No, Google didn't just create AI that could "build your genome"

Most scientists don't have their own PR machine to hype their work. After reading the announcement last week from Google's genomics group, I realized that's probably a good thing.

Wired article last Friday reported that "Google is giving away AI that can build your genome sequence." Sounds impressive–two high-tech innovations (AI and genomes) in the same title! Unfortunately, the truth is somewhat different. It turns out that Google's new "AI" software is little more than an incremental improvement over existing software, and it might be even less than that.

I'm going to have to get into the (technical) weeds a bit to explain this, but it's the only way to set the record straight. The Wired piece opens with this intriguing challenge:
"Today, a teaspoon of spit and a hundred bucks is all you need to get a snapshot of your DNA. But getting the full picture—all 3 billion base pairs of your genome—requires a much more laborious process."
Interesting, I thought. The writer (Megan Molteni) seems to be talking about genome assembly–the process of taking billions of tiny pieces of DNA sequence and putting them together to reconstruct whole chromosomes. This is something I've been working on for nearly 20 years, and it's a fascinating but very complex problem. (See our recent paper on the wheat genome, as one of dozens of examples I could cite.)

So does Google have a new genome assembly program, and is it based on some gee-whiz AI algorithm?

No. Not even close. Let's look at some of the ways that the Google announcement and the Wired article are misleading, over-hyped, or both.

1. The Google program doesn't assemble genomes. That's right: even though the Wired piece opens with the promise of "getting the full picture" of your genome, the new Google program, DeepVariant, doesn't do anything of the sort. DeepVariant is a program for identifying small mutations, mostly changes of a single letter (called SNPs). (It can find slightly larger changes too.) This is known as variant calling, or SNP calling, and it's been around for more than a decade. Lots of programs can do this, and most of them do it very well, with accuracy exceeding 99.9%.

How could Wired get this so wrong? Well, the Wired piece is based on a Google news release from a few days earlier, called "DeepVariant: Highly Accurate Genomes With Deep Neural Networks," written by the authors of the software itself. Those authors, who obviously know what their own software does, make the misleading statement that DeepVariant is
"a deep learning technology to reconstruct the true genome sequence from HTS sequencer data with significantly greater accuracy than previous classical methods."
If you read on, though, you quickly learn that DeepVariant is just a variant caller (as the name implies). This software does not "reconstruct the true genome sequence." That's just wrong. To reconstruct the sequence, you would need to use a program called a genome assembler, a far more complex algorithm. (I should add that many genome assemblers have been developed, and it's an active and thriving area of research. But I digress.)

The Wired article also points out that
"the data produced by today’s [sequencing] machines still only produce incomplete, patchy, and glitch-riddled genomes."
Yes, that's true. Again, though, DeepVariant does nothing to fix this problem. It can't assemble a genome, and it can't improve the assembly of an "incomplete, patchy" genome.

2. Wild hyperbole: the caption on the lead image in the Wired piece says "Deep Variant is more accurate than all the existing methods out there."  The Google press release, presumably the source for that caption, claims that DeepVariant has "significantly greater accuracy than previous classical methods."

No, it does not. This is the kind of claim you'd never get away with in a scientific paper, not unless you rigorously demonstrated your method was truly better than everything else. The Google team hasn't done that.

How good is it? First, let me remind you that variant calling programs have been around a long time, and they work very well. An incremental improvements would be nice, but not "transformative" or a "breakthrough"–words that the Google team didn't hesitate to use in their press release. They also used the word "significant," which they'd never get away with in a scientific paper, not without statistics to back it up. Press releases can throw around dramatic claims like these without anyone to check them. That's not a good thing.

About a year ago, the Google team released a preprint on bioRxiv that shows that their method is more accurate (on a limited data set) than an earlier method called GATK, which was developed by the same author, Mark DePristo, in his former job at MIT, which he left to join Google. GATK is quite good, and is very widely used, but other, newer methods are much faster and (at least sometimes) more accurate. The Google team basically ignored all of the other variant calling programs, so we just don't know if DeepVariant is better or worse than all of them. If they want to get this preprint published in a peer-reviewed journal, they're going to have to make a much better case.

(As an aside: a much-less hyped method called 16GT, published earlier this year by a former member of my lab, Ruibang Luo, is far faster than DeepVariant, just as accurate, and runs on commodity hardware, unlike DeepVariant which requires special resources only available in the Google Cloud. And it does all this with math and statistics–no AI required. But I digress.)

(Another aside: if we really wanted to get into the weeds, I would explain here that the "AI" solution in DeepVariant is transformation of the variant calling problem into an image recognition problem. The program then uses a method called deep neural networks to solve it. I have serious reservations about this approach, but suffice it to say that there's no particular reason why treating the problem as an image recognition task would provide a large boost over existing methods.)

3. More wild hyperbole. The Google news release opens with a sentence containing this:
"in the field of genomics, major breakthroughs have often resulted from new technologies."
It then goes on to describe several true breakthroughs in DNA sequencing technology, such as Sanger sequencing and microarrays, none of which had any contribution from the Google team. Then–pause for a deep breath and a paragraph break–we learn that "today, we announce the open source release of DeepVariant." Ta-da!

I can only shake my head in wonder. Does the Google team truly believe that DeepVariant is a breakthrough on a par with Sanger sequencing, which won Fred Sanger the 1980 Nobel Prize in Chemistry? This is breathtakingly arrogant.

4. DeepVariant is computationally inefficient. Even if it is better than earlier programs (and I'm not convinced of that), DeepVariant is far slower. While other programs run on commodity hardware, it appears that Google's DeepVariant requires a large, dedicated grid of computers working in parallel. The Wired article explains that two companies (DNAnexus and DNAStack) had to invest in new GPU-based computer hardware in order to run DeepVariant. An independent evaluation found that DeepVariant was 10 to 15 times slower than the competition. Coincidentally, perhaps, Google's press release also announces the availability of the Google Cloud Platform for those who want to run DeepVariant.

No thanks. My lab will continue to use 16GT, or Samtools, or other variant callers that do the job much faster, and just as well, without the need for the Google Cloud. As a colleague remarked on Twitter, the "magic pixie dust of 'deep learning' and 'google'" doesn't necessarily make something better.

Genomics is indeed making great progress, and although I applaud Google for dedicating some of its own scientific efforts to genomics, it's not helpful to exaggerate what they've done so far, especially when they take it to this level. Both the Google news release and the Wired article contain the sort of over-statements that make the public distrust science reporting. We don't need to do that to get people excited about science.

Soon your Internet will look just like cable

The new FCC chairman, Ajit Pai, formerly worked as a lawyer for Verizon. His plan to eliminate net neutrality is a bigger gift to Verizon than anything he's ever done before.

In just a few weeks, the FCC will vote to eliminate net neutrality. The vote isn't in doubt: with Pai in charge, the anti-neutrality votes have a 3-2 edge. Without net neutrality, Internet service providers will be able to charge web companies for "fast lanes," which they can't do now. Smaller companies and individual's websites may be slowed down so much as to render them unusable. The biggest service providers (Netflix, Google, Amazon, and others) will have to cough up extra money, but the consumers won't see any of that–all the benefits will go to the ISPs. Consumers will see their rates go up.

Higher fees for lousier service. Does this sound familiar? That's how cable companies have operated for years.

Not surprisingly, virtually everyone hates this idea except the cable companies themselves. The telecommunications industry, though, is very excited about the prospect of all the money they're going to make. When previous FCC commissioner Tom Wheeler proposed to weaken net neutrality just a couple of years ago, the ensuing public outcry convinced him to reverse himself, resulting in a strong ruling in 2015 preserving neutrality. This week, Wheeler blasted Pai's new rules, saying that "this proposal raises hypocrisy to new heights."

But don't take my word for it. Check out this terrific and entertaining explainer from John Oliver, earlier this year:


If Ajit Pai and his telecom buddies get their way, here's what your Internet service might look like next year–I altered the first line, just to convey the idea; the rest is from a list of Comcast's current cable TV services:
That's right: your Internet service provider (ISP) will be allowed to bundle websites just like they bundle television channels. Of course, ISPs claim they will do no such thing, but why should we trust them?

If net neutrality goes away, no longer will anyone be able to set up a website and turn it into a thriving business by offering popular content. They'll first need to raise money to pay the ISPs, or else face being throttled back before their business even has a chance..

No one wants this change except a few large telecom companies. Interviewed by The Nationformer FCC Commissioner Michael Copps said
"There can be no truly open internet without net neutrality. To believe otherwise is to be captive to special interest power brokers or to an old and discredited ideology that thinks monopoly and not government oversight best serves the nation."
Ajit Pai, our new FCC chairman, clearly belongs to the former. Verizon is now in charge of the FCC.


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.