At the turn of the twentieth century, a young Thorleif Schjelderup-Ebbe began vacationing with his wealthy parents, both sculptors, at a country retreat outside Kristiania (now Oslo), Norway, where he immersed himself in the lives of birds in the barnyard.
He gave them names, closely watched how they behaved, and learned how to recognize one from the other. He “became terribly interested in chickens, terribly interested,” Schjelderup-Ebbe’s son Dag recounted in 1986 in an interview published in Human Ethology Bulletin. Read More
Until recently, monarchs have mostly been at Mother Nature’s mercy—contending with disease, weather fluctuations, and heavy predation in the wild.
Lately, however, the efforts of a well-meaning public to bring monarch eggs and larvae indoors to raise to maturity, or to purchase large numbers of farmed monarchs for release into the wild, may be making life even more difficult for the beleaguered butterfly. Experts suggest such activities expose monarchs to disease, interfere with its genetic diversity, and stymie scientists’ efforts to track its migration patterns. Sadly, this isn’t the first time our good intentions toward monarchs have gone bad.
“People know monarchs have been in trouble. Their numbers in Mexico have been low for the past several years,” says Sonia Altizer, director of Project Monarch Health and a professor at the Odum School of Ecology at the University of Georgia. Scientists have observed declines by as much as 97 percent of historic highs and 97 percent of long-term population averages.
According to Sarina Jepsen, director of Endangered Species and Aquatic Programs at The Xerces Society for Invertebrate Conservation, “There were highs of almost a billion monarchs—like 800 million monarchs. Currently, this last year, I think we had counted in Mexico either 120 or 150 million.”
To help boost monarch populations, more and more gardeners and armchair naturalists are removing monarch eggs and larvae from the reach of predators, raising them indoors and subsequently releasing the adult butterflies back into the wild. Still others purchase large numbers of captive-bred monarchs from commercial butterfly farms for release into the wild. Sounds helpful, right? Wrong.
“I know people who purchase monarchs and use them in outreach and education, but, if you’re buying them with the goal of, ‘I’m going to release them and supplement the population,’ there are a lot of problems with that,” says Altizer says.
These practices troubled a group of leading entomologists and conservation biologists to such a degree that they set aside differences in opinion just long enough to issue a consensus statement against the release of purchased, mass-reared monarchs from butterfly farms. They also urged individuals rearing monarchs on their own to do so only while following safe rearing protocols and participating in citizen science programs such as the Monarch Larva Monitoring Project and Monarch Health.
Reaching that consensus wasn’t easy.
“There were some [conservationists] who thought people shouldn’t be rearing any [monarchs indoors.],” recalls Karen Oberhauser, a professor in the Department of Fisheries, Wildlife, and Conservation Biology at the University of Minnesota and director of the Monarch Larva Monitoring Project. “Well-meaning and smart people are going to disagree on a lot of things, and none of us has a monopoly on the truth.”
Elizabeth Howard, director of Journey North, an ongoing citizen science study of wildlife migration, notes, “I would say [the statement] could have been even stronger…. It’s such a balancing act, because all of us recognize how important the experience of raising monarchs is from a public education standpoint … Where it gets complicated is when you get into the question of how many. How many is enough? It’s the mass rearing that really raises concern.”
Most experts agree that mass monarch rearing—particularly via commercial butterfly farms—and mass butterfly releases (say for weddings, funerals, and other events) are nothing but trouble. On the topic of mass releases, famed lepidopterist Robert Michael Pyle writes, “When celebrants are misled into thinking that they are doing something ecologically acceptable, even positive, by tossing monarchs into the void at their events, they are in fact party to scientific vandalism; rather than acting ‘green,’ they are helping to undermine our ability to correctly interpret the response of wild monarchs to all the challenges they face.”
Hospice organizations across the U.S. have also adopted the practice. “The organization buys [farmed butterflies] and then they charge people to release them as part of their fundraiser. That’s why it’s becoming so embedded, because people are doing these annually now … they’re raising a lot of money,” says Howard.
“There is absolutely no educational message. In fact, if anything, there’s a disregard for what happens to the butterfly when everybody goes home,” she adds. For its part, the International Butterfly Breeder’s Association (IBBA) released its own statement in defense of mass butterfly releases.
On average, one dozen monarchs sell for about $100. A charity can then charge members of the public between $30 and $50 per butterfly, pocketing the difference. But the monarchs themselves may be paying a higher price.
Commercial butterfly farms are largely unregulated, and the quality and health of the butterflies they produce can vary widely.
“With some growers,” says Altizer, “every single one of their butterflies is heavily infected, and, with other growers, none are. I don’t want to point a blanket finger at all commercial growers, but, in general, the risk is there. We’ve found that at least half of the commercial growers that we’ve looked at have problems with disease.”
Overcrowded conditions and poor hygiene are often to blame for the spread of Ophryocystis elektroscirrha (OE), a harmful protozoan that can cause serious deformities in adult butterflies. Some affected adults may appear healthy but still spread OE to other butterflies and larvae through the release of OE spores. Whether raised in a commercial facility or by well-meaning amateurs, sick, captive-reared butterflies that are released into the wild can contaminate existing, wild monarch populations.
“One of the things that is not mentioned in [our] statement is that butterflies all fly to the same place for the winter. So, if ever you were to think of a bad situation for any sort of communicable disease, you have it right there.” says Howard.
“I think also, in terms of raising a few [monarchs] in your back yard, or many, many, many people raising a few, it’s a drop in the bucket,” she continues. “The growth in the population would only be linear in that way, whereas the risk of disease is exponential. So, in terms of a numbers game, for every monarch you’re releasing, you’re adding one to the pool, but you’re potentially introducing disease that will spread exponentially.”
Butterflies reared indoors don’t always develop the proper physiology to migrate either. They are often slightly smaller than their wild counterparts—and wings that are just a millimeter or two shorter than average can spell disaster for a butterfly on its long flight to Mexico.
Natural environmental cues like decreased day length, more extreme day-night temperatures, and deteriorating milkweed quality cause monarchs to enter a pre-migratory state known as reproductive diapause.
“When they’re exposed to one or more of those combinations of cues, they’re more likely to enter that migratory physiological state where, instead of having developed reproductive organs and being ready to breed, their reproductive organs are actually underdeveloped … and, instead, their bodies are primed to just tank up on fat and nectar,” Altizer explains.
Instead, monarchs raised indoors may be exposed to consistently long periods of artificial lighting, constant temperatures (thanks to air conditioning), and only the choicest milkweed (thanks to the keepers feeding them) while in captivity—thereby removing the environmental cues essential for triggering that pre-migratory state.
Despite the potential pitfalls, in some instances, researchers believe it is still appropriate for individuals to raise small numbers of monarchs indoors.
“As long as [people are] rearing [monarchs] carefully, it’s not going to hurt those individuals or the population, and, if they’re reporting their data to a citizen science project, it’s going to help us understand monarchs,” says Oberhauser.
Altizer agrees, “In my mind, it’s not cut-and-dried, black-and-white where I would say people should absolutely never rear monarchs … there are some people who go to great lengths to educate themselves about hygienic rearing practices and about monarch disease, and go to great lengths to keep the conditions as natural as possible.”
Not ready to commit to a citizen science project? You can still be part of the solution for monarchs by planting native milkweed as well as nectar-rich plants and donating to organizations dedicated to monarch preservation, such as the Monarch Butterfly Fund and The Xerces Society for Invertebrate Conservation.
Stone tools, like Acheulean hand axes, remain well-preserved for eons because they are stones first, tools second. Fired ceramics remain well-preserved for millennia because they are, in essence, human-made stone. Metal tools may, in some rare instances, endure for millennia, but their material hardness belies chemical fragility; most are not stable over the long term. Bone tools, like their metal counterparts, may remain well-preserved, but preservation is highly specific to local burial chemistry. Artifacts made of perishable plant and animal remains, such as clothing, shoes, nets, baskets, and many toys, are rarely well-preserved, and therefore not very well-understood. Read More
The turn of the 21st century was an exciting time in the history of genetics.
The first sequencing of the human genome was completed in 2003 and it provided numerous insights to the scientific community and society in general. In 2000, during his final State of the Union Address, President Bill Clinton made a point of how all humans share 99.9 percent of our genome — it’s actually more like 99.7 percent.
By honing in on the genetic variants, or mutations, that exist for certain genes in the human population, medical geneticists achieved a capability that would have looked like science fiction to physicians of the 1970s. Deciphering the genetics that underlay our existence has so far led to measurable success in gene therapy for certain conditions, but scientists are realizing that genes do not have the final say in what happens to a cell and its owner. Read More
Have you ever wondered how freshly baked bread gets its golden brown crust and why it smells so good? Or how nondescript green berries turn into beautiful brown coffee beans with a rich alluring aroma?
The answers to these questions lie in a series of complex of chemical reactions, known as Maillard reactions, which give many foods their familiar flavors and colors. These sensory properties even guide us in how we choose foods and help create our initial perceptions of their quality. Read More
A months-long Indian jumping ant Battle Royale is almost as brutal as the process to elect members of Congress. But after the dust settles in the ant colony and on the campaign trail, the hierarchies that emerge are, in a loose sense, similar.
When an Indian jumping ant (Harpegnathos saltator) colony’s queen dies, her distinctive I’m-having-babies pheromones stop circulating, and workers, alerted by the absence of her familiar scent, gather at the center of the colony and form a circle around the larvae and pupae. Read More
A recent expedition to Antarctica has returned with a cache of fossils and data gathered over the course of almost two months of work on the frozen continent.
Before you ask what they found, however, let’s get to the real question: What were they even doing there in the first place? Hunting for fossils in the most inaccessible and inhospitable continent on the planet, where over 99 percent of the ground is covered in solid ice, seems like a tall order, verging on an exercise in masochism. Antarctica may be possessed of bone-chilling winds and desolate tundras, but it also hides a trove of fossils from one of the most intriguing epochs of life on earth.
The Antarctic Peninsula Paleontology Project, or AP3 for short, is a diverse team of paleontologists and geologists, along with a large support staff, that has made three trips to Antarctica over the past seven years to prospect, explore and collect data. Their latest trip, which lasted from February 2 to March 24, was the longest and largest to date and built on their work from previous expeditions. This year, they returned with a wealth of fossils — still to be studied — that likely represent several new species and further illuminate one of the more mysterious moments in Earth’s history.
Although the paleontological rewards are big in Antarctica, every day tests researchers’ patience and grit in a new way.
In the vast emptiness of the Gobi Desert, the days are long and weary, and the searing sun does little to boost the spirit, even with the prospect of discovering new dinosaur species on the horizon.
Exhaustion and sunstroke are a hard-working paleontologist’s enemies out there, and staying well-hydrated is of utmost importance. Thus, an enemy to the paleontologist’s productivity emerges: frequent “relief” breaks out in the wilderness. But sometimes a diversion from the task at hand leads down the road to discovery.
During one such “relief” break in 2008, Michael Pittman and his international team of fossil hunters made the history books while prospecting in the region of Bayan Mandahu in Inner Mongolia, China. Pittman is the current head of the Vertebrate Paleontology Laboratory at the University of Hong Kong, and has spent years scouring the Gobi for fossils. Read More
Elizabeth (Liz) Parrish is the CEO of BioViva, a biotechnology company that focuses on developing gene therapies, and other regenerative therapies, to intervene with human aging.
Last September, Parrish added an interesting line to her job description: patient zero for two anti-aging therapies that the company is researching.
Parrish is receiving two kinds of injections, which are administered outside the United States: a myostatin inhibitor, which is expected to prevent age-associated muscle loss; and a telomerase gene therapy, which is expected to lengthen telomeres, segments of DNA at the ends of chromosomes whose shortening is associated with aging and degenerative disease.
The study will likely continue for many years. But last week, BioViva issued a press release describing an unexpected early result, offering a clue as to what the BioViva team might publish in the weeks or months to come.
It will be unclear exactly what the BioViva researchers have found until the results do go through the rigorous process of scientific peer-review, but the un-reviewed BioViva report is raising some eyebrows. Telomeres of T-lymphocytes in blood samples taken from Parrish in September were 6.71 kilobases. That’s shorter than normal for Parrish’s age, but lymphocytes from the samples taken in March after six months of gene therapy measured 7.33 kb, according to BioViva.
The company equates the reported 620-base increase to reversing the clock on Parrish’s chromosomes by twenty years. But there are numerous caveats noted by experts in genetics and laboratory medicine that were recently published by the non-profit group Genetics Expert News Service.
For one thing, telomeres are being tested only in her T-lymphocytes, as opposed to all tissue types of her body, so even if the test result were evidence for de-aging of T-lymphocytes it doesn’t necessarily prove her entire body de-aged.
“Long-lived T cells have shorter telomere lengths than newly generated naïve cells; and cells which have reached their maximum limit of cell divisions have shorter telomeres than any other cell type,” says Rita Effros, a professor of pathology and laboratory medicine at UCLA. “Thus, a simple change in the proportion of different cell types within the peripheral blood could easily explain the data.”
Furthermore, notes Dr. Bradley Johnson, Associate Professor of Pathology and Lab Medicine at the University of Pennsylvania, “Telomere length measurements typically have low precision, with variation in measurements of around 10 percent, which is in the range of the reported telomere lengthening apparently experienced by Elizabeth Parrish.”
These criticisms notwithstanding, Parrish serving as patient zero for a brand new treatment is a milestone in medicine, one that harkens back to the medical pioneers who regularly injected themselves with various new drugs over a century ago. Before BioViva’s news broke, Discover’s Dr. David Warmflash interviewed Parrish about the therapies and her feelings about being the first test subject.
Discover: What would you say makes BioViva stand out from other biotech or gene therapy companies? Is it that you’re using yourself as a test subject?
Liz Parrish: Yes, and number two is treating biological aging as a disease. Actually, that is probably number one. We’re going at the root cause of what makes most of the population sick. And then second, of course, we’re 100 percent behind the product.
We’re using them. We are not just a research company. BioViva is about saving lives, and lessons from history suggest that the use of multiple experimental therapies at once may be the shortest route to saving lives. When AIDS research first began, we saw the use of many drugs which, when used in isolation, helped with one mechanism of the disease, but patients still died from another mechanism of the same disease. It was only when doctors combined those drugs into cocktails we saw the first real advances in combating AIDS.
Do you feel any connection, or do you see yourself as carrying on a tradition of the those early medical researchers from the late 19th and early 20th century who tested different drugs on themselves?
LP: Yes, I guess so in retrospect. We didn’t do it in the spirit of that. We did it because it had to be done, because we needed a test patient on the gene therapy, but I think it is in that spirit and I wish more people had that spirit. The U.S. is 5 percent of the world population. We take 75 percent of all prescription drugs and yet have the shortest lifespan of every industrialized country, so I wish more people would get behind their drugs and other therapies. I think it would prove that what they have is something that you would want to take.
OK, so let’s talk about the therapies that you’re taking. Is there any concern the telomerase gene therapy could led to malignancy, to cancer, in any tissue?
LP: Telomerase has never been hypothesized to be the sole cause of cancer. Not all cancers have telomerase upregulated in them. Cancer cells can develop daily in your body from a very young age. But isn’t a youthful immune system is what keeps full-blown cancer at bay?
The confusion of longevity research with cancer research is a recurring misconception and implies correlations that have not been proven. There are two lines of research into telomerase: longevity and cancer. The two never intersect.
In longevity research we do not find ourselves looking at increases in cancerous cells from telomerase induction, but rather a protection against cancer.
In previous interviews with other people, you’ve alluded to the tragic story of Jesse Gelsinger, the 18-year-old boy who died in an early gene therapy clinical trial at the University of Pennsylvania in the 1990s.
Ethically, of course there’s a difference between Gelsinger and you; I’ve heard you say that this is worth risking your life for. But on top of the tragedy of Gelsinger losing his life, didn’t it also set the whole field of gene therapy back several years?
From that perspective, in the unlikely event that something goes terribly wrong in the experiment on you, do you worry what might happen to gene therapy research? Have you considered this a possible rationale for slowing down, maybe taking a more conservative approach?
LP: Gene therapy has come a long way since the 1999 tragedy of Jesse Gelsinger.
The relevant research did not stop [after the event], only the applications, and even then only temporarily. But the big game-changer now is that we have better delivery methods.
Hundreds of people are partaking in gene therapies today and none have the issues we saw 16 years ago in Jesse Gelsinger. We also need to put this in perspective: almost 100,000 people already die of adverse drug reactions (ADEs) every year in the USA alone, while nobody has ever died from this latest generation of gene therapies.
That being said, we at BioViva are very careful to ensure the safest possible outcome while still testing every limit. I would not have taken a gene therapy that would have likely killed the patient and nor would anybody at BioViva. I simply stated that all data are equally important, and that to that end I would accept any outcome, up to and including my own death, in order to move the science forward.
We as a company, and I as a person did take a risk, but a risk we believe will change the world for the better and kick-start an industry with the best approach to curing disease and increasing healthy lifespan.
What do you think about the idea that, the potential of the studies on you notwithstanding, you’re just one datum, so what will we really know?
LP: Yes, absolutely. That’s true, but N=1 from one human is worth 10,000 mice, but of course every human’s body is different and people are going to respond differently.
And of course the FDA since the 1970s has passed almost 50 drugs through the system to the market that it pulled later, despite going through gold standard testing. So that’s why we have to start now and see what happens. No matter what safety and efficacy you have, if you can have N=10,000, you’re probably going to have some adverse effects down the road.
Whether it’s directly related to the gene therapy or to something else in the patient’s life, it may take years to determine, so it’s very important to start now with gene therapy. Currently, over 100,000 people die of aging related diseases, so at what point do we realize that life is risky and that taking a chance may be our best bet?
Which tissues are they using to monitor your telomere length, given that telomeres vary between tissues? Generally, in telomere studies, lymphocytes are used, because they’re easy to access, but what factors went into deciding which tissues to use in you both for monitoring and targeting the therapy.
LP: We are using lymphocyte testing at this time, as it is the most advanced and well understood way to test telomere length today.
I also understand that to carry the therapeutic gene through your blood and into your cells, BioViva is using what’s called an AAV vector, which has the advantage of delivering the genetic payload so that it ends up as an episome (free floating gene), rather than being integrated into a chromosome.
Is this a safety measure, to minimize the risk of mutagenesis and oncogenic transformation? Is there any possible negative to that, such as decreased duration of the effects?
LP: We are not necessarily trying to integrate the gene, as studies have not proven the benefit of doing so.
We are trying to create an episome in the nucleus, which will code for the target protein. Integration is still an important discussion because past delivery methods, which we avoid due to them creating integrational mutagenesis (integrating into the chromosome in random areas that caused the cell to become unstable).
We want to separate our method from that older method. Our delivery method does not cause integrational mutagenesis, and when it does integrate, it does so into a safe harbor site on chromosome 19 where cancer is not an outcome.
Are there concerns among your team that treatment for slowing or reversing aging of healthy tissues could also prevent elimination of malignant or premalignant cells?
LP: Cancer cells can appear in people of any age, but the proliferation of cancer cells owes more to a decrease in immune system capability than an increase in telomerase activity. Not all cancers involve telomerase production, and a peer-reviewed paper in 2012 showed that old mice saw no increase in cancer with telomerase induction.
Telomerase induction may actually be our first line of defense against cancer, because a youthful immune system regularly rids the body of cancerous cells. The mechanism of telomerase could restore cells epigenetically to a youthful state exhibiting fewer aging gene biomarkers. An example would be turning off the genes that turn on as we age such as P53, a tumor-associated gene.
If you were to develop a common type of cancer, how would we know if it’s from the gene therapy, or because you would have gotten it anyway?
LP: If I was to be diagnosed with cancer, we could have that cancer sequenced to see if it had an extra copy of the target gene [from the gene therapy].
So, you’re getting telomerase gene therapy as well as a myostatin inhibitor. Was there any discussion about the merits of giving you two experimental therapies at the same time? Imagine it’s the year 2096, you’re 120 plus, looking and feeling exactly as you do today and you have the blood chemistry of a 25 year-old. How would we know which therapy did it?
LP: Such an amazing outcome, if it happened, would necessarily be due to both those two therapies or more.
We believe that these two types of therapy are synergistic, and will benefit each other in ways that will maximize outcome. One gene therapy is hypothesized to create better signaling with stem cells. The other creates stem cells that can potentially divide indefinitely, as stem cell depletion is a risk for older people.
These benefits, combined with the protection against frailty or sarcopenia (loss of muscle tissue) with a myostatin inhibitor, and the more youthful epigenetics of a cell with telomerase induction, makes this combined therapy very powerful.
Exactly why so many humans choose monogamous pair bonds over juggling multiple partners has long been a mystery to scientists. After all, having several partners at the same time should lead to more offspring — an outcome you’d think evolution would favor. Now a new study has linked the phenomenon to sexually transmitted diseases, arguing that monogamy could have evolved because it offered protection against the threat of infection.
Monogamy is, of course, the norm in Western societies. But there are many cultures where a husband can have more than one wife (polygyny) or, less commonly, a wife can have more than one husband (polyandry). This diversity of human mating systems is also hard to explain. What we do know, however, is that many hunter-gatherer societies, living in small groups, were most often polygynous (and many remaining groups still are). But with the rise of agriculture, societies tended to become more complex — and less polygynous. In the most strictly monogamous societies, there was often a social punishment for polygynists, either informally or, as in many modern societies, through a legal system. Read More