the perfect position for the female to eat, and more often than not, she goes for it.

Whether you think it romantic or horrific, there is something captivating about this ultimate sacrifice during the moment of climax. But because of this, the female redback may remain a lonely single after sex, albeit a little less hungry.

Black widows are also members of the Latrodectus genus to which redbacks belong.

This act of sexual sacrifice, called ‘terminal investment,’ has been extensively studied by the lab of Dr. Maydianne Andrade at UTSC, where thousands of black widows — notorious for their highly potent and neurotoxic venom — share refuge.

However, if you think it romantic, perhaps the male spider’s reasoning for sacrifice may make you think again. It appears that the male redback’s terminal investment serves an evolutionary, or depending on how you look at it, selfish purpose.

Though it may seem counterproductive for a male spider to sacrifice his entire existence for just a single shot at producing progeny, there are several adaptive advantages that he gains by taking this risk.

Self-sacrifice serves to enhance male paternity both by increasing the number of eggs the male spider fertilizes and by decreasing the chance that their female partner will mate with another competitor.

Andrade’s team found that six out of nine females that cannibalized their partners refused to mate with a second male, while only one in 23 females that didn’t have the pleasure of consuming their mates did the same.

Also, the chance that the male could mate again if he escapes the fangs of his lover is meagre. Therefore, his self-sacrifice offers a way to give it all he’s got by partaking in the ultimate act of evolutionary fitness.

Though female redbacks can be violent in their courtship, they do offer some mercy to the fittest of their male counterparts.

‘Premature cannibalism’ — which occurs before copulation is complete — is much less common if the male offers courtship for over 100 minutes, a marathon of sorts for the reward of paternity. However, males that are ready for this marathon must be wary of cheating competitors that can sneak in at the finish line, disguise themselves as the winner, and avoid being prematurely eaten.

And when it comes to being eaten by their mate, size does matter. Females are less likely to prematurely cannibalize a large marathon runner than a small sprinter.

However, more importantly, a male is less likely to be eaten by his female counterpart if she is well-fed — he only offers a meal sized at one or two per cent of her body mass.

Unfortunately for him, food is typically a rare commodity for a plump female redback in her native Australian habitat, so she may well take the meal that he offers in addition to her potential future offspring.

While this extreme sacrificial gesture and its violent ending could be seen as a spider’s ultimate Valentine’s Day gift, in the end, it is neither the life of the female nor the male redback that is rewarded, but their offspring that ultimately earn the gift of life — and go on to do the same.