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.
Planet Earth isn’t the most ideal place for solar power to thrive. Sunsets and weather afford solar panels a significant amount of downtime.
But there’s a place not too far from here where the sun never stops shining.
A handful of researchers, and more recently the Japanese corporation Shimizu, have been gearing up to develop solar power on the moon.
Shimizu took off with the idea in 2013 in the aftermath of Japan’s 2011 Fukishima accident, which produced a political climate demanding alternatives to nuclear power plants. Shimizu’s plans call for beginning construction of a lunar solar power base as early as 2035. The solar array would be 250 miles wide and span the lunar circumference of 6,800 miles. They’re calling it the Luna Ring. Read More
It’s a stereotype, but many of us have made the assumption that scientists are a bit rigid and less artistic than others. Artists, on the other hand, are often seen as being less rational than the rest of us. Sometimes described as the left side of the brain versus the right side – or simply logical thinking versus artistic creativity – the two are often seen as polar opposites.
Neuroscience has already shown that everyone uses both sides of the brain when performing any task. And while certain patterns of brain activity have sometimes been linked to artistic or logical thinking, it doesn’t really explain who is good at what – and why. That’s because the exact interplay of nature and nurture is notoriously difficult to tease out. But if we put the brain aside for a while and just focus on documented ability, is there any evidence to support the logic versus art stereotype? Read More
Sprinkling “Omm” mantras between “Ooh Rah!” battle cries can pay dividends for members of the Marine Corps and other branches of the military. According to a growing body of research, regular meditation improves the wellbeing of military members — both active duty and those who have previously served.
Meditation is rooted in spirituality, which affects personal wellness in its own way, but the neurological underpinnings of meditation’s other health benefits are being widely assessed by researchers, and they’re building a scientific case for its benefits. Read More
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
In a large walk-in freezer at the University of Minnesota, ground squirrels are quietly slumbering in the dark.
As the ground thaws this spring, a new crop of animals around the northern hemisphere will emerge from a long winter’s slumber. At the same time, squirrels in Matt Andrews’ lab at the University of Minnesota will be waking up from their own hibernation.
Andrews studies these hibernating squirrels, and the science may have applications for the health and well-being of astronauts, soldiers and anyone wishing to shed a few pounds. He’s spent decades investigating what happens inside the animals’ bodies as they lay quietly in cold temperatures.
His lab is filled with walk-in refrigerators that hold animals at a constant temperature – about 40 degrees Fahrenheit.
There’s something dark at work when it comes to certain human-animal interactions.
A recent report from the Ecological Society of America admits that calling attention to plants and animals in need of special protections can actually result in “perverse consequences,” ultimately putting some species in harm’s way—even in the face of stiff penalties.
Killing a bald eagle is a federal offense punishable by up to one year in prison and a $100,000 fine. “A subsequent conviction under the Bald and Golden Eagles Act, raises the maximum penalty up to two years in prison and a $250,000 fine,” says Neil Mendelsohn, assistant special agent in charge at the Northeast Regional Office of the U.S. Fish and Wildlife Service.
He’s currently investigating the mysterious deaths of 13 bald eagles discovered in Federalsburg, Maryland in late February. The reward for information now stands at $25,000. Necropsies show the birds didn’t die of disease or natural causes, and officials are keeping mum so far—other than to say human intervention is suspected.
Why do some people target and kill protected animals? It’s a question scientists have asked before. Read More
Unlovely, unloved and utterly necessary for controlling disease and stabilizing ecological health, vultures are under attack around the world.
In Africa, populations of a half-dozen species are nearing collapse due to a combination of human-caused killings ranging from poaching for bushmeat and religious objects to the deliberate poisoning of poached elephant carcasses to destroy the circling scavengers.
In southern Asia, and particularly in India, the chief villain has been a nonsteroidal anti-inflammatory drug called diclofenac, widely used to treat arthritis symptoms in cattle and water buffalo. Diclofenac causes acute kidney failure in vultures feeding from the carcasses of recently treated livestock, and has caused catastrophic declines in all three species of vulture populations in the genus Gyps, including the white-rumped, the long-billed and the slender-billed vultures; the first of these listed species declined by more than 99.9 percent between 1992 and 2007, with tens of millions of individuals dying across South Asia. Read More
They scrub in according to a strict protocol. All instruments are sterile, the patient is put to sleep, and an incision is cut and held open with retractors. Moving into the abdominal cavity, surgeons clamp bleeding arteries and cauterize tissues meticulously to prevent blood loss while also making the surgical field easier to see.
Thus far, it seems just like surgery today, but for the numerous people overlooking from elevated theater seats, dressed in formal Victorian outfits. That’s the operating room setting on the Cinemax period medical drama, The Knick. There are a host of other details that make the setting look ancient, but the differences from modern surgery are most striking when things start going wrong.
For instance, the patient’s heart rate becomes rapid, then erratic, and the surgeon knows this only because of a nurse listening to the patient with a stethoscope. She can’t report blood pressure, because no device is set up to measure it — there are no monitors of any sort. Those devices don’t exist in the era when The Knick is set, nor would they help much, since the time period denies doctors even the most basic tools of resuscitation. The year is 1900, when many basic principles of surgery have been developed, but safe transfusions, electrocardiography, and other vital tools still lay several years into the future. Read More