"I can repeat the question, but am I bright enough to ask it?"


"What are the pressing scientific issues for the nation and the world, and what is your advice on how I can begin to deal with them?"

As recognized pathogens develop multi-drug resistance, and as new pathogens are recognized, our tools for recognizing and treating these agents must keep up. At one time it was thought that infectious diseases had been practically vanquished. We must work hard to keep up.

Beatrice Golomb

Dear Mr. President:

Among the pressing issues that we face:

1. Natural pathogens (bacteria, viruses, fungi, parasites):

As recognized pathogens develop multi-drug resistance, and as new pathogens are recognized, our tools for recognizing and treating these agents must keep up. At one time it was thought that infectious diseases had been practically vanquished. We must work hard to keep up.

Conversely: Some microorganisms contribute to host health and defense. There is need to focus on studying and mining the benefits of beneficial organisms, as well as attending to those that produce harm. (Thus, there is evidence of altered gut "flora", i.e. altered balance of bacteria and fungi, in persons with irritable bowel syndrome; there is evidence that some "intestinal flora" are vital to gut function and nutrient absorption, and protect against invasion of pathogenic organisms; there is evidence that H. pylori, a bacterium that may contribute to gastroesophageal reflux, may also protect against esophageal cancer;

2. Biowarfare agents:

Additional work must go toward defense against pathogens and toxins developed as weapons of terrorism and biowarfare..

3. Chemical interactions and individual susceptibilities:

In our ever more chemically rich environment, certain health problems are escalating that are likely to be linked to exposures to certain chemicals and their combinations. Increasing evidence implicates certain chemical agents, and combinations of these agents, in chronic multisystem health problems to which a subset of the population appears susceptible; persons with fibromalgia/chemical sensitivity/chronic fatigue syndrome spectrum often report onset following chemical exposure and there is increasing evidence to support effects on membrane functioning, neurotransmitter systems, and mitochondria (the energy producing elements of cells) from these chemicals in susceptible persons. (Some genetic susceptibility factors have already been identified.)

Persons with such chronic multisystem problems are disproportionate users of healthcare resources. Fathoming the mechanisms of these problems and developing strategies to mitigate their onset and treat them when present will reduce healthcare costs and downstream litigation costs, and will enhance the health of many. Understanding these mechanisms may also lead to prevention, by permitting proper warnings to be placed regarding use of potentially hazardous agents, especially use in combination with agents that may have harmful interactions.

4. Chemical warfare and terrorism defense:

Because some of the classes of chemical implicated above, particularly carbamates and organophosphates (both of which act by inhibiting regulation of a key nerve and muscle signaling chemical that has widespread roles throughout the body), are used both to protect military persons in the event of nerve agent attack, and are used as nerve agents themselves, this work will have vital importance for military preparedness and health protection; for treatment of veterans in the event of renewed military conflict with nations that have or are suspected to have chemical warfare agents; and for civilian health protection.

5. Genomics and proteomics:

The time is ripe for increasing work to mine the genome, and more pertinently, to study how the balance of proteins and non-protein chemicals, using modern informatic and advanced statistical techniques, can:

• Predict illness susceptibility from various causes
• Show who will respond to particular treatments
• Track the benefits of particular treatments
• Design drugs that may mitigate and even cure chronic and uncurable diseases

6. Capitalize on existing databases to reap their full benefit:

There is much material that has never been culled from existing federally funded databases. A major reason is that the incentive system in academics rewards those who bring in large new grants, with the attendant overhead dollars. Thus, rather than spend time to study prior databases in detail, the incentive system encourages the time to be spent on procuring new grants. Additionally, there is a peculiar attitude, that must be changed, that major findings based on data initially procured by someone else are of lesser importance, even if they lead to paradigm shifts, than the expected next step that one performs oneself. There is need to change this attitude.

7. Scientific Reasoning:

Surprisingly, neither medical schools nor graduate schools have formal training in reasoning from evidence, the process of inference, fallacies in reasoning, and factors that influence the credibility of evidence. Even persons with a good grounding in statistics per se are not trained in these areas. In consequence, even many persons that are highly respected in the scientific community are ill-positioned to generate the recommendations from evidence that they are tasked to do. I can cite many instances in which failure of training and aptitude in this area has unnecessarily held back progress. I believe that such training should begin to be part of the core training process for graduate and medical schools. Arguably, reasoning skills ("how to think") should be an element of the core curriculum, at a more basic level, even among undergraduates. While this need not be legislated, it could certainly be strongly endorsed.

8. Informatics:

Additional focus should go to development and refinement of tools to handle large and incomplete databases.

9. Energy:

Efforts are needed to develop technologies to reduce dependency on foreign oil sources. This is an area in need of real leadership. We all recognize the importance of the oil industry in the US, and there is no reason that industry cannot participate in, or take a lead in, developing alternative technologies, or technologies to enhance efficiency of fuel use.

10. New means to disseminate scientific information:

The current structure of science leads to costly and needless delays in release of scientific information resulting from the structure of the publication process. Moreover, costly page charges lead to tightly written documents, but at the expense of key information being included. An antischolarly approach ensues: limitations in number of citations prevents all but limited literature from being cited, effectively leading to "loss" to the scientific community of valuable older information, the costs of which have already been expended. (Rather than it being required that each declarative statement should have a source cited, it is now possible for authors to make assertions that may have no basis in evidence—and if they do, the reader is not in a position to ascertain what that basis is.)

In the modern internet era, new approaches to speeding information dissemination, by capitalizing on internet technology should be seriously considered. (As one primordial suggestion, a system could be generated by which new research results could be posted on the internet. The system would have in place an opportunity for peer-review comments to be appended. This permits new readers to post their comments and expertise. A continually modifiable process of credentialing reviewers, with rankings by other readers, could allowing ranking of review comments. Among the advantages of this process, full database information could be provided, circumventing space limitations in journals, permitting others to perform their own analyses. Space limitations in journals often prevent pivotal information from being expressed.

Beatrice Golomb
Assistant Professor (of Medicine; Family and Preventive Medicine; and Psychology) at UCSD
Principal Investigator, UCSD Statin Study
University of California San Diego School of Medicine

John Brockman, Editor and Publisher
Russell Weinberger, Associate Publisher

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