

Can Open Source R&D reinvigorate Drug Research? - EGreg
http://www.nature.com/nrd/journal/v5/n9/full/nrd2131.html

======
EGreg
Open source software grew out of the Free Software movement, which was modeled
on the activities of scientists. Papers would be published in journals for
everyone to read. It was free to teach a scientific theory to your students.
Researchers built on each others' work.

Drug research is scientific research. The distribution of drugs is actually
pretty cheap -- once you know the formula, you can usually make the drug
rather inexpensively. It's the R&D that needs funding, and it's currently
funded by proprietary drug companies much like Microsoft, Adobe etc. built
THEIR software. But years later, IE still sucks and open source browsers have
helped the world a lot. Our mobile phones all run WebKit. We are lucky that
Netscape open sourced their codebase and formed Mozilla, which at the time was
an precedented move. These days, Apple, Google and Facebook work with the open
source community, whereas Microsoft is becoming more and more irrelevant. If
they joined with the open source communities instead of hiding their code they
would probably bounce back -- for example if they threw out their old
rendering engine and based IE10 on WebKit.

Certainly patents and software help the old business models that rely on them
(drug companies, newspapers, proprietary software companies). I think in
software we have shown that over time, free information and community
collaboration can produce better, more stable, more standards-compliant
products. The question is, can we do this in other areas?

I would argue that we have to separate the distribution network (Apple
distributing apps, etc.) and the R&D. The distribution networks have to
compete on price, efficiency, ease of access, etc. But the R&D is not
necessarily done by drug companies. What happened to all that money we raise
in "find the cure" walkathons? Where does it go? A lot of the drug research is
done in universities, where papers are published openly and freely. I expect
the drug companies to fight open source research just like Microsoft fought
open source. But at the end of the day, there has to be a good system in place
to fund R&D as a community that SHARES knowledge with the world.

Don't get me wrong, clinical trials cost money, and dealing with the FDA costs
money. But as far as innovation, there would be MORE innovation if people
freely published the knowledge and built upon what others have done. You made
a drug based on this gene sequence? I can make one that helps these gene
sequences. That's the future, imho.

The surprising truth about what motivates us:
<http://www.youtube.com/watch?v=u6XAPnuFjJc>

Smart people aren't just motivated by greed. Lots and lots of professors in
university are motivated simply by making a difference in their field, and in
their world. They want to make a breakthrough because they love their work.
Sometimes they donate everything they get back to the university. Similarly,
the kids who grew up with computers formed a hacker culture that loves to show
off what they did to others. I think the first steps should be to foster that
sort of "open source culture" among kids learning science in high school and
college, and to provide the infrastructure for better online journals. When
they finish grad school, they will often publish their research for free as a
matter of helping the world. The drug companies won't be able to charge a huge
markup on the drugs. The drugs would be manufactured at cost by the
distribution networks (which are regulated by the government, of course, so no
one slips a mickey in the drugs).

A great example of an open source drug is this "cure for cancer" discovered in
Canada:

<http://www.youtube.com/watch?v=7LXH-TJYS5w>

it may very well cure cancer in lots of different people. DCA has already been
produced for over 100 years and no one can patent it. Which is great for the
public at large. Imagine people taking DCA after the FDA has certified it, and
it being produced cheaply. Basically, I think that we are just starting to see
the ways in which a patent-less and copyright-less world can actually produce
more innovation and useful solutions for people, than one where information is
locked up in corporate silos and controlled by special interests.

~~~
logjam
Well said.

It is a colossal myth that pharma companies have to charge a lot for patented
medications because of development costs (this is the story pushed, of course,
by Big Pharma themselves). However, they spend most of their money on
advertising:

[http://www.sciencedaily.com/releases/2008/01/080105140107.ht...](http://www.sciencedaily.com/releases/2008/01/080105140107.htm)

Instead of innovation, a certain amount of pharma research is devoted near the
end of a drug's patent lifetime to merely tweaking that established, well-
studied drug a bit to produce a slightly different form. Product extensions
with these slight modiﬁcations, generally of dubious benefit, can get at least
3 years of market exclusivity if their developments involve clinical research.
Thus, what we get are slow rollouts of extended release, timed release,
buffered, etc., etc., formulations of some old drug. Here's a good paper on
some of the other strategies used by pharma to extend patent protection:

[http://nofta-
ip.jinbo.net/files/Patent%20term%20extension%20...](http://nofta-
ip.jinbo.net/files/Patent%20term%20extension%20strategies%20in%20the%20pharmaceutical%20industry.pdf)

"Second, the pharmaceutical industry is not especially innovative. As hard as
it is to believe, only a handful of truly important drugs have been brought to
market in recent years, and they were mostly based on taxpayer-funded research
at academic institutions, small biotechnology companies, or the National
Institutes of Health (NIH). The great majority of “new” drugs are not new at
all but merely variations of older drugs already on the market. These are
called “me-too” drugs. The idea is to grab a share of an established,
lucrative market by producing something very similar to a top-selling drug.
For instance, we now have six statins (Mevacor, Lipitor, Zocor, Pravachol,
Lescol, and the newest, Crestor) on the market to lower cholesterol, all
variants of the first. As Dr. Sharon Levine, associate executive director of
the Kaiser Permanente Medical Group, put it,

If I’m a manufacturer and I can change one molecule and get another twenty
years of patent rights, and convince physicians to prescribe and consumers to
demand the next form of Prilosec, or weekly Prozac instead of daily Prozac,
just as my patent expires, then why would I be spending money on a lot less
certain endeavor, which is looking for brand-new drugs?"

[http://www.nybooks.com/articles/archives/2004/jul/15/the-
tru...](http://www.nybooks.com/articles/archives/2004/jul/15/the-truth-about-
the-drug-companies/)

A formed editor of the New England Journal of Medicine noted, "The combined
profits for the ten drug companies in the Fortune 500 ($35.9 billion) were
more than the profits for all the other 490 businesses put together ($33.7
billion) [in 2002]. Over the past two decades the pharmaceutical industry has
moved very far from its original high purpose of discovering and producing
useful new drugs. Now primarily a marketing machine to sell drugs of dubious
benefit, this industry uses its wealth and power to co-opt every institution
that might stand in its way, including the US Congress, the FDA, academic
medical centers, and the medical profession itself."

<http://www.wanttoknow.info/healthcoverup>

~~~
EGreg
Thanks for bringing up those points. I can really only speak from my position
in the software industry and say that every time I see a patent suit in the
news, it seems to be harming innovation. Like I said, the big companies spend
a lot of money on squashing the competition, which already includes branding,
advertising, and so forth. Patents are a great weapon that may be marketed as
helping the little guy, the startup, protect themselves. But in reality, this
is the more likely scenario: startup gets a few patents. Big company sues them
for something, and startup runs risk of going bankrupt. Big company had more
patents, and more money.

When it comes to big companies, they use the patents as weapons against
competition and innovation (and why not, that is their fundamental purpose: to
enforce a monopoly). Google doesn't want to pay royalties to Apple for the
H.265 format or whatever. (That's one example that comes to mind.) If we
ignore startups for a moment, the big companies could compete directly instead
of invoking government-enforced monopoly rights. You could see how competition
on actual BENEFIT to the public would be improved if patents were out of the
picture. There would still be advertising budgets.

I have a question: We've had patents and big pharma for a long time now,
right? Why does all the mainstream medicine in this country have only one
answer for almost all diseases: PHARMA DRUGS? And how much better did they get
at curing cancer? More people get cancer today than 100 years ago, but how
much better did they get at improving people's quality of life with various
types of cancers?

Meanwhile, do you hear a lot about treatments to ANY major disease that are
not monetizable as drugs? Most doctors talking about this are marginalized by
the medical community. Can it really be that there are no other types of
treatments out there besides pills? And that there aren't any cures to be
found? The FDA requires clinical studies to be done before a drug can claim to
diagnose, prevent or treat any disease, understandably. But look at us as a
society. We need a better way of organizing and verifying medical information
about various drugs, research, conditions, etc.

It seems to me that the information the public is exposed to is dominated by
the pharma companies. They advertise to the public ("ask your doctor about
XYZ" -- really, I gotta tell my DOCTOR about it?). They push their products
which have been certified by the FDA ... and sometimes, they're wrong and
their drugs harm people. Meanwhile, most of the innovation comes from the
independents, the university labs. If they published information freely we
would all benefit. I'm not sure what could be done to reform the FDA system,
though.

~~~
dalke
"Mainstream medicine" doesn't have "only one answer for almost all diseases."
Think of the almost stereotypical statement from a doctor: "Stop smoking, eat
less, and exercise more." There's research in burn therapy and speech therapy
and many other fields which has nothing to do with drugs. The push for
mosquito netting is a prevention remedy for malaria. Go back in history and
you'll find that garbage collection in large cities was often run by the
public health department. Even the law that "all employees must wash hands
before going back to work" is there for a medical reason.

Here's what the WHO says about cancer:
<http://www.who.int/mediacentre/news/releases/2003/pr27/en/> . 1/3rd of the
cases can be prevented by "Reduction of tobacco consumption", "A healthy
lifestyle and diet", and "Early detection through screening". The first two of
those have nothing to do with drugs.

Also: "The predicted sharp increase in new cases – from 10 million new cases
globally in 2000, to 15 million in 2020 - will mainly be due to steadily
ageing populations in both developed and developing countries and also to
current trends in smoking prevalence and the growing adoption of unhealthy
lifestyles." Feel free to download the full report.

As for "treatments to ANY major disease that are not monetizable as drugs";
vaccines are not drugs. Getting the shot for tetanus is much less profitable
to a pharmaceutical company than going through treatment, but no one seriously
argues for removing the vaccine so pharmas can make more profit.

Economically, if there is a major disease then people will pay to not have the
disease. Therefore there's always going to be an issue of money involved, even
if it's promoting a diet or exercise program. The flip side of your question
is, do any major diseases have a remedy which can be done without
monetization? Most of the historically big ones are _solved_ (eg, by washing
hands before assisting in a birth, or making sure children get vitamin D).
Plus, the non "mainstream" medicines are also influenced by the money; look
how big the homeopatic industry is.

"There are no other types of treatments out there besides pills?" I just
listed a half-dozen.

"And that there aren't any cures to be found?" Pardon? Up until the 1980s the
treatment for gastric ulcers was "rest, bland foods, and drink milk." Now we
know most ulcers are caused by Helicobacter pylori and it's completely curable
with drugs. How is this not a cure? Or what is it you want?

As for "a better way of organizing and verifying medical information about
various drugs, research, conditions, etc." -- what is it you want? Go to
<http://cdc.gov/> . They've spent a lot of time compiling overview
information. Want more information? Medical researchers have spent a lot of
time providing exactly what you've asked for. What is it you want?

If anything, it's the paradox of choice. There's so much information that most
people ignore what's available, because they would rather not have to wade
through everything. Which is why drug ads, and dieting ads, and fitness ads,
and so on work. Sad to say.

The statement that "most of the innovation comes from the independents" is
just wrong. Read <http://www.nature.com/nrd/journal/v9/n11/abs/nrd3251.html> .
During 1998-2007, 252 new drugs were approved by the FDA. 58% had their origin
in pharmaceutical companies, 18% in biotech, and 24% from universities.

Besides, most of the university research _is_ published freely, although it
can cost money to access the journals (or a visit to a research library). And
just because a novel compound shows effectiveness in a research environment
doesn't mean it will become a good drug, and there's a lot of research which
needs to be done to get from "I have an idea which works in a test tube" to
"here's a new treatment for a disease", and most of the intermediate steps are
"doesn't work, try again."

~~~
EGreg
Thanks. I mostly posted my last message as a way to get informative responses,
which I think this is :) I sometimes like to learn more about a subject matter
I'm interested in, while discussing it, so it was late at night and I decided
that was a good way to learn a little more -- by overstating my case in my
ignorance and getting different viewpoints.

Although I do want to ask one thing ... to answer whether there are treatments
to ANYmajor disease that are not monetizable as drugs, you said that besides
drugs, there are also vaccines. But aren't vaccines developed the same way --
basically patented by pharma companies? Also, is there a list somewhere of
cures developed in the last 30 years? I just have this impression that the
pharma company is a big "sponsor" of medicine and that alternative treatments
or cures don't really take hold in the mainstream medical community (i.e. when
you go to a doctor) ... and that there is very little "official" information
about them. So it's hard to figure out what works and what doesn't when you
have a disease that may be cured using alternative methods, like some forms of
cancer etc.

~~~
dalke
So you want me (or others) to hand walk you through the field of medical
research, instead of doing 10 minutes of Google research?

Did you go to the FDA or NIH home pages to research your questions? FDA lists
a number of other non-drug remedies on their home page including medical
devices, radiation devices, xenotransplantation, and blood substitutes.

"Cures developed in the last 30 years" is highly judgmental. Does LASIK
surgery to correct nearsightedness count as a cure? Is being overweight a
disease? And gastric bypass one possible cure? What about hepatitis C
treatment which has a 90% likelihood of clearing the body of the disease, vs.
40% without the treatment? Do you count melanoma cures, by detecting the
disease early and removing affected tissue? Diabetes used to be deadly. Now is
isn't cured but it is easily treatable. Does that count? Cochlear implants so
that once deaf people can now hear? Artificial corneas so the blind can see
again? HIV treatments so that what was once a guaranteed death sentence within
5 years is now a manageable disease?

Did you at all try searching for the answers to your question? Just about
everything I listed here should be common knowledge.

Yet when I look for pages that talk about useful treatments and remedies, they
are overwhelmed by people like you who disbelieve all the successes, and are
_SURE_ that the pharmaceutical industry is hiding the real cures. Since you
know, employees at pharmaceutical companies and their friends and family never
get those major disease.

The reason there is little "official" information about alternative treatments
is that they've been tested over and over again, and not proven effective, and
in cases harmful.

Bear in mind that there's a big and mostly unregulated industry behind
alternative medicines, so there's also strong political pressure to keep those
so-called treatments available. The homeopathic industry in the US has
revenues of around US$1 billion. The chiropractic industry makes about $18
billion in revenue, with $430 million by sales of "supplements." Traditional
Chinese Medicine is about $5 billion and acupuncture about the same. This is
at least $10 billion of industry - surely they can provide rigorous tests.
Just how much of the alternative market is spent on research? Not much that I
can tell.

That gives a strong incentive to either castigate "mainstream" medicine or to
promote itself as "complementary", and little incentive to verify claims.
Since you overstate your case, I'll overstate mine - you are being brainwashed
by snakeoil charlatans.

There is no evidence other than anecdotal stories that alternative medicines
cure any sort of cancer.

~~~
EGreg
Makes sense. The situation is definitely more complex than I have thought
about.

When I said "non drug treatments" or "cures", what I meant was... are there
many examples where a disease was investigated and either

1) a treatment was found which was available using a non patented substance,
such as DCA (which was available for a hundred years), basically research
published by a pharma company that found you can treat a disease in a way that
doesn't make money for pharma companies via patents, or

2) a cure that basically eliminated the disease in most cases so no further
treatments were necessary.

I am not asking this with an agenda, I am just genuinely curious. I want to
find such a list.

It would also help me understand better whether the current system is capable
of producing and popularizing treatments (and cures) which may not be helping
the pharma company's bottom line. I don't want to parrot quacks who talk about
pharma "suppressing" this knowledge, just wondering how often knowledge like
this is willingly published, and where.

The reason it seems plausible to me that this issue might be a problem, is the
economics and incentives of it. If you were a pharma company and you sunk
$100M in research for a cure of disease X, and somehow you found two things
(in your own labs, say), that

a) there is a treatment that you can patent and charge a markup to recoup your
investment and make a profit, and

b) there is an equal or superior treatment which cannot be patented because it
was freely available or there is prior art

I don't see your promoting or even publishing (b) as being fiscally
responsible to your shareholders and your company's bottom line. So it seems
to me there would be a conflict of interest if a non patented treatment is
found. A similar case can be made for a cure. Why push the cure if pushing the
treatment generates a much bigger long term return on investment? It just
seems to me that there is some conflict between the interest of the
shareholders and actually publicizing a cure. Of course, there is some value
in the PR that your pharma company found the cure, but if it's estimated to be
less than the profit from the ongoing treatment, what is the incentive? What
is the company going to do?

~~~
dalke
You dismissed vaccines earlier, since can be covered under patent. But Salk
refused to patent the polio vaccine. In the mid-20th century, polio was
killing more American children than any other communicable disease. Now it's
nearly eradicated.

Just read <http://en.wikipedia.org/wiki/Jonas_Salk> . It brought tears to my
eyes. "By the time Thomas Francis stepped down from the podium, church bells
were ringing across the country, factories were observing moments of silence,
synagogues and churches were holding prayer meetings, and parents and teachers
were weeping." "It was as if a war had ended."

I'm sure companies could have made more profit selling tens of thousands of
iron lungs a year. I refuse to believe that sort of profit was a serious
consideration.

Something more prosaic - cavities are greatly reduced with fluoride treatment.
Fluoridated water and/or toothpastes have greatly reduced dental bills.

And I can't stress this enough: research consistently shows that exercise is
healthy, eating fruits and vegetables is healthy, and that cigarettes are not
healthy. There's almost no cost to these and there's no patent coverage at
all.

If you want something more disease like, then again I point to stomach ulcers.
Most are caused by H. pylori infection, and the first treatment was a standard
antibiotic, which was off-patent by the time the bacteria link was discovered.

Or cholera. The best treatment for that is oral rehydration therapy, which in
general "saves millions of children a year from death due to diarrhea - the
second leading cause of death in children under five." In the home-made
version, "1 liter of boiled water, 1 teaspoon of salt, 8 teaspoons of sugar,
and added mashed banana for potassium and to improve taste." People get better
faster with antibiotics, but they will recover so long as they are
sufficiently hydrated. Simple, but people in the 1800s didn't know this and
sometimes it killed up to 2/3rds of the people on the wagon trails out to the
US West.

This simple treatment didn't receive world-wide recognition until the 1970s,
based on fundamental research done in the 1960s. (There were people who
prescribed this sort of treatment earlier, but without enough studies to be
persuasive, nor with physical explanations of why it should be effective.) But
with it the mortality rate is under 1%, instead of 50%.

The best cure, btw, is prevention via improved water treatment. That has
nothing to do with pharmaceutical companies.

Your view of the patent system, pharmaceutical development, and the people who
work in them is woefully simplistic. If I worked for a company and found that
the cure for malaria/cancer/whatever was to eat an orange every day then
there's a huge personal incentive for me to publish. For one, that would
likely lead to a Nobel Prize. Remember also that most of the people doing drug
research got into the field because they want to cure or at least treat
disease. They think that drugs or vaccines are the most likely solution, but
that's a means, not an end. Do you really think that if a researcher found a
non-drug solution that they would be able to stay quiet?

Or like I said earlier - drug discovery researchers and their friends and
family come down with the same diseases as others in their community. Why
would someone want to "suppress" information which would lead to their parents
being treated for Alzheimer's, even if it isn't a drug treatment. Or do you
really think people working for pharmaceutical companies are so amoral and
concerned with the bottom line?

For that matter, look at organizations like the Novartis Institute for
Tropical Diseases. It's co-sponsored by the drug company Novartis, which has
said it "will seek to make treatments developed by the NITD available without
profit to the poor in developing nations in which these diseases are endemic."

I am not saying the drug companies are pure of heart. There's strong economic
incentives to find medicines which can treat heart disease, for example, in
part because people don't exercise, don't eat the right foods, and continue to
smoke. Given two diseases they are more likely to go after the first world
disease, where there's more money to be made, than a third world disease,
where there isn't. But the people who make up the drug companies are human,
and want to help other people.

Your argument about fiscal responsibility is a nearly worthless concept.
Consider that I am a CEO of a large company and I've said that we would
contribute $10 million to charity during the year. A shareholder might sue me
for irresponsibility. But that might be what's needed to keep me as head of
the company. Or it might be justified as improving morale, since its employees
feel better about how their work helps others. Or it might be good advertising
and improve the company's market image. Your statement assumes that immediate
short-term money is and should be the only concern in a company and that's
simply not the case, else no US company would ever donate money to charity.

Or as another example, do you think it's fiscally responsible for Oracle to
contribute money to Oracle Racing, which funds Larry Ellison's sailboat racing
interests?

Lastly, there are a lot of diseases in the world. Most attempts at a cure
fail. Most pharmaceutical researchers fail to discover even _one_ drug in a
career. Finding a non-pharmaceutical cure would, for the books, count as just
another failure. The odds of finding a non-pharmaceutical cure between the
time that a lot of money has been spent on finding a pharmaceutical one and
the time that it would have made most of its revenue, is small. It's much more
likely that another pharmaceutical company will introduce their own drug for
the same market during that time. Seriously, by the time someone's spent $100
million on a drug (so about 20% of the way to market), there's been a huge
amount of research on the disease, other forms of treatments, the drug
pathway, and so on, including research outside of the company. The case you
talked about is so unlikely that I can't see anyone making a decision based on
that possibility.

Now your homework is to read the Wikipedia pages for cholera, polio, Jonas
Salk, smallpox, typhoid, penicillin and Albert Alexander, and Helicobacter
pylori and Robin Warren.

~~~
EGreg
Reading this I thought, I'm glad that Hacker News has so many smart people. I
learned a lot :) Thank you for your thoughtful response. And I did follow up
by looking on Wikipedia!

