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Illumina Concedes on Long Reads, Buys PacBio

Author: 
Theral Timpson

At 1:02 pm today, there was a tremor in the world of genomics as it was announced that the two leaders in the field of sequencing have become one company. Goliath has opted to pick David up and put him on his shoulders. Upon first reaction, I'd say three things. 1. High quality long reads are the future of sequencing. Disrupting a standard carried for years in the drive toward the $1,000 genome of quantity over quality, PacBio stepped in and raised the bar for the technology of DNA sequencing. As Evan Eichler of UW put it to me in an interview once, "when long reads are just twice the price of short reads, short reads are dead."

 

2. Why now? Roche had a major deal with PacBio which ended this past year. Were the Illumina folks in the hallway when the Roche people closed the door and headed to the airport? This is Illumina’s biggest purchase ever, but they have the money. Did it take this long for Illumina to recognize the value of PacBio's long reads? Is PacBio facing some limitations with their technology, made more urgent with Oxford Nanopore appearing closer in the rearview mirror?

 

3. Is this good for science and medicine? Since Mike Hunkapillar took over at PacBio, the company has slowly and methodically built up the business based on this niche of high quality long reads. I remember the first interview I did with Mike back in 2014. I brought up Illumina. He quickly said, “oh you mean short reads...” He said it so diminishingly as he sat there at his desk in his plain red shirt looking down at the floor, then directly back up at me. At the time Illumina seemed absolutely unstoppable. And PacBio’s stock was at its lowest. Their instruments were way behind schedule, not doing what they were supposed to do, and having a terrible problem with errors.

 

My first reaction was, what a cocky guy. My second reaction was, what are short reads? It was the first I’d heard of the distinction. PacBio then went around the world educating one scientist after the other on the possibilities of their long read technology. And they demonstrated that their errors were random, and that with deep enough sequencing, the error rate could potentially be not a problem at all. Then scientists came to PacBio educating them on the possibilities of their long read technology. At that time we had a bioinformatician on the program by the name of Gene Myers, the same guy who worked for Craig Venter in the Celera days and wrote the Blast algorithm. Gene said he loved the PacBio long reads and was getting 100% accuracy! This was not what I was hearing from the critics of PacBio down in San Diego. It was painstaking work for PacBio when the whole world was buying up Illumina machines without a second thought. Soon scientists were collaborating with PacBio on very new and innovative projects such as exploring areas of the genome that had never been characterized, going back to the days of the Human Genome Project. A whole new field of structural variation blossomed and began to have meaningful impact on cancer and neurodegenerative disease. The folks at PacBio were having fun. There has been an atmosphere over there akin to a university institute. They have published and co-published thousands of papers. It’s been a unique company. Now let's move south. Illumina is more than just a company today. They are an ecosystem. I was just in San Diego at the Jay Flatley Innovation Center. Up here in the Bay Area they set up the world’s first genomics incubator. They got FDA approval of the first clinical next gen sequencing diagnostic test. Illumina is an ethos, and that ethos is boldness. They have kept an aggressive timeline in coming out with new products, and they have conquered new markets. They spun out a company called Grail for heaven's sake. It’s mission? To detect cancer before we have it. Illumina has also driven personal genomics. Years ago they began offering to sequence anyone's genome. They spun out the direct-to-consumer company, Helix. It seems DNA just can't replicate itself fast enough for this bold company. Here's my question: Will that boldness nurture or knock over PacBio’s methodical scientific collaboration laboratory? We’ve talked about the elephant in the room. And the monkey. We must mention the mouse. This year Oxford Nanopore, who Illumina divested it’s shares of a couple years ago, sequenced a whole human genome on their pocket sized synthesizer. The read lengths were much longer than PacBio’s read lengths. The scientists I listen to tell me that in the coming head-to head between PacBio and Nanopore, PacBio had nowhere to go with their technology, that Nanopore wins out on throughput and, already, on price. Is this a surrender on PacBio's part? Will Illumina be able to take the Sequel and advance it? And will we soon hear that Illumina will be buying Nanopore? Remember that Illumina's current technology, the tech that made them who they are was picked up in a buyout. That was Clive Brown's technology, who is the technologist at Oxford Nanopore. He already lost one instrument to Illumina, and I've heard he’s sworn never again. As I write this, I can't help but see that the engine of Illumina's boldness has been built on the assumption that gathering all this data about all the DNA in our whole world will mean a whole lot to a whole lot of people. (I'll never forget one bioinformatician on a panel in a very chic setting in San Francisco one night saying, "we're just sequencing for sequencing sake!") Some of it is very important. BRCA data mean a lot to many. New structural variants can mean a lot to some patients. Understanding how life works will go into our biology text books. Don't get me wrong. But the pace of sequencing should somewhat match the pace of our making sense of the data, the pace of our understanding. PacBio and their scientific partners have been pretty good at that.

Who Is Misleading Whom About Precision Medicine?

Author: 
Theral Timpson

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."

Headline of the Month, Maybe the Year . . .

Author: 
The Editors

Journalists and politicians have been hitting pharma companies pretty hard and heavy these days over high drug prices.  But we think a recent headline at STAT news about drug effectiveness might be going too far.  

The following appeared in my email inbox:

Opinion:  Drug effectiveness should influence what doctors prescribe.

What?  Drugs should work?  Isn’t this asking a bit much from physicians and pharma?   STAT is really going out on a limb here.  Next thing you know they’ll be saying people should get their genome sequenced.  Or asking that the American healthcare system make us healthier.  It’s just a gutsy call.

Remember the Woody Allen joke about the two old ladies going out for a fine dinner in upstate New York?

“This food is terrible!”  complains one.

“I agree,” says the other.  “And the portions are so small!” 

“Drugs don’t work,” one might say.

“I know, and they’re way too pricey.”

Perhaps to shield themselves from any liability for such an outlandish headline, STAT has labeled it as “Opinion.”  Unfortunately this didn’t mean the article was very creative. 

One can quickly think of several reasons why doctors should be prescribing drugs that have nothing to do with effectiveness.

1.  A tangible product.  Doctors need something to give us when we go see them, preferably something that doesn't work so we'll be back shortly.   And a little white pill that is ingested daily is much easier to produce than a brochure.  It doesn’t have to be shiny with neon colors.  It just needs to be bright enough to find when we drop it on the floor.     

2.  Target practice.  Here’s one I’ll bet you didn’t think of:  Drug prescribing could be a new Olympic sport.   Track and (medical) field.  A friend of mine who has recently been treated for breast cancer came up with this one.   She found it comforting to know that doctors have multiple drugs in their quiver to increase their chance of actually hitting something. 

3.  Exploration.  Drugs are the new frontier.  And there are all those awesome side effects out there to experience.  Gosh, dude.  So little time, so many side effects.

4.  A backup plan. For those squeamish doctors who don’t want to see blood and perform surgery, a little white pill is just the ticket.  In fact, all you need to do is write a ticket.  The patient can go find the pill themselves.

5.  Ritual.  It’s in our basic nature to need regular repetitive activities.  Taking a pill every morning can put one’s day together, without the need to avoid your spouse.  And at night, swallowing a little pill (not too much water) can assure one that the universe is continuing to expand at just the right rate for dropping off to sleep.  Our parents took whatever pills the doctor gave them proudly and without a fuss.  Let’s keep up the tradition.

39andRufus: Genetic Testing for Pets

Author: 
The Editors

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....

What Would You Do for Darwin Day?

Author: 
The Editors

This month a lone member of the House of Representatives from Connecticut, Jim Hines, proposed a bill to make February 12th Darwin Day.  It was totally symbolic, having as much a chance of survival as the dinosaurs after the meteorite.  For one thing, we live in America and Darwin is, of course, British.    

We think it's a great idea and to support Mr. Hines we reached out to some audience members to see how they might celebrate a Darwin Day:

 

“Bird hunting.  Ducks, not finches.”

-Rob from Minnetonka, Minnesota

 

“Drop out of medical school.”

-Jun Park from Providence, Rhode Island

 

“Darwin Day?  That’s easy.  I’d go buy a Beagle.”

-Mrs. Montromain from New York City, NY

 

"Probably stay home and watch old episodes of Survivor.”

Jenna from Orlando, FL

 

“Go to the zoo.  Maybe this time memorize the latin names of my ancestors.”

Jim from San Diego, CA

 

“Would listening to the Beatles count?”  

 Gita from Portland, OR

 

“I’d mend my socks.”

“Huh?”

“I’d mend my socks.  Did you say Darnin’ Day?”

“No. Darwin Day.”

“Oh, excuse me, dear.   Um . . . . I’d still mend my socks.”

-Donna from Rochester, NY

 

“Work on bringing back an extinct species.  Just to screw with his head.”

Richard from Cambridge, MA

A Republican Staffer on the Gottlieb Hearing

Author: 
The Editors

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.

Democracy and Science Have Tea at the White House

Author: 
The Editors

The wheels on his navy blue Toyota Prius could be heard squeeling as Science wound down the parking structure in Bethesda.  Yes, it's true, Science's parking spot involved two stories and some undwinding to get out on the open road.  Today Mr. Science was headed to the White House for tea with Ms. Democracy.

As it happens, on this particular day, our Mr. Science is a religious man.  One doesn't know how it happened.  It just happened.

“Lord, I need some help on this one.  Everyone said Doomsday was coming, but I still held out hope.   We’ve had such momentum since sequencing the genome.  How do we cut back now?”  

Science was getting nostalgic and sentimental.  If he was English, he’d go for a whiskey.   But he was American, so instead he was having a “Come to Jesus” chat . . .  with Jesus. 

“What can I say to her?  That we are ever so close on Alzheimer’s?  That we’re on the brink of the first ever treatment?  And cancer!  We’re on the brink of the brink!”  

Pulling into the parking lot from which he’d be shuttled to 1600 Pennsylvania Ave, Science carefully and efficiently put his sun glasses in the compartment at the roof of the car.  Security.  He took off his belt and put it with his iPhone into the grey container.

Democracy was already present when Science walked into the Yellow Oval Room. 

“Welcome, Science.”

She brought the tea service to the table herself.  He noticed her pride in the tea set.

“That’s a beautiful teapot,” he complimented.   I sound like an idiot, he said to himself.

“It’s very special to me,” replied Democracy. 

Now what to do about yesterday’s announcement about billions of dollars in budget cuts?   Science sat down waiting for his confidence to join him.  He felt naked without his slides and clicker.

“I’m very glad to meet you.  Can I pour you some tea?”

Democracy leaned forward in a black dress that came an inch above the knees.  Her hair hung free like a country girl on a swing.

“Thank you,” he said gathering his thoughts and fortitude.  He was used to the anger that comes from having to leave the lab and fight for his work with polite conversation over tea.

“First of all, I want to say what a great job you’ve done for America.  The President is a big admirer.  And he said to tell you he takes lots of vitamins every morning.”

The next thing she says will say everything, he thought.

“He says 'lots and lots,' and I guess he’s telling the truth.  He eats his breakfast at strange hours.”  She sipped from a rose and teal painted cup.  Her smile automatic.

“Madame Democracy, I hope . . .”

“I talked with the President last night.  And he wanted me to tell you that he’s a really big supporter.”

Science was familiar with her accent from television.  The scent she wore danced around him like Salome, making a play thing of his nose and turning his stomach.  Being distracted by the stirrings of arousal made him again angry.  "I hate her, and I hate that I hate her," he exclaimed to himself.  Still, he was curious why it is that his own biology would sabatage the future of biology.

“The President feels that his supporters in the red states aren't really benefiting that much from what you do. They’re more afraid of terrorism than they are of dying.  I mean like from disease or global warming or stuff like that.   And also,” she went on, “when drugs come out they are the much too expensive.  And besdies that, they are addictive."

Democracy pulled her skirt forward though it didn’t move at all.  She glanced hard at a blemish on one of her nails.  

"Oh Jesus, is this really happening?" Science asked himself.   "Has it come to this?  The future of the human race, the future of millions of patients with Alzheimer's, with rare diseases that can be solved!  Of all days, and this is the one where I nick myself shaving!  And my mustache needs a trim."  

The hard earned wave of confidence he had trained to come at times like this, along with the thought “I’m Science--I don’t have to look good,” didn’t come.  

“Excuse me, Madame Democracy, I must interject.”  She took her first sip of tea.  “Does cystic fibrosis choose between red and blue states?  Perhaps you don’t know, I discovered the gene for cystic fibrosis.  Shortly after that we had a treatment.  The first ever for the disease.  We are so close on Alzheimer's . . .“

"Alzheimer's is a terrible disease.  My uncle has it.  I see him now, and I can't believe I ever had crush on him."

"The future of  . . ." She cut him off.

"Maybe you should be more in the present, Science, and less in the future."

His mind was all over the place.  A recent grant to the Albert Einstein College of Medicine for a new center for diabetes research.  A new instrument for single cell sequencing.   Kathleen Sibelius standing to make another great announcement.  He was tired.  He should have let go in the Obama years.  Now he’d have to cut, the first major setback in years.   Which disease would he ignore?  Which world renowned scientists would he turn down?  He heard the next guest being prepped in the hallway.  Democracy was clearing her throat.

“It will be tough, but you’ll find a way.  There was one year where we--not 2005 as I’m sure you’ve seen--there was one year--there were years--where we had to cut back.  The President--he wasn't the President then of course-- said we had lost tons and tons of money.  I didn’t know how to do it at first.  I had to change the brand of coffee we drank in the morning.  It was terrible.  Science, can I share a recommendation to you?"

"Of course, you're Democracy."

"What if you were to just focus on one thing?  Cancer, for instance.  Just focus on cancer.  Put all the money there.  Make everything about cancer.  The media will really help you out.  It’s the best advice I ever received.  From my agent.  He said, Sweetheart, when you go for the man who has money, don’t mess with other men.  Sink it into one.  If he's a winner, you come up big.  If not, what do you have to lose?”

Science threw back the rest of his tea.

“Also, and the President would never say this, but here’s what I think."  She stood up.  He stood up. "You mention many breakthrough therapies.  But you’ve never come up with some real hair replacement treatment.  That's what people want.   If only you come up with something for hair.”  

She turned and leaning over with grace and ease, she set her cup down.

“And then there is the small of the President's hands.  Many times scientists say they come up with something for that department.  But it never happen."

“What about Viagra?” Science asked.

“Yes, true.  You have a point.”  She looked at the door.  “And I will talk to the President.  I'm afraid he's so focused on this Wall.  You see, it's his strategy too--sink all he has into one thing.  He doesn't care about me, if I live or die. His whole Presidency hangs on the Wall.  Now, I'm sorry, we have to be ending our chat.  It's been a pleasure to meet you.”  They walk toward the door.  “I hear you’re a religious person.  At first I chuckle.  I'm very religious.  And that you play the guitar?  That's amazing.  You have to come back to White House soon.”

“Thank you Madame Democracy.”

Science wondered, would they clear his teacup before the next guest was seated?  As a staff secretary walked him to the door,  he noticed that a member of the security team had a limp.  The secretary said, "polio when he was young."  

"That's one we got," Science mumbled to himself.

Homo Sapiens (D)Evolves into Homo Medicus

Author: 
The Editors

A well known science and medical author, Wades Tudeep, has proposed an upgrade to a famous Shakespeare quote from Hamlet:

“What a piece of work is a man! How noble in reason, how infinite in faculty! In form and moving how express and admirable!  In action how like an Angel!  In apprehension how like a god! . . . [proposed addition] . . . In DNA, what an  encyclopedia of disease!"

At a recent conference of medical futurists obsessed with human DNA, Wades Tudeep said, “with the sequencing of the human genome and all of you scientists’ fabulous efforts, we now know for sure there are three types of mankind:  (a) the sick, or those with disease,  (b) survivors, or those who lived through a disease, and (c) previvors, or those who are about to get a disease.”

Scientist superstar Kneels N. Thegrass was delighted with the discovery.  

“This is big.  This is so big.  We finally now have a name free of any romance or mystery for humans who are not sick.  The announcement today that most of us are “previvors” will be remembered for decades to come.  I’m so glad Tudeep’s new book, “The Ultimate Book on the Gene,” is being made into a documentary so that every previvor will know who he or she is and no longer continue with all this folderol. It's another giant step forward for science.”

Yale literary professor, Old Hare Bloomedalready was customarily nonplussed.  

"Darwin may have told us where we came from, but did that take the mystery out of it?  Go ahead;  call humans--who Shakespeare compared to gods and angels--ticking genetic time bombs.  I prefer the lingo from a former scientific time, that of homo sapiens, or wise man.    Yes, we’re ticking time bombs, but at least we’re wise ticking time bombs."

Wades Tudeep was quoted at the conference in a tweet by @LoveToTweetScience as saying that the “most important thing is to keep the human being in the center of the work.”

“Tudeep is confused,” tweeted back Dr. Bloomedalready.  “He doesn’t know whether he wants to be a scientist or a writer."

Update:  Since this article was published, a San Francisco artist has just announced her new show, Previvors.  The exhibition, a collection of framed printouts of human genetic code, is planned to tour the country and has heralded great acclaim.  

“This is big,” wrote New York Times art critic, Rob Art Withasmile, "this is so big.  It builds on every great work of art mankind has ever made about himself.  To show man as his--and her--genetically naked, vulnerable self always on the brink of destruction--it’s just awe inspiring.  With regard to the issue of content, the disjunctive perturbation of the spatial genetic relationships brings within the realm of artistic discourse a distinctive and quite formal juxtaposition. Who would have thought of it?” 

Why the Revolution Will Start in Biomedical Research or How I Learned to Love Antibodies

Author: 
Mike Simson

“The very word “secrecy” is repugnant in a free and open society; and we are as a people inherently and historically opposed to secret societies, to secret oaths and to secret proceedings. We decided long ago that the dangers of excessive and unwarranted concealment of pertinent facts far outweighed the dangers which are cited to justify it.”

This portion of a famous speech given by President Kennedy frames the problems we are facing not only in our government, but in biomedical research. These problems are caused by the lack of transparency and traceability under which the biomedical research industry operates, exemplified by research use antibodies.

Tim Bernard, head of the biotechnology consultancy Pivotal Scientific in Upper Heyford, UK says that the 2 million antibodies on the market probably represent 250,000–500,000 unique ‘core’ antibodies. If what Tim Bernard stated in this Nature article is true, then every antibody manufactured will be relabeled an average of 4 to 8 times. This means that the average antibody is available on at least 4 to 8 different vendors' catalogs, which appears to researchers as unique products offered by each vendor. In some cases, the same antibody can be offered in a dozen or more catalogs under different brand names. In the case of the first example presented above, the researcher buys all available products on the market to find out that only a few are unique.

This would not necessarily be an issue if there was not an all-time low public confidence in the findings published in scientific journals. A report released in 2012 stated as little as 11% of the most important published biomedical research could be reproduced by the industry's top scientists at the biotech giant, Amgen, which caused great alarm in the scientific community. A year prior to the Amgen report being released, a team at Bayer HealthCare in Germany supported the claim of low reproducibility with their conclusion that only about 25% of published preclinical studies could be validated to the point at which projects could continue.

It is the relabeling of scientific products which eliminates traceability for the future reproduction of scientific work, and is a business practice consistently used by most vendors. Even though this business practice is at the heart of the dilemma, it is rarely mentioned as a factor by many of the industry's key opinion leaders. Dr. Jan Voskuil, the former CSO of Everest Biotech and founder of Aeonian Biotech, makes it clear that manufacturers are under a "gag order" to not identify themselves as the makers of the products they sell to the vendors.

Because there is not traceability there is also no real accountability.

The vendors keep up the appearance that they themselves are the primary source of all their antibodies. This enables them to keep QC data on the product sheet that were generated many years ago, thus keeping the sales going, while the actual antibody that generated these data may have sold out and has been replaced by successive other batches (from different animals) and the current batch on sale may no longer be able to generate such data at all. Vendors accrue data from their own customers or from their own QC department, thus making the OEM product look unique. Even monoclonal antibodies that are theoretical genetic clones and therefore identical throughout time, suffer from batch-to-batch variations, but not to such severe extent as some types of polyclonal antibodies where the genetic variation is greater. Nonetheless, certain hybridoma clone numbers are still being used for decades while, just like with all cell lines, hybridomas cannot be the same after so many passages.

All the mess is amplified due to the vast network of vendors obtaining each other’s catalogue items. Consequently, the same antibody starts to occur several times in one catalogue. We can now understand how the practices of an industry undermine scientific pursuits.

Ordum Ab Chao

The reaction to these reports discovering the low levels of reproducibility in preclinical research has been rightful concern and alarm at the highest levels of the National Institutes of Health (NIH), which issued new criteria for grant reviews aimed at bolstering the reproducibility of NIH-funded research. Another direct result of this “Reproducibility Crisis” was the establishment of the Global Biological Standards Institute (GBSI) which released a study in the journal PLOS "The Economics of Reproducibility in Preclinical Research" which states $28 billion is spent in the United States each year on biomedical research that can’t be reproduced by other researchers. GBSI has now assembled committees to mandate new guidelines that all companies selling antibodies must follow.

Interestingly, members on these committees are comprised of the industry’s top companies which also practice the relabeling of other manufacturers' products. Some believe this may create a barrier to competition with those setting the guidelines eliminating smaller companies from the marketplace. One could draw a correlation with the ushering in of the “Patriot Act” after the terrorist attacks on “9/11”. It was passed into law under the guise for addressing holes in our national security, but has since been discovered to have turned over individual rights to the State. Is the GBSI promoting an enormous problem only to quickly manufacture a solution that will only serve to reinforce the powers that be?

The solution is quite simple, but extremely difficult to implement. It is like meditation where the act only requires you to stop thinking and only be aware of your bodily sensation--simple in theory, but very challenging in practice. Here, in preclinical research we need a platform that identifies original manufacturers and makes their products, i.e. antibodies, available in affordable sample amounts for parallel testing. The platform would also allow for feedback from researchers regarding their experiments and product performance to be submitted in the form of a review. These reviews would be interactive allowing manufacturers to offer guidance and optimization of protocols used. If we can create an egalitarian system in preclinical research, then maybe it will spread to other industries and the rest of the world. That’s how big this really could be if we get it right.

Click here to see a fuller version of this article.

Five Reasons Why Scientists Should Not March . . . And Five Reasons Why They Might Just Should

Author: 
Editors

Gene and Tonic

1.  There’s no good and elegant way for a scientist to march.  For one thing, there are no slide projectors.  In fact, there are really no tools for marching, except the bull horn.  And that takes someone who wants to talk loudly.   Duh!  Scientists don’t actually do things.  They get tools to do them.  

2.  Scientists marching in America would look too French.  Guillotines are for frogs and mice, not people.  

3.  Marches are boring.  It wouldn’t be two minutes before scientists at a march would be checking the microbiome of nearby fire hydrants, recording local temperatures, or objectively and systematically observing bystanders’ reactions to . . . a science march. How can you observe the mice when you are yourselves the mice, they'll ask.

4.  Science is not political, and scientists shouldn’t act like they are people.  Everyone knows that scientists must remain anonymous and never surrender to modern celebrity culture.  Watch out,  you might get elected to something.   Isn’t one of the steps of the scientific method to make sure you never piss off anyone in power?

5.  It’s a waste of time.  Scientists are too busy doing science to worry about whether they have the right to do science.  Besides, if they leave their labs, who would work on the next generation of nuclear toys for Donald to show off to Vladmir when he comes over for playtime at the White House?  

 

Still not convinced?  Neither are we.  Scientists must march because:  

1.  This is not your mom's lab anymore.  Science lost in the election.   Some have argued that a march would upset Trump's voters.  Oh, yes, because Trump voters are the epitome of restraint.   Republicans ran on an anti-science platform . . . and won.  Deal with it.

2.  It worked for Canada.   Ask Stephen Harper what happens when you muzzle scientists.

3.  OK, if not a march then a giant COLLECTION.  How about scientists walk across the country and collect all the life saving medications, the iPhones, the bridges, the pasteurized milk, and those cute glow-in-the dark fish.  

  Attention Americans: please have all products of science out on the street corner in bins ready for collection by Earthday.  And don’t forget your microwave and all those dildos!

4.  Go ahead! You know you want to. Show off that newly inscribed lab coat.   You think Trump's supporters are frightened of the way you think?  Wait ‘til they see you in uniform.

5.  And finally . . . because Laura Hercher said to.

Labcoats of the world, unite!



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