Transgenic stem cells lead to a miraculous cure

Sometimes I read a science paper and I just say "Holy cow, this is amazing." I don't have that reaction very often, but I did last week.

Amidst all the hype, the hope, and the controversy about gene therapy and stem cell research, some very real progress is being made. Scientists can create working versions of human genes, package them into a virus, and then use the virus to deliver the genes to a real person. This approach creates "transgenic" cells that have bits of virus DNA within them, but the virus can be engineered to be harmless.

Last week, scientists reported in the journal Nature how they saved the life of a 7-year-old boy using transgenic stem cells. Twenty years ago, this would have been science fiction. Even today it is nothing short of astonishing.

Here's the story, summarized from the paper by Tobias Hirsch, Michele de Luca, and their colleagues. In June 2015, a 7-year-old boy was admitted to the Burn Unit of Children’s Hospital of Ruhr University, in Bochum, Germany, where Hirsch and his colleagues (Tobias Rothoeft, Norbert Teig, and others) work. The child wasn't suffering from burns: he had a devastating genetic disease, junctional epidermolysis bullosa (JEB), that had caused him to lose 80% of his skin.

Figure 1b from Hirsch et al. Schematic
representation of the clinical picture.
The denuded skin is indicated in red;
blistering areas are indicated in green.
Flesh-colored areas indicate currently
non- blistering skin. Transgenic grafts
were applied on both red and green areas.
Children with JEB suffer from constant blistering, wounds, and scarring. The disease is uncurable and children often die before reaching their teens. The 7-year-old boy was near death when he was admitted to the hospital–his weight had dropped to 17 kilograms (38 pounds) and he had severe skin infections from streptococcus and pseudomonas bacteria.

Dr. Hirsch and his team were struggling to keep the boy alive, and they had no treatments to offer. In desperation, they searched the scientific literature and found a possible treatment using gene therapy, developed by Michele De Luca, of the Center for Regenerative Medicine at the University of Modena and Reggio Emilia in Italy. Dr. De Luca had only tried this treatment twice before, and even then only on tiny patches of skin. He had never tried it on such a severe case.

The boy and his parents had no other options to save his life. They agreed to let Dr. De Luca try.

In September of 2015, De Luca took a small patch of undamaged skin (4 square centimeters) back to his lab in Italy. There, he used a retrovirus containing a functioning copy of the LAMB3 gene–the gene that was mutated in the boy–to infect the skin cells. The retrovirus integrated itself into the genome of many of the skin cells, giving them the ability to function normally. Then De Luca grew the repaired cells into new skin grafts, enough to cover 80% of the child's body.

In a series of surgeries starting in October 2015, Hirsch and his colleagues applied the skin grafts to the young boy. The results were amazing.

As reported in the paper itself:
"Virtually complete epidermal regeneration was observed after 1 month.... Over the following weeks, the regenerated epidermis surrounding the open lesions and the epidermal islands spread and covered most of the denuded areas."
In other words, it worked. The new skin completely replaced the missing or damaged skin on 80% of the boy's body. What's even more remarkable is that two years later, his skin remains normal. The new skin is functioning perfectly and the young boy has returned to school.

The science behind this treatment represents the culmination of decades of research into gene therapy, stem cells, retroviruses, and genomics. To make it all work, we had to know: the identity of the gene that caused the disease (LAMB3); the DNA sequence of a normal LAMB3 gene; how to insert the human gene into a retrovirus; how to create a modified retrovirus that wouldn't harm humans; and much more.

The success of the therapy also revealed new insights into stem cells in human skin: the small patch of undamaged skin from the boy contained many cells, a few of which were stem cells (holoclones) that could replenish the skin indefinitely. It was these stem cells that allowed the skin grafts to take hold and continue to function, hopefully for the rest of the boy's life.

Sometimes science and medicine converge, and miracles happen.

(Note: the paper is "Regeneration of the entire human epidermis using transgenic stem cells" by T. Hirsch et al.)

The new Star Trek series gets biology terribly, terribly wrong.

The new Star Trek: Discovery series is based on a massive scientific error. Can it survive?

It didn't have to be this way. Those of us who have followed Star Trek through its many TV series and movies, including the excellent trio of recent moves (2016's Star Trek Beyond is the latest) were eager to jump on board the newest show, Star Trek: Discovery.

Despite some rather uneven acting in the pilot, I was willing to give it a chance. So were millions of other Star Trek fans.

But alas, the writers have stumbled into a scientific error so egregious, and so entangled in the entire plot line, that I fear the new Star Trek cannot recover. (Note: a few mild spoilers ahead.)

Episodes 4 and 5, released on October 8 and 15, revealed that the USS Discovery, the ship that the series revolves around, has an advanced form of transport that allows it to travel anywhere in the universe instantaneously. Unlike all previous Star Trek transport tech, this one uses a biological mechanism, based on mushrooms.

Yes, you read that right. The DASH (Displacement Activated Spore Hub) drive uses mushroom spores as its power source. They've discovered a special fungus whose root system extends "throughout subspace" all over the galaxy. Using spores from this fungus, the ship can jump into subspace (or something like that) and jump out somewhere else in real space, light years away, in a matter of seconds. As bizarre and this sounds, the worst is yet to come.

To power its DASH drive, the Discovery maintains a large greenhouse full of spore-producing mushrooms. (Mycologists might love this, but how big a fan base can they be?) The problem for the Discovery, in the first few episodes, is that the experimental drive will only let them jump short distances.

Then they discover the tardigrade. Tardigrades are a real thing: they are microscopic animals, only 0.5 millimeters long, that live all over the planet. Here's a picture of one:
Electron microscope image of Milnesium tardigradum,
from E. Schokraie et al., PLoS ONE 7(9): e45682.

They are also surprisingly cute for a microscopic animal, and they are colloquially known as water bears, moss piglets, or space bears. "Space bears" comes from their ability to survive in extreme environments, possibly including interplanetary space.

Star Trek Discovery's tardigrade is, shall we say, rather different. It looks a bit like the picture shown here, but it's the size of a large grizzly bear, incredibly strong, and extremely fierce. On the show they call it a "giant space tardigrade."

But that's not all. Thanks to a unique biological property that the show's writers apparently misunderstood, the space tardigrade can access the mushroom network to travel throughout the universe, wherever and whenever it chooses.

Here's how the space tardigrade accomplishes this remarkable feat of interstellar travel, as explained by Michael Burnham, the show's central character (in Episode 5, "Choose your pain"):
"Like its microscopic cousins on Earth, the tardigrade is able to incorporate foreign DNA into its own genome via horizontal gene transfer. When Ripper [the space tardigrade] borrows DNA from the mycelium [the mushroom], he's granted an all-access travel pass."
And just like that, not only the tardigrade but the entire spaceship jump across the galaxy. Is this sounding a bit crazy? It should.

Horizontal gene transfer (HGT) is a real thing. It's a process through which bacteria sometimes take up DNA from the environment and integrate it into their own genomes. Animals can't do HGT, but rather infamously, a paper was published in December 2015 that made the bold claim that tardigrades had a unique ability to absorb all kinds of DNA. That paper was instantly controversial in the scientific community, and not surprisingly its findings were being disputed in the Twittersphere within days of its appearance. Surprisingly, the same journal (PNAS) that published the bogus HGT claim published a second paper just a few months later showing that tardigrades do not absorb foreign DNA into their genome. That plus a third paper showed that the original paper had mistakenly identified contaminating DNA as part of the tardigrade's own genome. This rapid correction of the record was a win for science; I've used this example to demonstrate to my undergraduate class how sloppy science (the first paper) can lead one astray.

So: a minor scientific controversy, quickly debunked.

Until, that is, one of the Star Trek writers got their hands on it. Apparently one of them heard the tardigrade story, perhaps someone who'd had a bit of biology in college (I'm guessing here), and got so excited that they turned it into a wildly implausible premise for an intergalactic space drive.

The idea of using horizontally transferred DNA for space travel is so nutty, so bad, that it's not even wrong. Even if tardigrades could absorb foreign DNA (they can't), how the heck is this supposed to give them the ability to tap into the (wildly implausible) intergalactic spore network? DNA that's been taken up through HGT isn't connected to the source any longer. This is no more plausible than asserting that people could connect to the mushroom network by eating a plate of mushrooms. And how would the space-traveling tardigrade take the entire ship with it? Are we supposed to assume it's creating some kind of mushroom-DNA field?

Star Trek has had faster-than-light warp drives for 50 years. Although physically implausible, warp drive isn't laughably ridiculous. The DASH drive is.

And now the entire series seems to be based on a combination of magic (an intergalactic mushroom network in subspace) and scientific errors (horizontal gene transfer by tardigrades).

I can't watch this nonsense. I'm willing to suspend disbelief for the sake of a good story (warp drive!), but I can't accept obviously bogus claims. I don't know how the Star Trek writers can get themselves out of this one, but if they don't, then Star Trek Discovery is finished. If they're reading this, here's my plea: ditch the DASH drive and find something to replace it–and for god's sake, hire a competent science consultant.

Should we all be on statins? (reprise)

Should you be on statins? New guidelines and an online calculator may allow you to answer this question yourself.

Back in 2011, I asked whether we should all be on statins. At the time, it was clear that statins offered benefits for people who had already suffered heart attacks or other serious cardiovascular problems. But for the rest of us, it wasn't clear at all. A number of studies had been published suggesting that millions more people (in the U.S. alone) might benefit from statin therapy, but most of those studies were published by drug companies that made statins. As I wrote at the time, "we need more data from completely unbiased studies."

So has anything changed? Actually, it has. Last year, the U.S. Preventative Services Task Force (USPSTF) reviewed all of the evidence and updated its former (from 2008) recommendations. The evidence now suggests that some people–even those who have never suffered a heart attack–would benefit from statins.

Here's what the current USPSTF recommendations suggest. If you've never had a heart attack and have no history of heart disease, you still might benefit from statins if:

  • you're 40-75 years old,
  • you have one or more "risk factors" for cardiovascular disease (more about this below), AND
  • you have a 10-year risk of cardiovascular disease (CVD) of 7.5%-10%, using a "risk calculator" that I'll link to below.

Now let's look at those risk factors for CVD. There are four of these, and any one of them puts you in the category of people who might benefit from statins: diabetes, high blood pressure (hypertension), smoking, or dyslipidemia.

Most people already know their status for the first 3, but "dyslipidemia" needs a bit more explanation. This is simply an unhealthy level of blood cholesterol, defined by USPSTF as either "an LDL-C level greater than 130 mg/dL or a high-density lipoprotein cholesterol (HDL-C) level less than 40 mg/dL." You can ask your doctor about these numbers, or just look at your cholesterol tests yourself, where they should be clearly marked.

For that last item, how do you calculate you 10-year risk of CVD? Most people should ask their doctor, but if you want to see how it's done, the calculator is at the American College of Cardiology site here. It's quite simple and you can fill it in yourself to see your risk.

A big caveat here, as the USPSTF explains, is that the "risk calculator has been the source of some controversy, as several investigators not involved with its development have found that it overestimates risk when applied to more contemporary US cohorts."

Another problem that I noticed with the risk calculator is that using it for the statin recommendation involves some serious double counting. That's because the risk calculator relies in part on your cholesterol levels and blood pressure, but those same measurements are considered to be separate risk factors for CVD. This puts a lot of weight on cholesterol levels–but on the other hand, statins' biggest effect is to reduce those levels.

The USPSTF is a much more honest broker of statin recommendations than industry-funded drug studies, so we can probably trust these new guidelines. Note that if the risk calculator puts you in the 7.5%-10% range, you will only get a very small benefit from statins–as the USPSTF puts it, "Fewer persons in this population will benefit from the intervention."

Don't rush to go on statins without giving it some serious thought. As Dr. Malcolm Kendrik put it last year (quoted by Dr. Luisa Dillner in The Guardian),
“If I was taking a tablet every day for the rest of my life, I would want to know how long I would have extra to live. If you take statins for five years and you are at higher risk, then you reduce the risk of a heart attack by 36%. But if you rephrase the data, this means on average you will have an extra 4.1 days of life.” 
So no, we shouldn't all be on statins. But until something better comes along (and I hope it will), they are worth considering for anyone who is in a higher-risk group for cardiovascular disease.

Clever food hacks from Cornell Food Lab might all be fake

Have you heard that serving your food on smaller plates will make you eat less? I know I have. I even bought smaller plates for our kitchen when I first heard about that study, which was published in 2011.

And did you know that men eat more when other people are watching? Women, though, behave exactly the opposite: they eat about 1/3 less when spectators are present. Perhaps guys should eat alone if they're trying to lose weight.

Or how about this nifty idea: kids will eat more fruits and vegetables at school if the cafeteria labels them with cool-sounding names, like "x-ray vision carrots." Sounds like a great way to get kids to eat healthier foods.

Or this: you'll eat less if you serve food on plates that are different colors from the food. If the plate is the same color, the food blends in and it looks like you've got less on your plate.

And be sure to keep a bowl of fruit on your counter, because people who do that have lower BMIs.

Hang on a minute. All of the tips I just described might be wrong. The studies that support these clever-sounding food hacks all come from Cornell scientist Brian Wansink, whose research has come under withering criticism over the past year.

Wansink is a professor at Cornell University's College of Business, where he runs the Food and Brand Lab. Wansink has become famous for his "kitchen hacks" and healthy-eating tips, which have been featured on numerous media outlets, including the Rachel Ray show, Buzzfeed, USA Today, Mother Jones, and more.

Last week, Stephanie Lee at Buzzfeed wrote a lengthy exposé of Wansink's work, based on published critiques as well as internal emails that Buzzfeed obtained through a FOIA request. She called his work "bogus food science" and pointed out that
"a $22 million federally funded program that pushes healthy-eating strategies in almost 30,000 schools, is partly based on studies that contained flawed — or even missing — data."
Let's look at some of the clever food hacks I described at the top of this article. That study about labeling food with attractive names like "x-ray vision carrots"? Just last week, it was retracted and replaced by JAMA Pediatrics because of multiple serious problems with the data reporting and the statistical analysis.

The replacement supposedly fixes the problems. But wait a second: just a few days after that appeared, scientist Nick Brown went through it and found even more problems, including data that doesn't match what the (revised) methods describe and duplicated data.

How about the studies that showed people eat more food when others are watching? One of them, which found that men ate more pizza when women were watching, came under scrutiny after Wansink himself wrote a blog post describing his methods. Basically, when the data didn't support his initial hypothesis, he told his student to go back and try another idea, and then another, and another–until something comes up positive.

This is a classic example of p-hacking, or HARKing (hypothesizing after results are known), and it's a big no-no. Statistician Andrew Gelman took notice of this, and after looking at four of Wansink's papers, concluded:
"Brian Wansink refuses to let failure be an option. If he has cool data, he keeps going at it until he finds something, then he publishes, publishes, publishes."
Ouch. That is not a compliment.

Soon after Gelman's piece, scientists Jordan Anaya, Tim van der Zee, and Nick Brown examined four of the Wansink's papers and found 150 inconsistencies, which they published in July, in a paper titled "Statistical Heartburn: An attempt to digest four pizza publications from the Cornell Food and Brand Lab." Anaya subsequently found errors in 6 more of Wansink's papers.

It doesn't stop there. In a new preprint called "Statistical infarction," Anaya, van der Zee and Brown say they've now found problems with 45 papers from Wansink's lab. Their preprint gives all the details.

New York Magazine's Jesse Singal, who called Wansink's work "really shoddy research," concluded that
"Until Wansink can explain exactly what happened, no one should trust anything that comes out of his lab."
In response to these and other stories, Cornell University issued a statement in April about Wansink's work, saying they had investigated and concluded this was "not scientific misconduct," but that Cornell had "established a process in which Professor Wansink would engage external statistical experts" to review many of the papers that appeared to have flaws.

And there's more. Retraction Watch lists 14 papers of Wansink's that were either retracted or had other notices of concern. Most scientists spend their entire careers without a single retraction. One retraction can be explained, and maybe two or even three, but 14? That's a huge credibility problem: I wouldn't trust any paper coming out of a lab with a record like that.

But how about those clever-seeming food ideas I listed at the top of this article? They all sound plausible–and they might all be true. The problem is that the science supporting them is deeply flawed, so we just don't know.

Finally, an important note: Brian Wansink is a Professor of Marketing (not science) in Cornell's College of Business. He is not associated with Cornell's outstanding Food Science Department, and I don't think his sloppy methods should reflect upon their work. I can only imagine what the faculty in that department think about all this.

How much brain damage is too much? NFL players head for the exits.

The smartest player in the NFL just quit.

Not because he was unable to play, and certainly not because of his age–he's only 26. No, Baltimore Ravens' player John Urschel decided to quit because the risk of permanent, irreversible brain damage is just not worth it.

Urschel is a very smart guy. He's currently pursuing a Ph.D. in mathematics at MIT, one of the best and most demanding science universities in the world. Until this summer, he was (impressively) balancing his studies with being a full-time NFL player.

But when Dr. Ann McKee and colleagues published a new study showing that 110 out of 111 former NFL players had suffered serious brain damage, Urschel could no longer pretend he wasn't putting his future at grave risk. McKee's study, the largest study yet of chronic traumatic encephalopathy (CTE), showed alarmingly high rates of CTE in college and high school players as well (91% of former college players).

Let's get one point out of the way: everyone involved with the study, including Dr. McKee, knows that it was biased. The scientists examined brains of deceased players that had been donated to the study because family members–or the players themselves, before they died–suspected something was wrong. So perhaps the true risk of brain damage is lower than 99%. Maybe it's only 50%, or 20%. Do young men playing football want to take that risk?

John Urschel isn't the first player to quit because of the growing realization that football may cause irreversible brain damage. In 2015, San Francisco 49ers player Chris Borland retired at the age of 24, and in 2016 Kansas City Chiefs player Hussain Abdullah retired at 30, both over concerns about concussions and brain damage.

The NFL has been denying or downplaying the risk for years. A few years ago, after the suicide of former player Junior Seau, they announced a $30 million partnership with the NIH to study the risks of football on the brain. As results started coming in, showing that the risk was far more serious than most people knew, the NFL backed out of the deal with $16 million still unspent.

Meanwhile, the chorus of warnings has been growing steadily louder from the medical community. Last year, a former team doctor and a former football player and coach wrote in JAMA that
"unless there is a way to reduce the number of TBIs [traumatic brain injuries] caused by the sport, football will remain a threat to the brains and health futures of the players, including impaired cognitive function and reasoning, memory loss, emotional depression, and other sequelae that profoundly erode quality of life."
Earlier this year, a study out of the CDC reported that "3 high school or college football players die each year from traumatic brain and spinal cord injuries that occur on the field," most them as a result of being tackled during games.

Over the years, football players have grown ever larger (the average NFL lineman today weighs over 300 pounds) and the intensity of the violence on the field has grown with them. It's not just in the NFL, either: last year, three high school teams in the state of Washington forfeited their games against a local team out of a legitimate fear that players would be badly injured by the opposing team's 300-plus pound linemen. Their fears were justified: the human head simply wasn't built to withstand the repeated blows that players endure.

All players might do themselves a favor by listening to John Urschel. He explained his decision–and his abiding love for the game of football–in a lengthy interview on the Freakonomics podcast a couple of weeks ago. That interview should be required listening for young players, and even more so for parents who might be dreaming that their sons have a future career in football.


Houston, we have a problem. It's called global warming, whether you admit it or not.

Hurricane Harvey poured more rain on Texas and Louisiana last week than this country has ever seen from a single storm. The city of Houston is now suffering from historic flooding, with many calling this a "1000-year flood." Congress is likely to pass a huge bailout bill in the coming days, starting with a $14.5 billion "down payment," suggesting much more is to come.

The storm's eventual costs could rise even higher than the costs of 2005's Hurricane Katrina, which cost $160 billion according to NOAA.

Let's not dance around the issue: Hurricane Harvey was a direct consequence of global warming, which in turn is a direct consequence of human activities.

It's ironic that Texas (and Houston in particular) has an economy that is dominated by on oil and fossil fuels. Burning these fuels is what got us in this mess.

It's also ironic that Texas Senator Ted Cruz, who is now at the front of the line asking for a federal government rescue package, is a scientifically illiterate climate change denier. As I wrote shortly after he announced his candidacy for President in 2015, Cruz not only denied that global warming was happening, but he then went on to compare himself to Galileo, as if he were taking a brave and bold scientific position. Right.

A few facts: the Gulf of Mexico is 4 degrees warmer than normal this year, and it has been getting worse. Back in March of this year, the Washington Post's Jason Samenow reported that the Gulf was "freakishly warm, which could mean explosive springtime storms." Warm water feeds hurricanes, and Harvey feasted on it, sucking up energy and using it to dump ridiculous amounts of water onto south Texas.

Noted climate scientist Michael Mann, writing in The Guardian, took the slightly more nuanced position that "climate change made Hurricane Harvey more deadly." True enough: if you want to be strictly accurate, we can't prove that warming temperatures are the sole cause of Harvey. Maybe with cooler temperatures, we'd have had a hurricane anyway–but it would have been a far smaller one, and the damage would have been far less severe.

Mann also pointed out that global warming has already caused sea levels to rise over half a foot, which made the flooding in Houston significantly worse than it would have been otherwise.

Now it's time to rebuild, which raises a dilemma. The U.S. can't just abandon Houston, one of our country's largest cities, even if most of its residents deny the reality of global warming (and perhaps they don't). But given that global warming is well under way, with rising sea levels and warming oceans, more catastrophic flooding events like Harvey are highly likely. Should we pay to rebuild the city exactly as it was, basically ignoring the problems of floodwater management as Houston has done until now? Or should we use the government bailout funds to reduce the risk from future flooding?

Actually, it might do even more good to impose a simple requirement, before Texas gets any of our bailout funds. Let's require U.S. senators Ted Cruz and John Cornyn, and Texas governor Greg Abbot, to state publicly that global warming is real, that humans are making it worse, and that they will work in the future to mitigate the risks posed by continued climate change. Wouldn't that be something? A simple statement, nothing more, to unlock billions of dollars in aid.

If we just rebuild everything like before, then Houston will continue to have a problem.

(*Note about the title of this article. The original quote was "Houston, we've had a problem," famously utterly by Apollo 13 astronaut Jim Lovell. In the movie Apollo 13, actor Tom Hanks (playing Lovell) instead said, "Houston, we have a problem.")

NIH institute purges climate change references, but not very well

Last week, one of NIH's institutes, the National Institute for Environmental and Health Sciences (NIEHS), did something rather mysterious. The institute purged references to climate change on its website by replacing the phrase "climate change" with "climate."

For example, a page formerly titled "Health Impacts of Climate Change" is now titled "Health Impacts of Climate," a title that obscures the main point of the page's content, which is all about climate change. Another page formerly called "Climate Change and Human Health" is now called "Climate and Human Health." Ironically, the web addresses of both these pages still contains the term 'climatechange':

  •   https://www.niehs.nih.gov/research/programs/geh/climatechange/health_impacts/
  •   https://www.niehs.nih.gov/research/programs/geh/climatechange/

which is something of a smoking gun showing the after-the-fact alterations. The attempted purge was first revealed by the nonprofit group EDGI, a group dedicated to addressing "potential threats to federal environmental and energy policy." The Washington Post revealed that these changes were made by Christine Flowers, the NIEHS Director of Communications. As quoted in the Post, Flowers explained that:
"It’s a minor change to a title page, but the information we provide remains the same. In fact, it’s been expanded."
True, the contents of these pages seem to be unchanged. But in that case, why change the titles and headings? Clearly something more is afoot. Is NIEHS trying to pretend that climate change isn't real, or that it has no effect on human health? If so, this would undermine the very mission of the institute. Are the NIEHS staff fearful that one of Trump's minions will attack them for describing objective scientific facts? If so, perhaps they should get another job.

NIEHS's attempt to re-write its own history has been woefully ineffective. It's easy to find other NIEHS webpages devoted to climate change, such as:
https://www.niehs.nih.gov/health/topics/agents/climate-change
which has the title "Climate Change" right at the top, and which links to a major report called "The Impacts of Climate Change on Human Health in the United States: A Scientific Assessment." There's also the NIEHS Climate Change and Environmental Exposures Challenge, a competition sponsored by NIEHS to create graphical visualizations showing the effect of climate change on health.

The WashPost story did not mention whether the NIEHS director, Dr. Linda Birnbaum or her boss, NIH Director Dr. Francis Collins, had plans to restore the original language to the website. I've written to them both to ask, and I'll post an update here if they do.


Reject this incompetent Trump appointee

Sam Clovis standing next to Trump during the campaign.
Trump has nominated a non-scientist to be chief scientist at the U.S. Department of Agriculture. This is an outrageous slap in the face to science. It's also a slap in the face to Congress.

As I predicted back in May, Trump has nominated Sam Clovis, a former right-wing radio talk show host and failed Senate candidate from Iowa, to be the chief scientist of the USDA. ProPublica was the first to break this story, and they also pointed out that Clovis was a vocal climate change denialist. Clovis has an undergraduate degree in politics and graduate training in business, but he has no formal training in science at all.

Clovis does have one qualification, though. As ProPublica pointed out, he has been a "fiery pro-Trump advocate on television." Sounds like a good candidate for a chief scientist job to me.

Fortunately (perhaps), the Senate has to approve this appointment. The Senate itself stipulated, in a bill that Congress passed in 2008, that the USDA's chief scientist (the Under Secretary for Research, Education, and Economics) must be appointed from
"distinguished scientists with specialized or significant experience in agricultural research, education, and economics."
The law also says, just to make it crystal clear, that the Under Secretary "shall hold the title of Chief Scientist of the Department."

Why is this appointment so wrong? I'll repeat what I wrote back in May:
Overseeing the USDA's research programs requires strong expertise in biological science. A non-scientist has no basis for deciding which research is going well, or what questions need further study, or which questions present the most promising avenues for research. A non-scientist is simply incompetent to choose among them–and I mean this in the literal sense of the word; i.e., not having the knowledge or training to do the job. This does not mean that I think Sam Clovis is incompetent at other things; I don't know him and he might be very capable in other areas. Among other problems, a non-scientist leader of a scientific agency will be incapable of using scientific expertise to set priorities, and instead can make up his own priorities.
If the Senate has any backbone at all–if Republicans are willing to show that they are capable of doing something other than rubber-stamping every action, no matter how damaging, of our self-absorbed, ignorant President–then they will turn down this nomination. Sam Clovis is so obviously unqualified that this should be easy to do.

Actually, if Mr. Clovis cared about the USDA's mission, he would recognize that he's the wrong man for the job and refuse the nomination. Even Dan Glickman, the former Secretary of Agriculture, said "I wouldn't be qualified for that job" (about himself–he's a lawyer) in a recent interview about Clovis' appointment. The current and previous Chief Scientists at the USDA have Ph.D.s and extensive scientific publication records. Mr. Clovis does not. (Note that when I wrote to Mr. Clovis in May to ask about his pending appointment, he declined to respond on the record.)

The Senate's Republicans have confirmed all of Trump's nominees so far, and I fear they will rubber-stamp this one as well. Let's hope that a few of them (and only 3 have to object, assuming all 48 Democrats vote no) realize that appointing a non-scientist to be Chief Scientist of the USDA is a slap in the face not only to science, but to Congress itself, because the appointment scoffs at Congress's own law, passed during the George W. Bush administration.

Trump can find another political appointment for Sam Clovis, as he has for other Trump loyalists. But appointing a former talk radio host, a non-scientist who has never published a single scientific paper, as the Chief Scientist of the USDA is a gross insult to the thousands of hard-working real scientists at the USDA, and to millions more who depend on, and benefit from, the USDA's research programs. Senators: do the right thing and tell Trump to appoint a real scientist to this job.

Will this be the end of college football? The risk of brain damage is startlingly high.

Parents send their kids off to college with high hopes and great expectations. Universities, in turn, have a responsibility to provide an education in an environment that supports and also challenges the students.

Universities are not supposed to encourage activities that may result in permanent brain damage.

And yet, they do. As revealed in a new report by Jesse Mez and colleagues from Boston University, just published in the Journal of the American Medical Association, a shockingly high number of former football players, from both college and professional teams, suffered chronic traumatic encephalopathy (CTE) later in life, likely as a result of their years playing football.

The study authors looked at 202 deceased former football players whose brains had been donated for research, and found that 87% of them had some degree of CTE. The highest rates of CTE were among former NFL players, which affected 110 out of 111 players. CTE was nearly as bad in college football players, though, with 91% of them (48 out of 53) suffering from CTE.

Over half of the high school players (27) had "severe pathology." The authors noted that in deceased players with severe CTE, the most common cause of death was neurodegenerative disease. As they also explain:
"There is substantial evidence that CTE is a progressive, neurodegenerative disease."
In other words, CTE is a death sentence.

The authors of the study stated their conclusions carefully, noting that the study was not randomized, and that players and their families may have been motivated to participate because they were concerned about a possible link between football and CTE. Nonetheless, even if the risk of CTE is much lower than found in this study, universities should be taking a very hard look at the risks that they are exposing their students to.

Or to put it another way, is it okay to ask young men to play football if the risk of permanent brain damage is only 50%? What if it's just 10 or 20%? Is that okay? Is football that important?

Readers of this column know my answer: no. College is not about football, and if it disappears completely, universities will be just fine. The University of Chicago eliminated its football program in 1939, and brought it back in decades later as much-reduced program, now in NCAA Division III. The university itself has remained a powerhouse, routinely ranked in the top universities in the country academically.

As I've written before, football is corrupting our universities, blinding them to their true mission (education and research) in the pursuit of a profitable entertainment business. University presidents seem helpless to stop or even slow down the enormous machine that is big-time college football. For example, in 2015 the University of Maryland (where I used to be a professor) paid millions of dollars to buy out the football coach, so that he could quit a year early and the university could pay millions more to a new coach. Ironically, Maryland had done exactly the same thing in 2011 to buy out the previous coach, at a time when the entire state had hiring and salary freezes in place. None of these actions benefitted the university or its students.

All the while, universities pretend that they are educating the players. Here's a quote from Bleacher Report's interview with star UCLA quarterback Josh Rosen:
"Look, football and school don't go together. They just don't.... No one in their right mind should have a football player's schedule, and go to school."
This from one of the top college football players in the country. (On this topic, Taylor Branch's 2011 exposé in The Atlantic is particularly worth reading. Or this article by a disillusioned former Michigan fan.)

Universities now face an ethical dilemma far more serious than merely taking advantage of athletes' skills to entertain football fans and pay inflated salaries to coaches. The JAMA study reveals that by running a football program, universities are not just robbing young men of four years that might be better spent getting an education and preparing for life: they might be robbing their students of life itself.

ClinicalTrials.gov, a great resource for patients, is being abused to market bad medicine

This wasn't supposed to happen.

Since 1997, the National Institutes of Health has maintained a database of clinical trials, ClinicalTrials.gov, that lists trials under way in the U.S. and throughout the world. It's an invaluable resource, providing a single source for patients trying to find where to get the newest experimental treatments, and for doctors and scientists looking to enroll patients in their trials.

In recent years, companies offering questionable stem cell therapies got the bright idea that they could describe their treatments as clinical trials, register them on ClinicalTrials.gov, and thereby get some free advertising. Most stem cell treatments are not FDA-approved, and many have little or no data supporting their effectiveness, but clinics can still register their "trials" on the NIH site, making it appear that they are supported and endorsed by the government. A new study by Leigh Turner, published this week in Regenerative Medicine, reveals the growing extent of this problem.

What's especially worrisome is that some stem-cell treatment clinics charge patients very high fees to participate in their "trials." Some patients (perhaps most) don't know that legitimate clinical trials virtually never charge fees.

Consider this example, reported last July by Emily Bazar at Kaiser Health News: California resident Linda Smith has knee osteoarthritis, and was looking for treatments that could restore her knees to health without surgery. She found a stem cell trial at ClinicalTrials.gov that was run by StemGenex, a clinic in La Jolla. The clinic promised it could inject stem cells into her knees to replace lost cartilage. When she inquired about signing onto the trial, Smith was shocked to learn that StemGenex wanted a $14,000 fee for her to participate.

StemGenex claimed that “The actual treatment is not part of the study protocol”: you pay for the treatment, they explained, and the study is merely a followup to see how you did afterwards.

What nonsense. I checked the StemGenex site today (a year after the quotes above), and they proudly boast that they are registered on ClinicalTrials.gov, and that
"Stem cell therapy for Osteoarthritis is being studied for efficacy in improving the complications in patients through the use of their own stem cells."
Hmm. This sure sounds like the study is about the treatment. StemGenex's site strongly suggests that their therapy works wonders:
"The goal of each stem cell treatment is to inject the stem cells into the joint to create cartilage (chondryte cells)."
Sounds good, right? If only it were true.

I've got bad knees myself, so I've been following the research on stem cell treatments for cartilage replacement for years. I would love to be able to get a simple injection that could repair my damaged cartilage. Alas, though, no one has yet developed an effective stem cell treatment for bad knees, although it is plausible, and legitimate trials are under way right now (here's one).

Unfortunately, the lack of evidence hasn't stopped clinics from offering stem cell injections right now, accompanied by all sorts of promises that are not backed by science. It's not just knee injections, either: this past March, Sharon Begley at STAT reported on three women who were blinded by stem cell therapy injected into their eyes.

Most patients think, mistakenly, that if a clinic offers stem cell therapy, it must have been approved by the FDA. That's not true–clinics offering these therapies don't have FDA approval, and they argue that they don't need it (which might be correct, but that's a topic for another day).

Patients also assume that trials listed on ClincialTrials.gov must have been approved by some government agency, but that's not true either. The site is a clearinghouse that uses the honor system, nothing more, to ensure that trials listed there are legitimate. If you read their Disclaimer (but who does?), you find that studies listed on the site are not necessarily funded by NIH or approved by the FDA.

Turner's study found 7 trials that openly state they charge patients to participate. At least they're honest about it. Turner found many more (including several run by StemGenex) that appear to charge patients despite not explaining their policy on ClinicalTrials.gov. For example, a stem cell trial by Cell Surgical Network plans to enroll 3000 patients and will charge each of them $6000 or more to participate. As Turner writes
"Cell Surgical Network uses its registered ClinicalTrials.gov study as a powerful marketing device. Press releases and the websites of the clinics that are part of this network emphasize that the study is registered on ClinicalTrials.gov."
NIH needs to start policing this site before the situation gets worse. Coincidentally, I know just where they can find the resources to do it. NIH just announced that it's about to start regulating all sorts of basic science studies as clinical trials, a move that will cause a "massive amount of dysfunction and paperwork," according to one MIT scientist. Rather than over-regulating basic science, NIH should devote those same resources to cleaning up and then continuously monitoring the ClinicalTrials.gov database.

What these stem cell clinics are doing is not a clinical trial, and advertising their services through ClinicalTrials.gov is reprehensible. For now, if a doctor or clinic tries to charge you to participate in a clinical trial, your best course may be to find another trial–and another doctor.

CRISPR gene editing controversy - does it cause unexpected mutations?

Just over a month ago, a short paper appeared in Nature Methods saying that the gene editing technique known as CRISPR-Cas9 has a big problem: it creates unexpected mutations all over the genome. This was startling news for a technique that has been hailed worldwide as a dramatic breakthrough, not only because it is the easiest gene-editing method yet invented, but also because it is (supposedly) very precise.

This new paper, by Kellie Schaefer and colleagues, found hundreds of mutations (in experimental mice) that weren't supposed to be there. The results contradicted earlier studies that showed CRISPR caused very few of these "off-target" mutations. One of the authors, Stephen Tsang, commented that
"We feel it's critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR."
Not surprising, the resulting news headlines were gloomy. The stock in three companies trying to commercialize gene editing–Editas Medicine, Intellia Therapeutics, and CRISPR Therapeutics–all fell sharply.  (Interestingly, the stocks started falling on May 24, and bottomed out on May 31. The paper appeared online on May 30.) Scientists involved with these companies quickly responded, arguing that the study was flawed, but of course those scientists have a lot of money at stake.

Who was right? Well, a new paper by Caleb Lareau and colleagues, just released in the bioRxiv preprint repository, re-examines the same data and concludes that CRISPR is just fine. I've read both papers so you don't have to. Here's what seems to be going on.

The study by Schaefer et al. used CRISPR-Cas9 to create mutations in two mice (called F03 and F05), and then sequenced their genomes. They also sequenced the genome of a third mouse, called FVB. All three mice were supposed to be genetically identical.

Then they compared all three genomes to a "reference" mouse to find mutations. (Aside: this is something my own lab does all the time, so I know the techniques well.) They found over 1,500 mutations in each mouse (which wasn't surprising, because the reference mouse differs from their 3 lab animals), but they found hundreds more mutations in the two CRISPR-edited mice. That was the main surprise from Schaefer's paper, and it's the basis for their claim that CRISPR causes numerous off-target mutations.

I had a big problem with this claim even before reading Lareau's paper. Just TWO mice? That's a ridiculously tiny sample. But I digress.

Lareau et al. pointed out, correctly, that Schaefer's conclusion depends on the mice being genetically identical. But what if the two CRISPR mice (F03 and F05) were closer to each other than to the third mouse, FVB? (It's analogous to comparing two siblings with a first cousin, although these mice are much more inbred than any humans.) In that case, the result falls apart.

Fortunately, Schaefer et al. made all their data available (props to them for doing that), so Lareau could answer this question quite precisely.

It turns out that F03 and F05 are much closer to each other than either one is to FVB.  Lareau discovered that the two CRISPR mice share thousands of mutations that FVB doesn't have.

What does this mean? Lareau and colleagues conclude that the "unexpected" mutations in the CRISPR-edited mice were already there before the experiment began, and were not caused by gene editing. As they put it,
"the CRISPR-treated embryos most likely already harbored these private SNPs and indels prior to nuclease treatment whereas the control mouse did not."
In other words, it seems highly unlikely that CRISPR gene editing caused hundreds of unexpected mutations in these mice.

Even though CRISPR is being over-hyped right now, it is nonetheless genuinely exciting technology. Nature Methods was probably too eager to publish a controversial result, an all-too-common problem with big-name journals, and they seem to have done a poor job managing peer review. (Aside: I'd love to see what the reviewers said. Did they miss the obvious problems, or did the journal editors ignore the reviewers? I doubt we'll ever know.)

A final note: this kerfuffle illustrates the tremendous value of rapid publication through pre-print archives. Lareau et al.'s paper appeared a few days ago (July 5) on bioRxiv, along with all the data they used to support their arguments. We'll probably see a journal version too, but that will take months. Getting this paper out faster was a win for science.

(Postscript: two of the authors on the bioRxiv paper have financial interests in CRISPR technology companies, which they disclosed in the paper. I have no financial interests in any of these companies.)

Gwyneth! How did you learn so much about health?

Gwyneth Paltrow has invented stickers that promote healing. Yes, stickers. Little circular stick-on thingies that you might give to your 1st-grader as a reward for doing her homework.

Gwyneth, though, has discovered something much deeper about stickers. If you make them with just the right materials, and then stick them on your body in the right places, they "rebalance the energy frequency in our bodies."

(A quick warning: if you follow the links in this article, put down your coffee first. You might laugh so hard that you'll spill it all over yourself.)

Until a day or two ago, Gwyneth Paltrow's Goop website–a "lifestyle" business that sells all things Gwyneth–advertised these stickers as using "NASA space suit material," which presumably was the source of their magic healing properties. Then Gizmodo called someone at NASA to check out this claim, and got a very clear answer.

Nope. Goop's stickers are not made of space suit material. (Not that space suit material has healing properties in the first place–it doesn't.) Gizmodo's quote from a former NASA scientist, Mark Shelhamer, sums it up nicely:
“Wow,” Shelhamer told Gizmodo. “What a load of BS this is.”   
Goop quickly updated their site, and now they don't claim anything about NASA space suits in their stickers. But they didn't dial back any of their magical healing claims. Here's what Goop says now, in an article called "Wearable Stickers that Promote Healing (Really!)":
"Human bodies operate at an ideal energetic frequency, but everyday stresses and anxiety can throw off our internal balance, depleting our energy reserves and weakening our immune systems. Body Vibes stickers come pre-programmed to an ideal frequency, allowing them to target imbalances."
Wow. What gobbledygook. I see what that NASA scientist meant. But wait, there's more! Goop tells us:
"Studies have shown that when your frequency slips, your immune system is compromised, which opens the door to getting sick."
Studies? No such studies exist. People don't have a "frequency," and there's nothing to "slip." I think it's fair to say that the Goop claims about these stickers are so ridiculous that they're not even wrong.

These stickers are powerful, though, so you must be careful. Goop warns that
"We recommend starting with 1 or 2 for sensitive people. Wearing more than 4 may cause some dilution of the individual frequencies."
Oh boy.

Paltrow sells these magic stickers (and all of her products) using pictures of beautiful models doing healthy activities while wearing stickers. This is part of Goop's appeal: Paltrow is suggesting, in essence, "I'm beautiful and healthy and I'm in my forties, so I know the medical secrets that will keep you beautiful too."

Of course, the special Goop stickers aren't cheap: they cost $60 for a 10-pack.

Not surprisingly, Goop sells lots of overpriced dietary supplements too, such as a bottle of multivitamins with fish oil for $90, which comes with claims about keeping the immune system strong. Almost no one needs these supplements, and they don't do anything for your immune system, as I've explained before.

It took me just a few seconds to find that you can get a sheet with about 50 "dreams come true" stickers at stickersgalore.com for less than $2. These don't come with any wild health claims, but they do make kids happy. I recommend trying these before you get the Goop stickers.

Goop's (and Gwyneth's) claims about their stickers are so ridiculous, so laughably nutty, that I can't really feel sorry for the people who fall for them. Anyone who can afford to waste $60 for a pack of stickers probably has too much money and not enough sense. It's just too bad that they're giving their money to a wealthy actress rather than donating it to some worthy cause.

Finally, I should note that I've always liked Paltrow as an actress, in movies such as Emma and Shakespeare in Love from the 1990s through the recent Iron Man franchise. But why would her acting skills make her an expert on human health? They don't.

Apple's next iPhone iOS will save lives

There's no way that we can convince people to stop texting while driving. It's incredibly dangerous, selfish, and reckless. According to the National Highway Traffic Safety Administration, distracted driving killed at least 3,477 people in 2015 alone. Many states have outlawed texting while driving, including my own state of Maryland, but every day I pass people on busy roads who are looking at their phones.

The only solution is technological. The phone itself needs to stop distracting you while you're driving. People aren't going to put their phones down voluntarily.

Apple's iOS 11, coming this fall, finally offers a solution. It may not solve the problem entirely, but it will likely save lives.
Apple's IOS 11, coming in the fall of 2017,
will offer Do Not Disturb while driving
The solution is very simple, technically speaking. Your phone already knows when it's on a roadway, and it knows that it's moving. So the phone's software–iOS, if it's an Apple phone–can simply disable any apps that might cause distractions.

Apple's preview of iOS11 says it will do more than that. It will not only silence all incoming calls, text messages, and other notifications, but it will text people back automatically and tell them that you're driving.

You'll still be able to use maps and GPS for directions, which is an extremely useful feature that many people just can't do without (and that doesn't cause traffic accidents).

This is a great idea that is long overdue. Apparently, Apple couldn't resist allowing passengers in the car to override the do-not-disturb mode, which I think is a pretty terrible idea. I doubt that the phone will recognize when a passenger just hands it to the driver, but I'll have to wait and see how Apple implemented this override feature. I hope it's really hard to do.

iOS 11 is coming in the fall. Google hasn't yet said anything about whether Android phones will have a similar feature, but I hope they will. This is desperately needed, and it will save lives.

Google, the ball is in your court.

Germany takes action to stem measles outbreak. Anti-vaxxers to blame–again.

Measles is on the rise in Europe, driven by "vaccine gaps" which in turn are due to misinformation about the benefits of vaccines. Vaccines are possibly the single greatest contribution to human health in the past century. Literally millions of people are alive today who would not be, thanks to vaccines.

And yet: vaccine rates have dropped in recent years in multiple countries. In March, the BBC reported that measles had become endemic (meaning that it is self-sustaining, continuing to spread within the country) in France, Germany, Italy, Poland, Romania, Switzerland and Ukraine. The worst measles outbreak is in Romania, which reported over 3,400 cases and 17 deaths in just the first 3 months of this year.

Now measles is spreading in Germany, which is scrambling to contain it. Germany had 504 cases through mid-April, versus just 33 cases for the same period last year. At least one person, a young mother of three children, has died. The primary reason for the spread of the disease, as reported by the German news outlet RT, is unvaccinated individuals, and the reason their numbers are growing is simple: the anti-vaccine movement.

In the U.S., the anti-vaccine movement caused the worst measles outbreak in 20 years in 2015. The outbreak in Germany appears even worse, despite the fact that parents can be fined as much as €2500 ($2800) for failing to vaccinate their children. In a remarkable effort to try to get this outbreak under control, the German parliament has decided to require kindergartens to report parents who don't vaccinate their kids. Let's hope this works.

Vaccination is safe and remarkably effective, but the anti-vax movement is furiously trying to convince parents not to vaccinate. Their latest gambit is "Vaxxed," a conspiracy-mongering anti-vaccine screen produced by Andrew Wakefield, the notorious ex-doctor who published a fraudulent (and later retracted) study claiming that MMR vaccines caused autism. Nearly 20 years later, despite Wakefield losing his medical license because of his "elaborate fraud," he continues to push his debunked claims.

Fortunately, many people are now pushing back. Just last week, noted New Zealand physician Dr. Lance O'Sullivan jumped up on stage at a screening of "Vaxxed" to warn people in the audience that they were being defrauded. O'Sullivan was named New Zealander of the Year in 2014 for his efforts to bring health care to disadvantaged people in rural areas. I will close with his words from a Radio New Zealand story describing the dangers of vaccine refusal:
"We are trying to save a child's life, we put it on a helicopter, it flies to Starship Hospital. The kidneys are failing, its heart's failing, its lungs are failing. All because we didn't put a bloody $7.50 meningococcal vaccine into that child's thigh."

Trump to appoint non-scientist as chief scientist of USDA

Scientists work here now, but Trump's new overseer
will probably make them all want to flee.
This is how corruption starts.

Donald Trump's expected appointment for under-secretary for research at the USDA will be a right-wing talk radio host with no scientific credentials, according to a new report from ProPublica. The expected appointee, Sam Clovis, worked as a political aide to Trump on his transition team, and was installed at the USDA in a temporary role soon after Trump took office, to be Trump's "eyes and ears" until a permanent USDA director was approved.

Clovis has no scientific background or credentials. As ProPublica explained, he was a talk radio host in Iowa who ran unsuccessfully for the Senate in 2014. He majored in political science in college and studied business administration in graduate school, and has never published a scientific paper.

Now Trump is appointing Clovis to be Under Secretary for Research, Education, and Economics (REE) at the Department of Agriculture. This administrator is responsible for a large portfolio of research, both internal and external, conducted by and supported by the USDA, including NIFA, the National Institute for Food and Agriculture.

I've had several research grants supported by USDA's NIFA, through which my colleagues and I sequenced the genomes of many agriculturally important animals and plants. I've also collaborated with internal USDA scientists who work for the Agricultural Research Service, another branch of the USDA that will soon report to Sam Clovis. I've met many outstanding scientists, both inside and outside the USDA, through these projects.

Overseeing the USDA's research programs requires strong expertise in biological science. A non-scientist has no basis for deciding which research is going well, or what questions need further study, or which questions present the most promising avenues for research. A non-scientist is simply incompetent to choose among them–and I mean this in the literal sense of the word; i.e., not having the knowledge or training to do the job. (This does not mean that I think Sam Clovis is incompetent at other things; I don't know him and he might be very capable in other areas.) Among other problems, an non-scientist leader of a scientific agency will be incapable of using scientific expertise to set priorities, and instead can make up his own priorities. In the case of Sam Clovis, his history leads me to believe that his priorities will be based on his conservative political agenda.

The previous under secretary, Catherine Woteki, has a Ph.D. in human nutrition and was previously the dean of the school of agriculture at Iowa State University. The current Acting Under Secretary, Ann Bartuska, has a Ph.D. in ecology and has worked in many scientific positions, including high-level positions at the U.S. Forest Service and the Nature Conservancy.

Both Dr. Woteki and Dr. Bartuska could run circles around Sam Clovis on any of the scientific issues under the purview of the USDA's Under Secretary for Research. Nonetheless, Clovis will soon oversee thousands of scientists currently working at the USDA, despite the fact that he has no idea what they do. It is still possible that Trump will appoint someone else, or that the Senate will decline to confirm Clovis, but these possibilities seem unlikely.

When leaders are incompetent, they appoint people under them who are also incompetent. Trump's intention to appoint Sam Clovis as the chief scientist of the USDA isn't the first demonstration of his incompetence, and I don't expect it to be the last. What's most dangerous about this appointment (and others like it) is that incompetence enables and even encourages corruption, because the appointees don't understand or respect the mission of their own agencies. Instead, they follow their own agendas, whatever those might be.

The 2008 Farm Bill stipulated (section 7511) that the Under Secretary for REE must be chosen from
"distinguished scientists with specialized or significant experience in agricultural research, education, and economics."
Sam Clovis is not such a person, but Donald Trump just doesn't seem to care.

Trump's Energy Department just killed jobs in 19 states

ARPA-e's announcement sounded good. But now it turns out
to be just a tease.
It's a lot easier to kill jobs than to create them. It is much easier to kill innovation than to create it. Trump's Department of Energy, led by former Texas governor Rick Perry, seems to be taking the easy route.

As reported in the journal Science this week (and first reported by Politico Pro), DOE has halted its process to award $70 million in new grants that its research agency, ARPA-E, had announced this past December. ARPA-E is the Energy Department's Advanced Research Projects Agency, created to fund high-risk, high-reward new ideas about energy.

Even more alarming is that DOE has imposed a gag order on the program managers, so that scientists have no idea why their funding is being delayed, or it if will ever arrive. According to the Science story,
"The resulting uncertainty is having a devastating impact on research teams, scientists say, and even threatens the viability of small companies for whom these major awards are so important."
The move, which came with no warning, leaves many scientists, including young Ph.D.s just starting new jobs, suddenly without jobs. Bloomberg BNA was able to extract this tiny bit of explanation from an Energy Department spokesman:
"As with any transition from administration to administration, we have undertaken a full review of all department programs, policies and taxpayer-funded grants."
I'm sure that makes the unemployed scientists and struggling energy technology companies feel much better.

Cutting funding that has already been awarded–and which used money that was already appropriated by Congress–is especially disruptive. How can anyone hire new scientific staff when the federal agency might yank away a grant that it had already announced? The Science story described a young Ph.D. plant biologist from Penn State, Molly Hanlon, who was due to start work next week on one of the new ARPA-e projects, but now she might not have any job at all.

The 26 projects, all of them now on hold, were originally announced by DOE in December. Here are the states that are homes to the threatened projects:
California, Connecticut, Colorado, Delaware, Florida, Illinois, Iowa, Kansas, Massachusetts, Minnesota, New Mexico, New York, North Carolina, Pennsylvania, South Carolina, Texas, Utah, Washington, West Virginia 
15 of the 26 projects are led by companies, most of them small companies trying to creative innovative new technologies. The other 11 are housed at universities, including Energy Sec. Rick Perry's alma mater, Texas A&M (so at least we can't blame Perry for bias). And 9 of these 19 states voted for Trump last November.

This isn't even the whole story. Eight more projects under a different ARPA-E program, ENLITENED, were told in mid-March that they would be funded, Science reports. Just a week later, though, the press conference to announce the awards was cancelled, and the program now appears to be in danger of cancellation.

I'm sure that all of these project teams invested many months in preparing their winning proposals. Leaders of the projects announced back in December were poised to begin their research until the sudden announcement this week, with no explanation, that everything was on hold.

All that Mr. Trump has to do to save these valuable, high-tech jobs is nothing; just let the DOE's ARPA-E program do its work. Unfortunately, this seems to be too much to ask.


An aspirin a day keeps the grim reaper away

Low-dose aspirin is good for you. Any brand of aspirin 
will do, Bayer or otherwise.
Should you take an aspirin every day to prevent some types of cancer? The evidence is growing, and it all points to the same answer: yes.

In 2016, the US Preventive Services Task Force, a science-guided panel that reviews the evidence for a wide range of treatments, recommended regular low-dose aspirin use for people between the ages of 50 and 69 as a way to prevent heart attacks, strokes, and some types of cancer. For people younger than 50 or older than 69, the USPSTF said that the evidence was inconclusive.

The 2016 recommendations came with a caveat: long-term aspirin use carries a slightly increased risk of bleeding in the stomach and intestinal tract, and a small increase in the risk of a hemorrhagic stroke–although it reduces the risk of ischemic strokes. (Ischemic strokes are caused by blood clots in the brain, while hemorrhagic strokes are caused by bleeding. Aspirins reduces the blood's ability to clot, so this tradeoff makes sense physiologically.)

Later in 2016, a study by Yin Cao and colleagues at Harvard found that aspirin use reduced the risk of cancers, especially colon cancer. To be specific, they found a benefit from taking 0.5 to 1.5 aspirin tablets per week for at least 6 years (a standard tablet is 325 mg). For people who followed this regimen, the risk of colon cancer was about 19% lower.

Now, a new study also led by Yin Cao and others at Harvard, just reported in the annual meeting of the American Association for Cancer Research, shows even clearer benefit. They looked at long-term results in a group of 130,000 women (mostly nurses) and men (doctors and other health professionals) who have been followed since the 1980s. Overall, woman had a 7% reduction in the relative risk of dying from any cause and men had a 11% reduction.

Most of the reduction in mortality was due to the reduced risk in dying from colon cancer, breast cancer, and prostate cancer. Just as with the previous study, the benefit appeared in people who took 0.5 to 1.5 aspirin tablets per week for at least six years.

A decrease in the risk of dying by 7-11% seems like a mighty nice benefit from such a simple treatment. For those (like me) whose stomach is upset by aspirin, a low-dose aspirin tablet taken with food may be easier to tolerate. The low-dose pill contains 81mg, one-fourth of a standard tablet, so 2-6 of these per week is equivalent to the 0.5-1.5 tablets that provided a benefit in the latest study.

It's very encouraging when the evidence for a simple, low-cost treatment consistently shows the same benefit. An important caveat is that that if you have any bleeding problems, you should consult your doctor before taking aspirin.

As for me, I've already stocked up on low-dose aspirin. I'm trying the chewable ones first.

Guys: you don't need a PSA test for prostate cancer

Graphic depiction of risk without or with PSA tests, from
the Harding Center for Risk Literacy.
I learned a new word this week: pseudoepidemic. That's what happens when people start looking really hard for a disease that didn't get much attention earlier, and then–not surprisingly–the disease suddenly becomes much more prevalent.

This is precisely what happened with prostate cancer in the early 1990s, just after screening tests for prostate-specific antigen (PSA) became widely available. As explained by NIH's Paul Pinsky and colleagues in an article in the New England Journal of Medicine this week, prostate cancer rates rose from 135 (cases per year, per 100,000 men) in 1988 to 220 in 1992, a 63% increase in just four years. Rates slowly dropped after that, but they remained above 150 through 2009.

No one believes that this increase represented an actual increase in the rate of prostate cancer. Instead, it was an increase in the rate of diagnosis, made possible by the PSA test. After this simple blood test became available, millions of men started getting routine PSA testing. The idea was that, because prostate cancer increases the levels of PSA in the blood, this test could detect cancer early, which in turn would save lives.

It hasn't worked out that way. The problem is that, as a large body of evidence has now shown, most prostate cancers are slow-growing, "indolent" tumors that don't kill you, at least not before something else does.

What's worse is that the treatments for prostate cancer have very serious, life-altering side effects. 20-30% of men treated with surgery and radiation suffer from long-term incontinence, erectile dysfunction, or both.

This is especially problematic given that the false-positive rate of PSA testing is as high as 80%. In other words, if your doctor tells you that your test was positive, there's an 80% chance that you don't have cancer. Many men, though, elect for further, much more invasive testing after a positive result, because who can sleep at night without knowing for certain?

But how about the benefits of early detection? Alas, they did not materialize. Very large trials (including the PLCO study, with over 75,000 participants) showed that routine PSA screening did not prevent any deaths. The only study to show any benefit, ERSPC, had serious flaws, as explained by Ian Haines and George Miklos in the Journal of the National Cancer Institute.

Putting all these facts together, the US Preventative Services Task Force concluded that the harms of PSA testing substantially outweigh the benefits, and it recommends, bluntly:
"Do not use prostate-specific antigen (PSA)-based screening for prostate cancer."
The American Academy of Family Physicians agrees, stating:
"There is convincing evidence that PSA-based screening leads to substantial over-diagnosis of prostate tumors. Many tumors will not harm patients, while the risks of treatment are significant. Physicians should not offer or order PSA screening unless they are prepared to engage in shared decision making that enables an informed choice by patients."
Even the American Urological Association, which strongly opposed the USPSTF recommendation when it first appeared, now recommends against PSA screening except in one age group, men 55-69 years old. The AUA, though, is highly biased in favor of testing, because its members make significant income from PSA tests and the subsequent follow-ups.

Prostate cancer is a very serious disease among older men. According to the American College of Physicians, 1 out of 16 men will receive a diagnosis of prostate cancer in their lifetimes, although only 2.9% will die of it, most of them older than 75. Nonetheless, PSA screening does not help: it carries a significant risk of harm. In this week's NEJM article, Pinsky et al. conclude:
"Under the `first do no harm principle,' it seems reasonable to forgo mass screening as a public health policy at this point."
Someday we may have a better test for prostate cancer, but for now, we don't. If your doctor offers you a PSA test, your best response is probably to tell him no thanks.

[Aside: the article in the New England Journal of Medicine was written by scientists from the National Cancer Institute at NIH, yet it's behind a paywall that prevents anyone from reading it without paying a costly fee or an even more expensive subscription to the journal. Why do we have to pay a fee to read work that the taxpayers already paid for?]