Slashdot Mirror
Genomic Medicine, Finally
Daniel Dvorkin writes "When I first started studying bioinformatics almost fifteen years ago (!) what drew me to the field was the promise that we might soon be able to provide effective, personalized treatments for a wide variety of diseases. There have been some successes along the way, like genetic tests for warfarin dosage, but for the most part our gains in understanding of basic biology haven't been matched by clinical advances. Now it looks like that is at long last about to change, and it's about time.
Too many people suffer and die from too many diseases that we more or less understand, but can't effectively treat. I hated it when I worked in hands-on patient care, and I hate it now in the lab. We are, finally, getting there."
Too many people suffer and die from too many diseases that we more or less understand, but can't effectively treat. I hated it when I worked in hands-on patient care, and I hate it now in the lab. We are, finally, getting there."
Might as well have just done:
Title: GABBO
Summary: GABBO is coming!
Article: Who is GABBO? No one knows, but he's coming soon!
Healthy long lives are a result of the combination of active lifestyles, good diet and the ability to remove sickness with the least amount of permanent damage. You can eat a genetically pure diet with perfect amounts of nutrients and still end up getting skin cancer. Medicine should not be your first stop to trying to be healthy but at the same time, It's necessary.
It's pretty interesting that one of the endorsements over at the website for the "forksoverknives" whole foods regime documentary was this:
'"A film that can save your life." - Roger Ebert, Chicago Sun-Times '
oops...
You are welcome on my lawn.
Take two genomic pills and call me in the morning. Sounds affordable.
Better known as 318230.
It is my understanding, that FDA's current stance is that all such person-specific treatments/medicines must be individually approved... And, because the approval process is so horrendously difficult and expensive, few would be willing (nay, able) to do it. Companies do it for mass-market drugs, but for individually-tailored mixtures — where the expected market is numbered in mere scores or, at best, hundreds of people — it just makes no sense...
In Soviet Washington the swamp drains you.
never been a better time to be a bioinformatician that's for sure.
How do they deliver genetic payloads? I thought that was still a major stumbling block to genetic medicine.
move over "X is the year for linux on the desktop"...we have a new contender.
2014 is the year for medicine on the genome.
never bring a twinkie to a food fight.
How many diseases have cheap preventable causes? Many
How many cheap preventable causes are the medical "science" industry interested in finding? Zero
What is the likelihood that insurance companies will want to use genetics to exclude benefits? Very high
How long time will it take for new research to enter into medical practice? As long time as it will take for the practitioner to retire.
Genetics: Too much knowledge in the wrong hands is a bad thing.
People need to maintain the distinction in their head from gene finding (which still goes on and is one of the subjects of TFA) and clinical care. The impact of genomic medicine on clinical care is still limited and is likely to remain so for the forseeable future because of what genomic medicine is currently good at predicting.
There will be some benefits in selection of oncology protocols in the short term, but knowing cancer genomics does not actually lead to new chemotherapeutic agents except in the long term (even if a drug target is discovered today, if there is no currently approved drug on the market it could take 10-30 years to develop a drug targeting a new class of mutation).
For most other adult disease, the application will be limited to relatively rare outliers like the limb-girdle disease highlighted in the article. Genomic medicine isn't going to change the fact that huge swaths of patients need to take statins, for example. In fact, the 'success' submitter posits (Warfarin) is actually a bust. The actual benefits from pharmacogenetic testing for Warfarin metabolism are swamped by all the other factors which affect Warfarin metabolism (eg diet and other meds). As for Alzheimer's which TFA also mentions, they're still at the stage of recruiting their 40k subjects to sequence at $1000 a pop. The analysis will take thousands of man-hours just to generate some new hypotheses about Alzheimer's which will, in turn, take 10-30 years to lead to new therapeutics (if we're lucky).
The one area where whole exome sequencing and related technologies are likely to change care in a meaningful way is pediatrics and fetal medicine where there are tons of rare, fatal things due to rare point mutations. In these cases, early molecular diagnosis would reduce the diagnostic odyssey and allow early discussion of the goals of care.
Tell that to Winston Churchill. I think genetics probably explains at least as much of the variance as lifestyle. That said, folks should have a look at the promises made by the first generation of companies that cashed in on the Human Genome Project and compare them to Venter's promises now.
On "INVISO-POWER"...
The actual benefits from pharmacogenetic testing for Warfarin metabolism are swamped by all the other factors which affect Warfarin metabolism (eg diet and other meds).
The FDA disagrees, and so does the evidence. And there are a whole lot of areas where pharmacogenetics is starting to have an impact on treatment. In any case, pharmacogenetics is a subset of pharmacogenomics; for example, as I mentioned in another comment, the lab where I work is working on expression-based tests for prediction of altitude sickness and setting up drug trials.
The correlation between ignorance of statistics and using "correlation is not causation" as an argument is close to 1.
Oh yeah, gabbo, gabbo, bitch!
Filter error: Don't use so many caps. It's like YELLING.
DF? I only used twice.
Having genomic information about a particular patient and condition is only small part of the story some needs to take that information and develop an effective therapy which is not trivial and requires years of research and development.
Tell that to Winston Churchill. I think genetics probably explains at least as much of the variance as lifestyle.
That's an interesting hypothesis. Do you have data to support your hypothesis, or just an anecdote of one guy who got lucky?
"First they came for the slanderers and i said nothing."
Yes, this is what classical Greek rhetoric describes as a regressive mirage: the more you learn, the worse it gets, no matter how diseases you cure along the way.
Here's the amazing thing. Understanding tends to outpace effective intervention. Any snooker player can tell you which ball on the table he'd really like to move next. It's rarely the ball he's presently shooting at. In Genomics, we're talking 30,000 balls on the snooker table, and the snooker table is gravity golf in a twenty dimensional space. Even with your trillion dollar Laplacian pool cue, you're struggling to pull off exactly the shot you want.
When I was young and we were on a long trip and the moon was hanging there on the horizon, I always wanted to go faster, so we could see the other side.
Then I got a little bit older. Perhaps a month older. And I thought to myself, "you know, there are reasons why this is probably not going to happen the way I want it to".
For example, Wafarin/Coumadin is likely unneeded with good diet: http://www.diseaseproof.com/ar...
The article cited dosing for Wafarin/Coumadin as a motivation for genetic research -- ironically ignoring it is not needed at all with better nutrition (in probably almost every case, so talk to an informed medical practicioner etc..). The link above is from something Dr. Joel Fuhrman wrote in 2004 (just to show how people searching for a magic bullet ignore the obvious). From there: ...
"Coumadin, Vitamin K, and a Plant-Based Diet
Eat more healthfully and stop taking Coumadin. The main problem with the studies that show that patients at risk of stroke benefit from anticoagulation with Coumadin is that they tested mostly high-risk patients on the typical disease-creating American diet, not low-risk patients on a vegetable-heavy, plant-based diet. As one's diet changes to include more vegetation and less and less animal products and refined foods, one's cholesterol drops, one's blood pressure typically decreases, and one's risk of a heart attack or embolic stroke plummets.
A high-nutrient, plant-based diet already has been demonstrated in medical studies to have a powerful effect at decreasing the risk of embolic stroke as well as heart attacks. In fact, in the Nurses Health Study a mere 5 servings per day of fruits and vegetables reduced risk of embolic stroke by 30 percent (and this is still a poor diet by my standards). 2 Another study looking at the consumption of greens, vegetables, and daily fruit consumption found a dramatic decrease in stroke incidence (approaching 50 percent) when they compared high and low fruit and vegetable consumption.3 My dietary recommendations, extremely low in salt and offering the equivalent of more than 10 servings per day of stroke-protecting produce, have been demonstrated to dramatically lower cholesterol and offer a much greater resistance to both strokes and heart attacks than Coumadin therapy. For people following my nutritional advice, the use of Coumadin becomes ill-advised. The use of this dietary intervention quickly drops people from a high-risk to a low-risk status. In most cases, Coumadin is no longer needed.
Most people on Coumadin would be much safer if they ate an ideal diet with lots of vitamin K containing greens; took an aspirin, EPA/DHA fatty acids, and LDL protect daily; and stopped taking the Coumadin. The risk of all causes of death would decrease precipitously. Eating right will not cause you to bleed to death. Instead, it can save your life.
Natural anticoagulants to consider instead of Coumadin are tomato juice, pomegranate juice, fish oil, vitamin E, horse chestnut seed extract, and ginkgo biloba.
Is Coumadin the Only Hope?
For those who absolutely must take Coumadin, because of a recent thrombotic event, the danger of not eating a healthful diet exceeds the risk of increasing the Coumadin dose slightly to accommodate the healthier diet. As long as the amount of greens you eat is consistent, your doctor can adjust your Coumadin dose to accommodate it.
For the patient who must stay on Coumadin, the diet must be consistent from day to day to avoid fluctuations in the effectiveness of the drug. To keep the vitamin K amount constant, it is sensible to eat one large raw salad a day and one serving of dark green vegetables such as asparagus and string beans, but leave out the dark green leafy vegetables, such as steamed kale, collards, and spinach. Adding some of those to a soup is okay, however. The goal is to keep your vitamin K level stable, so the amount of blood thinning does not swing into a danger zone. A dangerous level of blood thinning can occur if the dose of Coumadin is adjusted to a high vitamin K intake and then suddenly the patient does not eat many vitamin K-containing foods for a few days. In other wo
A 21st century issue: the irony of technologies of abundance in the hands of those still thinking in terms of scarcity.
as someone working on front line seeing patients as well as doing genetics, genomic medicine remain a niche field and will remain so. most patients cant even get the basics right and you are talking about tweaking drug dosing by a little based on a polymorphism.
even if the only explanation of the only case that we have is 'he got lucky' that is still a deviation from 'lifestyle explains all' approach.
Btw: it may just be that our lifestyle or parts of it are affected by genetics and/or stuff in the middle like all this bacteria that live with us (in our gut etc). Life is not that easy as some morons like to see it be.
There have been some successes along the way, like genetic tests for warfarin dosage, but for the most part our gains in understanding of basic biology haven't been matched by clinical advances.
If you're spending thousands of dollars for genetic testing for a $4 a month drug like warfarin, you're doing it way wrong. It's like the proverbial million dollar cure for the common cold. You could either use one of the newer warfarin alternatives with more consistent pharmacokinetic profiles at a higher price or use the old tried-and-true trial and error dosing.
Either way, you're still doing weekly to monthly lab testing for warfarin dosing. And your warfarin effectiveness (or bleeding risk) is still going to be thrown way off if you vary your diet significantly or start new medications.
A much better example of genomic medicine payoff would be targeting therapies to specific cancer types, like the EGFR receptor mutations in some varieties of lung cancer.
Light a fire for a man and he'll be warm for a day. Light a man on fire and he'll be warm for the rest of his life.
Don't let narcissists like Venter sell you on this crap.
There's a lot of work yet, always check out sensation medical news with the best source for medical information on the net: Science-based medicine: http://www.sciencebasedmedicine.org/
As we know, science has a lot more to do with the sociology of research than we like to think (say hello to Alan Sokal). Bioinformatics has fallen short of its lofty initial goals because it became a prime example of what nefarious effects the struggle for publication can cause, and also of the alienation of a whole field of scientists by another field of...scientists (?)
The failures of Bioinformatics have to do with it becoming a gold mine for publication-hungry CS PhDs who - if you're familiar with some of the field's exploding literature in the early 00s (or "noughties" for some) - knew really close to nothing about the biology of what they were researching, and produced pile after pile of useless algorithms and "data driven discoveries" far removed from biological or clinical phenomena. A lot of these PhDs seemed to assume the medical and biological professionals had little to contribute, since they were utterly incapable of doing Math. That is how you got things like a room full of Mathematicians and Physicists discussing how to model viral activity, without a single real Biologist specialist in the room (I am not making this up).
So, the field quickly became inundated with research whose only sole purpose was carving out a name in the publication game for Physics and Computer Science majors who had failed to land a position in their original field. Naturally, real doctors and biologists looked at the sometimes infantile-minded simplifications (of Immunology, Metabolism, brain electric activity, genomic modelling, etc.) and sometimes downright asinine assumptions and just walked away. The literature become a huge pile of impenetrable research, to the delight of the graph algorithm researcher (to name one of these sub-fields), but completely alienated from bench biology. Since the clinical phenomena became an excuse for abstraction while the field exploded with new journals, I guess the real doctors and biologists continued on with their research, largely unimpressed with Bioinformatics. They could play their publication game all they liked, while doctors and biologist would continue doing their Real World research. It's a tale from the history of science that needs to be written, because it amounts to almost a decade of high hopes and lost expectations.
And all I mentioned can probably be researched, too. If you look at the papers and their impact, what do you see? How much of that is relevant for research that came later? What's the quantity of dead-end "data driven research"? I'm not thinking about the seminal algorithms, of course, but the spike of...noise that came later...
And to say nothing of the lack of real paradigmatic change in the way the Computer Science was done, with systems full of state, and the lack of theory for real concurrent biological systems. Which is nothing but a reflection of the poor state of the field of Computer Science for such systems. Likewise, the field seemed to approach things with brute force: throw more computing power at it, and metabolic networks will be solved, protein-folding will be solved. Seems like all that C++ and clock cycles weren't really cost-effective...ya think?
Main difference between the BSD license and the GPL license: one is from California and the other is from Massachusetts
There will be some benefits in selection of oncology protocols in the short term, but knowing cancer genomics does not actually lead to new chemotherapeutic agents except in the long term
What about vaccines? Any informed physician that looks at the data can explain to you that bioinformatics has contributed close to nothing in terms of new vaccines. Why is that?
With regards to cancer genomics, there are a bunch of questions that arise from potential treatment that the pharmacogenomics peddlers never mention: how will you conduct trials? Will you promote small clinical trials, with chemo agents that represent small molecular variations? How will you manufacture such molecular variants? What would they cost? When you finally give them to humans, how will you monitor the clinical trials? Will you have a large enough sample (in the statistical sense)? What's the control? BTW, when I mentioned peddlers, I mention peddlers. I don't want to generalize.
The one area where whole exome sequencing and related technologies are likely to change care in a meaningful way is pediatrics and fetal medicine where there are tons of rare, fatal things due to rare point mutations.
I beg to disagree. When you have very rare diseases, you get extremely low frequencies. That means not one doctor will get to specialize or gain experience in such rare diseases. Every time the disease pops up, it will be a novelty for the doctor. What you need, what we need in Medicine is a way to keep extremely long term databases. In this way, data can be accumulated and sifted, and patterns that arise here and there throughout decades, that could be mined. The deployment of these databases would revolutionize the care of patients burdened with extremely rare diseases. It's of little use detecting the condition if you don't know how to care for the patient.
Have any of you read A Fire Upon the Deep, by Vernor Vinge?
http://en.wikipedia.org/wiki/A...
In this book, the idea of databases spanning centuries is part of a central plot in the story.
Main difference between the BSD license and the GPL license: one is from California and the other is from Massachusetts
After reading the article, I'm unconvinced.
At least until the role of the genetic material in human gut flora is a proportional part of the equation, it seems to me the "progress" is at least partially intentionally retarded by industry and the FDA "working together" to maintain a status quo that benefits obscene profits, and the concurrent snails pace of medical progress, over the patient.
From Wiki :
"The human body carries about 100 trillion microorganisms in its intestines, a number ten times greater than the total number of human cells in the body.
The metabolic activities performed by these bacteria resemble those of an organ, leading some to liken gut bacteria to a "forgotten" organ.
It is estimated that these gut flora have around a hundred times as many genes in aggregate as there are in the human genome."
Instead of talking about how close we are (and the implicit need for more money), just make some real advances available to the general public. Until then, you're just making false promises to justify your funding.
I hope people so helped will be labeled. I don't want to marry a GMO person.
Go to Heaven for the climate, Hell for the company -- Mark Twain
Actually, around 50/50 is as good a breakdown of the normal variance as any, given the standard error of our current measures. (And as with any such, that's dependent on the distribution of both in the population; obviously, looking at the breakdown of the variance in schizoid alcoholics would give you a different result).
For a given individual, of course, the ability of change mortality/morbidity is entirely due to environment/lifestyle.
Star Trek transporters are just 3d printers.
For a given individual, of course, the ability of change mortality/morbidity is entirely due to environment/lifestyle.
True point
"First they came for the slanderers and i said nothing."