Blog

The last two years have had us on edge.  It had scientists marching in the street.  That was unprecedented.

So what does last week’s election mean for the genomics community?

Scientists can focus on science

A friend of mine put it this way, “When Obama was in office, I realized I’d been like a cat, relaxed and having my nap in the afternoon. When Trump was elected, I felt like a mouse, always on edge.”

There are studies showing (did we need studies for this?) that relaxed states are better for focus and creativity.  The Libertarians have been supportive of Trump and his doctrine of rolling back regulations and “draining the swamp” of professional governmenteers, saying this is good for innovation.   The opposing argument is that when we’re all wondering if the basic things that we’re used to counting on--our drinking water, basic education, respect for the planet and its limited resources--are all going to go to hell, we might not be innovat-ering at our optimal pace.  Not to mention such things as the funding of the NIH, which Trump proposed to cut by one fifth.

The stock market took a quick sigh of relief, and so too have a lot of scientists.  Something tells me even the data is happier this week.  Single HPLC peaks are showing beautifully.

Still, let’s agree too, that scientists--that we all--have become more aware of the precariousness of the fundamental values of the enlightenment, like reason and science: this has been a good outcome of the past two years.  And let's celebrate the fact that we can say now, “the past two years” with some knowledge that the next two will be different.    

Scientists have become more civically engaged.  Some even ran for office.  It was laudable.  At the same time it was horribly unfortunate that professors of science who had spent a lifetime, or half a lifetime, developing their minds in a special discipline and contributing to a body of research and to a community in pursuit of big fundamental questions of biology would have to go to Washington and fight for the basic right to be able to do such research.

John Adams wrote:

“The science of government it is my duty to study, more than all other sciences; the arts of legislation and administration and negotiation ought to take the place of, indeed exclude, in a manner, all other arts. I must study politics and war, that our sons may have liberty to study mathematics and philosophy. Our sons ought to study mathematics and philosophy, geography, natural history and naval architecture, navigation, commerce and agriculture in order to give their children a right to study painting, poetry, music, architecture, statuary, tapestry and porcelain.”

I wonder where he would have put evolutionary biology.

DTC Testing

Speaking of cats, some say there is one cat that came out of the bag with Trump’s election that won’t be going back in with this recent election.  DTC testing is having a heyday, and most of the thought leaders in our field think that now that Pandora’s box is open, it won’t be shut, even if a Democratic president is elected in 2020.

For years the FDA kept a tight lid on DTC testing.  Those days are over with the Trump administration.  I’ve just today seen the new Helix ad promising folks "100 times more data on important health and lifestyle information”.    Black Friday is upon us.   Last year, DTC tests were competing with the InstaPot on Amazon at this time of year.

What’s the problem with genetic testing going DTC without FDA oversight?  I encourage everyone to listen to Laura Hercher’s recent podcast with Matt Fender over at the Beagle Has Landed.  What struck me most about this interview was that Matt represents the next generation, one that is growing up with DTC testing as a part of life and assuming that the tests mean something.  Afterall, it’s our DNA.  Isn’t there ample scientific data connecting our genes with disease?  Matt went through terrible anxiety before he got to a doctor and a genetic counselor and did some confirmation testing with a clinical company which confirmed that he had nothing to worry about.

As I say, the clinical community has accepted this shift on DTC testing, and are now moving on, albeit with advice and caveats.   In a recent Mendelpsod interview with Daryl Pritchard of the Personalized Medicine Coalition, this was the warning he gave to anyone and all:

If you get a DTC test, don’t belive anything it says until you go to your doctor or unless it's approved by the FDA. 

Ummm . . . O . . . K . . .

But I'm not ok with it, and disagree with most others on this.  I think the cat has to go back in the bag.  And will when the first big scandal breaks, such as a woman getting a BRCA test from 23andMe that she thought was the real thing only to find out it wasn't.  She sues 23andMe.  And she sues the FDA when she hears how it could have been done right and is done right in some countries.  Why are we playing around with this?

Race and Genetics

Race was a big topic in the election, driven, as we all know, by the president himself. Amy Harmon wrote a piece in the New York Times that provoked the committee at ASHG to issue a statement on race and genetics.  No doubt the topic will die down somewhat now, but I think it’s an important conversation, and I plan to write more about it.   And whether scientists continue to run for office or not, they can always speak out more in public on the question of race and genetics.

Why is race not genetic?

We’ve heard on this program many times from geneticists how certain diseases are correlated with certain racial groups.   African American women have a higher rate of abnormal BRCA1 or BRCA2 genes.  Ashkenazy Jews have known for years they should be tested for the cystic fibrosis CTFR gene because of studies showing it runs higher in their population.  (There I go, conflating "population" with "race."  Come on, geneticists.  Work with me here, and quit dodging the question.)

That white nationalists in this country are now using studies such as these and other studies not always on the topic of health and disease to promote their despicable project of racial purity is abhorrent, and it needs to be answered in direct easy-to-understand language.  I’m talking about language one would use in the bar or at the barbershop.  We all have family.  What language are you going to use at the Thanksgiving table, for instance?

So, Uncle Bill, you’re reading science now?  What else have you learned--could you pass the candied yams?  Did you come across that article about the planet heating up as well?

Have you also read the science showing that the ancestry of all white Europeans goes back to Africa?  At what point did the Homo Sapiens who had walked out of Africa into Euorpe become pure? 6,000 years ago?  2,000?   When was the cut off?  And how do you define pure?

We also have to face the fact that Trump’s election and the populist movements around the world have exposed “some bone,” have caused many of us to face our own epistemic realities.  Whence science?  Whence truth and fact?   What is science?  Is there a special scientific method that spearates science from other knowledge gathering disciplines, such as cooking or gardening?   We all know the troubling statistic that a majority of biomedical research cannot be reproduced.   This soul searching journey will go on even after what's his name . . .that one guy . . . Melania's husband . . is gone from the White House, one way or another.

This month the New York Times put out an opinion article that was a reprint from Kaiser Health News written by Liz Szabo positing big doubts about the project of precision medicine. For the Times, it came with the title, “Are We Being Misled About Precision Medicine?” Unfortunately this piece does exactly what it warns against. It misleads.

Putting the headline in question form, rather than declaratory, reveals an insecure thesis. Why not just say it?

And let me ask a couple more questions. If not precision medicine, then what? And, misled by whom?

The subtitle runs: “Doctors and hospitals love to talk about the cancer patients they’ve saved, and reporters love to write about them. But deaths still vastly outnumber the rare successes.”

So that’s who’s misleading us: doctors, hospitals, and reporters. On the surface, I can see an incentive for those three groups of people to mislead us. They all want a paycheck. This may or may not be cynical, but it's possible. But that’s not where this editor and reporter go with the piece. Let’s stick with the subtitle, and ask what are we being misled about? Deaths and successes. I assume success here means success at staying alive. It turns out that deaths still outnumber successes at staying alive.

Is this news?

Are doctors, hospitals, and reporters irresponsible for telling us otherwise?

I’ve been reporting on precision medicine for seven years, interviewing doctors and scientists and many others who work in the healthcare system (providers, payers, policy makers, analysts, etc) and also other reporters, and I’ve never talked to someone who told me that we had cured death.

(To be honest, I have interviewed a few out of Silicon Valley who claim that we will “solve” disease and live much longer in the future.)

Ms. Szabo quotes the well known precision oncology pessimist in the field, Dr. Vinay Prasad, an associate professor at Oregon Health and Science University. Prasad is one researcher, and he is just concerned with oncology. Precision medicine is penetrating many fields (check out our latest show with a nephrologist and hear him talk about how single cell genomics has completely changed his field though it’s early days for clinical applications) including cardiology and rare disease. But cancer is certainly the big one. I have to say, Prasad has received tons of press. He is constantly quoted in article after article everywhere I go. I quote his studies regularly on the program as a check against hype and irrational exuberance.

“Targeted therapies tend to be least successful in patients who have exhausted all standard treatments,” says the article.

That’s because the patients have exhausted all standard treatments.

Let’s talk about how you define precision medicine. Prasad is looking at those with advanced forms of cancer who have already tried frontline and second line therapies and run out of options. But I consider many of those frontline therapies part of precision medicine. When a woman is tested for the BRCA gene, this is precision medicine already. Yet today, we think of it as routine care. When a woman with breast cancer tests estrogen receptor positive and receives Tamoxifen, this is already precision medicine. It’s the right drug for the right patient based on the genotype of her cancer. When you widen the definition, the numbers look a lot different.

For some, the term precision medicine has achieved this extremely narrow definition, this kind of rarified light, this great last hope for very very complicated late stage cancer patients, this . . . almost religion.

My favorite book on the topic this year is by Ramesh Hariharan, the CTO of Strand Life Sciences, a bioinformatics company doing genome interpretation. In the book, Ramesh details nine cases he worked on first-hand at the company analyzing patient genomes. In some cases, the patients die. (In all cases, patients will die.) In some cases, the company is able to help extend patients' lives. In the first case, his own, he finds out the genetic cause of his color blindness. In one case, two young children die early from a rare disease, but the team is able to help the parent understand why and then test the third pregnancy and determine that the baby is safe. Two of the other cases deal with cancer, one a childhood cancer. It’s not just about death and promises from a doctor all the time. It’s also about discoveries along the way and what we learn that helps the next group of patients.

Ramesh selected nine stories that would show how far genomic science has come. These are absolutely fascinating stories. The twists and turns. Just when you think Ramesh and his team have come to a dead end--and they do too--something comes to light, something gives, they find a study, they have an idea, they meet someone. The book reads like a thriller. Now . . . should Ramesh have chosen some stories where he and his team were completely baffled right away, didn’t even know where to begin, and they turned the case away? Those would have been very short stories indeed.

Humans need stories. And they need success stories. It’s how we live.

I remember when the price of sequencing a whole human genome was coming down, say to $100,000, and there were these wealthy individuals with cancer who could afford it (not the cancer, but sequencing), and who were having their genomes sequenced as a last hopeful effort. By today’s standards it sounds almost like stem cell treatment in Mexico. I had one such individual on the program. He was a well known science fiction author, Jay Lake. He had lung cancer, and he and his father (a former U.S. ambassador) were navigating the healthcare system pretty much on their own before we had much of the genomic medicine infrastructure that Ms. Szabo is able to write about today. I spoke to Jay and his dad just before Jay died. Jay’s dad talked about the difficulty managing the bureaucracy of the health system on their own. Jay shared his attitude in the face of his impending death. What I’ll never forget is that he called health a “privilege.”

It’s the underlying thinking that disturbs me about Ms. Szabo’s piece. It sounds so entitled. It sounds as though the entire public were at some point promised that we would all be cured of cancer by doctors, hospitals and reporters. It feeds a public mindset--or misleads--that health is owed us.

Did this happen? Is it happening now? Did I miss something?

I’m sure the Ms. DiCanto in Ms. Szabo’s article wouldn’t have done any different than pursued every option if she had the same circumstances again. There are so many more options today than we had even twenty years ago. Some cancers, such as breast cancer, are becoming a chronic illness. Go talk to Bonnie Addario, a lung cancer patient who began the Bonnie Addario Lung Cancer Foundation and made a new career out of fighting her cancer and sharing her journey of learning about the EGFR mutation with other lung cancer patients. We’ve come to joke on Mendelspod about how many patients have picked up the equivalent of a PhD in science with their own journeys in precision medicine.

Science is hard. Health is easy until it’s not. Then it’s hard. Healthcare is always hard. We should certainly talk and write and tell and publish about how hard it is. In my experience, that's not a problem in life. That's seems to come naturally. Walk into any bar on any given day. Sit in any waiting room in any hospital, Ms. Szabo if you want to hear how hard it is and how many things are not working. The New York Times doesn't have enough raw paper to print how hard it is. It's always our gains that we celebrate and mark on the calendar. Just because people die is not a reason to publish the journal, "Why Precision Medicine Doesn’t Work."

Inside Edition reported this week on the availability of genetic testing for dogs.  But the tests mostly serve the purpose of upsetting owners who find out that their man's best friend isn’t the pure bred man's best friend they thought it was.    We did some research and found some genetic testing for dogs and other animals that had pet owners much more enthusiastic.

Dogs

A company called 39andRufus recently announced that since the Food and Drug Administration for Animals (FDAA) had relaxed their stance on genetic testing, they would begin offering the following:

-The FIDO gene reveals the likeliness of a dog to be faithful to its owner.  Most dogs have the dominant gene here, and the company suggests that owners of dogs with the recessive type will no longer hound themselves about their hounds being promiscuous with other owners.

-The C-APOE gene is the canine version of the human APOE gene, a strong indicator for Alzheimer’s.  Dog owners already know well that when their pets age, the likeliness of running for the ball in the game of Fetch and then, forgetting about the game, running away and peeing on a tree or chasing a child happens all too often.  “Be prepared,” runs the company slogan for the test.  

-The Wisdom Panel.  “Dogs can’t talk, but their DNA can,” says the packaging of this test for an entire panel of genes.  Testing includes the CGIQ gene or the Canine Genetic Intelligence Quotient and the 1v2, or the one versus two ears up.  How wise is your dog?  Swab his or her cheek and find out.

Cats

Does your cat really hate you, or just hate you?  Felinity.com is now offering a genetic test for cats based on the HISS gene.  HISS1 is the wild type allele and is still dominant in many house cats.  But the company blog says that more and more cats are testing with the mutation, HISS2.  This second allele indicates that your cat will really hate your bloody guts.  The wild type--apparently the most sought after by pet owners who are willing to dump cats they don’t want-- indicates that your pet “feigns indifference.”   Felinity.com quotes a cat genetics expert who explains, “just because your cat tests positive for the wild type doesn’t mean that it doesn’t tolerate you or have some very mild form of affection.”

One customer who recently used the test said, “I just like knowing.  Now I know for sure that my cat can’t stand me.  Doesn’t mean I don’t love her.  In fact, that makes me love her more.”

The test can also be used for pairing cats up in the case an owner wants more than one.  Just like with the British dating app, Hater, cats who really hate their owner may do best together.

Birds

Have your parrot tested today for a gene common to many talking birds.  If your pet bird tests positive for TTP or Tell Truth to Power genotype,  you may have to put your bird in the back room when company comes over.  Parrots with the TTP gene have been known to reveal their owners' age and and weight without any warning.

Bees

Bees usually aren’t pets.   But beekeepers have been tracking the genetics of the honey bee for decades.  The latest test out:  SB or Showy Behavior.  Order the SB test to find out why some bees hover over your food and then disappear and why others hover over your food, do a little dance in your face, and then disappear.  The amazing modern world we live in!

Gerbils

Everyone loves themselves a cute little gerbil.  Because the lovable rodents are so easy to get rid of if you don’t want them anymore, genetic testing has boomed for gerbils.  Adorable Genetics has partnered up with some pet supply shops who will even sell you the pet with its genetic profile worked out in advance.     There are the endurance versus sprint runners. (Surely it was the endurance type who got Richard Gere into trouble.)  There are gerbil genotpyes who eat from left to right, and those who go right to left, and those who do the zizag left to right and back to left, and those who do the left to right then left to right again, and then those who go up and down, and then those who go . . .  there's basically 180 types for eating.  There are the flippers who do backward somersaults.  And the sleepers who don’t have to be kept in a cage at all--just throw a piece of lettuce or other wet garbage on the bed or to the floor.

“It’s a wonderful use of modern technology,” said Stanford pet geneticist, Mike Wonderbee.  “Pets are awesome test subjects.  People were just too complicated for me--not their genetics.  That was easy.  It's the afterwards part.    Because you can’t get rid of your dad if he tests positive for the APOE gene.”

Other Pets

There are more, but we can’t stop watching gerbil videos....

This week at a Senate hearing Scott Gottlieb defended his nomination to be FDA commisioner.  Last night at happy hour we caught up with a Republican staffer who was willing to be candid in exchange for remaining unnamed.

Staffer:  Oh, yeah, the Gottlieb nomination.  Sweet little thing.  The nomination, I mean.  Seems like the hearing was weeks ago with this whole “nuclear” warfare going on in the Senate over Gorsuch.  

Mendelspod:  The Republicans looked pretty pleased with Gottlieb, as did some of the Democrats.

Staffer:  It was a HUGE relief for Republicans! I mean we were trying to be prepared for anything, for the name of a coal miner!

Mendelspod:  Haha.  Yeah, it looks like. . .

Staffer:  When Gottlieb’s name came in, we wondered if something went wrong at the White House, you know.  Did Trump have some bad caviar, or something?  It’s like the first time a nominee’s career actually matched his post. 

Mendelspod:  Yes!

Staffer: Gottlieb hasn’t even been talking to any Russians.  This was a cinch for us.  Actually it’s the staffers on the other side who had to do some digging this time.  Which was super great to see.

Mendelspod:  Industry leaders seemed pretty relieved too.   We caught a tweet from the CEO at Innovative Drug Company that went something like, 

“Glad to see Gottlieb’s got this in the bag.   Even though he just had to say that he had heard of drugs before.”  

Was that a fair tweet?

Staffer:  Well, Gottlieb did admit there's no science connecting vaccines and autism.  And I’m sure . . .

Mendelspod:  But isn’t that a pretty low bar?  I mean, it’s like someone getting named CEO of Google because they’ve . . . searched on Google.  

Staffer:  At least. . .

Mendelspod:  It’s not a coal miner running the FDA, yahoo!!

Staffer:  Right.  At least Republicans got to show off that they know something about science.  

Mendelspod:  Yes.  Trump seems to bring out the nerd in Republican Senators.  

Staffer:  You mean like Senator Enzi showing off his knowledge that an "adaptive trial" wasn’t just the name of an episode of The Good Wife?  

Mendelspod:  Haha.  Yes.

Staffer:  Or the name of North Carolina's new bathroom bill?  

Mendelspod:  Chairman Alexander sounded pretty pissed off at Trump for wanting to cut resources and funding at the FDA and the NIH.

Staffer: Well yeah, the Chairman worked on the 21st Century Cures bill since . . . since . . .

Mendelspod:  Since Jesus invented opioids.

Staffer: Exactly.

Mendelspod: Did you catch that article in the Washington Pissed that called Gottlieb another con artist like Trump, just with better hair?

Staffer: I know that journalist personally.  We all do.  He’s been a raging alcoholic since a month after the election.   He's used that line with most of the nominees.  He’s assigned to cover these hearings, but he doesn’t even bother showing up anymore. It's really sad.

Mendelspod: There may be something to it.  Trump’s nominees tend to be good looking.  To Gottlieb’s credit, he did seem prepared for all the questions but one, even if he didn’t get to answer any of them.  

Staffer:  Oh, which one?

Mendelspod:  That if he solves the opioid crisis in America, who will be left to vote for Trump in 2020?

Staffer:  Right.  I think I’ll bow out on that one.