Monthly Archives: October 2012

Mastering the Art of Gametocyte Induction

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Everything seems harder the first time you do it. 

If you’ve made bread, or, for you scientists, designed PCR primers, think about the first time you did it. On the face of it these processes are simple, and share the same formula; you have a recipe, you follow it, you get the desired product. End of story. Yet, acquiring new skills often doesn’t feel simple.

I usually have some apprehension the very first time I try something – will the bread really rise like it’s supposed to? – and experience relief, satisfaction, and the sense that I’ve experienced some small miracle when ingredients have been turned into a loaf of bread, bands on a gel, etc. But the magic wears off. Later, looking back, it’s hard to remember what the big deal was.

So what makes learning new skills seem difficult?

At least two things – feel free to add more:

1) How intrinsically hard it is. Let’s face it, some things are just hard (e.g. requiring many steps, background knowledge, complex movements – see “expertise“, etc).  This is related to the learning curve, or the difficulty of the new skill. Not much skill necessary to boil an egg, and quite a bit to design working PCR primers. For simpler skills, learning happens in huge leaps early on, followed by smaller gains as there is less left to know, whereas for harder tasks the climb up the curve is just one long slow haul.

2) Level of familiarity, i.e. transferrable skills. If you apply previous experiences new skills seem much easier: PCR aids learning quantitative PCR. And, we actually do get better and faster with practice; this looks a lot like improving efficiency along an experience curve to me.

Right now I’m learning how to grow Plasmodium falciparum parasites in culture.

I’ve been told this is really straightforward, and the basic steps for growing an asexual culture seem to be – plus they are relatively hardy little buggers. But I’m interested in the life stage that can infect mosquitoes – the gametocytes. These are the sexual stage, the prima donna parasites, finicky about temperature changes, whether they get human or animal sera, fresh or less-than fresh RBCs, you name it. Unfortunately, even the people that do this for a living have told me gametocyte induction is really hard.

Why?  Well, as best I can tell it’s a combination of slightly technical challenges (sneeze in your culture and it’s all over), and the need for experience to know exactly when to do each step. The parasites are only convinced to become gametocytes by being stressed. Without stress, the asexuals would happily keep on growing, and might never make any gametocytes. In practice, this means that after I get the parasites growing I’m then stressing them to the point where some inevitably die, more have a near-death experience, but not stressing them so much that the whole flask of parasites kicks the bucket. (I find the parasites aren’t the only ones a little stressed by this particular step). Afterwards I make every effort to placate them with a cushy environment, the freshest red blood cells available, and try to make amends (all while selectively killing the other non-gametocyte-producing stages with heparin). After several days only gametocytes are in the culture. This is way more involved than any bread I’ve ever baked.

Feeling about as comfortable as Julia at a too-small stove...

But, as Julia Child said, “Anyone can cook in the French manner anywhere, with the right instruction” (Mastering the Art of French Cooking, introduction). [Translation – “Even Jessi can learn gametocyte induction techniques with the right instruction”].  And fortunately I have the written instruction of many other scientists that have tried this. Much more importantly I have the expert instruction of the members of the Cui lab. In particular, Feng’s advice and patient explanations continue to be invaluable in this process.

Having mentorship in learning complex techniques is vital, and nothing beats actually seeing the process through when first figuring it out. It has allowed me to jump along the experience curve to become more efficient much faster than I ever would have been able to without this type of help. With luck, and enough observation and practice, I’ll be bringing this skill to the Read/Thomas group sometime soon. I’m planning to use the same equipment and tools since familiarity makes the learning process easier, and reduces room for errors due to picking the wrong types of flasks and so on.

When an expert isn’t available there are often alternatives – perhaps this explains in part the popularity of cooking shows, or youtube instructional videos. Scientists are cluing into this – just check out the Journal of Visualized Experiments.

This week my parasites are on their way to becoming beautiful gametocytes. In fact, the precocious ones made their appearance this afternoon! They should continue to develop, barring any hurricane-related interruptions to their care. I’ll keep you posted.

How do we balance respect for individual privacy with the demands of epidemiological research?

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Human disease epidemiologists love Scandinavian countries. Not only are they delightful sites for conferences (side trip to Norway’s fjords, anyone?), they also maintain fanatically detailed health records for their citizens that they are more than willing to share with scientists. These datasets offer amazing opportunities for disease modeling and allow breakthroughs that simply wouldn’t be possible with less complete data. It’s much harder to do this type of work in the US. Our health records are incomplete, noncentralized and difficult to access. And when datasets are identified that do offer opportunities to bypass these problems (Guthrie cards, for instance), legal maneuvering by privacy advocates can make meaningful studies untenable.

As a researcher, I am awed by the potential of detailed personal health data to revolutionize disease management. We’re now able to track influenza outbreaks by analyzing Twitter streams; imagine what we could do with unrestricted access to Guthrie cards, computerized health records, network data from Facebook, GPS data from cell phones? But I also understand the perspective of the private citizen, who may or may not be informed about his data are being used, and who may be subject to increased insurance premiums, job discrimination or public shunning if these data are not properly handled.

Very few people would feel that private testing of infants for easily treatable genetic disorders is a bad thing. Likewise, very few would be comfortable with full public disclosure of all genetic data, health records and spatial information. But there is a huge gray area in between these two extremes that would respect individual privacy while allowing research to move forward. Public outreach and education, opt-in vs. opt-out programs and a firm commitment to privacy and transparency will increase public trust and facilitate scientific inquiry, but will this be enough? What kinds of safeguards and incentives do you think will be necessary to public health research forward in the US?

Success or failure?

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Lauren asserted at a lab meeting a few weeks back that we (Matt and I) don’t talk enough about our failures. What was she thinking? Of course we don’t. We’re blokes. But three times, NIH refused to fund Lauren’s work, even though her idea is excellent, her preliminary data good, her track record excellent, and Matt and I threw our best grantsmanship at the problem. We fund her work anyway, and Lauren now has some great results. Hopefully, a story of success despite the system. But Lauren’s point was that as mentors, we need to equip our people with the right expectations.

It turned out Matt and I had no idea what rejection rates to train people to expect. The national statistics are not much help because many people write bad grants. What you want are the numbers for people who are competitive. Matt and I had no idea how well even we were doing, so we dug up the data for a subsequent lab meeting. The numbers dropped out like this.

We submitted our first US grant in May 2008. Forty two (yes, 42) grant applications later, our success rate per application is 48%. This includes grants we did together, as well as our individual efforts, or grants one of us did with other collaborators. If we break it down by project, and ask what proportion of projects we eventually got funded, the rate is 78%. That includes things we flogged away at repeatedly (worst cases: success on the seventh go, success on the fourth attempt). The proportion of grants that got funded first time was 31%. The proportion of eventually-funded grants that got funded first time was 63%. We abandoned only two of the submitted proposals as having no future or being too low priority. The remaining 95% of applications led to external funding eventually or we continue to fund them internally because we believe in them. Total cash raised? Somewhere between $27-$28 million, of which the share coming to Penn State is about $11 million.

Is that a record of success or failure? Hard to say. We now have a large well-funded group filled with smart people I like a lot. That feels good.

From the expectations point of view, there seem to be three lessons.  First, even senior people with much experience get rejected a lot. In this game, you need to develop the ability to absorb rejection. Second, raising money requires huge effort. A Gates Grand Challenge Exploration grant takes just a few days to put together if you know what you want to do. An NIH R01 application, especially one with complex partnerships, might take 6-8 weeks to put together the first time, but only once it is clear in your head. An R01 re-submission takes perhaps 1-2 weeks if it was in good shape the first time round. Putting all that together, Matt and I estimate that over the last four years, we have each spent at least a day a week raising money.

The third important lesson I realized only after the lab meeting. According to the post-docs I talked with, the most sobering insight was prompted by Matt’s comment that the whole process never stops. And it doesn’t. It is professional combat sport: highly competitive and very bruising if you do not have the right mindset. But in sport, it’s unusual to compete at the highest level for more than a decade. In science, winning means you get the chance to keep competing with the world’s best — for thirty years or more.

Science on the Hill: How science can work with policy-makers

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Recently, a member of the House of Representaives Committee on Science, Space, and Technology made comments suggesting that human females could control internal fertilization (clip). Italian courts don’t seem to understand how to interpret a P-value. (see Katey’s post ). Politicians continue to fight about whether global climate is changing, instead of making policy decisions about whether we need to do anything about it.

There seems to be a general lack of understanding about the facts science produces, the processes by which scientists arrive at those facts, and what role science should play in policy. I find this trend deeply troubling. Scientists have clearly failed to communicate how we conduct science,  the methods we use to interpret results and the distinction between facts and opinions (interpretations of what our results mean) to policy makers. Attempting to bridge this disconnect seems impossible to me.

I have reached a place of complete frustration and think the situation might very well be hopeless. Clearly, I’m going to need help understanding the other point of view. I need to have a civil conversation with a Washington insider. I happen to know one and I think we can keep it civil. I actually love him. He is my dad after all.

Left, My father and I agree on many things. Surely we can have a reasonable conversation about a "real" issue. Right, Me at my father's desk assessing policy briefs circa 1984. Clearly, I've already had enough!

My father, Tom Cator, has worked on “on The Hill” for the last 36 years. He began as a staffer for the U.S Senate and for the last 30 years has worked as a lobbyist across a broad array of industries. We had a fairly long conversation about science on the hill this week. Here are the key points that we discussed.

“Follow the money.” Money is part of the reason that policy makers often will argue or ignore facts. For example, if most of your state’s income is dependent on oil and gas, you are not going to go on the record agreeing these industries have contributed to global warming. “Politicians often don’t come in with an open mind. Their view is often based on who paid for it and what constituents think.”

“They will try to take you down”. I posed a question, “So say a group of scientists descended on The Hill. We went door to door and we offered to answer scientific questions”.

My father responded to this with a slight sense of panic in his voice, as if he was imaging me running through the Rayburn Building with a mosquito net, “That won’t work. First, they won’t have questions for you. Presentations have to be timely, or appear timely, in a political context. Second, if your facts don’t support their agenda, they may go after you personally, attempt to impugn your credibility. They will find someone to poke holes in your research.”

“Everyone has an agenda.” This was troubling. Facts are facts. Science is objective. You can’t just poke holes in research unless there are actual weaknesses. Why don’t politicians understand that? My father continued to explain that many times politicians think scientists are playing political games. “If you came to me with data, I would want to know what your agenda is”.
I countered, “Facts don’t have an agenda.”
Do they? Well, sometimes.
Over the last twenty years, there has also been a noticeable increase in “think tanks”  in Washington. This term is broadly applied to many organizations, but some of the largest are privately funded entities. Many times politicians get their research from these sources. “Think tanks have to pay salaries and rent. It’s a business. Where do you think they get their money? Industry, organized labor, wealthy individuals, interest groups, and others.” my father points out.

“It is bleak and getting bleaker.” Over his career, Tom has noticed a disturbing shift in how business gets done in Washington. “It used to be that congressmen would get facts from lobbyists. A good lobbyist would approach a legislator with their case, represent all of the facts and facets of the issue, and then would explain why their policy position had merit. If an issue like climate change had come up 20 years ago there would have been multiple hearings with recognized experts. There would have been a long discussion about the facts. There is no longer a comprehensive look at the issue.”

There has also been a shift in how legislators define compromise. “It used to be you would find points on which you could agree and disagree and meet in the middle. Now, compromise tends to be ‘I don’t budge and you meet me here’.” This change in attitude has made debate, whether scientific, legal, or moral, stagnant.

“Nothing moves quickly”. “Policy does not change quickly. Within the next decade, Medicare is going to go bankrupt. They aren’t doing anything about that. You think they are going to jump on something like climate change? There is little effort to look at long term trends and how policy should respond. Statesmanship is needed.”

Acceptance of scientific findings is also very slow. “The system is rigged to not let real science percolate up, at least not in the short term”. We agreed that this was not necessarily a bad thing. Scientific debate and discovery moves very quickly. When we make policy decisions, we need to be very certain that the scientific debate is satisfactorily over.

“Strike back” At this point in the conversation I was not feeling particularly hopeful. How do we motivate these congressmen to listen and get something done?
“There has been a failure of science to address this issue.”

Politicians are in Washington to represent their constituents. If voters in their district care about something, then congressmen will care. “Getting the public, voters, and community leaders involved makes it much harder for a politician to walk away from facts”.

And then Tom got real personal.

“The academic community has fallen down. They don’t try to involve the public or policy makers. You live in a politically conservative county in Pennsylvania. What are you doing to educate your public on science?”

Caught off guard, I mumbled something about public lecture series.

“You can’t do it from 9 am-5pm. People work. What about continuing education at night? How about explaining how climate change is and will impact the farming industry in central PA?”.

I quipped back, “I don’t see how I can talk to people who don’t want to hear what I have to say”.

My father responded, “Find a reason for people to come and make it convenient for them. Go to a local high school science teacher and have her tell students, ‘Come to this thing tonight and you get extra credit, bring your parents and we will double it.’ Then present facts carefully and be as scrupulous as possible. Present work that has been rigorously peer-reviewed, and is complete and unbiased. Maintain objectivity and project a service. Engage them in a discussion.”

I do not feel anymore empathy for Washington, but I think this conversation did get my wheels turning. I have been going at this the wrong way. Changing the way science is viewed on The Hill needs to come from the ground up and it can start here with us. “The issue here is that we need to inspire constituents to become informed about science and communicate with their representatives.”

What if experts from CIDD gave an evening seminar series at State (or Altoona or Bald Eagle) High? What would the challenges be? Would scientists participate? Would anyone come? What topics could we cover? I have no idea how to answer these questions, but perhaps I should be thinking about them.

Tips, tricks and fixes from your favorite admin

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Hola!

My second blog (my manstand-blog is banned permanently…) is to provide solutions to some common blogging problems. This means that this post will be updated regularly, to include to latest information that should hopefully solve your blogging problems… if your (blogging) problem is not described below, do email me!

Post-title not linking to post-page and ‘Leave a reply’ not working Katey noticed it was not possible to leave a comment on Eleanore’s blog. Me thinks the problem is that Eleanore changed her blog title after publishing the post (or saved a draft version without a title). WordPress works with ‘slugs’, a few words that describe a post or a page (if you look at the url of this page, you’ll see that the slug for this post is ‘tips-tricks-and-fixes-from-your-favorite-admin’). It will use your first saved title (or generate a number if there is no title). If you make changes to your title, the slug wil not update automatically. So … you have to manually update it in one of the boxes in the ‘edit post’ screen. You cannot use commas, quotes, apostrophes, and other non-HTML favorable characters. They need to be changed and a dash is put between each word. If you don’t see the slug-area, click on the ‘Screen options‘ (upper right corner) and make sure to select ‘slug’.

I tried to solve this issue with a bit of extra coding, but Andrew’s website completely disappeared from the world-wide-web (no worries Andrew, for a few minutes only).

I am sure there will be more issues to deal with soon. But great job so far bloggers! The website is still working 😉

Fact-Checking and Science Journalism

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If you’ve been paying attention to the United States Presidential elections, you’re probably quite familiar with the term “fact-checking”; that is, the verification of the statements and claims made by candidates. Why don’t we see more fact-checking in science? The general public seems to quickly latch on to “facts” that have been “proven” by scientific studies and then reported (and possibly mangled) by mainstream media. Is the population’s lack of skepticism and critical thinking because of our less-than-stellar STEM education? Is it because somehow, the letters attached to the end of your name are directly proportional to the amount of trust invested by the general public?

I believe it is an intertwined combination of all of the above, in addition to the fact that there is a disconnect in the pipeline from manuscript to media; and the adage “if it bleeds, it leads” holds true in the case of the ongoing controversy of Monsanto GMO corn and rats developing rather nasty cancerous tumors.

In this study, researchers claim (we’re grasping at straws here) that GM corn is a causative agent of cancer in the rats. The blogosphere ignited. Here you can have a glance at the ever-so-reputable blog “Natural News” and their handle on the study, using heavy hyperbole, and citing the Daily Mail as a source. This angered me — even when I managed to push aside the fact that naturalnews.com usually nauseates me — not only because they were incorrectly interpreting the study, but because the writing was laden with self-righteousness, and reeked of “we’re right, you’re wrong, hahahahaha”.

In a frantic attempt to get a fix of rational thinking and skepticism, I found this post by Discovery News journalist Emily Sohn. Her description of the study itself and its flaws (and why they are flaws) is incredibly succinct and, although wordier than the average blog post, easily understood by educated Americans in and outside of science. This type of pop science journalism, disseminated by major media outlets, is a necessity in bridging the gap between researchers and the general public — and the responsibility rests upon both the scientists and the journalists to clearly and truthfully communicate information.

There is no perfect solution to fact-checking mainstream media reporting science. Scientists, by nature, will always be cautious of implying direct links and causation. Journalists will always sniff out the bleeding lead. However, ethical and explicit reporting of results, and encouragement of writers such as Ms. Sohn, will keep the media from repeating this incredibly fantastic template ad nauseum.

Quality control

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Delicious looking health care (photo from Wikimedia Commons).

At CIDD lunch this week, we discussed this paper by Kumar et al (2005). It’s a compilation of data from randomized clinical trials of cancer treatments in children conducted between 1955 and 1997, and it shows that on average, new treatments are no better or worse than standard care.

Although scientists are not getting better at producing more effective treatments in comparison to standard care, the overall survival rate for children with cancer has been increasing since the 1950s, which suggests that standard care has changed for the better. During the CIDD lunch, someone referred to this improvement as “moving the goal posts” for cancer treatments. In my mind, this raises the question of how standard is standard care at any given time, for any given doctor, in any given hospital?

At the end of the discussion, Andrew touched on one of the problems with standard care, which is that ineffectual or even detrimental treatment regimes can become common because of misplaced confidence in anecdotal observation. An op-ed published last August in the New York Times suggested that the solution to this problem is to throw money at it – and of course, medical researchers to spend the money. More specifically, take some small fraction of health care spending and put it towards testing current treatments.

Yet even if all treatments were well supported by data, the widespread and timely implementation of best practices is not assured, as it is a long and leaky pipeline from the NEJM or the Lancet to your general practitioner’s office. Dr. Atul Gawande wrote about this problem in the New Yorker, also published this past August. As an example of the inconsistency in standard practices, Dr. Gawande wrote about his mother’s knee replacement and the extensive variation between surgeons in all aspects of the procedures, from anesthesia to physical therapy. A solution to this problem, according to Dr. Gawande, is strict and centralized quality control, just like in the Cheesecake Factory and other chain restaurants.

Which brings me to my final question: how important is standard care? For double blind, randomized clinical trials (i.e. science) it’s quite important to know that your control group is being treated consistently but for patient care (i.e. medicine), I can see some benefits, as well as costs, from multiple approaches.

NB: My experience with health care has been largely within the U.S., which certainly colors my perspectives.

Scientists to be jailed for failing to predict earthquake

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Yesterday, seven Italian scientists were convicted of manslaughter and sentenced to six years in jail for, as many headlines asserted, failing to predict an earthquake that killed just over 300 people in L’Aquila, Italy in April 2009.

The formal details of the case are a bit more nuanced than the sound bites suggest, but that ultimate outcome is still disturbing, as a scientist. An “unidentified woman on Sky television” thought it was “just a tiny bit of justice so that it doesn’t happen again” (NY Times). I found it upsetting, that individuals would feel comforted by dumping the burden of the deaths of hundreds of people on someone for not pinpointing a natural disaster, and ridiculous that they would think this would somehow get negligent scientists back on their game. What do people think that scientists can/should do?

These scientists populated the country’s National Commission for the Forecast and Prevention of Major Risks. Given that the scientific consensus on the possibility of earthquake prediction seems to be something like “certainly not within a timeframe very useful for informing short term evacuations,” what did these scientists say they could do?

There are many interesting discussion points surrounding this case, beyond just the fundamental, scientific question about the extent to which different aspects of the world and life are predictable; my mind swirls with them. But I guess I’ll ask this mini-blogosphere directly if you think that this conclusion is a worrying precedent? Do you think it is likely to help or hurt more people, and, if so, how?

Other articles: 1, 2

Tussey Mountainback 2012

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The Read Group and the Thomas Lab are normally one coherent functioning team. Last Sunday however, all coherence was thrown out of the window during the Tussey Mountainback 50 mile relay race. Fierce between-group and even some within-group (depending on the genotype) competition broke loose. I regret to say the Read Group did not come out athletically the strongest. Despite this however, we had a great time on this beautiful sunny autumn day.
junior vs senior scientist

junior vs senior scientist

Why is cancer so hard to eradicate?

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Many infectious diseases can be completely cured—that is, totally eradicated from an individual—even when the parasite responsible has spread throughout the body, but when cancer has spread throughout the body, eradication is a dim hope. People often cite the similarities between cancerous and normal cells as a reason the disease is so difficult to treat, and that is certainly a problem, but I think the ecology of cancer is also fundamentally different from that of invading pathogens.

As Sandy Liebhold brought up in a recent talk, sometimes the ecology of a pest can assist in eradication efforts. Most organisms are subject to Allee effects, meaning that population growth is stunted when only small numbers of organisms are around. Animals that hunt in packs struggle to survive when there are too few organisms to form packs; sexual organisms fail to produce offspring when numbers are so low that finding mates is difficult. These Allee effects help populations on their way to extinction.

Parasites have to contend with Allee effects just like other organisms. Recent work suggests that malaria parasites have to face Allee effects in the form of early, non-specific immune measures. These immune measures appear to be overwhelmed when large numbers of parasites are injected into mice, but small numbers of parasites have a hard time of it. To use drugs to cure a patient of malaria, it is not necessary to kill every last parasite—just to kill enough parasites that immunity can mop up the rest. Cancer cells may not face the same limitations. As cells derived from the host, they are not likely to be vulnerable to non-specific immune measures. Small numbers of cancer cells might even do better, as they face less competition from other cancer cells and may fly under the radar of specific immune measures, which may tend to scale up with numbers. Therefore we may not be able to count on much help from the within-host ecology when we attempt to eradicate cancer from a person.

The situation is not hopeless—sometimes pests spread so far that eradication is deemed impractical. Aside from the economic limitations, it may be that the amount of chemical warfare required to eliminate the pest would decimate the ecosystem just as surely as the pest population would if it were allowed to grow out of control. People instead turn to monitoring the pest populations and treating so as to keep pest damage below a certain level. These ideas form the basis for adaptive therapy of cancer, which attempts to keep metastasized cancer at manageable levels instead of eradicating it altogether. Eradication may not be necessary to maintain individual patient health—managing the problem with a solid understanding of the ecology could be good enough.

A proposition for recognition by the Olympic Movement

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A lady with hair suspiciously like mine, running

Science should be recognized as a sport.

The parallels are undeniable. I accept that ‘The Loneliness of the Long-Haul Lab Worker’ doesn’t quite have the same ring to it but the repetition; the solitary hours spent at the bench or before the screen; all motivated by one goal – surely not unlike weights workouts; miles pounded.

This isn’t an original thought by any means, indeed it doesn’t take much to realize that members of the two fields are united by similar personality traits. Yesterday, Becky joked that scientists could be contained under the ‘masochist’ umbrella. Isn’t this also a term regularly applied to athletes and what our friends will say when we line up on Sunday to run fifty miles of hilly road at the Tussey MountainbackTM? What unites these activities is the quest for highs – unchartered ground, the answer, the win.

Of course with massive highs come lows. The first time I ran an experiment to test a novel ecologically-rooted theory of drug resistance management, all the signs of success were there. Yet, after analysis, the results revealed only failure. Blame fell on ‘Stochasticity’, scientists’ chance. But this morning, I sat down with ‘Coach’ (alright, the metaphor’s gone too far but did I just find a sufficiently annoying nickname for Andrew?!) after round two and showed him that this time we’d performed, the work had paid off.

There was a long silence.

“Blimey”, he said.

Gold.

The point of it.

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The mentoring issue Matt Thomas and I worry about most is writing. To produce papers that have impact, and to be successful in the brutal competition that is the modern grant system — in other words, to have a career in science — you just have to be able to communicate effectively. No matter how brilliant you are, no matter how fantastic your data or how earth-shattering your new idea, if you can’t sell it, you might as well not exist.

Yet good writing is one of the hardest skills to acquire. It is relatively straight forward to learn the latest lab techniques, and even statistics, reasoning, experimental design and knowledge of the literature. It’s even relatively easy to have good ideas. But writing well is hard. I have a theory that’s because scientists don’t practice telling stories, so when it comes time to write, they have no natural narrative or rhetorical skills. Rightly focussed on trying to get the science correct, trainee scientists can not tell the story in an elegant or simple way.

I think it helps to practice writing in a context which does not define a career. Hence this blog. My hope is that freed of the necessary discipline of writing a scientific paper, our people can practice engaging writing. A good thing about this blog is the potential audience: my mum, others in the group, academic colleagues, competitors – and future employers. Hopefully, the challenge of that diversity will enforce a professional discipline but also allow a bit of individualized spirit. It’s an experiment. Let’s see.

Meanwhile, here we all are on my 50th Birthday in September. Courtney was on holiday. Penny is on computer from England. Apart from Matt, a good looking bunch I reckon. Certainly a lot of brain power and energy. And for the PSU police, those bottles of bubbly on the table are non-alcoholic.