Work(s) in Progress

10+ years of ALS research

I am looking backwards today. I moved to Colorado with my first husband in 1995. I've been thinking of him recently. It was his birthday on Saturday (Happy Birthday rb).  A friend of mine is making a video for his son's wedding and I recommended that he use a song from when I married this former husband of mine, Chet Atkins & Suzy Bogguss, "you bring out the best in me." (you can play it here.) And no, this song is NOT jinxed or unlucky. My ex sent me a note today that reminded me that even though we've been divorced now for almost 10 years, he continues to inspire me to be the best I can be. His email is a post for another day. Today I have ALS (amyotrophic lateral sclerosis; Lou Gehrig's disease) on my mind.

When I've taught students about ALS, I generally have had them read a few posts from BrainHell - a wonderful first person account of experiencing ALS from diagnosis until death. I'm often asked why Stephen Hawking is still alive if he has ALS. Um, not exactly ALS, more likely a variant motor neuron disease know as spinal muscular atrophy type IV.

I started working on ALS in 1995. Soon after I established my own laboratory a few years later, or perhaps before, I met Ian Pearson who had recently been diagnosed with ALS. Unlike the majority of people with this diagnosis Ian has lived with this disease for many years. Tonight I received a number of emails from Ian about his current plight and changes to the Colorado Health Care system that may cut his life short. For this reason, I am going to copy his various emails into this post in their entirety. Please contact me if you would like Ian's contact information (it's the only thing I'm going to redact).

One of Ian's emails ended with this post script "The preceding text has been written using Ez-keys by Words plus, a communication program for people with physical disabilities. I use switch scanning and a piezoelectric sensor switch, mounted on a headband and activated with my eyebrow muscles. This document took roughly 40 hours to write. "

In my mind, the most horrible thing about ALS is the LACK of cognitive loss. Imagine, your brain is working perfectly; you cannot talk; you cannot move; if you are lucky, you might be able to blink or move an eyebrow that manages a cursor on a computer screen. Imagine now a decade of this. As you are thinking of these things, I ask you now to read Ian's letters.

Thank you.

May 12, 2009

Dear friends, family and other worthy souls,

For those of you who didn't already know, on Monday April 27, one of the local TV news stations ran a short piece about a change in Colorado Medicaid reimbursement policy that has effectively ended the program under which the facility where I live operates. If I have to go out to a hospital for an extended stay, I won't be allowed to return to where I have lived for more than the last five years and my only option for health care to stay alive. If the policy isn't reversed the entire program will end on July 1, 2010 and I will have to find a new place to live, possibly outside Colorado.

Here is a link to the story written out with the video on the top right corner: http://cbs4denver.com/health/medicaid.problems.patients.2.995937.html  

Below is my reply to the reporter who did the story. As you can read, I was very disappointed and frustrated with all that wasn't said and the missed opportunities of the piece. I've also attached the letter that I wrote back in March to the policy makers and affected parties. It explains the problem and gives my perspective on the situation. On March 10, a patients' father here, Doug Paris (in the video), held a meeting that he organized, to call attention to this critically important issue. He invited representatives from the state Medicaid board, hospitals, nursing homes, the media, local politicians and family members. That is how the TV news got involved. My letter was distributed at that meeting, the initial interviews were conducted (including with Kate), and Kate recommended that the reporter interview me. Unfortunately the reporter showed up without notice so I didn't have time to prepare anything to say (it takes a long time to write anything using my eyebrow).

I have a lot of things going on right now but I wanted to get the word out about this. I may follow this with information how you can help. I just got word today that the HCPF board is reviewing the financial statements from the two HBU facilities in Colorado. I am drafting a letter to the HCPF board to emphasize the key points against this flawed policy and may solicit your help to write your own versions of request that they reverse their Medicaid reimbursement policy for the HBU program. Please stay tuned for more information. Thank you for your interest, support and possible activism.

Thankful for all I've got and not letting it go without a fight,

Ian

April 30, 2009 (letter to the reporter Rick Sallinger)

Dear Mr. Sallinger,

Thank you for your efforts. However, for all of the time elapsed and information that was provided and available to you, I was very disappointed in your finished product. Perhaps your piece is just reflective of the sad devolution of television news into its current state of info-tainment. Both local and national coverage is light on useful information and heavy on sensationalism and triviality. In that vein, I thought that your piece was pretty thin on providing useful information; just a sympathy story with no sense of outrage. In general it's true that there is less substantive material to fill a local broadcast than national coverage but in this case, a paucity of substantive information wasn't the problem. This Medicaid reimbursement issue is somewhat complex and multi-dimensional but you missed providing the most critical information. Given that there is such limited material to fill the daily broadcast, the viewers' attention spans are brief and individual stories don't exceed 4 or 5 minutes; I think that you could have developed this story into a multi part series. Each episode could have examined one specific aspect; the historic context and nature of the issue (what was the motivation and justification for the State's policy change?), the personal impacts (as your piece focused) and the actions and consequences of the new State policy and the future implications.

The State HCPF is acting irresponsibly. The bottom line is that the State prematurely made an unnecessary policy change that is ethically, logistically and fiscally unsound. Colorado is effectively trying to save money by exporting and pawning off this patient population on other states. ALL of the affected parties including hospitals, nursing homes, the two existing hospital back up facilities and families/patients are unanimously opposed to it.

If you're going to condense the rather involved and complex issue down to a three minute piece, you have to chose a specific focus. Quite predictably, you chose the "Look at those poor people" track. Unfortunately this approach left out the most important points to communicate;

1) it didn't accurately describe the problem,

2) it didn't state that HCPF has changed the policy to save money without first reviewing with prospective new care providers (there aren't any) to determine whether the new plan was logistically possible (it isn't achievable, and a small pilot program would have revealed that) and,

3) no evaluation of the actual financial consequences was planned or conducted.

It didn't explain that people will be forced to go out of state BECAUSE the only two facilities in Colorado now with the remaining patients won't and can't afford to operate under the fixed rate schedule. The State's proposed alternative is to send us to nursing homes (none of which accept vented patients). The consequences are already being seen as patients who would normally go into the hospital back up program are stacking up in area hospitals, in some cases in ICUs (because their only vents and qualified staff are there), and racking up much greater expenses and consuming critical care staffing and resources unnecessarily. Someone has to be paying for these greater expenses. How are the hospitals passing through these costs? Don't they have enough of a financial stake to lead this fight with a PR blitz, if not with a legal suit?

This was the whole reason why the Hospital Back Up (HBU) program was established; to provide specialized care units for long term patients on ventilators with minimized costs and maximized efficiency. Only full service hospitals are capable of providing the same level of required care but at much greater cost. The two facilities in Colorado with HBU units operate on very thin financial margins. The imposition of a fixed rate reimbursement schedule (rather than being reimbursed for per patient operational expenses with all of the statutory Medicaid restrictions) is shutting down the HBU program without providing an alternative. The fixed rate reimbursement schedule was developed for Medicaid patients in nursing homes and doesn't take into account the additional expense of long term full time respiratory care of ventilator dependent patients.

Another dirty little secret about the HBU program is the demand for HBU beds exceeds the capacity of the two Colorado HBU facilities. Both facilities had waiting lists under cost basis reimbursement. The fact that there were no other HBU facilities operating prior to the State's policy change demonstrates that even cost basis Medicaid reimbursement isn't profitable. The two programs were established when governmental compensation more closely coincided with operational expenses and remain as vestiges of that time. It's shameful enough that Colorado has left it to market forces and a grossly inadequate state managed Medicaid program to care for a small vulnerable patient population with no other alternative for medical care. In a 2007 study by Public Citizen that evaluated Medicaid as administered by each state, Colorado was ranked 43rd overall. The individual ranks of the four parameters: eligibility, scope of services, quality of care and reimbursement were 41st, 40th, 42nd and 21st, respectively (p. 58, Unsettling Scores: A Ranking of State Medicaid Programs (2007), http://www2.citizen.org/hrg/medicaid/assets/reports/2007UnsettlingScores.pdf). The summary noted that the low Quality of Care score was attributable to very low quality nursing home care and very low rates of childhood immunization. The relatively moderate Reimbursement score was calculated from all providers under Medicaid (of which, the HBU program is too insignificant to affect an overall reimbursement score). It's worth noting that this assessment was done before the current economic crisis and state budgetary limitations. The effective elimination of the HBU program defies belief on the basis of ethics, responsible governance, viable logistics and intelligent fiscal management.

I will use the video of your piece with substantial supplementary information in an e-mail PR campaign to my personal and professional contacts to barrage the HCPF representatives with calls and e-mails until they see their wayward ways. I only wish that your reporting had more substance, carried a sense of outrage for bad governance and a message and vehicle for social activism to a much larger audience. I suppose that was too much to expect but for a man in my position, eternal optimism is standard operating procedure and, ultimately, I've learned to be my own best advocate.

Most sincerely,

Ian Pearson

March 8, 2009 (ironically my Birthday)

To all concerned,

Background I have been a Hospital Back Up (HBU) patient of the Skilled Nursing Facility (SNF) Unit at North Valley Hospital (recently renamed with the oxymoronic pleonasm, Vista View Care Center) since April 2004. Prior to coming here, I was resident at three other hospital facilities during the preceding eleven months. Over the last nearly six years I have come to a clear understanding of what is required to keep me (and others who require a comparable level of medical care) alive with an acceptable quality of life. I am writing this letter so that those who are making changes to the Medicaid reimbursement policy for facilities like this one better understand those medical requirements and the inevitable impacts of those policy changes. I am also writing to all other interested parties who may be able to influence and affect change to reverse this policy decision.

The Reimbursement Issue

The Colorado Department of Health Care Policy and Financing (HCPF) reduced reimbursement for new HBU patients, effective October 1, 2008. Existing patients were granted an exemption to the reimbursement change until July 1, 2010. The essence of the change is that reimbursement will now be made according to a fixed rate fee schedule rather than the existing restricted cost basis.

Historic Context and Existing Conditions

In order to understand the impacts of a reduced reimbursement one must understand the historic and current conditions under the cost basis reimbursement status.

For years, the SNF Unit here had been operated at a financial loss because of restrictions of Medicaid reimbursement, even under a cost basis, didn’t fully cover operational expenses. The hospital had other facilities that had a sufficient profit so that the extra cost of the SNF Unit was offset enough to be deemed acceptable. This mode of operation provided higher staffing levels, more auxiliary patient services (full time psychologist on staff, a comprehensive speech therapy department with an assistive technology program, a comprehensive and personalized physical therapy program and facilities, etc.), more frequent restorative therapy and showers and a more extensive recreation program than exist now.

After Vibra Healthcare purchased the hospital they fired many employees and closed or greatly reduced entire departments and facilities. Under this mode of operation the financially losing SNF Unit became a greater financial liability. In 2007 Vibra managers announced that they intended to close the SNF Unit, citing the financial burden. They later reversed their decision to close the SNF Unit and implemented a cost cutting strategic operation. Because the auxiliary patient services were already gone, cost savings were realized by increasing patient to staff ratios with reductions in Certified Nursing Assistants (CNAs), nurses and Respiratory Therapists (RTs) on all shifts. In addition, efforts were made to keep the patient population at capacity to minimize marginal costs and maintain more profitable economies of scale.

With fewer staff caring for more patients, stresses upon staff and patients increased and safely margins were reduced. Nurses were routinely required to care for 8 or 9 patients (many with complex, transient and extensive medical needs), CNAs, responsible for 10 to 12 and RTs, for12 to 14. Safe and reasonable patient to staff ratios should be roughly half these numbers for patients who require this level of care (and were under the previous management). Staff turnover required a greater reliance upon temporary agency staff, who individually vary considerably in competency and efficiency, and added to safety concerns.

After the announcement of the HCPF policy change, the Vista View management announced that they would no longer accept any new HBU patients under the new reimbursement protocol. In order to keep the SNF Unit filled to capacity, they began admitting patients with funding sources other than Medicaid. These patients have a wide variety of medical needs, often more complex and extensive than HBU patients and some have dementia, are belligerent or violent, or have other psychiatric issues. These conditions further tax the capabilities and resources of the already overworked staff and take them away from their regular responsibilities. There have been several instances when many, and sometimes all, staff on the unit have had to restrain one patient; on occasion, for up to an hour. During these times, the floor is left severely compromised, if not completely unattended. In addition, these patients have a high rate of turnover, adding a greater burden for nurses with frequent admissions and discharges.

Implications of Reduced Reimbursement

Even before the admission of non-HBU patients to the SNF Unit began, the staffing levels were marginally adequate. I can’t envision any scenario in which a facility could provide safe and adequate medical care to ventilator dependent HBU patients with less funding than under restricted cost basis reimbursement. There are no excesses to reduce or eliminate. If an established facility like Vista View, with well trained and experienced staff, isn’t willing or able to provide care to HBU patients with reduced reimbursement, what facility can? Nursing homes aren’t capable and regular hospitals don’t want us.

A handful of patients who have been discharged from here to facilities not oriented toward caring for HBU patients provide a vision of the future under the reduced reimbursement. All of these patients DIED within three months of leaving here. Lower staffing levels, less experienced and knowledgeable staff and the lack of full time RTs all contributed to the deaths.

Even if HBU patients don’t die within months of being transferred to a different facility under reduced reimbursement, our life expectancies and quality of life will definitely be diminished. What will be cut or reduced from existing programs like at Vista View? The only other facilities that are equipped to provide a comparable level of care are fully staffed/equipped regular hospitals. Operational expenses are much higher at hospitals and they aren’t set up for long term residency. That is why and how HBU units like at Vista View were established.

Personal Profile and Conclusions

I was diagnosed with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, at age 34. My wife and I were basking in the joy of the arrival of our second child,, born just five months before. I was steadily progressing in my career as a hydrogeologist at a small engineering and consulting firm in Denver. I had worked as a carpenter before attending graduate school and earning my Master’s degree. I was an endurance athlete and had always been very physically and intellectually active and had boundless energy and stamina.

I worked for another two years until the progression of physical disability forced me to retire. My illness put a tremendous physical and emotional burden on my wife and family as my wife cared for me at home.

In May 2003 a bad chest cold sent me to the emergency room where I conveniently went into respiratory distress with a blocked airway (if it had happened anywhere else, I would have suffocated). The next day I was given the choice of having a tracheostomy and going on a ventilator or doing nothing and likely dying within a week. I chose to stay alive.

In order to qualify for Medicaid and pay for my care, we sold our home, property and material assets, liquidated our savings and investments and my wife and children moved in with her parents. I am now almost completely paralyzed, confined to bed and am on a ventilator full time. The transformation to my current condition has been extremely difficult and I know that few people would be capable of following a similar path. I accept the life that I have now and maintain a positive attitude. I continue writing my life story and thoughts and beliefs that I want to convey to my children. I want to watch them grow up and leave them an enduring legacy of love and strength. I remain confident in my resolve to live for as long as I can keep having a positive impact in the lives of others.

I have fought too long and hard and my family has sacrificed too much for me to let a bureaucratic policy change lead to my final demise. I know what is required for my care. This reduction of Medicaid reimbursement can only lead to a reduction in the quality of care which has already been cut to marginally adequate levels here and now.

ALS is a relatively rare disease with no known cause, treatment or cure. The likelihood that anyone will get, much less, survive as long as I have with, a rare debilitating disease and would require the level of medical care that I receive, is very low. However, there are many things that can happen to anyone that would put them in a similar situation; paralyzed and on a ventilator, if they wanted to continue living. Just consider that YOU are one bad lane change, one infected wound, one mosquito bite (i.e. West Nile virus), or any variety of accidents, diagnoses or infections away from living like me. What will become of other Coloradoans who meet such a fate? Will the State subject them to a de facto death sentence by committing them to an inadequate health care facility? If not that severe, what quality of life will those people have?

I understand the motivations of the state Medicaid administrators to find all reasonable ways to reduce costs during these difficult economic times. I can’t understand how anyone could impose a policy change, regardless of motivation, without a clear understanding of the full financial, logistical and social ramifications. Furthermore, if, in this case, the policy change is made with knowledge of those impacts, I believe that its time to examine the ethical and moral standards that allow a small vulnerable population to be dangerously compromised for the sake of relatively modest cost savings.

Most sincerely,

Ian Pearson

The preceding text has been written using Ez-keys by Words plus, a communication program for people with physical disabilities. I use switch scanning and a piezoelectric sensor switch, mounted on a headband and activated with my eyebrow muscles. This document took roughly 40 hours to write.

Leaving Research

Sometimes people ask me how it is that I could walk away from a career of 20+ years as a scientist, most of them spent investigating amyotrophic lateral sclerosis(ALS; Lou Gehrig's disease). Sometimes I give a trite answer about changing careers a few times in one's life or simply moving on to new things that interest me. These are true answers but not the complete truth.

The crux of the issue was the sadness and futility such as that caused to this family: Man's suicide death to be shown on TV. While this is OK in Europe at this time, this is what Jack Kevorkian went to jail for in the US back in the late 1990's.

Scientific Humor

A good friend of mine sent me this image today. Nature is one of the premiere scientific journals in the world, some would argue the #1 journal in which to publish. It is however based in Europe and not the US. I'm sure that when they placed the advertisement on the back cover, that they had no idea what would be on the front cover.

 

I was not the only one to notice. 

Boobs and more

I've now been blogging regularly over the last 4 years. It's given me an outlet for my half-formed thoughts. It's a place for me to collect random things that interest me around the Internet and to keep track of major events in my life. My life is currently in transition and I find there are so many things that I feel I should not write about, at least not in any meaningful way.

My soon-to-be ex moved out a few weeks ago. He took the cats. I miss them but not getting my eyeball licked (by one of the cats) at 3AM.

I joined an online dating site curious to see what dating at 40 would look like. Wow, has it been illuminating. Went for coffee with someone I met there. It was nice. It was also odd to do this when the paperwork on my divorce has not yet been signed by the judge. Of course I started dating my soon-to-be ex much sooner than this after the end of my first marriage.

It's odd having a house on the market. Each day when I leave I have to make sure that if I get a random call in the afternoon it's ready to show. No personal items anywhere. Not all of the Realtors lock the house up after they have been through. I hate that. Need to add more signs at the doors.

This morning I had a mammogram because I turned 40 this year. This triggered something in the Kaiser system that I now need these each year. I'd had one about 10 years ago at a posh imaging clinic in Cherry Creek - that was all about women, silk robes, hot tea, and comfort. This morning was boobs in a vice with a big guy manhandling said boobs to make decent images. Why does my male primary care physician need a women to come in if he's going to touch my breasts but the male X-ray tech can be with me all alone?

The care in HMO fascinates me. I'm healthy so I don't really mind the Grease Monkey approach to well care. I get that it is all algorithm based. It surprised me that they want to image my breasts (I can check these out) each year but have gone to once every three years on my cervix (pretty much hidden).  I'm sure there is a sound cost/risk reason for this but it seems pretty strange.

And speaking of those nether regions, did you know that you can relate the female orgasm ability to style of walking? Who knew. My friend, who used to be an editor for one of the premiere global science journals, sent me this link today. I'll quote from the link: "The results showed that the appropriately trained sexologists were able to correctly infer vaginal orgasm through watching the way the women walked over 80 percent of the time. " Fascinating. As I am about to go review a set of grants focused on a fatal disease, amyotrophic lateral sclerosis (Lou Gehrig's disease), for federal funding, I can only ponder that someone FUNDED this study. Clearly these researchers have different priorities.

Choose Research

A former lab technician of mine who is now a graduate student in a Department of Biological Sciences sent this to me today.  It may not be meaningful to anyone who has not spent time as an academic scientist but it made me laugh. Sadly there is much truth in this. If the text is hard to read, then click the image and it should open in a new larger format (warning, profanity).

People ask if I regret my career shift which is moving me away from the lab, away from research. Um, no. Never.

Do I still believe that basic biomedical research is the best way to understand and one day cure disease? Absolutely. Does it need to be me doing the work? Not anymore.

Pondering Memory

I sometimes feel like Judith in Clive Barker's Imajica. If you have not read this stunning masterpiece, this reference will be meaningless to you. Judith, at least the first Judith you meet, is a replica, her memories of things beyond about 5 years past are simply missing. For so many things, this is true for me. I simply do not hold on to most memories the way others appear to. If I were a computer, I'd say the memories were compressed and archived somewhere or perhaps the cache was simply cleared. On the upside, my fine brain has great processing speed, uncluttered by older unused memories.

Some learning theorists suggest that there is an advantage to suppressing old material to learn new. Obviously there are advantages to recovering the old information eventually, but sometimes you really do need to forget what you "know" to learn something new.

I'd say it was aging in my case but I've been like this for as long as I can remember. And granted, 5 years is an over-statement, but only barely. I was sitting watching the season 1 episodes of the X-Files today. Skinner made his first appearance. I know he is important. I felt an immediate joy at seeing him. I have/had a huge crush on Skinner but I have no idea why. Yeah, just call me Judith.

Pondering Watson

James Watson, the Nobel Laureate, recently made headlines for his controversial remarks on race. While he is known in the scientific community for his generally controversial and inflammatory nature, he may be remembered for these words and not for his role in the discovery of the structure of DNA: 

A profile quoted him as saying that he's "inherently gloomy about the prospect of Africa" because "all our social policies are based on the fact that their intelligence is the same as ours — whereas all the testing says not really." He said that while he hopes everyone is equal, "people who have to deal with black employees find this is not true."

After apologizing, he did try to clarify his words:

"We do not yet adequately understand the way in which the different environments in the world have selected over time the genes which determine our capacity to do different things," he is quoted as saying. "The overwhelming desire of society today is to assume that equal powers of reason are a universal heritage of humanity."

"It may well be. But simply wanting this to be the case is not enough. This is not science. To question this is not to give in to racism. This is not a discussion about superiority or inferiority, it is about seeking to understand differences, about why some of us are great musicians and others great engineers."

Many scientists and groups hastily distanced themselves from Watson, who has now retired from his position as the Chancellor of the Cold Spring Harbor Laboratory after nearly 40 years of service to the organization.

Similarly, the American Society for Human Genetics, of which I am a member, is preparing a rebuttal of Watson's controversial claims. Their statement, still in draft form, reads,

"The American Society of Human Genetics is committed to scientific integrity, and values the contributions of researchers and clinicians to the advancement of human genetics.

We consider the recent statements attributed to James Watson in the London times to be tragically misguided because there is no scientific evidence for differences in intellectual ability among racial groups.

Our organization promotes accurate reporting and rigorous interpretation of all scientific data to insure benefit to all people."

I started reading Guns, Germs, and Steel: The fates of human societies by Jared Diamond today. So far, it is fascinating reading, a brief history of the world from about 13,000 BC to present. Why did human populations around the globe develop and utilize technologies at different rates? The goal of this work, and I do not yet know the answer, is why some societies became "civilized" while others did not. With Watson's bias on my mind, these two paragraphs of Diamond's really stood out in stark contrast. How differently these two scientists approach the same question, the same set of "facts."

It seems logical to suppose that history's pattern reflects innate differences among people themselves. Of course, we're taught that it's not polite to say so in public. We read of technical studies claiming to demonstrate inborn differences, and we also read rebuttals claiming that those studies suffer from technical flaws. We see in our daily lives that some of the conquered peoples continue to form an underclass, centuries after the conquests or slave imports took place. We're told that this too is to be attributed not to any biological shortcomings but to social disadvantages and limited opportunities.

Nevertheless, we have to wonder. We keep seeing all those glaring, persistent differences in people's status. We're assured that the seemingly transparent biological explanation for the world's inequalities as of AD 1500 is wrong, but we're not told what the correct explanation is. Until we have some convincing, detailed, agreed-upon explanation for the broad pattern of history, most people will continue to suspect that the racist biological explanation is correct after all. That seems to me the strongest argument for writing this book.

I have another 400 pages to go, but I suspect it will be fascinating reading. If nothing else, it will serve as a reminder that perhaps the most important quality a scientist can have is an open mind. 

A note to new investigators

Academic scientists like myself have three major responsibilities: teaching, scholarship (i.e. research), and service to one's discipline. As part of that service component, I review grants for the National Institutes of Health (NIH) through the Center for Scientific Review (CSR) several times a year.

I have a love-hate relationship with this aspect of my career. On the one hand, I get to see the science before it has been done. The ideas to be tested. Innovative new techniques. The potential not yet realized. I love this. On the other hand, most grants (more than 90% in my discipline) will fail. Most very good and even excellent proposals will not be funded. This is depressing. There are very few other funding sources which means that these scientists, especially new scientists, may end up not succeeding in their academic careers. I could write about what this will mean for the quality of higher education in the coming years but I have a different sort of rant in mind today.

This cycle I have several proposals from new investigators. Like everything else, grant writing is a SKILL. You must practice it to become proficient. Graduate education in the US generally provides only a small opportunity (e.g. 1 class with 1 or 2 mock proposals) to develop this expertise. Thus, most new investigators make many mistakes in grantsmanship when they first start submitting proposals. I have a few otherwise interesting proposals in my stack this time from new investigators. However, flaws in grant writing with the current funding environment, mean that it is very likely that these proposals will be seen again by this or another study section.

I will confess that my business education has shortened my attention span. I am looking for explicit, not implicit, explanations. If you think that your proposal may go to me or someone like me then please consider the following:

1. Use the spell check function of your word processor. If you cannot pay attention to this tiny detail why would I trust you with millions of our hard won tax dollars? The answer is, I would not.
2. Tell me explicitly why your work is important. How will your experiments make things better for many of us on the planet, or even a small group of us suffering from your favorite orphan disease?  Given where the funding line is, your work must be important and have "impact." Remember, these are our tax dollars at work. What is the win?
3. Do not ask for 2 years of funding when you are proposing 4 years of work. One criterion that I must assess is feasibility. Is it feasible for you to do 4 years of work with 2 years of funding? That would be no.
4. Do not propose every possible experiment related to your disorder of interest. Yes these are all reasonable things to do but it is unlikely for one person to do all of them within the given grant period.
5. Do not propose to utilize a variety of technically challenging techniques that you have never done before as the basis for your proposal. Again, this is a feasibility issue. Is it feasible for you to develop these techniques within the proposed grant period without having lined up experts to help you with them? That would be NO. If you need a technique that you have not yet mastered, please do identify and get a letter from someone who can assist with the technique.
6. Please do tell me how this proposal will lead to the next proposal. This is related to the win. If all of your experiments succeed as proposed, how will science be different? What new avenues of research will open because of your results? Please do answer the question: and then you will what?
7. If you show me bar graphs and tell me some factor is reduced by 50%, please tell me whether this data has reached statistical or biological significance. I am not impressed by n = 1. Please do share your p values, statistical tests chosen and sample sizes. Did your experiment have sufficient power to detect a difference?
8. Are you using animal or human subjects? Select agents? Have you completed all of the regulatory sections appropriately? Have you justified your sample sizes (see #7)? Are the protections adequate? I will flag your proposal for administrative review if you have not addressed these sections adequately.
9. Can we talk about independence? If you have matured into an independent position but are still sharing space with a former mentor, please address this explicitly. We will talk about it at the meeting. We want you to succeed. We want you to have your own lab and your own office. We want to see letters of support from you mentor or department chair that should you win this proposal that these will be granted to you. A collaboration is great. Indentured servitude is not.
10. How about format? Grant proposals with all of their supporting documents can run more than 100 pages. Furthermore, you can submit up to 10 appendices. I would be very grateful if you did not. We get the proposals on disk & now need to print them ourselves. I do mine at home since it is not a grant appropriate expense for me. If you need to include one or two to prove you have the expertise great, please do, but otherwise, spare my toner cartridge.
11. What about white space? Please oh please do not overwhelm me with half-inch margins and no spaces between paragraphs. Please do break your large paragraphs into smaller ones. Please do include figures or tables or bulleted lists. It's daunting when it is just page after page of the smallest font allowed.
12. I read the shortest grants first. The 150 page documents overwhelm me so I start with the shorter ones. Yes some proposal need all those pages (e.g. clinical trials, epidemiological studies, and multi-PI proposals) but most do not. Less is more. Truly.
13. Letters of collaboration. This may seem obvious but if you say in your proposal that Dr. X is going to do amazing technique Y for you, you need to have a letter from Dr. X that enthusiastically agrees to this. Also, be sure that the letter from Dr. X is current, not from 5 years ago.
14. Laboratory resources. If you tell me that you are going to do amazing technique Z, please have all of the required instrumentation needed for amazing technique Z. At the very least, have it in your budget to purchase it. If the nearest instrumentation is 3 states away, please line up a collaborator with access to that instrumentation.
15. Innovation. This is a tough one. We are asked to review and rank it yet at times this criterion competes with feasibility. It may be innovative but if no one has done this is it feasible? Yes I know this is not fair. Reviewers vary individually as to how they weigh these at times opposing criteria. At the very least, use some state of the art methodology perhaps to a problem that has not yet been approached this way. The creation of new models using old methods is still considered innovative.
16. Acronyms. Please define all of your acronyms at least once. Feeling especially kind? Put all of your abbreviations in a single list somewhere for me to refer to. Making lots of mutants in a gene family, please be kind and make me a table to summarize them all. Even better, add a comment as to why you chose these specific mutants. I am sure you had a reason so please do share it in a clear easy to find way.
17. Expertise. Do not assume that your reviewers are experts in every aspect of your proposal. Perhaps we use the same model system. Perhaps we use the same techniques. Perhaps we study the same pathway using different methods. It is unlikely that we are a 100% match since that would put us in a conflict of interest situation where we needed to recuse ourselves from reviewing your proposal. For example, if your proposal uses both mouse models and in vitro culture assays, one reviewer may have mouse experience, one reviewer may have the in vitro assay experience and a third reviewer may study your same biochemical pathway. Be kind to all of us and put your experiments in context in a general way at least in your specific aims.
18. Resubmissions. These days it is very likely you will end up resubmitting your grant. Our reviews will likely make you angry and upset since we will have missed some points or misunderstood others. However, you need to respond to us when you try again. BE POLITE. I do not care how angry you are, your introduction should begin with something appropriately obsequious like "I would like to thank the reviewers for their astute and insightful comments. I have greatly improved the proposal based on their comments. Reviewer 1 noticed X. Based on his/her comment, I have now revised specific aim 1 to address this concern." Be sure that you somehow mark the changes in the revised document (e.g. thick line down the border, change of font, etc.). You may hate this advice.  But we reviewers spend hours reading your proposal and writing our reviews. We want to help you win your grant. We are trying to share with you, in a polite way, our concerns and recommendations so that should we see your grant again we can improve our enthusiasm (i.e. score). You may think we are idiots just please do not write this into your grant resubmission.
19. Sob stories. Please do not share these. Many of us are in the position where if we do not get our next grant we will not keep our jobs. Do not burden your reviewer with this. We are sorry. This is a hard path and many will not succeed. But, it will not help your score to whine about it. The major exception to this is an act of nature. Baylor flooded a few years back. New Orleans was decimated by Katrina. By all means if your laboratory tools were ruined by acts of nature and your resources lost, please do explain why your productivity is down.
20. Time lines. These are not required but they are incredibly helpful. Please do create some sort of GAANT chart that shows when each specific aim or sub aim will be worked on during the grant period. Often times we are asked to cut 5 year proposals into 4 years proposals and this will help us see what will be lost or whether the proposed request is reasonable.
21. Dependencies. This one is tricky. If you have a 5 year grant with 4 aims, you do not want all of the aims to be dependent on the success of a single aim. That is, do not have the majority of experiments dependent on the success of Aim #1 which is to be completed in year #1. Have a back up plan. Have alternative approaches. Be sure to share these with the reviewers. Be sure to explicitly tell us what the anticipated results are and how you will proceed if the experiment fails - either in outcome or technique. Have related parallel plans.
22. Review criteria. A final reminder. We review you (can you do it?), your institution (do you have everything you need?), your approach (is this the best way to do it?), the significance of your work (do we care?), the innovation of your work (is it shiny?), your budget (is it realistic?) and your compliance with regulatory issues (will you follow the rules?). Together these need to make a strong package. Failure to address any one of them can kill a proposal these days.

Pondering Probiotics

Last year I became intolerant to both wheat and dairy. These were foods that I ate on a daily basis that suddenly caused me acute abdominal pain and nausea with a skin rash developing within 24 to 48 hours, generally on my belly with scaling skin on my hands and scalp. Through food elimination I was able to get rid of the skin symptoms and identify the "causes." The solution has been simple: avoid wheat (and gluten on general principles) and dairy (especially casein).

These symptoms coincided with the development and treatment of an ulcer, most likely caused by too many NSAIDS that I'd been taking for running pain and headaches. After a year of generic prilosec I'm working to wean myself off the medication. Currently I'm pain free taking it every other day.

There are some people who believe that intestinal permeability causes something called "leaky gut syndrome" which may cause food intolerance.

A few days ago I came across an article on Medscape (registration may be required) that used probiotics to ameliorate childhood atopic dermatitis. This was after all conventional treatments had failed. Atopic dermatitis is that itchy skin rash with no immediate known causes, but perhaps can be induced by food allergy.

Importantly, in this study "The children who received Lactobacillus also had a greater reduction in symptom severity over the first 3 weeks of treatment than did those receiving placebo, the authors reported." OK so this is only children, but are there any real risks for adults taking probiotics?

Here was the kicker for me: "Patients with atopic dermatitis seem to have increased intestinal permeability, and this disruption in intestinal barrier function may contribute to the development of atopic dermatitis, according to Dr. Glick. Probiotics have been shown to reverse increased intestinal permeability, and they also modulate the mucosal immune response and decrease inflammation in infants with food allergies, she explained." I have no idea whether this is my problem and whether this natural treatment works in adults. However, probiotics are sold just about everywhere and are not considered drugs.

I bought some Lactobacillus today. I figure I will take it daily for about a month and then perhaps eat a glorius slice of buttered bread or perhaps a decadent piece of pizza and see what happens. The worst case is that I will have immediate abdominal pain followed by a skin rash for a few days. Generally this is not worth it to me, but for the sake of science, why not?

Sometimes my job is not fun

I think that people sometimes think that my job as the acting director of a biomedical research institute is somehow glamorous or exciting. People who know the realities of my job know better.

This week has been long. It started with the 2AM phone call Monday to inform me that the air conditioning in my work was not functioning. We use a local service to walk our building at night to ensure that all of the lab equipment is functioning appropriately. If a -80 C freezer goes down in the night, scientific careers can literally end. So, while we have some equipment on electronic monitors, we also pay to have human beings tour the facility. This week their services have been worth every dime.

In most places loss of an air conditioner would be inconvenient but not a disaster. However, we have some unique genetically engineered mice that model human disorders in our building. It would take years to replace or recreate some of these. Mice can survive cold much more easily than heat. Luckily, the mice survived the temperature spike and the temperature has been stable since then.

Mid-week, I got the same 2AM phone call this time telling me that there was some water on a basement floor & there appeared to be a leak. Luckily this turned out to be a humidifier problem in our ventilation system. Not a lot of water, no damage.

Today's 2 AM call was much more exciting. The walk-through person noticed a small amount of water on a laboratory floor that had damaged some card-board boxes that were stacked there. He could not tell where the water was coming from as the areas under the two nearby sinks looked dry. He could not tell me the room number and given the floor location I feared it was my laboratory. I dragged my husband with me to go see the problem.

We found this (click image for a larger view). Minor I thought, nothing to worry about and not my laboratory. We moved the wet boxes up on the counters & I notified the director of this laboratory so he could assess the damage. Whew. 

But then I decided that we should check upstairs (un-renovated floor) to see where the leak was coming from, since like the security folks, we could not find the source of the leak inside the laboratory. We found water pouring in from the ceiling and pooling in the hallway. I could have cried. Luckily we have many large rolling trash bins and I was able to put these under the major drip locations.

I realized that I needed to check that location (NE corner) in the building on every floor. The worst hit area was our conference room. The other laboratory floors had minimal leakage like the first picture. I think the floor drains on those floors help.

Luckily our facilities folks are on emergency pagers and their cell phone numbers are posted around the building. Within about an hour, a liaison was on site. We discovered that a roof drain had clogged and the pooled roof water was leaking in. The drain was re-opened and the rain had stopped so the flow of new water into the facility also  stopped. By the time I left a company that remediates water damage was on its way. My husband and I got home just as the sun was rising.

I just got a call from another scientist that the remediation was on-going (fans & dehumidifiers everywhere) and there did not seem to be any major areas of concern or damage. We got lucky.