The size of a large pill, the magnetic microswimmer will travel at several millimeters per second through your intestine while looking for cancer.

For years medicine has struggled to kill off all the little parasites swimming inside the human body. Now they’re ready to add their own. Researchers from Tel Aviv University in Israel and Brigham & Women’s Hospital in Boston have collaborated to create a robot that will be able to swim through the intestines. The size of a large pill, the “microswimmer” is powered by the strong magnetic fields generated by an MRI machine. A tail measuring 20mm x 5mm made of copper and flexible polymer vibrates due to the magnets and propels the little microrobot through the gut. Still in early testing, the magnetic microswimmer has been shown to maneuver well in a water tank. Eventually its creators hope that the robot will be able to quickly explore the intestines, sending back pictures to diagnosticians, and helping detect the early stages of cancer. As disturbing as it sounds to have a robot doing laps in your colon, such a device could save the lives of millions of people in the years ahead.

Current methods for detecting gastrointestinal cancer rely on various forms of endoscopy. For the better part of the last century, doctors have been able to insert a camera into the colon to detect precancerous or cancerous growths. More modern forms of detection include “capsule endoscopy” where a pill-sized camera is swallowed and pictures taken every half second or so until the device is passed. Even such improved forms of endoscopy, however, have their limitations. A swallowed pill is essentially at the mercy of the movements of the GI tract.

Not so with the microswimmer. Developed by Gabor Kosa (TAU), Peter Jakab (B&W) and their colleagues, the tiny robot is powered and propelled by magnetic fields. As explained in the recent paper published in Biomedical Microdevices, 3T MRI machines are able to get the little device moving at speeds of several millimeters per second – more than adequate for this type of endoscopy. With such controlled movement, doctors would be able to aim the microswimmer towards different portions of the GI tract depending on the needs for each patient. Part of the ingenuity of the microswimmer is its reliance upon the MRI machine. Rather than worry about embedding large power supplies or propulsion systems that would make the device untenable, they can instead rely upon an instrument that is nearly ubiquitous in larger modern hospitals. Furthermore, the copper and polymer tail hinders MRI scans very little, leaving just a modest shadow on the image.

As imaging technology continues to shrink, engineers are creating ever smaller and more versatile cameras. Some are so miniscule they can fit on the tips of wires, others contain onboard legs that can be used to crawl through the GI tract, and now Kosa, Jakab and the rest of their team have even introduced a swimming version. Taken collectively these devices suggest that in the near future doctors will be able to image the interior of the body at will. Eventually, such micro-explorers may even be able to reside inside humans on a permanent basis. Not everything that swims in your gut is bad for you.

[image via American Friends of Tel Aviv University and taken at Brigham and Women's Hospital]
[source: Kosa et al Biomedical Microdevices 2011, Kosa et al Robotics and Automation 2008]

Dream team researchers – and married couple – Wadih Arap and Renata Pasqualini have created a drug that fights obesity by killing blood vessels that vascularize fat cells.

Do we finally have a miracle weight loss drug? I mean, for real this time? The data seems to support such a claim, at least for overweight monkeys that simply can’t drop those extra pounds no matter what they try. After receiving the drug for just four weeks, the monkeys lost between 7 and 15 percent of the body weight, and averaged a more than 38 percent loss of total body fat.

The study, published November 9th in the journal Science Translational Medicine, was headed by husband-and-wife team Wadih Arap and Renata Pasqualini at the M.D. Anderson Cancer Center in Houston. Their drug, called Adipotide, targets the blood vessels that feed fat cells, or adipocytes. Attacking those blood vessels chokes off the nutrient supply that the fat cells need to survive and they either die or become stressed to the point that they don’t function.

Of course, blood vessels are needed to keep all cells alive. But the major medical advancement that adipotide brings is its ability to kill blood vessels associated with fat cells while leaving other blood vessels alone. The strategy has been long sought after by cancer biologists trying to kill cancer cells while leaving normal cells unharmed. Where others had failed, Arap and Pasqualini, cancer biologists themselves, succeeded by taking an approach that was novel in multiple ways.

A typical approach to drug development is to find or manufacture compounds that somehow slows or stops a disease. But instead of a targeted approach, the Arap and Pasqualini cast a wide net. Proteins in the body bind to other proteins, and which proteins get together is determined by their amino acid sequences. The Arap-Pasqualini team chopped up proteins into bits of peptide, or short chains of amino acids, injected them into the body and simply tracked where the peptides ended up. It’s as if the different parts of the body have different “zip codes” and each peptide sequence is drawn to a specific zip code. What made the study possible was the case of a brain-dead man who happen to be at M.D. Anderson Cancer Center. The man had wanted his organs donated but his cancer had advanced too far. After explaining their experiment, the man’s family agreed to allow Arap and Pasqualini to inject their peptides into the man’s body. Afterwards, tissue from the man’s skin, muscle, bone marrow, fat, and prostate were collected to see if any peptides had specifically bound to one tissue and not the others. They found one that bound only to blood vessels in the prostrate.

Body measurements such as body mass index and abdominal fat were measured using MRI.

In 2004 they conducted a study that bridges the gap between the cancer work and the current study. In the study they discovered a peptide that binds specifically to the blood vessels of fat tissue. Experimenting in obese mice, they showed that attaching a deadly substance to the peptide reversed the animals’ obesity, as they lost 30 percent of their body weight. In addition, metabolic impairments associated with obesity were also normalized.

The current study is essentially the mouse study repeated in rhesus monkeys. Importantly, the monkeys were naturally obese – eating more an being less physically active than the other monkeys – and thus did not require any special interventions to make them overweight. After four weeks of treatment the monkeys experienced an average loss of 11 percent of their body weight. Physical measurements such as body mass index (BMI) and waistline – abdominal fat dropped 27 percent – were also reduced. Adipotide goes after the so-called white adipose tissue, or the unhealthy type that amasses beneath the skin and around the abdomen. The fat cells that die after having their blood supply cut off are reabsorbed by the body. Conversely, giving the drug to monkeys of normal size resulted in slight weight gain.

As with obese humans, obese monkeys displayed an increased resistance to insulin. After a meal insulin is produced by the pancreas and released into the bloodstream to promote sugar uptake by muscles. Thus, insulin resistance can lead to high level of blood sugar levels which, in turn, can lead to complications such as kidney failure, heart disease, and blindness. Insulin resistance is also a hallmark of type 2 diabetes, the devastating condition that, along with obesity, is fast on the rise in the US and the rest of the developed world. Adipotide showed additional promise as a diabetes drug, as it decreased insulin resistance in obese monkeys by 50 percent. Arap and Pasqualini discuss the study in the following video.

The demonstration in monkeys is a major step if Adipotide is ever to be realized as a treatment as many drugs have shown success in rodents but not primates. “All rodent models of obesity are faulty because their metabolism and central nervous system control of appetite and satiety are very different from primates, including humans,” Pasqualini explained in a press release.

So how soon could Adipotide benefit humans? The group is currently preparing for clinical trials that could begin as early as next year. They plan on giving the drug to obese patients that have advanced prostrate cancer. Mortality with prostrate cancer who are also obese is much higher than that with patients of normal weight. The patients will be given the drug for four weeks with the intent to battle both body weight and cancer simultaneously. The monkeys that took the drug displayed no indications that the drug made them feel sick, a reassuring sign that Adipotide might not have major side-effects. The monkeys did, however, show a modest degree of kidney failure. Side-effects will be a major concern during the human trials as treatment is expected to be given to the patients long term.

Another major question, of course, is whether or not the zip code strategy will be as effective in humans. If it’s less selective and attacks other blood vessels, side-effects could be dangerous. Obesity and cancer aside, the fact that it worked in monkeys is already scientifically interesting. It shows that not all blood vessels are the same, that blood vessels which supply blood to the, say, kidneys are different from those that supply blood to the prostrate. The finding opens up the possibility for site-specific drug delivery in other types of cancer and other diseases. Two companies are already working with Arap and Pasqualini to translate their drug targeting strategy to actual treatments. Ablaris Therapeutics is already working with the Food and Drug Administration to begin clinical trials testing Adiplotide’s potential as an obesity therapy. Alvos Therapeutics will do the same with a drug that targets prostrate-supplying blood vessels to treat prostrate cancer. A study on the drug has already been completed at M.D. Anderson but the results haven’t been reported yet.

In scientific circles, hypothesis-driven experiments are vaunted while “fishing expeditions,” such as throwing a drug at the body and seeing where it sticks, are often viewed as not ‘true’ science. But it’s hard to argue that Arap and Pasqualini’s blind, wide net approach to battling disease should be discouraged. I wonder what other “zip codes” these cancer-turned-obesity scientists discovered with their peptides. Certainly we haven’t seen the last of that data. For the sake of medicine, let’s hope that there were plenty more fish in the sea.

[image credits: Popfi, Chron.com]
[video credits: mdandersonorg via YouTube]
image 1: Obese monkeys
image 2: Scientists
video: MD Anderson

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

Comparing mobile phone users and non-users over a period of up to 27 years, Danish researchers find no link between mobile phones and brain tumors.

The largest study of its kind to date found no evidence for a link between mobile phone use and brain cancer. With a dataset including over 350,000 mobile phone users across nearly 30 years, the study has finally put to rest the debate of whether or not we’re paying for the handheld amenities with our health.

Hold the phone, say cell phone awareness groups and some fellow researchers. According to them, the study is “seriously flawed” and should be considered “worthless.”

To get their cohorts, the research team at the Institute of Cancer Epidemiology in Copenhagan took advantage of Denmark’s registry system that has a record of every Danish resident since 1968. Many health outcomes, including cancer, are recorded in the registry, so the researchers simply broke the population into phone subscribers and non-subscribers and compared the two groups. The subscription holders totaled 358,403, which, combined with the non-subscription holders,  included essentially the entire Danish adult population.

Gliomas – so-called because they arise from glial cells surrounding neurons – are tumors that occur in the spinal cord or brain. Meningiomas arise from the meninges, the membrane surrounding the spinal cord and brain. The study showed no association between the formation of either tumor and mobile phone use, even when they only considered people who’d been using mobile phones for at least 10 years. Nor did they see an effect when analyzing the brain region closest to the handset. The negative findings are consistent with most studies that have tried to determine if mobile phone adversely affects health.

Hogwash, says the UK non-profit Powerwatch that concerns itself with the safety of electromagnetic fields and microwave radiation. They’re staffed with seemingly reputable experts such as Denis Henshaw, a professor of physics and head of the Human Radiation Effect Group at the University of Bristol. What did Dr. Henshaw have to say about the Danish report?

“This seriously flawed study misleads the public and decision makers about the safety of mobile phone use. I consider that their claims are worthless.”

Tell us how you really feel?

The effects of radiofrequency exposure from mobile phones are still largely unknown.

Powerwatch says the researchers misclassified 88 percent of the Danish population who began using mobile phones after 1995 for which there is no subscription information due to legal reasons. Erroneously classifying these people as non-users, Powerwatch insists, will distort the data. They also take issue with the fact that corporate subscribers – who could very well use mobile phones the most – were excluded from analysis.

The researchers acknowledged the limitations themselves in the report:

“Because we excluded corporate subscriptions, mobile phone users who do not have a subscription in their own name will have been misclassified as unexposed. Also, as data on mobile phone subscriptions were available only until 1995, individuals with a subscription in 1996 or later were classified as non-users.”

They then go on to defend their methods by saying there was no difference between subscription holders of 13 years or more and non-subscription holders. They reason that the proportion of people who use a mobile phone for 13 years or more without a subscription would be exceedingly small. Thus, they maintain, their comparison is a valid one.

With more than five billion mobile phone subscriptions worldwide, it’s understandable – and sensible – to explore the possibility that the signals sent out from our handsets via our brains is dangerous. Current study and issues aside, what do we know about the long-term use of mobile phones?

We know that mobile phones emit radiofrequency energy. It’s a non-ionizing type of electromagnetic radiation, as opposed to the ionizing radiation used in radiation therapy, for example. According to the FDA, the consensus is that the only known effect of radiofrequency energy on biology is heating, the way microwaves in microwave ovens are able to heat food. The energy from cell phones also cause heating, but to such a small degree as to not cause concern. One study, though, performed by the FDA showed that using a phone for 50 minutes caused brain tissue on the antenna-side of the head to metabolize more glucose than tissue on the opposite side of the brain.

Spooky.

And while the negative results of the current study consistent with most like studies performed in the past, there are some exceptions. Swedish researchers reported an increased risk for brain tumors after just five years of mobile phone use. An editorial about the current study, however, points out that such a powerful effect would have shown up in the country’s cancer statistics – but it did not, placing the validity of the study in question.

Another study performed by multiple brain research centers across 14 countries showed, as a whole, mobile phone users were no more likely to develop cancer than non-users. However, for the ten percent that used their phones the most, they did show increased risk.

Again, it’s worth keeping in mind that studies showing an effect are rare. According to Professors Anders Ahlbom and Maria Feychting of the Institute of Environmental Medicine at the Karolinska Institute, the score is 13 to 2 in favor of there being no effect.

But don’t take their word for it. The following graphs track the incidence of gliomas in Swedish men and women between 1979 and 2000. The 20 year period saw no increase in risk for this most dangerous of brain tumors.

credit: Ahlbom and Feychting, BMJ Open

But mobile phones were introduced in Sweden in 1987. Their popularity rose quickly and steadily such that by 2002, 87 percent of people between 16 and 75 years old were using them. One would think that, were mobile phones tumorigenic, we’d see a rise in tumors.

Personally, I find the graphs reassuring. But there are yet still other critics who say the “long-term” users weren’t long enough, that tumors require even more time to develop. These people would claim, then, that no one knows anything.

And so the debate rages on. What’s the take-home then? Feel reassured, but not too reassured. As the authors state in their final sentence: “…further studies with large study populations, where the potential for misclassification of exposure and selection bias is minimized, are warranted.”

[image credits: Symptom Brain Cance, The Telegraph, and BMJ Open]
image 1: brain
image 2: phone
image 3: BMJ Open

Scientists were finally able to grow sperm in the lab–from mice. It still remains to be shown if the same procedure can be used for humans.

In an amazing technical feat researchers in Japan have accomplished something that has stymied the field for the past half century: they successfully grew sperm in the lab. They then used the sperm to impregnate female mice and produce a healthy litter. The breakthrough holds promise for millions of men worldwide with infertility.

Published recently in Nature, the work was pioneered by Takehiko Ogawa and colleagues at Yokohama City University. The procedure involves taking biopsies of mouse testes, breaking them up into 1 to 3 mm pieces, placing them on agarose that has been partially soaked with a special medium, and letting them be for two months. If all goes according to plan, the chemicals in the medium would induce the gonadal stem cells to differentiate into mature sperm. Getting the ingredients of that medium right has been the major confound since efforts to produce sperm in the lab began in the 1960s.

To make their lives easier they used mice genetically modified with green fluorescence protein (GFP) that would only become activated in cells that had differentiated into viable sperm. The researchers could then just look through the microscope and all of the stem cells that had successfully differentiated to sperm would glow green.

Imagine, after years of frustration, peering into the microscope and seeing a lovely field of glowing green. But Ogawa and his crew didn’t pop the champagne just yet. The ultimate proof was then to see if their homegrown sperm was healthy and functional–could they be used to successfully fertilize an egg and produce normal, healthy offspring. Using two different methods they fertilized 23 and 35 oocytes, respectively. The dams gave birth to 7 and 5 live offspring who survived to adulthood and were able to produce offspring of their own.

Now it’s time to break out the champagne.

Sperm is often stored frozen in sperm banks for future use. To simulate this scenario Ogawa’s team cryopreserved the sperm in liquid nitrogen for 4 to 25 days. When the cells were thawed and cultured, expression of the GFP marker confirmed that they resumed full spermatogenesis in culture. They have yet to demonstrate that the freeze-thaw cycle leaves their cultured sperm intact well enough to produce healthy offspring that are in turn able to produce healthy offspring. It remains possible that freezing and thawing the cells left some as yet undetected structural damage, for example, or caused some epigenetic changes–changes in the molecules bound to genetic material that affects gene expression. Nevertheless, their demonstration is already an amazing accomplishment.

After 50 years of effort researchers have finally discovered a way to grow sperm in the lab. Swapping out a commonly-used culture ingredient may be the key.

Given the increasing number of successfully grown tissues and stem cell acrobatics flipping one type of cell to another, we may be getting the impression that simply growing sperm in a dish isn’t all that groundbreaking. You half expect those rambunctious miniature tadpoles to will themselves alive on their own. But growing sperm–a gamete–is much more complicated than growing somatic—rest of the body–cells. It is a sequential, multistep process involving a complex list of players named primordial germ cell, spermatogonium, primary spermatocyte, secondary spermatocyte, spermatid and mature sperm. Each of these stages requires an equally complex battery of signals provided by the non-germ cells that surround them. The whole process of going from stem to sperm cell takes over 60 days in humans; in mice (and most other mammals) it takes over a month. Successfully commanding a month long differentiation is a daunting challenge. We’d been trying since the 1960s but, until Ogawa’s study, we’d failed every time.

Through much trial and error, the researchers happened upon a key modification to their protocol that seemed to make all the difference. When trying to grow sperm in a dish a researcher would typically use fetal bovine serum (FBS), serum from the blood of newborn calves. FBS is a widely-used supplement in mammalian tissue cultures. Ogawa’s group had had some success with FBS in the past, but they decided to try replacing their FBS with what’s called knockout serum replacement (Ko-SR). This was a strange move, as Ko-SR is essentially FBS with most of the ingredients that promote the differentiation of cells removed. It’s typically used by stem cell researchers who want their stem cells to remain in an undifferentiated state. Surprisingly, and to the delight of Ogawa and colleagues, the Ko-SR had just the opposite effect: it promoted the differentiation of the sperm stem cells into mature sperm. It’s still unclear why the Ko-SR worked, but Ogawa suspects it’s due to one of the differentiation-inducing ingredients that still remains, called parvalbumin. If this turns out to be true, not only would the study give us a new tool to treat infertility, it will teach us something new about the basic biology of sperm maturation.

The team’s 12 newborn mice mark the triumph of a half a century’s effort. When you’re dealing with biological complexity slow and incremental is not only the pace of progress, it’s safer. It would be a tragedy if we were to give a man who had already conquered cancer the hope of having children, only to hand him the devastation of an unhealthy child. Taking genes into our own hands is risky business (let’s not forget that Dolly had progressive lung disease) and it remains to be seen whether or not the strategy can be used to make human sperm and to make human beings. Nevertheless, the team’s 12 newborn mice are a testament to power of relentless tinkering. And as they continue to tinker I don’t expect we will have to wait another sixty years to hear their good news.

[image credit: Rama and pdimages.com/web9 via wikicommons]

image 1: wikicommons_mouse

image 2: wikicommons_sperm

Can Johnson & Johnson help turn this prototype into the next big thing in cancer diagnostics?

As Singularity Hub followers are well aware, it’s an exciting time in cancer screening. We’ve recently highlighted a number of new technologies that are in the works, such as Bio-Nano-Chips, a handheld microNMR detection system, and a tiny biomarker sensing implant, but these technologies are still early in their development cycle, and their future, though promising, is uncertain. However, one screening method that’s been around for five years has taken a big step toward becoming a viable kit for the clinic. Researchers at Massachusetts General Hospital Cancer Center (MGH) announced a $30 million, 5-year partnership with Johnson & Johnson to transform their cancer cell-detecting, microfluidic chip system into an easy-to-use liquid biopsy test. Dr. Daniel Haber, a lead researcher for the device, said, “We’re limited by our ability to make [a chip] fast, easy, cheap, and something that could be done on a global scale.”

Hopefully, that won’t be the case for long.

The story of this technology begins back in 2007 with a Nature paper and a NEJM article from Dr. Haber, Dr. Mehmet Toner, and colleagues at MGH reporting the breakthrough of a circulating tumor cell (CTC) device, dubbed the CTC-chip, that could selectively separate tumor cells from whole blood. This is a very needle-in-the-haystack problem since only one of the billion cells floating by will be a tumor cell.  The CTC-chip was designed with 80,000 antibody-coated silicon columns within the microfluidic channels, so that proteins on the surface of passing tumor cells would bind to the antibodies as the blood flows through the channels. The researchers demonstrated that the method could isolate an average of 132 tumor cells from one milliliter of blood from patients with metastatic lung, prostate, pancreatic, breast and colon cancer. Furthermore, in a very small trial of patients receiving therapy for early-stage prostate cancer, the CTC-chip could be used to monitor patients’ response to anti-cancer treatment.

A cancerous cell binds to one of the posts in the CTC-chip, isolating it from the multitude of other cells around it.

To really appreciate the promise of this technology, it’s important to recall that cancer is assessed in stages. Though a variety of staging systems exist for solid tumors, in general, lower stage cancer is localized and contained in the organ or tissue that the tumor develops within. Subsequent stages reflect more extensive tumor growth and the degree of its spread, especially to local lymph nodes. Finally the highest stage reflects the extensive spread of a tumor with cancerous cells breaking away and entering into blood and/or lymphatic vessels where they circulate to remote locations in the body. This is known as metastatic disease and is problematic not only because tumor cells are being carried everywhere, but tumors that develop are from their original cells. This means that tumors in the brain could be from cancerous breast or lung tissue, complicating treatment.

So in the studies with the CTC-chip, monitoring of tumor cells in the blood was essential in metastatic disease as a way of determining how many of these cells were in circulation, which could cause tumors to grow throughout the body. In the second trial, the amount of tumor cells in the blood could be correlated with treatment received, as a way of correlating decreases in circulating tumor cells with the effectiveness of a particular therapy. So not only could the cancerous cells be characterized, doctors could monitor how the disease was affected by the drugs that the patients received.

With a promising new technology that had potential for real cancer breakthroughs, the researchers assembled a Dream Team as part of the Stand Up to Cancer initiative launched by the Entertainment industry Foundation. The SU2C challenge is an exciting endeavor, not only because numerous celebrities are raising awareness about cancer research, but because the core of the challenge is collaboration, where scientists, researchers, and clinicians across a variety of disciplines are communicating and working cohesively to make big strides of progress. The CTC-Chip Dream Team brought together researchers at MIT, Memorial Sloan-Kettering Cancer Center, Dana-Farber Cancer Institute and M.D. Anderson Cancer Center. In 2009, the Team was awarded $15 million by the American Association of Cancer Research to support the CTC-chip development.

So now it’s two years later and the CTC-chip development has been moving along. However, each chip still costs about $500, and getting the chips out of research labs and into clinics remains a challenge. And this is where Johnson & Johnson comes in. The $30-million partnership between MGH researchers and two arms of Johnson & Johnson — Veridex, LLC, which produces their own CTC detection system, and Ortho Biotech Oncology R&D — is aimed at commercializing the device, which will involve finding a way to make it cheap and effective, and navigating through the regulatory passes and clinical trials required to get the chip to market. It’s a five-year partnership, which is hopefully a realistic timeframe for this technology to finally get into widespread use.

The CTC-chip story is an amazing and inspiring story because of the strides that collaborative, interdisciplinary research can make when players abandon the everyone-is-an-island approach to scientific and medical research. This story isn’t over, but fortunately organizations like Stand Up to Cancer are utilizing familiar faces in the entertainment industry to bring public awareness not only to the need for cancer research, but also to the individual researchers behind the scenes.

To see members of the MGH Dream Team and other cancer researchers talk about the power of collaboration, check out the following video, which is just one of the many that Stand Up to Cancer has produced:

[Images: Massachusetts General Hospital]

[SOURCE: Boston Globe, MGH, Nature, Nature Medicine, NCI, NEJM, Stand Up to Cancer]

This tiny implant is only 8mm wide, but it contains enough nanotechnology to detect heart damage that would otherwise go unnoticed.

Heart attacks and cancer account for nearly half of all deaths in the United States – they’re the two biggest killers walking the streets, but MIT isn’t afraid. Michael Cima and his team developed an implantable sensor that uses antibodies attached to nanoparticles to detect cancer related biomarkers. In 2009 Cima showed that he could implant these devices into human tumors in mice and then ‘read’ the cancer growth using MRI. No biopsies need. Over the past few years, Cima and his team have adapted their work to create a very similar device that measures biomarkers related to heart damage. This month they published work in Nature that demonstrated how their implant could detect heart attacks in mice. Watch Cima discuss some of the potential of this technology in the video below. While these implants aren’t ready for the clinic (Cima thinks 5 years for some applications) they are just too cool to ignore. Once fully realized, implants like these could be inserted into cells via a needle and read with a hand held scanner. Heart attacks, cancer…those bastards would never have the chance to sneak up on you again.

Biopsies, the standard method for testing clumps of cells for cancer, is an invasive procedure. Mild heart attacks can go unnoticed or ignored, but still leave behind serious damage that could later lead to death. What is needed in both cases is a method of safely and reliably monitoring the body, preferably from the inside where signals are stronger. That’s why the MIT implants are so ingenious. They can detect small changes in cells and relate that information to a medical professional without having to be removed. Developed by Cima and his team, graduate student Christophoros Vassiliou was able to get the devices small enough to fit inside a biopsy needle. You can inject them into the tissue you want to monitor. Once there, they not only can warn you of dangerous changes, they can help you directly control the treatment of patients so that their therapy matches their current needs. Cima describes this further in the following video:

While they have a different shape, and monitor for vastly different biomarkers, the two sensors share a common technique. Each implant is filled with magnetic nanoparticles (iron-oxide) that are bonded to antibodies. Those antibodies will respond to different biomarkers around them and cause the nanoparticles to clump together. This changes the magnetic properties of the implant. When you scan the body with MRI, a change in the device’s magnetic response alerts you to the presence of the biomarkers you were looking for.

Many cancers produce characteristically high levels of certain hormones that can be monitored. In a 2009 article in the journal Biosensors and Bioelectronics, Cima and his team found that implants in cancerous tumors showed a signal that was about 20% stronger than in control cases. The bigger the signal, the more cancer cells you’re likely to have in the region.

MRI images after heart attack (top) and control (bottom). The disk shaped implant showed much greater magnetic response (red) in the mouse that suffered a heart attack due to its detection of key biomarkers released after heart cells were damaged.

In the more recent 2011 article in Nature, the MIT team (along with associates at Harvard Medical and Mass General Hospital) were looking for three proteins heart cells release when they are damaged. Implants inside mice were used to detect these biomarkers up to 72 hours after a heart attack was induced. Sure enough, the stronger the signal seen in the MRI, the more damage caused. Not only that, but the signal was cumulative. These implants could help us see not just how cells are being damaged now, but how much they’ve been damaged recently – a very necessary distinction if you want to detect patients who have injured hearts but who may not be actively showing signs of distress.

This work is very exciting, but still very early in development. As we’ve said many times before, successes with mice experiments and successes with human experiments can be miles apart. The 5mm cylindrical cancer implant and the 8mm heart monitoring disk both need more time to be perfected. The antibodies used to detect biomarkers have a limited lifetime in the body. Currently an implant probably wouldn’t last much longer than two months. Also, while MRI is non-invasive, it’s also not portable. Cima and his colleagues are working on upgrading the implants so that they can be read by handheld magnetic instruments.

If MIT continues to see good results with these early prototypes, there’s a good chance we’ll see similar devices in clinical trials in the near future. Cima thinks that such experiments could be as little as five years away. The lowest hanging fruit are implants that could monitor for pH levels – acidity is often a hallmark of cancer cells. After that, we may see versions that can accurately detect hormone levels and drug responses.

Cancer and heart attacks may be vicious killers, but they’re also really dumb. They leave traces of their presence we can watch for, and they often rely upon a patient’s ignorance to succeed. We need to be smarter than these bullies, and to know more about what they are up to. The implants out of the Cima Lab are a great solution and they’re not alone. We’ve seen handheld testing devices and lab-on-chip technology that will likewise help us track cancer in our cells and damage in our hearts. Along with a more general trend towards continuous body monitoring, these systems will help us stay vigilant against the most prevalent causes of death. One day we’ll all have these technologies inside us, implanted well ahead of time so that we’ll know the second something goes wrong. Information well used is the best weapon in medicine, and with developments like the ones we’ve seen from MIT, we’ll soon have more than enough to help keep us alive for a very long time.

[image credit: Michael Cima/MIT via New Scientist]
[video credit: MIT TechTV]
[sources: Ling et al Nature 2011, Daniel et al Biosensors and Bioelectronics 2009, MIT Media Relations]

The microNMR-smartphone system - a tool for rapid and accurate cancer screening

If you’re a smartphone naysayer, here’s some news that might make you drink the Kool-Aid along with nearly half of Americans: of the 652 app applications submitted just to Apple every day, an increasing number of healthcare-related apps are starting to trickle in that could actually help save lives. An exciting example comes from the scientists at the Center for Systems Biology at Massachusetts General Hospital that have knocked it out of the park by integrating a microNMR device that accurately detects cancer cells to a smartphone. Though just a prototype, this device enables a clinician to extract small amounts of cells from a mass inside of a patient, analyze the sample on the spot, acquire the results in an hour, and pass the results to other clinicians and into medical records rapidly. How much does the device cost to make? $200. Seriously, smartphones just got their own Samuel L. Jackson-esque wallet.

Considering that more than 1,500 Americans a day will die of cancer according to the American Cancer Society, which translates into almost 1 in 4 deaths, oncologists have needed a rapid, minimally intrusive, and accurate method for cancer screening for a long time. The beauty of the microNMR device is that it solves a handful of problems that plague current cancer screening methods starting with the risks involved in biopsying tissue. If a suspicious lump is found through a mammogram or a colonoscopy, there is no way to be certain if it’s malignant or benign without testing the tissue directly. In some cases, the patient has to undergo surgery just to have a sufficient amount of tissue removed for testing. But in other cases, a needle biopsy can be performed, which involves inserting a needle into the mass and extracting a small amount of cells. Some doctors and patients are wary of biopsies because of the risks versus the benefits, especially if a biopsy is being repeated due to an inconclusive result. But one of the main reasons cancer rates in the US have been dropping for years is early detection. In fact, early detection is known to lower mortality rates in breast, colon, rectal, and cervical cancer. Ideally, screening of a suspicious lump should involve the least invasive method possible that would produce accurate results, which would ultimately lower hesitations by doctors or patients to test.

The microNMR device uses very minimal amounts of tissue, approximately 4,000 cells, which is acquired using fine needles that are minimally invasive. Small amounts of cells can be tested because of the various technologies within the microNMR. Back in 2000, the group reported the development of magnetic nanoparticles connected to ligands. When small amounts of the ligands bind to proteins inside of cells, the nanoparticles assemble together and become visible using magnetic resonance imaging (MRI). Building on this work, by 2008, they had developed a miniaturized system the size of a coffee mug that allowed for rapid and accurate measurements. This system utilizes a small magnet and microcoil array to create a miniaturized nuclear magnetic resonance (NMR) device, a technique that has literally transformed chemistry and molecular biology. Samples for testing are delivered to this microNMR chip via another success story in modern science, low-cost easily fabricated microfluidic systems.

By integrating these components together, the microNMR is an awesome device in its own right, but it also solves another screening dilemma: rapid and accurate analysis. Unfortunately, modern biopsy analysis has an 84 percent accuracy rate and can take three to four days to produce results. Furthermore, tissue can degrade during transport to an external testing site and current immunohistochemistry methods can produce false positives. In their latest report, the researchers describe how they addressed these issues by connecting the microNMR to a smartphone for data analysis. This allows a clinician to extract cells from the patient and analyze them immediately rather than sending them away for testing. Through trial and error, the researchers identified four cancer marker proteins that would serve as a screening panel. The result? The system detects cancerous cells from freshly acquired patient samples in an hour with an accuracy of 96 percent in one trial and 100 percent in another across a range of cancer types.

Nanoparticle-linked ligands bound to proteins pass through the microNMR for analysis

Bridging the microNMR with a smartphone allows the researchers to address the problems of convenient visualization and communication of the results by wisely capitalizing on a technology that many doctors and nurses are already comfortable with. Many medical devices that have their own displays and data handling require training for that particular device. The data output may also be awkward or indecipherable and record keeping may not be convenient. However, as smartphones are intuitive devices and their platforms allow for an easy way to visualize data, training is significantly reduced and data is more accessible. This means that instead of doctors just telling patients, “You have cancer,” they can actually review the data with them on the handheld device.  The results can also be immediately transmitted to other doctors or into patient records without worrying about compatibility issues.

Together, this device holds an enormous potential for changing the experience of finding out that you have cancer. Imagine your doctor finds a suspicious lump in your body and schedules you for a biopsy. First, you have to undergo surgery to have a sample removed. Then you face anxiety-filled days as the result looms in your mind. Finally, you get the phone call: if it’s negative, you have a huge sigh of relief though you may feel exhausted over the worrisome ordeal. If it’s positive, you now have to schedule an appointment to see your doctor to discuss plans moving forward. Those can be excruciating days of uncertainty as the result hangs like a death sentence for you, family and friends. Now contrast this scenario with one that the microNMR device may someday make possible: a suspicious lump is found, a clinician inserts a small needle into the site on your body, and you sit in the waiting room for about an hour. You’re called in and your doctor uses a smartphone to show you all the results of the test. If it’s negative, you walk out of the office and put cancer out of your mind. If it’s positive, you can immediately discuss a game plan and treatment options with your doctor. Emotionally, that is a world of difference.

The next decade may very well go down as the decade of the smartphone, but it’s comforting to know that it may be due to more than just texting, gaming, and watching YouTube. With an increasing number of healthcare-related apps, smartphones have the potential to bridge the gap between doctors and patients through convenient and rapid access to medical data. We’ve already highlighted health-related apps that will measure blood-sugar levels and monitor vital signs, but some new apps are aimed at helping doctors by interfacing with medical devices where the smartphone becomes the tool for data handling, visualization, and communication. Devices like the microNMR, the digital stethoscope, and another app that changes a smartphone into a skin cancer screening tool promise to make smartphones revolutionary platforms that improve medicine for both clinicians and patients.

To see a video that features Dr. Ralph Weissleder, the principal investigator for the microNMR, discussing molecular imaging, check out this 2008 video:

[Image source: Center for Systems Biology]

[Sources: American Cancer Society, Center for Systems Biology, Nature, Science Translational Medicine]

The way doctors do diagnosis could change soon. The programmable core of the Bio-Nano-Chip.

We often find out too late what’s happening inside our bodies when it’s stricken by disease or cancer, but those days could be coming to an end. The McDevitt Lab of Rice University has developed a Programmable Bio-Nano-Chip (PBNC), an alternative to the costly, time-consuming, and sometimes painful procedures for diagnosis. By using nanoscale fluorescent labeling to look for biomarkers linked to disease, these credit-card size chips could enable physicians to recognize heart disease or cancer with just a small saliva sample, no catheterizations or biopsy required. PBNCs also represent an exciting milestone for the “lab-on-a-chip.” In the past, this technology could analyze very small samples, but it has been economically impractical and still required a full-scale laboratory. PBNCs don’t have these issues. Chips for various conditions are already in clinical trials, so the McDevitt team’s PBNC  is quickly forging a path to a facility near you. The arrival of this technology would enormously benefit the healthcare system by improving clinical outcomes and reducing costs. PBNCs also hint at other possibilities, like detecting the earliest signs of disease. If these devices ever become implants, then the Body 2.0 upgrade we’ve been waiting for could be within reach. Your body’s health, right down to its biochemistry, could be as easy to read as your wristwatch.

PBNCs fit the functionality of a diagnostic laboratory on a small silicon chip. Rice University developers applied fluorescent antibody labeling (FAL), a technique in which fluorophore-tagged antibodies attach to specific unbound or cell membrane proteins in order to determine concentration. The team miniaturized this method so that it could detect these protein biomarkers down to a few billionths of a gram. This allowed the device to discern when certain indicators of pathology (i.e. abnormal concentrations or uncontrolled cell proliferation) appear in the body, using only a saliva sample. When the McDevitt lab combined miniaturized detection with microfluidics, a stand-alone reader, and a reprogrammable sample processing core, the PBNC was born.

The video below highlights the functionality of the device as well as its potential fiscal benefits. At 1:26, Dr. McDevitt describes the grim situation of conventional heart disease diagnosis, pointing out that too often “the first symptom they get is they die.”  Then, a lab member divulges the technical details of the PBNC-based diagnostics (1:55). He shows a case of a test performed on a man who was complaining of chest pains, with the nine central beads emitting more fluorescence compared to a non-heart attack patient. This indicated an elevated concentration of cardiac troponin I, a revealing biomarker for cardiovascular damage. The video wraps up with Dr. Vivian Ho (4:32) describing how PBNCs conflict with the dogma of healthcare economics: better technology inevitably leads to rising costs. However, according to Dr. McDevitt, mass chip production could drive the cost of PBNCs down to a few dollars per test. Compare that to other diagnostics in the table below the video. If PBNCs lead to both better health and less financial strain, we could have our cake and eat it too.

The monetary and temporal costs of lab tests. PBNCs for heart damage, prostate cancer, HIV, and ovarian cancer are currently in clinical trials.

So when will these tests reach hospitals and clinics? According to Dr. McDevitt:

More than 20,000 scientific-discovery papers for cancer and 6,000 for cardiac disease have been published, yet only about one biomarker per year for all diagnostics areas received FDA approval from 1995 to 2005.

While regulatory protocol has impeded biomarker-based testing in the past, Dr. McDevitt’s promising technology has prompted the FDA to set PBNCs on the fast-track for approval. Chips for heart disease and three different kinds of cancer are already in Phase III clinical trials. For those unfamiliar with the FDA approval process, Phase III is one of the last steps before drugs or medical devices are allowed to be marketed. Barring any significant issues during the multi-site trials, it appears PBNCs could be just around the corner.

If these devices ever become widespread, I wonder what other disorders these chips will be able to detect in the future. The biomarker signatures for many diseases are still being worked out, but once they are found, it’s not unreasonable to assume that PBNCs could be reprogrammed for them as well. For example, there has been headway using biomarkers to detect neuropsychiatric dysfunction. Currently, the blood test for schizophrenia costs around $2500, so a PBNC version of this test could make it much more accessible. One issue to consider is that a PBNC for schizophrenia would need to assess 51 biomarkers, and the PBNCs in clinical trials right now only quantify three or four. While there will be logistical concerns if these chips expand to testing other diseases, I’m confident that these challenges will be surmountable.

Looking even further ahead, could PBNCs ever be integrated with our biology? We’ve seen cyborg retinas, a silicon pancreas, and a vitals clip-on, but what can PBNCs offer to Body 2.0? Not much . . . for now. The chips are exclusively body-external for both sample collection and analysis. However, reflecting the general trend in microelectronics, I would expect that PBNCs will continue to miniaturize. After confronting issues with biocompatibility to ensure the body does not reject the device, then PBNCs could be surgically implanted. The chips would constantly monitor the levels of biomarkers for any disease imaginable. It could also be combined with a peripheral transmitter that relays biometric data to a receiver outside the body for analysis. Such an apparatus would enable us to detect disorders as they emerge in real-time, the pinnacle of preventative medicine. While this might sound like a medical pipe dream, there is considerable interest in implantable biochips. In fact, this technology has received big-time government funding in the past.

I am very excited about this technology and hope the FDA places similar tests on the fast-track of approval. Like countless others out there, cancer has been a scourge of my family. Getting a biopsy, waiting for the results, and paying for the costly lab tests can take a toll. While waiting for any life-determining test result isn’t easy, I would much prefer a 20 minute delay and avoid a painful biopsy. As PBNCs make their way through clinical trials, I will be watching the headlines, patiently waiting for the day that the grueling diagnosis process gets a little bit easier.

To learn more about PBNCs and how it could impact global health, watch this in-depth presentation by Dr. McDevitt given at Berkeley.

<Image Credits: Screenshot of Rice University News and Media Relations PBNC Video>

<Video Credit: Rice University News and Media Relations>

<Sources: Rice University News and Media Relations>

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.

The vaccine has already passed Phase I and II clinical trials with promising results: previous studies have shown that BiovaxID significantly increases both the time interval between relapses (44.2 months, as compared with 30.6 months in a placebo group) as well as patients’ overall survival rates. In some cases, the vaccine reportedly clears cancer completely from the body. Phase III trials have expanded the subject pool, and are currently studying the vaccine’s long-term effectiveness on 375 NHL patients. If all goes well, BiovaxID will then be passed on to the FDA for market approval.

Non-Hodgkin’s lymphoma is actually an umbrella term for 16 different types of blood cancer that show up in the lymphatic system. Every year, about 65,000 people are diagnosed with some form of NHL in the United States alone. BiovaxID is being developed and tested for follicular lymphoma, an indolent but ultimately fatal subtype of the disease that affects B-cells in the blood. The disease goes through periods of remission and relapse, with 90% of follicular lymphoma patients dying of the disease within 7 years of diagnosis. Current treatments involve a combination of chemotherapy, radiation and monoclonal antibodies. These therapies often show initial success, but fail in subsequent relapses as the cancer develops resistance.

So how does the vaccine work? Normally, NHL cancer cells are ignored by the immune system because their cell surfaces aren’t distinguished as abnormal when compared to healthy cells. Accentia takes cancer cell samples from an individual’s body and identifies a tumor-specific molecular marker (an antigen) along the cell surface. Next, they link up the cancerous cell with a protein molecule which makes it easier for the immune system to recognize the tumor-specific marker as foreign or undesirable. What results is a patient-specific vaccine, which teaches the body’s own immune system how to separate the good cells from the bad.

BiovaxID is a vaccine specifically tailored to the patient's particular lymphoma cells

But follicular lymphoma isn’t the only cancer type that Biovest and Accentia want to target. Last month at the Active Immunotherapeutics Forum, Accentia’s chief science officer Dr. Carlos Santos reported positive findings in Phase II clinical trials to treat mantle cell lymphoma. This subtype is particularly deadly, and carries a 36-month median survival rate. Early results show that after a average follow-up of 46 months, 89% of mantle cell lymphoma patients are still alive. Other B-cell lymphomas could also potentially be treated using the vaccine, including multiple myeloma and chronic lymophocytic leukemia. These subtypes also exhibit cell surface markers that can be exploited by the vaccine.

The patient-specific vaccines also represent another big step for personalized medicine.  We’ve recently covered the lung-on-a-chip that can be used for individualized drug testing, and back in January we hosted a booth at the Personalized Medicine Conference. As biotech becomes more individually tailored, treatments can be developed that fit case specifics instead of generalized trends, and that means better treatment all around.

Most of these vaccines will probably be used in combination with radiation and chemotherapy, as is currently the case in Phase III trials (the vaccine cleans up residual cancer cells following an initial chemo treatment). Still, the potential that a vaccine could eventually phase out chemo or radiation therapy is a pretty exciting prospect. As anyone familiar with these therapies knows, the treatment can often be worse than the disease. Vaccines that can destroy lymphoma without destroying healthy tissue will be welcome news to millions of cancer patients.

Here’s a quick video of Dr. Santos explaining BiovaxID and how it works:

[image credit: Biovest International]

Varian's TrueBeam is the latest automated radiation system that can kill tumors with sniper-like precision.

Radiation therapy may be a great way to kill a tumor, but when doctors zap cancer cells they end up hitting healthy ones too. Thankfully, the last decade has given us super-accurate radiation-blasting robotic systems that can target and fire with millimeter precision. Snipe the cancer, leave the healthy cells standing. For years Accuray (NASDAQ:ARAY) and TomoTherapy (NASDAQ:TOMO) have been the big names in the field, but last month med-tech giant Varian (NYSE:VAR) released their own automated radiation system, the TrueBeam, with even better accuracy than the others. Join us as we take a look at these life-saving machines that are helping patients recover faster and safer with robotics.

While each of these systems work slightly differently, they all provide the same basic service: killing cancer cells in tumors using high energy radiation (x-rays). In years past, this work was done using linear accelerators and required tedious (and nerve wracking) alignments by a technician. Inevitably, such machines kill healthy cells along with cancerous ones.

The new breed of radiation robots is lowering the rate of dead healthy cells. They all have one large advantage over traditional radiation therapy methods: accuracy. Accuray’s automated radiation machine, Cyberknife, pivots and tilts around you to find the best access point to irradiate a tumor, and can hit a target within a millimeter or so. TomoTherapy uses a shuttering system on their machine to achieve similar precision. Varian’s TrueBeam machine couples with their RapidArc software to provide dynamic adjustments with only 10 ms delay, giving them sub-millimeter precision. In each case, doctors can program the desired target area in the body and let the machine pivot and adjust to hit the tumor on its own. They are used to treat a wide variety of cancers from brain to prostate.

I don’t want to display too much preference among these three systems, so I’ll try to let each company speak for itself.
TomoTherapy:

I love the restraining mask at 1:32 in the following video from Accuray…sometimes medicine is really trippy:

Varian only released their TrueBeam/RapidArc system in April, with its first use seen in Zurich. As such, their demo is only a simulation without a narrative. Still, I think you can get the idea of what’s happening:

Cancer has a huge social and economic impact on the US and the rest of the industrialized world. According to the National Cancer Institute’s latest update, more than $100 billion was spent on cancer treatments in 2006 in the US (the most recent year for which information is available). Another $130 billion was lost due to cancer related deaths. Preventative medicine is set to undergo a revolution based on increased health monitoring and medical data, which will hopefully lead to a dramatic reduction in cancer rates. Yet we will still need radiation therapies and surgeries, and we will want them to be as accurate, fast, and safe as possible.

It’s clear that advanced radiation robots could really work to bring down cancer mortality. With improved precision, they are able to eliminate more cancerous cells in each treatment, leading to lower radiation exposure for each patient. This leads to better success in eliminating tumors and reduces the incidence of radiation therapy related sickness. Fewer deaths and less time in the hospital – these are things we can all be happy about.

Just as importantly though, these tumor sniping systems could work to bring down healthcare costs as well. While they are expensive (each of these systems cost between $2.5 and $4.5 million) hospitals are able to treat patients much faster with these automated systems. Accuray and TomoTherapy will argue over who’s quicker, but both seem to have average session lengths in the 30-90 minute range. Data from Varian is still coming in, but they’re looking at less than a 60 minutes session. Most of this time involves setup and patient interactions, not actual treatment (which can take less than 120 seconds). Varian has specifically targeted the time lost to setup by making TrueBeam’s controls simpler with fewer buttons. No matter which system a hospital uses, however, they are looking at increased throughput and fewer complications. These are things that hospitals administrations can be happy about.

This is a developing field, with billions of dollars at stake and customers (hospitals) willing to shop between systems before making their investment. Hopefully the competition between these three companies will help drive down prices and ramp up innovation. Varian’s TrueBeam system, the newest of three, already displays better precision, faster adjustments to patient movement, and a better integration of the imaging/targeting mechanics. Cyberknife’s gone through several improvements in the last decade, as have TomoTherapy’s machines. In the years ahead, we may see the precision of the radiation robots continue to improve, allowing doctors to target smaller and smaller groups of cells, destroying tumors and nothing but tumors. So three cheers for the competition between TomoTherapy, Accuray, and Varian. No matter who loses, it looks like the patients are going to win.

[image credit: Varian]
[video credits: Accuray, Tomo Therapy, Varian]
[source: Varian, Accuray, TomoTherapy, National Cancer Institute]

Caltech's research has shown that it can get nanoparticles and RNA into cancer cells. Cool, but this isn't a cure for cancer yet.

Maybe you’ve read about the amazing “cancer-killing nanobots” from Caltech that use RNA as a weapon. They’ve been making waves in news media all week.  The truth is that many headlines, and stories, are grossly misleading. Caltech, along with biotech firm Calando, has developed a method of using nanoparticles to cause RNA interference in cancer cells. The news has caused a nice jump in the stock of Calando’s parent company, Arrowhead Research (NASDAQ: ARWR). But all the talk about Caltech striking a major blow against cancer is premature. We don’t know if this RNA interference will actually destroy cancer cells, or even be safe to use  because it’s still in phase I clinical trials. As often happens with science linked to cancer research, the media has over-hyped a promising technology, pressuring it to perform before it is able.

What’s even more aggravating is the often hilarious misuse of the term ‘nanobots’. Look at some of these headlines:

• Human-Tested Nanobot Delivers New Cancer Therapy With Success!
• Cancer Gene Therapy by Nanotech Robots
  
• Nanobots Flip Off Cancer Switch in Cells
• Tiny Robots Deliver Gene Therapy To Treat Cancer
• Nanotech robots deliver gene therapy through blood (from Reuters no less!)
  

or the even more unfortunate rehash:

• Nanobots robots used to deliver gene therapy through blood

‘Nanobots’ conjures up images of tiny little robots in the minds of readers, maybe even tiny little spaceships floating through the body. That’s just not what Calando created. Their nanoparticle is a 70nm spheroid with RNA embedded inside. When it’s absorbed into a cell, the particle falls apart, releasing the RNA. If we have to use a bad metaphor for it wouldn’t Trojan Horse be more apt? Maybe nano-grenade?

This is a nanoparticle, not a nanobot. Maybe we can compromise and call it a RNA-fueled nano-grenade?

The truth is that the first real ‘nanobots’ we use aren’t even going to look like robots. They’ll be our own cells that have been commandeered to perform other tasks, or they’ll be tiny spheres that float through the body and act very similar to cells or other biological systems.

Even forgetting the nanobot issue, I still think the Caltech research is  being over-hyped. The  nanoparticle has been found to reliably show up in cancerous cells and deliver strands of RNA that disturb the creation of a certain protein. According to the paper recently published in Nature, this is the first time that a nanoparticle has been shown to systematically appear in higher levels in a cancer cell as the dose to a patient increases. The Caltech/Calando nanoparticle system is called RONDEL, and according to Nature News, it targets cancer cells by the “leaky” blood vessels that often connect to them. While that targeting method now has proven dose-dependence (that is, more nanoparticles in blood equals more in cancer cells), there’s no reliable measure of its potency. Does it kill cancer cells? Does it even slow their growth? Is this RNA interference actually going to be an effective treatment?

For that matter, we don’t know anything about it’s safety either. Does it ever target the wrong cells? Doctors have biopsied skin melanomas (the cancer used in the trials) and found RONDEL in good amounts, but I can’t find any mention of how often it makes its way into non cancerous cells.

RONDEL delivers RNA, a special version (siRNA) that is double stranded and that interacts with a cell’s programming to “turn off” a certain protein. That’s a very cool system, and the original discovery of this RNA interference earned the 2006 Nobel Prize in Medicine (for work performed in 1998). The biopsies of cancer cells showed all the signs of RNA interference: cleaved RNA strands, lower protein levels (in one case), and disrupted messenger RNA. That’s great, but again, we have no idea if this RNA interference will translate into real-world benefits for a patient.

The problem is that we’re talking about only one aspect of a phase I clinical trial that isn’t even over yet. We won’t know the results (i.e. safety and efficacy) until later in the year. And the trial is only on 15 patients. That’s a tiny dataset.  It would take phase II and phase III (years of testing) before we’re sure this is really a proven way to “fight-cancer”. The discovery of nanoparticles in cancer cells is like knowing gasoline got to the engine in your car. It’s an important step, but it doesn’t give us any clue as to whether or not the car is actually driving down the road.

Caltech’s research and Calando’s nanoparticle are promising. A reliable means of creating RNA interference in a cell could be a great mechanism to fight cancer, to provide gene/protein therapy, and may have other powerful applications. It’s just too soon to know how reliable RONDEL is at the moment. Dose-dependence is just one factor we care about, we also need to know how selective that delivery is. And we have no idea about how effective this particular RNA interference trial will be in actually fighting cancer. It’s just too soon to say. For now, let’s praise this research for creating a RNA interference delivery system with proven dose-dependence and call it a day.

[Image credits: Caltech: Swaroop Mishra, Derek Bartlett]
[source: California Institute of Technology, Calando Pharmaceuticals, Nature]

A new chip out of the University of Toronto detects RNA strands that indicate the presence of cancer.

So there’s this period of time during a visit to the doctor’s when you’re left alone in the office. You just saw the nurse or PA, and the doctor is playing golf somewhere, so you have to wait in your little paper dress. I was once stranded in that limbo for an hour. Wouldn’t it be nice if that time could be put to good use? Researchers at the University of Toronto have developed a microchip that works with nano-materials to detect biomarkers associated with cancer. Bottom line, in about 30 minutes the new biosensor can determine if you’ve got the ‘Big C’. Having already been proven to work with prostate cancer, the device could one day even be adapted to detect HIV, or H1N1 swine flu. Now that’s a good use of my time.

Development of the cancer biosensor was published in ACS, and more recently in Nature Nanotechnology. Shana Kelley, team leader for the project, says that the cancer detection microchip is the size of a fingertip. It and related electronics could fit into a hand held device the size of a Blackberry™. That means the detection of cancer would not only be much quicker (30 minutes vs. days of lab work) but it could be portable and relatively cheap as well. Hand held detection of major diseases and illnesses would revolutionize medicine, making it more accessible and more informative.

The biosensor works by pairing three components: biological detectors, nanowires, and standard silicon chip technology. The biological detectors are attached to the end of nanowires (typically made of gold) and will bond to the biomarkers that indicate the presence of cancer. These biomarkers are strands of micro RNA or messenger RNA produced by the mutated genetics of cancer cells and so the biodetectors are called nucleic acid probes. When the RNA interacts with the nucleic acid probes, electric currents are induced along the gold nanowire. These currents are detected and decoded by the silicon chip technology to determine if cancer is present in a sample.

When RNA interacts with the nucleic probes attached to a gold nanowire, an electric current lets the chip know something has been detected.

The method for collecting and processing the biological sample will depend on the cancer in question. The real trick advantage over traditional testing of these samples comes from working on the nanoscale. By increasing the number of nucleic acid probes, the rate of interaction between biomarkers and probes gets much quicker. This is how the biosensor can work in just 30 minutes. Kelley and her colleagues have created versions of the chip that are multiplexed – detect more than one thing at once. They could conceivably create a model of their device that detects all of the most prevalent forms of cancer at one time.

If the combination of biological detectors, tiny wires, and integrated circuits seems familiar, it should. These same basic elements are what allowed for the creation of the oral cancer in spit detector, the bacteria biosensor, and the DNA Electronics genetic testing device. The lung cancer breathalyser works in a somewhat similar fashion but uses nanoparticles to detect chemicals rather than biomarkers. Collectively, these five devices (and many others we haven’t discussed yet) indicate that we are about to enter the age of ‘labs on a chip’. That is, the testing and detection processes that used to require days and entire laboratories of researchers are soon to replaced with fast acting biosensors that fit in the palms of our hands.

Give these technologies five to ten years (or less in some cases), and I am certain that the trips to our doctors will change dramatically. Almost every important disease or illness will have an associated hand held biosensor chip associated with it. Infectious diseases like swine flu, or HIV, or even a bio-terrorist weapon? You’ll know what you have in minutes. Getting older and want to be tested for prostate, oral, lung, or breast cancer? It’ll be done while you wait. Access to quick and reliable information about our health is going to help us live longer and healthier so that we have more time to enjoy. You can even sit around in a paper dress if you get nostalgic.

Why are Americans living longer? (Left) Why aren't we living as long as everyone else? (Right)

Almost half of all deaths (48.5%) in this country are due to heart disease or cancer. The overall death rates for stroke, heart disease, hypertension, and cancer fell between 2006 and 2007, and lifespan rose as a result. It’s clear that those two culprits are what is keeping the US from the longevity it might otherwise have.

And longevity means a lot to us here at the hub. We’ve shown you surgical advances, and promising medical developments. We’ve given you a look at some of the oldest people in the world, and some of the healthiest places in the world. The one thing we’ve learned through it all is that the secret to a long life is really, really simple: lifestyle.

You think a futurist blog would talk about advanced nutrients, or remarkable medical cures, but the truth is much more low-tech. People live longer when they focus on wellness, not illness. In other words, the daily routines we follow have a statistically bigger impact than trips to the doctor or hospital. As we mentioned in our discussion of blue zones, a longevity-lifestyle includes daily exercise, a diet low in fats, sugars, & meats and high in fruits, vegetables, & (some kinds of) fish, and avoiding stress. These things won’t just help you live longer, they’ll help you live healthier and happier lives.

Exercise. It helps you live.

Let’s take another look at heart disease and cancer. Exercise, good diet, and low stress reduce weight gain which is linked to obesity, diabetes and heart disease. Even cancer might be avoidable through our simple plan. As Dr. Terry Grossman mentioned at Singularity University, cancer cells live almost exclusively off of glucose in the bloodstream. Avoid high glycemic indexed foods and you starve the cancer.

The US has a “health care equals medical treatment” mind set. We focus on curing diseases, not living healthier lives. Our signature meal is a burger, fries, and a soda. Many of us complain when we have to walk across a large parking lot. We avoid routine visits to the doctor, but then rely on expensive surgeries, prescriptions, and other treatments when we get horribly ill. And we let ourselves grow very stressed over almost everything. It’s a recipe for disaster.

The ongoing debate about how to insure Americans is missing a vital point. Taking more people into any insurance system, public or private, is just treating the symptom, not the condition. As a country we need to change the way we live. Complaining about how trillions of dollars are used, may be less important than figuring out why we have to spend the money in the first place.

Have those trillions of dollars been wasted? The CDC report shows, in fact, that when it comes to diseases unrelated to exercise and diet, the US is doing very well. Take HIV/AIDS, who’s death toll was just over eleven thousand people in 2007, despite an increase in the number of cases. That’s a 10% drop from 2006 – the largest decrease in almost a decade. Improvements in treatments are obviously making a dent in the disease. Influenza and pneumonia also saw appreciable drops.

I think the CDC report reveals that we are living longer despite our bad habits. Imagine our longevity if we kept our medical funding, and also improved our lifestyle! Some of this may already be happening. I hope that the US starts to realize that health care starts in our homes, not our doctor’s office. There are some really amazing things in our future – modular robots, tactile holograms, and the singularity! We just need to live long enough to enjoy them, and a better lifestyle is more likely than a more expensive doctor to get you there.