Scientists say "sloppy science" more serious than fraud

An article on Nature: INDEX reports on a recent survey of scientists: Cutting corners a bigger problem than research fraud. The subtitle says it all: Scientists are more concerned about the impact of sloppy science than outright scientific fraud.

The survey was published on BioMed Central.

How to read the scientific literature?

Science addressed the problem of How to (seriously) read a scientific paper by asking a group of Ph.D. students, post-docs, and scientists how they read the scientific literature. None of the answers will surprise you. The general theme is that you read the abstract to see if the work is relevant then skim the figures and the conclusions before buckling down to slog through the entire paper.

None of the respondents address the most serious problems such as trying to figure out what the researchers actually did while not having a clue how they did it. Nor do they address the serious issue of misleading conclusions and faulty logic.

I asked on Facebook whether we could teach undergraduates to read the primary scientific literature. I'm skeptical since I believe it takes a great deal of experience to be able to profitably read recent scientific papers and it takes a great deal of knowledge of fundamental concepts and principles. We know from experience that many professional scientists can be taken in by papers that are published in the scientific literature. Arseniclife is one example and the ENCODE papers published in September 2012 are another. If professional scientists can be fooled, how are we going to teach undergraduates to be skeptical?

Model organisms and translational research

Ewan Birney (Genomic's Big Talker of ENCODE notoriety) has a new post called In defence of model organisms.

He brings up two points that are worth discussing.

What is a model organism?

There are two common definitions. Birney leans toward defining a model organism as one that models human biochemistry and physiology. This is a common definition. It emphasizes the meaning of "model" as "model of something."

Here's why Alain Beaudet, President of the Canadian Institutes of Health Research, should resign

The Canadian Institutes of Health Research (CIHR) is the main source of research funding for Canadian health researchers, including those doing basic research like most of the researchers in my biochemistry department.

A few years ago, CIHR decided to revamp the process of applying for and obtaining research grants. They did this without taking into consideration the wishes of most applicants. (They did "consult," but consulting isn't the same as listening.)

The result has been a disaster. Most researchers are confused and discouraged by the new process and there's great fear that the results of the next competitions will be harmful to basic research and harmful to new investigators.

But even before the new rules came into play the funding of basic, curiosity-motivated, science was taking a major hit. Many mid-career basic researchers at the University of Toronto have lost their grants or are struggling to make do with a lot less money. This is partly due to a lack of money in the system but it's been exacerbated by a deliberate shift in priorities under the previous Conservative government of former Prime Minister Stephen Harper.

These are some of the reasons why Canadian researchers have been calling for Alain Beuadet to resign [Support basic research with new leaders at the Canadian Institutes of Health Research (CIHR)].

Support basic research with new leaders at the Canadian Institutes of Health Research (CIHR)

An important article in the Ottawa Citizen calls for the resignation of Alain Beaudet, recently reappointed President of the Canadian Institutes of Health Research (CIHR) ['Demoralized' scientists demand changes at $1B health research agency]. Criticism comes from Michael Rudnicki but he is merely voicing what lots of other researchers feel.

“He has rammed through what he calls reforms which have radically altered the grant delivery system and the system for evaluating grants has been done in a way that distorts the entire process,” said Rudnicki of changes brought in by Beaudet.

Top research scientists from across the country, in interviews with the Citizen, described their mood as demoralized and deeply disturbed by what has been going on at the CIHR. “There is a lot of scorched earth out there,” said one.

According to researchers, the malaise cannot be fixed by simply unmuzzling government scientists. The federal government needs to support basic scientific research, they say, with more money and with a system that is transparent and designed to reward the country’s best and brightest researchers. Instead, researchers say, a series of recent changes at the agency that funds a billion dollars of research each year, notably to the peer review system, have done the opposite.

“The entire research community is very upset and extremely concerned about these changes,” said Rudnicki.

Among concerns are that basic research is getting an ever-smaller share of flatlined funding, in favour of applied or targeted research. Some independent scientists working in labs — doing the kind of work that has led to discoveries such as stem cells — are finding it increasingly difficult to keep going.

The President of CIHR is essentially a government appointee and he or she is not beholding to the researchers (clients) in any legal way. However, I have long advocated that the leadership of CIHR, and the other government funding agencies, should deserve the confidence of the Canadian Research Community and they should resign if they do not have that confidence.

That time has come. Not only has CIHR discouraged basic curiosity-motivated research but the effect of their policies has encouraged university administrators to do the same. We see more and more university resources going into directed research on specific applied targets and the few remaining basic researchers are treated as second class citizens left in the oldest, out-dated, facilities with the fewest university resources.

I will gladly sign any petition calling for the resignation of the CIHR leaders and anyone else who supports their disastrous policies.

---

Muzzled and mad Canadian scientists

---

Canadian Institutes of Health Research (CIHR) Strategic Plan

 
The Canadian Institutes of Health Research (CIHR) provides most of the funding for health-related research, including most of the basic research that goes on in Canadian Medical Schools. CIHR has recently issued a draft strategic plan that will guide its priorities in the future. The strategic plan is based on the Government of Canada's Science & Technology Strategy: Mobilizing Science and Technology to Canada's Advantage. This is a plan developed by the current Conservative government. It is based on the premise that research should be directed toward specific goals; namely, the health of Canadian citizens and the profitability of Canadian companies.

Clearly, the governing body of CIHR feels obligated to carry out the wishes of the current government in developing a long-range plan. On the surface it seems logical that a government agency should be doing what the government orders. However, there are two problems with this logic: (1) the strategy goes against the wishes of most Canadian scientists, and (2) governments change but strategic decisions are difficult to reverse.

This is the biggest problem. Government funding agencies should be advising the government, not vice versa. Government funding agencies should have an "arms length" relationship to the government of the day. Scientists should have more input.

My colleague, Tania Watts, is the current President of the Canadian Society for Immunology. She has written a letter to Alain Beaudet. the President of CIHR in which she defends basic research [see CSI Response to CIHR Stategic Plan]. Tania's letter makes a lot of sense.

---

What Happened to 30 Biochemistry Graduate Students at Yale?

 
In 1991 there were 30 young people beginning graduate school in the Molecular Biophysics and Biochemistry Progam at Yale University. Where are they now? How many have tenure at a university? The answer might surprise you. Read about the fate of these students in this week's issue of Science [And Then There Was One].

Looking at my own department, there are about 10 Ph.D.'s from a similar cohort and four of them have academic positions in 2008.

---

[Hat Tip: Chance and Necsssity]

Big Ideas: Saturday September 29, 2007

 
Every weekend TV Ontario broadcasts talks given by prominent thinkers at lectures given in Toronto. The broadcasts are at 4pm Saturday, repeated at 4pm on Sunday. You can also watch them on the Big Ideas website. The host, Andrew Moodie (photo below), often has insightful comments so it's better to watch the actual TV broadcast than the website video presentations. While Moodie is good, he's not as good as the previous host, Irshad Manji, in my opinion.

Today's lecturers will be of interest to Sandwalk readers. University of Toronto students will be familiar with Sue Varmuza.

Mark Abrahams
Marc Abrahams, editor of The Annals of Improbable Research and one of the organizers of the annual Ig-Nobel Prize ceremonies at Harvard University, discusses the work of scientists and academics that, "first makes you laugh, and then makes you think". Highlights of the lecture include discussions of a study that proves that Kansas is flatter than a pancake and a paper investigating The Forces Required to Drag Sheep Over Various Surfaces.

Sue Varmuza
The second lecture in this episode of Big Ideas is by University of Toronto Zoology researcher Susannah Varmuza who discusses the evolving field of Epigenetics and what research into such things as mouse coat colour is telling scientists about the age-old "nature versus nurture" debate.

Here's the link: Susannah Varmusa.

Is There a Correct Way to Do Science?

 
I think there are incorrect ways of doing science and I think that much of today's scientific literature is an example of bad science. This isn't news. Back in 1963 Peter Medawar felt the same way and he expressed this viewpoint on a BBC radio show. The transcript, Is the scientific paper a fraud, is published in Medawar's collection of essays called "The Strange Case of the Spotted Mice" (Medawar, 1996). (The title of the book refers to a scientific fraud in immunology that Medawar uncovered in the early 1970's.)

Medawar says,

... the scientific paper may be a fraud because it misrepresents the processes of thought that accompanied or gave rise to the work that is described in the paper.

Janet Stemwedel discuses this paper on her blog Adventures in Ethics and Science [Why does Medawar hate the scientific paper?]. Janet uses the paper as a way of introducing some key concepts in epistemology—loosely defined as "the investigation of the origin, nature, methods, and limits of knowldege." (Burr and Goldinger, 1980). Read Janet's blog and the comments in order to see this perspective.

I want to take the discussion in another direction. Medawar's complaint is that the scientific paper distorts the real process of science by misrepresenting the steps that are actually followed in a scientific investigation. In particular, the typical paper suggests that induction is the main mechanism of scientific discovery. Here's how Medawar describes the naive scientific method,

What induction implies in its cruder form is roughly speaking this: scientific discovery, or the formulation of scientific theory, starts with the unvarnished and unembroidered evidence of the senses. It starts with simple observation—simple, unbiased, unprejudiced, naïve, or innocent observation—and out of this sensory evidence, embroidered in the form of simple propositions or declarations of fact, generalizations will grow up and take shape, almost as if some process of crystallization or condensation were taking place. Out of a disorderly array of facts, an orderly theory, an orderly general statement, will somehow emerge.

Now, nobody has ever accused Peter Medawar of being stupid so before you start to quibble about this sort of generalization, be aware that Medawar does not apply it to all of science and every scientific paper. He's talking about common, but not exclusive, practice.

One of the reasons why pure inductive reasoning is misleading is because we never start an investigation with a clean slate.

... the starting point of induction, naïve observation, innocent observation, is a mere philosophic fiction. There is no such thing as unprejudiced observation. Every act of observation we make is biased. What we see or otherwise sense is a function of what we have seen or sensed n the past.

This seems like something that's so obvious that it hardly deserves mentioning. But it does deserve mentioning. Medawar was right to have brought it out into the open and it's something we always need to keep in mind.

Now we get to a famous quotation from Medawar's talk. Janet Stemwedel discusses it in the context of Popper and falsification—conveniently ignoring Kuhn, who is far more relevant—but I want to use it to talk about adaptationism.

We wish to question a deeply engrained habit of thinking among students of evolution. We call it the adaptationist programme,
or the Panglossian paradigm.

Gould and Lewontin (1979)What is wrong with the traditional form of the scientific paper is simply this: that all scientific work of an experimental or exploratory character starts with some expectation about the outcome of the inquiry. This expectation one starts with, this hypothesis one formulates, provides the initiative and incentive for the inquiry and governs its actual form. It is in the light of this expectation that some observations are held relevant and others not; that some methods are chosen, others discarded; that some experiments are done rather than others. It is only in the light of this prior expectation that the activities the scientist reports in his scientific papers really have any meaning at all.

The debate between the adaptationists and the pluralists is often dismissed—usually by the adaptationists—as mere quibbling about scientific data. After all, they argue, all we need to do is collect data on each characteristic under discussion in order to resolve the question; is it an adaptation or an accident?

They are wrong. This is not a debate about facts at all. It's a debate about the the prior expectations that one has before any data is collected. Criticism of the adaptationist program focuses on the state of mind that researchers posses when they are designing experiments and formulating hypotheses to test. In other words, it's what Medawar refers to when he says that scientists start with "some expectation of the outcome of the enquiry." It's their bias or prejudice that's being questioned and not just whether the horns of an Indian rhinoceros are adaptations or not [Visible Mutations and Evolution by Natural Selection].

One of the main arguments of the Intelligent Design Creationists is that modern scientists adopt a naturalist assumption whenever they do science. This rules out creationism by definition. Some scientists attempt to deny that scientists have any pre-conceived notions at all. They promote the myth of pure inductive reasoning driven only by facts and evidence. It would be wise to drop this form of argument since it is obviously false. Scientists do have prejudices and biases. We need to recognize them and try to deal with them. The essence of skepticism is to always question your assumptions and discard them if they cease to become useful. That's what distinguishes the scientist from the preacher.

---

Burr, John, R. and Goldinger, Milton (1980) Philosophy and Contemporary Issues Macmillan Publishing Co., New York

Gould, S.J. and Lewontin, R.C. (1979) The Spandrels of San Marco and the Panglossian paradigm: a critique of the adaptationist programme. Proc. R. Soc. Lond. B 205:581-598.

P. B. Medawar (1996) "Is the Scientific Paper Fradulent?" in THE STRANGE CASE OF THE SPOTTED MICE, Oxford University Press, Oxford.

Why Children Love Their Security Blankets

 
A recent study examined Why Children Love Their Security Blankets. This is a subject most parents are familiar with and not just because of Linus. The photo on the left shows my daughter when she was much younger. She was trying to retrieve her pink blanket ("Cubby") after it had been washed and hung out to dry. The photo below is of my son showing off "Baba" after five years of continuous use—I think he still misses Baba. (There're probably going to kill me for posting these photos.)

The study asked whether children felt a special attachment to their favorite things ...

New research, published today in the international journal Cognition, suggests that this might be because children think the toy or blanket has a unique property or ‘essence’.

To support this theory, Professor Bruce Hood from the University of Bristol and his colleague Dr Paul Bloom of Yale University, USA, showed that 3-6 year-old children have a preference for their cherished items over apparently identical duplicates.

Children were introduced to a scientific looking machine that could copy any object but was in fact a conjurer’s cabinet where an accomplice inserted replica items from behind a screen.

Professor Hood said: “When offered the choice of originals and copies, children showed no preference for duplicates of their toys unless the object to be copied was the special one that they took to bed every night. A quarter of children refused to have their favourite object copied at all, and most of those who were persuaded to put their toy in the copying machine wanted the original back.”

Duh!

I have a favorite coffee mug, a favorite chair, a favorite shirt, a favorite pair of sunglasses, and a favorite blogger. I don't want no friggin' copies either and I wouldn't put any of those things in the copy machine. (Well, ... maybe I'd try putting PZ Myers in the copier, just to see what happens .... )

Security blankets and other things don't have any special "essence" that needs to be explained. Their unique property is their history. There's only one thing that was given to you by some special person and uniquely belongs to you. You can't copy that. Children aren't stupid. They know the difference between the original and some cheap copy.

This looks like the kind of study that discovered exactly what everyone expects but they have to hype the results in order to make it look exciting. Did anyone really think that my daughter or my son would have traded their very special blankets for a mere copy? How many of you have tried to con your kids when the security blanket got lost, as they invariably do? Didn't work, did it?

Don't anyone try and swap my coffee mug. If you break it, you die.

Jennifer Smith Is Going to Meet Stéphane Dion

 
You remember Jennifer Smith, don't you? She lives in Milton, Ontario. That's the place made famous by PZ Myers 'cause he stopped for a few days to get his car fixed.

Well, it turns out that Jennifer went to a town hall meeting with her MP, the newly Liberalized Garth Turner. During the meeting she so impressed her MP that he invited her to meet with our future Prime Minister next week [All Politics Are Local]. (That's Dion in the picture, with his dog Kyoto.)

Hey, Jennifer, ask him if he'll increase reseach funding when we elect him next Fall.

All Seven Continents

 
I was just checking to see where you all were coming from when I realized that in the past few hours I've had visitors from all seven continents!!!

Isn't that amazing? (I'm pretty sure there are Sandwalk readers in Antarctica—you just can't see the white dots against the snow.)

A Typical Graduate Course in Biochemistry

 
Vince LiCata was kind enough to publish a generic course syllabus that applies to most graduate courses—and many senior undergraduate courses. Read it at MY NEW GRADUATE COURSE OFFERING.

[Hat Tip: The World's Fair]

Ageism in Science

 
I'd like to address a thorny issue; namely, discrimination on the basis of age. The focus of this particular posting is the widespread belief that "young" investigators are more valuable to the research community than "old" ones.

By "young" I mean scientists who have graduated with a Ph.D. and completed several years of post-doc. They are either about to be hired as principle investigators for the first time or have already been hired within the past 7 years. Typically, they are under 40 years old and if they have a university position it will be as an Assistant Professor. They do not have tenure.

"Old," or senior, investigators are those over 40. There are two sub-categories: those between the ages of 40 and 55 who are thought to be in their prime and those over 55 who are thought to be well past their prime.

I was prompted to bring up this issue by the recent funding crisis in Canada and especially by some comments made in an open letter from Alan Bernstein, the President of CIHR (but see Old Professors). Alan's opinion, as expressed in the letter, is not that much different from the opinion of most of my colleagues. The difference is that Alan is in a position to act on his view of Canadian scientists. He can redirect funding.

Here's what Alan says about young investigators,

I am very concerned about the impact this situation will have on all members of the research community - new investigators, mid-level established investigators and Canada's most senior researchers. And I am particularly concerned about the impact on new investigators who are at the beginning of their careers. These new investigators represent the future of health research in Canada. Failure to secure grant support for their research in those critical first years can have a lasting detrimental effect on their subsequent careers. Clearly, all of us need to think about how to improve the situation for the very group of investigators who are bringing their energy, superb training and new approaches to health research.

At first glance this seems like a typical harmless motherhood statement that nobody questions. After all, doesn't everyone agree that youth represents the future? Doesn't everyone agree that energy and new approaches come from young investigators and not from old ones? Doesn't everyone agree that failure to get a grant can threaten the careers of young investigators?

Yes and no. There's a lot more going on than what's implied by such facile statements. Let's try and unpack Alan's paragraph and see what we can learn.

Like Alan, I am very concerned about the impact of the funding crisis on all members of the research community. Unlike Alan, I don't reserve any special concerns for young investigators at the expense of older ones. The loss of a grant in the middle of a promising career is just as devastating as the failure to get one in the first place. Perhaps more so, since the mid-career investigator has a lab full of graduate students, post-docs, and research assistants who have to be let go or moved. Given the choice between funding a mid-career investigator with a decent publication track record and a young investigator with no track record, why should we favor the unproven over the proven? Does such a bias make sense?

I question the common belief that young investigators represent the "future" of research. It suggests that a 45-year old doesn't have a future even though they may still have 20-30 years of productive research ahead of them.

Are young investigators more energetic? Perhaps, but I know lots of enthusiastic and energetic investigators who are no longer young. Besides, wisdom and maturity can often beat out energy in a head-to-head competition to do good research.

What about the idea that youth is more innovative? Is there any truth to that myth? Not really. There are lots and lots of senior investigators who are right up there on the cutting edge of science. I daresay there's more innovative work done in the labs of senior investigators than in the labs of young investigators, at least in my field. Part of this is due to the system. You can't take too many risks until you've become established. Part of it is due to experience. Experience is a good teacher—you can see productive new directions once you've mastered the old ones.

None of this means we should abandon young investigators in favor of senior investigators. But, by the same token, we shouldn't sacrifice senior investigators in order to fund younger ones. The excuses used to promote the "youth" strategy need to be questioned to see if they are truly valid. I don't think they are.

In the recent grant competitions, there was a tilt toward funding young investigators at the expense of renewing the grants of senior investigators. That's not right. It's discrimination on the basis of age and it must stop now.

(In the interests of full disclosure, I am not competing for grants from any granting agency. I do not have a direct stake in this issue other than to promote what's good for research and good for my colleagues. If we don't have enough money to support our current crop of researchers then it's stupid to hire more.)

Front Page News: CIHR Funding Crisis

 
Last week the Canadian Institutes of Health Research (CIHR) Funding crisis made the front page of the Globe and Mail (lower left corner)[Cash crunch spurs research warning]. I blogged about this earlier (Massacre in Canada) in order to publicize the effect it was having on my colleagues. We need to do something before we destroy researchers in the most productive part of their careers.

The President of the CIHR is Alan Bernstein. He responded to the crisis by publishing a President's Message to the Research Community - January, 2007. The message does not inspire confidence. The current mess was caused by a downturn in government funding but that downturn might have been foreseen. It could have been managed better.

The crisis is also due, in part, to the diversion of basic research money to new goals; namely, "relevant" research that might lead directly to improvements in health.

Alan has just published a article in an online magazine where he explains his philosophy [Publicly-Funded Research and Innovation: Canada’s Key to the 21st Century]. He says,

The world is in the midst of profound social, scientific, and technological change. How Canada responds to these changes will determine our future quality of life, career opportunities for young Canadians, and whether we will be globally competitive and productive.

Our future success as a nation will depend on our ability to attract and retain top scientific talent (what The Economist magazine recently called “The world’s most sought-after commodity on the planet”), to generate new ideas and transfer them into new products, new policies, and new services.

Real, cutting-edge research is tough to do. But, transforming research into action is even tougher. This process, called knowledge translation or innovation, involves meaningful interaction between researchers and the users of research.

It's the conflict between "knowledge translation" (God, how I hate buzzwords) and pure basic research that's causing angst. I don't see any evidence that the President of CIHR is willing to stand up for curiosity motivated research—the kind done on university campuses across the nation. He talks a lot about competitiveness and new products but not about knowledge and understanding.

This is very disappointing. It suggests that Alan has lost touch with the goals of his former colleagues (he used to be a research scientist at the University of Toronto). If the President of CIHR won't stand up for basic research then we're in big trouble. Maybe it's time to look for a new President who understands that support for basic science is crucial.

How to Fix NIH and NSF

 
I recently commented on the funding crisis in Canada. Less than 20% of grants will be funded in the latest CIHR competition. Canadian scientists are trying to see what needs to be done to fix the problem.

There's a similar problem in the USA. At the 2007 Science Blogging Conference we received a flyer from Geoff Davis and Peter Fiske asking people to go to their blog and get involved in the discussion about how to fix NIH and NSF. Here's the site: [Zerhouni for a Day: A challenge].

So far the main suggestions under discussion are to limit the size of grants and to cut back on funding interdisciplinary centers. Both suggestions are worth serious consideration.

What Is "Systems Biology?"

It's an interesting question. One of our departments here at the University of Toronto just renamed itself Cell and Systems Biology so you'd think they would know what "systems biology" is, wouldn't you?

Well, they don't. And neither do I. And neither, as it turns out, does Michael White over at Adaptive Complexity. Read his posting: Is Systems Biology Teaching Us Anything New?. Here's a teaser,

What I find most exciting about basic molecular biology today is the prospect of building a quantitative understanding of how a cell works. Many other scientists are excited about this as well, leading to the current popularity of what's being called 'systems biology.' The idea is that maybe we can understand the design principles behind a cellular process - how the behavior of a cell emerges from all of those detailed physical interactions among proteins, nucleic acids and other components of the cell. If that sounds vague to you, well, that's because it is vague. It's a nice sentiment, but I think biologists still have a hard time defining just what it is we want to learn.

Reciting The Lord's Prayer at City Council Meetings

I recently became aware of the fact that reciting the Lord's Prayer before city council meetiings is still happening in southern Ontario. The latest kerfulffle is in Durham Region, just east of Toronto. Apparently the Regional Council members have been reciting the Lord's Prayer and a group called Secular Ontario wants them to stop.

The practice was declared illegal following an Ontario Court of Appeals ruling in 1999. Illegal or not, it should stop. It's a really dumb idea.

But that's not what the Council Members of Durham Region think, according to an article in today's Toronto Star [Durham praises the Lord]. The Mayor of Oshawa, John Gray says,

God is the Supreme Being. Period. Full stop

The locals came out in force to support the council. Apparently they want to make sure everyone who attends Council meetings gets the message. Durham is a Christian county—nobody else is welcome.

What are they thinking? What possible benefits come from reciting the Lord's Prayer in a public meeting? If you're a Christian who really needs help from God before deciding anything, then surely you can mumble quietly to yourself before taking your seat?

If you're not a Christian council member then being forced to listen to a Christian prayer is at best useless, and at worst damn annoying and insulting. The only benefit is the bigoted message it sends to everyone else in the room. It says "we're a bunch of Christians" nobody else should run for office.

The real shocker came from seeing the two other councils that recite the Lord's Prayer before meetings: Mississauga and Brampton. That's my neck of the woods. I've written to my council member Katie Mahoney.

Gap Penalties

Reed A. Cartwright (De Rerum Natura) has just posted a summary of his recently published paper on the effect of gap costs in sequence alignment [Logarithmic gap costs decrease alignment accuracy].

It sounds esoteric but, in fact, it's a very important problem. Computer driven sequence alignments are behind a great deal of the bioinformatics that's being published today. Surprisingly, no computer program can do as good a job at global sequence alignment as a competent student. This should be cause for concern since it means that all the published work is known to be sub-optimal because the algorithms aren't up to the task. Most workers don't acknowledge this—I suspect they simply don't realize that the alignment programs are inefficient.

Reed looked at a particular problem in sequence alignment. The only difficult part about sequence alignment is placing the gaps that are due to insertions and deletions (indels) arising from the time that two sequences diverged from a common ancestor. During automated sequence alignment the program has to assign a penalty, or cost, for inserting gaps in the alignment. If there was no penalty associated with indels then the program would insert gaps willy-nilly to bring every position into perfect alignment. The idea is to limit the placement of gaps to only those locations where they truly represent an evolutionary event.

The standard penalty is represented by the formula G_k a + bk where G_k is the gap penalty. There are two components to the penalty: "a" is the penalty for creating a gap, and "b" is the penalty for extending it by "k" residues.

Reed tested several other types of gap penalties to see if they did a better job at aligning sequences. You should read his posting to see the surprising result. His paper is available here.

Here's an example of a computer generated multiple sequence alignment from the Pfam database [HSP70 alignments]. The protein is HSP70, the major protein chaperone. If you look at the right-hand side of the first page you can see how the algorithm placed the gaps (represented by dots). Most of you coud do a better job with just a little practice.