How to cure a disease...fast
By Steve Kirsch
In August 2007, I was diagnosed with a rare, incurable blood cancer Waldenstrom's Macroglobulinemia (WM). Statistically, I'm likely to be dead in 6.4 years (from the date of diagnosis), either from the disease or the treatments. So I don't have a lot of time left to find a cure. Some people think I'll live longer than that, but I think it's better to be safe and assume for the moment that I don't have a lot of time left.
The first thing that occurred to me is that I'm toast no matter what I do. Given that the average drug takes 7 years to get to market and there are no promising drugs in the pipeline, this looks like a lost cause for me to try to expend energy to find a cure. Even if I succeed, it will be too late to save my life.
The second thing that occurred to me is that the chance of my coming up with some great idea or strategy to cure this disease is zero. The disease has been around for over 60 years. There are lots of people who are smarter than I am who have been working on a cure for this disease (both in terms of doing the research as well as determining what the research strategy should be) for a lot longer than me. I should just try to learn from them and follow their instructions since they've probably already thought through any of the ideas I am likely to bring up and I'd just be wasting their time.
As I learned more, I discovered, to my surprise, that both of these assumptions were wrong. I now believe there is enough time, and I also believe that I have the potential to make a tremendous difference in what can be accomplished. It will not be easy and there is a high chance of failure, but there is a small chance of success.
This web page summarizes the key things I learned from others and the steps I am taking to find a cure for WM. Most of the things I learned are applicable to other diseases. So this page is a generic "how to cure a disease" page.
OK, I know what you are thinking. You are thinking, "Wow, that seems awfully pretentious. You have no medical background whatsoever and you are writing a "how to" page on how to cure any disease? Give me a break!"
Well, you're right. It is awfully pretentious. And if anyone had pointed me to a web page saying "you should read this for how to approach curing your disease" then I would have read it. Instead, people pointed me to lots of information sources and a few books like "Patient from Hell" and "Chasing Daylight" but no proven "how to" guide for the shortest path to a cure.
In my search for the best success models for finding faster cures, one of the most remarkable people that I talked to is a college student named Josh Sommer. Josh has chordoma which is an extremely rare (only about 300 people per year) slow moving malignant neoplasm. Currently, the average life expectancy from diagnosis is 7 years. So he's in a situation very similar to me.
Rather than sit around and hope for a cure, Josh and his mother Simone are making a huge difference. Check out this presentation on how to cure chordoma that Josh shared with me. Or the website on chordoma that they set up. It was eye opening what just 2 people can do in less than 1 year. They even convinced the NIH to hold a workshop on chordoma and pulled it off in just months. Nobody else has done for chordoma anywhere close to what they've accomplished in just months. They've accomplished more in less than one year that larger organizations take years to accomplish.
When Josh told me his story, I told him, "Wow, you've just done an amazing job of all this. But why did you have to learn all this stuff from scratch? How come there isn't a web page somewhere on the net that explains all the steps you should take to cure an orphan disease? You can then just find that page and you can just follow the checklist. It would tell you all about how to use the NIH Chemical Genomics Center, how to convince NIH to host a workshop on your disease, resources such as Gene Logic, CombinatoRx, Genetic Alliance BioBank, and all the other key resources and contacts that you had to discover on your own that are critical to your success." Josh said if I found such a web page he'd love to read it because it would have saved him a lot of time! I told Josh I didn't know of any such page, but if there was, I'm sure he would have found it since he seems to have found just about everything else that might be helpful to his disease. So I suggested that he should write it! It should include the key learnings, the key resources, and the most helpful and knowledgeable people that he's run across (such as Chris Austin of NCGC and Sharon Terry of Genetic Alliance).
One thing I found really fascinating is that Josh told me that the NIH funds this organization called the NIH Chemical Genomics Center (NCGC). This center can test your disease against 2,000 FDA approved drugs and 300,000 other compounds to see which ones are effective against your disease. The cost? Free (since it is government funded). Now you'd think that such a center would be just swamped with work wouldn't you? Amazingly, the opposite is true; they provide their service for free and have to beg people use their service but few people do. Why is that? Well, as Josh is fond of saying, "In medicine, the right hand doesn't know what the left hand is doing." That's not to mean people are not competent. It simply is because there is an awful lot going on in medicine and nobody knows it all because if you spent all your time being informed of what others are doing, you wouldn't get anything done yourself!
There are a number of foundation that are trying some very innovative approaches to finding faster cures. The smartest foundations first study the most successful and then set themselves up to copy the best practices and innovate from there.
In the meantime, until Josh (or someone else) writes his page, I'll offer my humble contribution to the "how to cure a disease" page by summarizing for you what I've learned over the past 2 months and the approach I plan to take for curing WM.
The first thing to recognize is that the medical research is done very inefficiently. For example:
The main point is that the competitive grant proposal process set up by the NIH scales well in terms of management and suitability to large government bureaucracies, but it is an inefficient way to get results quickly. It does nothing to encourage sharing. In fact, it creates the opposite effect. As Debi Brooks of the Michael J. Foundation has said:
However, in the last 10 years, the newer NIH grants, such as large, multi-year SPORE grants start to move things in the right direction. SPORE grants support innovative, multidisciplinary translational research approaches that potentially may have an immediate impact on improving cancer care and prevention. But there is still a long way to go.
So the next question you'd ask is, "Surely, there must be somebody out there doing it right!"
Andy Grove is one of the smartest people I know. He has Parkinson's and he did a lot of research on what others were doing so that he could learn from the best. I know that because the most innovative foundations I talked to mentioned that Andy talked to them. So I asked him which foundation's approach to faster cures most impressed him. He said nobody impressed him.
If you want to impress someone like Andy you have to have a consistent track record of breakthroughs or cures, i.e., you'd have to prove your research process has a proven track record of results that matter to patients. So if your foundation is cranking out one miracle drug a year (e.g., one Gleevec a year), you are clearly doing something right that others should emulate. Nobody is doing anything close to that now.
Nor is it clear that there is a "holy grail" model for how to do medical research. I'm in the anti-spam business trying to find a magic filter that filters out just the spam without impacting the good mail. There is no research process you can describe to solve this problem. Hundreds of people have tried to solve it both in companies and universities. Nobody has figured it out. The solution just popped into my head about 4 years after trying different things. I now have a precise and elegant mathematical model for spam. I can describe the algorithm to others who would say, "That is so simple. Why didn't we see that before?" Is medical research any different?
Based on what I learned, the process you should follow if you want to cure a disease quickly looks something like this:
Time is your enemy. You'll never get the perfect plan on day one and if you keep researching in step #2 and #5 to optimize, you aren't going to get anything done. There will be some stuff that you can figure out that you need to do no matter what. For WM, for example, it is to get validated cell lines and genomic analysis. Get started with stuff that is not controversial now and you can add other stuff later. And don't try to scale everything now, e.g., getting 3 good cell lines gets you most of the way there; you don't need 50.
Lee Iacocca has said management is no more complicated than people and priorities. It's the same for medical research. Getting truly outstanding people working on the problem is fundamentally important and prioritizing what needs to be done ASAP and making the decision to fund it now (rather than waiting until all pieces of the strategic plan are in place) are critical.
There is benefit to collaboration but there is also benefit to isolation. I never would have solved the spam problem if I wasn't off in a corner and forced to think independently. The solution was completely opposite to the way everyone else had been thinking about the problem. So exposure to other approaches and collaboration would have been, in this case, very detrimental. It would have caused me to think conventionally about the problem and I would never have solved it. Instead, the isolation caused me to think in ways that eluded everyone.
It's also theoretically possible to re-direct an existing foundation to adopt these new approaches rather than having to start your own. I say theoretically because I'm not aware of any cases where this has been done. However, there are some foundations that are slowly moving in this direction.
There are 700 breast-cancer related organizations in this country. If you have to start a new foundation, you want to be sure there is a good reason. If the foundation(s) that already exist for your disease are slow moving and won't change, that can be a good reason for starting a new foundation.
Andy Grove and Michael J. Fox both started new foundations for the same disease. Fox felt there was a need for a more focused, aggressive and efficient research effort to find a cure for Parkinson's Disease (PD) which is why he started a new foundation. One of the first tasks Fox and Debi Brooks (co-founder of the foundation) undertook was to seek out best practices in building an effective foundation.Grove took a similar approach. But they ended up with different answers. Grove and Fox found that while their mission was the same, their strategies and tactics were not which created both challenges and opportunities. Also, another key difference is that MJFF is funded mostly from public money while Grove is the sole funder of Kinetics. This gives Kinetics far more freedom to take risks, focus resources, and move swiftly. Conversely, MJFF has ten times as much money per year to spend on research than Kinetics does.
Here is the philosophy of the Kinetics Foundation:
In general, the larger the foundation the harder it is to change. For example, an executive at one innovative foundation was invited by a board member of the American Cancer Society to make a presentation and the board member suggested that they do a small pilot project to try out these new concepts. The full board denied the request. I find it strange that they are willing to risk funding hypothesis driven research but are unwilling to experiment with things that might improve the process.
The plan is typically not a "put all your eggs in one basket" type of plan. None of these foundation makes a single strategic bet or adheres to a single approach to research. And even when they do make investments along one strategic direction, they will often make multiple investments. For example, Andy Grove's foundation (Kinetics Foundation) supported six different "moon shot" projects to cure Parkinson's disease but each one failed to land on the moon. In this case, a "moon shot" was a project that could test a set of unproven hypothesis in attempting to reach a given end goal. Grove’s logic was it might save the field time if something were proven to work before the details of how it actually worked were discovered
Along the way, you learn that trying to get extra government funding for your disease is probably a long shot. For example, many years ago, when Geraldine Ferraro was diagnosed with multiple myeloma, she got a $250M authorization from Congress for research into blood cancers. The amount Congress actually appropriated in the budget: zero. So they pass a law, but then block the funds for it.
The other thing I've learned to do is to share what I learn There is no strategic advantage to keeping my diagnosis or anything I learn secret. Someone can benefit from what I wrote and often, people stumble on this page and bring important information to my attention.
For my disease, I found that money could be raised. In just one month, I was able to locate sources that could be tapped for more than $5M per year. In fact, a survey of just 72 people with WM showed that there was the potential to raise over $3M per year from those 72 people alone. Yet there are about 5,000 people living with the disease. So the money is there. The problem is coming up with a strategic plan for the best way to spend the money to maximize the chance of success. A plan that the donors will be excited to fund.
One untapped potentially large source of funds is friends of people who have a disease who make a donations targeted to their friend. Here's a simple example. There are only two existing cell lines for WM. Suppose it costs $50,000 to develop a new cell line for WM. There is a huge advantage towards having your own personal cells be the basis for that cell line. You may not be able make a charitable contribution and specify that your cells be used (this is a gray area). But your friends can! That is because your friends don't personally benefit at all from the contribution. So they can aid the science, and aid you at the same time by specifying that their donation helps the disease as it pertains to you specifically. So it is targeted charitable giving. So as a victim, there can be tremendous motivation for you to help raise funds for the disease since the funds can be targeted more directly to benefit you.
Here's a list of Success models for curing a disease.
On November 30, 2007, at the recommendation of Andy Grove, I talked to Marc Shuman a hematologist at UCSF. I asked him about doing a nerve conduction test to establish a baseline to see if I am getting worse and might be at risk for developing PN and he thought it was a good idea. But the main focus of the conversation was on how to give money away effectively. Marc thinks the NIH is a terrible model and things have actually gotten worse, even with SPORE grants. He thinks there are two basic approaches that a funder should consider:
Marc suggested I talk to former National Academy of Sciences President Bruce Alberts for ideas on who to appoint. Alberts spent 12 years at NAS and returned to UCSF to find not much had changed in terms of process (a lot of inertia in the system). He also suggested talking to Sophia Colamarino for other ideas on how to fund research on curing diseases.