2009 Predictions

There are not many companies left in Seattle. There are more than the CCS is aware of but many of the big players went down or were at least knocked down a peg last year. 2007 was already covered at the beginning of 2008. Dismal. But what about the upcoming year? I know that people will have a bias that the CCS is optimistic about the upcoming year of scientific discovery among the scientists of Biotech. But wait, I've got to admit that I can be a little negative from time to time. For example:

Gilead is expanding and hiring: http://blog.seattlepi.nwsource.com/thelifesciencesblog/archives/141124.asp

I predict they will grow in the most foolish ways imaginable. They have the brass from the ruins of Corus and they have no idea what they are doing. They do have a lot of money to spend however and they will do so for the sole purpose of creating a Cargo Cult Airport. It will be a nice facility with lots of promises presented on all of the lastest equipment available from Dell and software from Microsoft.

But I can also be positive. For example:

Amgen will rebound. http://seattlepi.nwsource.com/xconomy/392982_xconomy7075.html
It's an untestable osteoporesis drug. No harm means no foul. Lots of money will be handed over and the leadership will go back to spending the profits on their own Cargo Cult airports within the organization. Their RNAi projects will quietly start to fade and antibody work will be pumped up using new technologies bought from smaller companies.

I'm not an insider. I'll find out what is going on nonetheless. It makes life in the biz much more interesting.

How Can You Lose?

"Harry is an experienced portfolio manager who has a proven track record of success."

So says Adam Banker, a spokesman for Fidelity Investments. Harry Lange runs Fidelity Investments' Magellan Fund. The Magellan Fund has seen assets decline 83 percent since reaching a peak eight years ago. The 18.6 billion dollar fund declined 52 percent this year, trailing 99 percent of competing funds.

Somebody had to finish towards rock bottom. It makes you wonder what funds trailed the Magellan Fund. Did their managers also have a proven track record of success?

My interest in the financial worlds folly is directly tied to Cargo Cult philosophy. Clearly the world has seen behind the Wizard of Ozs' curtain. They didn't see failure coming anymore than they saw success in the past. These are the same people who invest in Biotech. Someone points out that RNAi is a hot investment because SIRNA sold for over a billion dollars. Fund managers get their clients checkbooks out and go looking for RNAi companies. Meanwhile it is no certainty that any of these people know what RNA is, let alone RNAi.

I'll end with a funny story about a biotech investor. This person was looking for investments in a hot biotech field he had just heard about. He called the investor relations department. A very nice lady who had just started in the department answered the phone. She had just been promoted up from her previous position as receptionist. Before that she spent 7 years as a secretary at the local high school. The investor spoke authoritatively to the nice lady. "Yes, can you tell me if you have any research taking place involving monoclonal antibiotics?"

Wallstreet Logic and Biotech

Why is it that Treasury Secretary Henry Paulson didn't originally ask for 1.5 billion dollars for his bailout plan? The original amount of 700 billion was a shock. The 800 billion seemed to be less appalling. Not only is it 100 billion dollars more, it comes right on the heals of the 700 billion. The most likely answer is that Paulson knew he needed a blank check but knew better than to ask for one. So he went about it this way. Creating an illusion of stability is the plan. Investors will buy into illusions.

This is clearly a Cargo Cult approach. We've noticed that during more prosperous times our bankers were flush with cash. Now they are all facing annihilation. If we slather them with cash then they will appear to be well again. But what about the fact that they ran out of that cash? Will they run out again?

Biotech financing works this way as well. We don't know how much we'll need. Give us millions and we'll get started. Give us more millions and we'll keep up the good work. And just keep on giving until we succeed. But we rarely succeed. Now we are watching our government give billions to individuals who also have a promise.

Another issue is whether or not the meltdown is really bad for us. Gas is now 1.85 per gallon. Real estate is dropping which is bad for the profits I would have needed to make a downpayment on the next place. But I now get to select from a whole new set of properties for my next place. I'll have less to put down but I won't need as much. It appears that our economy is merely correcting for a decade or more of inflation.

If 100 people live on an island with only enough food to comfortably feed 100 people then you have to figure out how to ration the daily intake. If you do it wrong then some will have too much and some will have too little. It takes a special kind of person to admit that they are getting more than their share. They must also decide who gets their extra food. What is needed is a governing body on this island that knows how to ration. Some will gather the food, some will prepare the food and some will search for new sources. All will need food. The important thing for the governing body is to not make any one group of the team so important that another is eliminated.

The main point today is that money fuels wallstreet and it fuels biotech. It's great when you have it but humiliating when it's gone. So somewhere along the way to failure we have to take a look at how effectively were using our limited resource, money. Once again... Dr. Richard Feynman:

"So we really ought to look into theories that don't work, and science that isn't science."

And I might add, look into it sooner than later.

DOH!!!

http://health.msn.com/health-topics/colon-cancer/articlepage.aspx?cp-documentid=100220689

Chaulk up another swing-and-a-miss for medical science.

Back to RNAi

We recently put the flame of Nastech out. Tight junction technology didn't work!!! Nastech lit the side of our runway for many years. Then one day it ended. The name was changed, the CEO was replaced and the stock became a steal at 15 cents a share. The name of the company was changed to MDRNA, as in RNAi. The new CEO was in fact the old CEO of SIRNA, as in siRNA. The latest addition to the MDRNA staff is the old CSO of SIRNA. SIRNA was sold for 1.1 billion dollars to Merck. Can lightening strike twice?

The first question is, what has Merck done with their aquisition of SIRNA? Any regrets? 1.1 billion is a lot of money. One might hope to make that kind of money from an approved product. Merck did not buy an approved product. The second question is, what does MDRNAs new brain trust plan to do with the 12 million bucks left behind by Nastech? The SIRNA patents are in the hands of Merck leaving only the brain power behind SIRNA and the power of RNAi.

The brains behind this new flame along our runway have a major obstacle. Can they stay in business long enough to get a drug approved? The villagers must be very enthusiastic, but will they hand over their money? If not this latest RNAi project will not get off the ground. If they get funds they will be free to conduct the science. We are watching.

A Villager Speaks Up

One of the most outspoken villager, who looks up daily to spot the cargo planes, has detected a way to spot a false profit: http://www.thestreet.com/story/10443120/1/dont-get-burned-by-the-next-cell-genesys.html?puc=googlefi&cm_ven=GOOGLEFI&cm_cat=FREE&cm_ite=NA

Mr Feuerstein makes a living telling the other villagers, who look to the sky, what it is they should expect to see any day now. But he speaks from the investment perspective. The science is something he peppers into his columns. He doesn't know. It would be interesting to see an accounting of his ability to predict good from bad investments. Are his predictions best measured by his understanding of the science? Would a random stock pick make more or less?

Keep looking up Mr. Feuerstein.

Once again, Feynman; "So they've arranged to imitate things like runways, to put fires along the sides of the runways, to make awooden hut for a man to sit in, with two wooden pieces on his headlike headphones and bars of bamboo sticking out like antennas--he's the controller--and they wait for the airplanes to land."

I will promote Feuerstain to control tower supervisor.

A Cancer in the Health Care System

What if there were doctors for the health care industry. A company like Pfizer goes to the doctors office compaining of a weakness in sales and a bleak outlook for the future of their research efforts. The doctor says, "take off your marketing department please."

Pfizer: Things like this keep happening to us:

http://ap.google.com/article/ALeqM5g--AosBLRVpNsiYYtzTePEXOUzoQD93S9NGG0

Doctor: Hmm. I see you have an honesty problem.

http://www.nytimes.com/2008/10/08/health/research/08drug.html

Pfizer: Well, we have to make money.


We continue to be shocked at the lack of outrage against these common practices. Which executives made the decisions that led to the conclusions in the second article? What about repeating such dishonesty over and over and occasionally getting caught? The industry has a disease. It is incapable of being honest when negative data presents itself. What is the cure?

Cargo Cult Scientist Gets Snubbed

The Nobel Prize committee for medicine has failed to honor Dr. Robert Gallo for his contributions to the HIV/AIDS hypothesis. While it's true that he appropriated the HIV virus from Luc Montagnier, he did convince the masses that this was the cause of HIV. A true Cargo Cult Scientist does not succeed by solving tough questions. He succeeds by convincing people that he knows how to make the airplanes come from the sky. The better the Cargo Cult Scientist the longer he can keep the masses looking up and waiting. The message from Stockholm today seems to say that it was not Dr. Gallo who started us all looking up.

Now would be a good time for the national media to explain why Dr. Gallo was snubbed. He was snubbed because he is a dishonest person. Many people know this yet he continues to work in science. Dr. Prusiner, the 1997 winner of the prize put it this way: http://aidscience.org/science/298(5599)1726b.html.

There are many prizes for the many promises.

Have a Plan

Lately I've been thinking about the way in which ideas become accepted. The Cargo Cult natives saw the cargo emerging from the big metal birds and a desired outcome was born. Now all they needed was a plan. They watched the Allied forces carefully and began piecing together their plan. The desired outcome however was the most important piece of the plan. The ideas of how to acheive the outcome took a back seat while the leaders dreamed of the cargo.

We recently experienced the Republican and Democratic national conventions. The mission was to convince the majority of America that one party will provide a better future than the other. The melt down of wall street however is an excellent example of our political and corporate leaders ability to predict and shape the future. Our government is going to put up 700 billion dollars (this week!) to "fix" the problem.

But what about 2 weeks ago? Was anyone preparing for the bailout? What was being done 2 months ago? When did this government bailout start to take shape? We now have our desired outcome. We want the economy to be strong. That is our cargo. What is our plan? Bail out the banks so they can go back to making loans.

How did the ideas that went into the bail out plan gain acceptance?

The 700 billion dollar bailout does not guarentee success. It is a plan however. For the politicians, a plan is all that is needed. Even if the plans spells the end to the great American era. It doesn't occur to the Cargo Cults that there plan is not working. Simply carrying out any plan gives off the impression that work is being done.

Only a proper scientific method will bring about a proper change. Compare the actual outcome to the desired outcome. The ideas that were accepted may have lead you astray.

The Psychology of RNAi

This summers reading brought me in contact with a most beautiful book on the subject of randomness. The book is called "The Black Swan". In it you will find heretical discussions such as, "Academic success is partly (but significantly) a lottery. It's easy to test the effect of reputation. One way would be to find papers that were written by famous scientists, had their authors identities changed by mistake and got rejected. You could verify how many of these rejections were subsequently overturned after the true identities of the authors were established."

The painful truth about science is that it is run on the most non-scientific means of judging a persons work. Reputations rule. Good solid science will do you no good if you cannot convince the powers that be that they have missed something. This is not an easy task due to the arrogance of power. If you dare challenge someone like a David Baltimore or Craig Mello you had better have a powerful group of cohorts willing to back you in your battle.

The CCS knows this and is under no delusions that he is actually battling the powers that be. This is rather an exercise in psychology. What does any person have to do to affectively be heard? Write a blog? Ha! Have a great idea? Ha again. Great ideas can have just as hard of a time being sold as bad ones. In fact, the scientific merits of an idea is not as important as its presentation. Who is presenting the idea. Are they confident? Is the idea presented in peer reviewed journals, scientific meetings or books? Does the idea fly in the face of current thinking?

Billions of dollars have been spent and many more are on their way out the door for RNAi to be used as a drug. Beyond that, RNAi has been the bane of many a research associate whose job it is to use RNAi to knock out genes. It's like using a feather to hammer nails. But no one is going to listen to a guy who wears a white lab coat daily. No one is going to publish a paper stating that RNAi has yet again failed to produce knockout data. The idea that it doesn't work is no longer being accepted. Like gene therapy however, it will cease to impress and thus be put on the back burner. One day the real story behind what happened in the early studies of RNAi will be known. Until then we must accept that we are in the middle of a common situation in the history of human reasoning. We are convinced that we know the truth. We no longer require evidence to the contrary. Yet the planes are not landing.

http://www-tech.mit.edu/V125/N50/50van_parijs.html

This is an old story. This marks a new chapter in the CCS. We will now make it our mission to explain why this (RNAi) happened and how it will end. We have learned much from gene therapy and the demise of hundreds of biotech companies. Tens of billions of dollars are gone but there is something to be learned.

Just for fun, we start with a Harvard PhD who is fired from MIT after a rather successful beginning to his career. As you read about this story please think about the environment that make it possible. Harvard? MIT!!! But... but... PhDs? 461 citations. But there was a Nobel prize awarded for the RNAi story. Why would anyone in such a world have to cheat?

One Flame Out, One Flame Close Behind

http://seattlepi.nwsource.com/business/366495_nastech11.html
http://blog.seattlepi.nwsource.com/thelifesciencesblog/archives/141684.asp

Nastech is no more. Therapeutics will be done soon as well. Notice the name change at Nastech however. Cell Therapeutics may do the same thing. There is much to learn from companies like these who promise the cures. They take until they can no longer get away with it. Then they change their names and go back for more.

Sirna Sold For 1.1 Billion!!!

As I mentioned in the last post, a company called PhaseRx boasted that they are an RNAi company. What's the big deal about that you ask? SIRNA SOLD FOR 1.1 BILLION DOLLARS! So let's give PhaseRx some money!

Do you think that is a silly thing to say? How can a bunch of grown men with PHDs and MDs get together and hoodwink investors so easily? Does PhaseRx not have to present the scientific merits of their RNAi company?

In more recent news, the notorious Dr. Quay of Nastech Pharmaceuticals discussed the ruins of his biotech company today. In an attempt to ease the suffering of his investors he spoke glowingly about his spin-off 'MDRNA' a new RNAi company. There wasn't much information about the last five years of RNAi research under the old banner of Nastech. But he did mention this interesting fact:

SIRNA SOLD FOR 1.1 BILLION DOLLARS!

Who will be the first to go? MDRNA or PhaseRx? Will Merck keep spending money on SIRNA projects? The CCS will be on the lookout. Our eyes cast to the skies, we look for the kind of cargo that only billions of dollars can summon.

Would You Work for This Company???

Seattle Biotech has a new management team that has been sued by their investors. http://seattletimes.nwsource.com/html/businesstechnology/2004127544_cellcyte16.html

Okay, so that is old news. We also have a new fire to light our runway. And they specialize in RNAi!!! They have the old Nastech CSO who was "resigned" recently after years of not making RNAi work there.
http://seattletimes.nwsource.com/html/businesstechnology/2004247523_biovc28.html

Welcome to the airport.

What's in the News

'In the South Seas there is a cargo cult of people. During the war they saw airplanes with lots of good materials, and they want the same thing to happen now. So they've arranged to make things like runways, to put fires along the sides of the runways..."


We here at the CCS look at each biotech hub as a cargo cult airport. Seatte, the bay area, San Diego, Boston, North Carolina are all airports. The fires along the runways are small biotech companies.

The seattle cargo cults had a bad week.

Cell Therapeutics throws a 30K$ party after laying off 31 employees to save money.
http://seattlepi.nwsource.com/business/351048_cti13.html?source=rss
Amgen lays off 130 employees... up from the 50 they anticipated. They found more useless people than they originally thought they had hired?
http://seattlepi.nwsource.com/business/351138_amgen14.html
Dendreon can't get a break!
http://seattlepi.nwsource.com/business/351210_dendreon14.html
Nastech is one step closer to the end.
http://seattlepi.nwsource.com/business/350985_nastech13.html
Zymogenetics has layoffs after finally getting a drug approved.
http://seattlepi.nwsource.com/business/351223_zymogenetics14.html
CellCyte is a ridiculous company!!!
http://seattlepi.nwsource.com/business/351230_cellcyte15.html
The CellCyte CEO did lied?
http://www.sequence-inc.com/fraudfiles/2008/01/13/usana-executives-arent-the-only-ones-lying-about-their-credentials/

Sheesh!!!

A Burning Flame Going Dim

We think of biotech companies as bright burning flames that illuminate the runway of our Cargo Cult airport. We think of technologies such as RNAi as the fuel for the flames. Today we are concerned about our Nastech flame.

On January 16, 2008, Novo Nordisk A/S ("Novo") advised Nastech Pharmaceutical Company Inc. that Novo intends to cease development under the feasibility study agreement that the parties entered into in March 2006.

Jan 22 (Reuters) - Nastech Pharmaceutical Company Inc (NSTK.O: Quote, Profile, Research) said it may periodically sell up to $50 million in debt securities, common and preferred stock, warrants and units.

The company said it intends to use the proceeds in part to fund its clinical research and development programs.

Is the end coming soon? How will it end? Will they rebound??? We are watching.

A New Set of Questions for Scientists

Merck and Schering Plough make a drug called Vytorin which combines Zocor, a cholesterol lowering statin, with Zetia, a drug that limits cholesterol's absorption into the body. The ran a trial that was hoped to show that this drug was more effective than Zocor alone in slowing the growth of arterial plaque, which can lead to heart attacks. It wasn't. Vytorin users did see a larger drop ini cholesterol than Zocor users. The decline however didn't result in a improved arterial health. http://www.revolutionhealth.com/news/?id=hd-611715&s_kwcid=vytorin934891494

Shocking news to the scientists and doctors working for the drug companies. They just had no clue this would happen.

Folkmans Delivery Problems

Dr. Judah Folkman was a rising star with several publications and patents on anti-angiogenisis factors. The problem was that no one was able to reproduce his results. From his book "Dr. Folkmans War":

Soon after he began shipping endostatin to researchers around the country, Folkman heard that the drug had become inactive by the time it got to some of the laboratories... The recipients reported that the drugs were having little or no effect on cancer-bearing animals. Folkman was alarmed, needless to say. Any such report carries with it the suggestion that somehow the original research was wrong, or worse, that the results had been embellished.

Folkman and his colleagues soon noticed that the problem seemed to be only with batches that were shipped to distant places. The endostatin being tested in local labs was fine. So the problem, in all likelihood, was in the shipping.Like many drugs or biomedical compounds, the endostatin was being frozen in small plastic vials, packed in dry ice, and was sent out via Fed Ex. Folkman began doing experiments to figure out what might be going wrong. First, they found that the problem was not caused by freezing. When they froze a vial of endostatin, then thawed it, the drug worked normally. So how could transportation hurt it? Hoping to find clues they packed a sample in dry ice, stowed it in the trunk of a car, and drove around Boston with it. Sure enough, when they brought it back into the lab and thawed it, the endostatin didn't work. But why?"

The answer they later came up with was that the dry ice that the drug was packed in bathed the solution in carbon dioxide that had seeped through the vials. The result was the lowering of the pH that inactivated the drug. The solution to the problem was to put the drug into glass vials for shipping. The results of this experiment were not covered in the book.

Judah Folkman Is Dead

No sacred cows here. Dr. Juday Folkman died of a heart attack this past week at the airport in Denver. He had a great career in medicine. He was an MD surgeon who had a second career as a PI in a laboratory that explored the involvement of blood vessel in tumor growth.

The CCS does respect Dr. Folkman for offering up a new idea to the establishment and proving that tumors need blood. But then all cells need blood for oxygen and to carry away their waste. This should have been less heresy than it was. The real issue we have with Dr. Folkman however is his role in bringing corporate america into academia.

Dr. Folkman had spent a long time looking for a tumor angiogenesis factor that he decided had to be secreted by the tumor. What he needed was money to grow up large amounts of tumor cells to increase the odds of finding the factor. Monsanto was eager to give him what he wanted. The grant he was given and the terms of the deal swung the academic doors wide open for the corporate world. Their money could now buy access to the usefulness of our university system.

What they wanted of course were patents. They wanted to lay claim to the good work being done, not in their laboratories, but in the superior labs of university scientists. In my next post I will recount a humorous ending to one of Dr. Folkmans corporate sponsored R&D projects. For now I will end with the moral of this story:

The introduction of corporate minds and money into the world of science has been a disaster. In many ways, it began with Dr. Folkmans desire to become a scientist.

Is It Dishonest?

Nastech Pharmaceutical Company Inc. (Nasdaq: NSTK) announced today that the U.S. Patent and Trademark Office (USPTO) has issued a Notice of Allowance for U.S. patent application No. 10/976,942, entitled "Phage Displayed Trp Cage Ligands." The patent application has claims that relate to a novel, high-throughput method for identifying peptides which can bind to specific cell types.

"A major obstacle in the development of safe and effective medicines today is the inability to target the therapeutic directly to the cells of interest," stated Steven C. Quay, M.D., Ph.D., Chairman and CEO of Nastech. "The technology of this allowed patent provides Nastech with a process for rapidly identifying peptides that target specific cells. These targeting peptides can then be combined with therapeutics to enhance overall delivery and overcome this key challenge in drug development."

Why then did Nastech sack the Phage Display group in 2006. The Cargo Cult Scientist knew members of this team and the reason they were given was contrary to the above quote from the CEO. It just wasn't working. The question then is simple. Is this dishonest?

In Cargo Cult terms, yes this is dishonest. They stood at the airport and employed their technology. They looked to the sky and no planes came. They sent the staff home. A couple of years later they still talk about the technology. Their government has given them a nod of approval but no planes have come.