Cancer cells under a microscope. Colored stains
mark different compartments in the cell. The nucleus is
red and lysosomes (which break down waste) are purple.
(Image: Carolin Zehetmeier, Morphosys AG, Germany)

Dr. Susan Love thinks breast cancer researchers need to get over their addiction to rodents.

America’s most famous breast cancer surgeon started treating women some 30 years ago. “And we’re still doing the same thing we did when I started,” she told a crowd in San Francisco last month at the Sage Bionetworks conference, aimed at transforming biomedical research.

“Surgery radiation, chemotherapy, hormones, and now we’ve added a little bit of targeted therapies,” said Love, a clinical professor of surgery at UCLA. “We never subtract anything, mind you, we only add things on top. And our results are about the same.”

Although breast cancer incidence and mortality have decreased since 1998, by 1.3% and 2% respectively, more than 200,000 women will be diagnosed with breast cancer this year and more than 40,000 will die from it. Nearly 110 women die from breast cancer every day.

Experts think earlier detection and better treatments account for the decline in deaths, but screening carries risks. With mass screening comes overdiagnosis—that is, diagnosing a condition that would not prove symptomatic or fatal—and with overdiagnosis comes overtreatment and other potential harms (see video below). Screening technology can’t distinguish between aggressive and harmless tumors, which can shrink or even disappear on their own. Overdiagnosis will likely just increase as imaging technology finds smaller and smaller tumors.

Medical experts acknowledged in an editorial in the Annals of Internal Medicine last month that it’s time to recognize overdiagnosis as a serious problem. Most patient-education materials don’t even mention overdiagnosis and most women aren’t aware of the possibility, the authors said. As they pointed out, and any woman knows, “the impact of a cancer diagnosis lasts a lifetime.”

It’s hard to think of a physician who’s done more to acknowledge the trauma of breast cancer than the author of the best-selling “Dr. Susan Love’s Breast Book,” now in its fifth edition.

That book, along with Love's early refusal to accept the oxymoronic (emphasis on moronic) “early detection is your best prevention” mantra of mainstream cancer and advocacy organizations, won her a place of honor among frustrated breast cancer activists, who know all too well that if you can diagnose cancer, you haven't prevented it. Detecting it, by definition, means it's there.

The surgical tools used on breast cancer
patients in the 18th century look gruesome, but
aren't really so far removed from the "slash, burn
and poison" approach to breast cancer today.
(Illustration: Louis-Jacques Goussier)

Activists have long pushed researchers to shift their focus from treatments and cures to true prevention.

Despite $4 billion spent on breast cancer research, researchers still don’t know what causes it or how to prevent it. Yet Love believes that the tools exist to “eradicate breast cancer within our lifetime” if we ask the right questions.

And for decades, Love has helped shine the spotlight on causes, not cures, to spare women from that dreaded diagnosis. But that goal will remain elusive, she believes, as long as researchers keep studying the disease in rodents. That’s because mice and rats don’t get breast cancer. Researchers have to give it to them.

So she’s been trying to wean researchers off rodents. “I can say this is a good study, you could do that in women, and they say, ‘Let me tell you about my rats.’ ”

Yet researchers can learn valuable insights into the origins of disease by comparing people with an illness to matched cohorts of healthy people, as the legendary Nurses’ Health Study has demonstrated for heart disease, diabetes and other conditions.

Finding the causes and, ultimately, how to prevent breast cancer requires a radical shift in thinking, Love said. And that means that at least some researchers have to give up their rats and mice and start working with the people who get the disease.

Researchers used to tell Love that even if they did want to study women, they didn’t know how to find them. But she knew that was the easy part. So for more than three years, the Dr. Susan Love Research Foundation has been recruiting an online "army of women" with a target of enrolling “one million women and a few good men.”

Dr. Susan Love spoke at the Sage Bionetworks conference in San Francisco last month. The Seattle-based nonprofit is dedicated to “moving beyond the current medical information system and its rewards.”

“Scientists come to us with studies that need people, and we e-blast them out to everybody in the army,” Love said.

So far, they’ve recruited 365,000 women for about 60 studies. Seven in 10 of the women don’t have breast cancer, but are "altruistic,” Love said. They’re willing to undergo unpleasant procedures to help researchers figure out root causes. In one study, women in the control group had to endure a sigmoidoscopy and a biopsy. And Love got more enrollees than researchers could use.

By the end of this summer, the foundation will be launching its own Health of Women Study. The large online breast cancer cohort study will follow women with and without a diagnosis to identify new risk factors. It will also follow breast cancer survivors to identify factors that predict long-term survival and consequences of different therapies.

Any woman over 18 can register online or with a mobile phone. (Men are welcome, too.)

Love’s study will let participants suggest questions they’d
like to see tested, because she thinks you don’t
need a PhD to come up with a good idea.

She told her San Francisco audience that early theories about the cause of human papillomavirus (HPV) came from observations of people who knew a man whose wife died of cervical cancer, and who then married a second woman who died of the same cancer. “They said, well maybe it’s the guy.”

“And then we figured out it was sexually transmitted, then we figured out it was a virus and now we have a vaccine.”

Potentially, Love reminds us, “Everybody is a patient.” She thinks eliminating disease is something we should all do together.

“”

Technique to reduce radioactivity in tobacco would have lowered the strength of nicotine, so the tobacco industry ignored it. Photo courtesy of Valentin.Ottone

While most of us probably never considered the tobacco industry to be particularly good people, the latest report based on 13 million documents released since a court-ordered legal settlement in 1998 should disturb even the most optimistic of industry supporters.

Scientists at UCLA have examined millions of previously secret internal records from the tobacco industry looking for clues as to how they handled potential health concerns regarding cigarette smoke. From these documents, two previous reports revealed that the presence of the radioactive isotope polonium 210 in tobacco and its associated increase in lung cancer risk from smoking was common knowledge among top industry executives as early as 1964. These reports showed that tobacco companies not only failed to inform consumers of the risk of smoking, but also refused to take action to reduce the radioactive potential.

The latest study, published this week in the journal Nicotine and Tobacco Research, uncovered that the tobacco industry had detailed knowledge of the presence of radioactive substances as early as 1959.

According to the report, the authors were “surprised to discover the industry's scientists had actually made, as early as the 1960s, quantitative and realistic radiobiological calculations of the long-term radiation absorption dose of ionizing alpha particles and reached the conclusion that the alpha particles in cigarette smoke in promoting ‘cancerous growth’ in the lungs of smokers was ‘not an unlikely event’.”

Amazingly, the tobacco industry was also aware of an acid washing process by which the radioactive potential of cigarette smoke could be dramatically reduced. Autopsies from smokers indicate that the majority of tumors occur where the alpha particles accumulate in the lungs. This acid wash technique is effective at removing the radioisotope from tobacco plants, and has the potential to significantly reduce cancer risk.

Though the industry frequently cited cost and environmental concerns for why they did not adopt the technique, the UCLA team found evidence that the industry was primarily worried that the technique would reduce the addictive potential of nicotine.

“The industry was concerned that the acid media would ionize the nicotine, making it more difficult to be absorbed into the brains of smokers and depriving them of that instant nicotine rush that fuels their addiction,” said Hrayr S. Karagueuzian, the first author of the study.

So not only was the industry aware that tobacco causes cancer, they intentionally hid this information from consumers and refused to take steps to reduce the danger because they wanted their customers to remain addicted to their product.

While this raises many frightening questions for consumers of any ingestible product (food industry, I’m looking in your direction), what bothers me most is the uncertainty over who will be held accountable for this crime.

According to the report, polonium 210 is still present in all commercially available domestic and foreign cigarette brands.

Sex may have evolved to cut down on genetic variation.

No, I don’t mean in the red light district of Amsterdam or at Mustang Ranch. What I am talking about is the high biological cost of sex. In fact, it is so expensive it can be hard to imagine how it ever evolved in the first place.

The main reason sex is so costly is it takes two parents to have a kid. Asexual creatures can do it on their own.

This doesn’t sound like much of an advantage, but it is. Some computer simulations show that a single asexual individual can overtake a population of one million sexual creatures in about 50 generations. That is about 1000 years for people and only 8 years for mice.

So sex needs to have some pretty big advantages to have ever evolved in the first place. Otherwise the first sexual creature would have been quickly swamped out by all of its asexual brethren as soon as it appeared.

In the past, scientists have pointed to variation as one of sex’s big advantage. This probably isn’t the whole story though. Or even most of it.

Sex does create additional variety through the mixing of genes but it probably isn’t enough to explain the rise of sex. You’d have to live in some pretty chaotic times for this variation to offer enough an advantage to an individual to overcome its cost. Eight or a thousand years just isn’t that long in an evolutionary time scale.

A new review out is bringing up an old idea that Muller came up with back in 1932. The main advantage of sex is to provide a safe time to recombine our DNA.

Recombination is simply the swapping of DNA between two identical (or nearly identical) pieces of DNA. For us that means swapping between the chromosomes we got from mom and dad. So DNA is swapped between our two chromosome 1’s our two chromosome 2’s and so on.

This is where part of that variation we were talking about earlier comes from. But more importantly, recombination actually helps repair DNA damage. You can see the effects of no recombination by looking at our sad little Y chromosome which is slowly disappearing because it has no one to recombine with except itself.

But recombination is a double edged sword. Cells need it to repair their DNA but it can cause lots of DNA damage if it isn’t controlled. For example, even with all of our controls in place, 1 in 1000 humans still ends up with one chromosome stuck to another.

You can see what happens with uncontrolled recombination by looking at cancer cells. These cells end up with extra chromosomes, chromosomes stuck together, and lots of other chromosomal problems because they recombine willy-nilly. They do well for themselves but are definitely bad for the individual.

So it makes sense to contain recombination to some easily controlled time. Sex may have arisen and took over the world because it provides a safer way to keep harmful DNA damage in check. The variation that everyone goes on about may simply have been a beneficial side effect.

After just nine generations, the sexual beasts on the left are already being swamped out by the asexual ones on the right.

See the following for more information:

Muller’s Ratchet
Extra chromosomes and new species

The earth at night as viewed from a space, in a composite image from NASA.

The world is not as dark as it used to be. Streetlights, parking lot security lights, office building lights, and neon signs shine all through the night. Light pollution can come directly from light bulbs, or it can bounce off of dust and water droplets in the air, creating a bright haze called skyglow. This 24-7 illumination can be seen from space, and it has negative effects on humans and wildlife. But there are ways to dim the lights and reduce their effects—and save energy in the process.

Astronomers have long aware of the problems associated with nighttime illumination—it makes stars disappear. Big telescopes are built away from big cities for this reason, although bright lights have a way of encroaching. QUEST blogger Ben Burress talks about light pollution and astronomy here and here.

Non-astronomers are affected by nighttime lighting, too; exposure to light at night affects our circadian rhythm, the 24-hour cycle deep inside our bodies. Seeing light at night can cause sleep disorders. And long-term exposure to light at night has been linked to breast cancer, because light inhibits the production of melatonin, which slows the growth of cancer cells.

Exposure to light affects animals, too. Anyone who has sat next to a porch light on a summer evening knows that moths are drawn to light—along with a multitude of other insects. Outdoor lights disturb insects’ nighttime navigation, and affect their feeding and mating. Lizards are often found feeding on the tasty insect snacks that gather around lights. Often, these lizards are not normally nocturnal—staying up at night gives them access to a “night-light niche” and an abundant food source. It also creates the opportunity for interactions between animals that would never meet in the dark conditions of previous centuries. Some lizards get a double benefit, basking in the warmth given off by artificial lights (incandescent lights are really inefficient; most of the energy they use goes to producing heat, not light).

Night lights make birds sing at odd hours, and mess with their mating and migration schedules. During migration, birds are drawn to the light from tall buildings and towers, resulting in deadly collisions.

Sea turtles are perhaps the most famous example of animals affected by light. Hatchlings swim towards the light—historically the horizon above the ocean. But now that beaches are backed by well-lit condos and hotels, baby turtles crawl further onshore instead of out to sea. There is evidence that sea turtles are drawn to light with short wavelengths, and using bulbs with longer wavelengths or using filters that cut out short light wavelengths reduces the number of baby turtles crawling in the wrong direction.

Simple fixes, like different bulbs or shades that focus light on the ground, can do a lot to re-darken the night sky, as does turning off unnecessary lighting. Dimmer, more efficient bulbs that provide enough light for human needs—but not too much—are a step in the right direction, and can save on energy costs. Dark sky conservation and stricter lighting ordinances will help.

I was surprised by the negative health effects of exposure to nighttime lighting—something to keep in mind as I work late into the night, basking like a lizard in the glow of my computer screen.

37.879329 -122.2463347

Mistletoe grows on the branch of an oak tree in Briones Regional Park. Photo: kqedquest.

Have you been hanging out under the mistletoe at holiday parties, hoping for a kiss? Well, that mistletoe is more than a Christmas kissing custom. It’s a parasite that can harm trees—and a potential treatment for cancer.

Mistletoe lives on the branches of trees, and is a hemi-parasite; it produces some of its own food (it has green, photosynthetic leaves), but it gets nutrients and water from its host plant (its roots tap into the host plant, rather than the soil). If the mistletoe grows big enough, they can do some damage. Large mistletoe plants can weigh down tree branches and make them more likely to break off during a storm. If there are many mistletoe plants in a single tree, they can stunt the tree’s growth, make it more susceptible to disease, and even kill it.

There are several species of mistletoe living in California. Pacific mistletoe, Phoradendron villosum, lives in the western US, and is a parasite on oak trees. European mistletoe, Viscum album, parasitizes a wide range of species, including apple trees and maples.

Mistletoe is spread from tree to tree by birds. They eat the white berries and spread the sticky seeds with their beaks or in their excrement.

Despite its parasitic tendencies, mistletoe has long been thought to have healing powers. In Greek legends and druid folklore, mistletoe was used to treat disease. And since the 1920s, scientists have been investigating mistletoe extract as potential cancer drug.

Several laboratory studies have shown that mistletoe extract can kill cancer cells—though other studies have shown that the extract has no effect. It seems that mistletoe growing on different types of trees (like apple, pine, oak, or elm) may have different medicinal properties.

Mistletoe extract seems to boost the immune system, by increasing the production and activity of white blood cells. (Don’t try this at home—mistletoe can be poisonous.) Several clinical trials, mostly in Europe, have tested mistletoe extract as a form of adjuvant therapy—a treatment that is given to cancer patients after their primary treatment, to decrease the risk that cancer will return. Patients were treated with mistletoe extract (injected under the skin), along with radiation and chemotherapy. Patience who received the mistletoe extract fared better than their counterparts who did not receive it. Additional studies are underway: check out the National Cancer Institute’s Questions and Answers About Mistletoe.

While you’re standing awkwardly under the mistletoe at your next cocktail party, you can wait quietly for that special someone, or you can strike up a conversation about mistletoe’s medicinal properties.

Related posts:
Briones Regional Park Exploration

37.879329 -122.2463347

If he drinks a lot, he can be up to 56 times more likely to
end up with esophageal cancer compared to a nondrinker.

Many people of East Asian descent react to alcohol with a red face, a racing heartbeat and a slight sick feeling in their stomach. This “Asian glow” is more than just annoying though. If they keep drinking anyway, it can be downright dangerous.

In addition to its obvious charms, drinking alcohol definitely has some drawbacks (besides beer goggles and nasty hangovers). One of these is an increased risk for getting cancer of the esophagus. One study I saw claimed that heavy drinkers are 18 times more likely to end up with esophageal cancer compared to teetotalers.

The risk is even higher for blushers. They are 56 times more likely to end up with this particular cancer if they are heavy drinkers. And even if they just have a couple of drinks a day, they are still at a 5 times higher risk.

Unfortunately, the alcohol flushing response is pretty common. Scientists estimate that 36% of people of East Asian descent respond to alcohol this way. That’s over 500 million people worldwide.

All of these statistics are especially scary because esophageal cancer is so common. For example, it is the 7th leading cause of cancer death worldwide and the 7th most common cancer in men in the U.S. In some parts of Russia and China, the rates of this cancer range from 30-800 cases per 100,000 people. The rate in the U.S is 3-6 per 100,000.

Many if not most of these cancers happen because the patients drank too much alcohol and smoked too many cigarettes. One review article estimated that if heavy drinking blushers from Japan switched to just two drinks per day, the number of cases of esophageal cancer there would be cut in half. Undoubtedly the same thing is true elsewhere.

Everyone is at a higher risk for esophageal cancer when they drink because of how alcohol is broken down in the body. On the way to converting alcohol to the safer acetic acid, our bodies first turn it into acetaldehyde. And that is some nasty stuff!

Acetaldehyde likes to stick to and damage our DNA. Not only that, it also keeps our cells from repairing the damage. Since cancer happens because of DNA damage, it isn’t surprising that alcohol causes an increased risk for cancer.

People who blush from alcohol have a certain version of the ALDH2 gene that has trouble converting alcohol into acetaldehyde. The end result is a build up of acetaldehyde that can damage DNA and so cause esophageal cancer.

Again, there is no increased risk if they don’t drink. In the absence of alcohol, they are just like anyone else. They just need to lay off the liquor.

Maybe these people need to find a new social lubricant. I guess it's too bad Prop 19 didn’t pass…

A fun activity to learn more about the genetics and biology of the alcohol flushing response.

A review article that raises an alarm about the risks of drinking alcohol as a blusher.

37.7749295 -122.4194155

Dermatologists must be aware that their recommendations to avoid sun exposure may be inadvertently creating other health problems. Image courtesy of thanker212.

UV radiation from sun exposure is associated with an increased risk of skin cancer. But too little sun can result in severe vitamin D deficiency, a common condition that is also linked to cancer. Additionally, low vitamin D is associated with autoimmune disorders and several other diseases.

New research from Stanford University suggests that dermatologists must be aware that their recommendations to avoid sun exposure, particularly for patients at high risk of skin cancer, may be inadvertently creating other health problems.

The study was published in the October issue of the Archives of Dermatology and examined vitamin D levels in patients with a genetic pre-disposition to sun-related skin cancer called basal cell nevus syndrome (BCNS). Vitamin D levels of BCNS patients were significantly lower than control subjects matched for age, skin tone and geographic location.

The best predictors of vitamin D levels in patients were the time of year—levels were higher in the summer—and body mass index. Obesity is known to be linked to vitamin D deficiency since fat soluble vitamin D is more easily sequestered in extraneous body fat.

Lead researcher Dr. Jean Tang says, “Our study shows that skin cancer patients who vigilantly photoprotect are three times at risk for vitamin D deficiency.”

According to Tang, while it is important to warn patients of the dangers of excessive sun exposure, it is equally important to remind them that vitamin D supplementation should be part of their daily regimen to ensure adequate blood levels. The authors of the study recommend at least 1000IU of vitamin D for patients, particularly in winter months.

The research is also relevant to the general population, particularly those who are overweight, have an indoor lifestyle or live north of 35° latitude, all risk factors for vitamin D deficiency. Ideal vitamin D levels should be above 30 ng/mL.

37.427648 -122.166793

Henrietta Lacks circa 1945

HeLa cells were obviously a tremendous gift to science, but an investigation into their history brings to light a more compelling tale. HeLa cells were named after the woman they wee taken from: Henrietta Lacks. Henrietta was a poor, African American woman who happened to be treated for cervical cancer at Johns Hopkins University, one of the premier medical research hospitals in the world. Before she passed away, a sample of her cervical cells were taken without her consent, as was the standard practice at the time. Fast forward almost thirty years, her family were largely unaware of the HeLa cell line. This line had been multiplied and sold for millions over that time, yet the destitute family never profited. No scientist had really ever explained to the under-educated family what a cell even looks like.

Enter author and science writer Rebecca Skloot. She just published her 1st book, the Immortal Life of Henrietta Lacks, now a New York times Bestseller. She spent 10 years researching, breaking barriers, and fighting to tell Henrietta's tale. I just read the book as part of the Down to a Science book club, I thought it was an eye opening discussion of science, ethics, race, and class. In fact, I found Rebecca's years of frustration trying to break through to the family the most compelling parts of the book. The overt distrust of science, particularly of medicine, seems an appropriate tale in these tough times for science communication.

She will be in the Bay Area the last week of April to discuss the book. Below are her local appearances:
Dr. Kiki's Science Hour
When: Thursday, April 22nd, 3-4 PM
Details: Local science personality Kirsten Sanford will interview Rebecca on her weekly science program.

Book Passage Cafe
When: Sunday, April 25th, 2-4 PM
Where: Corte Madera
Details: Rebecca will give a short talk with a book signing to follow.

Ask a Scientist
When: Monday, April 26th, 7-9 PM
Where: Horatius Cafe
Cost: $3 donation
Details: Rebecca will give a longer talk on the development of the book with a book signing to follow.

37.777125 -122.419644

You've probably heard about some of the breakthroughs in personal genome sequencing, where companies take a look at your DNA and send back your risk profile. That can be confusing information to have (check out this post from Quest blogger Dr. Barry Starr for his take on it). But there's a flip side to all this genetic research that doesn't have to do with risk: personalized medicine. That's where doctors can customize medical treatments to fit your genetic profile.

Right now, there are only a handful of drugs that are labeled with genetic information, so doctors can take it into consideration. (Here's an article from the New York Times that gives an overview).  But that doesn't mean existing medications are left out.  I spent some time with Deanna Kroetz in this story, who studies pharmacogenomics at UC San Francisco.  She explained that differences in our DNA can cause some of us to process drugs at different rates. We all metabolize drugs with enzymes in the liver, but based on expression of our DNA, we may have different levels of enzymes or our enzymes may not function as well.

There are plenty of other things that affect how we process drugs, like our diet or other drugs we're taking. But these genetic differences mean some people metabolize drugs quickly and others metabolize them slowly. One example that many people are familiar with is codeine.  Codeine is converted into morphine by our bodies and it's the morphine that actually has an effect — but that conversion depends on a particular enzyme. Some people have very low levels of the enzyme that's needed, so codeine doesn't do much for them.

They're also studying another drug response mechanism at UCSF and it has to do with our cells. Many drugs have to go inside our cells in order to have an effect, but if you think back to high school biology, you might remember that cells are protected by membranes.  It takes transporters – those special gatekeepers sitting on the cell membranes — to allow things in.  They also can spit things out of cells.

I spent some time in the lab with Rachel LaFond, a graduate student at UCSF.  She was running experiments on one particular transporter known as ABCG2. This transporter is particularly good at spitting things out of cells. Normally its job is to kick toxins out, but some cancers have been able to hijack this machinery.  Cancer cells with an over expression of this transporter can spit out chemotherapy drugs, which means they aren't helping the patient.  LaFond is working to understand this variation better, so they could one day develop a genetic test for it.

Listen to the Personalized Medicine radio report online.

37.769196 -122.39106