731 replies to this topic

[sthira]

Any guess how much of a weight loss 10 day fast could involve ?
I practice Trf ( time restrictive eating) with occasional 1-2 days fasts and dont really have any spare weight at bmi just barely more then 18. Dont wanna look anorexic ))

I lose about a half kg per day, mostly water weight. My BMI hovers around 18.5 before a fast, so when I fast for longer time periods I get even thinner. This is a side effect to consider. Weight loss, lower blood sugar, lower blood pressure, higher blood ketones, reduced cholesterol are all either side effects or benefits depending on who's fasting. The water weight loss tends to come right back; fasting for obesity prevention usually fails long term.

What's counter-intuitive is lean muscle tends to increase, not decrease during a prolonged fast. The caveat is you rest, don't overuse resting muscles, do nothing too strenuous, and this would be an appeal of group retreat fasting: everyone else is lazy, too, all of us are fasting together and giving bodies deserved vacations from the crazyworld.

Bacteria basically eat, digest and excrete the food you eat, so yes; we all live on bacteria shit!
So its good idea to approve of the bacteria who's excrement you are living on and try to feed the good guys while starving and/or killing off the bad.

Improved gut health appears to be one of the benefits of a whole food plant based diet.

"The vegan gut profile appears to be unique in several characteristics, including a reduced abundance of pathobionts and a greater abundance of protective species. Reduced levels of inflammation may be the key feature linking the vegan gut microbiota with protective health effects. However, it is still unclear whether a therapeutic vegan diet can be prescribed to alter the gut microflora for long-term health benefits."

https://www.ncbi.nlm...les/PMC4245565/

For a happier microbiome you might want vegetable, fruit, legume, and seed variety. Prebiotics feed them critters, too: dandelion greens, Jerusalem artichokes, garlic, leeks, onions, chicory root, asparagus, jicama, wheat bran...

For expensive probiotics, the VSL#3 thing might be a go -- anyone here splurged?

[Longevitarian]

L&G

 

I received requests for information regarding the earlier interventions  tried

on HUMster. At this moment I have to postpone writing about them. The simple

reason is lack of time to go back with the analysis and the mess I am in due

to flood of information from the experiments, which yet have to be processed.

 

Initially I never expected to get access to so many , difficult to obtain interventions.

So when I was lucky, it was like ..."OK ...great , lets try it and see what happens" ....

trying to observe, analyse and memorise whatever happened.

No writings , no pictures from that early period ....but still I have quite many medical

test results ......and huge volume of memories,still waiting to be put on paper.

It quickly became obvious that I should have become more organized

and more scientific about it otherwise I may miss , or forget some

important observations and markers. It was more so when the opportunities

for interventions started to show up more often than I expected ....on the

average one every half a year.

 

At this stage I document everything in the form of medical tests, pictures,

meticulous daily entries into diary, random thoughts and science coming

from elsewhere. I am in constant hunt for new interventions , access to

medical tests and trying to  keep up with latest in research and many

more related activities.

 

Never expected that to become so time consuming and so elaborate.

Ms. HUMster is generally very supportive but occassionally in hissy fits

she complains "IT WILL NEVER END .....!!!!!!!!".....The question is "do

we want it to end at all.....and if so, under what circumstances?  

 

Basically at this stage I  accumulated huge amounts of data. Piles of papers

littering my home and computer records still  awaiting to be properly organized

and analysed which I hope to start begining of next year. This is when

more specific info about past interventions will become available to the

public, (and to me too. .)

 

However, I do intend to write to the forum more about my experiences

with D+Q+F.....in next  couple of days. The information will cover things

which I did not write about in my previous postings. So to get the whole

picture I suggest you go back and read them too.

 

I think the information will be of value for those who wil receive their

supply soon and who want to build their expertise on that subject 

and get better organized before they try it on their humsters.

 

Thank you for attention

 

 

[sthira]

Your senescent cell killing excursions and documentation aren't wasted here, Longevitarian, I hope I'm speaking for all when I say thank you for N1 reports.

[Logic]

Dasatinib Group Buy Progress Report:

 

The lab has let me know that they have completed the analysis.
The D is as advertised and they hope to get the report to me later today.
I will post a redacted version here and a Niner will look at the original report  and the COA from the supplier and post. (Hopefully:  He hasn't been here for over a week)

 

[slotrite]

Has anyone seen this? http://www.cell.com/...8674(17)30246-5

[Andey]

Has anyone seen this? http://www.cell.com/...8674(17)30246-5

 

 

"Quercetin and Dasatinib have been reported to be non-specific (Chang et al., 2016). We found no selectivity toward senescent IMR90 (Figure S3B), and therefore this cocktail was not explored further."

 

 

When any new supplement appears, I think you have to hurry up and use it while it still works. © maxwatt 

))

 

On a serious note, as I understand they tried it on fibroblast cells model. It was never claimed that D+Q should work on that type of cells.

What is alarming is the rate of control cells lost after treatment with D+Q. I am not sure with dosages they used.

Edited by Andey, 23 March 2017 - 06:48 PM.

[Nate-2004]

1. Logic will they ship out from the lab or ship back to you for you to ship to us?

2. Nevermind it looks like D+Q doesn't even work? *sigh*

 

Here's the study referenced.

[VP.]

New senolytic compound with no side effects?

http://www.sciencema...n=miceage-11924

 

Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging

 

FOXO4 D-Retro-Inverso peptide H-ltlrkepaseiaqsileaysqngwanrrsggkrppprrrqrrkkrg-OH

 

http://www.cell.com/...8674(17)30246-5

 

Edited by VP., 23 March 2017 - 08:55 PM.

[Nate-2004]

New senolytic compound with no side effects?

http://www.sciencema...n=miceage-11924

 

Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging

 

FOXO4 D-Retro-Inverso peptide H-ltlrkepaseiaqsileaysqngwanrrsggkrppprrrqrrkkrg-OH

 

http://www.cell.com/...8674(17)30246-5

 

"“I don’t think you should start treating frail people in their 90s.”

 

Why the fuck not? I understand caution but people in their 90's are in their 90's... They don't have much time left anyway and if they want to try they should be able to.

[TaiChiKid]

1. Logic will they ship out from the lab or ship back to you for you to ship to us?

2. Nevermind it looks like D+Q doesn't even work? *sigh*

 

Here's the study referenced.

 

While D&Q works as a senolytic, it just is not as highly specific in targeting senescent cells as FOXO4-DR1.  There is little chance in getting such a conjugated protein like FOXO4-DR1 though...

[Fafner55]

Dasatinib works, just not as effectively, or with the specificity, and probably doesn't target as many types of tissues as drugs yet to come. We have always known that it is a "generation 0" senolytic. It is encouraging that we have dasatinib now and tangible hopes for better drugs.

 

[Longevitarian]

 

1. Logic will they ship out from the lab or ship back to you for you to ship to us?

2. Nevermind it looks like D+Q doesn't even work? *sigh*

 

Here's the study referenced.

 

While D&Q works as a senolytic, it just is not as highly specific in targeting senescent cells as FOXO4-DR1.  There is little chance in getting such a conjugated protein like FOXO4-DR1 though...

 

Completely agree with TaiChiKid, they compare action of the three interventions on senescent  IMR90

myofibroblasts, which is already known to not to be senolysed by D+Q from earlier research. D+Q is

selectively targeting senescent  preadipocytes and endothelial senescent cells, but not senescent

IMR90 cells.

On top of this the concentration of D used to kill the senescent cells in this study is extremely high....

going into hundreds of mmols ....obviously such dosing is toxic to both, the healthy cells and

senescent cells

,.

The lesser toxicity to the senescent IMR90 cells is not supprising either since the D+Q does not

target survival machanisms of senescent IMR90 cells......

 

I think this study is important and of high value .... but highly misleading regarding

effectiveness of D+Q. It  tries to compare apples and oranges , figuratively speaking....

Expect strong critical response from the original authors of the D+Q papers.....

 

 

[DareDevil]

Has anyone seen this? http://www.cell.com/...8674(17)30246-5

 

Hi Slotrite,

 

 

That is most interesting, it seems that we're on the threshold of a new substance which proposes to boost our immune system as well as help engineer age reversal.

 

 

FOXO4-DRI Disrupts PML/DNA-SCARS and Releases Active p53 in Senescent Cells

http://www.cell.com/...8674(17)30246-5

 

"To facilitate cellular uptake of FOXO4-DRI, it was designed as a fusion with HIV-TAT, a basic and hydrophilic sequence that allows energy-independent cellular uptake of cargo through transient pore formation. Using an antibody against HIV-TAT, we observed FOXO4-DRI to be taken up as soon as 2–4 hr after administration and to remain detectable for at least 72 hr. Given that the affinity of antibodies is generally low, this indicates FOXO4-DRI effectively enters senescent cells at high intracellular concentrations, which remain abundant and stable over a prolonged period of time. Following its uptake, FOXO4-DRI reduced the number of senescence-induced FOXO4 foci, PML bodies, and 53BP1 DNA-SCARS while not affecting the number of small 53BP1 foci."

 

 

Regarding the use of an HIV TAT as a carrier, this is apparently tried and tested as safe. Using HIV-1 TAT would also provide the added benefit of vaccinating against AIDS:

 

 

ITALIAN NATIONAL AIDS CENTER COMPLETES PHASE II TRIAL OF VACCINE AGAINST HIV INFECTION BASED ON HIV-1 TAT PROTEIN

http://www.hiv1tat-v...cal_studies.htm

 

"When the studies were completed, the independent Committee for the evaluation of adverse events certified the safety of the vaccine in both HIV-negative and HIV-positive individuals. This certification confirmed that the primary and secondary end-points were fully achieved for both the preventive and therapeutic trials. All the reports were submitted to Regulatory Bodies."

 

 

I wonder how far beyond our in-house biochemistry resources it would be, to hire a lab to fuse FOXO4-DRI to HIV-1 TAT. I think that there are already several lab mice ready to test the result.

 

 

DareDevil 

[DareDevil]

On another note, I was quoted $995/gram for Navitoclax

Pricing on the basis of a group purchase of several grams.

 

Prohibitive at dosage requirements of 100mg/day.

 

DareDevil

[DareDevil]

Returning to the topic of Dasatinib.

Are the flu symptoms of D+Q in reaction to Lysis?

 

In reference to the better known Tumor Lysis Syndrome:

We might call this Senescence Lysis Syndrome - SLS

 

https://en.wikipedia..._lysis_syndrome

 

If this is the case, an adjunct might be necessary.

Something that clears out the toxicity of the lysis.

 

DD

[jmorris]

On another note, I was quoted $995/gram for Navitoclax

Pricing on the basis of a group purchase of several grams.

 

Prohibitive at dosage requirements of 100mg/day.

 

DareDevil

 

I'm not saying I want to, but I would pay $1/mg for Navitoclax.

 

$300 per treatment two or three times per year is a small price to pay compared to the alternative.

 

Let's hope that Logic finds a price better than this.

[DareDevil]

 

I was quoted $995/gram for Navitoclax

 

 

I'm not saying I want to, but I would pay $1/mg for Navitoclax.

 

$300 per treatment two or three times per year is a small price to pay compared to the alternative.

 

Hi jmorris,

 

If one only needed to take 3 days of treatment that would maybe make sense. However, I took 10 days of Dasatinib at 100mg/day purchased from TLR and, for a third of the price of Navitoclax, I still have remaining most of that purchase available for future treatments. And this price (which included 10 grams Quercetin per gram of Dasatinib) doesn't come close to Logic's greadt Group Buy price where I bought 30 grams of Dasatinib for one third the price of 1 gram of Navitoclax - that's 1% of the price!

 

At similar dosages Navitoclax at this moment of our present purchasing options costs 100 times more than Dasatinib. Hopefully this will change soon. I don't know the chemistry involved. But it seems unlikely that the loss of expensive primary chemicals in the synthesis process could explain such a large price discrepancy. It may be that the more cost-effective labs may not have geared up to produce it? Let's hope Logic can find a supplier at a much lower cost.

 

Edited by DareDevil, 24 March 2017 - 11:20 AM.

[Logic]

1. Logic will they ship out from the lab or ship back to you for you to ship to us?

2. Nevermind it looks like D+Q doesn't even work? *sigh*

 

Here's the study referenced.

 

1: The D will ship from the lab in the USA.

 

2:

Nate you are looking at the results from a lab that is hoping to commercialise a competing substance...!
They tested, in-vitro, on one particular cell type and were careful to choose a type not affected by D+Q and used a huge dose.  A dose big enough to also kill off non senescent cells...
if anything this study teaches the, as always, important lesson: The Devil's in the dosage!

This kind of thing goes on all the time and there is a study proving that as much as 50% (IIRC) of studies are wrong.

https://www.ncbi.nlm...les/PMC1182327/

 

BHT causes cancer is my pet example:  Yes, at 30 grams per day, for life, and/or with a nice dose of carcinogens to get things started. (I dont recall the details offhand)
Then there is the case of Big Pharma going ballistic every time chelation therapy shows positive results.  To me thats a big red flag saying "Look here! Look here!" and sure enough heavy metals catalyse (Look catalyse up and think about that!) AGE formation and cause senescence in cells.

This is a big part of the reason you joined this forum right?  To be able to sort the wheat from the chaff with the help of other members..?  

Edit:
I see TaiChiKid has already answered this.
I can tell that he has done more study than most in biology and longevity and takes note of things like in-vitro or in-vivo, dosage etc...

Edited by Logic, 24 March 2017 - 01:09 PM.

[DareDevil]

I'm about to take another dose of D+Q and hope to reduce the flu-like symptoms.

I think they are caused by the toxins released when senescent cells are killed off.

Last week the fever from a single dose kept me in bed and I missed a day's work.

 

This is however different from Tumor Lysis which involves hematologic cancers.

I think it is closer to a drug induced minor form of blood poisoning aka SEPSIS.

Obviously this isn't life threatening or requiring hospitalization like Sepsis does.

 

QUOTE:

 

"Some medical researchers consider sepsis to have three stages. The first stage is the least severe and usually has symptoms of fever and an increased heart rate. The second stage is more severe and is characterized by symptoms of difficulty breathing and possible organ malfunctions, while the third is the most severe stage (septic shock or severe sepsis) with life-threatening low blood pressure. Not all researchers agree with these stages; some researchers choose not to consider sepsis in stages."

 

http://www.medicinen...epsis/page3.htm

 

 

Possibly bacteria isn't all that is released, maybe also heavy metals, etc.

What can we take to clean out our organism during the intake of senolytics?

 

 

There is no need for antibiotics because a few days' fever will usually fix it.

However it would be nice if our body was supported/assisted in the clean-up.

 

For starters this D+Q intake I will take Curcumin (Tumeric) supplementation.

I am using Full Spectrum Curcumin sourced from NOVASOL.

This type of Curcumin claims 185 times higher Bioavailability.

40mg dose x 185 = 7400mg or 7.4 grams of standard powder.

This is approximately the maximum dosage for cancer treatment:

 

QUOTE:

"Curcumin in large dosage is known to cause issues if taken for a very long time. Studies done have found curcumin dosage of even 12 gms day to be safe till 3 months. Thus it is unlikely to cause any serious issues."

 

Week 1: Start with small dosage of 1 gm curcumin per day. If you see no side effects, take it for a week and proceed to dosage of

Week 2: Increase the dosage of curcumin to 2 gm/ day. Again check for any issues side effects etc. If everything looks fine, take it.

Week 3: Double the dosage again to 4 gm / day. Again if things look fine, continue for a week and go for final step.

 

 

 

Week 4-8: Double again to 8 gm / day. Continue this for 5 weeks

 

http://www.turmericf...scientific-plan

 

 

So I'm taking a single 40mg dose of NOVASOL Curcumin today.

If you have other ideas, thanks for your suggestions!

 

DareDevil

Edited by DareDevil, 26 March 2017 - 10:23 AM.

[Rocket]

I'm about to take another dose of D+Q and hope to reduce the flu-like symptoms.
I think they are caused by the toxins released when senescent cells are killed off.
Last week the fever from a single dose kept me in bed and I missed a day's work.

This is however different from Tumor Lysis which involves hematologic cancers.
I think it is closer to a drug induced minor form of blood poisoning aka SEPSIS.
Obviously this isn't life threatening or requiring hospitalization like Sepsis does.

QUOTE:

"Some medical researchers consider sepsis to have three stages. The first stage is the least severe and usually has symptoms of fever and an increased heart rate. The second stage is more severe and is characterized by symptoms of difficulty breathing and possible organ malfunctions, while the third is the most severe stage (septic shock or severe sepsis) with life-threatening low blood pressure. Not all researchers agree with these stages; some researchers choose not to consider sepsis in stages."

http://www.medicinen...epsis/page3.htm


Possibly bacteria isn't all that is released, maybe also heavy metals, etc.
What can we take to clean out our organism during the intake of senolytics?


There is no need for antibiotics because a few days' fever will usually fix it.
However it would be nice if our body was supported/assisted in the clean-up.

For starters this D+Q intake I will take Curcumin (Tumeric) supplementation.
I am using Full Spectrum Curcumin sourced from NOVASOL.
This type of Curcumin claims 185 times higher Bioavailability.
40mg dose x 185 = 7400mg or 7.4 grams of standard powder.
This is approximately the maximum dosage for cancer treatment:

QUOTE:
"Curcumin in large dosage is known to cause issues if taken for a very long time. Studies done have found curcumin dosage of even 12 gms day to be safe till 3 months. Thus it is unlikely to cause any serious issues."

Week 1: Start with small dosage of 1 gm curcumin per day. If you see no side effects, take it for a week and proceed to dosage of
Week 2: Increase the dosage of curcumin to 2 gm/ day. Again check for any issues side effects etc. If everything looks fine, take it.
Week 3: Double the dosage again to 4 gm / day. Again if things look fine, continue for a week and go for final step.



Week 4-8: Double again to 8 gm / day. Continue this for 5 weeks

http://www.turmericf...scientific-plan


So I'm taking a single 40mg dose of NOVASOL Curcumin today.
If you have other ideas, thanks for your suggestions!

DareDevil

Is there a consensus about the fever and flu symptoms? And how much did you dose that you got a fever? It took 2 consecutive 300mg doses to affect my lab rat.

[aribadabar]

...

Possibly bacteria isn't all that is released, maybe also heavy metals, etc.

What can we take to clean out our organism during the intake of senolytics?

......

 

If you have other ideas, thanks for your suggestions!

 

DareDevil

 

If you suspect bacteria - coconut oil/ honey/olive leaf extract act as mild anti-bacterials and are side effect-free.

For heavy metals - modified citrus pectin (MCP), bentonite clay, cilantro, EDTA are good chelators with no sides.

[TaiChiKid]

 

...

Possibly bacteria isn't all that is released, maybe also heavy metals, etc.

What can we take to clean out our organism during the intake of senolytics?

......

 

If you have other ideas, thanks for your suggestions!

 

DareDevil

 

If you suspect bacteria - coconut oil/ honey/olive leaf extract act as mild anti-bacterials and are side effect-free.

For heavy metals - modified citrus pectin (MCP), bentonite clay, cilantro, EDTA are good chelators with no sides.

 

 

Daredevil,

 

You can take all the 'clear out your system' supplements, such as EDTA for two days -before- you treat your pet rat with DQF.  The other toxins and heavy metals accumulate slowly.  For example you need only take EDTA for a couple of days every few years to clear out metals such as mercury leaching from old fillings and the like.

 

By doing this, you will not confuse the effect you get or compound the symptoms from taking DQF with other supplements.

 

[DareDevil]

Thanks for the great suggestions. What about this thread which suggests another Chelator?

 

http://www.longecity...ator-group-buy/

[Logic]

Thanks for the great suggestions. What about this thread which suggests another Chelator?

 

http://www.longecity...lator-group-buy

 

Yes Tiron is very promising as an intracellular and even intra-mitochondrial chelator, but it is very new and there is little research to suggest an optimal dosage or schedule.
Also what happens to the iron etc it chelates once that Iron is extracellular??
ie:  You most likely need an extracellular chelator to 'pick up the ball' when Tiron drops it or you just redistribute heavy/metals and do more harm than good.

https://www.google.c...tra "in vivo"&*

 

Also; the half life of a chelator is very important!
You dont want it pooping out and dropping the ball before those metals are in the toilet where they cant do more damage!

 

Big Pharma gets VERY antsy and even downright threatening when studies show good results from chelation and/or AGE breaking:
I see this as a huge blinking neon sign saying "Look here! LOOK HERE!!!"

http://www.longecity...rapy-with-edta/

http://www.longecity...-via-chelation/

http://www.longecity...aminoguanidine/

 

On top of that, there is evidence that heavy metals cause senescense:

http://toxsci.oxford...t/99/1/126.full

https://www.ncbi.nlm...pubmed/20618956

https://www.ncbi.nlm...pubmed/23828460

https://www.ncbi.nlm...pubmed/25157103

What I am trying to say, before I get carried away, is that working out an effective chelation and anti AGE stack/therapy and doing group buys of the necessary is high on my anti aging list!
Higher even than senolytics due to the new evidence above.
In fact I would say that it should be at the very top of everyone's list! 
New thread coming..!

 

In the meantime:

As its a good idea to stop these metals from getting into circulation and also messing up the gut lining in the 1st place, I have been eating a tablespoon full of Black Sesame Seed with meals:

http://www.longecity...ndpost&p=766829

[Logic]

Dasatinib Group Buy Progress report:
 

I have received the Lab Report:
https://drive.google...iew?usp=sharing

 

The lab:  "...Most has been packed and ready to ship. Will follow with tracking..."

[DareDevil]

Hi Logic,

 

Thanks for returning and giving us more inspiring insight !

 

Chelators probably should rank above Senescent Cell Genocide on our checklist. 

 

This opinion is after doing my own Cellular Warfare with Dasatinib and Quercetin.

 

We must first master the containment and evacuation of toxins before releasing them.

 

Here is an article that specifically mentions what is released when senescent cells die:

 

Senescence-messaging secretome: SMS-ing cellular stress

http://www.nature.co...bs/nrc2560.html

 

Is SMS only present before senescent cells die?

Unfortunately, I can't access the entire article.

Ideas on what we must clean out are welcome.

 

Cheers,

 

DareDevil

Edited by DareDevil, 28 March 2017 - 07:25 PM.

[Nate-2004]

I don't know how the topic changed to chelation, I guess it was when Logic mentioned it as an example of something Pharma goes nuts about when it works. Imagine how differently they might behave if we ended the patent system and they didn't have the government protecting them from competition on every product they try to produce. We might actually have effective drugs on the market.

 

I'm so glad the Dasatanib is shipping now. Here's to the first clearance attempt.

 

Is there a known average number of senescent cells that build up in humans by specific ages? 

 

I just received my 23 and Me report yesterday and downloaded the raw data. Turns out my FOXO3 genes, the two major ones at least, have the ideal alleles. Meaning there's a good chance I'll live beyond 100 as it is. I know FOXO3 is relevant to senescence and preventing senescence. So knowing that I wonder if there's going to be all that much to clear for me at 42 yrs.

[DareDevil]

No idea about numbers but if what I've seen outwardly of changes in people's general physical condition and appearance at your age, you may have only a quarter of the senescent cells of someone in their seventies? Just a wild guess of course. However, this still means there are senescent cells to clear. Also, what do we call senescent? It's like calling someone old. A teenager will call a thirty year-old old. A thirty year-old will call someone in their fifties old. A fifty year-old will call someone in their seventies old, etc. What is our frame of reference for senescent cells? I wager that we can start to call them senescent as soon as they start to act erratically and mess with our biological processes. I would rather call them deficient than old. After all, if we can extend our telomere length and improve our cellular function, then we may onde day have healthy old cells? FWIW.

[Longevitarian]

Just to add my $0.02 to the topic on chelators.

 

The overmineralisation of the tissue is indeed one of the major drivers of age related

pathologies. The iron and other metals are highly sought after by most of the organisms,

but there is no established mechanism of getting rid of excess of them (with exception

of menstruation in premenopausal women and shedding of epithelial tissue).This

causes pleiotropic effect of overaccumulation of minerals in tissues leading to multiple

pathologies. This include accumulation of toxic metals which play no role in normally

functioning organism.

There is one problem with use of chelators : unless the chelation will be

followed by the blood loss the excess of minerals will be eventually

reabsorbed by the tissues.So, visit nearest blood bank for blood donation

after dosing your humster with Tirone otherwise it will be waste of your

hard earned money....it will not work.

[Nate-2004]

OOor just take carnosine regularly. Like I have been for the last year or more. I bought a year's supply from BulkSupplements. You can also, simultaneously, use Rosmarinic Acid with Piperine, which I just combine with my curcumin's piperine instead. There's not enough research about either though, needs a lot more but there's no money in it for Pharma because patent system.