With 3D printing, doctors can now create better bone implants at less cost than with conventional implants.

An 83-year-old woman suffering from a lower jaw infection became the first person to receive a jaw implant manufactured with a 3D printer. Infections such as hers are normally remedied with reconstructive surgery, but doctor’s deemed the procedure too risky because of her age and health. Instead they turned to LayerWise, a company that specializes in 3D printing of metallic structures.

Titanium powder was melted with a high-precision laser into layers guided by a computer model of the jaw. The computer model was digitally divided into 2D layers and printed at 33 layers per millimeter. The 3D printing made it possible to create an implant that just as intricate as the real thing. With articulated joints, cavities that foster muscle attachment, and grooves to guide nerve and vein regrowth, the new jaw was an intricate piece of hardware. It normally takes several days to make a custom implant, but the 3D printed implant took just a few hours to print. After the implant was made it was treated with a bioceramic coating by Cam Bioceramics BV. The surgery to attach a jaw implant normally takes around 20 hours. But because the printed implant fit so well surgeons were able to attach it in just four hours. A shorter surgery makes for a shorter recovery. The patient was able to go home with her new jaw after only four days. Normally recovery takes weeks. She was able to speak a few words after waking up, and the following day she was able to swallow again. Being made of titanium, the new jaw weighs 107 grams or about a third heavier than the patient’s own jaw. The doctors think she’ll adjust easily.

The implant is treated with a bioceramic coating prior to implantation.

The new method was made possible by research performed at the Biomed research group at the University of Hasselt in Belgium and researchers at four other universities. The surgery was performed last June but is only now being announced. Later this month the patient will undergo a follow-up surgery to remove healing implants which have served as place-holders for the patient’s teeth. After they’re removed, false teeth will be screwed into their place.

The structures that can be produced by the layer-by-layer materialization of 3D printing are practically limitless. By comparison, creating medical implants with conventional metalworking is time-consuming, expensive, and the implants don’t match the original as well. Last year an orthopedic surgeon used a 3D printer to make bone models from CT scan images that doctors could use to prepare for surgeries. Others are trying to push the medical implant envelope by printing organs! It will be a while before our bodies’ organic material will provide us a reliable ‘ink,’ says Ruben Wauthle at LayerWise, citing many biological and chemical issues that are yet unresolved. Even so, 3D printing could be a major boon for medicine in the near future. No doubt others will adopt printing for jaw and other types of bone replacements. The patients will be better off, and hospitals will save time and money.

[image credits: LayerWise]
images: LayerWise

What do you think are the odds that you will die during the next year? Try to put a number to it — 1 in 100? 1 in 10,000? Whatever it is, it will be twice as large 8 years from now.

This startling fact was first noticed by the British actuary Benjamin Gompertz in 1825 and is now called the “Gompertz Law of human mortality.” Your probability of dying during a given year doubles every 8 years. For me, a 25-year-old American, the probability of dying during the next year is a fairly miniscule 0.03% — about 1 in 3,000. When I’m 33 it will be about 1 in 1,500, when I’m 42 it will be about 1 in 750, and so on. By the time I reach age 100 (and I do plan on it) the probability of living to 101 will only be about 50%. This is seriously fast growth — my mortality rate is increasing exponentially with age.

And if my mortality rate (the probability of dying during the next year, or during the next second, however you want to phrase it) is rising exponentially, that means that the probability of me surviving to a particular age is falling super-exponentially. Below are some statistics for mortality rates in the United States in 2005, as reported by the US Census Bureau (and displayed by Wolfram Alpha):

This data fits the Gompertz law almost perfectly, with death rates doubling every 8 years. The graph on the right also agrees with the Gompertz law, and you can see the precipitous fall in survival rates starting at age 80 or so. That decline is no joke; the sharp fall in survival rates can be expressed mathematically as an exponential within an exponential:

Exponential decay is sharp, but an exponential within an exponential is so sharp that I can say with 99.999999% certainty that no human will ever live to the age of 130. (Ignoring, of course, the upward shift in the lifetime distribution that will result from future medical advances)

Surprisingly enough, the Gompertz law holds across a large number of countries, time periods, and even different species. While the actual average lifespan changes quite a bit from country to country and from animal to animal, the same general rule that “your probability of dying doubles every X years” holds true. It’s an amazing fact, and no one understands why it’s true.

There is one important lesson, however, to be learned from Benjamin Gompertz’s mysterious observation. By looking at theories of human mortality that are clearly wrong, we can deduce that our fast-rising mortality is not the result of a dangerous environment, but of a body that has a built-in expiration date.

The lightning bolt theory

If you had never seen any mortality statistics (or known very many old people), you might subscribe to what I call the “lightning bolt theory” of mortality. In this view, death is the result of a sudden and unexpected event over which you have no control. It’s sort of an ancient Greek perspective: there are angry gods carousing carelessly overhead, and every so often they hurl a lightning bolt toward Earth, which kills you if you happen to be in the wrong place at the wrong time. These are the “lightning bolts” of disease and cancer and car accidents, things that you can escape for a long time if you’re lucky but will eventually catch up to you.

The problem with this theory is that it would produce mortality rates that are nothing like what we see. Your probability of dying during a given year would be constant, and wouldn’t increase from one year to the next. Anyone who paid attention during introductory statistics will recognize that your probability of survival to age t would follow a Poisson distribution, which means exponential decay (and not super-exponential decay).

Just to make things concrete, imagine a world where every year a “lightning bolt” gets hurled in your general direction and has a 1 in 80 chance of hitting you. Your average life span will be 80 years, just like it is in the US today, but the distribution will be very different:

Your probability of survival according to the "Lightning Bolt Theory"

What a crazy world! The average lifespan would be the same, but out of every 100 people 31 would die before age 30 and 2 of them would live to be more than 300 years old. Clearly we do not live in a world where mortality is governed by “lightning bolts”.

The accumulated lightning bolt theory

I think most people will see pretty quickly why the “lightning bolt theory” is flawed. Our bodies accumulate damage as they get older. With each misfortune our defenses are weakened — a car accident might leave me paralyzed, or a knee injury could give me arthritis, or a childhood bout with pneumonia could leave me with a compromised immune system. Maybe dying is a matter of accumulating a number of “lightning strikes”; none of them individually will do you in, but the accumulated effect leads to death. I think of it something like Monty Python’s Black Knight: the first four blows are just flesh wounds, but the fifth is the end of the line.

Your probability of survival according to the "accumulated lightning bolt" theory

Fortunately, this theory is also completely testable. And, as it turns out, completely wrong. Shown above are the results from a simulated world where “lightning bolts” of misfortune hit people on average every 16 years, and death occurs at the fifth hit. This world also has an average lifespan of 80 years (16*5 = 80), and its distribution is a little less ridiculous than the previous case. Still, it’s no Gompertz Law: look at all those 160-year-olds! You can try playing around with different “lightning strike rates” and different number of hits required for death, but nothing will reproduce the Gompertz Law. No explanation based on careless gods, no matter how plentiful or how strong their blows are, will reproduce the strong upper limit to human lifespan that we actually observe.

The cops and criminals inside your body

Like I said before, no one knows why our lifespans follow the Gompertz law. But it isn’t impossible to come up with a theoretical world that follows the same law. The following argument comes from this short paper, produced by the Theoretical Physics Institute at the University of Minnesota [update: also published here in the journal Theory in Biosciences].

Imagine that within your body is an ongoing battle between cops and criminals. And, in general, the cops are winning. They patrol randomly through your body, and when they happen to come across a criminal he is promptly removed. The cops can always defeat a criminal they come across, unless the criminal has been allowed to sit in the same spot for a long time. A criminal that remains in one place for long enough (say, one day) can build a “fortress” which is too strong to be assailed by the police. If this happens, you die.

Lucky for you, the cops are plentiful, and on average they pass by every spot 14 times a day. The likelihood of them missing a particular spot for an entire day is given (as you’ve learned by now) by the Poisson distribution: it is a mere .

But what happens if your internal police force starts to dwindle? Suppose that as you age the police force suffers a slight reduction, so that they can only cover every spot 12 times a day. Then the probability of them missing a criminal for an entire day decreases to . The difference between 14 and 12 doesn’t seem like a big deal, but the result was that your chance of dying during a given day jumped by more than 10 times. And if the strength of your police force drops linearly in time, your mortality rate will rise exponentially.

This is the Gompertz law, in cartoon form: your body is deteriorating over time at a particular rate. When its “internal policemen” are good enough to patrol every spot that might contain a criminal 14 times a day, then you have the body of a 25-year-old and a 0.03% chance of dying this year. But by the time your police force can only patrol every spot 7 times per day, you have the body of a 95-year-old with only a 2-in-3 chance of making it through the year.

More questions than answers

The example above is tantalizing. The language of “cops and criminals” lends itself very easily to a discussion of the immune system fighting infection and random mutation. Particularly heartening is the fact that rates of cancer incidence also follow the Gompertz law, doubling every 8 years or so. Maybe something in the immune system is degrading over time, becoming worse at finding and destroying mutated and potentially dangerous cells.

Unfortunately, the full complexity of human biology does not lend itself readily to cartoons about cops and criminals. There are a lot of difficult questions for anyone who tries to put together a serious theory of human aging. Who are the criminals and who are the cops that kill them? What is the “incubation time” for a criminal, and why does it give “him” enough strength to fight off the immune response? Why is the police force dwindling over time? For that matter, what kind of “clock” does your body have that measures time at all?

There have been attempts to describe DNA degradation (through the shortening of your telomeres or through methylation) as an increase in “criminals” that slowly overwhelm the body’s DNA-repair mechanisms, but nothing has come of it so far. I can only hope that someday some brilliant biologist will be charmed by the simplistic physicist’s language of cops and criminals and provide us with real insight into why we age the way we do.

UPDATE: G&L reader Michael has made a cool-looking (if slightly morbid) web calculator to evaluate the Gompertz law prediction for different ages. If you want to know what the law implies for you in particular, and are not terribly handy with a calculator, then you might want to check it out.

Do you really need all those pills? Some researchers say dietary supplements help only those who need them, and don't make healthy people healthier.

“Don’t forget to take your vitamins?”

That healthful reminder from mom may soon become a thing of the past. While dietary supplements remain popular in the US, a continuous stream of studies are casting increasing doubt that the widely-accepted benefits are real. Researchers and regulators are taking notice, and some are beginning to deliver a different message.

Two studies published earlier this month are the most recent examples. One takes aim at vitamin E, the other at multivitamin supplements for women.

The Selenium and Vitamin E Cancer Prevention Trial (SELECT) put to test the common “wisdom” that vitamin E lowers men’s risk for prostate cancer. A total of 35,533 men in the US, Canada, and Puerto Rico, received one of four treatments: vitamin E, selenium (an essential mineral thought to lower the risk of cancer when taken with vitamin E), both together, or a placebo. They found that taking vitamin E actually increased the risk for prostate cancer. Taken together with selenium, however, seemed to mitigate the increased risk that comes with taking vitamin E.

Bottom line, though, is that taking vitamin E or selenium – or both – did not reduce risk of prostate cancer.

The Iowa Women’s Health Study assessed the health affects of vitamins and minerals in over 38,000 older women. With a maximum follow up of about 20 years, the study showed that taking common vitamins and mineral supplements was actually associated with an increase in mortality rate, compared to women who did not take supplements.

We have to keep in mind, though, that studying the effects of vitamins and supplements is tricky. People don’t just eat them one at a time. The subjects in the SELECT trial took their vitamin E along with their normal diet. Other vitamins and minerals can interact with vitamin E in complex ways that researchers are far from understanding. So studies that try to parse out the effects of a single supplement have to be taken, pardon me for saying, with a grain of salt.

But while any single trial is not conclusive, a pattern emerges when one takes a broader view, according to Marion Nestle, New York University professor of nutrition, food studies, and public health. “The better the quality of research, the less benefit [supplements] show,” he told the Wall Street Journal. “It’s fair to say from the research that supplements don’t make healthy people healthier.”

There's nothing like the real thing.

Others agree. The Office of Dietary Supplements, part of the National Institutes of Health, says that while vitamin C has long been a popular remedy for the common cold, research shows that, for most people, vitamin C does not reduce the risk for getting a cold. On the other hand, taking too much vitamin C can cause diarrhea, nausea, and stomach cramps. And while taking vitamin B-6 and B-12 is commonly thought to reduce risk for cardiovascular disease, the data is not conclusive. In a 2006 statement, the American Heart Association said “evidence is inadequate to recommend…B vitamin supplements as a means to reduce cardiovascular disease risk.” There’s no disputing that calcium is important for bone health, but efforts to show it reduces the risk of cancer and heart disease have fallen short. And taking calcium supplements can increase risk for kidney stones.

Early studies suggested beta-carotene decreased risk for lung cancer. But two large studies published in 1994 and 1996 showed that smokers taking beta-carotene supplements were actually more likely to develop lung cancer than smokers who didn’t take the supplement. A follow up to the studies was performed in 2004. It concluded that beta-carotene was harmful to those at risk for lung cancer, even though the subjects hadn’t taken the supplement for years.

But that doesn’t mean all of us should stop taking our vitamins. For those with specific deficiencies or the malnourished, supplements are a necessary part of the diet. It’s recommended, for example, that pregnant women take folic acid. Folic acid is important for the kind of rapid cell growth that occurs during pregnancy. Taking it helps reduce the risk of birth defects.

Large studies that evaluate supplements, such as SELECT, are rare. In fact, many supplements remain untested, not only for their effectiveness, but for their safety as well. The FDA has a separate set of regulations for supplements than they do for drugs or “conventional” foods. According to these regulations, the “manufacturer is responsible for ensuring that a dietary supplement or ingredient is safe before it is marketed.” The FDA is responsible, however, for taking action if a supplement has adverse effects once people start taking them.

Sounds arse-backwards if you ask me. But no one’s asking me, and the fact is the supplement industry is big business. According to a National Health and Nutrition Examination Survey report published earlier this year, in 2006 about half of Americans were popping at least one supplement a month. In 2010 the supplement industry raked in $28 billion in sales, a 4.4 percent increase from 2009. Despite the growing number of studies that show a given supplement doesn’t work, people continue to take them.

Joseph Fortunato, chief executive of supplement retail giant GNC Corp., is quite okay with that. The Wall Street Journal quotes Fortunato from a company conference call transcript: “The thing you do with [reports of studies] is just ride them out, and literally we see no impact on our business.”

That may soon change if the National Center for Complementary and Alternative Medicine (part of the NIH) and other health institutes have their way. The growing body of data that consistently fails to show benefits has prompted them to push for more studies that explore how nutrients work – a body of knowledge that is surprisingly lacking.

So what do we do with all this uncertainty? If you’re considering taking a dietary supplement, get informed. Read up and talk to your doctor. But as professor Nestle says, it might be a waste of money for people without specific deficits. The best way to get the vitamins and minerals you need? The old fashioned way: a balanced diet.

[image credits: Johns Hopkins Bloomberg School of Public Health and Dietary Supplements For Health And Fitness]
image 1: pills
image 2: balanced

For those unfamiliar with her work, Sonia Arrison has been on the science beat for a decade, covering emerging technology for TechNewsWorld, their ramifications for Pacific Research Institute, and publishing two other books on modern tech issues. She’s also one of the associate founders of Singularity University, and presents there often. Here’s a quick overview of Arrison as it pertains to her new book on longevity – the SU class of 2011 makes an appearance around 2:00.

Here’s another promotional video, this one more focused on the technology discussed in 100+:

I’d start off by describing the technology that Arrison thinks will help humanity extend its lifespan, but you already know all about it. To regular readers of Singularity Hub, the first few chapters of 100+ will be more than familiar. Regenerative medicine based on stem cell treatments, genetic modification, and lab-grown organs – we talk about this all the time. Arrison puts it all together in a concise and compelling best hits list of modern science, attracting much needed attention to the successes we’ve already seen in repairing and replacing failed parts of people as they age or get injured. With straight forward prose and a palpable sense of enjoyment, Arrison steps you through all these advancements and lets you feel the awe of what we’ve already achieved.

That’s part of the purpose of the book. As Arrison told me, she crafted 100+ in order to “make it readable for the average Joe on the street.” She was inspired to explore the science of longevity after watching ‘extreme makeover’ type reality TV shows like The Swan. If people were crying in joy from having plastic surgery, how else might we want to change ourselves? From cosmetic augmentation to real transhumanism, Arrison realized that “the more [she] looked at it, the more it seemed like reality, not just science fiction.”

People want to be happier, healthier, and experience more life. That’s one of the fundamental arguments of 100+, and Arrison states her case strongly enough to convince almost anyone, and in a style that will be as accessible to your techno-phobic Uncle Walter as it is to your computer loving self. But if humanity wants more out of life, why haven’t we made more of a push for radical life extension? Partly, Arrison supposes, because we don’t realize regenerative medicine is so possible. “If everybody knew about it, we’d all put more energy into it and we’d all live longer, healthier, happier, lives.” To me, 100+ serves as a sort of evangelical text for those looking to spread the word about longevity.

Arrison, however, sees it a little differently: “some may call it ‘evangelical’ but I think of it as sort of a myth-busting book.” From the beginning, 100+ addresses the standard philosophical and pessimistic arguments against longevity. Bring up radical life extension with a large group and you’re bound to have someone posit that it’s natural to die, that we’re not made to live forever. Others will argue that humans have a negative impact on the environment, that aged people will bring down the economy, and that all rising populations are checked by disease and famine as Malthus surmised centuries ago. Well, “Malthus was wrong,” says Arrison, “because he didn’t account for human capital.” More people means more brains working on solving the world’s problems. And if longevity works the way she thinks it will, those minds will be have the vitality of youth, but with many decades of experience. 100+ spends a good deal of its literary real estate debunking the anxieties and barriers society throws up so it won’t have to seriously consider the consequences of humanity successfully living longer lives.

If disaster isn’t going to strike, what will? In what impresses me as the most daring, and yet most satisfying part of 100+, Arrison explores the impact 150 year lifespans will have on finance, family, and religion. People will have to plan on having money for decades longer, pushing us to be more responsible, more investment minded. Arrison thinks we’ll want to do more with that money because ultimately, “death limits our ambition.” Our families will transform to account for generations that span centuries and family trees whose branches split off in ways we don’t see today. With ovarian cell grafts, in vitro fertilization, and other emerging reproductive technologies women could have their own biological children at 80…100…even 120. Siblings could be born sixty years apart. The centers of our world will be radically different.

Arrison thinks religion will have to change with it. She originally thought ending the threat of natural death would kill religiosity. After all, why do we need an afterlife when we have endless life here and now? Yet to her surprise, Arrison’s research showed that religion doesn’t fade as people gain longer lives, that instead religions are adapting to focus more on the purpose of life. In her opinion, the religions that thrive will be those that help people find meaning and satisfaction with their extended time on this Earth.

While I’m much more of a nuts and bolts technophile, I found Arrison’s extrapolation of longevity’s impact on the social side of things very intriguing. True to its aim to be accessible to the masses, 100+ explores the impact on finance, family, and faith in a way that explains rather than condemns, and enlightens rather than proclaims. Without comprising her vision for the importance of life extension, Arrison still manages to be respectful of humanity’s more conservative elements. A bit of a tight-rope walk, but she pulls it off.

So there’s really little reason 100+ couldn’t be given to almost anyone in your extended social circle to get them thinking about the realities and possibilities of longevity. But what then? “Change has to come from the bottom up.” 100+ outlines the people, the institutions, and the trends we’ll need if we want to encourage life-extension science to be ready in our lifetimes. Arrison ends the book with a look at the movers and shakers that are actively pursuing immortality. Here her Silicon Vally insider credentials shine. Arrison also vents an often stated Bay Area frustration with the FDA, a bureaucracy that doesn’t even have an approval process in place for age-related treatments. To satisfy Arrison’s thirst for the fountain of youth we’ll need media outlets discussing longevity more regularly – “Instead of the healthcare crisis why aren’t we talking about making people healthier?” We’ll need philanthropists and governments to push for age-related research, and we’ll need everyone to make longevity a priority.

If 100+ is right about the escalation of longevity science in the next few decades, and I think it’s certainly likely we’ll have great advances there, then we could see the end to physical aging in our lifetimes. That’s something to marvel at. I asked Arrison what she would do with her extra time. Fitting for someone who confesses that she never feels like she has enough time, she gave many different answers. Family, traveling, charity, education… I bet many of our own lists would look similar. There’s so much for us to do with our time, and we haven’t even seen a fraction of what the future holds in store. 100 years ago, most people didn’t have indoor plumbing. Now we have the internet (a different series of tubes). Live to 150 and beyond and you’ll see things, you’ll be things, that you never imagined were possible. Sonia Arrison makes those possibilities seem within our grasp. All we have to do is accept our right to challenge death, and fund the science that could make it end. We’ve already had more successes than most of us know about. We could achieve much, much more.

[image credits: 100plusbook.com]
[video credits: Arrison Project]
[sources: Sonia Arrison, 100+]

One big happy. Unregulated fertility clinics have allowed the number of half-siblings – such as these three – to grow to groups as large as 150.

Imagine finding out you had a half-sister. You might want to contact her, find out where she lives, what she does for a living, and whether or not she likes sushi.

Now multiply that by 150.

At the same time that artificial insemination is a miracle for so many couples who can’t conceive children, it’s also an example of how slack regulation can lead to unhealthy consequences. The New York Times recently reported that a single sperm donor has fathered 150 children, and his fertile seeds of life are still being used to impregnate more women still.

The Waltons would have needed the show’s entire hour to say goodnight.

This particular cohort is one of the largest to be found on the Web-based registry that tracks children born from specific donor numbers – donor identities are kept anonymous. But more and more there are groups of 50 or more half-siblings.

Cynthia Daily, who’s child is among the group of 150 siblings, told the New York Times, “It’s wild when we see them all together – they all look alike.”

Not only is this strange, it’s worrisome.

What if, for example, the donor had a genetic defect that he’s unwittingly – or worse, wittingly – passing on to all of these children? Logically one might think that fertility clinics would disqualify someone who had, for example, a genetic heart defect. But fertility clinics aren’t thinking logically, they’re thinking with their…um…test tubes. The FDA requires that donors in the US are tested for “communicable disease agents and diseases.” Screening includes a medical history interview and tests for infectious diseases such as hepatitis and HIV.

How effective is the screening? Just ask Tyler Blackwell. Curious about his biological father, Tyler and his mother located him and sent him a letter suggesting they might meet. They got no response. Later, the donor’s sister contacted Tyler and his mother – not to help Tyler meet his father, but to tell him there was a good chance that he had a genetic heart defect. Tyler’s biological father had almost died at the age of 43 when his aorta ruptured. Two of the man’s brothers have the disorder, as well as his mother. And by the way, the family has a history of a connective tissue disorder called Marfan’s syndrome. Tyler’s biological father had never told the three clinics at which he donated sperm of his genetic conditions. His sperm has been used to father at least 24 children, yet he was never required to update his medical history with the clinics.

Three half-siblings pictured with their mothers.

“It didn’t occur to anyone to tell us.”
A much more egregious example recently occurred in the Netherlands. A man with Asperger’s Syndrome, a mild form of autism that affects a person’s ability to socialize and communicate effectively with others, was able to donate sperm by lying to a clinic. After telling the clinic that he was perfectly healthy, his sperm was used for 18 months to father at least 22 children. Some of the children are already showing signs of autism. The man had also been previously treated for depression, which is also thought to have a strong genetic component. Inexplicably, the man is still at large and he’s still finding women who will use his sperm for artificial insemination or even by having intercourse with him.

The above examples illustrate the need for better monitoring and more comprehensive regulations. The US has been slow to adopt regulations. While Britain, France, Sweden, and other countries set limits to how many children a single donor can father, no such limit exists in the US. “We have more rules that go into place when you buy a used car than when you buy sperm,” Debora L. Spar, president of Barnard College and author of “The Baby Business: How Money, Science and Politics Drive the Commerce of Conception” told the New York Times.

Because there is no formal registry from which donor offspring can get information or make connections, a Donor Sibling Registry was created by and for the donor-conceived community. Half-siblings that share a mutual desire to make a connection can find each other through the registry. The registry can also potentially be a lifesaver by connecting offspring with their donors, thus giving them access to medical information that fertility clinics can’t be bothered to collect. “There are no rules or regulations about donor identification, testing donors, monitoring numbers of children or medical records.” Wendy Kramer, co-founder of the registry told ABC News. “No one is watching. There are no laws. They don’t keep track.”

Genetic diseases aside, how wise is it to alter the gene pool so rapidly and disproportionately as when fathering 150 children or more? Rare diseases could spread, and then there’s the increased likelihood of accidental incest. As a mother of a donor-conceived teenager told the New York Times, “My daughter knows her donor’s number for this very reason. She’s been in school with numerous kids who were born through donors. She’s had crushes on boys who are donor children.”

Given the industry’s lack of regulation, it’s not surprising that we don’t really know how many children from sperm donors are born per year in the US. Estimates range from 30,000 to 60,000. Although sperm banks ask mothers of donor children to report when a child is born, only about 20 to 40 percent of mothers do.

When Louise Brown became the first baby born using in vitro fertilization back in 1978, the British government charged a committee with the task of recommending regulations for what was sure to become a big international industry. What they produced was called the Warnock Report, named after the philosopher who led the group. The report recommended limiting the number of children a donor father could have to 10. The New York Times points out that “the regulations have become a model for industry practices in other countries.”

Obviously, the US is not one of them.

[image credits: CBC and MSNBC]
image 1: children
image 2: with mothers

A substance extracted from pigs has allowed Marine Corporal Isaias Hernandez to regain much of the muscle he lost to a mortar explosion while serving in Afghanistan.

It was only a year ago that ACell’s “miracle powder” was sprinkled on amputated fingers and shown to stimulate the regeneration of fingertips. The world was both awed and skeptical of the powder’s regenerative power, touting that it would revolutionize regenerative medicine or calling it was quack science.

A fingertip is one thing. A thigh, quite another.

After losing most of his thigh muscle in a battlefield explosion, one marine was given a second chance when another such miracle powder caused much of his thigh to grow back. It’s not only a wonderful feel-good story, but demonstrating that the same substance can grow back different tissues suggests that we may have only seen a small part of its full regenerative potential.

October 12, 2004, Afghanistan

At the time the mortar exploded, U.S. Marine Corporal Isaias Hernandez and his companion were working to repair a truck. If he hadn’t been carrying a television at that moment he, like his companion, would have been killed. The TV absorbed most of the shrapnel, but what it missed tore through Hernandez’s arms and legs. His right thigh got the worst of it: 70 percent of its muscle was sheered off and the femur was fractured. For the next four years the Corporal underwent multiple surgeries and constant physical therapy, but his leg wasn’t getting stronger. His only option was amputation, as is the fate of the vast majority of limbs with severe muscle damage.

Enter Dr. Stephen Badylak, Director of Tissue Engineering at the University of Pittsburg’s McGowan Institute for Regenerative Medicine. Dr. Badylak and colleagues offered Corporal Hernandez an alternative to amputation: regrow the muscle. The key to this seemingly miraculous procedure is a material obtained from pig bladders. As the material’s name, the extracellular matrix implies, it is the mix of chemicals that fills the space surrounding the body’s cells. It’s a complex mixture of hormones, structural proteins, and other molecules that maintain the health and function of the cells, as well as mediates cell-to-cell communication. It also guides tissue growth. Following an intense physical therapy program to strengthen the 30 percent of muscle he had left, doctors made an incision deep into Hernandez’s thigh and applied the extracellular matrix. Instead of a powder like ACell’s, Dr. Badylak’s group turned the material into a gel form. “You can’t use a powder to replace a tendon,” remarked Dr. Badylak. It went to work, spurring not only the growth of muscle tissue but tendons, as he mentioned, and the proper vasculature as well. About six weeks after the surgery the Marine began to feel his strength returning. What’s more, he saw muscle bulking up in the area that the extracellular matrix had been applied. “I used to have a hard time walking and going up and down stairs,” he told Purdue alumnus magazine in a feature story on star alum Dr. Badylak. “I can pretty much walk and do stairs fine now.”

After more than a decade since Dr. Badylak first treated a patient with the extracellular matrix material he still doesn’t quite know how it does what it does. A few things researchers do know: the extracellular matrix becomes part of the tissue it is placed into; as part of the tissue it can grow and heal; it somehow recruits the body’s own stem cells to its location; and it changes the body’s immune response from attacking to “constructive remodeling.”

The decision to use extracellular matrix from pig bladders was not a scientific one, but an economic one. Pig parts were in abundance in butcher-happy Indiana near Purdue University where Dr. Badylak first began the research.

Pig extracellular matrix does more than just regrow thigh muscle. ACell's remarkable MatriStem powder has been used to regrow fingers.

The fact that the extracellular matrix recruits the body’s own stem cells is huge because it obviates the need to introduce stem cells from an outside source. As we’ve discussed before, even genetically-identical cells derived from the patient can be problematic. Reprogramming skin cells, for instance, into heart cells requires significant molecular manipulation, and these manipulations can lead to side effects such as rejection or cancer. The fact that the extracellular matrix puts the body’s own stem cells to work is simpler and safer. It may also get Dr. Badylak’s treatment into clinics sooner. “It…simplifies treatment because it’s much easier to get FDA approval with stem cell research when you don’t have to harvest them,” he told Purdue alumnus.

As Dr. Badylak and his colleagues know, every little bit helps. Their ‘MiracleGro For Muscles’ wasn’t always seen as such. Even after years of watching the extracellular matrix successfully morph into whatever tissue it was inserted into–from nerve cells to muscle and bone–the research stubbornly refused to get funded. As Dr. Badylak told the Purdue alumnus, “Nobody thought it was worth funding because it was such a crazy idea. Why would anyone want to put pig tissue in a human?” But profit-minded entrepreneurialism saved the day from pundit-advised conservatism. Eli Lilly and Co. and DuPuy, an orthopedic company in Indiana, put real money into the idea. With the help of drug company coffers Dr. Badylak’s research took off and eventually Washington came aboard. The current study that gave Corporal Hernandez much of his thigh back is a trial in collaboration with the U.S. government. As part of a $70 million government program for regenerative medicine, it’s hoped that Hernandez’s will be the first of many such success stories.

Given that the U.S. is currently fighting two wars, the victory for regenerative medicine couldn’t have come at a better time. “I get six to eight emails a day (from potential patients),” Dr. Badylak said in December of last year, long before news of Corporal Hernandez’s regrown thigh. Let’s hope that this treatment makes it to the clinic soon, so that Dr. Badylak can answer not only their emails, but their prayers as well.

[image credits: dailymail.co.uk, Acell]
image 1: Hernandez
image 2: Acell

Behold: the Cornucopia of Youth?

When lunchtime rolls around, what are you thinking about: your health or your hunger? We all want to eat healthier in theory, but for many of us, attempts at healthier diets tend to be sporadic and short lived. Which is unfortunate on the one hand, since reams of medical research is showing that eating “right” has a probabilistic effect on health — and lifespan! On a demographic level and in controlled individual trials, people who eat better can live decades longer in excellent health.  Meanwhile, the rest of us are getting by on whatever diet we’ve lucked into and relying on doctors to do the rest.  But how long will we have to wait before researchers develop bio-technologies that will halt or even repair the damage caused to your body by aging? Are we doing enough in the mean time?

If it were up to David Murdock, he’d tell you to be doing more. A billionaire several times over, Murdock has lived the American dream, starting out destitute and penniless after World War II and later rising to prominence and fortune through business. But losing both his wife and mother to cancer several years ago radically altered his priorities and made him a man on a mission. Now he’s investing his time and money to improve the state of health, biotechnology, and personal longevity… including his own. (He plans to live to 125!). His message: No matter what you pack for lunch there’s likely lots of room for improvement — and he’s not afraid to tell you so. He’s been featured on the Hub before, along with others of his cohort who believe the key to longevity is eating right and exercising.  Average lifespan (and health-span) are correlated with lifestyle and diet is a big component of that.  Individual supplements are touted as essential for anyone who wants to improve their chances of ultra-longevity – Ray Kurzweil famously takes over a hundred on a daily basis.  And some people take this ethos to heart, devoting a huge portion of their lives to optimizing their meals and exercising so they can spend even longer doing it.

But there are reasons to be skeptical of claims like these too.  Sure, Murdock enjoys enviable health and he’s in his late eighties.  But he didn’t start his extreme healthful habits until his sixties and has always been “naturally slender”: if he’d been predisposed to accumulate damage from eating his choice of less-saintly foods, it would have built up by the time he began his crusade.  His wife Gabriele’s cancer killed her when she was 43: she wasn’t lucky enough to last until he learned the nutritional secrets he believes could have saved her.

Billionaire David Murdock intends to live to 125

Meanwhile, others who have lived long past their 100th birthdays such as Sakhan Dosova (who may have been as old as 130 when she died) rarely list their favorite foods as carrots or cantaloupe. Her favorite food: cottage cheese and ground wheat.  We wouldn’t have heard about her, or her predilection for dairy and carbs, if she hadn’t gotten to such an impressive age – but by the same token, we would never have heard of someone like Murdock who used the same diet and wasn’t doing as well.  Why attribute health to diet, and not good genes, or any of the other predictors of low mortality? Murdock also has the advantage of being a billionaire: that helps.

Let’s optimistically assume that Murdock and other who overhaul their lives to extend them are doing something right, and will get more years for their trouble.  Even so, some people don’t want to settle for lifestyle-based methods and the – at best – a few extra decades of extended life.  SENS has been working on regenerative medicine, which is intended to remove cumulative harm done to the body using bio-technology that we can use to possibly repair damage.  If it works as advertised, it doesn’t have the upper bound of efficacy that lifestyle-based choices seem to have: you could keep patching yourself up until you were several centuries old, not just the one and a quarter Murdock plans for.

However, research in general progresses slowly, and you can’t yet check in to a rejuvenation pod and emerge looking twenty-something every time you have another birthday.  As long as there’s a hint that passing on the bacon and filling up on blueberries will help, take advantage: they might let you live long enough to see the really snazzy tech.

[image credit: Jemal Countess/Getty Images]

Eye Robot

Robots have been trying to invade our bodies for years. Now they’ve found a way to get in our eyes and–if we’re lucky–we won’t even know about it.

Bradley Nelson is a Professor of Robotics and Intelligent Systems at ETH-Zürich and is the founder of the Institute of Robotics and Intelligent Systems where he leads the Multi-Scale Robotics Lab. Dr. Nelson and his team have created a robot that, once injected into the eye, can be moved forwards, backwards, and turned in place–all by remote control. If they can shrink their micrometer-scale robot enough to fit into a 23 gauge needle it could be injected into the eye with little or no anesthetic.

The MagMite, as it’s called, is driven by magnetic propulsion. At the center of 8 overlapping magnetic fields (and their magnets) the MagMite’s movements are the net result of changes in the strengths of the magnetic fields. It has a mass of 30-50 µg and, measuring 300 µm x 300 µm x 70 µm, the microbot (a nanobot, of course, would have dimensions in the hundreds of nanometers) is comparable in size to the blood vessels in the human retina having diameters of approximately 150 µm. This is important as Dr. Nelson hopes MagMite will one day be used to treat retinal vein occlusion, a common cause of glaucoma or macular edema. The spatial resolution afforded by the MagMite would allow physicians to deliver drugs in a precise, site-specific manner. People with age-related macular degeneration, the most common cause of blindness among older people, would also benefit. Age-related macular degeneration is often treated with injections directly into the eye. But this leads to rapid diffusion of the drug and the need for regular injections. MagMite could remain in the eye for months, dispensing the drug in a time-release fashion.

So far it’s only been tested in synthetic eyes or eyes dissected from animals (the demonstration in the clip below is in a pig eye). Plans are in the works for human trials. Any takers? Try not to look at the needle headed right for your eye. Remember, it probably won’t hurt.

The magnetic control system developed by Dr. Nelson’s group is a major improvement over robotic propulsions systems of the past. A common strategy for designing medical robots has been to give it a kind of motor with the idea of enabling them to swim their way to targets in the body such as a tumor where they could deliver local chemotherapy. As we’ve pointed out before these mechanical approaches have several drawbacks including tissue damage caused by moving parts and the possibility of the motor getting snagged. These robots would also require nano-sized batteries which simply don’t exist yet. The ideal situation would be a robot that doesn’t require internal propulsion or power. That’s what Dr. Nelson has in his MagMites. We can conceive of letting them course through the bloodstream, passively going with the flow, until they near their target where the magnets could then be turned on and guide it the rest of the way.

The MagMite is a major achievement, but there are some additional major advances that need to be developed before anything like the scenario I described above becomes a reality. For one, the robot has to be seen. Dr. Nelson’s group chose to develop their MagMite in the eye because they can watch it from the outside-in (I’m certain it was experimental feasibility rather than a desire to treat eye conditions that drove their test target–but I digress). But even the eye presented difficulties. The various types of tissues that make up the eye scatter light differently. It was a major challenge for the team to tweak the optics so they could properly monitor the MagMite’s movements. Good luck trying to reach that lung tumor. For that to happen, the MagMite technology will probably have to be merged with that of carbon nanotube transmitters that would transmit the robot’s precise location. Again, this technology is a ways off yet.

Dr. Bradley Nelson's remotely-controlled MagMite may pave the way to future nanotechnology-based medicine.

But Dr. Nelson’s proof of principle is indeed a beautiful display of technological finesse. To manipulate 8 magnetic fields with such a soft touch as to precisely control a micrometer-sized robot is mastery. The MagMite’s speed tops out at 12.5 mm/s or 42 times the robot’s body length per second. At such speeds the robot can produce enough force to push objects of comparable size. It’s easy to get excited about the prospects of using MagMites for noninvasive surgery, at least in the eye where small changes in structure lead to big changes in vision. And the magnetic power required to move it is 2 mT, about 50 times the average magnetic field of the Earth and a thousand times less power than a typical MRI magnet.

At this point, the MagMite is really just a small magnet, not much of a robot at all. But that’ll change soon when Dr. Nelson enables it with drug delivery capabilities. At hundreds of microns the MagMite is not the ideal vehicle for drug delivery. Nanobots, with dimensions in the hundreds of nanometers, would be able to go where MagMite cannot (nanoparticles small enough to pass through cell membranes are already being created in labs). The dream application, of course, is to unleash trillions of robots into the body that would deliver drugs to specific sites, including specific organelles inside of cells. And yes, again, this technology is quite a ways off. But with Dr. Nelson’s demonstration, it was brought that much closer.

[image credits: NewScientist, Institute of Robotics and Intelligent Systems]
[video credit: NewScientist via youtube]

image: Bradley Nelson
video: NewScientist

If asking nicely doesn't work, maybe science can reveal the secrets of the immortal jellyfish!

The search for the fountain of youth has been ongoing ever since man decided that dying wasn’t all that appealing. And now, it appears that this elusive holy grail has been found, albeit by a species that is not ours! So who is the lucky winner of the everlasting life sweepstakes? None other than the humble and dime-sized jellyfish known as Turritopsis nutricula. This creature has accomplished what no other biological being on our planet has ever been known to do: reverse it’s aging to become young again after reaching full maturity! As early as 1992, scientists had observed this phenomenon in Turritopsis and research into its secrets was ongoing. However, a recent spike in the numbers and geographic distribution of this species has once again brought it to the attention of the greater scientific community because of the many important breakthroughs we have witnessed in stem cell research in the past decade. As regenerative medicine continues to grow into the future of medicine, it’s clear that this tiny jellyfish may hold the answers to not only addressing the many aging-related ailments we face, but also our own mortality!

In the picture below, you can see the typical lifecycle of a jellyfish. It starts out as a larva that eventually sinks to the bottom of the ocean and attaches to a sturdy substrate and continues development into a polyp that resembles a sea plant. The polyp then matures to become a free-floating medusa, what we commonly recognize as jellyfish resembling an upside down saucer with tentacles. Not much excitement so far, but Turritopsis has put an interesting twist to this process. It undergoes development much like what I’ve described above and what many of its relatives go through. However, during times of stress like a shortage of food, Turritopsis responds by beginning to reverse the process before eventually becoming a polyp again. From this point then, it can again develop into a sexually mature medusa when conditions become more favorable. Theoretically, it can repeat this process indefinitely as its cells undergo a process called transdifferentiation, a rare biological process whereby any non-stem cell can become a different cell entirely. It is still unclear whether only specific cells can only become other specific cells or if any cell in Turritopsis has the potential to become any other cell.

The typical lifecycle of a jellyfish. Exciting, isn't it?

Ok, what Turritopsis does is admittedly cool, but why would we care? As you know, here at the Hub, one of our favorite topics are stem cells and all the promise they hold for regenerating tissue and treating a vast array of ailments. And while stem cells are one avenue to reach the goal of regenerating damaged or diseased tissues, transdifferentiation is another option that can get us to that goal.

Allow me to digress here and clarify the difference between these two systems (also see the below figure). Stem cells are cells that can differentiate into any type of cell. They can be isolated from a natural state i.e. embryonic stem cells (ESCs), or created by taking already differentiated cells and coaxing them to undifferentiate into stem cells, becoming induced pluripotent stem cells (iPSCs). These stem cells can then differentiate into another type of cell. On the other hand, transdifferentiation doesn’t require the middle step of becoming a stem cell. Any differentiated cell can become any other differentiated cell, given of course that it receives the correct signals.

If transdifferentiation can be harnessed in the lab, we may be able to avoid using stem cells altogether.

Much of the advances in stem cell technology have come from having an understanding of how stem cells naturally develop into different cell types. Thus, nature’s methods are teaching us how to manipulate stem cells and turn them into the desired cell type. And when it comes to transdifferentiation, the hope is that we will eventually be able to learn how creatures like Turritopsis skip the stem cell step and go directly from one cell type to another. As such, a recent breakthrough in using transdifferentiation for therapeutic purposes was reached in the laboratory of Dr. Deepak Srivastava of the Gladstone Institute of Cardiovascular Disease at the University of California, San Francisco. In a recent article in the journal Cell, Dr. Srivastava’s group describes their success in getting architectural cells in the heart called fibroblasts to differentiate into cardiomyocyte-like cells. In case you’re rusty on your cardiac anatomy, cardiomyocytes are the cells in the heart that contract and result in it’s rhythmic beating. And as Dr. Srivastava explains in the video below, it is the loss of these cells and the development of scar tissue that is debilitating to those fortunate enough to survive a heart attack. So by just switching on three genes in the fibroblasts, the researchers were able to coax them to transdifferentiate into cardiomyocyte-like cells that looked and behaved like cardiomyocytes. Taking it one step further, they implanted these cells into the hearts of mice and found that they behaved just as one would expect them to. In a previous post, we had described similar results, but in that work, the researchers had to first produce stem cells from skin cells before producing the cardiomyocytes. Clearly, Dr. Srivastava’s group has taken this to another level.

So while we still have some hurdles to overcome before this type of treatment is available for use in humans, it is indeed on its way. The amazing work being done in laboratories such as Dr. Srivastava’s are inching us closer to the day when perhaps we’ll be able to not only treat various ailments, but also to turn back the hands of time and reverse our aging like Turritopsis has been able to do. A recent press release by Advanced Cell Technology (ACT) hints at some potentially new technologies they are developing to take advantage of transdifferentiation. While most of their work thus far has focused on stem cell-based treatments, it’s encouraging to see companies like ACT put time and money into exploring transdifferentiation-based treatments as well. Sure everyone is working to get to the same goal, but there may be more than one way to get there!

[Sources: Cell, National Geographic, Wikipedia, Advanced Cell Technology, Gladstone Institute of Cardiovascular Disease, Nature Reviews Genetics, KQED TV]
[Image Credits: Russel McAvoy, Nature Reviews Genetics]
[Video Credit: KQED TV]

Patients can control a computer with their thoughts using ECoG electrodes placed directly on the brain.

A temporary surgical implant enabled patients to “talk” to a computer. Just by thinking the words aloud in their head they were able to control a cursor on a computer screen. The brain-computer interface (BCI) technology could one day be used to help people who are unable to talk or have other physical disabilities due to brain injury. The technology could one day be used to read a person’s mind.

Published April 7 in the Journal of Neuroengineering, the study was carried out by scientists at the Center for Innovation in Neurosciences and Technology at Washington University in St. Louis. The team was led by Dr. Eric Leuthardt, a pioneer in the field who previously developed a BCI that enabled people to play video games with their thoughts. In the current study a net of ECoG (electrocorticographic) electrodes was temporarily placed beneath the dura, a layer of connective tissue surrounding the brain. Rather than performing a craniotomy and placing electrodes on the brain for an experiment–might be hard to get approval for that–the original purpose of the electrodes was to map activity in patients with intractable epilepsy so that those areas could be surgically removed. As human brain studies are often brought about, Dr. Leuthardt combined his clinical aims with experimental. The ECoG electrodes detect the activity of underlying neurons and transmit the signals to a computer that then uses the signals to perform a task. In the current study the patients’ brain activity was used to control a cursor on a computer screen. Remarkably, the patients were able to accurately control the cursor in as little as 4 minutes. The slowest of them took 15 minutes. The ease with which the patents were able to perform the task is an encouraging sign that the technology could be applied to prosthetics control.

Other researchers have successfully used a BCI to interact with a computer. What’s novel about Leuthardt’s study was the region of the brain they recorded from. Building off work in monkeys where a mathematical relationship was found between the activity of motor cortex neurons and movements produced, early work in neural interfaces for prosthetic control logically focused efforts of how to use the motor cortex as the brain activity source. Leuthardt’s group, however, took a different approach. They hypothesized that, instead of imagining an arm movement–from right to left, for example–the patient could control the cursor with sounds either spoken aloud or imagined.

Instead of recording from the motor cortex, the researchers needed to record from the speech centers of the brain: Wernicke’s area in the temporal lobe and Broca’s area in the frontal lobe. The patients were asked to say or think of four sounds: oo, ah, ee, and eh. The computer then associated the patterns of brain activity that represented each of the sounds and tied specific cursor movements to the sounds. When the patient said or thought “ah” for example, the cursor would move left.

Spoken or imaginary sounds generate brain waves which are recorded by ECoG electrodes and sent to a computer to control the movements of a cursor.

Using the brain’s speech centers instead of the motor area was a major achievement. Human speech has been studied extensively with brain imaging techniques such as positron emission tomography (PET) or functional magnetic resonance imaging (fMRI). Data from these experiments have revealed a great deal about how different parts of the speech network work together to produce and understand language. But prior to Leuthardt’s demonstration it was not known if speech network activity could be used in BCI control.

Will the computer understand us if we simply talk to it? This is important for neuroprosthetic devices of the future as it expands the repertoire of brain function that clinicians can potentially use to control a robotic limb.

Another way to phrase the above question: can the computer read our minds? Amazingly, the answer seems to be yes. But simple oos and ahs are one thing, articulated thoughts are quite another. When we talk–either to each other or internally to ourselves–our thoughts aren’t limited to the words we’re using. Our brain relates to the words in intuitive ways, as in all of the imagery and associations that pop up in our heads when we hear a simple word like “ninja.” BCIs are a long way off from extracting the tremendously more complex idea of ninja our brain conjures up, but understanding overt statements from the brain is a step in that direction. It’s fun to think that this technology might be used someday to record our thoughts in the same way tape recorders are used. Brain implants could enable us to “jot down” lecture notes in our thoughts and retrieve them from the computer later. You’ll definitely want to keep those notes heavily guarded, lest someone hacks in and realizes that your mind kept wandering to the cute girl in the row next to you.

The video below from Russia TV Today is a great summary of the state of BCI technology today. Instead of using surgically-implanted ECoG electrodes, the Russian scientists in the video use a much more user-friendly “shower cap” of EEG electrodes that can read brain waves from outside the head. The video nicely illustrates the technology, including the difficulties of calibrating BCIs. Check it out as users solve puzzles, drive a remote controlled car, and move a ball across the floor using only their thoughts.

Computers are already being used to read our minds–and companies are cashing in on the data. Neuromarketing is a field born when a neuroscientist performed the Pepsi Challenge while scanning people’s brain activity with fMRI. The study showed that a part of the brain called the medial prefrontal cortex lights up when people really like a product. As before, Pepsi beat Coke and when they drank Pepsi the MPC lit up. But then why, if more people prefer Pepsi, does Coke dominate the market? The answer came when researchers uncovered the labels. Now that the people knew what they were drinking, the MPC lit up with Coke, not Pepsi. The conclusion was that Coke’s advertising was much more effective than Pepsi’s: even though people preferred Pepsi, they thought they preferred Coke. Lighting up the MPC meant a refreshed and satisfied Coke drinker. Thus, a cottage industry was born. Companies began putting people in MRI machines and testing their slogans and ad campaigns, and watching to see if the MPC lit up. If it did, it meant the consumer was thinking, “I need that pair of shoes.”

The potential of combining mind and machine is limitless. The two are being brought ever closer as developments in BCI technology proceed in parallel with our increasing understanding of the how the brain works. The future of BCIs will take us in even more exciting and unpredictable directions. Whether it improves the lives of disabled people, enhances our use of information, makes video games more fun, or makes companies money only time will tell. Eventually, I have no doubt, it will be all of the above and more.

[image credits: Journal of Neuroengineering]
[video credit: moscowbci via youtube]

video: Russia TV Today

Coming To A Town Near You - Antibiotic Resistant Bacteria

Be afraid. Be very afraid.

The widespread misuse of antibiotics is rapidly rendering them powerless against infection. Common infections that are easily cured today are going to become deadly, and it’s going to happen sooner than you think.

The World Health Organization reports:

* Each year there are about 440,000 new cases of multi-drug resistant tuberculosis, resulting in at least 150,000 deaths.

* Resistance to antimalarial drugs chloroquine and sulfadoxine-pyrimethamine is now widespread in most malaria-endemic countries, leading to the resurgence of malaria in areas where the disease had previously been eradicated.

* A large proportion of infections contracted in hospitals are caused by highly resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA).

* An estimated 25,000 patients in the European Union die each year from drug-resistant infections.

Antibiotic resistance arises when the treatment doesn’t kill off the entire infectious population. The genetic variability of bacteria will inevitably make a small portion of them resistant to the antibiotic. These surviving members are then left to proliferate and spread their antibiotic-resistant genes. It’s a consequence that today’s caregivers are aware of, but the rate at which antibiotic resistance is spreading indicates that we’re not doing enough to slow the process.

And maybe we should. Like, now.

Dr. Margaret Chan, the Director-General of WHO, paints a dire picture of our immediate future. Speaking on April 7th in a World Health Day 2011 podcast, Dr. Chan says, “The message on this World Health Day is loud and clear. The world is on the brink of losing these miracle cures. In the absence of urgent corrective and protective actions, the world is heading towards a post-antibiotic era, in which many common infections will no longer have a cure and, once again, kill unabated.” Watch the video and sit in the hot seat and receive a tongue-lashing on behalf of the entire developed world from Dr. Chan.

So why are antibiotics losing their effectiveness? There are a number of factors, but most of the blame lies with doctors who overprescribe the drugs. They’ll prescribe antibiotics that kill many types of bacteria even when the patient is at risk for a specific infection. Unbelievably, doctors will give antibiotics to patients to “cure” conditions that are caused by viruses, such as the common cold. Why? Because the patient insists. Sometimes the doctor is simply too busy to explain to the patient why he or she doesn’t need antibiotics, but in the interest of time prescribes it anyway. Are you kidding me?! Documentation of these incredible findings can be found here.

She looks all smiles but WHO Director-General Margaret Chan means business as she sounds the alarm to halt practices that promote the spread of antimicrobial resistance.

But doctors don’t shoulder all of the blame. Patients who don’t stick with the prescribed regimen and complete the treatment properly end up feeling better, but they also allow some of the infectious microbes to remain alive, thus allowing them and their resistant genes to proliferate.

Another huge problem is the use of antibiotics in food-producing animals. Approximately half of all antibiotic production is used in agriculture. Factory farms routinely give perfectly healthy animals antimicrobials both as a precaution against infection and to promote growth. This leads to resistant bacteria, which can then spread to humans through the consumption of meat, direct animal contact, or via environmental spread through, for example, contaminated water. This is confounded with veterinarians in many countries whose income is largely derived from the drugs they sell. Try convincing one of these vets to take a hit in the pocketbook for the good of humanity.

For World Health Day 2011 the WHO issued a six point Policy Package To Combat Antimicrobial Resistance. A common component among the points was multi-agency cooperation: governments, doctors, patients, and communities worldwide all working together to stem the antimicrobial tide. A lovely thought, but it’s not going to happen.

Antimicrobial resistance is inevitable. What’s not inevitable is, as Dr. Chan says, “losing these miracle cures.” But, in my opinion, the WHO package is simply unfeasible. At the risk of drawing Dr. Chan’s ire, I think our best hope in fighting antibacterial resistance lies, not in the well-wishing hands of policymakers, but in the self-serving craft of economic forces. Think of MRSA as a new disease, which it is. Drug companies will want to cash in. Each time a new strain crops up that’s resistant to current antibiotics drug companies will scramble over each other to get their pills out first. Speaking of MRSA, Merck and Intercell are well underway testing a vaccine for it in humans. See what I mean?

Granted, a microbial arms race is not the ideal approach. It would be great if governments and doctors and patients would all work together in perfect harmony with the world’s long-term health in mind.

World peace would be great too.

Our misprescribing of pneumonia taught us a lesson: too many antibiotics = high resistance. It seems that we, unlike the microbes, are slow to learn. (From Albrich et al., 2004)

The business of making antibiotics, however, is a lot tougher than it used to be. Since the use of antibiotics became widespread in the 1940s the field has seen a single Golden Age come and go. In the 1950s and 60s developers produced multiple classes of antibiotics to battle diverse types of infections. In the 1980s and 90s they were able only to make improvements within a class. The trend begs the question of whether or not we’ve hit the wall on this one. Have we tapped our antibiotic reserves for every last drop? If so, shouldn’t we be witnessing, now, the emergence of a resistant time bomb? The SARS virus and the avian flu outbreaks had us staring nervously at news flashes as the boundaries of the impending epidemic crept from the far reaches of the globe toward our homes.

And then they were gone.

Vaccines were developed for both, but the SARS epidemic was contained years before its vaccine ever saw the light of day. A rapid, global public health response is what stopped it. Apparenlty, we can work together–when we’re scared to death.

I use SARS as an example of how changing habits in the absence of a cure-all antibiotic or vaccine can be extremely effective–within 6 weeks of its discovery the SARS virus had infected thousands of people on 6 continents–and may be the reason we have yet to see a resistant time bomb. The fear of H1N1 put hand sanitizer dispensers in the lobbies of hospitals, schools, and offices. And they’re there to stay. Now you feel guilty walking by one and not squirting your hands sterile. Everyone’s doing it. Everyone’s hands are sterile.

Simple improvements in hygiene practices are probably behind the recent decrease in MRSA infections contracted in hospitals (healthcare-associated MRSA). Likewise, the continued problem of MRSA infections that begin outside of hospitals (community-associated MRSA) is probably due to a lack of change.

It’s hard to predict the future. The world’s a pretty crowded place. Will the resistance time bomb explode and a microbial butterfly in China cause a pandemic hurricane in Canada? Has the bomb already gone off but we just don’t know it? Or are we kind of like the little buggers themselves, modifying our strategy to counter theirs using a mixture of greed and panic instead of genetic variation?

I’m going to try and not worry about it too much. I’ll take all of my pills (only the necessary ones!), sanitize my hands, and drink my orange juice. And I’ll try to shut out Dr. Chan’s shrill voice, over and over again heeding her warning “…once again, kill unabated…once again, kill unabated.”

[image credits: Fabio Pozzebom, Agencia Brasil via wikicommons; CDC]

image 1: wikicommons_chan

image 2: CDC_emerging_infectious_diseases

video: Dr. Chan

A labrador retriever was trained to detect cancer in patients just by smelling their breath.

Maybe you’ve heard that line about dogs being able to tell whether or not someone has cancer just by smelling their breath. And maybe you think it’s baloney, kind of like eating chocolate will kill a dog, or cats can tell when a person is going to die?

Wrong. Wrong. Um, I have no idea.

It may surprise you to know that the ability of dogs to smell cancer is well documented. A 1989 report marked the first medical record of what had been known anecdotally in communities around the world for hundreds of years. Subsequent studies have quantified just how skilled dogs are at detecting different cancers including lung, breast, ovarian, and bladder cancers, and skin melanoma. Incredibly, they can do this just by smelling the patient’s breath.

The top three killer cancers worldwide are lung, stomach, and liver cancers. Number four is colorectal cancer (1.2 million new cases in 2008). A recent study published in the journal Gut, adds colorectal cancer (CRC) to the list of cancers that our canine friends can sniff out. Kyushu University’s Yoshihiko Maehara and colleagues began by training a Labrador retriever (named Marine) in scent detection of cancer by exposing it to the breaths of healthy people without cancer and patients with confirmed colorectal cancer. They also trained Marine with watery stool samples to compare her performance to the fecal occult test, a common CRC screen. Thirty-three patients and 132 healthy controls were tested. For each trial Marine sniffed five samples, four from healthy controls and one from a patient. She was taught to lie down on the floor upon positive identification of a patient. Marine’s accuracy was astounding. Of the patients conventionally diagnosed by colonoscopy she correctly identified 91 percent based on the smell of their breaths—making the distinction between cancerous and benign polyps—and she was correct in excluding 99 percent of the healthy samples. When she was presented with the water stool samples her accuracy increased to 97 percent. Compare that to a 70 percent accuracy of fecal occult tests. What’s more, Marine was better at detecting early-stage cancers.

I told you it was astounding.

The potential here is obvious. Every dog park in the world is populated by highly-accurate, non-invasive cancer screens. Patients with familial adenomatous polyposos or Lynch syndrome—different forms of CRC—are subject to frequent colonoscopy to minimize the morbidity and mortality associated with CRC. Imagine if they had only to blow into a bag.

So why not bring Marine and her friends into the clinic?

“Come right in Mr. Jones. Put on this robe and have a seat on the table next to Fido.”

In fact, some people are pushing to get dogs into the clinic. But there’s resistance to that, and it’s understandable. The oft cited argument against this was in fact mentioned in the current study: “It may be difficult to introduce canine scent judgement into clinical practice owing to the expense and time required for the dog trainer and for dog education.”

I don’t buy that. Recent research shows that among the causes of death in the world cancer has the most devastating impact on economy. I admit I haven’t crunched the numbers to determine just how much a dog would cost a clinic—but I’m still not buying it.

I suspect it’s something else. I suspect it comes down to confidence in Fido, despite what the data says they can do. Usually when a person is diagnosed with cancer he’s looking at a mass in an MRI scan or results from a biopsy. This is hard, tangible evidence with a good track record. How many of us would immediately commit to the frightful regimen of chemotherapy and surgery that follows a cancer diagnosis because a dog lay down on the floor? What if the dog was too good at early detection and follow-up verification showed negative? What do you do then? What would you do?

The much more accepted approach is to bring dogs not to the clinic, but to the lab. The goal here is to identify the compounds in a person’s breath that signals to the dog cancer. But that’s a really, really tough task.

We all know that a dog’s sense of smell is far better than that of a human. A dog can detect odor molecules at concentrations as low as one part per trillion while the limits of human detection top out at about one part in several billion. Obviously there’s something unique about the odor of cancers otherwise the dogs wouldn’t be able to distinguish diseased breath from normal breath. Numbered among the normal odorants in the patient’s breath is (are) molecule(s) produced solely by the tumor, and the fact that they’re detectable in the breath means they’re systemic.

A cell becomes cancerous when the replication machinery malfunctions and the cell proliferates out of control, resulting in a tumor. This process involves gene and/or protein changes that may result in peroxidation of lipids that make up the cellular membranes. These peroxidized lipids then generate what are called volatile organic compounds (VOCs). Dogs, as well as other animals, are currently used in research to screen for tumor-specific VOCs in the hopes of identifying them. If we can identify them, then we could build chemical sensors to detect them. But it’s estimated that a single breath contains hundreds of thousands of compounds. To identify them all and rule out those not produced by the tumor is a daunting task to say the least.

But maybe we don’t have to.

Dr. Hossam Haick of Israel Institute of Technology invented an "electronic nose" able to detect cancer in the breaths of patients. He was named one of the "Ten Most Promising Young Israeli Scientists" in 2010.

Gene arrays that compare gene expression patterns between healthy and diseased cells often show differences in tens or hundreds of different genes. From a diagnostic standpoint, that’s enough. If, instead of trying to identify the VOCs generated by tumors, what if we simply compared VOC concentrations in healthy individuals with those of cancer patients. If the VOC profiles between the two groups are sufficiently different it would make for a very effective screen.

Hossam Haick at the Russell Berrie Nanotechnology Institute, Israel Institute of Technology, has built such a screen. Described in a study last August, Dr. Haick’s group developed a kind of “electronic nose” that can “smell” VOCs. The nose is actually a nanosensor array of organically functionalized gold particles that can detect trace amounts of VOCs. Single, exhaled breaths of patients with lung, colon, breast, and prostate cancer were analyzed with the array and compared with the breaths of people without cancer. The results showed a distinct difference in the VOC profile of cancer patients compared to the cancer-free group. The differences were then confirmed with gas chromatography linked to mass spectrometry, technology commonly used to quantify chemical concentrations.

This is an incredible example of technology imitating biology and I’m extremely eager to see how the electronic nose is put to use. If we do find ourselves one day soon, blowing into a bag as a normal part of our checkup, we should remember to thank our canine friends when we get home. Were it not for dogs like Marine pointing the way, researchers like Haick might not have known to look in the first place. And while the electronic nose looks promising, it is as yet still unproven in the clinic. That leaves us with only our dogs to sniff out cancer. And thus it is unfortunate that their use in cancer detection is not more widespread as a tool that could at least assist, if not replace current diagnostic tools.

[image credit: Peter Wadsworth via WikiCommons]

[image credit: Russell Berrie Nanotechnology Institute at the Technion -- Israel Institute of Technology]

Image 1: http://commons.wikimedia.org/wiki/File:Labrador_Retriever_black_portrait_Flickr.jpg

Image 2: http://rbni.technion.ac.il/.upload/hossam35.JPG

One liver failure, coming right up!

We have heard for years that diabetes is a serious problem in America, but people really do not like to listen. The result of such stupidity is 52% of Americans being diabetic or pre-diabetic by 2020, as predicted by United Health Group. That is more than two times the amount of diabetes cases registered in 2010 (24 million, in case you were wondering). What is really disturbing is that this trend is continuing despite rapid improvements in science and technology, all due to extremely poor lifestyle choices made by the majority of the population.

Diabetes is a metabolic condition characterized by an abnormally high blood sugar level, which disrupts the normal functioning of multiple organs. There are two main types of the disease. In Type I diabetes, the body simply does not produce enough insulin, the primary hormone in the body responsible for regulating the level of sugar within our bloodstream. This condition can usually be treated fairly effectively with supplemental insulin injections. Type I diabetes is a relatively rare immunological disorder. Sadly, however, 95% of diabetes cases are Type II diabetes, a mostly avoidable type of diabetes caused almost entirely by obesity and living an unhealthy lifestyle.

In Type II diabetes, the body’s cells simply become insensitive to insulin, and it does not matter how much of it the body produces, or someone injects into his or her self.  Normally, muscle cells are meant to store sugar, but in obese individuals, excess fat, which no longer fits in the body’s fat cells, is being stored in muscle. This prevents the muscle cells from using sugar for energy, as they are now made to use fat. All the sugar that would have been stored in the muscle is now left free to float around in the blood. The excess fat also blocks muscle cells’ insulin receptors, thus significantly lowering their sensitivity to insulin. Diabetes, over the course of many years, leads to a terrible bouquet of complications such as coronary heart disease, kidney failure, blindness, and chronic wounds with a very possible development of gangrene. Sure, it all seems like a long way off, but if you ask me, a daily junk food fix is not worth the risk of having half your fingers and toes amputated by the time you reach sixty.

As much as we may hate to admit it, the comforts afforded by today’s post-industrial lifestyle come at a very high price. The average person’s day consists of sitting in an office chair for 8-10 hours and then migrating to the living-room couch to sit in front of the TV. This sedentary routine is interrupted usually only for meals, which consist of very liberal amounts of sugar and salted meats with little, if any, fruits or vegetables. The only time physical exertion enters into such average people’s lives is when they are exercising the gas pedal on the way to and from work, or, for those who are more fortunate, when they are taking the ten minute walk to the nearest subway station. Should it come as a surprise that almost 68% of Americans are subject to the number one risk factor of diabetes – obesity?

Type II diabetes is not a result of infection, nor can it really be chalked up to genetic pre-disposition. Contracting this disease or not depends almost entirely on the lifestyle one leads. A fairly recent study by the Salk Institute has described a second link between obesity and diabetes. Excess fat stores in the body hamper protein production, which, in turn, triggers the inappropriate start of gluconeogenesis, a biochemical pathway used for glucose synthesis. With such a strong correlation between diabetes and obesity, it is only common sense that the disease can be largely, if not 100%, prevented through proper lifestyle decisions. That means eating a healthy diet – significantly reducing consumption of refined sugars and saturated fats, eating more vegetables and foods rich in vitamins, especially A, C, and E, and incorporating regular exercise into one’s daily routine.

Let us briefly consider the economic side of the growing diabetes epidemic. The past year, $194 billion were spent on diabetes-related care alone, which already accounts for 7% of total US healthcare costs. That number is said to rise to $500 billion in 2020, totaling a lofty $3.4 trillion over the next ten years, all according to the same United Health Group report. To make it more understandable, on a personal scale, diabetes cost $8,000-$12,000 per year not counting the cost of prescription drugs. However, that is all just the tip of the iceberg. Imagine a country, more than half of whose population is suffering from a debilitating and expensive disease.  How productive will such people be in the country’s economy? How many days of work will have to be missed for health reasons? In fact, it is very likely that the rise in diabetes cases will be coupled with a marked decrease of production in most sectors of industry.

Living a long life has always been respectable, regardless of time, place, or occupation. All over the world, centenarians, those lucky individuals who live to see their 100^th birthday, are recognized by gifts and certificates or official letters from their governments. However, in today’s post-industrial society, people have become too dependent on technology and medical innovations to prolong their lives. True, the last hundred years have witnessed astonishing progress: in 1911, we still rode horses as a main mode of transportation; in 2011, we send rockets to space every other week, but technology is still not at the level where it can miraculously fix all of our problems, nor will it be there any time soon. The most efficient way to live a long and, most importantly, healthy life is to make good lifestyle choices such as eating a correct diet and exercising regularly. There are no magic pills – at least not yet. Making the right choices is exactly how the residents of the so-called blue zones, which we have covered here at Singularity Hub before, achieve their longevity. Nevertheless, people continue to invest all of their hopes in technology while taking little to no responsibility for their health and making terrible lifestyle choices. The result is nearly 70% of Americans suffering from almost entirely preventable chronic illnesses such as heart disease, lung and liver cancer, and, of course, Type II diabetes.

Scared yet? You should be. This is a very real problem and not some fantasy concocted for a horror film by an insane writer. In the end, the one wielding the most power to affect a person’s health is himself, and the fact that a growing epidemic of such proportions is almost completely self-inflicted is ridiculous, not to say downright crazy. We are all very eager to reach the Singularity, but until we actually do, we have to learn to take responsibility for our actions, including our health, leaving medical devices such as the iPhone glucose tester and the silicon pancreas a no more than supporting role. Otherwise, we simply might not live long enough to see it.

[Image Credit: Sly Jones, Graham Richardson]

[Source: CDC, Salk Institute, United Health Group]

A completely random picture of a lab mouse

According to those idiots over at the Guardian, “Harvard scientists reverse the ageing process in mice – now for humans”. As if that were not miraculous enough, the Guardian also claims that “Now they believe they might be able to regenerate human organs”. Here at the Hub we would love nothing more than for this story to be true, but alas it is one of the hugest piles of sensationalist bullshit I have seen on the net in quite a while. The scientific research cited by the Guardian does not support these sensationalist claims and the Guardian knows this. But they don’t give a damn because sensationalism sells – big time! The Guardian knows that sloppy, idiotic bloggers and news organizations across the web will regurgitate anything they see without hardly the slightest attempt at fact checking. And hence this bogus story has been an enormous hit. The story already has more than 15,000 Facebook likes and this number is sure to grow.  It has been picked up and rehashed as a legitimate scientific story by major news outlets, including the Wall Street Journal, Digg, Endgadget, Wired, and many more. Congratulations to the Guardian and the author of the story, Ian Sample – you have created a story that sells well, but your reputation is utter crap.

First let us take a brief look at the scientific research that Guardian correspondent Ian Sample claims will reverse aging and allow us to regenerate human organs.  Scientists at Harvard genetically altered mice so that they lacked an enzyme, telomerase, that is responsible for maintaining proper telomeres.  Telomeres are repeated sequences of DNA at the ends of our DNA that protect the DNA from damage.  Without the ability to produce the telomerase enzyme, the mice had essentially nonfunctioning telomeres, leaving their DNA unprotected and prone to extensive damage and malfunction over time.  To no one’s surprise, as these mice grew and lived out their lives within the laboratory their bodies quickly broke down.  Their organs began to fail – they lost their sense of smell, they became infertile, they were weak.  With the mice now in this degraded state (that we are lead to believe approximates aging), the Harvard researchers then proceeded to give the mice regular injections to reactivate the telomerase enzyme to see what would happen to them.

So what happened to the mice once their broken, dying bodies were finally given injections to activate the vital telomerase enzyme that they had thus far been denied?  In what will be a surprise to nobody (except apparently the Harvard researchers and Ian Sample at the Guardian) the bodies of the mice stopped their decay.  As if this were not miraculous enough, the bodies of the mice also seemed to regain some of their lost vitality and function now that their DNA was allowed to function properly.  Isn’t that amazing?

Any reasonable person would quickly summarize this research as something like “take away a vital enzyme from an organism and it starts to decay, give the enzyme back to the organism and decay stops, allowing the natural process of repair and growth in the organism to proceed”.  The research sheds some light on how crucial telomerase and telomeres are to the proper function of an organism, but unless you are an expert in that field this is a non-story.  This research is a long, long way from leading to a reversal in aging.  Unless, that is, you are Ian Sample working for the Guardian, in which case apparently you have just stumbled upon a fantastic piece of research that you can use to create a misleading and sensationalist story that will sell to mindless readers and bloggers.

I can’t figure out what is more ridiculous here.  Is the Guardian story itself the most ridiculous thing, or is the fact that the story was blindly syndicated by thousands of news outlets and believed by millions of readers across the world even more ridiculous?  Ian Sample and the Guardian must be laughing all the way to the bank with the traffic this story is generating for them.  Readers will correctly point out that I am only aiding their little game by giving the story even more prominence and calling it out in this post.  To that all I can say is that I can’t stop people from reading the Guardian’s BS, but at least I can do my part to show the world what complete crap it is.  The Guardian has gained itself a hugely popular story, but at what cost to it’s reputation?  Sadly, most people probably won’t even care.  But I can hope.

Image source [rama]

Between 1991 and 2006, cancer death rates dropped 21% in men and 12.3% in women. Fewer people are getting cancer in the first place: the incidence of cancer has decreased 1.3% per year in men from 2000 to 2006, and 0.5% per year in women from 1998 to 2006.

Most cancer deaths in men are caused by lung (29%), prostate (11%), and colon/rectal cancers (9%). The number of deaths caused by these cancers is on the decline; together, they account for 80% of the dropping death rate. In men especially, lower smoking rates have contributed to the decrease in lung cancer. Early detection has also had a big effect, with more men receiving regular prostate exams and colonoscopies to catch and treat cancer early.

Research at the ASC suggests that in 2010 alone, there will be 1,529,560 new cancer cases and 569,490 cancer-related deaths. Women are most likely to die from lung (26%), breast (15%), or colon/rectal cancer (9%). While lung cancer death rates in women have stayed roughly the same, decreases in breast and colorectal cancers account for 60% of the overall decline. Again, early detection through mammography and colonoscopy has been largely credited with the lowered rates.

Both cancer incidence and mortality have been declining since the early 90's

It should be noted that these dropping rates of incidence and death are not equally enjoyed across the population. African American men are still much more likely than white men to get cancer (14% higher incidence) and to die from it (34% higher death rate). African American women are less likely to get cancer, but more likely to die if they do, than white women. These demographic discrepancies are credited by the ACS to unequal access to quality healthcare, including being diagnosed in later stages of disease.

Cancer is the second leading cause of death (after accident) for children under the age of 14. However, survival rates for pediatric cancer have drastically improved in the past few decades. A child diagnosed with cancer between 1975-1977 only had a 58% chance of surviving for five years. Between 1999 and 2005, that likelihood increased to 81%. As research is underway to unlock the genetic causes of pediatric cancer, there is good reason to expect that incidence rates will decline in future years as well.

Many of these trends are the consequences of policy and healthcare shifts that took place decades ago. Some of the most exciting research on cancer is being done today: new treatments are not only treating existent tumors, but preparing the immune system to fight cancer before it starts. We’ve reported on the new BiovaxID vaccine for non-Hodgkin’s lymphoma, as well as gene therapy that teaches the immune system to fight melanoma (and can be watched in real time). The new drug Crizotinib is being used to inhibit genetic mutations in lung cancer patients, which has been effective in 90% of patients.

It will be interesting to see how these new treatments alter cancer incidence and mortality in coming years, especially if cancer vaccines can get off the ground.